bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unified Theory Of Early Visual Representations From Retina To Cortex Through Anatomically Constrained Deep CNNs
Authors: Lindsey Jack , Ocko Samuel A. , Ganguli Surya , Deny Stephane 
Published: January 2019

AbstractThe vertebrate visual system is hierarchically organized to process visual information in successive stages. Neural representations vary drastically across the first stages of visual processing: at the output of the retina, ganglion cell receptive fields (RFs) exhibit a clear antagonistic center-surround structure, whereas in the primary visual cortex (V1), typical RFs are sharply tuned to a precise orientation. There is currently no unified theory explaining these differences in representations across layers. Here, using a deep convolutional neural network trained on image recognition as a model of the visual system, we show that such differences in representation can emerge as a direct consequence of different neural resource constraints on the retinal and cortical networks, and for the first time we find a single model from which both geometries spontaneously emerge at the appropriate stages of visual processing. The key constraint is a reduced number of neurons at the retinal output, consistent with the anatomy of the optic nerve as a stringent bottleneck. Second, we find that, for simple downstream cortical networks, visual representations at the retinal output emerge as nonlinear and lossy feature detectors, whereas they emerge as linear and faithful encoders of the visual scene for more complex cortical networks. This result predicts that the retinas of small vertebrates (e.g. salamander, frog) should perform sophisticated nonlinear computations, extracting features directly relevant to behavior, whereas retinas of large animals such as primates should mostly encode the visual scene linearly and respond to a much broader range of stimuli. These predictions could reconcile the two seemingly incompatible views of the retina as either performing feature extraction or efficient coding of natural scenes, by suggesting that all vertebrates lie on a spectrum between these two objectives, depending on the degree of neural resources allocated to their visual system.
No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm
Authors: Madsen Kristoffer Hougaard , Karabanov Anke Ninija , Krohne Lærke Gebser , Safeldt Mads Gylling , Tomasevic Leo , Siebner Hartwig Roman 
Published: January 2019

AbstractBackgroundThe motor potentials evoked by transcranial magnetic stimulation (TMS) over the motor hand area (M1-HAND) show substantial inter-trial variability. Pericentral mu-rhythm oscillations, might contribute to inter-trial variability. Recent studies targeting mu-activity based on real-time electroencephalography (EEG) reported an influence of mu-power and mu-phase on the amplitude of motor evoked potentials (MEPs) in a preselected group with strong pericentral mu-activity. Other studies that determined mu-power or mu-phase based on post-hoc trial sorting according in non-preselected individuals were largely negative.ObjectivesTo reassess if cortico-spinal activity is modulated by the mu-rhythm, we applied single-pulse TMS to the M1-HAND conditional on the phase of the intrinsically expressed pericentral mu-rhythm in 14 non-preselected healthy young participants.MethodsTMS was given at 0, 90, 180, and 270 degrees of the mu-phase. Based on the absence of effects of mu-phase or mu-power when analyzing the mean MEP amplitudes, we also computed a linear mixed effects model, which included mu-phase, mu-power, inter-stimulus interval (ISIs) as fixed effects, treating the subject factor as a random effect.ResultsMixed model analysis revealed a significant effect of mu-power and ISI, but no effect of mu-phase and no interactions. MEP amplitude scaled linearly with lower mu-power or longer ISIs, but these modulatory effects were very small relative to inter-trial MEP variability.ConclusionOur largely negative results are in agreement with previous offline TMS-EEG studies and point to a possible influence of ISI. Future research needs to clarify under which circumstances the responsiveness of human the M1-HAND to TMS depends on the synchronicity with mu-power and mu-phase.HighlightsPhase-triggered TMS at four distinct phases of the ongoing mu-oscillations is technically feasible in non-preselected young volunteersTargeting the ongoing mu-activity did not reveal consistent modulatory effect of mu-phase on corticospinal excitability in a non-preselected groupMixed-effects analysis revealed a weak but significant effect of pre-stimulus mu-power and ISI on corticospinal excitability
A stress response that allows highly mutated eukaryotic cells to survive and proliferate
Authors: Zabinsky Rebecca A. , Mares Jonathan , She Richard , Zeman Michelle K. , Silvers Thomas R. , Jarosz Daniel F. 
Published: January 2019

ABSTRACTRapid mutation fuels the evolution of many cancers and pathogens. Much of the ensuing genetic variation is detrimental, but cells can survive by limiting the cost of accumulating mutation burden. We investigated this behavior by propagating hypermutating yeast lineages to create independent populations harboring thousands of distinct genetic variants. Mutation rate and spectrum remained unchanged throughout the experiment, yet lesions that arose early were more deleterious than those that arose later. Although the lineages shared no mutations in common, each mounted a similar transcriptional response to mutation burden. The proteins involved in this response formed a highly connected network that has not previously been identified. Inhibiting this response increased the cost of accumulated mutations, selectively killing highly mutated cells. A similar gene expression program exists in hypermutating human cancers and is linked to survival. Our data thus define a conserved stress response that buffers the cost of accumulating genetic lesions and further suggest that this network could be targeted therapeutically.
Association of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis
Authors: Richardson Marty , Kirkham Jamie , Dwan Kerry , Sloan Derek J , Davies Geraint , Jorgensen Andrea L 
Published: January 2019

AbstractBackgroundIndividuals receiving treatment with anti-tuberculosis (TB) drugs may experience serious side-effects, such as anti-TB drug-induced hepatotoxicity (ATDH). Genetic variants, such as polymorphisms of the GST gene and other genes, may increase the risk of experiencing such toxicity events. This systematic review and meta-analysis provides a comprehensive evaluation of the evidence base for associations between variants of the GST gene and other genes and toxicity outcomes related to anti-TB drugs.MethodsWe searched for relevant studies in MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science. We pooled effect estimates for each genotype on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies.ResultsWe included data from 28 distinct cohorts of patients in the review. The methodological quality of included studies was variable, with several important areas of concern. For GSTM1, patients with the homozygous null genotype were significantly more likely to experience hepatotoxicity than patients with heterozygous or homozygous present genotype (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.15, 1.82). Moderate heterogeneity was observed in this analysis (I2=51.2%). No significant difference was observed for the GSTT1 null polymorphism. For the rs3814057 polymorphism of the PXR gene, both heterozygous genotype and homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (heterozygous versus homozygous wild-type: OR=1.98, 95% CI 1.06, 3.69; I2=0%; homozygous mutant-type versus homozygous wild-type: OR=2.18, 95% CI 1.07, 4.44; I2=0%).ConclusionsWe found that it is challenging to perform robust synthesis of the evidence base for associations between GST and other genetic variants and toxicity related to anti-TB drugs. We identified significant associations between the GSTM1 null and PXR rs3814057 polymorphisms and ATDH. To the best of our knowledge, no meta-analyses on genetic variants other than variants of the NAT2, CYP2E1, GSTM1 and GSTT1 genes have been published. Our results therefore add to the existing understanding of the association between genetic variants and hepatotoxicity.
Character displacement within the breeding area questions reinforcement inFicedulaflycatchers
Authors: Grinkov Vladimir G. , Palko Igor V. , Sternberg Helmut 
Published: January 2019

AbstractAt present, studies of reinforcement should be focused on demonstrating how often this process occurs in nature and how important it is for speciation. Here we study the character displacement within the breeding area in the Pied Flycatcher to check the validity of the reinforcement inFicedulaflycatchers. We used point-referenced spatial data and a random forest to find the most important explanatory factors of the character displacement, and to reconstruct the phenotypic structure of the populations. The environmental temperature, and not the distance to sympatry, were proven to better describe the geographic pattern of the mean breeding plumage colour of the Pied Flycatcher populations. We conclude that ecologically distinct adaptations drive the morphological differentiation of the Old World flycatchers, and not reinforcement.
Plasmids for independently tunable, low-noise expression of two genes
Authors: Silva João P. N. , Vidigal Lopes Soraia , Grilo Diogo J. , Hensel Zach 
Published: January 2019

AbstractSome microbiology experiments and biotechnology applications can be improved if it is possible to tune the expression of two different genes at the same time with cell-to-cell variation at or below the level of genes constitutively expressed from the chromosome (the “extrinsic noise limit”). This was recently achieved for a single gene by exploiting negative autoregulation by the tetracycline repressor (TetR) and bicistronic gene expression to reduce gene expression noise. We report new plasmids that use the same principles to achieve simultaneous, low-noise expression for two genes. The TetR system was moved to a compatible plasmid backbone, and a system based on the lac repressor (LacI) was found to also exhibit gene expression noise below the extrinsic noise limit. We characterize gene expression mean and noise across the range of induction levels for these plasmids, apply the LacI system to tune expression for single-molecule mRNA detection in two different growth conditions, and show that two plasmids can be co-transformed to independently tune expression of two different genes.
Multivoxel Pattern Analysis Reveals Dissociations Between Subjective Fear and Its Physiological Correlates
Authors: Taschereau-Dumouchel Vincent , Kawato Mitsuo , Lau Hakwan 
Published: January 2019

AbstractIn studies of anxiety and other affective disorders, objectively measured physiological responses have commonly been used as a proxy for measuring subjective experiences associated with pathology. However, this commonly adopted ‘biosignal’ approach has recently been called into question on the grounds that subjective experiences and objective physiological responses may dissociate. We performed machine-learning based analysis on functional magnetic resonance imaging (fMRI) data to assess this issue in the case of fear. Participants were presented with pictures of commonly feared animals in an fMRI experiment. Multivoxel brain activity decoders were trained to predict participants’ subjective fear ratings and their skin conductance reactivity, respectively. While subjective fear and objective physiological responses were correlated in general, the respective whole-brain multivoxel decoders for the two measures were not identical. Some key brain regions such as the amygdala and insula appear to be primarily involved in the prediction of physiological reactivity, while some regions previously associated with metacognition and conscious perception, including some areas in the prefrontal cortex, appear to be primarily predictive of the subjective experience of fear. The present findings are in support of the recent call for caution in assuming a one-to-one mapping between subjective sufferings and their putative biosignals, despite the clear advantages in the latter’s being objectively and continuously measurable in physiological terms.
Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages
Authors: Desgrange Audrey , Lokmer Johanna , Marchiol Carmen , Houyel Lucile , Meilhac Sigolène M. 
Published: January 2019

AbstractLaterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the lack of a standardised and exhaustive procedure in mouse models, for phenotyping left/right asymmetries of all visceral organs. Here, we have developed a multimodality imaging pipeline, which combines non-invasive micro-ultrasound imaging, micro-CT and HREM, to acquire 3D images at multiple stages of development and at multiple scales. Based on the position in the uterine horns, we track, in a single individual, the progression of organ asymmetry, thesitusof all visceral organs in their thoracic or abdominal environment, together with fine anatomical left/right asymmetries of cardiac segments. We provide reference anatomical images and organ reconstructions in the mouse, and discuss differences with humans. This standardised pipeline, which we validated in a mouse model of heterotaxy, offers a fast and easy-to-implement framework. The extensive 3D phenotyping of organ asymmetry in the mouse uses the clinical nomenclature for direct comparison with patient phenotypes. It is compatible with automated and quantitative image analyses, which is essential to compare mutant phenotypes with incomplete penetrance and gain mechanistic insight into laterality defects.Summary statementLaterality defects, which combine anomalies in several visceral organs, are challenging to phenotype. We have now developed a standardised approach for multimodality 3D imaging in mice, generating quantifiable phenotypes.
The persistent influence of caste on under-five mortality: Factors that explain the caste-based gap in high focus Indian states
Authors: Bora Jayanta Kumar , Raushan Rajesh , Lutz Wolfgang 
Published: January 2019

AbstractObjectiveAlthough under-five mortality (U5M) is declining in India, it is still high in a few selected states and among the scheduled caste (SC) and scheduled tribe (ST) population of the country. This study re-examines the association between castes and U5M in high focus Indian states following the implementation of the country’s National Rural Health Mission (NRHM) program. In addition, we aim to quantify the contribution of socioeconomic determinants in explaining the gap in U5M between the SC/ST population and non-SC/ST population in high focus states in India.Data and methodUsing data from the National Family Health Survey (NFHS), we calculated the under-five mortality rate (U5MR) by applying a synthetic cohort probability approach. We applied a binary logistic regression model to examine the association of U5M with the selected covariates. Further, we used Fairlie’s decomposition technique to understand the relative contribution of socioeconomic variables on U5M risk between the caste groups.FindingsIn high focus Indian states, the parallel gap in U5M between well-off and deprived caste children has disappeared in the post-NRHM period, indicating a positive impact in terms of reducing caste-based inequalities in the high focus states. Despite the reduction in U5M, particularly among children belonging to STs, children belonging to the SC and ST population still experience higher mortality rates than children belonging to the non-SC/ST population from 1992 to 2016. Both macro level (district level mortality rates) and individual (regression analysis) analyses showed that children belonging to SCs experience the highest likelihood of dying before their fifth birthday. A decomposition analysis revealed that 78% of the caste-based gap in U5M is due to the effect of women’s level of educational attainment and household wealth between the SC/ST and non-SC/ST population. Program indicators such as place of delivery and number of antenatal care (ANC) visits also contributed significantly to widening caste-based gaps in U5M.ConclusionThe study indicates that there is still scope to improve access to health facilities for mothers and children belonging to deprived caste groups in India. Continuous efforts to raise the level of maternal education and the economic status of people belonging to deprived caste groups should be pursued simultaneously.
Cell non-autonomous functions of S100a4 drive fibrotic tendon healing
Authors: Ackerman Jessica E. , Studentsova Valentina , Best Katherine T. , Knapp Emma , Loiselle Alayna E. 
Published: January 2019

AbstractIdentification of pro-regenerative approaches to improve tendon healing is of critical importance given the diminished quality of life and physical function that accompanies the typical fibrotic response to tendon injury. S100a4 modulates fibrosis through tissue-type dependent mechanisms, and the role of S100a4 in fibrotic, scar-mediated tendon healing has not been established. In the present study we tested the hypothesis that inhibition of S100a4 improves tendon function following acute injury and surgical repair. We demonstrate cell non-autonomous functions of S100a4 as S100a4 haploinsufficiency promotes regenerative tendon healing, including decreased scar formation and improved mechanical properties. Moreover, inhibition of S100a4 via antagonism of its putative receptor, the Receptor for Advanced Glycation Endproducts (RAGE), also decreases scar formation. Mechanistically, knock-down of S100a4 decreases myofibroblast and macrophage content at the site of injury, with both cell populations being key drivers of fibrotic progression. In contrast, S100a4+ cell depletion displays time-dependent effects on scar formation, and consistent impairments in restoration of mechanical properties, indicating a critical role for these cells in re-establishing tendon strength after injury. Finally, we demonstrate, that S100a4-lineage cells become α-SMA+ myofibroblasts, via loss of S100a4 expression. Using a combination of genetic mouse models, small molecule inhibitors and in vitro studies we have defined S100a4 as a novel, promising therapeutic candidate to improve tendon function after acute injury.
A keeper of many crypts: the parasitoidEuderus setmanipulates the behavior of a taxonomically diverse array of oak gall wasp species
Authors: Ward Anna K. G. , Khodor Omar S. , Egan Scott P. , Weinersmith Kelly L. , Forbes Andrew A. 
Published: January 2019

AbstractParasites of animals and plants can encounter trade-offs between their specificity to any single host and their fitness on alternative hosts. For parasites that manipulate their host’s behavior, the complexity of that manipulation may further limit the parasite’s host range. The recently described crypt-keeper wasp,Euderus set, changes the behavior of the gall waspBassettia pallidasuch thatB. pallidachews an incomplete exit hole in the side of its larval chamber and “plugs” that hole with its head.E. setbenefits from this head plug, as it facilitates the escape of the parasitoid from the crypt after it completes development. Here, we ask whether this behavioral manipulator is limited toBassettiahosts. We find thatE. setattacks and manipulates the behavior of at least six additional gall wasp species, and that these hosts are taxonomically diverse. Interestingly, each ofE. set’s hosts has converged upon similarities in their extended phenotypes: the galls they induce on oaks share characters that may make them vulnerable to attack byE. set. Behavioral manipulation in this parasitoid system may be less important to its host range than other dimensions of the host-parasitoid interaction, like the host’s physical defenses.
Probing complexity of microalgae mixtures with novel spectral flow cytometry approach and “virtual filtering”
Authors: Barteneva Natasha S. , Dashkova Veronika , Vorobjev Ivan 
Published: January 2019

AbstractFluorescence methods are widely applied for the study of the marine and freshwater phytoplankton communities. However, identification of different microalgae populations by autofluorescent pigments remains a challenge because of the very strong signal from chlorophyll. Addressing the issue we developed a novel approach using the flexibility of spectral flow cytometry analysis (SFC) and generated a matrix of virtual filters (VF) capable to of differentiating non-chlorophyll parts of the spectrum. Using this matrix spectral emission regions of algae species were analyzed, and five major algal taxa were discriminated. These results were further applied for tracing particular microalgae taxa in the complex mixtures of laboratory and environmental algal populations. An integrated analysis of single algal events combined with unique spectral emission fingerprints and light scattering parameters of microalgae can be further used to differentiate major microalgal taxa. Our results demonstrate that spectral flow cytometer (SFC-VF) and virtual filtering approach can provide a quantitative assessing of heterogenous phytoplankton communities at single cell level spectra and be helpful in the monitoring of phytoplankton blooms.The research was partly presented during AQUAFLUO II Colloquium 2017, Sydney, Australia and ISAC Congress, Boston 2017
Cortical network mechanisms of anodal and cathodal transcranial direct current stimulation in awake primates
Authors: Bogaard Andrew R. , Lajoie Guillaume , Boyd Hayley , Morse Andrew , Zanos Stavros , Fetz Eberhard E. 
Published: January 2019

AbstractTranscranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that is widely used to stimulate the sensorimotor cortex, and yet the mechanism by which it influences the natural activity of cortical networks is still under debate. Here, we characterize the effects of anodal and cathodal tDCS on underlying neurons in active macaque sensorimotor cortex across a range of doses. We find changes in spike rates that are sensitive to both current intensity and polarity, behavioral state, and that are cell-type specific. At high currents, effects persist after the offset of stimulation, and the spatiotemporal activity associated with motor activity of the contralateral limb, measured by dynamics of neural ensembles, are altered. These data suggest that tDCS induces reproducible and noticeable changes in cortical neuron activity and support the theory that it affects brain activity through a combination of single neuron polarization and network interactions.