bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPPER: A new image analysis pipeline unmasks differential regulation ofDrosophilawing features
Authors: Kumar Nilay , Huizar Francisco , Robinett Trent , Farfán-Pira Keity J. , Soundarrajan Dharsan , Unger Maria , Brodskiy Pavel , Nahmad Marcos , Zartman Jeremiah J.
Published: December 2020

Phenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines forDrosophilawings, a powerful model for studying morphogenesis, are limited in speed, versatility, and precision. To overcome these limitations, we developed MAPPER, a fully-automated machine learning-based pipeline that quantifies high dimensional phenotypic signatures, with each dimension representing a unique morphological feature. MAPPER magnifies the power ofDrosophilagenetics by rapidly identifying subtle phenotypic differences in sample populations. To demonstrate its widespread utility, we used MAPPER to reveal new insights connecting patterning and growth acrossDrosophilagenotypes and species. The morphological features extracted using MAPPER identified the presence of a uniform scaling of proximal-distal axis length across four different species ofDrosophila. Observation of morphological features extracted by MAPPER fromDrosophilawings by modulating insulin signaling pathway activity revealed the presence of a scaling gradient across the anterior-posterior axis. Additionally, batch processing of samples with MAPPER revealed a key function for the mechanosensitive calcium channel, Piezo, in regulating bilateral symmetry and robust organ growth. MAPPER is an open source tool for rapid analysis of large volumes of imaging data. Overall, MAPPER provides new capabilities to rigorously and systematically identify genotype-to-phenotype relationships in an automated, high throughput fashion.

Graphical abstract
Rate-of-change analysis in palaeoecology revisited: a new approach
Authors: Mottl Ondřej , Grytnes John-Arvid , Seddon Alistair W.R. , Steinbauer Manuel J. , Bhatta Kuber P. , Felde Vivian A. , Flantua Suzette G.A. , Birks H. John B.
Published: December 2020

Abstract

Dynamics in the rate of compositional change (rate-of-change; RoC) of biotic or abiotic assemblages preserved in palaeoecological sequences, are thought to reflect changes due to exogenous drivers such as climate and human forcing as well as endogenous factors linked to local dynamics and biotic interactions. However, changes in sedimentation rates and sampling strategies can result in an uneven distribution of time intervals and are known to affect RoC estimates. Furthermore, there has been relatively little exploration of the implications of these challenges in quantifying RoC in palaeoecology.

Here, we introduceR-Ratepol– an easy-to-use R package – that provides a robust numerical technique for detecting and summarising RoC patterns in complex multivariate time-ordered stratigraphical sequences. First, we compare the performance of common methods of estimating RoC and detecting periods of high RoC (peak-point) using simulated pollen-stratigraphical data with known patterns of compositional change and temporal resolution. In addition, we propose a new method of binning with a moving window, which shows a more than 5-fold increase in the correct detection of peak-points compared to the more traditional way of using individual levels.

Next, we apply our new methodology to four representative European pollen sequences and show that our approach also performs well in detecting periods of significant compositional change during known onsets of human activity, early land-use transformation, and changes in fire frequency.

Expanding the approach usingR-Ratepolto open-access paleoecological datasets in global databases, such as Neotoma, will allow future palaeoecological and macroecological studies to quantify major changes in biotic composition or in sets of abiotic variables across broad spatio-temporal scales.
Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants
Authors: Teruel Natália , Mailhot Olivier , Najmanovich Rafael Josef
Published: December 2020

The SARS-CoV-2 Spike protein needs to be in an open-state conformation to interact with ACE2 as part of the viral entry mechanism. We utilise coarse-grained normal-mode analyses to model the dynamics of Spike and calculate transition probabilities between states for 17081 Spike variants. Our results correctly model an increase in open-state occupancy for the more infectious D614G via an increase in flexibility of the closed-state and decrease of flexibility of the open-state. We predict the same effect for several mutations on Glycine residues (404, 416, 504, 252) as well as residues K417, D467 and N501, including the N501Y mutation, explaining the higher infectivity of the B.1.1.7 and 501.V2 strains. This is, to our knowledge, the first use of normal-mode analysis to model conformational state transitions and the effect of mutations thereon. The specific mutations of Spike identified here may guide future studies to increase our understanding of SARS-CoV-2 infection mechanisms and guide public health in their surveillance efforts.
Temporal Shifts in Antibiotic Resistance Elements Govern Virus-Pathogen Conflicts
Authors: LeGault Kristen , Hays Stephanie G. , Angermeyer Angus , McKitterick Amelia C. , Johura Fatema-tuz , Sultana Marzia , Alam Munirul , Seed Kimberley D.
Published: December 2020

Bacteriophage predation selects for diverse anti-phage systems that frequently cluster on mobilizable defense islands in bacterial genomes. However, there remains a lack of molecular insight into the reciprocal dynamics of phage-bacterial adaptations in nature, particularly in clinical contexts where there is need to inform phage therapy efforts and understand how phages drive pathogen evolution. Here, using time-shift experiments we show that fluctuations in SXT integrative and conjugative elements (ICEs), which notoriously confer antibiotic resistance, govern Vibrio choleraes susceptibility to phages in clinical samples. We find that SXT ICEs, which are widespread in Gammaproteobacteria, invariably encode phage defense and function to protect other genera from phage attack following conjugation. We discover phage counter-adaptation to SXT-mediated restriction in clinical samples, and show that heterogeneity in SXT ICEs allows for re-emergence of phage resistance. Further, phage infection stimulates high frequency SXT ICE conjugation, leading to the concurrent dissemination of phage and antibiotic resistance.
A possible molecular mechanism for mechanotransduction at cellular focal adhesion complexes
Authors: Kim Jichul
Published: December 2020

Mechanotransduction at focal adhesion complexes is key for various cellular events. Theoretical analyses were performed to predict a potential role of lipid membranes in modulating mechanotransduction at focal adhesions. Calculations suggest that the nanoscale geometric changes and mechanical pulling applied on lipid membranes affect the generation of cellular traction forces and signaling transduction at focal adhesions. This work provides predictions on how lipid membranes contribute to mechanotransduction at cellular focal adhesions.

Significance statement

Focal adhesion machinery formed across cell membranes orchestrates a variety of signaling and adhesive molecules to function for important cellular physiologies. Although there are evidences that lipid membranes are involved in mechanical transduction at focal adhesions, how the detailed mechanical response of membranes contributes to the process is not identified yet. With numerous data previously identified, predictions made by theoretical modeling suggest that the nonlinear pulling response of lipid membranes serves as a key factor to interpret mechanotransduction at focal adhesions.
Population dynamics and ranging behaviours of provisioned silvered langur (Trachypithecus cristatus) in Peninsular Malaysia
Authors: Mohd-Daut Norlinda , Matsuda Ikki , Abidin Kamaruddin Zainul , Md-Zain Badrul Munir
Published: December 2020

Tourists are attracted to the Bukit Melawati Kuala Selangor (BMKS) of Peninsular Malaysia, a small hill park, both for its status as a historical site and the free-ranging silvered langurs (Trachypithecus cristatus) that come for provisioning. We assessed the population trends and group sizes ofT. cristatusover 10 years in the BMKS and examined their ranging patterns. Comparisons of observed populations between 2005 (190 individuals) and 2017 (193 individuals) revealed the stable demography and group sizes of the sixT. cristatusgroups in the BMKS. Based on a total of 185 location points of the six groups in 2017, their mean ranging area was 3.6 ha with a range of 0.86 to 6.93 ha with extensive spatial overlap. We also found a significant positive relationship between the six groups’ ranges and group sizes in 2017. Additionally, qualitative ecological comparisons with a previous study onT. cristatusin 1965 (before provisioning) suggest that the artificial food supply in the study area could modify the population dynamics and socioecology ofT. cristatus. The modifications might alter their range size and territoriality in the BMKS. Overall, we found that provisioning had negative effects on the ecology ofT. cristatusin the BMKS. Therefore, modifying management policies, such as banning feeding and implementing educational programs, may contribute to their proper conservation.
Molecular diversity analysis of the spike glycoprotein (S) gene from Hong Kong - China
Authors: Da Silva Eduarda Doralice Alves Braz , Venâncio Dallynne Bárbara Ramos , de Albuquerque Rosane Maria , Ramos Robson da Silva , Felix Pierre Teodósio
Published: December 2020

In this work, 37 haplotypes of spike glycoprotein of SARS-CoV-2 from Hong Kong, China, were used. All sequences were publicly available on the Platform of the National Center for Biotechnology Information (NCBI) and were analyzed for their Molecular Variance (AMOVA), haplotypic diversity, mismatch, demographic and spatial expansion, molecular diversity and time of evolutionary divergence. The results suggested that there was a low diversity among haplotypes, with very low numbers of transitions, transversions, indels-type mutations and with total absence of population expansion perceived in the neutrality tests. The estimators used in this study supported the uniformity among all the results found and confirm the evolutionary conservation of the gene, as well as its protein product, a fact that stimulates the use of therapies based on neutralizing antibodies, such as vaccines based on protein S.
An enhanced yeast display platform demonstrates the binding plasticity under various selection pressures
Authors: Zahradník Jiří , Dey Debabrata , Marciano Shir , Schreiber Gideon
Published: December 2020

Yeast surface display is popularin vitroevolution method. Here, we enhanced the method by multiple rounds of DNA and protein engineering, resulting in increased protein stabilities, surface expression, and enhanced fluorescence. The pCTcon2 yeast display vector was rebuild, introducing surface exposure tailored reporters – eUnaG2 and DnbALFA, creating a new platform of C and N terminal fusion vectors. In addition to gains in simplicity, speed, and cost, new applications were included to monitor protein surface exposure and protein retention in the secretion pathway. The enhanced methodologies were applied to investigatede-novoevolution of protein-protein interaction sites. Selecting binding from a mix of 6 protein-libraries towards two targets using high stringency selection led to the isolations of single high-affinity binders to each of the targets, without the need for high complexity libraries. Conversely, low-stringency selection resulted in the creation of many solutions for weak binding, demonstrating the plasticity of weakde-novointeractions.
Virtual care with digital technologies for rural and remote Canadians living with cardiovascular disease
Authors: Buyting Ryan , Melville Sarah , Chatur Hanif , White Christopher W. , Légaré Jean-François , Lutchmedial Sohrab , Brunt Keith R.
Published: December 2020

Canada is a wealthy nation with a geographically diverse population, seeking health innovations to better serve patients in accordance with the Canada Health Act. In this country, population and geography converge with social determinants, policy, procurement regulations, and technological advances, in order to achieve equity in the management and distribution of healthcare. Rural and remote patients are a vulnerable population; when managing chronic conditions such as cardiovascular disease, there is inequity when it comes to accessing specialist physicians at the recommended frequency—increasing the likelihood of poor health outcomes. Ensuring equitable care for this population is an unrealized priority of several provincial and federal government mandates. Virtual care technology may provide practical, economical, and innovative solutions to remedy this discrepancy. Here we review the literature pertaining to the use of virtual care technologies to monitor patients with cardiovascular disease living in rural areas of Canada. A search strategy was developed to identify the literature specific to this context across three bibliographic databases. 166 unique citations were ultimately assessed for eligibility, of which 36 met the inclusion criteria. In our assessment of these articles, we provide a summary of the interventions studied, their reported effectiveness in reducing adverse events and mortality, the challenges to implementation, and the receptivity of these technologies amongst patients, providers and policy makers. Further, we glean insight into the barriers and opportunities to ensure equitable care for rural patients and conclude that there is an ongoing need for clinical trials assessing virtual care technologies in this context.

Patients living in rural and remote communities’ experience diverse challenges to receiving equitable healthcare as is mandated by the Canada Health Act. Advances in virtual care technology may provide practical, economical, and innovative solutions to ensure this for patients in remote and rural living situations. Here we provide a state-of-the-art review of virtual care technologies available to patients with cardiovascular disease living in rural areas of Canada.
Prevalence of functional dyspepsia in medical students: protocol for a systematic review and meta-analysis
Authors: Caldas Giulior A. Marrull , Farfán Nicolas Silva , Sauca Andres Penny , Ortega Steffi N. Roca , Zafra-Tanaka Jessica Hanae
Published: December 2020

Background

Dyspepsia is defined as a syndrome that comprises a series of chronic and recurrent disorders in the upper digestive tract. According to a meta-analysis carried out in 2014, the worldwide prevalence of dyspepsia is 20.8%, being the highest prevalence found in South America with 37.7%. It was found that there are populations that present a higher prevalence of dyspepsia that is associated with high levels of stress, such as those that can be found in medical students, so It would be important to evaluate the population of medical students, since the medical career, by its nature, represents a great academic load on the student who may later suffer from gastrointestinal diseases.

Review question

What is the prevalence of functional dyspepsia in medical students?

Objective

To determine the prevalence of dyspepsia in medical students and to assess genre differences

Methods

We will conduct a systematic review and meta-analysis. We will use the following search engines: PubMed, Global Index Medicus and EMBASE using search terms related to functional dyspepsia and medical students. We will include observational studies (either cross-sectional or cohort studies) that assessed the prevalence of functional dyspepsia among this particular population.

Conclusion

Currently, no systematic review or meta-analysis has been conducted about the prevalence of functional dyspepsia among this population of students. The aim of this work is to summarize the available literature regarding this topic.
Risk Factors for SARS-CoV-2 Seropositivity in a Health Care Worker Population
Authors: Schubl Sebastian D. , Figueroa Cesar , Palma Anton M. , de Assis Rafael R. , Jain Aarti , Nakajima Rie , Jasinkas Alguimantas , Brabender Danielle , Naaseh Ariana , Dominguez Oscar Hernandez , Runge Ava , Skochko Shannon , Chinn Justine , Kelsey Adam James , Lai Kieu Thai , Zhao Weian , Horvath Peter , Tifrea Delia , Grigorian Areg , Gonzales Abran , Adelsohn Suzanne , Zaldivar Frank , Edwards Robert , Amin Alpesh N. , Stamos Michael J. , Barie Philip S. , Felgner Philip L. , Khan Saahir
Published: December 2020

Background

Protecting health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic is essential. Serologic testing can identify HCWs who had minimally symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that were missed by occupational screening based on daily symptom and temperature checks. Recent studies report conflicting results regarding the impact of occupational factors on SARS-CoV-2 seropositivity amongst HCWs.

Methods

The study population included all hospital workers at an academic medical center in Orange County, California. SARS-CoV-2 seropositivity was assessed from a fingerstick blood specimen using a coronavirus antigen microarray, which compares IgM and IgG antibodies against a panel of SARS-CoV-2 antigens with positive and negative controls to identify prior SARS-CoV-2 infection with 98% specificity and 93% sensitivity. Demographic, occupational, and clinical factors were surveyed and their effect on seropositivity estimated using multivariable logistic regression analysis.

Results

Amongst 1,557 HCWs with complete data, SARS-CoV-2 seropositivity was 10.8%. Risk factors for increased seropositivity included male gender, exposure to COVID-19 outside of work, working in food or environmental services, and working in COVID-19 units. Amongst the 1,103 HCW who were seropositive but missed by occupational screening, additional risk factors included younger age and working in administration.

Conclusions

SARS-CoV-2 seropositivity is significantly higher than reported case counts even amongst HCWs who are meticulously screened. Seropositive HCWs missed by occupational screening were more likely to be younger, work roles without direct patient care, or have COVID-19 exposure outside of work.

Key Points

SARS-CoV-2 seropositivity risk factors amongst health care workers included male gender, nonoccupational exposure, food or environmental services role, and COVID-19 unit location. Those missed by occupational screening were younger, in roles without direct patient care, or exposed outside of work.
TUGDA: Task uncertainty guided domain adaptation for robust generalization of cancer drug response prediction fromin vitrotoin vivosettings
Authors: da Silva Rafael Peres , Suphavilai Chayaporn , Nagarajan Niranjan
Published: December 2020

Over the last decade, large-scale cancer omics studies have highlighted the diversity of patient molecular profiles and the importance of leveraging this information to deliver the right drug to the right patient at the right time. Key challenges in learning predictive models for this include the high-dimensionality of omics data, limitations in the number of data points available, and heterogeneity in biological and clinical factors affecting patient response. The use of multi-task learning (MTL) techniques has been widely explored to address dataset limitations forin vitrodrug response models, while domain adaptation (DA) has been employed to extend them to predict in vivo response. In both of these transfer learning settings, noisy data for some tasks (or domains) can substantially reduce the performance for others compared to single-task (domain) learners, i.e. lead to negative transfer (NT). We describe a novel multi-task unsupervised domain adaptation method (TUGDA) that addresses these limitations in a unified framework by quantifying uncertainty in predictors and weighting their influence on shared domain/task feature representations. TUGDA’s ability to rely more on predictors with low-uncertainty allowed it to notably reduce cases of negative transfer forin vitromodels (63% for drugs with limited data and 94% overall) compared to state-of-the-art methods. For domain adaptation toin vivosettings, TUGDA improved performance for 6 out of 12 drugs in patient-derived xenografts, and 7 out of 22 drugs in TCGA patient datasets, despite being trained in an unsupervised fashion. TUGDA’s ability to avoid negative transfer thus provides a key capability as we try to integrate diverse drug-response datasets to build consistent predictive models within vivoutility.

Availability

https://github.com/CSB5/TUGDA
The jasmine (Jasminum sambac) genome and flower fragrances
Authors: Chen Gang , Mostafa Salma , Lu Zhaogeng , Du Ran , Cui Jiawen , Wang Yun , Liao Qinggang , Lu Jinkai , Mao Xinyu , Chang Bang , Wang Li , Jia Zhichao , Yang Xiulian , Zhu Yingfang , Yan Jianbin , Jin Biao
Published: December 2020

Jasminum sambac, a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the firstde novogenome ofJ. sambacwith 550.12 Mb (scaffold N50 = 40.1 Mb) assembled into 13 pseudochromosomes. Terpene synthase genes associated with flower fragrance are significantly amplified in the form of gene clusters through tandem duplications in the genome. Eleven homolog genes within the SABATH super-family were identified as related to phenylpropanoid/benzenoid compounds. Several key genes regulating jasmonate biosynthesis were duplicated causing increased copy numbers. Furthermore, multi-omics analyses identified various aromatic compounds and the key genes involved in fragrance biosynthesis pathways. Our genome ofJ. sambacoffers a basic genetic resource for studying floral scent biosynthesis and provides an essential foundation for functional genomic research and variety improvements inJasminum.
Atg4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system
Authors: Nguyen Thanh Ngoc , Padman Benjamin Scott , Zellner Susanne , Uoselis Louise , Skulsuppaisarn Marvin , Behrends Christian , Lazarou Michael
Published: December 2020

The sequestration of damaged mitochondria within double-membrane structures termed autophagosomes is a key step of PINK1/Parkin mitophagy. The Atg4 family of proteases are thought to regulate autophagosome formation exclusively by processing the ubiquitin-like Atg8 family (LC3/GABARAPs). We make the unexpected discovery that human Atg4s can directly promote autophagosome formation independently of their protease activity and of Atg8 family processing. High resolution structures of phagophores generated with artificial intelligence-directed 3D electron microscopy reveal a role for the Atg4 family in promoting phagophore-ER contacts during the lipid-transfer phase of autophagosome formation. Atg4 proximity interaction networks stimulated by PINK1/Parkin mitophagy are consistent with roles for Atg4s in protein/vesicle transport and lipid modification. We also show that Atg8 removal during autophagosome maturation does not depend on Atg4 de-lipidation activity as previously thought. Instead, we find that Atg4s can disassemble Atg8-protein conjugates, revealing a role for Atg4s as deubiquitinating-like enzymes. These findings establish non-canonical roles of the Atg4 family beyond the Atg8 lipidation axis and provide an AI driven framework for high-throughput 3D electron microscopy.
Body mass and latitude predict the presence of multiple stressors in global vertebrate populations
Authors: Noviello Nicola , McRae Louise , Freeman Robin , Clements Chris
Published: December 2020

Multiple stressors are recognised as a key threat to biodiversity, but our understanding of what might predispose species to multiple stressors remains limited. Here we analyse a global dataset of over 7000 marine, freshwater, and terrestrial vertebrate populations, alongside species-specific trait data, to identify factors which influence the number of stressors a species is subjected to at the population level. We find that body mass and latitude can both influence the number of stressors a population is subjected to across ecosystems, with large-bodied species tending to be more threatened, except terrestrial amphibians which show the opposite trend. Latitudinal forecasts predict higher stressor numbers between 20°N and 40°N, and towards the poles. Global stressor distributions suggest a link between human population centres and stressor frequency generally impacting larger-bodied species. Latitude and body mass hence provide key predictive tools to identify which vertebrate populations are likely to be highly threatened, despite the strength of these trends differing between ecological system and taxonomic class.
Conformational plasticity and dynamic interactions of the N-terminal domain of the chemokine receptor CXCR1
Authors: Kharche Shalmali , Joshi Manali , Chattopadhyay Amitabha , Sengupta Durba
Published: December 2020

Dynamic interactions between G protein-coupled receptors (GPCRs) and their cognate protein partners at the membrane interface control several cellular signaling pathways. An important example is the association of CXC chemokine receptor 1 (CXCR1) with its cognate chemokine, interleukin-8 (IL8 or CXCL8) that regulates neutrophil-mediated immune responses. Although the N-terminal domain of the receptor is known to confer ligand selectivity, the conformational dynamics of this intrinsically disordered region of CXCR1 in particular, and chemokine receptors in general, remains unresolved. In this work, we have explored the interaction of CXCR1 with IL8 by microsecond time scale coarse-grain simulations that were validated by atomistic models and NMR chemical shift predictions. We show that the conformational plasticity of theapo-receptorN-terminal region is restricted upon ligand binding, driving it to an open C-shaped conformation. Importantly, we validated the dynamic complex sampled in our simulations against chemical shift perturbations reported by previous NMR studies. Our results indicate that caution should be exercised when chemical shift perturbation is used as a reporter of residue contacts in such dynamic associations. We believe our results represent a step forward in devising a strategy to understand intrinsically disordered regions in GPCRs and how they acquire functionally important conformational ensembles in dynamic protein-protein interfaces.

Author summary

How cells communicate with the outside environment is intricately controlled and regulated by a large family of receptors on the cell membrane (G protein-coupled receptors or GPCRs) that respond to external signals (termed ligands). Chemokine receptors belong to this GPCR family and regulate immune responses. We analyze here the first step of binding of a representative chemokine receptor (CXCR1) with its natural ligand, interleukin 8 (IL8) by an extensive set of molecular dynamics simulations. Our work complements previous mutational and NMR experiments which lack molecular-level resolution. We show that in the inactive state, one of the extracellular domains of the CXCR1 receptor, namely the N-terminal domain, is highly flexible and like a “shape-shifter” can exist in multiple conformational states. However, when IL8 binds, the N-terminal domain undergoes a conformational freezing, and acquires a C-shaped “claw-like” structure. The complex between the receptor and IL8 is still quite dynamic as this C-shaped N-terminal domain forms an extensive but slippery interface with the ligand. We further validated these results by quantitative comparison with NMR and mutagenesis studies. Our work helps clarify the inherent disorder in N-terminal domains of chemokine receptors and demonstrates how this domain can acquire functionally important conformational states in dynamic protein-protein interfaces.
Chromosome-scale genome assembly of Japanese pear (Pyrus pyrifolia) variety ‘Nijisseiki’
Authors: Shirasawa Kenta , Itai Akihiro , Isobe Sachiko
Published: December 2020

Aim

The Japanese pear (P. pyrifolia) variety ‘Nijisseiki’ is valued for its superior flesh texture, which has led to its use as a breeding parent for most Japanese pear cultivars. However, in the absence of genomic resources for Japanese pear, the parents of the ‘Nijisseiki’ cultivar remain unknown, as does the genetic basis of its favorable texture. The genomes of pear and related species are complex due to ancestral whole genome duplication and high heterozygosity, and long-sequencing technology was used to address this.

Methods and Results

De novo assembly of long sequence reads covered 136× of the Japanese pear genome and generated 503.9 Mb contigs consisting of 114 sequences with an N50 value of 7.6□Mb. Contigs were assigned to Japanese pear genetic maps to establish 17 chromosome-scale sequences. In total, 44,876 protein-encoding genes were predicted, 84.3% of which were supported by predicted genes and transcriptome data from Japanese pear relatives. As expected, evidence of whole genome duplication was observed, consistent with related species.

Conclusion and Perspective

This is the first genome sequence analysis reported for Japanese pear, and this resource will support breeding programs and provide new insights into the physiology and evolutionary history of Japanese pear.
Do initial concentration and activated sludge seasonality affect pharmaceutical biodegradation rate constants?
Authors: van Bergen Tamara J.H.M. , Rios-Miguel Ana B. , Nolte Tom M. , Ragas Ad M.J. , van Zelm Rosalie , Graumans Martien , Scheepers Paul , Jetten Mike S.M. , Hendriks A. Jan , Welte Cornelia U.
Published: December 2020

Pharmaceuticals find their way to the aquatic environment via wastewater treatment plants (WWTPs) and biodegradation plays an important role in mitigating environmental risks, however a mechanistic understanding of involved processes is limited. The aim of this study was to evaluate potential relationships between first-order biodegradation rate constants (kb) of nine pharmaceuticals and initial concentration of the selected compounds, and sampling season of the used activated sludge inocula. Four-day bottle experiments were performed with activated sludge from WWTP Groesbeek (The Netherlands) of two different seasons, summer and winter, spiked with two environmentally relevant concentrations (3 and 30 nM) of pharmaceuticals. Concentrations of the compounds were measured by LC-MS/MS, microbial community composition was assessed by 16S rRNA gene amplicon sequencing and kbvalues were calculated. The biodegradable pharmaceuticals, ranked from high to low biodegradation rates, were acetaminophen, metformin, metoprolol, terbutaline, and phenazone. Carbamazepine, diatrizoic acid, diclofenac and fluoxetine were not converted. Summer and winter inocula did not show significant differences in microbial community composition, but resulted in a slightly different kbfor some pharmaceuticals. Likely microbial activity was responsible instead of community composition. In the same inoculum different kbvalues were measured, depending on initial concentration. In general, biodegradable compounds had a higher kbwhen the initial concentration was higher. This demonstrates that Michealis-Menten kinetics theory has shortcomings for some pharmaceuticals at low, environmentally relevant concentrations and that the pharmaceutical concentration should be taken into account when measuring the kbin order to reliably predict the fate of pharmaceuticals in the WWTP.
Clustered Loss of Dendritic Spines Characterizes Encoding of Related Memory
Authors: Kumar Suraj , Kumar Meenakshi Prabod , Kaushik Yagika , Jayaprakash Balaji
Published: December 2020

Generation of new spines is often thought of as a correlate of memory and loss of spines is considered representing memory loss. Contrary to common belief, we observe that spine loss has functional value in distinctly encoding related life events rather than causing memory loss. Using spatial autocorrelation of dendritic morphology obtained from in vivo longitudinal imaging, we show that clustered loss, rather than gain, of new spines characterizes the formation of related memory. This spatially selective dendritic spine loss occurs closer to new spines formed during the acquisition of initial memory. Thus, enabling the dendrites to store multiple memories and their inter relationship. Remarkably, we find acquisition of related memory in the absence of NMDAR activation increases the fraction of such correlated spine loss.
Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior
Authors: Kantonen Tatu , Karjalainen Tomi , Pekkarinen Laura , Isojärvi Janne , Kalliokoski Kari , Kaasinen Valtteri , Hirvonen Jussi , Nuutila Pirjo , Nummenmaa Lauri
Published: December 2020

Eating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central µ-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain’s opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating – individuals with low MORs reported being more likely to eat in response to environment’s palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.
Using physiological signals to predict temporal defense responses: a multi-modality analysis
Authors: Choi Tae-jun , Lee Honggu
Published: December 2020

Defense responses are a highly conserved behavioral response set across species. Defense responses motivate organisms to detect and react to threats and potential danger as a precursor to anxiety. Accurate measurement of temporal defense responses is important for understanding clinical anxiety and mood disorders, such as post-traumatic stress disorder, obsessive compulsive disorder, and generalized anxiety disorder. Within these conditions, anxiety is defined as a state of prolonged defense response elicitation to a threat that is ambiguous or unspecific. In this study, we aimed to develop a data-driven approach to capture temporal defense response elicitation through a multi-modality data analysis of physiological signals, including electroencephalogram (EEG), electrocardiogram (ECG), and eye-tracking information. A fear conditioning paradigm was adopted to develop a defense response classification model. From a classification model based on 42 feature sets, a higher order crossing feature set-based model was chosen for further analysis with cross-validation loss of 0.0462 (SEM: 0.0077). To validate our model, we compared predicted defense response occurrence ratios from a comprehensive situation that generates defense responses by watching movie clips with fear awareness and threat existence predictability, which have been reported to correlate with defense response elicitation in previous studies. We observed that defense response occurrence ratios are correlated with threat existence predictability, but not with fear awareness. These results are similar to those of previous studies using comprehensive situations. Our study provides insight into measurement of temporal defense responses via a novel approach, which can improve understanding of anxiety and related clinical disorders for neurobiological and clinical researchers.
Genome-wide DNA mutations inArabidopsisplants after multigenerational exposure to high temperature
Authors: Lu Zhaogeng , Cui Jiawen , Wang Li , Teng Nianjun , Zhang Shoudong , Lam Hon-Ming , Zhu Yingfang , Xiao Siwei , Ke Wensi , Lin Jinxing , Xu Chenwu , Jin Biao
Published: December 2020

Background

Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown.

Results

Here we report that multigenerational exposure ofArabidopsisto extreme heat and moderate warming resulted in significantly increased mutation rates in single-nucleotide variants (SNVs) and small indels. We observed distinctive mutational spectra under extreme and moderately elevated temperatures, with significant increases in transition (C:G→T:A) and transversion (A:T→T:A) frequencies. Mutation occurred more frequently in intergenic regions, coding regions (especially nonsynonymous mutations), and transposable elements (TEs). At elevated temperatures, more mutations accumulated in genes associated with defense responses, DNA repair, and signaling, including the transcriptional response–related genesHSP70andHSFA1A. Methylation was observed more frequently at mutation sites, indicating that it contributed significantly to the mutation process at elevated temperatures. Moreover, the mutations in lines and populations grown under elevated temperatures were significantly biased toward low gene density regions, special trinucleotides (GC context), tandem repeats, and adjacent simple repeats. Additionally, 24% (n= 64) of SNVs and 43% (n= 40) of indels found in all mutation accumulation lines overlapped significantly with genetic variations reported in 1001 Genomes, suggesting a non-uniform distribution of de novo mutations through the genome.

Conclusion

Collectively, our results suggest that elevated temperatures can accelerate the accumulation, and alter the molecular profiles, of DNA mutations in plants, thus providing significant insight into how environmental temperatures fuel plant evolution.
Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19
Authors: Povysil Gundula , Butler-Laporte Guillaume , Shang Ning , Weng Chen , Khan Atlas , Alaamery Manal , Nakanishi Tomoko , Zhou Sirui , Forgetta Vincenzo , Eveleigh Robert , Bourgey Mathieu , Aziz Naveed , Jones Steven , Knoppers Bartha , Scherer Stephen , Strug Lisa , Lepage Pierre , Ragoussis Jiannis , Bourque Guillaume , Alghamdi Jahad , Aljawini Nora , Albes Nour , Al-Afghani Hani M. , Alghamdi Bader , Almutair Mansour , Mahmoud Ebrahim Sabri , Safie Leen Abu , Bardisy Hadeel El , Harthi Fawz S. Al , Alshareef Abdulraheem , Suliman Bandar Ali , Alqahtani Saleh , AlMalik Abdulaziz , Alrashed May M. , Massadeh Salam , Mooser Vincent , Lathrop Mark , Arabi Yaseen , Mbarek Hamdi , Saad Chadi , Al-Muftah Wadha , Badji Radja , Thani Asma Al , Ismail Said I. , Gharavi Ali G. , Abedalthagafi Malak S. , Richards J Brent , Goldstein David B. , Kiryluk Krzysztof
Published: December 2020

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.
Consensus based framework for digital mobility monitoring
Authors: Kluge Felix , Din Silvia Del , Cereatti Andrea , Gaßner Heiko , Hansen Clint , Helbostad Jorunn L , Klucken Jochen , Küderle Arne , Müller Arne , Rochester Lynn , Ullrich Martin , Eskofier Bjoern M , Mazzà Claudia ,   Mobilise-D consortium
Published: December 2020

Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient’s natural environment. It enables the monitoring of health status and disease progression and the evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. Hence, there is a need for a terminological framework guiding further implementation of digital measures for gait assessment. We used an objective methodology based on an adapted Delphi process to obtain consensus on specific terminology related to real-world walking by asking a diverse panel of clinical, scientific, and industrial stakeholders. Six constituents (‘real-world’, ‘walking’, ‘purposeful’, ‘walking bout’, ‘walking speed’, ‘turning’) have successfully been defined in two feedback rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment.
Population Changes in Seroprevalence among a Statewide Sample in the United States
Authors: Malecki Kristen , Nikodemova Maria , Schultz Amy A. , Bersch Andrew , Walsh Matthew C , Sethi Ajay K , Peppard Paul , Engelman Corinne , Cadmus-Bertram Lisa , Safdar Nasia , Bateman Allen , Westergaard Ryan
Published: December 2020

Antibody surveillance provides essential information for public health officials to work with communities to discuss the spread and impact of COVID-19. At the start of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the United States, diagnostic testing was limited with many asymptomatic and thus undetected cases. Irrespective of symptom severity, antibodies develop within two to three weeks after exposure and may persist 6 months or more.; Thus, antibody surveillance is an important tool for tracking trends in past infections across diverse populations. This study includes adults and children (≥12 years old) recruited from a statewide sample of past 2014-2020 Survey of the Health of Wisconsin (SHOW) participants. SHOW, an ongoing population-based health examination study including a randomly selected sample of households, partnered with the Wisconsin Department of Health Services and the Wisconsin State Laboratory of Hygiene to conduct longitudinal antibody surveillance using the Abbott Architect SARS-CoV-2 IgG antibody test, which detects antibodies against the nucleocapsid protein. Three WAVES of sample collection were completed in 2020-2021, tracking mid-summer, late fall, and early spring COVID-19 trends prior to vaccine availability. Crude estimates of seroprevalence in the total study population increased ten-fold from 1.4% during WAVE I to 11.5% in WAVE III. Within the statewide probability sample, weighted estimates increased from 1.6% (95% CI:0.6-2.5%), to 6.8% (95% CI:4.3-9.4%) in WAVE II and to 11.4% (95% CI:8.2, 14.6%) in WAVE III. Longitudinal trends in seroprevalence match statewide case counts. Local seroprevalence showed variation by state health region with increasing prevalence among higher income (>200% poverty income ratio), and rural health regions of the state seeing the highest increase in COVID-19 prevalence over time. Significant disparities in prevalence by racial and ethnic groups also exist, with greater than two times seroprevalence among Latino and black participants compared to non-Hispanic whites. This public health and academic partnership provides critical data for the ongoing pandemic response and lays the foundation for future research into longer-term immunity, health impacts and population-level disparities.
SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of MS patients
Authors: Ostendorf Lennard , Dittert Philipp , Biesen Robert , Duchow Ankelien , Stiglbauer Victoria , Ruprecht Klemens , Seelow Dominik , Niesner Raluca A. , Hauser Anja E. , Paul Friedemann , Radbruch Helena
Published: December 2020

Objective

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in Multiple Sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the specificity of SIGLEC1+ myeloid cells for demyelinating diseases

Methods

We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases.

Results

We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions.

Conclusion

In our cohort, SIGLEC1 expression on monocytes was – apart from those patients receiving interferon treatment – not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.
TFMLAB: a MATLAB toolbox for 4D traction force microscopy
Authors: Barrasa Fano Jorge , Shapeti Apeksha , Jorge-Penas Alvaro , Barzegari Mojtaba , Sanz Herrera Jose A , Van Oosterwyck Hans
Published: December 2020

We present TFMLAB, a MATLAB software package for 4D (x;y;z;t) Traction Force Microscopy (TFM). While various TFM computational workflows are available in the literature, open-source programs that are easy to use by researchers with limited technical experience and that can analyze 4D in vitro systems do not exist. TFMLAB integrates all the computational steps to compute active cellular forces from confocal microscopy images, including image processing, cell segmentation, image alignment, matrix displacement measurement and force recovery. Moreover, TFMLAB eases usability by means of interactive graphical user interfaces. This work describes the package's functionalities and analyses its performance on a real TFM case.