bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural covariance networks are coupled to expression of genes enriched in supragranular layers of the human cortex
Authors: Romero-Garcia Rafael , Whitaker Kirstie J , Váša František , Seidlitz Jakob , Shinn Maxwell , Fonagy Peter , Dolan Raymond J , Jones Peter B , Goodyer Ian M ,   the NSPN Consortium, Bullmore Edward T , Vértes Petra E
Published: July 2017

Complex network topology is characteristic of many biological systems, including anatomical and functional brain networks (connectomes). Here, we first constructed a structural covariance network (SCN) from MRI measures of cortical thickness on 296 healthy volunteers, aged 14-24 years. Next, we designed a new algorithm for matching sample locations from the Allen Brain Atlas to the nodes of the SCN. Subsequently we use this to define, transcriptomic brain networks (TBN) by estimating gene co-expression between pairs of cortical regions. Finally, we explore the hypothesis that TBN and the SCN are coupled.

TBN and SCN were correlated across connection weights and showed qualitatively similar complex topological properties. There were differences between networks in degree and distance distributions. However, cortical areas connected to each other within modules of the SCN network had significantly higher levels of whole genome co-expression than expected by chance.

Nodes connected in the SCN had significantly higher levels of expression and co-expression of a Human Supragranular Enriched (HSE) gene set that are known to be important for large-scale cortico-cortical connectivity. This coupling of brain transcriptome and connectome topologies was largely but not completely related to the common constraint of physical distance on both networks.
A real-time compression library for microscopy images
Authors: Balázs Bálint , Deschamps Joran , Albert Marvin , Ries Jonas , Hufnagel Lars
Published: July 2017

Fluorescence imaging techniques such as single molecule localization microscopy, high-content screening and light-sheet microscopy are producing ever-larger datasets, which poses increasing challenges in data handling and data sharing. Here, we introduce a real-time compression library that allows for very fast (beyond 1 GB/s) compression and de-compression of microscopy datasets during acquisition. In addition to an efficient lossless mode, our algorithm also includes a lossy option, which limits pixel deviations to the intrinsic noise level of the image and yields compression ratio of up to 100-fold. We present a detailed performance analysis of the different compression modes for various biological samples and imaging modalities.
Coat color allele and mtDNA haplotype distributions in Russian cat populations: a citizen-science research
Authors: Zaytseva Olga O. , Tsepilov Yakov A. , Yudayeva Ekaterina S. , Kasianov Artem , Kulakovskiy Ivan V. , Logacheva Maria , Belayeva Daria , Gracheva Anna A. , Homenko Ksenia , Knyazeva Anastasia , Kolesnikova Ekaterina , Nikolayeva Daria , Bevova Mariana R. , Borodin Pavel M. , Aulchenko Yurii S.
Published: July 2017

This work has started as a project for the summer school in molecular and theoretical biology. Efficient teaching and learning modern methods of molecular biology and population genetics in a two-week study course for high school students needs an attractive subject. We chose phylogeography of the domestic cat as the subject of our project because 1) everybody likes cats; 2) cats are polymorphic for several coat color mutations, which can be easily detected by street survey or in the photographs; 3) samples for DNA extraction are easy to collect without posing ethical and biosafety problems; 4) rich background information of geographical distribution of coat color alleles and variation in mtDNA is available; 5) phylogeography of cat population in Russia is poorly studied and therefore new data collected in this large territory may shed a light on the global cat distribution and on the origin of the fancy breeds.

During the project students studied coat color and mitotype distribution across Russian random bred cats. The basics of field (observations of natural cat populations, hair collection), formal (inheritance of coat colors), mathematical population (allele frequency distributions and their comparisons, building phylogenetic trees, multidimensional scaling), and molecular (DNA extraction and amplification, quality control of DNA sequencing data) genetics were covered.

We scored coat color phenotypes in 1182 cats and sequenced mtDNA control region from hair samples of 38 cats from 18 geographical sites. Analysis of coat color alleles frequencies and mitotype distribution confirmed relative homogeneity of gene pools of Russian cat populations, indicating their recent origin. We found several unique mitotypes and demonstrated that OL1 mitotype, previously found only in Siberian fancy breed, was present in random bred cats from several Russian cities. This contributes to the discussion on the origin of the Siberian breed of cats, and supports the view that Siberians is a recent breed created in the 1980s by breeding of selected representatives of the random bred population.
Differential epigenetic landscapes and transcription factors explain X-linked gene behaviours during X-chromosome reactivation in the mouse inner cell mass
Authors: Borensztein Maud , Okamoto Ikuhiro , Syx Laurène , Guilbaud Guillaume , Picard Christel , Ancelin Katia , Galupa Rafael , Diabangouaya Patricia , Servant Nicolas , Barillot Emmanuel , Surani Azim , Saitou Mitinori , Chen Chong-Jian , Anastassiadis Konstantinos , Heard Edith
Published: July 2017

X-chromosome inactivation (XCI) is established in two waves during mouse development. First, silencing of the paternal X chromosome (Xp) is triggered, with transcriptional repression of most genes and enrichment of epigenetic marks such as H3K27me3 being achieved in all cells by the early blastocyst stage. XCI is then reversed in the inner cell mass (ICM), followed by a second wave of maternal or paternal XCI, in the embryo-proper. Although the role of Xist RNA in triggering XCI is now clear, the mechanisms underlying Xp reactivation in the inner cell mass have remained enigmatic. Here we usein vivosingle cell approaches (allele-specific RNAseq, nascent RNA FISH and immunofluorescence) and find that different genes show very different timing of reactivation. We observe that the genes reactivate at different stages and that initial enrichment in H3K27me3 anti-correlates with the speed of reactivation. To define whether this repressive histone mark is lost actively or passively, we investigate embryos mutant for the X-encoded H3K27me3 demethylase, UTX. Xp genes that normally reactivate slowly are retarded in their reactivation inUtxmutants, while those that reactive rapidly are unaffected. Therefore, efficient reprogramming of some X-linked genes in the inner cell mass is very rapid, indicating minimal epigenetic memory and potentially driven by transcription factors, whereas others may require active erasure of chromatin marks such as H3K27me3.
Modeling cell-substrate de-adhesion dynamics under fluid shear
Authors: Maan Renu , Rani Garima , Menon Gautam I. , Pullarkat Pramod A.
Published: July 2017

Changes in cell-substrate adhesion are believed to signal the onset of cancer metastasis, but such changes must be quantified against background levels of intrinsic heterogeneity between cells. Variations in cell-substrate adhesion strengths can be probed through biophysical measurements of cell detachment from substrates upon the application of an external force. Here, we investigate, theoretically and experimentally, the detachment of cells adhered to substrates when these cells are subjected to fluid shear. We present a theoretical framework within which we calculate the fraction of detached cells as a function of shear stress for fast ramps as well as for the decay in the fraction of detached cells at fixed shear stress as a function of time. Using HEK and 3T3 fibroblast cells as experimental model systems, we extract characteristic force scales for cell adhesion as well as characteristic detachment times. We estimate force-scales of ~ 500pNassociated to a single focal contact, and characteristic time-scales of 190 ≤τ≤ 350s representing cell-spread-area dependent mean first passage times to the detached state at intermediate values of the shear stress. Variations in adhesion across cell types are especially prominent when cell detachment is probed by applying a time-varying shear stress. These methods can be applied to characterizing changes in cell adhesion in a variety of contexts, including metastasis.
Loss of CHIP Expression Perturbs Glucose Homeostasis and Leads to Type II Diabetes through Defects in Microtubule Polymerization and Glucose Transporter Localization
Authors: McDonough Holly , Lenhart Kaitlin C. , Ronnebaum Sarah M. , Zhang Chunlian , An Jie , Portbury Andrea , Newgard Christopher B. , Willis Monte S. , Patterson Cam , Schisler Jonathan C.
Published: July 2017

Recent evidence has implicated CHIP (carboxyl terminus of Hsc/Hsp70-interacting protein), a co-chaperone and ubiquitin ligase, in the functional support of several metabolism-related proteins, including AMPK and SirT6. In addition to previously reported aging and stress intolerance phenotypes, we find that CHIP-/-mice also demonstrate a Type II diabetes-like phenotype, including poor glucose tolerance, decreased sensitivity to insulin, and decreased insulin-stimulated glucose uptake in isolated skeletal muscle, characteristic of insulin resistance. In CHIP-deficient cells, glucose stimulation fails to induce translocation of Glut4 to the plasma membrane. This impairment in Glut4 translocation in CHIP-deficient cells is accompanied by decreased tubulin polymerization associated with decreased phosphorylation of stathmin, a microtubule-associated protein required for polymerization-dependent protein trafficking within the cell. Together, these data describe a novel role for CHIP in regulating microtubule polymerization that assists in glucose transporter translocation, promoting whole-body glucose homeostasis and sensitivity to insulin.
Decision and navigation in mouse parietal cortex
Authors: Krumin Michael , Lee Julie J , Harris Kenneth D , Carandini Matteo
Published: July 2017

Posterior parietal cortex (PPC) has been implicated in navigation, in the control of body movement, and in visually-guided decisions. Seeking to relate these views, we measured activity in populations of PPC neurons while mice performed a virtual navigation task driven by visual decisions. We found that PPC neurons are selective for specific combinations of the animal’s spatial position and heading angle. This selectivity closely predicted both the activity of individual PPC neurons, and the arrangement of their collective firing patterns in choice-selective sequences. These sequences reflected the influence on PPC of the animal’s navigation trajectory. An alternative model in which PPC activity encoded position and decision performed more poorly, and a model with all three variables barely outperformed the simple position-heading model. Alternative models based on visual or motor variables were inferior. We conclude that when mice use vision to choose their trajectories, a large fraction of parietal cortex activity can be predicted from simple attributes such as spatial position and heading.
Predicting eye movements from deep neural network activity decoded from fMRI responses to natural scenes
Authors: O’Connell Thomas P. , Chun Marvin M.
Published: July 2017

Computational models of selective spatial attention can reliably predict eye movements to complex images. However, researchers lack a simple way to measure covert representations of spatial attention in the brain and their link to overt eye movement behavior, especially in response to natural scenes. Here, we predict eye movement patterns from spatial priority maps reconstructed from brain activity measured with functional magnetic resonance imaging (fMRI). First, we define a computational spatial attention model using a deep convolutional neural network (CNN) pre-trained for scene categorization. Next, we decode CNN unit activity from fMRI activity and reconstruct spatial priority maps by applying our computational spatial attention model to decoded CNN activity. Finally, we predict eye movements in a subsequent behavioral experiment within and between individuals using reconstructed spatial priority maps. These results demonstrate that features represented in CNN unit activity can guide spatial attention and eye movements, providing a crucial link between CNN models, brain activity, and behavior.
Dramatic expansion of microbial groups that shape the global sulfur cycle
Authors: Anantharaman Karthik , Jungbluth Sean P. , Kantor Rose S. , Lavy Adi , Warren Lesley A. , Rappé Michael S. , Thomas Brian C. , Banfield Jillian F.
Published: July 2017

The biogeochemical cycle of sulfur on Earth is driven by microbial sulfate reduction, yet organisms from relatively few lineages have been implicated in this process. Recent studies using functional marker genes have detected abundant, novel dissimilatory sulfite reductases that confer the capacity for microbial sulfate reduction and could do not be affiliated with known organisms. Thus, the identity of a significant fraction of sulfate reducing microbes has remained elusive. Here we report the discovery of the capacity for sulfate reduction in the genomes of organisms from twelve bacterial and archaeal phyla, thereby doubling the number of microbial phyla associated with this process. Eight of the twelve newly identified groups are candidate phyla that lack isolated representatives, a finding only possible given genomes from metagenomes. Two candidate phyla,CandidatusRokubacteria andCandidatusHydrothermarchaeota contain the earliest evolved genes. The capacity for sulfate reduction has been laterally transferred in multiple events within some phyla, and a key gene potentially capable of switching sulfur oxidation to sulfate reduction in associated cells has been acquired by putatively symbiotic bacteria. We conclude that functional predictions based on phylogeny will significantly underestimate the extent of sulfate reduction across Earth’s ecosystems. Understanding the prevalence of this capacity is integral to interpreting the carbon cycle because sulfate reduction is often coupled to turnover of buried organic carbon. Our findings expand the diversity of microbial groups associated with sulfur transformations in the environment and motivate revision of biogeochemical process models based on microbial community composition.
Time-gated detection of protein-protein interactions with transcriptional readout
Authors: Kim Min Woo , Wang Wenjing , Sanchez Mateo I. , Coukos Robert , Zastrow Mark Von , Ting Alice Y.
Published: July 2017

Transcriptional assays such as yeast two hybrid, split ubiquitin, and Tango that convert transient protein-protein interactions (PPIs) in cells into stable expression of transgenes are powerful tools for PPI discovery, high-throughput screens, and analysis of large cell populations. However, these assays frequently suffer from high background and they lose all information about PPI dynamics. To address these limitations, we developed a light-gated transcriptional assay for PPI detection called PPI-FLARE (PPI-Fast Light- and Activity-Regulated Expression). PPI-FLARE requiresbotha PPI to deliver TEV protease proximal to its cleavage peptide,andexternally-applied blue light to uncage the cleavage peptide, in order to release a membrane-tethered transcription factor (TF) for translocation to the nucleus. We used PPI-FLARE to detect the ligand-induced association of 12 different PPIs in living mammalian cells, with a temporal resolution of 5 minutes and a ±ligand signal ratio up to 37. By systematically shifting the light irradiation window, we could reconstruct PPI time-courses, distinguishing between GPCRs that engage in transient versus sustained interactions with the cytosolic effector arrestin. When combined with FACS, PPI-FLARE enabled >100-fold enrichment of cells experiencing a specific GPCR-arrestin PPI during a short 10-minute light window over cells missing that PPI during the same time window. Due to its high specificity, sensitivity, and generality, PPI-FLARE should be a broadly useful tool for PPI analysis and discovery.
Frank-Starling Mechanism and Short-Term Adjustment of Cardiac Flow
Authors: Chaui-Berlinck José Guilherme , Monteiro Luiz Henrique Alves
Published: July 2017

The Frank-Starling Law of the heart is a filling-force mechanism, a positive relationship between the distension of a ventricular chamber and its force of ejection. The functioning of the cardiovascular system is usually described by means of two intersecting curves: the cardiac and vascular functions, the former related to the contractility of the heart and the latter related to the after-load imposed to the ventricle. The crossing of these functions is the so-called operation point, and the filling-force mechanism is supposed to play a stabilizing role for the short-term variations in the working of the system. In the present study, we analyze whether the filling-force mechanism is responsible for such a stability within two different settings: one-ventricle, as in fishes, and two-ventricle hearts, as in birds and mammals. Each setting was analyzed under two scenarios: presence of the filling-force mechanism and its absence. To approach the query, we linearized the region around an arbitrary operation point and put forward a dynamical system of differential equations to describe the relationship among volumes of ventricular chambers and volumes of vascular beds in face of blood flows governed by pressure differences between adjacent compartments. Our results show that the filling-force mechanism is not necessary to give stability to an operation point. The results indicate that the role of the filling-force mechanism is related to decrease the controlling effort over the circulatory system, to smooth out perturbations and to guarantee faster transitions among operation points.

Summary Statement

We address the role of the Frank-Starling mechanism and show that it has no role in the stability of the circulatory system. Rather, it accounts for decreasing the controlling effort and speeding up changes in cardiac output.
ISG15 induces IL-10 production in human monocytes and is a biomarker of disease severity during active tuberculosis
Authors: dos Santos Paula Fernandes , Van Weyenbergh Johan , Delgobo Murilo , de Oliveira Patricio Daniel , Ferguson Brian J. , Guabiraba Rodrigo , Dierckx Tim , Menezes Soraya Maria , Báfica André , Mansur Daniel Santos
Published: July 2017

Interferon stimulated gene 15 (ISG15) deficiency in humans leads to severe interferonopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. Here, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. Employingex vivosystems analysis of human transcriptome datasets, we observed a significant correlation of ISG15-induced monocyte IL-10 and lymphocyte IFNγ expression. This effect was associated with p38 MAPK and PI3K signalling in healthy volunteers. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmedin vitrousing CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, thisISG15/IL10axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB, revealing a potential biomarker for disease severity in this major human disease.
Automated analysis of internally programmed grooming behavior inDrosophilausing ak-nearest neighbors classifier
Authors: Qiao Bing , Li Chiyuan , Allen Victoria W. , Shirasu-Hiza Mimi M. , Syed Sheyum
Published: July 2017

Despite being pervasive, the control of programmed grooming is poorly understood. We have addressed this gap in knowledge by developing a high-throughput platform that allows long-term detection of grooming in the fruit flyDrosophila melanogaster. Automatic classification of daily behavior shows flies spend 30% of their active time grooming. We show that a large proportion of this behavior is driven by two major internal programs. One of these programs is the circadian clock that modulates rhythms in daily grooming. The second program depends oncycleandclockand regulates the amount of time flies spend grooming. This emerging dual control model of programmed grooming in which one regulator controls the timing and another controls the duration, resembles the well-established two-process regulatory model of fly sleep. Together, our quantitative approach inDrosophilahas revealed that grooming is an important internally driven behavior under the control of two regulatory programs.
Locomotor and Reinforcing Effects of Pentedrone, Pentylone and Methylone in Rats
Authors: Javadi-Paydar Mehrak , Nguyen Jacques D. , Vandewater Sophia A. , Dickerson Tobin J. , Taffe Michael A.
Published: July 2017

The broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the α-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous self-administration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for α-PVP and α-pyrrolidinohexiophenone (α-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5-10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 °C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 °C) was observed for four hours after 10 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than α-PVP or α-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone.
Three-dimensional mobility and muscle attachments in the pectoral limb of the Triassic cynodontMassetognathus pascuali
Authors: Lai Phil H. , Biewener Andrew A. , Pierce Stephanie E.
Published: July 2017

The musculoskeletal configuration of the mammalian pectoral limb has been heralded as a key anatomical feature leading to the adaptive radiation of mammals, but limb function in the cynodont outgroup remains unresolved. Conflicting reconstructions of abducted and adducted posture are based on mutually-incompatible interpretations of ambiguous osteology. We reconstruct the pectoral limb of the Triassic non-mammalian cynodontMassetognathus pascualiin three dimensions, by combining skeletal morphology from micro-computed tomography with muscle anatomy from an extended extant phylogenetic bracket. Conservative tests of maximum range of motion suggest a degree of girdle mobility, as well as substantial freedom at the shoulder and the elbow joints. The glenoid fossa supports a neutral pose in which the distal end of the humerus points 45° posterolaterally from the body wall, intermediate between classically “sprawling” and “parasagittal” limb postures.Massetognathusis reconstructed as having a near-mammalian complement of shoulder muscles, including an incipient rotator cuff (m. subscapularis, m. infraspinatus, m. supraspinatus, and m. teres minor). Based on close inspection of the morphology of the glenoid fossa, we hypothesize a posture-driven scenario for the evolution of the therian ball-and-socket shoulder joint. The musculoskeletal reconstruction presented here provides the anatomical scaffolding for more detailed examination of locomotor evolution in the precursors to mammals.
Zinc availability modulates plant growth and immune responses viaAZI1
Authors: Bouain Nadia , Satbhai Santosh B. , Saenchai Chorpet , Desbrosses Guilhem , Berthomieu Pierre , Busch Wolfgang , Rouached Hatem
Published: July 2017

Zinc is an essential micronutrient for all living organisms and is involved in a plethora of processes including growth and development, and immunity. However, it is unknown if there is a common genetic and molecular basis underlying multiple facets of zinc function. Here we used natural variation inArabidopsis thalianato study the role of zinc in regulating growth. We identify allelic variation of the systemic immunity geneAZI1as a key for determining root growth responses to low zinc conditions. We further demonstrate that this gene is important for modulating root growth depending on the zinc and defence status. Finally, we show that the interaction of the immunity signal azelaic acid and zinc level to regulate root growth is conserved in rice. This work demonstrates that there is a common genetic and molecular basis for multiple zinc dependent processes and that nutrient cues can determine the balance of plant growth and immune responses in plants.
Systematic mapping of chromatin state landscapes during mouse development
Authors: Gorkin David U. , Barozzi Iros , Zhang Yanxiao , Lee Ah Young , Li Bin , Zhao Yuan , Wildberg Andre , Ding Bo , Zhang Bo , Wang Mengchi , Strattan J. Seth , Davidson Jean M. , Qiu Yunjiang , Afzal Veena , Akiyama Jennifer A. , Plajzer-Frick Ingrid , Pickle Catherine S. , Kato Momoe , Garvin Tyler H. , Pham Quan T. , Harrington Anne N. , Mannion Brandon J. , Lee Elizabeth A. , Fukuda-Yuzawa Yoko , He Yupeng , Preissl Sebastian , Chee Sora , Williams Brian A. , Trout Diane , Amrhein Henry , Yang Hongbo , Cherry J. Michael , Shen Yin , Ecker Joseph R. , Wang Wei , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Ren Bing
Published: July 2017

Embryogenesis requires epigenetic information that allows each cell to respond appropriately to developmental cues. Histone modifications are core components of a cell’s epigenome, giving rise to chromatin states that modulate genome function. Here, we systematically profile histone modifications in a diverse panel of mouse tissues at 8 developmental stages from 10.5 days post conception until birth, performing a total of 1,128 ChIP-seq assays across 72 distinct tissue-stages. We combine these histone modification profiles into a unified set of chromatin state annotations, and track their activity across developmental time and space. Through integrative analysis we identify dynamic enhancers, reveal key transcriptional regulators, and characterize the role of chromatin-based repression in developmental gene regulation. We also leverage these data to link enhancers to putative target genes, revealing connections between coding and non-coding sequence variation in disease etiology. Our study provides a compendium of resources for biomedical researchers, and achieves the most comprehensive view of embryonic chromatin states to date.
Asymmetric compression of representational space for object animacy categorization under degraded viewing conditions
Authors: Grootswagers Tijl , Ritchie J. Brendan , Wardle Susan G. , Heathcote Andrew , Carlson Thomas A.
Published: July 2017

Animacy is a robust organizing principle amongst object category representations in the human brain. Using multivariate pattern analysis methods (MVPA), it has been shown that distance to the decision boundary of a classifier trained to discriminate neural activation patterns for animate and inanimate objects correlates with observer reaction times for the same animacy categorization task (Carlson, Ritchie, Kriegeskorte, Durvasula, & Ma, 2014; Ritchie, Tovar, & Carlson, 2015). Using MEG decoding, we tested if the same relationship holds when a stimulus manipulation (degradation) increases task difficulty, which we predicted would systematically decrease the distance of activation patterns from the decision boundary, and increase reaction times. In addition, we tested whether distance to the classifier boundary correlates with drift rates in the Linear Ballistic Accumulator (Brown & Heathcote, 2008). We found that distance to the classifier boundary correlated with reaction time, accuracy, and drift rates in an animacy categorization task. Split by animacy, the correlations between brain and behavior were sustained for longer over the time course for animate than for inanimate stimuli. Interestingly, when examining the distance to the classifier boundary during the peak correlation between brain and behavior, we found that only degraded versions of animate, but not inanimate, objects had systematically shifted towards the classifier decision boundary as predicted. Our results support an asymmetry in the representation of animate and inanimate object categories in the human brain.
Screening and directed evolution of transporters to improve xylodextrin utilization in the yeastSaccharomyces cerevisiae
Authors: Zhang Chenlu , Acosta-Sampson Ligia , Yu Vivian Yaci , Cate Jamie H. D.
Published: July 2017

The economic production of cellulosic biofuel requires efficient and full utilization of all abundant carbohydrates naturally released from plant biomass by enzyme cocktails. Recently, we reconstituted theNeurospora crassaxylodextrin transport and consumption system inSaccharomyces cerevisiae, enabling growth of yeast on xylodextrins aerobically. However, the consumption rate of xylodextrin requires improvement for industrial applications, including consumption in anaerobic conditions. As a first step in this improvement, we report analysis of orthologues of theN. crassatransporters CDT-1 and CDT-2. Transporter ST16 fromTrichoderma virensenables faster aerobic growth ofS. cerevisiaeon xylodextrins compared to CDT-2. ST16 is a xylodextrin-specific transporter, and the xylobiose transport activity of ST16 is not inhibited by cellobiose. Other transporters identified in the screen also enable growth on xylodextrins including xylotriose. Taken together, these results indicate that multiple transporters might prove useful to improve xylodextrin utilization inS. cerevisiae. Efforts to use directed evolution to improve ST16 from a chromosomally-integrated copy were not successful, due to background growth of yeast on other carbon sources present in the selection medium. Future experiments will require increasing the baseline growth rate of the yeast population on xylodextrins, to ensure that the selective pressure exerted on xylodextrin transport can lead to isolation of improved xylodextrin transporters.
RECoN: Rice Environment Coexpression Network for Systems Level Analysis of Abiotic-Stress Response
Authors: Krishnan Arjun , Gupta Chirag , Ambavaram Madana M.R. , Pereira Andy
Published: July 2017

Transcriptional profiling is a prevalent and powerful approach for capturing the response of crop plants to environmental stresses, e.g. response of rice to drought. However, functionally interpreting the resulting genome-wide gene expression changes is severely hampered by the large gaps in our genomic knowledge about which genes work together in cellular pathways/processes in rice. Here, we present a new web resource – RECoN – that relies on a network-based approach to go beyond currently limited annotations in delineating functional and regulatory perturbations in new rice stress transcriptome datasets generated by a researcher. To build RECoN, we first enumerated 1,744 stress-specific gene modules covering 28,421 rice genes (>72% of the genes in the genome). Each module contains a group of genes tightly coexpressed across a large number of environmental conditions and, thus, is likely to be functionally coherent. When a user provides a new differential expression profile, RECoN identifies modules substantially perturbed in their experiment and further suggests deregulated functional and regulatory mechanisms based on the enrichment of current annotations within the predefined modules. We demonstrate the utility of this resource by analyzing new drought transcriptomes of rice in three developmental stages, which revealed large-scale insights into the cellular processes and regulatory mechanisms involved in common and stage-specific drought responses. RECoN enables biologists to functionally explore new data from all abiotic stresses on a genome-scale and to uncover gene candidates, including those that are currently functionally uncharacterized, for engineering stress tolerance.
Progesterone regulates hypothalamic-pituitary-thyroid axis
Authors: Zhong Chunyun , Xiong Kewen , Wang Xin
Published: July 2017

Progesterone is a natural steroid hormone excreted by animals and humans, which has been frequently detected in the aquatic ecosystems. The effects of the residual progesterone on fish are unclear. In this study, we aimed to examine the effects of progesterone on the hypothalamic-pituitary-thyroid (HPT) axis by detecting the gene transcriptional expression levels. Zebrafish embryos were treated with different concentrations of progesterone from 12 hours post-fertilization (hpf) to 120 hpf. Total mRNA was extracted and the transcriptional profiles of genes involved in HPT axis were examined using qPCR. The genes related to thyroid hormone metabolism and thyroid hormone synthesis were up-regulated in zebrafish exposed to progesterone. These results indicated that progesterone affected the mRNA expression of genes involved in the HPT axis, which might interrupt the endocrine system in zebrafish. Our data also suggested that zebrafish is a useful tool for evaluating the effects of chemicals on the thyroid endocrine system.
Varying-Censoring Aware Matrix Factorization for Single Cell RNA-Sequencing
Authors: Townes F. William , Hicks Stephanie C. , Aryee Martin J. , Irizarry Rafael A.
Published: July 2017

Single cell RNA-Seq (scRNA-Seq) has become the most widely used high-throughput technology for gene expression profiling of individual cells. The potential of being able to measure cell-to-cell variability at a high-dimensional genomic scale opens numerous new lines of investigation in basic and clinical research. For example, by identifying groups of cells with expression profiles unlike those observed in cells with known phenotypes, new cell types may be discovered. Dimension reduction followed by unsupervised clustering are the quantitative approaches typically used to facilitate such discoveries. However, a challenge for this approach is that most scRNA-Seq datasets are sparse, with the percentages of measurements reported as zero ranging from 35% to 99% across cells, and these zeros are partially explained by experimental inefficiencies that lead to censored data. Furthermore, the observed across-cell differences in the percentages of zeros are partly due to technical artifacts rather than biological differences. Unfortunately, standard dimension reduction approaches treat these censored values as true zeros, which leads to the identification of distorted low-dimensional factors. When these factors are used for clustering, the distortion leads to incorrect identification of biological groups. Here, we propose an approach that accounts for cell-specific censoring with a varying-censoring aware matrix factorization (VAMF) model that permits the identification of factors in the presence of the above described systematic bias. We demonstrate the advantages of our approach on published scRNA-Seq data and confirm these on simulated data.
A Modular Photosynthetic Microbial Fuel Cell With Interchangeable Algae Solar Compartments
Authors: Fleury Daniel
Published: July 2017

This project trial provides a novel small-scale solar harnessing technology which increases environmental effectiveness while maintaining optimal energy efficiency. Although modern solar panels are purposed in producing clean energy, the materials and byproducts of solar cell manufacturing are not eco-friendly. Thus, considering an organic, renewable and energy efficient solar cell model is necessary. Investigations explored multiple highly-photosynthetic algal species which were later integrated into a controlled microbial fuel cell system (MFC). The MFC1 contained algae culture species, including Chlorella Vulgaris, Nannochloropsis, and Spirulina. Parameters, such as periodic lipid yields, algal biomass, and light absorption were assessed throughout the cultivation process while maintaining a controlled environment. After 30 days of cultivation, the culture was transferred to an anode chamber in a closed loop small-scale MFC. Following the first day of algae transfer, microwatt output was analyzed from independent test trials. Statistical comparisons were drawn between electrical energy and light absorption, finding a generally positive correlation. Thus, it is concluded that mid-high algae concentrations significantly increased electrical micro-wattage in highly absorptive algal cultures. The optimal electric levels occurred at 286 A (absorbance) and 35 mW-Nannochloropsis, 123 A-Chlorella (30.2 mW), and 142 A (31 mW)-Spirulina culture. Due to higher absorption rates in the Nannochloropsis culture, this corresponds with the record high voltage levels. The analysis of data indicates that Algae-based MFCs are proven hopeful for alternative high-yield energy production.
Competition for synaptic building blocks shapes synaptic plasticity
Authors: Triesch Jochen , Vo Anh Duong , Hafner Anne-Sophie
Published: July 2017

Changes in the efficacies of synapses are thought to be the neurobiological basis of learning and memory. The efficacy of a synapse depends on its current number of neurotransmitter receptors. Recent experiments have shown that these receptors are highly dynamic, moving back and forth between synapses on time scales of seconds and minutes. This suggests spontaneous fluctuations in synaptic efficacies and a competition of nearby synapses for available receptors. Here we propose a mathematical model of this competition of synapses for neurotransmitter receptors from a local dendritic pool. Using minimal assumptions, the model produces a fast multiplicative scaling behavior of synapses. Furthermore, the model explains a transient form of heterosynaptic plasticity and predicts that its amount is inversely related to the size of the local receptor pool. Overall, our model reveals logistical tradeoffs during the induction of synaptic plasticity due to the rapid exchange of neurotransmitter receptors between synapses.
De NovoGenes are “Frozen Accidents” which Escaped Rapid Turnover of Pervasively Transcribed ORFs
Authors: Schmitz Jonathan , Ullrich Kristian , Bornberg-Bauer Erich
Published: July 2017

A recent surge of studies suggested that many novel genes arisede novofrom previously non-coding DNA and not by duplication. However, since most studies concentrated on longer evolutionary time scales and rarely considered protein structural properties, it remains unclear how these properties are shaped by evolution, depend on genetic mechanisms and influence gene survival. Here we compare open reading frames (ORFs) from high coverage transcriptomes from mouse and another four mammals covering 160 million years of evolution. We find that novel ORFs pervasively emerge from intergenic and intronic regions but are rapidly lost again while relatively fewer arise from duplications but are retained over much longer times. Surprisingly, disorder and other protein properties of young ORFs do not change with gene age. Only length and nucleotide composition change, probably to avoid aggregation. Thus de novo genes resemble frozen accidents of randomly emerged ORFs which survived initial purging, likely because they are functional.
BGP: Branched Gaussian processes for identifying gene-specific branching dynamics in single cell data
Authors: Boukouvalas Alexis , Hensman James , Rattray Magnus
Published: July 2017

High-throughput single-cell gene expression experiments can be used to uncover branching dynamics in cell populations undergoing differentiation through use of pseudotime methods. We develop the branching Gaussian process (BGP), a non-parametric model that is able to identify branching dynamics for individual genes and provides an estimate of branching times for each gene with an associated credible region. We demonstrate the effectiveness of our method on both synthetic data and a published single-cell gene expression hematopoiesis study. The method requires prior information about pseudotime and global cellular branching for each cell but the probabilistic nature of the method means that it is robust to errors in these global branch labels and can be used to discover early branching genes which diverge before the inferred global cell branching. The code is open-source and available at https://github.com/ManchesterBioinference/BranchedGP.
Biomass increase under zinc deficiency caused by delay of early flowering in Arabidopsis
Authors: Chen Xiaochao , Ludewig Uwe
Published: July 2017

Plants generally produce more biomass when all nutrients are available in sufficient amounts. In addition to environmental constraints, genetic and developmental factors, such as the transition from vegetative to reproductive growth, restrict maximal yield. Here we report the peculiar observation that a subset of early flowering Arabidopsis thaliana accessions produced larger shoot rosette diameters when grown in zinc (Zn)-deficient conditions, compared with Zn-sufficient conditions. This was associated with early flowering that restricted the leaf length under Zn sufficiency. Zinc deficiency repressed FLOWERING LOCUS T (FT) expression, a major regulator of flowering. Repression or loss of FT increased the rosette diameter by a delay of the transition to flowering, a longer phase of leaf proliferation and increased leaf number. The transition to flowering reduced, but not terminated, the proliferation of established leaves. The size of individual leaf mesophyll cells was not affected by Zn deficiency or loss of FT, indicating that the larger rosette diameter was caused by maintained proliferation of vegetative tissue. As a consequence, early flowering accessions under Zn deficiency grew larger rosette diameters due to a delay of flowering, which explains the unusual increase of vegetative biomass under nutrient deficiency.

Highlight

An increase in biomass of some Arabidopsis accessions under Zn-deficiency is caused by retardation of flowering, prolonging vegetative growth.

Abbreviations

DAS

days after sowing

GWA

genome-wide association

SNP

single nucleotide polymorphism

Zn

zinc
Persistent patterns of high alpha and low beta diversity in tropical parasitic and free-living protists
Authors: Lentendu Guillaume , Mahé Frédéric , Bass David , Rueckert Sonja , Stoeck Thorsten , Dunthorn Micah
Published: July 2017

Animal and plant communities in tropical rainforests are known to have high alpha diversity within forests, but low beta diversity between forests. By contrast, it is unknown if the microbial protists inhabiting the same ecosystems exhibit similar biogeographic patterns. To evaluate the biogeographies of soil protists in three lowland Neotropical rainforests using metabarcoding data, we estimated taxa-area and distance-decay relationships for three large protist taxa and their subtaxa, at both the OTU and phylogenetic levels, with presence-absence and abundance based measures, and compared the estimates to null models. High local alpha and low regional beta diversity patterns were persistently found for both the parasitic Apicomplexa and the free-living Cercozoa and Ciliophora, even though they have different ecological functions and different dispersal modes. In comparison to the null models, both OTU and phylogenetic diversities showed spatial structures between forests, but only phylogenetic diversity showed spatial patterns within forests. These results suggest that the biogeographies of macro-and micro-organismal eukaryotes in lowland Neotropical rainforests are partially structured by the same general processes. As with arthropods, the protists’ high alpha diversity within forests presents problems for estimating their local diversity, and shows that regional diversity cannot be easily estimated because of low turnover between forests.
Large scalein vivorecording of sensory neuron activity with GCaMP6
Authors: Chisholm Kim I , Khovanov Nikita , Lopes Douglas M , La Russa Federica , McMahon Stephen B
Published: July 2017

Greater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging in the central nervous system, while the peripheral system remains largely unexplored. To assess large networks of sensory neurons we selectively label primary afferents with GCaMP6s and visualise their functional responsesin vivoto peripheral stimulation. We show that we are able to monitor simultaneously the activity of hundreds of sensory neurons with sensitivity sufficient to detect, in most cases, single action potentials with a typical rise time of around 200 milliseconds, and an exponential decay with a time constant of approximately 700 milliseconds. Using this sensitive technique we are able to show that large scale recordings demonstrate the recently disputed polymodality of nociceptive primary afferents with between 40-80% of thermally sensitive DRG neurons responding also to noxious mechanical stimulation. We also specifically assess the small population of peripheral cold fibres and demonstrate significant sensitisation to cooling after a model of sterile and persistent inflammation, with significantly increased sensitivity already at decreases of 5°C when compared to uninflamed responses. This not only reveals interesting new insights into the (patho)physiology of the peripheral nervous system but also demonstrates the sensitivity of this imaging technique to physiological changes in primary afferents.

Significance Statement

Most of our functional understanding of the peripheral nervous system has come from single unit recordings. However, the acquisition of such data is labour-intensive and usually ‘low yield’. Moreover, some questions are best addressed by studying populations of neurons. To this end we report on a system that monitors activity in hundreds of single sensory neurons simultaneously, with sufficient sensitivity to detect in most cases single action potentials. We use this technique to characterise nociceptor properties and demonstrate polymodality in the majority of neurons and their sensitization under inflammatory conditions. We therefore believe this approach will be very useful for the studies of the somatosensory system in general and pain in particular.