bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient storage and analysis of quantitative genomics data with the Dense Depth Data Dump (D4) format and d4tools
Authors: Hou Hao , Pedersen Brent , Quinlan Aaron 
Published: October 2020

AbstractModern DNA sequencing is used as a readout for diverse assays, with the count of aligned sequences, or “read depth”, serving as the quantitative signal for many underlying cellular phenomena. Despite wide use and thousands of datasets, existing formats used for the storage and analysis of read depths are limited with respect to both file size and analysis speed. For example, it is faster to recalculate sequencing depth from an alignment file than it is to analyze the text output from that calculation. We sought to improve on existing formats such as BigWig and compressed BED files by creating the Dense Depth Data Dump (D4) format and tool suite. The D4 format is adaptive in that it profiles a random sample of aligned sequence depth from the input BAM or CRAM file to determine an optimal encoding that often affords reductions in file size, while also enabling fast data access. We show that D4 uses less storage for both RNA-Seq and whole-genome sequencing and offers 3 to 440-fold speed improvements over existing formats for random access, aggregation and summarization. This performance enables scalable downstream analyses that would be otherwise difficult. The D4 tool suite (d4tools) is freely available under an MIT license at:https://github.com/38/d4-format.
Shortfalls and opportunities in terrestrial vertebrate species discovery
Authors: Moura Mario R. , Jetz Walter 
Published: October 2020

AbstractMeter-resolution imagery of our world and myriad biodiversity records collected through citizen scientists and automated sensors belie the fact that much of the planet’s biodiversity remains undiscovered. Conservative estimates suggest only 13 to 18% of all living species may be known at this point1–4, although this number could be as low as 1.5%5. This biodiversity shortfall6,7strongly impedes the sustainable management of our planet’s resources, as the potential ecological and economic relevance of undiscovered species remains unrecognized8. Here we use model-based predictions of terrestrial vertebrate species discovery to estimate future taxonomic and geographic discovery opportunities. Our model identifies distinct taxonomic and geographic unevenness in future discovery potential, with greatest opportunities for amphibians and reptiles and for Neotropical and IndoMalayan forests. Brazil, Indonesia, Madagascar, and Colombia emerge as holding greatest discovery opportunities, with a quarter of future species descriptions expected there. These findings highlight the significance of international support for taxonomic initiatives and the potential of quantitative models to aid the discovery of species before their functions are lost in ignorance8. As nations draw up new policy goals under the post-2020 global biodiversity framework, a better understanding of the magnitude and geography of this known unknown is critical to inform goals and priorities9and to minimize future discoveries lost to extinction10.
Target lipidomics reveals associations between serum sphingolipids and insulin sensitivity by the glucose clamp
Authors: Ye Jingya , Ye Xuan , Jiang Wanzi , Lu Chenyan , Geng Xiaomei , Zhao Chenxi , Ma Yizhe , Yang Panpan , Lam Sin Man , Shui Guanghou , Yang Tao , Li John Zhong , Gong Yingyun , Fu Zhenzhen , Zhou Hongwen 
Published: October 2020

AbstractBackgroundThis study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity.ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria.ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.
Machine Learning Framework for Fully Automatic Quality Checking of Rigid and Affine Registrations in Big Data Brain MRI
Authors: Tummala Sudhakar , Focke Niels K. 
Published: October 2020

ABSTRACTRigid and affine registrations to a common template are the essential steps during pre-processing of brain structural magnetic resonance imaging (MRI) data. Manual quality check (QC) of these registrations is quite tedious if the data contains several thousands of images. Therefore, we propose a machine learning (ML) framework for fully automatic QC of these registrations via local computation of the similarity functions such as normalized cross-correlation, normalized mutual-information, and correlation ratio, and using these as features for training of different ML classifiers. To facilitate supervised learning, misaligned images are generated. A structural MRI dataset consisting of 215 subjects from autism brain imaging data exchange is used for 5-fold cross-validation and testing. Few classifiers such askNN,AdaBoost, andrandom forestreached testing F1-scores of 0.98 for QC of both rigid and affine registrations. These tested ML models could be deployed for practical use.
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model
Authors: Errecalde J. , Lifschitz A. , Vecchioli G. , Ceballos L. , Errecalde F. , Ballent M. , Marín G. , Daniele M. , Turic E. , Spitzer E. , Toneguzzo F. , Gold S. , Krolewiecki A. , Alvarez L. , Lanusse C. 
Published: October 2020

AbstractHigh ivermectin (IVM) concentrations suppressin vitroSARS-CoV-2 replication. Nasal IVM spray (N-IVM-spray) administration may contribute to attaining high drug concentrations in nasopharyngeal (NP) tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performance of a new N-IVM spray formulation in a piglet model were assessed. Crossbred piglets (10–12 kg) were treated with either one or two (12 h apart) doses of N-IVM-spray (2 mg, 1 puff/nostril) or orally (0.2 mg/kg). The overall safety of N-IVM-spray was assessed (clinical, haematological, serum biochemical determinations), and histopathology evaluation of the application site tissues performed. The IVM concentration profiles measured in plasma and respiratory tract tissues (nasopharynx and lungs) after the nasal spray treatment (one and two applications) were compared with those achieved after the oral administration. Animals tolerated well the novel N–IVM-spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in NP and lung tissues. Significant increases in IVM concentration profiles in both NP-tissue and lungs were observed after the 2-dose nasal administrations. The nasal/oral IVM concentration ratios in NP and lung tissues (at 6 h post-dose) markedely increased by repeating the spray application. The fast attainment of high and persistent IVM concentrations in NP tissue is the main advantage of the nasal over the oral route. These original results are encouraging to support the undertaking of further clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the treatment and/or prevention of COVID-19.
Robust Cortical Criticality and Diverse Neural Network Dynamics Resulting from Functional Specification
Authors: Gu Lei , Wu Ruqian 
Published: October 2020

AbstractDespite recognized layered structure and increasing evidence for criticality in the cortex, how the specification of input, output and computational layers affects the self-organized criticality has been surprisingly neglected. By constructing heterogeneous structures with a well-accepted model of leaky neurons, we found that the specification can lead to robust criticality almost insensitive to the strength of external stimuli. This naturally unifies the adaptation to strong inputs without extra synaptic plasticity mechanisms. Presence of output neurons constitutes an alternative explanation to subcriticality other than the high frequency inputs.Degree of recurrenceis proposed as a network metric to account for the signal termination due to output neurons. Unlike fully recurrent networks where external stimuli always render subcriticality, the dynamics of networks with sufficient feed-forward connections can be driven to criticality and supercriticality. These findings indicate that functional and structural specification and their interplay with external stimuli are of crucial importance for the network dynamics. The robust criticality puts forward networks of the leaky neurons as a promising platform for realizing artificial neural networks that work in the vicinity of critical points.
Cortical Responses to the Amplitude Envelopes of Sounds Change with Age
Authors: Irsik Vanessa C. , Almanaseer Ala , Johnsrude Ingrid S. , Herrmann Björn 
Published: October 2020

AbstractMany older listeners have difficulty understanding speech in noise, when cues to speech-sound identity are less redundant. The amplitude envelope of speech fluctuates dramatically over time, and features such as the rate of amplitude change at onsets (attack) and offsets (decay) signal critical information about the identity of speech sounds. Aging is also thought to be accompanied by increases in cortical excitability, which may differentially alter sensitivity to envelope dynamics. Here, we recorded electroencephalography in younger and older human adults (of both sexes) to investigate how aging affects neural synchronization to 4-Hz amplitude-modulated noises with different envelope shapes(ramped:slow attack & sharp decay;damped:sharp attack & slow decay). We observed that subcortical responses did not differ between age groups, whereas older compared to younger adults exhibited larger cortical responses to sound onsets, consistent with an increase in auditory cortical excitability. Neural activity in older adults synchronized more strongly with rapid-onset, slow-offset (damped) envelopes, was less sinusoidal, and more peaked. Younger adults demonstrated the opposite pattern, showing stronger synchronization with slow-onset, rapid-offset (ramped) envelopes, as well as a more sinusoidal neural response shape. The current results suggest that age-related changes in the excitability of auditory cortex alter responses to envelope dynamics. This may be part of the reason why older adults experience difficulty understanding speech in noise.Significance StatementMany middle aged and older adults report difficulty understanding speech when there is background noise, which can trigger social withdrawal and negative psychosocial health outcomes. The difficulty may be related to age-related changes in how the brain processes temporal sound features. We tested younger and older people on their sensitivity to different envelope shapes, using EEG. Our results demonstrate that aging is associated with heightened sensitivity to sounds with a sharp attack and gradual decay, and sharper neural responses that deviate from the sinusoidal features of the stimulus, perhaps reflecting increased excitability in the aged auditory cortex. Altered responses to temporal sound features may be part of the reason why older adults often experience difficulty understanding speech in social situations.
N-myristoyltransferase: Tracing Steps Backwards to Find a Way Forward
Authors: Reddick Dean , Udenwobele Daniel I , Datzkiw David , Mukherjee Revanti , Shrivastav Shailly Varma , Good Sara , Shrivastav Anuraag 
Published: October 2020

AbstractN-myristoylation refers to the attachment of a 14-carbon fatty acid onto the N-terminal glycine residue of a target protein. The myristoylation reaction, catalyzed by N-myristoyltrasnferase (NMT), is essential for regulating cellular activities such as signal transduction, proliferation, migration, differentiation, and transformation. Although a considerable amount of research is performed on the overexpression of NMT in pathogenic conditions, a fundamental knowledge gap exists on the evolution of NMT and the functional impact of myristoylation for normal cellular development and functions. We performed evolutionary analyses of the NMT gene and found that most non-vertebrates harbor a single nmt gene and all vertebrates examined harbor two genes; nmt1 and nmt2. For the first time, we report that teleosts harbor two copies of nmt1, named nmt1a and nmt1b. We traced the evolutionary history of the chromosomal fragments hosting NMT1 and NMT2 in humans and found that NMT1 and NMT2 trace back to a single vertebrate ancestral chromosome. We also report the presence of putative nuclear localization sequence (NLS) and amino acid residues flanking NLS. The presence of phosphorylatable amino acid residues flanking the NLS suggests that nuclear localization of NMT is regulated by phosphorylation. The nuclear localization of NMT suggest its potential role in gene transcription.
Life history tradeoffs, division of labor and evolutionary transitions in individuality
Authors: Doulcier Guilhem , Hammerschmidt Katrin , Bourrat Pierrick 
Published: October 2020

AbstractReproductive division of labor has been proposed to play a key role for evolutionary transitions in individuality (ETIs). This chapter provides a guide to a theoretical model that addresses the role of a tradeoff between life-history traits in selecting for a reproductive division of labor during the transition from unicellular to multicellular organisms. In particular, it focuses on the five key assumptions of the model, namely (1) fitness is viability times fecundity; (2) collective traits are linear functions of their cellular counterparts; (3) there is a tradeoff between cell viability and fecundity; (4) cell contribution to the collective is optimal; and (5) there is an initial reproductive cost in large collectives. Thereafter the chapter contrasts two interpretations of the model in the context of ETIs. Originally, the model was interpreted as showing that during the transition to multicellularity the fitness of the lower-level (the cells) is “transferred” to the higher level (the collective). Despite its apparent intuitiveness, fitness transfer may obscure actual mechanisms in metaphorical language. Thus, an alternative and more conservative interpretation of the model that focuses on cell traits and the evolutionary constraints that link them is advocated. In addition, it allows for pursuing subsequent questions, such as the evolution of development.
Fast and exact single and double mutation-response scanning of proteins
Authors: Echave Julian 
Published: October 2020

AbstractStudying the effect of perturbations on protein structure is a basic approach in protein research. Important problems, such as predicting pathological mutations and understanding patterns structural evolution, have been addressed by computational simulations based on modelling mutations as forces and predicting deformations using the Linear Response Approximation. In single mutation-response scanning simulations, a sensitivity matrix is obtained by averaging deformations over point mutations. In double mutation-response scanning simulations, a compensation matrix is obtained by minimizing deformations over pairs of mutations. These very useful simulation-based methods may be too slow to deal with large supra-molecular complexes, such as a ribosome or a virus capsid, or large number of proteins, such as the human proteome, which limits their applicability. To address this issue, I derived analytical closed formulas to calculate the sensitivity and compensation matrices directly, without simulations. Here, I present these derivations and show that the resulting analytical methods are much faster than their simulation counterparts, and that where the simulation methods are approximate, the analytical methods are exact by design.
Exceptional Late Devonian arthropods document the origin of decapod crustaceans
Authors: Gueriau Pierre , Rak Štěpán , Broda Krzysztof , Kumpan Tomáš , Viktorýn Tomáš , Valach Petr , Zatoń Michał , Charbonnier Sylvain , Luque Javier 
Published: October 2020

AbstractWith over 15,000 extant species, Decapoda—or ten-legged crustaceans such as crabs, shrimp, lobsters, and relatives— are among the most speciose and economically important group of crustaceans. Despite of their diversity, anatomical disparity, and remarkable fossil record extending back to the Late Paleozoic, the origins of Decapoda and their phylogenetic relationships with eumalacostracans remains elusive and inconclusive. Molecular dating suggests that decapods originated in the Late Ordovician (~450 Mya), but no reliable fossil crown groups are found until the Late Devonian. Moreover, there is no consensus on which lineages belong to stem groups, obscuring our understanding of the roots of the ten-legged decapod body plans as a whole, and how they relate to other non-decapod crustaceans. We present new, exceptional fossils from the Late Devonian of Czech Republic and Poland that belong to †Angustidontida, an odd shrimp-looking crustacean with a combination of anatomical features unlike those of any crown eumalacostracan known—extinct or extant. Our phylogenetic analyses, including representatives of all major lineages of crown eumalacostracans plus †Angustidontida, identify angustidontids as the only known stem-group decapod, and give hints about the transformation series, polarity of change, and evolutionary pathways leading to the modern decapod body plans seen today.
Phylogenomic systematics of the spotted skunks (Carnivora, Mephitidae,Spilogale): Additional species diversity and Pleistocene climate change as a major driver of diversification
Authors: McDonough Molly M. , Ferguson Adam W. , Dowler Robert C. , Gompper Matthew E. , Maldonado Jesús E. 
Published: October 2020

AbstractFour species of spotted skunks (Carnivora, Mephitidae,Spilogale) are currently recognized:Spilogale angustifrons,S. gracilis,S. putorius, andS. pygmaea. Understanding species boundaries within this group is critical for effective conservation given that regional populations or subspecies (e.g.,S. p. interrupta) have experienced significant population declines. Further, there may be currently unrecognized diversity within this genus as some taxa (e.g.,S. angustifrons) and geographic regions (e.g., Central America) never have been assessed using DNA sequence data. We analyzed species limits and diversification patterns in spotted skunks using multilocus nuclear (ultraconserved elements) and mitochondrial (whole mitogenomes and single gene analysis) data sets from broad geographic sampling representing all currently recognized species and subspecies. We found a high degree of genetic divergence amongSpilogalethat reflects seven distinct species and eight unique mitochondrial lineages. Initial divergence betweenS. pygmaeaand all otherSpilogaleoccurred 29 in the Early Pliocene (~ 5.0 million years ago) which was followed by subsequent diversification of the remainingSpilogaleinto an “eastern” and “western” lineage during the Early Pleistocene (~1.5 million years ago). These two lineages experienced temporally coincident patterns of diversification at ~0.66 and ~0.35 million years ago into two and ultimately three distinct evolutionary units, respectively. Diversification was confined almost entirely within the Pleistocene during a timeframe characterized by alternating glacial-interglacial cycles, with the origin of this diversity occurring in northeastern Mexico and the southwestern United States of America. Mitochondrial-nuclear discordance was recovered across three lineages in geographic regions consistent with secondary contact, including a distinct mitochondrial lineage confined to the Sonoran Desert. Our results have direct consequences for conservation of threatened populations, or species, as well as for our understanding of the evolution of delayed implantation in this enigmatic group of small carnivores.
Longitudinal Network Re-organization Across Learning and Development
Authors: McCormick Ethan M. , Peters Sabine , Crone Eveline A. , Telzer Eva H. 
Published: October 2020

AbstractWhile it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8-29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naïve subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals.