bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPGAN v2: Machine Learning Guided Design of Antimicrobial Peptides
Authors: Van Oort Colin M. , Ferrell Jonathon B. , Remington Jacob M. , Wshah Safwan , Li Jianing 
Published: November 2020

AbstractAntibiotic resistance is a critical public health problem. Each year ~2.8 million resistant infections lead to more than 35,000 deaths in the U.S. alone. Antimicrobial peptides (AMPs) show promise in treating resistant infections. However, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the development of AMP-based treatments it is necessary to create design approaches with higher precision and selectivity towards resistant targets.Previously we developed AMPGAN and obtained proof-of-concept evidence for the generative approach to design AMPs with experimental validation. Building on the success of AMPGAN, we present AMPGAN v2 a bidirectional conditional generative adversarial network (BiCGAN) based approach for rational AMP design. AMPGAN v2 uses generator-discriminator dynamics to learn data driven priors and controls generation using conditioning variables. The bidirectional component, implemented using a learned encoder to map data samples into the latent space of the generator, aids iterative manipulation of candidate peptides. These elements allow AMPGAN v2 to generate of candidates that are novel, diverse, and tailored for specific applications—making it an efficient AMP design tool.
Cas12a-Capture: a novel, low-cost, and scalable method for targeted sequencing
Authors: Mighell Taylor L. , Nishida Andrew , O’Connell Brendan L. , Miller Caitlin V. , Grindstaff Sally , Thornton Casey A. , Adey Andrew C. , Doherty Daniel , O’Roak Brian J. 
Published: November 2020

AbstractTargeted sequencing remains a valuable technique for clinical and research applications. However, many existing technologies suffer from pervasive GC sequence content bias, high input DNA requirements, and high cost for custom panels. We have developed Cas12a-Capture, a low-cost and highly scalable method for targeted sequencing. The method utilizes preprogramed guide RNAs to direct CRISPR-Cas12a cleavage of double stranded DNAin vitroand then takes advantage of the resulting four to five nucleotide overhangs for selective ligation with a custom sequencing adapter. Addition of a second sequencing adapter and enrichment for ligation products generates a targeted sequence library. We first performed a pilot experiment with 7,176 guides targeting 3.5 megabases of DNA. Using these data, we modeled the sequence determinants of Cas12a-Capture efficiency, then designed an optimized set of 11,438 guides targeting 3.0 megabases. The optimized guide set achieves an average 64-fold enrichment of targeted regions with minimal GC bias. Cas12a-Capture variant calls had strong concordance with Illumina Platinum Genome calls, especially for SNVs, which could be improved by applying basic variant quality heuristics. We believe Cas12a-Capture has a wide variety of potential clinical and research applications and is amendable for selective enrichment for any double stranded DNA template or genome.
Taxonomic sampling and rare genomic changes overcome long-branch attraction in the phylogenetic placement of pseudoscorpions
Authors: Ontano Andrew Z. , Gainett Guilherme , Aharon Shlomi , Ballesteros Jesús A. , Benavides Ligia R. , Corbett Kevin F. , Gavish-Regev Efrat , Harvey Mark S. , Monsma Scott , Santibáñez-López Carlos E. , Setton Emily V.W. , Zehms Jakob T. , Zeh Jeanne A. , Zeh David W. , Sharma Prashant P. 
Published: November 2020

AbstractLong-branch attraction is a systematic artifact that results in erroneous groupings of fast-evolving taxa. The combination of short, deep internodes in tandem with LBA artifacts has produced empirically intractable parts of the Tree of Life. One such group is the arthropod subphylum Chelicerata, whose backbone phylogeny has remained unstable despite improvements in phylogenetic methods and genome-scale datasets. Pseudoscorpion placement is particularly variable across datasets and analytical frameworks, with this group either clustering with other long-branch orders or with Arachnopulmonata (scorpions and tetrapulmonates). To surmount LBA, we investigated the effect of taxonomic sampling via sequential deletion of basally branching pseudoscorpion superfamilies, as well as varying gene occupancy thresholds in supermatrices. We show that concatenated supermatrices and coalescent-based summary species tree approaches support a sister group relationship of pseudoscorpions and scorpions, when more of the basally branching taxa are sampled. Matrix completeness had demonstrably less influence on tree topology. As an external arbiter of phylogenetic placement, we leveraged the recent discovery of an ancient genome duplication in the common ancestor of Arachnopulmonata as a litmus test for competing hypotheses of pseudoscorpion relationships. We generated a high-quality developmental transcriptome and the first genome for pseudoscorpions to assess the incidence of arachnopulmonate-specific duplications (e.g., homeobox genes and miRNAs). Our results support the inclusion of pseudoscorpions in Arachnopulmonata, as the sister group of scorpions. Panscorpiones (new name) is proposed for the clade uniting Scorpiones and Pseudoscorpiones.
Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin
Authors: Elleman Anna V. , Devienne Gabrielle , Makinson Christopher D. , Haynes Allison L. , Huguenard John R. , Du Bois J. 
Published: November 2020

SummaryHere we report the pharmacologic blockade of voltage-gated sodium ion channels (NaV) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaV blockade to interrupt action potentials (APs) in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of NaVs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to NaV-dependent alterations in AP propagation, with unmyelinated axons preferentially showing reduced AP fidelity under conditions of partial NaV blockade. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and AP generation.
Recurrent circuit based neural population codes for stimulus representation and inference
Authors: Zhang Wen-Hao , Wu Si , Josić Krešimir , Doiron Brent 
Published: November 2020

AbstractA large part of the synaptic input received by cortical neurons comes from local cortico-cortical connectivity. Despite their abundance, the role of local recurrent connections in cortical function is unclear, and in simple coding schemes it is often the case that a circuit with no recurrent connections performs optimally. We consider a recurrent excitatory-inhibitory circuit model of a cortical hypercolumn which performs sampling-based Bayesian inference to infer latent hierarchical stimulus features. We show that local recurrent connections can store an internal model of the correlations between stimulus features that are present in the external world. When the resulting recurrent input is combined with feedforward input it produces a population code from which the posterior over the stimulus features can be linearly read out. Internal Poisson spiking variability provides the proper fluctuations for the population to sample stimulus features, yet the resultant population variability is aligned along the stimulus feature direction, producingdifferential correlations. Importantly, the amplitude of these internally generated differential correlations is determined by the associative prior in the model stored in the recurrent connections. This provides experimentally testable predictions for how population connectivity and response variability are related to the structure of latent external stimuli.
Two new hybrid zones expand the swordtail hybridization model system
Authors: Powell Daniel L. , Moran Ben , Kim Bernard , Banerjee Shreya M. , Aguillon Stepfanie M. , Fascinetto-Zago Paola , Langdon Quinn , Schumer Molly 
Published: November 2020

AbstractNatural hybridization events provide unique windows into the barriers that keep species apart as well as the consequences of their breakdown. Here we characterize hybrid populations formed between the northern swordtail fishXiphophorus corteziandX. birchmannifrom collection sites on two rivers. We develop sensitive and accurate local ancestry calling for this system based on low coverage whole genome sequencing. Strikingly, we find that hybrid populations on both rivers consist of two genetically distinct subpopulations: a cluster of nearly pureX. birchmanniindividuals and one of phenotypically intermediate hybrids that derive ~85-90% of their genome fromX. cortezi. Simulations and empirical data suggest that at both sites initial hybridization occurred ~150 generations ago, with little evidence for contemporary gene flow between subpopulations, likely due to strong assortative mating. The patterns of population structure uncovered here mirror those seen in hybridization betweenX. birchmanniand its sister species,X. malinche. Future comparisons will provide a window into the repeatability of the outcomes of hybridization not only across independent hybridization events between the same species but also across distinct species pairs.
Pupil dilation predicts individual success in emotion regulation and dietary self-control
Authors: Maier Silvia , Grueschow Marcus 
Published: November 2020

AbstractMultiple theories have proposed that increasing central arousal through the brain’s locus coeruleus – norepinephrine system may facilitate cognitive control and memory. However, for emotion research this hypothesis poses a puzzle, because conventionally, successful emotion regulation is associated with a decrease in arousal.Pupil diameter is a proxy to infer upon the central arousal state. We employed an emotion regulation paradigm with a combination of design features that allowed us to dissociate regulation- from stimulus-associated arousal in the pupil diameter time course of healthy adults. A pupil diameter increase during regulation predicted individual differences in emotion regulation success beyond task difficulty. Moreover, the extent of this individual arousal boost predicted performance in another self-control task, dietary health challenges. Participants who harnessed more regulation-associated arousal during emotion regulation were also more successful in choosing healthier foods. These results suggest that a common arousal-based facilitation mechanism may support an individual’s self-control across domains.
Mapping the common and distinct neural correlates of visual, rule and motor conflict
Authors: Mew Bryony Goulding , Custovic Darije , Soreq Eyal , Lorenz Romy , Violante Ines , Sandrone Stefano , Hampshire Adam 
Published: November 2020

AbstractFlexible behaviour requires cognitive-control mechanisms to efficiently resolve conflict between competing information and alternative actions. Whether a global neural resource mediates all forms of conflict or this is achieved within domainspecific systems remains debated. We use a novel fMRI paradigm to orthogonally manipulate rule, response and stimulus-based conflict within a full-factorial design. Whole-brain voxelwise analyses show that activation patterns associated with these conflict types are distinct but partially overlapping within Multiple Demand Cortex (MDC), the brain regions that are most commonly active during cognitive tasks. Region of interest analysis shows that most MDC sub-regions are activated for all conflict types, but to significantly varying levels. We propose that conflict resolution is an emergent property of distributed brain networks, the functional-anatomical components of which place on a continuous, not categorical, scale from domain-specialised to domain general. MDC brain regions place towards one end of that scale but display considerable functional heterogeneity.
Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation
Authors: Agostinis C. , Zorzet S. , Balduit A. , Zito G. , Mangogna A. , Macor Paolo , Romano F. , Toffoli M. , Belmonte B. , Martorana A. , Borelli V. , Ricci G. , Kishore U. , Bulla R. 
Published: November 2020

AbstractThe pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. This study offers an opportunity for novel therapeutic intervention in EM, a difficult to treat gynecological condition.SummaryC3 produced by the endometriotic tissue is involved in the lesion development through mast cell activation
Paracrine regulation of neural crest EMT by placodal MMP28
Authors: Gouignard Nadège , Bibonne Anne , Mata Joao F , Bajanca Fernanda , Berki Bianka , Barriga Elias H , Saint-Jeannet Jean-Pierre , Theveneau Eric 
Published: November 2020

AbstractEpithelial-Mesenchymal Transition (EMT) is an early event in cell dissemination from epithelial tissues. EMT endows cells with migratory, and sometimes invasive, capabilities and is thus a key process in embryo morphogenesis and cancer progression. So far, Matrix Metalloproteinases (MMPs) have not been considered as key players in EMT but rather studied for their role in matrix remodelling in later events such as cell migrationper se. Here we usedXenopusneural crest cells to assess the role of MMP28 in EMT and migrationin vivo. We provide strong evidence indicating that MMP28 produced by neighbouring placode cells is imported in the nucleus of neural crest cells for EMT and migration to occur.
MR1-restricted MAIT cells from the human lung mucosal surface have distinct phenotypic, functional, and transcriptomic features that are preserved in HIV infection
Authors: Khuzwayo Sharon , Mthembu Maphe , Meermeier Erin W. , Prakadan Sanjay M. , Kazer Samuel W. , Bassett Thierry , Nyamande Kennedy , Khan Dilshaad Fakey , Maharaj Priya , Mitha Mohammed , Suleman Moosa , Mhlane Zoey , Ramjit Dirhona , Karim Farina , Shalek Alex K. , Lewinsohn David M. , Ndung’u Thumbi , Wong Emily B. 
Published: November 2020

AbstractMucosal associated invariant T (MAIT) cells are a class of innate-like T cells that utilize a semi-invariant αβ T cell receptor to recognize small molecule ligands produced by bacteria and fungi. Despite growing evidence that immune cells at mucosal surfaces are often phenotypically and functionally distinct from those in the peripheral circulation, knowledge about the characteristics of MAIT cells at the lung mucosal surface, the site of exposure to respiratory pathogens, is limited. HIV infection has been shown to have a profound effect on the number and function of MAIT cells in the peripheral blood, but its effect on lung mucosal MAIT cells is unknown. We examined the phenotypic, functional, and transcriptomic features of MR1 restricted MAIT cells from the peripheral blood and bronchoalveolar compartments of otherwise healthy individuals with latentMycobacterium tuberculosis (Mtb)infection who were either HIV uninfected or HIV infected. Peripheral blood MAIT cells consistently co-expressed typical MAIT cell surface markers CD161 and CD26 in healthy individuals, while paired bronchoalveolar MAIT cells displayed heterogenous expression of these markers. Bronchoalveolar MAIT cells produced lower levels of pro-inflammatory cytokine IFN-γ and expressed higher levels of co-inhibitory markers PD-1 and TIM-3 than peripheral MAIT cells. HIV infection resulted in decreased frequencies and pro-inflammatory function of peripheral blood MAIT cells, while in the bronchoalveolar compartment MAIT cell frequency was decreased but phenotype and function were not significantly altered. Single-cell transcriptomic analysis demonstrated greater heterogeneity among bronchoalveolar compared to peripheral blood MAIT cells and suggested a distinct subset in the bronchoalveolar compartment. The transcriptional features of this bronchoalveolar subset were associated with atypical MAIT cells and tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in healthy people. In HIV infection, we found numeric depletion of MAIT cells in both anatomical compartments but preservation of the novel phenotypic and transcriptional features of bronchoalveolar MAIT cells.
Dramatic changes in mitochondrial substrate use at critically high temperatures: a comparative study usingDrosophila
Authors: Jørgensen Lisa Bjerregaard , Overgaard Johannes , Hunter-Manseau Florence , Pichaud Nicolas 
Published: November 2020

AbstractEctotherm thermal tolerance is critical to species distribution, but at present the physiological underpinnings of heat tolerance remain poorly understood. Mitochondrial function is perturbed at critically high temperatures in some ectotherms, including insects, suggesting that heat tolerance of these animals is linked to failure of oxidative phosphorylation (OXPHOS) and/or ATP production. To test this hypothesis we measured mitochondrial oxygen consumption rates in sixDrosophilaspecies with different heat tolerance using high-resolution respirometry. Using a substrate-uncoupler-inhibitor titration protocol we examined specific steps of the electron transport system to study how temperatures below, bracketing and above organismal heat limits affected mitochondrial function and substrate oxidation. At benign temperatures (19 and 30°C), complex I-supported respiration (CI-OXPHOS) was the most significant contributor to maximal OXPHOS. At higher temperatures (34, 38, 42 and 46°C), CI-OXPHOS decreased considerably, ultimately to very low levels at 42 and 46°C. The enzymatic catalytic capacity of complex I was intact across all temperatures and accordingly the decreased CI-OXPHOS is unlikely to be caused directly by hyperthermic denaturation/inactivation of complex I. Despite the reduction in CI-OXPHOS, maximal OXPHOS capacities were maintained in all species, through oxidation of alternative substrates; proline, succinate and, particularly, glycerol-3-phosphate, suggesting important mitochondrial flexibility at temperatures exceeding the organismal heat limit. Interestingly, this compensatory oxidation of alternative substrates occurred at temperatures that tended to correlate with species heat tolerance, such that heat-tolerant species could defend “normal” mitochondrial function at higher temperatures than sensitive species. Future studies should investigate why CI-OXPHOS is perturbed and how this potentially affects ATP production rates.
Loss of active neurogenesis in the adult shark retina
Authors: Hernández-Núñez Ismael , Robledo Diego , Mayeur Hélène , Mazan Sylvie , Sánchez Laura , Adrio Fátima , Barreiro-Iglesias Antón , Candal Eva 
Published: November 2020

AbstractNeurogenesis is the process by which progenitor cells generate new neurons. As development progresses neurogenesis becomes restricted to concrete neurogenic niches, where it persists during postnatal life. The retina of teleost fishes is thought to proliferate and produce new cells throughout life. Whether this capacity may be an ancestral characteristic of jawed vertebrates, shared with chondrichthyans, which diverged from osteichthyans prior to the gnathostome radiation is completely unknown. Previous work from our group revealed that the juvenile retina of the catshark Scyliorhinus canicula shows active proliferation and neurogenesis. Here, we compared the morphology and proliferative status of the retina between catshark juveniles and adults. Histological analyses revealed an important reduction in the size of the peripheral retina (where progenitor cells are mainly located), an increase in the thickness of the plexiform layers and a decrease in the thickness of the inner nuclear layer in adults. Contrary to what has been reported in teleost fish, we did not observe active mitotic activity in the catshark retina after sexual maturation, suggesting that there is no significant proliferation and neurogenesis in adult specimens. Based on these results, we carried out RNA-Sequencing (RNA-Seq) analyses comparing the retinal transcriptome of juveniles and adults, which revealed a statistically significant decrease in the expression of many genes involved in cell proliferation and neurogenesis in adult catsharks. Our RNA-Seq data provides an excellent resource to identify new signaling pathways controlling neurogenesis in the vertebrate retina.
TimeCycle: Topology Inspired MEthod for the Detection of Cycling Transcripts in Circadian Time-Series Data
Authors: Ness-Cohn Elan , Braun Rosemary 
Published: November 2020

AbstractMotivationThe circadian rhythm drives the oscillatory expression of thousands of genes across all tissues. The recent revolution in high-throughput transcriptomics, coupled with the significant implications of the circadian clock for human health, has sparked an interest in circadian profiling studies to discover genes under circadian control.ResultWe present TimeCycle: a topology-based rhythm detection method designed to identify cycling transcripts. For a given time-series, the method reconstructs the state space using time-delay embedding, a data transformation technique from dynamical systems theory. In the embedded space, Takens’ theorem proves that the dynamics of a rhythmic signal will exhibit circular patterns. The degree of circularity of the embedding is calculated as a persistence score using persistent homology, an algebraic method for discerning the topological features of data. By comparing the persistence scores to a bootstrapped null distribution, cycling genes are identified. Results in both synthetic and biological data highlight Time-Cycle’s ability to identify cycling genes across a range of sampling schemes, number of replicates, and missing data. Comparison to competing methods highlights their relative strengths, providing guidance as to the optimal choice of cycling detection method.Availability and ImplementationA fully documented open-source R package implementing Time-Cycle is available at:https://nesscoder.github.io/TimeCycle/.
Deep neural network models reveal interplay of peripheral coding and stimulus statistics in pitch perception
Authors: Saddler Mark R. , Gonzalez Ray , McDermott Josh H. 
Published: November 2020

ABSTRACTPerception is thought to be shaped by the environments for which organisms are optimized. These influences are difficult to test in biological organisms but may be revealed by machine perceptual systems optimized under different conditions. We investigated environmental and physiological influences on pitch perception, whose properties are commonly linked to peripheral neural coding limits. We first trained artificial neural networks to estimate fundamental frequency from biologically faithful cochlear representations of natural sounds. The best-performing networks replicated many characteristics of human pitch judgments. To probe the origins of these characteristics, we then optimized networks given altered cochleae or sound statistics. Human-like behavior emerged only when cochleae had high temporal fidelity and when models were optimized for naturalistic sounds. The results suggest pitch perception is critically shaped by the constraints of natural environments in addition to those of the cochlea, illustrating the use of artificial neural networks to reveal underpinnings of behavior.