bluuebunny/crossref_metadata_2025 huggingface dataset:
Coastal regions of the northern Antarctic Peninsula are key for gentoo populations
Authors: Korczak-Abshire Malgorzata , Hinke Jefferson T. , Milinevsky Gennadi , Juáres Mariana A. , Watters George M.
Published: January 2021

Southern Ocean ecosystems are rapidly changing due to climate variability. An apparent beneficiary of such change in the western Antarctic Peninsula (WAP) is the gentoo penguinPygoscelis papua, which has increased its population size and expanded its range southward in the last 20 years. To better understand how this species has responded to large-scale changes, we tracked individuals during the non-breeding winter period from five colonies across the latitudinal range of breeding sites in the WAP, including from a recently established colony. Results highlight latitudinal gradients in movement; strong associations with shallow, coastal habitats along the entire Antarctic Peninsula; and movements that are independent of, yet constrained by, sea ice. It is clear that coastal habitats essential to gentoo penguins during the breeding season are similarly critical during winter. Larger movements of birds from northern colonies in the WAP further suggest that leap-frog migration may influence colonization events by facilitating nest-area prospecting and use of new haul-out sites. Our results support efforts to develop a marine protected area around the WAP. Winter habitats used by gentoo penguins outline high priority areas for improving the management of the spatio-temporally concentrated krill (Euphausia superba) fishery that operates in this region during winter.
The benefits of peer transparency in safe workplace operation post pandemic lockdown
Authors: Wey Arkady , Champneys Alan , Dyson Rosemary J. , Alwan Nisreen A. , Barker Mary
Published: January 2021

The benefits of different levels of engagement with test, trace and isolate procedures are investigated for a pandemic in which there is little population immunity, in terms of productivity and public health. Simple mathematical modelling is used in the context of a single, relatively closed workplace such as a factory or back-office where, in normal operation, each worker has lengthy interactions with a fixed set of colleagues. A discrete-time SEIR model on a fixed interaction graph is simulated with parameters that are motivated by the recent COVID-19 pandemic in the UK during a post-peak phase, including a small risk of viral infection from outside the working environment. Two kinds of worker are assumed,transparentswho regularly test, share their results with colleagues and isolate as soon as a contact tests positive for the disease, andopaqueswho do none of these. Moreover, the simulations are constructed as a ‘playable model’ in which the transparency level, disease parameters and mean interaction degree can be varied by the user. The model is also analysed in the continuum limit. All simulations point to the double benefit of transparency in both maximizing productivity and minimizing overall infection rates. Based on these findings, public policy implications are discussed for how to incentivise this mutually beneficial behaviour in different kinds of workplace, and simple recommendations are made.
Structure, composition and fibril-reinforced poroviscoelastic properties of bovine knee ligaments and patellar tendon
Authors: Ristaniemi Aapo , Regmi Dristi , Mondal Diponkor , Torniainen Jari , Tanska Petri , Stenroth Lauri , Finnilä Mikko A. J. , Töyräs Juha , Korhonen Rami K.
Published: January 2021

Tissue-level stress-relaxation of ligaments and tendons in the toe region is characterized by fast and long-term relaxations and an increase in relaxation magnitude with strain. Characterizing the compositional and structural origins of these phenomena helps in the understanding of mechanisms of ligament and tendon function and adaptation in health and disease. A three-step tensile stress-relaxation test was conducted on dumbbell-shaped pieces of bovine knee ligaments and patellar tendon (PT) (
n
= 10 knees). Their mechanical behaviour was characterized by a fibril-reinforced poroviscoelastic material model, able to describe characteristic times and magnitudes of fast and long-term relaxations. The crimp angle and length of tissues were measured with polarized light microscopy, while biochemical contents were determined by colorimetric biochemical methods. The long-term relaxation time was longer in the anterior cruciate ligament (ACL) and PT compared with collateral ligaments (
p
< 0.05). High hydroxyproline content predicted greater magnitude and shorter time of both fast and long-term relaxation. High uronic acid content predicted longer time of long-term relaxation, whereas high crimp angle predicted higher magnitude of long-term relaxation. ACL and PT are better long-term stabilizers than collateral ligaments. The long-term relaxation behaviour is affected or implied by proteoglycans and crimp angle, possibly relating to slow structural reorganization of the tissue.
A multizone cerebellar chip for bioinspired adaptive robot control and sensorimotor processing
Authors: Wilson Emma D. , Assaf Tareq , Rossiter Jonathan M. , Dean Paul , Porrill John , Anderson Sean R. , Pearson Martin J.
Published: January 2021

The cerebellum is a neural structure essential for learning, which is connected via multiple zones to many different regions of the brain, and is thought to improve human performance in a large range of sensory, motor and even cognitive processing tasks. An intriguing possibility for the control of complex robotic systems would be to develop an artificial cerebellar chip with multiple zones that could be similarly connected to a variety of subsystems to optimize performance. The novel aim of this paper, therefore, is to propose and investigate a multizone cerebellar chip applied to a range of tasks in robot adaptive control and sensorimotor processing. The multizone cerebellar chip was evaluated using a custom robotic platform consisting of an array of tactile sensors driven by dielectric electroactive polymers mounted upon a standard industrial robot arm. The results demonstrate that the performance in each task was improved by the concurrent, stable learning in each cerebellar zone. This paper, therefore, provides the first empirical demonstration that a synthetic, multizone, cerebellar chip could be embodied within existing robotic systems to improve performance in a diverse range of tasks, much like the cerebellum in a biological system.
A homology independent sequence replacement strategy in human cells using a CRISPR nuclease
Authors: Danner Eric , Lebedin Mikhail , de la Rosa Kathrin , Kühn Ralf
Published: January 2021

Precision genomic alterations largely rely on homology directed repair (HDR), but targeting without homology using the non-homologous end-joining (NHEJ) pathway has gained attention as a promising alternative. Previous studies demonstrated precise insertions formed by the ligation of donor DNA into a targeted genomic double-strand break in both dividing and non-dividing cells. Here, we demonstrate the use of NHEJ repair to
replace
genomic segments with donor sequences; we name this method ‘Replace’ editing (
R
ational
e
nd-joining
p
rotocol de
l
ivering
a
targeted sequen
c
e
e
xchange). Using CRISPR/Cas9, we create two genomic breaks and ligate a donor sequence in-between. This exchange of a genomic for a donor sequence uses neither microhomology nor homology arms. We target four loci in cell lines and show successful exchange of exons in 16–54% of human cells. Using linear amplification methods and deep sequencing, we quantify the diversity of outcomes following Replace editing and profile the ligated interfaces. The ability to replace exons or other genomic sequences in cells not efficiently modified by HDR holds promise for both basic research and medicine.
A novel approach for evaluating contact patterns and risk mitigation strategies for COVID-19 in English primary schools with application of structured expert judgement
Authors: Sparks R. S. J. , Aspinall W. P. , Brooks-Pollock E. , Cooke R. M. , Danon L. , Barclay J. , Scarrow J. H. , Cox J.
Published: January 2021

Personal contacts drive COVID-19 infections. After being closed (23 March 2020) UK primary schools partially re-opened on 1 June 2020 with social distancing and new risk mitigation strategies. We conducted a structured expert elicitation of teachers to quantify primary school contact patterns and how contact rates changed upon re-opening with risk mitigation measures in place. These rates, with uncertainties, were determined using a performance-based algorithm. We report mean number of contacts per day for four cohorts within schools, with associated 90% confidence ranges. Prior to lockdown, younger children (Reception and Year 1) made 15 contacts per day [range 8.35] within school, older children (Year 6) 18 contacts [range 5.55], teaching staff 25 contacts [range 4.55] and non-classroom staff 11 contacts [range 2.27]. After re-opening, the mean number of contacts was reduced by 53% for young children, 62% for older children, 60% for classroom staff and 64% for other staff. Contacts between teaching and non-teaching staff reduced by 80%. The distributions of contacts per person are asymmetric with heavy tail reflecting a few individuals with high contact numbers. Questions on risk mitigation and supplementary structured interviews elucidated how new measures reduced daily contacts in-school and contribute to infection risk reduction.
The Polycentric Dynamics of Melbourne and Sydney: suburb attractiveness divides a city at the home ownership level
Authors: Crosato Emanuele , Prokopenko Mikhail , Harré Michael S.
Published: January 2021

Urban dynamics in large metropolitan areas result from complex interactions across social, economic and political factors, including population distribution, flows of wealth and infrastructure requirements. We develop a Census-calibrated model of urban dynamics for the Greater Sydney and Melbourne areas for 2011 and 2016, highlighting the evolution of population distributions and the housing market structure in these two cities in terms of their mortgage and rent distributions. We show that there is a tendency to homophily between renters and mortgage holders: renters tend to cluster nearer commercial centres, whereas mortgagors tend to populate the outskirts of these centres. We also identify a critical threshold at which the long-term evolution of these two cities will bifurcate between a ‘sprawling’ and a ‘polycentric’ configuration, showing that both cities lie on the polycentric side of the critical point in the long-run. Importantly, there is a divergence of these centric tendencies between the renters and mortgage holders. The polycentric patterns characterizing the mortgagors are focused around commercial centres, and we show that the emergent housing patterns follow the major transport routes through the cities.
Simulation of pandemics in real cities: enhanced and accurate digital laboratories
Authors: Alexiadis A. , Albano A. , Rahmat A. , Yildiz M. , Kefal A. , Ozbulut M. , Bakirci N. , Garzón-Alvarado D. A. , Duque-Daza C. A. , Eslava-Schmalbach J. H.
Published: January 2021

This study develops a modelling framework for simulating the spread of infectious diseases within real cities. Digital copies of Birmingham (UK) and Bogotá (Colombia) are generated, reproducing their urban environment, infrastructure and population. The digital inhabitants have the same statistical features of the real population. Their motion is a combination of predictable trips (commute to work, school, etc.) and random walks (shopping, leisure, etc.). Millions of individuals, their encounters and the spread of the disease are simulated by means of high-performance computing and massively parallel algorithms for several months and a time resolution of 1 minute. Simulations accurately reproduce the COVID-19 data for Birmingham and Bogotá both before and during the lockdown. The model has only one adjustable parameter calculable in the early stages of the pandemic. Policymakers can use our digital cities as virtual laboratories for testing, predicting and comparing the effects of policies aimed at containing epidemics.
Beat gestures influence which speech sounds you hear
Authors: Bosker Hans Rutger , Peeters David
Published: January 2021

Beat gestures—spontaneously produced biphasic movements of the hand—are among the most frequently encountered co-speech gestures in human communication. They are closely temporally aligned to the prosodic characteristics of the speech signal, typically occurring on lexically stressed syllables. Despite their prevalence across speakers of the world's languages, how beat gestures impact spoken word recognition is unclear. Can these simple ‘flicks of the hand' influence speech perception? Across a range of experiments, we demonstrate that beat gestures influence the explicit and implicit perception of lexical stress (e.g. distinguishingOBjectfromobJECT), and in turn can influence what vowels listeners hear. Thus, we provide converging evidence for a manual McGurk effect: relatively simple and widely occurring hand movements influence which speech sounds we hear.
A biologist's guide to model selection and causal inference
Authors: Laubach Zachary M. , Murray Eleanor J. , Hoke Kim L. , Safran Rebecca J. , Perng Wei
Published: January 2021

A goal of many research programmes in biology is to extract meaningful insights from large, complex datasets. Researchers in ecology, evolution and behavior (EEB) often grapple with long-term, observational datasets from which they construct models to test causal hypotheses about biological processes. Similarly, epidemiologists analyse large, complex observational datasets to understand the distribution and determinants of human health. A key difference in the analytical workflows for these two distinct areas of biology is the delineation of data analysis tasks and explicit use of causal directed acyclic graphs (DAGs), widely adopted by epidemiologists. Here, we review the most recent causal inference literature and describe an analytical workflow that has direct applications for EEB. We start this commentary by defining four distinct analytical tasks (description, prediction, association, causal inference). The remainder of the text is dedicated to causal inference, specifically focusing on the use of DAGs to inform the modelling strategy. Given the increasing interest in causal inference and misperceptions regarding this task, we seek to facilitate an exchange of ideas between disciplinary silos and provide an analytical framework that is particularly relevant for making causal inference from observational data.
Exact mapping of Illumina blind spots in the Mycobacterium tuberculosis genome reveals platform-wide and workflow-specific biases
Authors: Modlin Samuel J. , Robinhold Cassidy , Morrissey Christopher , Mitchell Scott N. , Ramirez-Busby Sarah M. , Shmaya Tal , Valafar Faramarz
Published: January 2021

Whole-genome sequencing (WGS) is fundamental to

Mycobacterium tuberculosis

basic research and many clinical applications. Coverage across Illumina-sequenced

M. tuberculosis

genomes is known to vary with sequence context, but this bias is poorly characterized. Here, through a novel application of phylogenomics that distinguishes genuine coverage bias from deletions, we discern Illumina ‘blind spots’ in the

M. tuberculosis

reference genome for seven sequencing workflows. We find blind spots to be widespread, affecting 529 genes, and provide their exact coordinates, enabling salvage of unaffected regions. Fifty-seven pe/ppe genes (the primary families assumed to exhibit Illumina bias) lack blind spots entirely, while the remaining pe/ppe genes account for 55.1 % of blind spots. Surprisingly, we find coverage bias persists in homopolymers as short as 6 bp, shorter tracts than previously reported. While G+C-rich regions challenge all Illumina sequencing workflows, a modified Nextera library preparation that amplifies DNA with a high-fidelity polymerase markedly attenuates coverage bias in G+C-rich and homopolymeric sequences, expanding the ‘Illumina-sequenceable’ genome. Through these findings, and by defining workflow-specific exclusion criteria, we spotlight effective strategies for handling bias in

M. tuberculosis

Illumina WGS. This empirical analysis framework may be used to systematically evaluate coverage bias in other species using existing sequencing data.
Colonization with Staphylococcus aureus and Klebsiella pneumoniae causes infections in a Vietnamese intensive care unit
Authors: Thuy Duong Bich , Campbell James , Thuy Cao Thu , Hoang Nguyen Van Minh , Voong Vinh Phat , Nguyen To Nguyen Thi , Nguyen Ngoc Minh Chau , Pham Duy Thanh , Rabaa Maia A. , Lan Nguyen Phu Huong , Hao Nguyen Van , Thwaites Guy E. , Thwaites C. Louise , Baker Stephen , Chau Nguyen Van Vinh , Chung The Hao
Published: January 2021

Pre-existing colonization with

Staphylococcus aureus

or

Klebsiella pneumoniae

has been found to increase the risk of infection in intensive care patients. We previously conducted a longitudinal study to characterize colonization of these two organisms in patients admitted to intensive care in a hospital in southern Vietnam. Here, using genomic and phylogenetic analyses, we aimed to assess the contribution these colonizing organisms made to infections. We found that in the majority of patients infected with

S. aureus

or

K. pneumoniae

, the sequence type of the disease-causing (infecting) isolate was identical to that of corresponding colonizing organisms in the respective patient. Further in-depth analysis revealed that in patients infected by

S. aureus

ST188 and by

K. pneumoniae

ST17, ST23, ST25 and ST86, the infecting isolate was closely related to and exhibited limited genetic variation relative to pre-infection colonizing isolates. Multidrug-resistant

S. aureus

ST188 was identified as the predominant agent of colonization and infection. Colonization and infection by

K. pneumoniae

were characterized by organisms with limited antimicrobial resistance profiles but extensive repertoires of virulence genes. Our findings augment the understanding of the link between bacterial colonization and infection in a low-resource setting, and could facilitate the development of novel evidence-based approaches to prevent and treat infections in high-risk patients in intensive care.
AI-driven Deep Visual Proteomics defines cell identity and heterogeneity
Authors: Mund Andreas , Coscia Fabian , Hollandi Réka , Kovács Ferenc , Kriston András , Brunner Andreas-David , Bzorek Michael , Naimy Soraya , Rahbek Gjerdrum Lise Mette , Dyring-Andersen Beatrice , Bulkescher Jutta , Lukas Claudia , Gnann Christian , Lundberg Emma , Horvath Peter , Mann Matthias
Published: January 2021

The systems-wide analysis of biomolecules in time and space is key to our understanding of cellular function and heterogeneity in health and disease1. Remarkable technological progress in microscopy and multi-omics technologies enable increasingly data-rich descriptions of tissue heterogeneity2,3,4,5. Single cell sequencing, in particular, now routinely allows the mapping of cell types and states uncovering tremendous complexity6. Yet, an unaddressed challenge is the development of a method that would directly connect the visual dimension with the molecular phenotype and in particular with the unbiased characterization of proteomes, a close proxy for cellular function. Here we introduce Deep Visual Proteomics (DVP), which combines advances in artificial intelligence (AI)-driven image analysis of cellular phenotypes with automated single cell laser microdissection and ultra-high sensitivity mass spectrometry7. DVP links protein abundance to complex cellular or subcellular phenotypes while preserving spatial context. Individually excising nuclei from cell culture, we classified distinct cell states with proteomic profiles defined by known and novel proteins. AI also discovered rare cells with distinct morphology, whose potential function was revealed by proteomics. Applied to archival tissue of salivary gland carcinoma, our generic workflow characterized proteomic differences between normal-appearing and adjacent cancer cells, without admixture of background from unrelated cells or extracellular matrix. In melanoma, DVP revealed immune system and DNA replication related prognostic markers that appeared only in specific tumor regions. Thus, DVP provides unprecedented molecular insights into cell and disease biology while retaining spatial information.
A joint analysis of longevity and age-related disease variants for gene expression association
Authors: Zeng Lu , Peng Shouneng , Kim Seungsoo , Zhu Jun , Zhang Bin , Suh Yousin , Tu Zhidong
Published: January 2021

A large number of genetic variants associated with human longevity have been reported but how they play their functions remains elusive. We performed an integrative analysis on 113 genome-wide significant longevity and 14,529 age-related disease variants in the context of putative gene expression regulation. We found that most of the longevity allele types were different from the genotype of disease alleles when they were localized at the same chromosomal positions. Longevity variants were about eight times more likely to be associated with gene expression than randomly selected variants. The directions of the gene expression association were more likely to be opposite between longevity and disease variants when the association occurred to the same gene. Many longevity variants likely function through down-regulating inflammatory response and up-regulating healthy lipid metabolisms. In conclusion, this work helps to elucidate the potential mechanisms of longevity variants for follow-up studies to discover methods to extend human healthspan.
PIP2regulation of TRPC5 channel activation and desensitization
Authors: Ningoo Mehek , Plant Leigh D. , Greka Anna , Logothetis Diomedes E.
Published: January 2021

Transient receptor potential canonical type 5 (TRPC5) channels are expressed in the brain and kidney, and have been identified as promising therapeutic targets whose selective inhibition can protect against diseases driven by a leaky kidney filter. They are activated by elevated levels of extracellular Ca2+or application of lanthanide ions but also by G protein (Gq/11) stimulation. Phosphatidylinositol bis-phosphate (PIP2) hydrolysis leads to protein kinase C- (PKC-) mediated phosphorylation of TRPC5 channels and desensitization of their activity. Even though PIP2regulation of TRP channels is being widely studied, the roles of PIP2in maintaining TRPC5 channel activity, the PIP2involvement in channel stimulation by its hydrolysis product diacyl glycerol (DAG), or the desensitization of activity by DAG-stimulated PKC activity remain unclear. Here, we show that PIP2controls both the PKC-mediated inhibition of TRPC5 currents as well as the activation by DAG and lanthanides and that it accomplishes this through control of gating rather than channel cell surface density. The mechanistic insights achieved by the present work promise to aid in the development of more selective and precise molecules to block TRPC5 channel activity and illuminate new therapeutic opportunities for targeted therapies for a group of diseases for which there is currently a great unmet need.
Transposable elements contribute to genome dynamics and gene expression variation in the fungal plant pathogenVerticillium dahliae
Authors: Torres David E , Thomma Bart PHJ , Seidl Michael F
Published: January 2021

Transposable elements (TEs) are a major source of genetic and regulatory variation in their host genome and are consequently thought to play important roles in evolution. Many fungal and oomycete plant pathogens have evolved dynamic and TE-rich genomic regions containing genes that are implicated in host colonization. TEs embedded in these regions have typically been thought to accelerate the evolution of these genomic compartments, but little is known about their dynamics in strains that harbor them. Here, we used whole-genome sequencing data of 42 strains of the fungal plant pathogenVerticillium dahliaeto systematically identify polymorphic TEs that may be implicated in genomic as well as in gene expression variation. We identified 2,523 TE polymorphisms and characterize a subset of 8% of the TEs as dynamic elements that are evolutionary younger, less methylated, and more highly expressed when compared with the remaining 92% of the TE complement. As expected, the dynamic TEs are enriched in the dynamic genomic regions. Besides, we observed an association of dynamic TEs with pathogenicity-related genes that localize nearby and that display high expression levels. Collectively, our analyses demonstrate that TE dynamics inV. dahliaecontributes to genomic variation, correlates with expression of pathogenicity-related genes, and potentially impacts the evolution of dynamic genomic regions.

Significance statement

Transposable elements (TEs) are ubiquitous components of genomes and are major sources of genetic and regulatory variation. Many plant pathogens have evolved TE-rich genomic regions containing genes with roles in host colonization, and TEs are thought to contribute to accelerated evolution of these dynamic regions. We analyzed the fungal plant pathogenVerticillium dahliaeto identify TE variation between strains and to demonstrate that polymorphic TEs have specific characteristic that separates them from the majority of TEs. Polymorphic TEs are enriched in dynamic genomic regions and are associated with structural variants and highly expressed pathogenicity-related genes. Collectively, our results provide evidence for the hypothesis that dynamic TEs contribute to increased genomic diversity, functional variation, and the evolution of dynamic genomic regions.
The Genetic Diversity of Two Subpopulations of Shenxian Pigs as Revealed by Genome Resequencing
Authors: Diao Liu , Hongzhan Cao , Chunlian Lu , Shang Li , Mengyu Jia , Sai Li , Liqin Ren
Published: January 2021

Shenxian pigs can be divided into two main strains from their shape and appearance: Huangguazui and Wuhuatou. There are significant differences in the phenotypic characters between the two subpopulations. The Shenxian pig, as the only local pig breed listed in China Pig Breeds in Hebei Province, has the excellent traits of Chinese local pigs. In order to explore the genetic diversity and genetic distance of the different subpopulations of Shenxian pig, as well as understand their evolutionary process, whole genome resequencing and genetic structure analyses were performed for the two sub-population types of Shenxian pigs.The results showed that a total of 14,509,223 SNP sites were detected in the Huangguazui type and 13,660,201 SNP sites were detected in the Wuhuatou type. This study’s principal component analysis results showed that the genetic differentiation of the Shenxian pig population was serious, and there was obvious stratification in the population. The phylogenetic tree analysis results indicated that there was a certain genetic distance between the Huangguazui and Wuhuatou types.
Optimal use of simplified social information in sequential decision-making
Authors: Mann Richard P.
Published: January 2021

Abstract

Social animals can improve their decisions by attending to the choices made by others. The rewards gained by attending to this social information must be balanced against the costs of obtaining and processing it. Previous work has investigated the behaviour of rational agents that respond optimally to a full sequence of prior decisions. However, such full sequences are potentially difficult to perceive and costly to process. As such, real animals are likely to rely on simpler forms of information when making decisions, which in turn will affect the social behaviour they exhibit. In this paper I derive the optimal policy for rational agents responding to specific simplified forms of social information. I show how the behaviour of agents attending to the total aggregate number of previous choices differs from those attending to more dynamic information provided by the most recent prior decision, and I propose a hybrid strategy that incorporates both information sources to give a highly accurate approximation to the optimal policy with the full sequence. Finally I analyse the evolutionary stability of each strategy depending on the cost of cognition and perception, showing that a hybrid strategy dominates when this cost is low but non-zero, while attending to the most recent decision is dominant when costs are high. These results show that agents can employ highly effective social decision-making rules without requiring unrealistic cognitive capacities, and point to likely ecological variation in the social information different animals attend to.
Revisiting the role of synaptic plasticity and network dynamics for fast learning in spiking neural networks
Authors: Subramoney Anand , Bellec Guillaume , Scherr Franz , Legenstein Robert , Maass Wolfgang
Published: January 2021

Spike-based neural network models have so far not been able to reproduce the capability of the brain to learn from very few, often even from just a single example. We show that this deficiency of models disappears if one allows synaptic weights to store priors and other information that optimize the learning process, while using the network state to quickly absorb information from new examples. For that, it suffices to include biologically realistic neurons with spike frequency adaptation in the neural network model, and to optimize the learning process through meta-learning. We demonstrate this on a variety of tasks, including fast learning and deletion of attractors, adaptation of motor control to changes in the body, and solving the Morris water maze task – a paradigm for fast learning of navigation to a new goal.

Significance Statement

It has often been conjectured that STDP or other rules for synaptic plasticity can only explain some of the learning capabilities of brains. In particular, learning a new task from few trials is likely to engage additional mechanisms. Results from machine learning show that artificial neural networks can learn from few trials by storing information about them in their network state, rather than encoding them in synaptic weights. But these machine learning methods require neural networks with biologically unrealistic LSTM (Long Short Term Memory) units. We show that biologically quite realistic models for neural networks of the brain can exhibit similar capabilities. In particular, these networks are able to store priors that enable learning from very few examples.
Microbial population dynamics and evolutionary outcomes under extreme energy-limitation
Authors: Shoemaker William R. , Jones Stuart E. , Muscarella Mario E. , Behringer Megan G. , Lehmkuhl Brent K. , Lennon Jay T.
Published: January 2021

As the most abundant and diverse form of life on Earth, microorganisms commonly inhabit energy-limited environments where cellular maintenance and growth is highly constrained. To gain insight into how microorganisms persist under such conditions, we derived demographic parameters from a diverse collection of bacteria by censusing 100 populations in a closed system for 1,000 days. All but one taxon survived prolonged resource scarcity, yielding estimated times-to-extinction ranging over four orders of magnitude from 100– 105years. These findings corroborate reports of long-lived bacteria that have been recovered from ancient environmental samples, while providing insight into mechanisms of persistence. Critically, we found that as death rates declined over time, lifespan was extended through the scavenging of dead cells. Although growth and reproduction were dramatically suppressed in the absence of an exogenous resource supply, bacterial populations continued to evolve. Hundreds of mutations were acquired, contributing to genome-wide signatures of negative selection as well as molecular signals of adaptation. Remarkable consistency in the ecological and evolutionary dynamics indicate that distantly related bacteria respond to energy-limitation in a similar and predictable manner, which likely contributes to the stability and robustness of microbial life.
Analyzing cancer gene expression data through the lens of normal tissue-specificity
Authors: Frost H. Robert
Published: January 2021

The genetic alterations that underlie cancer development are highly tissue-specific with the majority of driving alterations occurring in only a few cancer types and with alterations common to multiple cancer types often showing a tissue-specific functional impact. This tissue-specificity means that the biology of normal tissues carries important information regarding the pathophysiology of the associated cancers, information that can be leveraged to improve the power and accuracy of cancer genomic analyses. Research exploring the use of normal tissue data for the analysis of cancer genomics has primarily focused on the paired analysis of tumor and adjacent normal samples. Efforts to leverage the general characteristics of normal tissue for cancer analysis has received less attention with most investigations focusing on understanding the tissue-specific factors that lead to individual genomic alterations or dysregulated pathways within a single cancer type. To address this gap and support scenarios where adjacent normal tissue samples are not available, we explored the genome-wide association between the transcriptomes of 21 solid human cancers and their associated normal tissues as profiled in healthy individuals. While the average gene expression profiles of normal and cancerous tissue may appear distinct, with normal tissues more similar to other normal tissues than to the associated cancer types, when transformed into relative expression values, i.e., the ratio of expression in one tissue or cancer relative to the mean in other tissues or cancers, the close association between gene activity in normal tissues and related cancers is revealed. As we demonstrate through an analysis of tumor data from The Cancer Genome Atlas and normal tissue data from the Human Protein Atlas, this association between tissue-specific and cancer-specific expression values can be leveraged to improve the prognostic modeling of cancer, the comparative analysis of different cancer types, and the analysis of cancer and normal tissue pairs.
Training Data: How can we best prepare instructors to teach data science in undergraduate biology and environmental science courses?
Authors: Emery Nathan , Crispo Erika , Supp Sarah R. , Kerkhoff Andrew J. , Farrell Kaitlin J. , Bledsoe Ellen K. , O’Donnell Kelly L. , McCall Andrew C. , Aiello-Lammens Matthew
Published: January 2021

There is a clear and concrete need for greater quantitative literacy in the biological and environmental sciences. Data science training for students in higher education necessitates well-equipped and confident instructors across curricula. However, not all instructors are versed in data science skills or research-based teaching practices. Our study sought to survey the state of data science education across institutions of higher learning, identify instructor needs, and illuminate barriers to teaching data science in the classroom. We distributed a survey to instructors around the world, focused on the United States, and received 106 complete responses. Our results indicate that instructors across institutions use, teach, and view data management, analysis, and visualization as important for students to learn. Code, modeling, and reproducibility were less valued by instructors, although there were differences by institution type (doctoral, masters, or baccalaureate), and career stage (time since terminal degree). While there were a variety of barriers highlighted by respondents, instructor background, student background, and space in the curriculum were the greatest barriers of note. Interestingly, instructors were most interested in receiving training for how to teach code and data analysis in the undergraduate classroom. Our study provides an important window into how data science is taught in higher education as well as suggestions for how we can best move forward with empowering instructors across disciplines.
Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques
Authors: Crooks C. M. , Weiler A. M. , Rybarczyk S. L. , Bliss M. I. , Jaeger A. S. , Murphy M. E. , Simmons H. A. , Mejia A. , Fritsch M. K. , Hayes J. M. , Eickhoff J. C. , Mitzey A. M. , Razo E. , Braun K. M. , Brown E. A. , Yamamoto K. , Shepherd P. M. , Possell A. , Weaver K. , Antony K. M. , Morgan T. K. , Newman C. M. , Dudley D. M. , Schultz-Darken N. , Peterson E. , Katzelnick L. C. , Balmaseda A. , Harris E. , O’Connor D. H. , Mohr E. L. , Golos T. G. , Friedrich T. C. , Aliota M. T.
Published: January 2021

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.
Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7
Authors: Murugan N. Arul , Javali Prashanth S. , Pandian Chitra Jeyaraj , Ali Muhammad Akhtar , Srivastava Vaibhav , Jeyaraman Jeyakanthan
Published: January 2021

New variants of SARS-CoV-2 are being reported worldwide. More specifically, the variants reported in South Africa (501Y.V2) and United Kingdom (B.1.1.7) were found to be more contagious than the wild type. There are also speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19, occurs through the interaction of receptor binding domain (RBD) of the spike protein with peptidase domain of the human ACE-2 (hACE-2) receptor. So, possibly the mutations in the RBD domain of spike protein in the new variants could modulate the protein-protein interaction with hACE-2 receptor leading to the increased virulence. In this study, we aim to get molecular level understanding into the mechanism behind the increased infection rate due to such mutations in these variants. We have computationally studied the interaction of the spike protein in both wild-type and B.1.1.7 variant with hACE-2 receptor using combined molecular dynamics and binding free energy calculations using molecular mechanics-Generalized Born surface area (MM-GBSA) approach. The binding free energies computed using configurations from minimization run and low temperature simulation show that mutant variant of spike protein has increased binding affinity for hACE-2 receptor (i.e. ΔΔG(N501Y,A570D) is in the range −20.4 to −21.4 kcal/mol)The residue-wise decomposition analysis and intermolecular hydrogen bond analysis evidenced that the N501Y mutation has increased interaction between RBD of spike protein with ACE-2 receptor. We have also carried out calculations using density functional theory and the results evidenced the increased interaction between three pairs of residues (TYR449 (spike)-ASP38 (ACE-2), TYR453-HIE34 and TYR501-LYS353) in the variant that could be attributed to its increased virulence. The free energies of wild-type and mutant variants of the spike protein computed from MM-GBSA approach suggests that latter variant is stable by about −10.4 kcal/mol when compared to wild type suggesting that it will be retained in the evolution due to increased stability. We demonstrate that with the use of the state-of-the art of computational approaches, we can in advance predict the more virulent nature of variants of SARS-CoV-2 and alert the world health-care system.
Fallow time determination in dentistry using aerosol measurement
Authors: Shahdad Shakeel , Hindocha Annika , Patel Tulsi , Cagney Neil , Mueller Jens-Dominik , Kochid Amine , Seoudi Noha , Morgan Claire , Fleming Padhraig , Din Ahmed Riaz
Published: January 2021

Aim

To calculate fallow time (FT) required following dental aerosol generating procedures (AGPs) in both a dental hospital (mechanically ventilated) and primary care (non-mechanically ventilated). Secondary outcomes were to identify spread and persistence of aerosol in open clinics compared to closed surgeries (mechanically ventilated environment), and identify if extra-oral scavenging (EOS) reduces production of aerosol and FT.

Methods

In vitro simulation of fast handpiece (FHP) cavity preparations using a manikin was conducted in a mechanically and non-mechanically ventilated environment using Optical Particle Sizer™ and NanoScan™ at baseline, during the procedure and fallow period.

Results

AGPs carried out in the non-mechanically, non-ventilated environment failed to achieve baseline particle levels after one hour. In contrast, when windows were opened after AGP, there was an immediate reduction in all particle sizes.

In mechanically ventilated environments the baseline levels of particles were very low and particle count returned to baseline within 10 minutes following AGP. There was no detectable difference between particles in mechanically ventilated open bays and closed surgeries.

The effect of the EOS was greater in non-mechanically ventilated environment on reducing the particle count; additionally, it also reduced the spikes in particle counts in mechanically ventilated environments.

Conclusion

High-efficiency particulate air filtered mechanical ventilation along with mitigating factors (high-volume suction) resulted in reduction of FT (10 minutes). Non-ventilated rooms failed to reach baseline level even after one hour of FT. There was no difference in particle counts in open bay or closed surgeries in mechanically ventilated settings. The use of an EOS device can reduce the particulate spikes during procedures in both mechanical and non-mechanical environments.

This study confirms that AGPs are not recommended in dental surgeries where no ventilation is possible. No difference was demonstrated in FT required in open bays and closed surgeries in mechanically ventilated settings.

Clinical significance

AGPs should not be carried out in surgeries where ventilation is not possible. Mechanical ventilation for AGPs should be gold standard; where not available or practical then the use of natural ventilation with EOS helps reduce FT. AGPs can be carried out in open bay environment with a minimum of 6 air changes per hour of mechanical ventilation. Four-handed dentistry with high-volume suction and saliva ejector are essential mitigating factors during AGPs.
Baseline cell proliferation rates and response to UV differ in Lymphoblastoid Cell Lines derived from healthy individuals of extreme constitution types
Authors: Chakraborty Sumita , Singhmar Sunanda , Singh Dayanidhi , Maulik Mahua , Patil Rutuja , Agrawal Satyam Kumar , Mishra Anushree , Ghazi Madeeha , Vats Archana , Natarajan Vivek T , Juvekar Sanjay , Prasher Bhavana , Mukerji Mitali
Published: January 2021

Differences in human phenotypes and susceptibility to complex diseases are an outcome of genetic and environmental interactions. This is evident in diseases that progress through a common set of intermediate patho-endophenotypes. Precision medicine aims to delineate the molecular players for individualized and early interventions. Functional studies in Lymphoblastoid Cell Line (LCL) model of phenotypically well characterized healthy individuals can help deconvolute and validate these molecular mechanisms. We developed LCLs from eight healthy individuals belonging to three extreme constitution types, deep phenotyped on the basis of Ayurveda. LCLs were characterized by karyotyping and immunophenotyping. Growth characteristics and response to UV was studied in these LCLs. We observed significant differences in cell proliferation rates between the contrasting groups such that one type (Kapha) proliferates significantly slower than the other two (Vata, Pitta). In response to UV, one fast growing group (Vata) shows higher cell death but recovers its numbers due to inherent higher rates of proliferation. The baseline differences in cell proliferation are key to understanding the survival of cells in UV stress. Variability in baseline cellular phenotypes not only explains the cellular basis of different constitutions types but can also help set priors during designing an individualized therapy with DNA damaging agents. This is the first study of its kind that shows variability of intermediate patho-phenotypes amongst healthy individuals that have implications in precision medicine.
L-WNK1 is required for BK channel activation in intercalated cells
Authors: Ray Evan C. , Carrisoza-Gaytan Rolando , Al-Bataineh Mohammad , Marciszyn Allison L. , Nkashama Lubika J. , Chen Jingxin , Winfrey Aaliyah , Flores Daniel , Wu Peng , Wang WenHui , Huang Chou-Long , Subramanya Arohan R. , Kleyman Thomas R. , Satlin Lisa M.
Published: January 2021

BK channels expressed in intercalated cells (ICs) in the aldosterone-sensitive distal nephron (ASDN) mediate flow-induced K+secretion. In the ASDN of mice and rabbits, IC BK channel expression and activity increase with a high K+diet. In cell culture, the long isoform of the kinase WNK1 (L-WNK1) increases BK channel expression and activity. Apical L-WNK1 expression is selectively enhanced in ICs in the ASDN of rabbits on a high K+diet, suggesting that L-WNK1 contributes to BK channel regulation by dietary K+. We examined the role of IC L-WNK1 expression in enhancing BK channel activity in response to a high K+diet. Mice with an IC-selective deletion of L-WNK1 (IC-L-WNK1-KO) and littermate control mice were placed on a high K+(5% K+as KCl) diet for at least 10 days. IC-L-WNK1-KO mice exhibited higher blood K+concentrations ([K+]) than controls. BK channel-dependent whole-cell currents in ICs from cortical collecting ducts of high K+fed IC-L-WNK1-KO mice were reduced compared to controls. Six-hour urinary K+excretion in response a saline load was similar in IC-L-WNK1-KO mice and controls. The observations that IC-L-WNK1-KO mice have higher blood [K+] and reduced IC BK channel currents are consistent with impaired urinary K+secretion, and suggest that IC L-WNK1 has a role in the renal adaptation to a high K+diet.