It is worth noting that in rodents, preOLs have been defined mostly by immunostaining profiles and it is not clear if they have a fleeting lifetime or they actually contribute as a stable subpopulation to the entire oligodendroglia lineage  OPCs receive a tonic muscarinic input capable to inhibit their differentiation into mature OLs and that (ii) disruption of this muscarinic-dependent pathway can increase the number of differentiated OLs, which improve myelin repair.Later, by using microarray analysis the authors found that M3 mAChR was a well-suited candidate to control hOPC differentiation into OLs. Application of muscarinic-agonist oxotremorine to hOPC cultures reduced the proportion of resultant OLs (Abiraman et al., in vivo is mediated by direct action of mAChRs expressed by hOPCs. Experiments performed by subcutaneous solifenacin injections cannot entirely rule out the indirect activation of other cell types such as white matter astrocytes (Butt et al., corpus callosum? In the study reviewed here, experiments performed in wild type mice showed similar results to those using the xenografted hOPCs paradigm: an increased number of callosal OLs after solifenacin treatment. A similar result was reported in mice treated with benztropine, an anticholinergic M1/M3 mAChR agent (Deshmukh et al., corpus callosum are glutamatergic (Restani et al., bona fide axon-OPC synapses in both control and demyelinating lesions (Ziskin et al., corpus callosum boundaries, as well as astrocytes present in white matter (Butt et al., corpus callosum, as it is involved in the correct transition from preOL to myelinating OLs (Michel et al., A crucial unanswered point, however, is whether the muscarinic antagonist effect In conclusion, Abiraman et al.  shed ligThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The two cases reported by Lukinmaa et al3 were limited in the same quadrant of the jaw, and hence, were declared by Cho et al4 as single hyperplastic dental follicles (SCHDF) and not MCHDF. Thus, the case report by Jamshidi et al2 should be suitably considered as the 9th case of MCHDF in the literature and not 11th in number.Multiple calcifying hyperplastic dental follicles (MCHDF) are disorders characterized by multiple unerupted teeth with abundant calcifications and rests of odontogenic epithelium in enlarged dental follicles.2 is given in the The detailed summary of all the nine cases, including the case reported by Jamshidi et al2 The reviewer stated that the statement by Jamshidi et al—“to date, 10 cases of MCHDF have been published worldwide”—was mainly based on the paper of Cho et al,4 in which the authors report five cases of MCHDF. Cho et al4 claim, in the beginning of the discussion section, that there were only five published cases of MCHDF before their paper, but continue to discuss, later in the text, that the two cases reported by Lukinmaa et al3 should be regarded as single calcifying hyperplastic dental follicle. Our reviewer stated that if the two cases of Lukinmaa et al3 are considered as single, not multiple, then the claim raised in this letter is reasonable.The concern raised in this letter was shared with a reviewer of the paper of Jamshidi et al.The author declares no competing interest with regards to authorship and/or publication of this article.2Table. Summary of multiple calcifying hyperplastic dental follicles cases until the report of Jamshidi et al


In this commentary, we explain why the recent manuscript by Hardcastle et al. , which cMinimal doses of exercise for health are somewhat limited within exercise recommendations (Garber et al., 2 reserve (Ekkekakis et al., To advocate for decreased pleasure with increasing intensity, Hardcastle et al.  employ aIt is our opinion that the motivation provided by positive health improvements and the time-efficiency of SIT/HIIT exceeds their potential aversive effects. Moreover, the assumption that these protocols have low adherence is not confirmed, with studies in elderly individuals showing a preference for interval protocols (Guiraud et al., Further, SIT has shown to improve motivation, particularly with regard to appearance and maintenance of body mass, as well as quality of life scores in elderly sedentary people (Knowles et al., The studies used to convince the reader that SIT is strenuous and can increase feelings of low self-esteem, potential failure, and incompetence tended to address generic issues and did not specifically involve SIT or HIIT (Hein and Hagger, Additionally, the sense of self-esteem, motivation, and competence is relative and can be enhanced by health professionals, as we believe that few people should perform exercise without supervision or guidance with regard to medical clearance, gradual progression, and appropriate monitoring. In this context, the exercise intensity is relative to the individual's current health and emotional status. Often sedentary or obese people and individual's with medical restrictions, have such low physical fitness that it would be impossible to conduct MICE. For example, a person with COPD, if a 30 min exercise is recommended, should exercise at 2.4–3.5 km/h (Rugbjerg et al., Hardcastle et al.  argue thHardcastle et al.  should bThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Plasmodium host cell invasion. Fundamentally, while the essential or non‐essential nature of different parasite proteins is becoming clearer, their actual function and how each comes together to govern invasion are poorly understood. Furthermore, in recent years an emerging world view is shifting focus away from the parasite actin–myosin motor being the sole force responsible for entry to an appreciation of host cell dynamics and forces and their contribution to the process. In this review, we discuss merozoite invasion of the erythrocyte, focusing on the complex set of pre‐invasion events and how these might prime the red cell to facilitate invasion. While traditionally parasite interactions at this stage have been viewed simplistically as mediating adhesion only, recent work makes it apparent that by interacting with a number of host receptors and signalling pathways, combined with secretion of parasite‐derived lipid material, that the merozoite may initiate cytoskeletal re‐arrangements and biophysical changes in the erythrocyte that greatly reduce energy barriers for entry. Seen in this light Plasmodium invasion may well turn out to be a balance between host and parasite forces, much like that of other pathogen infection mechanisms.Despite decades of research, we still know little about the mechanics of  Plasmodium  do.Systems biology has entirely transformed our understanding of the malaria parasites, protozoan pathogens from the genus et al., Plasmodium proteins described in any molecular detail  where host cell cytoskeletal re‐arrangement and re‐organization can be clearly seen during invasion  interaction then the merozoite will re‐orientate to its apex, without any additional energetic input  and reticulocyte binding‐like  protein families  core surface elements of the erythrocyte that link to its cytoskeleton – a hexagonal mesh underlying the lipid bilayer primarily consisting of spectrin and actin  in et al., et al., et al., et al., et al., et al., et al., et al., et al., The erythrocyte cytoskeleton is tethered vertically to the membrane through protein complexes such as the junctional and ankyrin complex  would now appear to be of key importance for sialic acid‐dependent and independent invasion. Basigin is a widely expressed multifunctional transmembrane protein implicated in inflammation and tumour invasion, but little is known with regard to its function or signalling mechanisms in the erythrocyte  or the ability of a protein to bind a defined receptor, functional classification must move towards assessing what proteins mechanistically do during invasion if we are to wholly understand the process. Combining these concepts, shifting our world view to a balanced interaction between parasite and host underpinning infection, we may discover new, and innovative, ways to stop the process as a way to treat or prevent disease.With so many uncertainties remaining regarding the roles of most


The paper “Nonsyndromic Mandibular Symphysis Cleft” by Leela Krishna Guttikonda et al. was interesting. However, we would like to point out a factual error in the discussion in this paper. In the seventh paragraph of discussion the authors have attributed one theory for the formation of this cleft to Rana et al. for an article published in Indian Journal of Plastic Surgery in 2004. This is factually incorrect.In that article the authors Rana et al.  have refWe feel that such errors should be avoided and due credit should be given to the first authors, namely, Oostrom et al.


Can you make yourself smarter? For over a century, cognitive enhancement has been an elusive endeavor in cognitive psychology. Training on a particular task meant specific, hardly-transferable, improvements (e.g., Ericsson et al., Before we delve into the means to maximize cognitive enhancement, let us rationalize our idea of combining interventions. The field of cognitive training has been at the core of fairly heated debates in the past few years; for example, what should count as evidence for the effectiveness of an intervention has brought much disagreement (see for example Boot et al., From a theoretical point of view, therefore, combining different interventions often obscures experimental results, as each combination needs to be compared against each single treatment it contains. However, when the goal is to benefit human populations, such combinations can be particularly powerful. For example, this idea has led to training programs bridging together physical and cognitive demands, either separately Shatil,  or withiThe past decade has seen the rise of brain stimulation techniques not only as a way to gain a more accurate understanding of human neural circuitry but also to alter patterns of neural activation. In essence, tDCS is a non-invasive stimulation technique that can either facilitate or suppress brain excitability by applying anodal or cathodal electrical stimulation through surface electrodes (Nitsche et al., One of the most effective uses of tDCS might be in combination with other methods of cognitive enhancement. In particular, recent research has shown that cognitive training can improve cognitive task performance (Anguera et al., Given the promising results of non-invasive brain stimulation in the laboratory, one might ask whether there is any way to further maximize the size and the durability of improvements. We argue that one possible approach is to combine brain stimulation with physical exercise. Cognitive enhancement has recently been associated with sport and exercise experience (Hillman et al., The impact of a combination of brain stimulations and physical training will ultimately depend on the identification of their precise neural underpinnings. To our knowledge, limited research has investigated the effect of combining physical exercise and brain stimulation, presumably because studies often aim to single out one source of facilitation instead of combining a variety of variables for maximized gain. However, studies have shown that the beneficial effect of aerobic fitness on cognition is most evident in the integrity of white matter (Voss et al., during the practice session. If we view the practice session as a form of cognitive training, these studies might suggest that there is much to be gained by combining cognitive training with brain stimulation (e.g., Ditye et al., When considering more complex activities such as sports, predicting the outcome of a combination with tDCS becomes slightly more complicated. This is because the cognitive demands of sustained sports training mostly tap long-term changes in cortical areas, and thus adding tDCS to stimulate the same areas might not produce an additive effect. This rationale is supported by a recent study by Bortoletto et al. , where aMoreover, one study recently demonstrated that tDCS-related enhancement in motor learning and temporal processing involves BDNF secretion that regulates synaptic plasticity (Fritsch et al., We have presented herein our views on combining tDCS with other well-established interventions such as physical exercise. The rationale we advocated goes beyond this particular combination, and others have been presented as valid, such as tDCS with cognitive training (e.g., Martin et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Preventing Chronic Disease, Moodley et al  and open-source free applications such as Ushahidi (www.ushahidi.com/product/ushahidi/).Although the main objective of Moodley et al was to provide a descriptive analysis of the intensity of SSB advertising, their approach to using technology deserves to be highlighted because it may be of great value to public health practitioners. To this end, Many recently published studies illustrate how this technological approach has been used in the field. Braun et al  providedBethlehem et al  discusseMobile technology is changing rapidly, and so are the innovative applications for using it. Curtis et al  collecteMoodley et al provide a case study of how a group of researchers with a defined research question for a well-documented public health concern used readily available low-cost technology to create a unique spatial database of environmental exposures. This approach has relevance to many different geographic settings and exposures, including data that may be available from commercial vendors but prohibitively expensive , as well as exposures that are more ephemeral, such as advertising billboards, where existing data sets may not be current for the period studied. Their data collection methods can be adopted by researchers and communities interested in various chronic disease–related exposures or assets (either harmful or protective), such as alcohol and tobacco advertising, fast-food outlets, and farmers markets. Public health practitioners could either adopt their approach of using a handheld GPS in combination with a digital camera or use similar approaches that are available through ready-made commercial or open-source smartphone applications, as this brief sampling of literature suggests.


Synesthesia is a rare experience where one property of a stimulus evokes a second experience not associated with the first. For example, in lexical-gustatory synesthesia words evoke the experience of tastes (Ward and Simner, Several authors focus on discussing what synesthesia is and how it relates to typical cross-modal interactions. Mylopoulos and Ro  provide Moos et al.  touch onHaigh et al.  examine In addition to Simner's  proposalMoving to neural mechanisms, O'Hanlon et al.  provide Finally Chiou and Rich  discuss Several authors highlight that synesthetes show different performance on tasks that are not directly related to their synesthetic experience. For example, Chun and Hupé  address In relation to cognitive differences between synesthetes and non-synesthetes, Ward et al.  address In summary, this Research Topic provides a novel collection of articles on synesthesia addressing a range of issues. We envisage that many of these will provide productive new research areas, and conceptual frameworks for the future study of synesthesia and related processes.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


During speech production, Broca's area is not the only area that becomes active, but there is an extended brain system including not only cortical but also subcortical areas. Classical Broca's area represents just a step in the brain language production system. Noteworthy, damage in other areas of this language production system  can also result in language production deficits (Papathanasiou et al., In conclusion we propose that lesions confined to the canonical Broca's area do not result in classical Broca's aphasia due to the large functional connectivity of this area with adjacent frontal and subcortical areas.AA, Primary writing; BB, fMRI analyses; MR, literature review; final writing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The type I interferon system plays a critical role in host defense in health, and a growing body of literature suggests that type I interferon is a critical mediator of human autoimmune disease . Type I This Research Topic features a number of Original Research Articles, including a study by Mavragani et al. examining type I interferon levels in the organ-specific autoimmune disorders type I diabetes and autoimmune thyroid disease . They deThe Research Topic also features a number of Review Articles focusing on various disease states. Liu et al. review murine models of systemic lupus erythematosus that are interferon-inducible, providing model systems of autoimmunity related to type I interferon . Wu et aThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Modern life sciences, biotechnology and synthetic biology are heavily dependent on state-of-the-art genetic engineering. This has led to great advances in biomedical and biotechnological applications, such as the identification of novel drug targets, the production of pharmaceuticals by use of novel engineered pathways, high-yield production of enzymes and, last but not least, the production of biofuels.et al., et al., However, in some other large application areas, in particular food and environmental applications, the use of genetically engineered microbes, is far behind, or even non-existent  the use of laboratory transformation protocols like electroporation, and (iii) the use of specific selection markers, frequently antibiotic resistance genes. This technology has proven to be very specific, making the risk of unwanted modifications very low. Moreover, current genomic technologies like re-sequencing of strains by next generation sequencing (NGS) can identify any undesired event. Taken together the vast majority of scientists do agree that safety offered by GMO is by far larger than that of classically modified organisms  because these latter approaches give rise to large numbers of mutations or re-arrangements in the genome that have nothing to do with the desired phenotype. Despite this notion, many consumers and consumer organizations are reluctant to accept this and persist in expressing their (unfounded) fears. This debate has been going on for the last 30 years, without a good perspective for a change in opinion  have faced societal resistance ever since their first mention. The main objections against the use of genetically modified microorganisms, commonly put forward by opponents of gene technology, are their presumed uncontrolled use, ‘unnatural'-ness, their likely spreading in the environment, possible negative effects on biodiversity, possible toxicity of new variants, supposed lack of good risk assessment protocols and negative effects on the economy of developing countries in view of intellectual property rights held mainly by multinationals. Genetically modified organisms are characterized by three main features: (i) the use of However, the wish still exists to produce healthier, better tasting, longer lasting, less processed, and attractive looking and smelling foods. Is there a way to circumvent the problems stated above?I think there is.et al., et al., et al., et al., et al., More than half a century ago, before the onset of genetic engineering, horizontal gene transfer was already known to occur in nature, via mechanisms such as conjugation, phage transduction and competence (McKay et al., et al., et al., et al., et al., With the advanced understanding of these processes, combined with the potential of millions of microbial strains in nature, current powerful technologies of re-sequencing by powerful, cheap and fast NGS, the use of biomolecular markers such as GFP, experimental evolution approaches and use of the aforementioned natural transfer methods, will now enable the screening of large numbers of environmental strains for suitable plasmids, conjugative transposons, phages and other transfer vehicles m (McKay None declared.


Dear Editor,The association of genetic factors with treatment induced hepatitis C clearance in Pakistani patients was recently demonstrated by Tipu et al. . They evCombined effect of SNPs which refers to independent impact of each SNP;Causal and Tag SNPs which is defined by the linkage disequilibrium (LD) between few tag SNPs and a causal SNP (sometimes undiscovered or untested).Most of the SNPs in IFNL region including the SNPs found by Tipu et al.  to be as


The formation and uplift of mountain ranges constitute major geological phenomena that can have long-lasting effects on the evolutionary diversification of living organisms. They provide opportunities for adaptive evolution through an increase of spatial heterogeneity of the landscape, including elevation, and the generation of a wide variety of ecologically diverse biotopes, and affect the migration of organisms and the distribution of species since mountain ranges can act as both biological corridors and ecological barriers. Hence, it should come as no surprise that mountain ranges host a large proportion of the biological diversity on earth (Barthlott et al., Hypericum in the northern Andes (Nürk et al., Hypericum. This pattern of diversification is also seen in other endemic plant groups of the Páramo flora, and the region has the highest average diversification rate among all biodiversity hotspots in the world (Madriñán et al., Rapid diversification processes are documented for the Páramo clade of the plant genus Campanula. Polyploid species of this genus are concentrated in the Campanula rotundifolia-complex, a mountain clade of Pliocene origin (Mansion et al., Penstemon species by Kramer et al. (Mutke et al.  report tr et al. .The different studies reported in this Research Topic clearly illustrate the potential effects of mountain uplift and formation on species diversification, at least in two major mountain regions of the world. A synthesis of biological diversification on mountains is, however, still far from being achieved and the potentially high complexity of the involved history, geography and biological processes encourages further research (Hoorn et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


DEAR EDITOR,et al, recently published in IJOTM [ I read with great interest an article of Ezzatzadegan, in IJOTM . They reI agree that the recent reports show a decline in the number of IFIs after kidney transplantation; however, IFIs are associated with high mortality after solid organ transplantation . In Tranet al, reported that Cryptococcus neoformans accounted for 50% of all IFIs [Aspergillus and Candida were responsible for more than 80% of IFIs in organ transplant recipients [et al, found—they reported only one case of mucormycosis in their kidney transplant patients [On the contrary to what Ezzatzadegan, all IFIs , we founcipients . In 2410I appreciate that advanced age of recipients is a risk factor for developing IFI, as noted by Ezzatzadegan and colleagues , but in et al [According to Ezzatzadegan, et al , the meaet al . In our et al . In addiet al ,5.


Correlated and synchronous activity in populations of neurons has been observed in many brain regions and has been shown to play a crucial role in cortical coding, attention, and network dynamics  How are pairwise and higher order correlations generated in networks and which of them are important for a given network? and (2) How should we uncover and interpret spike train correlations in a given dataset?Four studies Zhou et al. , GrytskyZhou et al.  investigGrytskyy et al.  have addIn a complementary study, Barreiro et al.  have focJahnke et al.  focused A team lead by Sonja Grün has tackled the second question, how spike correlations may be detected in a given data set. Torre et al.  have extIn an opinion article, Zanin and Papo  also addA third group of studies in this Research Topic addresses the computational advantages of neuronal correlations in the brain. Kilpatrick  studied In another study, Dipoppa and Gutkin  found thPrevious works have showed that synchronization between neuronal ensembles might play an important role in the binding of features belonging to a same object (Engel and Singer, In a study where the LFP and single-cell activity were recorded in the hippocampal formation of epileptic patients, Alvarado-Rojas et al.  found thThese studies give conspicuous examples for the ambivalent nature of neuronal correlations: in some conditions correlations might be a signature of dynamic instability of the network, but in other conditions correlations might be used to perform complex and flexible computations, such as binding or information gating. Although these works have provided new clues about the role of neuronal correlations, there are yet many unsolved questions, such as how neuronal correlations are generated and propagated (Moreno et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The mapping of signalling networks is one of biology’s most important goals. However, given their size, complexity and dynamic nature, obtaining comprehensive descriptions of these networks has proven extremely challenging. A fast and cost-effective means to infer connectivity between genes on a systems-level is by quantifying the similarity between high-dimensional cellular phenotypes following systematic gene depletion. This review describes the methodology used to map signalling networks using data generated in the context of RNAi screens. Specifically, signalling networks involve 1000s of different components, signalling pathways are highly interconnected, proteins act as part of large complexes, information propagation occurs via both linear and nonlinear ways (e.g. by feedback and oscillations) and these networks are dynamical in nature , it is clear that these representations are not reflective of Saccharomyces cerevisiae growing in one type of media , but failed in the late stages of cytokinesis. Thus, based on the shapes of the nuclei and the cell itself following gene depletion, we can infer that these genes regulate the same function (assembly of the contractile ring during cytokinesis), potentially make physical interactions, and may regulate the spatiotemporal activity of each other. All of these inferences regarding RacGAP50C, Rho1, Pbl and Pavarotti have in fact been validated using both forward genetic and biochemical methods in a number of different organisms , noisy (vary in nonmeaningful ways), and be highly correlated. For example, in Figure a priori, and then algorithms are used that select a subset of features that can discriminate these phenotypes from wild-type cells. Unsupervised approaches do not require any prior knowledge about the data, and attempt to identify the main trends of variability in the data by representing these trends in low-dimensional space. Principal component analysis (PCA) is a popular method of unsupervised dimensionality reduction. However, a caveat to using unsupervised methods like PCA is that it weighs features based on their variance rather than their relevance to the phenotypes of interest.Dimensionality reduction can be performed in either a supervised or unsupervised fashion. In supervised methods, a set of mutant phenotypes must be first identified et al., et al., We have previously made use of supervised approaches where we used machine learning algorithms to find combinations of features, or classifiers, that best explain our data (Bakal et al., et al., et al., et al., et al., et al., et al. generated models that assume different cells will have different phenotypes following depletion of the same gene by RNAi based on their position in multicellular colonies. Accounting for positional effects essentially ‘normalizes’ some of the phenotypic heterogeneity that is commonly observed following RNAi (Snijder et al., A nontrivial aspect to the analysis of high-content screens and the inference of signalling networks is how to derive a single phenotypic signature of highly heterogeneous cell populations. The most straightforward, and frequently used, method to calculate a single signature for a gene is to calculate the average phenotypic signature of cells from all populations where RNAi has depleted the gene, and this has been frequently used in the past. However, it is clear that even wild-type/untreated cells can exhibit high levels of phenotypic heterogeneity that may be driven by stochastic fluctuations in transcription, protein levels, signalling activity and cytoskeletal polymerisation (Mitchison & Kirschner, et al., et al., et al., Once a multidimensional gene specific signature has been calculated, measuring the similarity between signatures, and inferring connectivity, can be straightforward. A common method to infer interactions between genes is to use clustering methods that group gene signatures into ‘phenoclusters’ based on a given similarity metric, such as Euclidean Distance or Pearson correlation. In a screen for genes regulating cell morphology, we have shown that co-membership in a phenocluster strongly suggests that two genes encode members of the same signalling pathway/complex (Bakal One caveat to the use of similarity-based classification schemes such as hierarchical clustering is that phenoclusters are essentially complete graphs where each gene/protein is connected to all other in the cluster, and all clusters are ultimately connected to each other. Unfortunately, although clustering recapitulates the idea that many proteins that regulate a common function often act as part of large signalling complexes, it cannot be used to describe finer aspects of signalling network architecture and dynamics. For example, it is unlikely that all proteins assigned to a particular phenocluster physically interact. Moreover, using clustering it is essentially impossible to identify situations where a particular protein may act as an upstream regulator of another.et al., et al., et al., To overcome these problems, two methods have been successfully implemented to use phenotypic data generated by screens to infer more physiological aspects of signalling network architecture and dynamics. The first is to integrate phenotypic data with other data sources, such as coexpression or PPI data (Gunsalus In the past many groups, including our own, have been focused on development of the methods themselves, but the challenge now is to use these methods across many different cell lines and/or conditions in a genome-wide fashion to gain insight into how genetic backgrounds and environmental conditions affect network architecture. Furthermore, it is essential that new computational methods be developed which can be used to model aspects of signalling dynamics such as information flow, oscillatory behaviour and feedback. Finally, as imaging instrumentation becomes faster, and data storage ever cheaper, the task of analysing extremely large datasets in an efficient manner will require new solutions. In particular, solving the curse of dimensionality with regards to high-content data will require extensive collaborations between cell biologists and mathematicians.


Frontiers in Human Neuroscience) have tried to investigate how the semantic processing of graspable objects involves an activation of the motor cortex in line with the affordance hypothesis originally proposed by Gibson (Marino et al.  in theiry Gibson . They dey Gibson , 2005, iThere is mounting research evidence suggesting that the simple viewing of objects with action significance can stimulate the motor cortex into generating appropriate motor plans, even in cases that there is no action intention (Tucker and Ellis, per se, but instead an effect of purely attentional processes. Nevertheless, this is only an alternative proposition to the current findings by Marino et al. (premotor theory of attention, Rizzolatti et al., Furthermore, Cisek , 2007 hao et al.  and evenOverall, it is apparent that the affordance effect remains a compelling topic within cognitive psychology and neuroscience, as it is the need to better understand the underlying visual, attention and motor processes. Theories of a direct or indirect route between visual perception, semantic processing and motor planning may appear contradicting, but in our opinion it could be that they are all providing a valuable insight in the better understanding of human cognition and perception. Hence, it is important for future research to validate or expand upon these insights.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


M. avium subspecies paratuberculosis, hereafter referred to as MAP, is a significant veterinary pathogen that causes Johne's disease in ruminants, including cattle, sheep, and goats. This chronic intestinal disease is distributed worldwide and exacts a heavy economic toll on animal producers. For example, the dairy industry incurs substantial economic losses due to reduced milk production, premature culling, and reduced slaughter value (Raizman et al., MAP used has varied greatly in those studies. Then in 2007, an effort was made to standardize the challenge models used to test new vaccines for combating Johne's disease (Hines et al., Among the first large-scale vaccine trials for Johne's disease began in the early 1990s using killed whole cells in oil injected into cattle (Kormendy, MAP (Li et al., MAP (Shin et al., The genome sequence and re-sequence of MAP are thought to be the best approach for vaccination against Johne's disease. Although traditional inactivated and LAV candidates cannot satisfy the DIVA approach, they will completely stimulate both cell-mediated and humoral immune responses (Park et al., MAP infection, as suggested before in both the murine (Ghosh et al., Live attenuated vaccine strains of MAP through a series of three gated trials (Bannantine et al., relA (Park et al., To summarize the contributions to this research topic, the opening article reviews efforts by the Johne's disease research community to test available LAV strains of The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


As researchers in the field of self-control, we read the recent publication by Bushman et al.  with greFrom their results, Bushman et al.  concludeThe work by Bushman et al. draws on the proposal that “self-control requires brain food in the form of glucose” (p. 3). However, the glucose model of self-control . To date, however, experimental evidence is insufficient to support a significant role of glucose in self-control fatigue (Kurzban et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In two behavioral experiments, Marino et al.  investigSome previous papers (Tucker and Ellis, In principle, one cannot rule out the attentional hypothesis, as an alternative explanation to the findings of Marino et al. . HoweverThe time course of the recruitment of the motor system during semantic processing of objects and nouns is still a matter of debate. However, there is increasing evidence of an early involvement of the motor system during semantic tasks involving language material. Neurophysiological studies (for review see Pulvermüeller et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We mistakenly did not cite the reference Gontia-Mishra et al.  in the tHansenula saturnus (Minami et al., Issatchenkia occidentalis (Palmer et al., Penicillium citrinum and Trichoderma asperellum, and a stramnopile, Phytophthora sojae (Jia et al., Arabidopsis thaliana, poplar, and tomato plant (McDonnell et al., As reviewed in Gontia-Mishra et al. , among eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


According to Liu et al.  acupunctLiu et al. criticise several trials because acupuncture was not used appropriately according to traditional practice. However, all treatments being offered to patients should be subject to the highest standards of clinical testing whether they conform to traditional practice or are innovative in nature.It is nearly two decades since the WHO asked for acupuncture to be tested by the best clinical methods and the world is still waiting for sound evidence to show that acupuncture is superior to placebo. Whilst there is an enormous quantity of poor quality positive studies there are now many high quality negative studies.Some Comments on Liu et al.'s Higher Rated Trials. Effective blinding and appropriate controls are essential elements of a good clinical trial. Only one study was rated by Liu et al. with a Jadad top score of 5: Park et al. [k et al. . This moIn contrast, Smith et al. , rated aComparing the results of these two studies, whilst one result was entirely to be expected the other was unpredictable. One result was physical and the other psychological. Park et al.'s rationale was a doubt concerning the safety of previous trials. Liu et al. may say that moxibustion was an inappropriate treatment. That is not the fault of Park et al. who were justified in undertaking a new study with superior methodology to test dubious results of previous studies.These two contrasting RCTs show that what is important is not a general comparison of overall rates of quality of blinding across positive and negative studies. Indeed, that comparison can be misleading. What matters is the quality and relevance of each individual study. In other words, each trial must be judged on its own merits. The minimal blinding in Smith et al. was irrelevant since the result was a foregone conclusion. The absence of a sham control was the most severe failing of this study. Double blinding and sham control in Park et al. meant the result was not a foregone conclusion.Other positive trials were given a high Jadad rating: Paterson et al. ; ShifletThese Studies All Have Serious Problems. Paterson et al.'s trial does not qualify for a Jadad score of 4 because it was not a double blind trial. It was an open trial exposed to high risk of bias.P = 0.047) though it was not for pain relief. The rationale for this reanalysis was to see if it confirmed another reanalysis using their methodology, on another trial from the set, in which acupuncture and amitriptyline were both found to be more effective than placebo for pain relief, contradicting the findings of the original trial. This means that the two reanalyses of the two earlier studies, using a different methodology to the original trials, which produced consistent results across the set of trials, themselves produced contradictory results. The relevance of their results is questionable.Shiflett and Schwartz reanalysed one trial out of a set of three, designed to assess the value of acupuncture and amitriptyline for pain relief from peripheral neuropathy in HIV males. The set of trials was negative. Employing different statistical methodology to the original trials, Shiflett and Schwartz found a nominal statistical difference for acupuncture (Liodden et al.'s trial does not qualify for a Jadad score of 4. It was an open trial, whose authors acknowledge was wide open to bias.Two trials employed commendable methodology: Modlock et al.  and PastThey both found acupuncture to fare no better than placebo.On the question of the validity of placebo forms of acupuncture, if acupuncture is so variably defined as to render a valid placebo form of acupuncture quite impossible, then acupuncture cannot claim to be more than a placebo on any other basis than pure faith.In relation to the vast variability of acupuncture, another trial included in Liu et al. is instructive: Rogha et al. . This waOn the evidence presented in the study by Liu et al. acupuncture trials worldwide are routinely exposed to high risk of bias, knowingly or otherwise. Good methodology results in acupuncture failing to outperform placebo.


Behavioral biologists are unlikely to make such a concession. Unless we accept separate lineage-specific definitions for animals and plants, a new definition should encompass a consensus between animal-oriented and plant-oriented biologists. Levitis et al.  an exclusive one, represented by the working definition proposed by Levitis et al. , possibls et al.  found suliving entities,” understood as automomous agents .” This would also legitimize the existing use of the concept of behavior in cell-level studies  in the physical space. By no means does the use of this word imply involvement of a mind or consciousness. In our sense, flipping a metabolically or genetically wired switch also is a choice if its probability depends on outside stimuli and internal settings (previous history) of the biological system concerned.Taking into account the considerations discussed above, we propose defining behavior as “more easily understood as developmental changes” (Levitis et al., Nevertheless, a new definition may not be enough, unless accompanied by a certain shift of perspective. Carefully mapping the trench separating behavioral phenomena from those “FC drafted the manuscript and performed the final editing. VŽ and AM contributed ideas and parts of the text, and participated in editing the manuscript. All authors have approved the final version prior to submission.This work has been supported by the Ministry of Education, Youth, and Sports of the Czech Republic project LO1417.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In a recently published paper using space-time satellite data to determine air temperature (Ta), Kloog et al. concluded that Ta during pregnancy was associated with lower birth weight and shorter gestational age in the study population. The results obtained pointed to associations between Ta and birth weight during the last trimester, and between Ta and preterm delivery and low birth weight during the entire pregnancy. These results agree with those obtained by There are many epidemiological studies reporting a nonlinear J- or U-shaped relationship between Ta and health indicators such as mortality  and morbA study conducted in Rome with time-series analysis methodology  showed tThis suggests heat waves are an acute stressor on pregnant women, not the chronic stressor described by Kloog et al. The mechanism is unclear by which high temperatures may increase the risk of preterm birth, but there is evidence in the literature that supports a relationship . This shAlthough Kloog et al. introduced Ta values with linear components, from our point of view introducing Ta as a linear component and not taking into account the effects of heat and cold separately minimizes the authors’ ability to draw conclusions about potential impacts. The effects of high temperatures may be offset by cold temperatures. Therefore, it would be interesting to improve the analysis of Kloog et al. by taking into account the effect of Ta, but separating its effect by warm and cold seasons, especially for days within heat and cold waves.


In their recent article, Strüber et al.  demonstrAn important question is whether at these smaller time scales, the lack of prolonged entrainment during the post stimulation session necessarily reflect a lack of tACS efficacy. Alternatively, these results might also suggest that for 1s stimulation paradigms, we are simply looking at the wrong electrophysiological measure. At these smaller time scales, changes in measures such as spike rate adaptation (Fernandez et al., The effects of tACS on the underlying cortex often depends on the presence of an experimental task that actively recruits the underlying brain area or otherwise, produces a specific brain state. For instance, Kar and Krekelberg  demonstrChoosing the stimulation intensity is also a key consideration during tACS studies (Groppa et al., The Strüber et al.  study prThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A growing number of studies in multicellular organisms highlight low or moderate frequencies of paternal transmission of cytoplasmic organelles, including both mitochondria and chloroplasts. It is well established that strict maternal inheritance is selectively blind to cytoplasmic elements that are deleterious to males – ’mother's curse’. But it is not known how sensitive this conclusion is to slight levels of paternal cytoplasmic leakage. We assess the scope for polymorphism when individuals bear multiple cytoplasmic alleles in the presence of paternal leakage, bottlenecks and recurrent mutation. When fitness interactions among cytoplasmic elements within an individual are additive, we find that sexually antagonistic polymorphism is restricted to cases of strong selection on males. However, when fitness interactions among cytoplasmic elements are nonlinear, much more extensive polymorphism can be supported in the cytoplasm. In particular, mitochondrial mutants that have strong beneficial fitness effects in males and weak deleterious fitness effects in females when rare (i.e. ’reverse dominance’) are strongly favoured under paternal leakage. We discuss how such epistasis could arise through preferential segregation of mitochondria in sex-specific somatic tissues. Our analysis shows how paternal leakage can dampen the evolution of deleterious male effects associated with predominant maternal inheritance of cytoplasm, potentially explaining why ’mother's curse’ is less pervasive than predicted by earlier work. We first focus on paternal leakage in the population genetics model studied by Frank & Hurst  individual mitochondria mutate independently of each other with probability μ, (iii) individuals then undergo sex-specific selection according to the equations in Table B mitochondria are sampled from the M original mitochondria  at a Birky, , 2001, aM = 200), polymorphism does not differ from the haploid model  impact on the parameter space in which polymorphism is found under paternal leakage. Considering an illustrative bottleneck size of additive  or  is ddominant . Howeverdominant d–f, we fdominant , reducinWolbachia – is widely understood to lead to mother's curse . Consequently, the majority of detrimental fitness effects of these male-benefit mitochondria would be masked in females (as they lack these tissues), while positively contributing to fitness in males, for example by allowing for a rate of mitochondrial biogenesis and energy metabolism closer to the male optimum for such tissues.et al., et al., et al., et al., et al., Mytilus, in which male-benefit mitochondria are specifically targeted to male gonads and female-benefit mitochondria to male somatic tissues, demonstrates that the segregation of mitochondria to male-specific tissues can and does occur (Breton et al., A mechanism based on preferential segregation of different mitochondrial types to different somatic tissues is supported by a number of recent studies using highly sensitive genetic techniques. These have shown that mitochondria in heteroplasmic individuals do indeed segregate in a tissue-specific fashion (Battersby et al., Differential tissue segregation need not be specific for male tissues if the fitness effects of male-benefit mitochondria are recessive in female tissues but dominant in male tissues with high energetic demand, including reproductive tissues. Given that males typically have higher metabolic demands (Mittwoch, et al., et al., et al., et al., et al., We also showed that the severe homogenizing effect of bottlenecks in mitochondrial number could be important in those cases that favoured polymorphism. Bottlenecks are considered to be widespread in animals (Bergstrom & Pritchard, et al., et al., et al., et al., Although considerable attention has been devoted to the study of interactions between cytoplasm and nucleus (e.g. Rand et al., et al., et al., et al., et al., et al., Our study opens up several avenues for future work. Foremost, the current study considers leakage to be a fixed parameter, whereas it is likely to be a heritable character amenable to selection and evolutionary change. Modelling the evolution of leakage may shed light on the question of whether leakage is a sporadic aberration that mainly occurs in outbred or hybrid crosses (e.g. Fontaine


Aluminium phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide which is commonly used for grain preservation. AlP has currently aroused interest with a rising number of cases in the past four decades due to increased use for agricultural and non-agricultural purposes. Its easy availability in the markets has increased also its misuse for committing suicide. Phosphine inhibits cellular oxygen utilization and can induce lipid peroxidation. Poisoning with AlP has often occurred in attempts to commit suicide, and that more often in adults than in teenagers. This is a case of suicidal consumption of aluminium phosphide by a 32-year-old young medical anesthetist. Toxicological analyses detected aluminium phosphide. We believe that free access of celphos tablets in grain markets should be prohibited by law. In India it is marketed as a tablet of celphos, alphos, quick phos, phostoxin, et al., This highly toxic chemical is cheap and usually formulated in tablets or pellets, granules and as powder. Upon contact with moisture, aluminium phosphide liberates phosphine, which is the active pesticidal component Sudakin, . Human tet al., et al., et al., et al. et al., In India, this poisoning was not known before 1980. The first case in India was reported in 1981 from M.G.M. Medical College, Indore (Kabra In France, aluminium phosphide is used for crop protection and because of its toxicity to humans and domestic animals, the use of AlP is strictly controlled and it cannot be freely supplied.This is a case of suicidal consumption of aluminium phosphide by a 32-year-old young medical anesthetist who was under training at a reputed hospital. He visited the walled city and hired a room in a suburb. He was determined to consume the lethal dose but due to the prolonged effect, he survived initially and started vomiting, alerted the hotel staff complaining of an upset stomach and was rushed to hospital. There on arrival he gave his details, fell unconscious and later succumbed to the effects of the poison, which was identified by the remaining unused tablets later recovered from his luggage at the hotel. The reason which was revealed by the investigating officer later was depression as he belonged to a disturbed family with problems that made him take this extreme step.post-mortem examination, cyanosis was present over the nail bed. On opening the body, fishy or garlicky smell of phosphine gas was present. All the internal organs were congested with petechial hemorrhages. The lungs were congested and edematous with rupture of alveoli, gastrointestinal mucosal congestion (On ngestion , and petetc. It is available in small and large packs containing grayish-white tablets weighing about 3 g each, containing 56% aluminium phosphide and 44% aluminium carbonate, capable of releasing 1 g of phosphine.Aluminium phosphide is marketed in India as tablets of Celphos, Quickphos, et al., et al., et al., Following oral ingestion, AlP reacts with water and stomach acid to produce phosphine gas, which may account in large part for its observed toxicity. Phosphine generated in the gastrointestinal tract is readily absorbed into the blood stream. Phosphine may denature or reduce oxyhemoglobin in addition to enzymes important for respiration and metabolism and may also affect cellular membranes. The exact mechanism of action of phosphine is still not clear. Some authors have claimed it to be an inhibitor of cytochrome oxidase in animals (Chefurka et al., Symptoms of severe toxicity by AlP ingestion include diarrhea, cyanosis, breathing difficulty, pulmonary edema, respiratory failure, tachycardia, hypotension, dizziness, and death. The most common abnormality seen in the serum of 42% of poisoned patients was hypoxemia with severe metabolic acidosis (Khosla et al. in Phosphides, like phosphine, are toxic to the central nervous system, which is excited and then depressed. Arora et al. in et al., et al., et al., et al., et al., et al., et al., et al., The results of postmortem examinations of victims of phosphine poisoning generally indicate hypoxia with evidence of local trauma in the gastrointestinal tract, liver, kidneys, and central nervous system. The fatal dose of aluminium phosphide was stated to be in the range of 150–500 mg/70 kg by Chugh et al. in et al. and 100% in Jain et al. (et al. reported in The manner of death was reported to be suicidal in 87% of the cases by Dalbir n et al.  with allet al., et al., et al. et al. (et al., et al., Suicide was the most common mode of poisoning deaths, with overall mortality varying between 70–100%. Mortality is higher in those who consume more than two tablets and none of the patients survived who had ingested more than 3 tablets (Siwach . et al.  the patt et al., . PoisoniExposure to phosphine gas released from ALP fumigants increases risks of major morbidity and mortality. People handling this fumigant must be aware of its lethal aspects. An important preventive measure lies in better regulated supply of ALP, which otherwise is an excellent and safe fumigant as it leaves little residue on grain. Legislative and administrative measures have been suggested to restrict and modify its supply in India. Unfortunately there has been a failure in their implementation. Except the largest producer of it in India, it has been marketed as granulated powder in 10 g plastic sachets. Vendors and shop keepers should not sell the tablets to young people and children without proper verification and confirmation.


Neurological Science, Park and colleagues investigated the relationship among gait and speech disorders in patients with Parkinson's disease (PD) (Park et al., In a recent study in The findings on the relationship among different motor processes were previously reported in the literature in healthy subjects as well as patient populations. For example, one study found an overlapped representation in the brain for hand and leg movement (Ehrsson et al., Nonetheless, research on the relationship among different motor effectors is rather limited. Most researchers focus on only one kind of motor process—gait, speech, handwriting, eye movement or other. Thus, there is a dearth of knowledge on how the brain controls the different motor effectors, and whether they are similar or not. Further, it is not clear how and why such processes correlate. Park and colleagues suggest that executive and perceptual dysfunction may underlie both gait and speech deficits in PD, and that sensory cortex projections to the basal ganglia may be the neural mechanism underlying these deficits (Park et al., Computational modeling studies have the potential to explain why such motor processes correlate. Computational modeling approaches suggest that both gait, reaching, handwriting, and speech share more or less the same elemental motor processes, which include the selection of appropriate motor actions at every time step, sequencing of movements, coordination of different motor effectors, as well as correct performance of these responses. Other relevant processes include suppression of alternative motor plans (Aron et al., Motor cortical areas were repeatedly found to play a role in sequencing and maintaining motor plans in working memory to actively execute a plan (Dagher et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Sense of agency (SoAg) refers to the feeling of control over one's actions and forms an integral part of our cognitive and social lives  and neurological  disorders. While in recent years a number of studies have examined SoAg in these clinical groups, one group of individuals that have not yet been examined are those with mirror-touch synaesthesia (MTS). This opinion article seeks to explain why changes in SoAg may occur in MTS and also why mirror-touch synaesthetes could offer unique insights into the neurocognitive basis of SoAg.For most of us, observing another person being touched activates neural regions in the somatosensory cortex that are also involved in experiencing touch (e.g., Keysers et al., Recent studies (e.g., Aimola-Davies and White, This self-other blurring may be significant for SoAg. Experimental work in neurotypical individuals has shown how the deliberate blurring of the boundaries between self and other can have dramatic effects on SoAg. A good example of this is the so-called “Vicarious Agency” illusion, first demonstrated by Wegner et al. . In thisconsequence of these fundamental disturbances in sense of ownership. Intriguingly, the relationship between agency and ownership can also work in the opposite direction. Previous research in neurotypical adults has shown that SoAg can play a role in structuring bodily awareness (e.g., Tsakiris et al., Another line of enquiry worth pursuing is whether or not these putative agency effects in MTS are mediated by the changes in the sense of body ownership associated with the condition (e.g., Aimola-Davies and White, A further benefit of examining of SoAg in MTS is that it may help constrain our understanding of how inter-individual differences in self-other representations involved in SoAg and sense of body ownership interact to structure bodily awareness. Indeed, it has been shown that patients with impairments in self-other discrimination perform poorly on agency tasks: in particular, Daprati et al.  showed tIn the context of existing models of SoAg there are also some specific predictions about agency processing in MTS that could be tested. For example, the so-called comparator model of SoAg (e.g., Blakemore et al., networks and mechanisms underpinning it (see David, The final benefit of research on MTS that we wish to highlight concerns the brain basis of SoAg. Although a great deal of work has been done on the neural correlates of SoAg, we still know relatively little about the neural In summary, MTS refers to a rare experience in which observing touch or pain to another person evokes a tactile experience on the observer's body. There is growing evidence to suggest that this is linked to a blurring of self-other representation. In this article we have discussed how this disturbance may produce changes in SoAg in MTS. We have also discussed the ways in which research on MTS can improve our understanding of the neurocognitive basis of SoAg. In light of these discussions we believe that future research on SoAg in MTS is likely to provide valuable insights, both for those with a primary interest in MTS and for those with a primary interest in SoAg.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A single cell is inherently noisy. This noise is observed as a variability or heterogeneity between individual cells' responses in an isogenic population, and emerges from fundamental physical process governing state of the cell over time. In practice, states of two seemingly identical cells may be different in the same environment; and in fact the behavior of the population average my not correspond to any of the individual cells. Recent decades brought a technological breakthrough in many areas in our ability to measure and interpret cellular heterogeneity, including live-cell imaging  methods. They rely on targeting transcripts with fluorescently labeled oligonucleotide probes in fixed cells  that is capable of targeting transcripts, when tagged with a specific recognition motif  systems now enable measurements of up to 20 parameters simultaneously (Chattopadhyay et al., A major step change in the field occurred when the well-established “omics” technology, in particular next generation sequencing was applied to single cells. This, over few recent years transformed our ability to measure cellular heterogeneity from monitoring few sometimes arbitrarily selected markers into unbiased genome-wide analyses (Eberwine et al., Single-cell genomics is still very much an emerging field and thus many questions remain about reproducibility of data and normalization standards required (Wu et al., The picture emerging from the single-cell methods is that of unprecedented, previously unobservable levels of noise and heterogeneity in single cells. This noise emerges via all-on-nothing (Tay et al., However, is the static measurement going to be sufficient for studying associations? One could expect that integrated genome-wide studies would enable correlating for example epigenetic, transcriptomic, and proteomic heterogeneity. However, existing analyses already suggested that this correlation might be in fact smaller than expected (Taniguchi et al., statistical power and causality comes from the quantitative and temporal rather than static measurements under informative perturbation. This is best exemplified by a number of theoretical analyses and inference of cellular noise (Bowsher and Swain, In the inference of dynamical systems the Biological systems are inherently complex, and a noisy cell is their common denominator. The single cell biology approach is ideally suited to resolve this noise and heterogeneity with further developments of more integrated and quantitative approaches.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The purpose of the research topic “Ecophysiology of root systems-environment interactions” was to shed light on belowground processes—in an effort to further enhance its understanding, but also to increase the awareness of the research community and funding bodies toward this utmost important part of plants and ecosystems.2 levels, a factor which in itself affects plant and root growth, but is also expected to increase the intensity of climatic and edaphic extremes. In addition, other stresses such as salinization and heavy metal contamination of soils are either increasing or continue to persist world-wide. To secure crop yield and soil quality, and to understand the functioning, and thus the resilience and resistance of pristine ecosystems under changing environmental conditions, an increased understanding of acclimation and adaptation processes is imperative. In the past, plant sciences' research has focused predominantly on parameters above ground—resulting in disproportional less knowledge regarding root systems and the way root system functioning is affected by both internal and external factors. Similarly, soil scientists have often preferred studying bulk soil over the rhizosphere and as a consequence root-driven soil processes are still far less studied. Because it is “better to light a candle than curse the darkness” (Herron et al., Why is it important to increase our understanding and awareness? The new challenge of global climate change is driven by an increase in atmospheric CO2 can alter source–sink relations of plant organs. In this research topic, Easlon and Bloom (2 levels. Addressing water availability, Carminati (Increased net photosynthesis and decreased shoot nitrogen and water use under elevated COnd Bloom  emphasizarminati  shows tharminati  address arminati  focus onThe response of roots to abiotic stress can be modified by some root-associated bacteria and fungi. This is expressed as modification of root morphology and whole plant ecophysiology, which often enhances plant growth under stress (Alavi et al., Besides abiotic stress, root-microbe and root-fauna interactions, plant-plant interactions below ground are common and can influence plant performance considerably. For example, Bolte et al.  show thaCryptomeria japonica root morphology than on root biomass. Studying ectomycorrhizal short roots, Ostonen et al. (Poplar demes. As highlighted by Fort (in situ and in silica (Bodner et al., In the past years an increasing awareness has developed that understanding root traits will help to understand plant functioning. Since resources are acquired by the root system, breeding for crops with root traits/phenotypes increasing water and nutrient acquisition should increase yields on infertile soils and under a range of other abiotic stresses such as drought (Comas et al., n et al.  found thn et al.  evidencen et al.  found di by Fort , their rFagus sylvatica fine roots in relation to different stand characteristics resulting from conversion of coppiced forests to high forests. The fine-root C:N ratio was higher in coppiced than in converted stands and showed an inverse relationship with fine-root turnover rate, illustrating a significant change of fine-root status under different management practices—likely influencing e.g., the C sequestration potential of stands. Chairungsee et al. (In addition to articles on basic research which often accentuate the uncertainties in the field of root research, some articles already outline the application of knowledge of root traits in applied plant production systems. The study by Kerbiriou et al.  providese et al.  revealedWhen taken as a whole, the 28 contributions to this research topic cover many, although by no means all, aspects of root and rhizosphere research. The number of articles collected within a relatively short period of time, and other recently published special issues addressing root-environmental interactions (e.g., Annals of Botany, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Front. Integr. Neurosci. 7:47). Belmonte et al. (Biolinguistics). We hope that steps of the sort we take will eventually help us better understand the comorbidity, heterogeneity, and variability of ASD, but also the biological underpinnings of the human faculty of language.In their paper “Oral motor deficits in speech-impaired children with autism”  and for the concomitant rewiring of different connections between cortical and sub-cortical  structures, which provide the scaffolding for our species-specific mode of cognition . Many components of these three sets show fixed changes in modern humans compared to Neanderthals/Denisovans, which affect their regulatory regions, their coding regions, or both. Overall, we think that most of the genetic changes that brought about our language-readiness did not occur in a mosaic fashion, but rather revolved around changes in skull/brain morphology and neural connectivity that resulted in a more globular brain.The first set of genes is centered around RUNX2 one finds CTNNB1  and the fronto-temporal network connecting Wernicke's and Broca's areas (Hickok and Poeppel, TBR1. Specifically, disruptions of TBR1 give rise to severe speech and language deficits, autistic problems, and moderate to severe intellectual disability (Palumbo et al., TBR1 interacts with FOXP2 (Deriziotis et al., TBR1 seems to act as a master regulator controlling several other ASD-candidate genes (Chuang et al., Auts2 regulators we find both Runx2 and Foxp2 (Oksenberg et al., TBR1 contributes to the establishment of neocortical connectivity with the thalamus (McKenna et al., Tbr1 haploinsufficiency also results in defective axonal projections of amygdalar neurons, which give rise to a deficit in ultrasonic vocalization, social interaction, and associative memory and cognitive flexibility (Huang et al., Returning to our initial concern of the heterogeneity, variability, and specifically, comorbidity between motor and cognitive disorders observed in ASD, this frequent outcome of research and of clinical practice may be explained by the fact that the three set of genes we highlight here, involved in different aspects of cognition and motor behavior, are functionally interconnected. For example, as we mentioned earlier, some people suffering from autism bear a defective copy of It is also of interest that many of the genes we have focused on have changed after our split from Neanderthals and Denisovans (see Boeckx and Benítez-Burraco, In sum, we regard the motor approach to language dysfunction in autism of outstanding interest for autism research, but also for our understanding of the biological nature of the human faculty for language. We believe that the genetic aspects highlighted here may contribute to gain a better understanding of the way in which cognitive and motor behaviors affect each other in people with ASD.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Contemplative practices like meditation and mindfulness have recently gained increased acceptance in science and clinical practice, although a number of issues related to their phenomenology and to experimental designs still remain (Dahl et al., Significant progress has been made in the area of the neuroimaging of meditation and mindfulness, leading to increased understanding of the neural mechanisms underlying different techniques and stages of meditation (Lutz et al., The effects of meditation and mindfulness on physiological measures have been researched extensively. Although some of these findings have been challenged over the years, others, such as cortisol level decrease, enhanced immune response, decreased chronic pain, etc. have held. Recent findings of epigenetic changes due to relaxation response (Bhasin et al., Increasingly, studies point to beneficial effects of meditation and mindfulness on cognition, affect, and social behavior, though the findings can be contradictory at times and the effect sizes small (Braboszcz et al., The validity of introspection has been a perennial issues for contemplative traditions. Though experienced meditation practitioners may be more accurate in reporting their experiences than average subjects (Lutz et al., Meditation and mindfulness practices can also generate intense and unusual experiences and altered states of consciousness, such as states of reduced phenomenal content, or absorptions (Lutz et al., One of the most challenging issues for meditation studies is the lack of accurate indices of subjects' experience during meditation, independent from subjects' reports. Several neurophysiological measures have been proposed over the years, however, it is not likely that any single measure can adequately capture the complexity of meditation experience (Davis and Vago, Several persistent methodological issues have plagued meditation research studies since the early days (Nash and Newberg, The extraordinary multiplicity of meditation techniques and seemingly contradictory effects they produce pose a significant challenge for researchers. While the current research-oriented taxonomies have addressed this problem through categorizing meditation techniques into two or three major styles (Lutz et al., Contrary to popular “one-size-fits-all” approaches and advertisements, different meditations can have differential effects depending on one's psychological and physical makeup, and on the stage of one's practice. Adverse effects of meditation and mindfulness, which are often discounted in traditional contexts, can be significant and are only recently being studied in a systematic way (Garland et al., Taking meditation out of its cultural, religious, and philosophical contexts may miss the influences that these contexts can have on the observed results. Future research will need to include spiritual and religious motivations, ethical concerns, as well as interpersonal and cultural contexts (Nash and Newberg, Science alone, in its present form, may not be able to answer ontological and metaphysical questions about the nature of consciousness that are the focus of contemplative traditions (Delorme et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Warburg effect was first described as a mechanism by which the tumor cells rely on glycolysis to power proliferation and biosynthesis (Hsu and Sabatini, S. aureus sepsis, indicating that this pathway is important for septic responses.The mechanism of such metabolic switching remains unclear but a recent article by Cheng et al. sheds light on this crucial process (Cheng et al., This important study by Cheng et al. adds to a growing number of recent studies that have demonstrated that glycolytic flux and metabolic intermediates are drivers of immune responses. For example, macrophages exposed to LPS show a shift from oxidative phosphorylation to glycolysis (Rodríguez-Prados et al., Sepsis, a systemic inflammatory reaction to infection, is the leading cause of death in the world. The incidence of sepsis worldwide is 18 million every year with 30% mortality. The economic impact of sepsis is substantial with costs of up to $50,000/patient and $17 billion annually in United States alone (Slade et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Although orexinergic neurons are localized to less than 100,000 hypothalamic neurons in the human brain, orexin receptors exhibit overlapping and distinct expression throughout the CNS, with significant expression in brain regions associated with arousal and vigilance state, as well as reward and stress processing.The current special topics issue of Frontiers in Neuroscience “Insomnia and Beyond—Exploring the Therapeutic Potential of Orexin Receptor Antagonists” comprises 20 papers from leaders in the orexin/hypocretin field presenting their latest findings and thorough reviews, and will undoubtedly serve as an important reference for others engaged in this field of study. Since the independent identification of the orexin/hypocretin system in 1998 by two teams investigating hypothalamic signaling  that have undergone clinical evaluation. Two pharmacological papers from Morairty et al. (1R and OX2R on non-REM and REM sleep architecture.The identification of a neuropeptide system with restricted expression, key functions in fundamental CNS processes and approachability of discrete GPCR subtypes has made orexin receptors valuable targets for the next generation of CNS therapeutics, with multiple teams actively characterizing small molecules to understand the pharmacology and potential therapeutic applications of targeting the orexin system. Equihua et al.  takes thy et al.  (work byy et al.  (Merck Ry et al.  (Kanazawy et al.  (Jansseny et al.  (team fo2R selective antagonist, and its effects on rodent models of ethanol addiction and depression relative to a DORA and OX1R selective antagonist. In addition, (Steiner et al., 1R blockade in a rat model of diet-induced obesity.With regard to other potential indications for OXR antagonists beyond insomnia, two manuscripts from teams at Lilly Research Laboratories and MUSC (Anderson et al., A further area of orexin research which is being actively investigated focuses on the impact of orexin signaling on sympathetic autonomous nervous system activation, both during sleep and wake stages, as well as during heightened arousal and stress. Two excellent reviews from leaders in the field Carrive,  provide Together with the increasing availability of pharmacological tools, investigations of the role of orexin in limbic emotional processing have also intensified during the last 3–4 years. Two detailed reviews shed light on this topic, from both academic and industry perspectives (Yeoh et al., Importantly, this special issue highlights the exquisite foundational and translational work being conducted by teams at leading academic and biopharmaceutical laboratories, focused on investigating a range of therapeutic opportunities. Although it has only been 16 years since the identification of the orexin/hypocretin system, the wealth of knowledge obtained thus far has set the stage for the next decade of orexin research. It is with great appreciation to the contributing authors and with much enthusiasm that we present this special topics issue of Frontiers in Neuroscience.Michel Steiner is employed by Actelion Pharmaceuticals. Christopher Winrow is employed by Merck. Both companies are actively involved in the development of orexin receptor antagonists for clinical applications.


The reference of the following sentence should be Adani et al.  rather t“Adani et al. (2010) and Adani (unpublished) found that both English and Italian speaking children showed better performance in a sentence-picture matching task when the object and the subject of the object relative clause mismatched in number .”Adani et al.  should tThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The idea that we can influence neurons with electricity is not new. Earlier this century patients were treated, and still are, with electro convulsive therapy as a treatment for severe depression Fink, . FortunaSo far, VNS has been used to study cognitive functioning only in patients with epilepsy and major depression (Vonck et al., In rats, it has been demonstrated that VNS leads to an intensity-dependent increase in brain NE in response to stimulation of the left vagus nerve (Roosevelt et al., NE plays an important role not only in PES but also in emotional memory (Chamberlain et al., VNS seems to increase the levels of free GABA in the cerebrospinal fluid (Ben-Menachem et al., In rats, VNS has been found to attenuate the systemic inflammatory response to endotoxin via ACh release (Borovikova et al., tVNS seems to exhibit an inverted U-shaped relationship between stimulation intensity and memory performance. Indeed, Clark et al.  showed ttVNS may be a useful tool to further investigate the neuromodulation of cognitive processes related to NE, GABA and ACh, the three main neurotransmitters targeted by VNS. Yet, in healthy humans studies on how tVNS may modulate noradrenergic, GABAergic and cholinergic cognitive functions are lacking. Keeping in mind safety guidelines, we suggest that future studies on tVNS should take into account stimulation intensity to achieve a better theoretical understanding of the effect of tVNS on cognition.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Vibrio parahaemolyticus is a very versatile halophilic organism that can adapt to a wide variety of environments and can cause infections in both humans and aquatic animals. This versatility in terms of host and habitat is attributable to the ability to acquire genes that improve fitness of the organism in different situations. Several genomic islands have been described in this organism. Human pathogenic strains are characterized by the presence of pathogenicity islands that encode certain specific Type Three Secretion Systems (TTSS) and hemolysins that are not present in most environmental strains (Chen et al., V. parahaemolyticus strains have plasmid borne virulence genes (Sirikharin et al., V. parahaemolyticus is associated with zooplankton like copepods in off-shore waters and same genotype has been found over large areas (Martinez-Urtaza et al., V. parahaemolyticus has been attributed to the El Nino phenomenon characterized by the arrival of equatorial warm waters to South American coast in a sequence of invasive waves lasting about 6 months in 1997 (Martinez-Urtaza et al., V. parahaemolyticus in environmental samples and in understanding their global spread.V. parahaemolyticus has global distribution, occurring wherever environmental conditions are favorable. V. parahaemolyticus is a model organism for the “one health” concept, which recognizes that human health is connected to the health of animals and the environment. In order to better manage both public health and aquatic animal health, we need a better understanding of the factors effecting the ecology of this organism, the virulence factors present in human and animal pathogenic strains.Thus, this organism has attracted attention of both seafood safety managers as well as aquatic animal health professionals. Being an autochthonous aquatic organism, V. parahaemolyticus: ecology, virulence, and detection. Lopez-Joven et al. discuss the prevalence of pathogenic and non-pathogenic strains in association with molluscs while Zavala-Norzagaray et al. describe Vibrio spp. associated with sea turtles in Mexico. Host colonization depends on the ability of the organism to acquire difficult to get nutrients such as iron. León-Sicairos et al. describe strategies of V. parahaemolyticus to obtain iron. Improvements in the detection methods of pathogenic strains has been presented by Escalante-Maldonado et al. Genetic characterization of clinical and environmental strains has enabled Xu et al. to understand the emergence of indigenous and non-indegenous pathogen lineages. Genomic and molecular typing studies provide insights into the environmental reservoirs and genetic diversity of pathogenic and pandemic strains as described by Hazen et al., de Jesús Hernández-Díaz et al., Lüdeke et al., and Haendiges et al. Function of genes involved in Type IV secretion system of V. parahemolyticus has been investigated by Yu et al. and conditions leading to loss of plasmid in this organism has been described by Letchumanan et al.Raghunath presented insights into the role of virulence genes involved in human infections. Thus, the articles presented in this research topic contribute to a better understanding of the ecology, virulence, and detection of this important aquatic organism that impacts for both public health and aquaculture.The papers in this research topic cover the three major aspects of pathogenic and pandemic All authors listed, have made substantial, direct, and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Bjorklund and Kipp  provide  Self-regulation is the capacity to select actions that lead to favorable outcomes and avoid actions that lead to unfavorable outcomes. Bjorklund and Kipp  examine However, Bjorklund and Kipp  propose In the 1970s, Walter Mischel created the delay of gratification paradigm to test children's ability to resist temptation and forgo a small immediate reward in order to obtain a larger delayed reward. The paradigm consists of preschool children being asked to observe one marshmallow, without touching or eating it. The research assistant leaves the child alone and if the child can resist the temptation to touch the marshmallow and is able to wait until the research assistant returns voluntarily, the child is given the opportunity to have two marshmallows. This elegant and simple paradigm allows researchers to test children's ability to select a large delayed reward in favor of small immediate reward , the results on a related measure (delay discounting) are contradictory. Delay discounting is a task used to measure impulsive choice by asking participants to select between a large reward delivered at variable delays  and a smaller immediate reward. As the length of the delayed reward increases, participants are more inclined to select the smaller immediate reward. However, there is variability in how quickly participants discount the value of the larger delayed reward and this variation can be used as a measure of impulsive choice; in other words, greater discounting is indicative of impulsive choice  and has projections to the nucleus accumbens (NAc), bed nucleus of stria terminalis (BNST), and the frontal cortex. GABAergic, glutamatergic, and opioid peptidergic systems modulate activity in the VTA and NAc , affinity (Kd), and binding potential (Bmax/Kd) using positron emission tomography (PET) and [11C]raclopride (a D2 receptor radioligand) in healthy adult volunteers. Their results indicate that generally, women have lower D2 receptor affinity in the striatum compared to men. The lower D2 receptor affinity suggests an increase in endogenous striatal dopamine concentrations in women  and confirmed that women have higher striatal dopamine synthesis capacity than men; furthermore, there was an effect of aging such that there was a decrease in dopamine activity with age in men but not women (Laakso et al., 11C]raclopride. In stark contrast to the findings reported by Laakso et al. (In addition to the above purely structural studies, numerous other research groups have investigated both structural and functional sex differences. For example, Pohjalainen et al.  investigo et al. , the reso et al.  study reo et al. ; howevero et al.  report to et al. . In the To explore the possibility that the MCLP is modulated by gonadal hormones in humans, Dreher et al.  obtainedThere are a few recent studies that suggest that females are less impulsive during fertile phases of the menstrual cycle (Pine and Fletcher, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The relationship of Gantzer muscle to the median and anterior interosseous nerve is debated.  Ìn an anatomical study with 80 limbs from 40 cadavers the incidence, origin, insertion, nerve supply and relations of Gantzer muscle have been documented.  The muscle was found in 54 forearms (68% of limbs) and was supplied by the anterior interosseous nerve. It arose from the deep surface of the flexor digitorum superficialis muscle, (42 limbs), coronoid process (eight limbs) and medial epicondyle (seven limbs). Its insertion was to the ulnar part of flexor pollicis longus muscle. The Gantzer muscle always lay posterior to both the median and anterior interosseous nerve.  The Gantzer muscle may contribute to the median nerve and anterior interosseous nerve compression. The muscle was found in 68% of limbs and should be considered a normal anatomical pattern rather than an anatomical variation. . The relation of Gantzer muscle with the anterior interosseous nerve and the median nerve is controversial. ManginiThe objective of this study was to analyze the incidence, origin, insertion, and innervation of the Gantzer muscle. We analyzed the anatomical and topographic relationship regarding the anterior interosseous nerve and the median nerve, verifying the possibility of Gantzer muscle being the cause of the anterior interosseous nerve and the pronator teres syndrome (median nerve compression near the elbow). The interosseous nerve compression causes weakness or paralysis of the flexor pollicis lungus, flexor digitorum profundus and square pronator muscle, and the median nerve compression causes paralysis of the muscles of the thenar region and changes in sensitivity in important discriminating area of the hand. In both situations the functional deficit is important, leading to prehension and digital pinch disability.The study was approved by the Ethics Committee of Faculdade de Medicina de Sorocaba da Pontifícia Universidade Católica de São Paulo, Sorocaba, SP, Brazil.Eighty forearms of 40 adult cadavers belonging to the discipline of Anatomy, Faculdade de Medicina de Sorocaba (PUC-SP) were dissected to perform this study, 38 cadavers were male and two were female.Their ages ranged between 45 and 77 years old, 23 were white and 17 were non-white, 28 pieces were previously prepared with formaldehyde solution at 10% and 12 forearms were freshly dissected.Forearm deformed by trauma, malformations and scars were excluded.The dissection was performed through a midline incision on the forearm around the lower third of the arm; two flaps including skin and subcutaneous have been folded on the radial and ulnar sides, respectively, the same was done for the fascia of the forearm exposing, thus, all muscles.All the muscles of the forearm were dissected, analyzing its innervation and the presence of nerve communication between the nerves of the forearm. All anatomical variations found were registered, recorded and photographed. We used a 2.5x Keeler magnifying glass (Germany) for magnification. The relationship of the Gantzer Muscle with the previous interosseous and median nerves was analyzed.The incidence of the Gantzer muscle was acknowledged in 54 of the 80 dissected forearms (68%). In 42 forearms the muscle originated from the deep portion of the flexor superficialis muscle.  In eightThe Gantzer muscle was inserted in the flexor pollicis lungus in 36 forearms and in the flexor digitorum profundus in 21, totaling 57 insertions in 54 forearms. In three forearms, the Gantzer muscle was duplicate.  In two tThe Gantzer muscle presented fusiform shape entering through a tendon in the flexor pollicis lungus or flexor digitorum profundus.In all forearms we observed that the Gantzer muscle received exclusive innervation from the anterior interosseous nerve.  The anteIn 30 forearms the Gantzer muscle was positioned posterior to the anterior interosseous nerve, in 18 forearms it was located anterir to the nerve.  In six fOf the four forearms of two female corpses, we found the Gantzer muscle in only one. We recorded the Gantzer muscle bilaterally hypertrophied in six forearms of three male patients.et al.,et al.,et al.et al.et al.et al.et al.et al.The incidence of the Gantzer muscle was recorded in 54 of the 80 dissected forearms 68%). This is close to the percentage observed by Mangini 8%. This et al.Saxena et al.The important difference between our results with those of Tamang et al.et al.We noticed that the Gantzer muscle occurred more frequently bilaterally than unilaterally, agreeing with the findings of Jones et al.,et al.et al.et al.Regarding the most frequent location of Gantzer muscle origin a major disagreement stands among most authors. According to Manginiet al.We agree with Jones et al.et al.et al.et al.,13 who also dissected using a magnifying glass, showed results similar to ours.Regarding duplication, we recorded in three cases, Shirali et al.et al.et al.Regarding the insertion, Al Qattanet al.Our findings are very close to those of Jones et al.,et al.,et al.,et al.,et al.The classic Anatomy treaties such as Testutet al.We observed that the anterior interosseous nerve was more frequently crossed by the muscular component of Gantzer of muscle in only nine limbs (16.6%) the anterior interosseous nerve was crossed by the tendon component, which is in agreement with Oh et al.et al.It is controversial whether the Gantzer muscle can cause the anterior interosseous nerve syndrome or even the pronator teres syndrome. Ballesteros Al QattanKaplan and report Spinner7 since it was registered in 31 forearms dissected that the muscle is always situated posterior to the nerve as its tendon could pass anterior to the branch to the square pronator.Dellon and MackinnonWe affirm that the hypertrophied Gantzer muscle can cause the anterior interosseous nerve syndrome, but this was an uncommon finding in only six forearms (11%), all bilaterally we recorded the hypertrophied muscle.et al.Tabit et al.Hill The Gantzer muscle, especially when hypertrophied and positioned anterior to the median nerve and to the anterior interosseous nerve may be the cause of nerve compression. Present in 68% of cases, in our view, the Gantzer muscle should be considered a normal anatomical pattern and not an anatomical variation.


Sula granti) in the Galapagos. Their analysis covered two separate investigations: a human capture-restraint stressor applied to adult boobies, and observations of nestlings maltreated by Non-parental Adult Visitors (NAVs). The authors conclude that the temporal sequence of yawning following these stressors provides support for the newly termed arousal reduction hypothesis, an idea initially proposed by Dourish and Cooper  to a more relaxed state” (p. 38), i.e., the arousal reduction hypothesis. This is quite misleading as the experiments reported were not designed as a direct test of this hypothesis, which is proposed later in the discussion. Useful development of the hypothesis would include a sketch of how it would work in the context of the results. In fact, the reported patterns—nocturnal yawning by adult boobies and particularly yawning by nestlings in the absence of parents or responses by nearby nestlings—raise doubts about evolved signal function, which generally requires selection in terms of receivers and senders  (Miller et al., Liang et al.  state thLiang et al.'s  own explIdeally, a new hypothesis illuminates and perhaps accounts for previously documented effects better than standing theories, but at the least, it should offer a better, internally coherent account of the data on which it is based. In this case, the arousal reduction hypothesis offers no clear explanation for previously reported empirical patterns, for example, yawning and ambient temperature variation (see Gallup, Overall we believe the results reported by Liang et al.  are impoThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Glioblastoma (GBM), a World Health Organization (WHO) grade IV astrocytoma, is the most common and difficult primary brain tumor to treat . They are invisible to the naked eye, typically measuring 1–100 nm in diameter , a subclass of superparamagnetic MNPs, are the most effective types of MNPs that can be used for imaging purposes (Thorek et al., Hyperthermia for the treatment of different cancers has been well described in the past. Elevation of targeted areas of the body above 40°C can result in cancer cell death (Wust et al., While local or regional hyperthermia can be effective in treating cancer involving different parts of the body, treating brain tumors is difficult due to the surrounding skull (Jordan et al., Due to the side effects and toxicities of subjecting the entire brain to hyperthermia for extended periods of time, localized treatment is necessary for effective brain tumor therapy. Direct implantation of MNPs into brain tumors can bypass the BBB and allow for a maximum hyperthermic effect provided in a targeted manner Figure The localized hyperthermic effect, known as thermotherapy, involves the application of an alternating magnetic field (Maier-Hauff et al., Thermotherapy does induce the death of malignant cells (Marcos-Campos et al., in vitro samples (Issels, in vitro (Rhee et al., in vivo models. One explanation for this difference is that the vascular network within the tumor is abnormal which can lead to areas that have a difference in pH as well as decreased availability of oxygen (Issels, The decreased resistance to heat observed in GBM cells is not as clearly presented when conducting experiments with  Issels, . Cancer  Issels, .Thermotherapy involving the use of an AMF in conjunction with MNPs has proven to be an effective method for treating patients with GBM. Initial tests have shown that MNPs have minimal toxicities to patients, though further testing must be done to confirm these findings (Mahmoudi et al., With further research, scientists can bioengineer multitasking MNPs that can be used for imaging, drug delivery, and localized thermotherapy (Hadjipanayis et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.