bluuebunny/crossref_metadata_2025 huggingface dataset:
ClustENMD: efficient sampling of biomolecular conformational space at atomic resolution
Authors: Kaynak Burak T , Zhang She , Bahar Ivet , Doruker Pemra
Published: July 2021

Efficient sampling of conformational space is essential for elucidating functional/allosteric mechanisms of proteins and generating ensembles of conformers for docking applications. However, unbiased sampling is still a challenge especially for highly flexible and/or large systems. To address this challenge, we describe a new implementation of our computationally efficient algorithm ClustENMD that is integrated with ProDy and OpenMM softwares. This hybrid method performs iterative cycles of conformer generation using elastic network model for deformations along global modes, followed by clustering and short molecular dynamics simulations. ProDy framework enables full automation and analysis of generated conformers and visualization of their distributions in the essential subspace.

Availability and implementation

ClustENMD is open-source and freely available under MIT License from https://github.com/prody/ProDy.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical characteristics and risk stratification of desmoplakin cardiomyopathy
Authors: Wang Weijia , Murray Brittney , Tichnell Crystal , Gilotra Nisha A , Zimmerman Stefan L , Gasperetti Alessio , Scheel Paul , Tandri Harikrishna , Calkins Hugh , James Cynthia A
Published: July 2021

Aims

Desmoplakin (DSP) cardiomyopathy is an increasingly recognized form of arrhythmogenic cardiomyopathy. With a genotype-specific approach, we characterized the diagnosis, natural history, and risk for ventricular arrhythmia and heart failure in DSP cardiomyopathy.

Methods and results

We followed 91 individuals [45 probands, 34% male, median age 27.5 years (interquartile interval 20.0–43.9)] with pathogenic or likely pathogenic DSP variants for a median of 4.3 years. Regarding the ventricular involvement, left predominance was most common (n = 22, 28%) followed by bi-ventricular in 12 (15%) and right predominance in 5 (6%). Myocardial injury (chest pain, elevated troponin, normal coronary angiogram) occurred in 20 (22%) individuals. Incidence rates of sustained ventricular arrhythmia and heart failure (ventricular dysfunction ± symptoms) were 5.9 [95% confidence interval (CI): 3.9–9.1] and 6.7 (95% CI: 4.5–9.8) per 100 person-years, respectively. In univariate regression, myocardial injury was associated with sustained ventricular arrhythmia [hazard ratio (HR) 2.53, 95% CI: 1.05–6.11] and heart failure (HR 7.53, 95% CI: 3.10–18.26). After adjustment, left ventricular ejection fraction <35% and right ventricular dysfunction were prognostic for sustained ventricular arrhythmia while proband status and myocardial injury were prognostic for heart failure (all P < 0.05). The sensitivity of the arrhythmogenic right ventricular cardiomyopathy Task Force Criteria in diagnosing left dominant disease was 0.73; 5/22 (23%) of patients with sustained ventricular arrhythmias did not meet these criteria.

Conclusion

DSP cardiomyopathy affects both ventricles and carries high risk for ventricular arrhythmia and heart failure. Myocardial injury is associated with worse disease outcomes. Both diagnosis and risk stratification of DSP cardiomyopathy need refinement.
Understanding Elderspeak: An Evolutionary Concept Analysis
Authors: Shaw Clarissa A , Gordon Jean K
Published: July 2021

Background and Objectives

Elderspeak is an inappropriate simplified speech register that sounds like baby talk and is used with older adults, especially in health care settings. Understanding the concept of elderspeak is challenging due to varying views about which communicative components constitute elderspeak and whether elderspeak is beneficial or harmful for older adults.

Research Design and Methods

Rodgers’ evolutionary concept analysis method was used to evaluate the concept of elderspeak through identification of elderspeak’s attributes, antecedents, and consequences. A systematic search using the PubMed, CINAHL, PsycINFO, and Embase databases was completed.

Results

Eighty-three theoretical or research articles from 1981 to 2020 were identified. Elderspeak characteristics were categorized by semantic, syntactic, pragmatic, paralinguistic, and nonverbal attributes. The primary antecedent to elderspeak is implicit ageism, in which old age cues and signs of functional or cognitive impairment led to simplified communication, usually from a younger caregiver. Research studies varied in reporting whether elderspeak facilitated or interfered with comprehension by older adults, in part depending on the operational definition of elderspeak and experimental manipulations. Exaggerated prosody, a key feature of elderspeak, was found to reduce comprehension. Elderspeak was generally perceived as patronizing by older adults and speakers were perceived as less respectful. In persons with dementia, elderspeak also increases the probability of resistiveness to care, which is an important correlate of behavioral and psychological symptoms of dementia.

Discussion and Implications

Based on this concept analysis, a new definition of elderspeak is proposed, in which attributes that have been found to enhance comprehension are differentiated from those that do not. Recommendations for consistent operationalization of elderspeak in future research are made.
Free Rosenthal Inequalities on Vector-Valued Symmetric Operator Spaces
Authors: Jiao Yong , Sukochev Fedor , Xie Guangheng , Zanin Dmitriy
Published: July 2021

Let $\mathcal{M}$ be a finite von Neumann algebra and let $E$ be an interpolation space between $L_1(0,1)$ and $L_{\infty }(0,1)$. For every $q\in [1,\infty ]$, we introduce a general notion of a vector-valued symmetric operator space $E(\mathcal{M};\ell _q)$ via $K$-functional of the couple $(L_1(\mathcal M;\ell _q),L_{\infty }(\mathcal M;\ell _q))$. We then establish free Rosenthal inequalities on $E(\mathcal{M};\ell _q)$, which provide an equivalent characterization of the quantity $\|(x_k)_{k\geq 0}\|_{E(\mathcal{M};\ell _q)},$ where $(x_k)_{k\geq 0}\subset E(\mathcal{M})$ is a sequence of freely independent random variables.
Constructing Menger Manifold C*-Diagonals in Classifiable C*-Algebras
Authors: Li Xin
Published: July 2021

We initiate a detailed analysis of $C^{\ast }$-diagonals in classifiable $C^{\ast }$-algebras, answering natural questions concerning topological properties of their spectra and uniqueness questions. Firstly, we construct $C^{\ast }$-diagonals with connected spectra in all classifiable stably finite $C^{\ast }$-algebras, which are unital or stably projectionless with continuous scale. Secondly, for classifiable stably finite $C^{\ast }$-algebras with torsion-free $K_0$ and trivial $K_1$, we further determine the spectra of the $C^{\ast }$-diagonals up to homeomorphism. In the unital case, the underlying space turns out to be the Menger curve. In the stably projectionless case, the space is obtained by removing a non-locally-separating copy of the Cantor space from the Menger curve. Thirdly, we show that each of our classifiable $C^{\ast }$-algebras has continuum many pairwise non-conjugate such Menger manifold$C^{\ast }$-diagonals.
In-silico pharmacophore and Molecular Docking based drug discovery against Marburg Virus’s Viral Protein 35; A potent of MAVD
Authors: Quazi Sameer , Gavas Shreelaxmi , Malik Javed Ahmad , Suman Komal Singh , Haider Zeshan
Published: July 2021

Marburg virus is a member of filoviridae and spreads severe Marburg hemorrhagic illness in humans and animals. Nowadays, there is no vaccine available that can completely stop the replication of Marburg replication. Therefore, this study is designed to repurpose the effective therapeutic antiviral drug by using a computational approach against exploring the mechanism of Marburg virus Viral protein 35. We have retrieved about 40570 drug-like small compounds from the ZINC database using the “ZINC Pharmer” online tool. Molecular docking of the ligands from the ready-to-dock database has been carried out using MOE. The five drugs have been identified to bind with VP35 possibly. A study was also performed to evaluate the drug-like characteristics of the substances for absorption, distribution, metabolism, and excretion (ADME). The findings clearly showed that ligands are interacting with the MARV VP35 protein. Interestingly, Lipinski’s rule of five was observed by all ligands. These findings provide the foundation for reconstituting and utilizing molecules as a possible therapy for Marburg Virus Disease (MVD).
Accurate profiling of forensic autosomal STRs using the Oxford Nanopore Technologies MinION device
Authors: Hall Courtney L. , Kesharwani Rupesh K. , Phillips Nicole R. , Planz John V. , Sedlazeck Fritz J. , Zascavage Roxanne R.
Published: July 2021

The high variability characteristic of short tandem repeat (STR) markers is harnessed for human identification in forensic genetic analyses. Despite the power and reliability of current typing techniques, sequence-level information both within and around STRs are masked in the length-based profiles generated. Forensic STR typing using next generation sequencing (NGS) has therefore gained attention as an alternative to traditional capillary electrophoresis (CE) approaches. In this proof-of-principle study, we evaluate the forensic applicability of the newest and smallest NGS platform available – the Oxford Nanopore Technologies (ONT) MinION device. Although nanopore sequencing on the handheld MinION offers numerous advantages, including on-site sample processing, the relatively high error rate and lack of forensic-specific analysis software has prevented accurate profiling across STR panels in previous studies. Here we present STRspy, a streamlined method capable of producing length- and sequence-based STR allele designations from noisy, long-read data. To demonstrate the capabilities of STRspy, seven reference samples (female: n = 2; male: n = 5) were amplified at 15 and 30 PCR cycles using the Promega PowerSeq 46GY System and sequenced on the ONT MinION device in triplicate. Basecalled reads were processed with STRspy using a custom database containing alleles reported in the STRSeq BioProject NIST 1036 dataset. Resultant STR allele designations and flanking region single nucleotide polymorphism (SNP) calls were compared to the manufacturer-validated genotypes for each sample. STRspy generated robust and reliable genotypes across all autosomal STR loci amplified with 30 PCR cycles, achieving 100% concordance based on both length and sequence. Furthermore, we were able to identify flanking region SNPs with >90% accuracy. These results demonstrate that nanopore sequencing platforms are capable of revealing additional variation in and around STR loci depending on read coverage. As the first long-read platform-specific method to successfully profile the entire panel of autosomal STRs amplified by a commercially available multiplex, STRspy significantly increases the feasibility of nanopore sequencing in forensic applications.
Strong phylogenetic signal despite high phylogenomic complexity in an Andean plant radiation (Freziera,Pentaphylacaceae)
Authors: Frost Laura , Bedoya Ana M. , Lagomarsino Laura
Published: July 2021

Abstract

The Andes mountains of western South America are a globally important biodiversity hotspot, yet there is a paucity of resolved phylogenies for plant clades from this region. Filling an important gap to our understanding of the World’s richest flora, we present the first phylogeny ofFreziera(Pentaphylacaceae), an Andean-centered, cloud forest radiation. Our dataset was obtained via hybrid-enriched target sequence capture of Angiosperms353 universal loci for 50 of the ca. 75 spp., obtained almost entirely from herbarium specimens. We identify high phylogenomic complexity inFreziera, including the presence of data artifacts. Via by-eye observation of gene trees, detailed examination of warnings from recently improved assembly pipelines, and gene tree filtering, we identified that artifactual orthologs (i.e., the presence of only one copy of a multi-copy gene due to differential assembly) were an important source of gene tree heterogeneity that had a negative impact on phylogenetic inference and support. These artifactual orthologs may be common in plant phylogenomic datasets, where multiple instances of genome duplication are common. After accounting for artifactual orthologs as source of gene tree error, we identified a significant, but non-specific signal of introgression using Patterson’s D and f4 statistics. Despite phylogenomic complexity, we were able to resolveFrezierainto nine well-supported subclades whose evolution has been shaped by multiple evolutionary processes, including incomplete lineage sorting, historical gene flow, and gene duplication. Our results highlight the complexities of plant phylogenomics, which are heightened in Andean radiations, and show the impact of filtering data processing artifacts and standard filtering approaches on phylogenetic inference.
We get by with a little help from our friends: shared adaptive variation provides a bridge to novel ecological specialists during adaptive radiation
Authors: Richards Emilie J. , Martin Christopher H.
Published: July 2021

Adaptive radiations involve astounding bursts of phenotypic, ecological, and species diversity. However, the microevolutionary processes that underlie the origins of these bursts are still poorly understood. We report the discovery of an intermediate ‘wide-mouth’ scale-eating ecomorph in a sympatric radiation of Cyprinodon pupfishes, illuminating the transition from a widespread algae-eating generalist to a novel microendemic scale-eating specialist. We first show that this ecomorph occurs in sympatry with generalist C. variegatus and scale-eating specialist C. desquamator on San Salvador Island, Bahamas, but is genetically differentiated, morphologically distinct, and often consumes scales. We then compared the timing of selective sweeps on shared and unique adaptive variants in trophic specialists to characterize their adaptive walk. Shared adaptive regions swept first in both the specialist desquamator and the intermediate ‘wide-mouth’ ecomorph, followed by unique sweeps of introgressed variation in ‘wide-mouth’ and de novo variation in desquamator. The two scale-eating populations additionally shared 9% of their hard selective sweeps with molluscivores C. brontotheroides, despite no single common ancestor among specialists. Our work provides a new microevolutionary framework for investigating how major ecological transitions occur and illustrates how both shared and unique genetic variation can provide a bridge for multiple species to access novel ecological niches.
The spatial transcriptomic landscape of the healing intestine following damage
Authors: Parigi Sara M. , Larsson Ludvig , Das Srustidhar , Ramirez Flores Ricardo O. , Frede Annika , Tripathi Kumar P. , Diaz Oscar E. , Selin Katja , Morales Rodrigo A. , Luo Xinxin , Monasterio Gustavo , Engblom Camilla , Gagliani Nicola , Saez-Rodriguez Julio , Lundeberg Joakim , Villablanca Eduardo J.
Published: July 2021

The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics (ST) to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we used our resource to map transcriptomics modules associated with human diseases demonstrating that ST can be used to inform clinical practice. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.
FishExp: a comprehensive database and analysis platform for gene expression and alternative splicing of fish species
Authors: Tan Suxu , Wang Wenwen , Jie Wencai , Liu Jinding
Published: July 2021

The publicly archived RNA-seq data has grown exponentially, but its valuable information has not yet been fully discovered and utilized, especially for alternative splicing. This is true for fish species, which play important roles in ecology, research, and the food industry. To mitigate this, we present FishExp, a web-based data platform covering gene expression and alternative splicing in 26,081 RNA-seq experiments from 44 fishes. In addition to searching by gene identifiers and symbols, FishExp allows users to query the data using various functional terms and BLAST alignment. Notably, the user can customize experiments and tools to perform differential/specific expression and alternative splicing analysis, provided with functional enrichments. The results of retrieval and analysis can be visualized on the gene-, transcript- and splicing event-level webpage in a highly interactive and intuitive manner. The manually curated sample information, uniform data processing and visualization tools make it efficient for users to gain new insights from these large datasets. All data in FishExp can be downloaded for more in-depth analysis. FishExp is freely accessible at https://bioinfo.njau.edu.cn/fishExp.
Single cell characterization of CRISPR-modified transcript isoforms with nanopore sequencing
Authors: Kim Heon Seok , Grimes Susan M , Hooker Anna C , Lau Billy T , Ji Hanlee P
Published: July 2021

Transcript isoforms are mRNAs that arise from alternative splicing events. During RNA processing, different combinations of a gene's exons lead to a diverse set of isoforms. Polymorphisms or mutations at splice junctions can generate alternative splicing events. Various splicing factors also impact the representation of a gene's transcript isoforms. To assess how these two features contribute to alternative splicing, we developed a single cell approach to introduce CRISPR edits that modify mRNA transcript structure. Our method combines (1) long-read sequencing to characterize the expressed transcripts and identify the edit at single cell resolution; (2) short-read sequencing to match the single cell gene expression profiles of the cells with the altered isoform. First, we modify target exon-intron segments with CRISPR-Cas9. Second, using cDNAs with cell barcodes, we use long read sequencing to directly identify the changes in transcript isoforms from the targeted CRISPR edits. As a variation on this approach, we also determined how modifying specific splicing factors influence isoform expression and structure. Overall, we demonstrate how the integration of single cell long read analysis and CRISPR engineering can be used to directly confirm transcript isoform and target genomic edits at single cell resolution. This approach will improve our understanding of the role of alternative splicing in transcriptional regulation.
Inducible Yeast Two-Hybrid with Quantitative Measures
Authors: Hernandez Jesus , Ross Kevin D. , Hamilton Bruce A.
Published: July 2021

The yeast two-hybrid (Y2H) assay has long been used to identify new protein-protein interaction pairs and to compare relative interaction strengths. Traditional Y2H formats may be limited, however, by use of constitutive strong promoters if expressed proteins have toxic effects or post-transcriptional expression differences in yeast among a comparison group. As a step toward more quantitative Y2H assays, we modified a common vector to use an inducible CUP1 promoter, which showed quantitative induction of several “bait” proteins with increasing copper concentration. Using mouse Nxf1 (homologous to yeast Mex67p) as a model bait, copper titration achieved levels that bracket levels obtained with the constitutive ADH1 promoter. Using a liquid growth assay for an auxotrophic reporter in multiwell plates allowed log-phase growth rate to be used as a measure of interaction strength. These data demonstrate the potential for quantitative comparisons of protein-protein interactions using the Y2H system.
Characterizing collaborative transcription regulation with a graph-based deep learning approach
Authors: Zhang Zhenhao , Feng Fan , Yao Yuan , Liu Jie
Published: July 2021

Human epigenome and transcription activities have been characterized by a number of sequence-based deep learning approaches which only utilize the DNA sequences. However, transcription factors interact with each other, and their collaborative regulatory activities go beyond the linear DNA sequence. Therefore leveraging the informative 3D chromatin organization to investigate the collaborations among transcription factors is critical. We developed ECHO, a graph-based neural network, to predict chromatin features and characterize the collaboration among them by incorporating 3D chromatin organization from 200-bp high-resolution Micro-C contact maps. ECHO predicts 2, 583 chromatin features with significantly higher average AUROC and AUPR than the best sequence-based model. We observed that chromatin contacts of different distances affected different types of chromatin features’ prediction in diverse ways, suggesting complex and divergent collaborative regulatory mechanisms. Moreover, ECHO was interpretable via gradient-based attribution methods. The attributions on chromatin contacts identify important contacts relevant to chromatin features. The attributions on DNA sequences identify TF binding motifs and TF collaborative binding. Furthermore, combining the attributions on contacts and sequences reveals important sequence patterns in the neighborhood which are relevant to target sequence’s chromatin feature prediction. The attribution results that reveal TF collaboration activities are provided on a website https://echo.dcmb.med.umich.edu/echo/.
Evolution and diversity of bat and rodent Paramyxoviruses from North America
Authors: Larsen Brendan B. , Gryseels Sophie , Otto Hans W. , Worobey Michael
Published: July 2021

Paramyxoviruses are a diverse group of negative-sense, single-stranded RNA viruses of which several species cause significant mortality and morbidity. In recent years the collection of paramyxoviruses sequences detected in wild mammals has substantially grown, however little is known about paramyxovirus diversity in North American mammals. To better understand natural paramyxovirus diversity, host range, and host specificity, we sought to comprehensively characterize paramyxoviruses across a range of diverse co-occurring wild small mammals in Southern Arizona. We used highly degenerate primers to screen fecal and urine samples and obtained a total of 55 paramyxovirus sequences from 12 rodent species and 6 bat species. We also performed illumina RNA-seq and de novo assembly on 14 of the positive samples to recover a total of 5 near full-length viral genomes. We show there are at least 2 clades of rodent-borne paramyxoviruses in Arizona, while bat-associated paramyxoviruses formed a putative single clade. Using structural homology modeling of the viral attachment protein, we infer that three of the five novel viruses likely bind sialic acid in a manner similar to other Respiroviruses, while the other two viruses from Heteromyid rodents likely bind a novel host receptor. We find no evidence for cross-species transmission, even among closely related sympatric host species. Taken together, these data suggest paramyxoviruses are a common viral infection in some bat and rodent species present in North America, and illuminate the evolution of these viruses.

Importance

There are a number of viral lineages that are potential zoonotic threats to humans. One of these, paramyxoviruses, have jumped into humans multiple times from wild and domestic animals. We conducted one of the largest viral surveys of wild mammals in the United States to better understand paramyxovirus diversity and evolution.
Development and Validation of a High-Throughput Short Sequence Typing Scheme forSerratia marcescensPure Culture and Environmental DNA
Authors: Bourdin Thibault , Monnier Alizée , Benoit Marie-Ève , Bédard Emilie , Prévost Michèle , Quach Caroline , Déziel Eric , Constant Philippe
Published: July 2021

Molecular typing methods are used to characterize the relatedness between bacterial isolates involved in infections. These approaches rely mostly on discrete loci or whole genome sequences (WGS) analyses of pure cultures. On the other hand, their application to environmental DNA profiling to evaluate epidemiological relatedness amongst patients and environments has received less attention. We developed a specific, high-throughput short sequence typing (HiSST) method for the opportunistic human pathogenSerratia marcescens. Genes displaying the highest polymorphism were retrieved from the core genome of 60S. marcescensstrains. Bioinformatics analyses showed that use of only three loci (withinbssA, gabRanddhaM) distinguished strains with the same level of efficiency than average nucleotide identity scores of whole genomes. This HiSST scheme was applied to an epidemiological survey ofS. marcescensin a neonatal intensive care unit (NICU). In a first case study, a strain responsible for an outbreak in the NICU was found in a sink drain of this unit, by using HiSST scheme and confirmed by WGS. The HiSST scheme was also applied to environmental DNA extracted from sink-environment samples. Diversity ofS. marcescenswas modest, with 11, 6 and 4 different sequence types (ST) ofgabR, bssAanddhaMloci amongst 19 sink drains, respectively. Epidemiological relationships amongst sinks were inferred on the basis of pairwise comparisons of ST profiles. Further research aimed at relating ST distribution patterns to environmental features encompassing sink location, utilization and microbial diversity is needed to improve the surveillance and management of opportunistic pathogens.
Loss of GdpP function in Staphylococcus aureus leads to β-lactam tolerance and enhanced evolution of β-lactam resistance
Authors: Poon Raymond , Basuino Li , Satishkumar Nidhi , Chatterjee Aditi , Mukkayyan Nagaraja , Buggeln Emma , Huang Liusheng , Nair Vinod , Argudín Maria A. , Datta Sandip K. , Chambers Henry F. , Chatterjee Som S.
Published: July 2021

Synopsis

Background

We previously reported the presence of mutations in gdpP among Staphylococcus aureus strains that were obtained by serial passaging in β-lactam drugs. gdpP codes for a phosphodiesterase that cleaves cyclic-di-AMP (CDA), a newly discovered second messenger.

Objectives

We sought to identify the role of gdpP in β-lactam resistance of S. aureus.

Methods

CDA concentrations in bacterial cytosol were measured through mass-spectrometric analysis. gdpP deletion mutagenesis and their complemented strains were created in clinically relevant S. aureus strains to characterize its function.

Results

gdpP associated mutations among passaged strains were identified to cause loss of phosphodiesterase function, leading to increased CDA accumulation in the bacterial cytosol. Deletion of gdpP led to an enhanced ability of the bacteria to withstand a β-lactam challenge (two to three log increase in bacterial colony forming units) by promoting tolerance without enhancing MICs of β-lactam antibiotics. Our results demonstrate that increased drug tolerance due to loss of GdpP function can provide a selective advantage in acquisition of high-level β-lactam resistance and could lead to β-lactam treatment failure of S. aureus infections.

Conclusions

Loss of GdpP function increases tolerance to β-lactams that can lead to its therapy failure and can permit β-lactam resistance to occur more readily.
Network diffusion model predicts neurodegeneration in limb-onset amyotrophic lateral sclerosis
Authors: Bhattarai Anjan , Chen Zhaolin , Chua Phyllis , Talman Paul , Mathers Susan , Chapman Caron , Howe James , Lee CM Sarah , Lie Yenni , Poudel Govinda R , Egan Gary F
Published: July 2021

The trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS. We measured degeneration in limb-onset ALS patients (n=14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n=12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.
Aboveground biomass increments over 26 years (1993–2019) in an old-growth cool-temperate forest in northern Japan
Authors: Noguchi Mahoko , Hoshizaki Kazuhiko , Matsushita Michinari , Sugiura Daiki , Yagihashi Tsutomu , Saitoh Tomoyuki , Itabashi Tomohiro , Kazuhide Ohta , Shibata Mitsue , Hoshino Daisuke , Masaki Takashi , Osumi Katsuhiro , Takahashi Kazunori , Suzuki Wajirou
Published: July 2021

Assessing long-term changes in biomass of old-growth forests is critical in evaluating forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993–2019) of repeated tree census data in an old-growth, cool-temperate, deciduous mixed forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean temperature during the current summer but smaller in those with higher mean temperature during the previous autumn, synchronously in all topographic units. The decadal climate trends of warming are likely to have contributed to the steady increase in AGB in this old-growth forest.
Wild lab: A naturalistic free viewing experiment reveals previously unknown EEG signatures of face processing
Authors: Gert Anna L. , Ehinger Benedikt V. , Timm Silja , Kietzmann Tim C. , König Peter
Published: July 2021

Neural mechanisms of face perception are predominantly studied in well-controlled experimental settings that involve random stimulus sequences and fixed eye positions. While powerful, the employed paradigms are far from what constitutes natural vision. Here, we demonstrate the feasibility of ecologically more valid experimental paradigms using natural viewing behavior, by combining a free viewing paradigm on natural scenes, free of photographer bias, with advanced data processing techniques that correct for overlap effects and co-varying nonlinear dependencies of multiple eye movement parameters. We validate this approach by replicating classic N170 effects in neural responses, triggered by fixation onsets (fERPs). Importantly, our more natural stimulus paradigm yielded smaller variability between subjects than the classic setup. Moving beyond classic temporal and spatial effect locations, our experiment furthermore revealed previously unknown signatures of face processing. This includes modulation of early fERP components, as well as category-specific adaptation effects across subsequent fixations that emerge even before fixation onset.
Mapping Protein Numbers in Living Cells
Authors: Thirstrup Derek J , Yao Jie , Sherman Jamie , Mueller Irina A , Wiegraebe Winfried
Published: July 2021

We introduce a new, robust method to map the numbers of proteins in living cells. The method can be applied to laser scanning, spinning disk, and lattice light-sheet microscopes in a robust, reproducible, and scalable fashion. The method uses calibrated EGFP solutions that are imaged with the appropriate microscope modality to create a calibration curve that is then applied to convert the fluorescence intensities from 3D microscope images into molecule numbers. We applied this method to human induced pluripotent stem cells in which proteins representing key cellular structures were endogenously tagged with mEGFP. We used the ratio of mEGFP-tagged proteins to total proteins to create 3D maps of live cells showing the density of total proteins measured in molecules per µm3. The method opens the door to new quantitative single cell analyses of cellular protein numbers in the context of single cell gene expression, associations with cellular complexes, and changes in cellular behaviors. The method is capable of quantifying protein numbers, over three orders of magnitude, in the cytoplasm or within various cellular structures while offering the unique advantages of each microscopy modality.
Eukaryotic stress induced mutagenesis is limited by a local control of Translesion Synthesis
Authors: Masłowska Katarzyna H. , Villafañez Florencia , Laureti Luisa , Iwai Shigenori , Pagès Vincent
Published: July 2021

The DNA Damage Response (DDR) preserves the genetic integrity of the cell by sensing and repairing damages after a genotoxic stress. Translesion Synthesis (TLS), an error-prone DNA damage tolerance pathway, is controlled by PCNA ubiquitination. In this report, we raise the question whether TLS is controlled locally, or globally. Using a recently developed method that allows to follow the bypass of a single lesion inserted into the yeast genome, we show that: i) TLS is controlled locally at each individual lesion by PCNA ubiquitination, ii) a single lesion is enough to induce PCNA ubiquitination, and iii) PCNA ubiquitination is an imperative requirement for TLS to occur. More importantly, we show that global PCNA ubiquitination that follows a genotoxic stress does not increase TLS at individual lesions. We conclude that unlike the SOS response in bacteria, the eukaryotic DDR does not promote TLS and mutagenesis.
Biochemical and subcellular characterization of a squid hnRNPA/B-like protein in osmotic stress activated cells reflects molecular properties conserved in this protein family
Authors: Lopes Gabriel S. , Lico Diego T. P.
Published: July 2021

In previous works, we characterized a novel, strongly basic, squid hnRNPA/B-like Protein 2 in presynaptic terminals of squid neurons. Here, we show that squid hnRNPA/B-like Protein 2 are exclusively nuclear localization and relocated to cytoplasmic granules containing hnRNPA1 and Poly-A binding protein-1 (PABP-1) when the cells are treated with sorbitol. Also, we show an interaction of hnRNPA/B like Protein 2 with squid RNA, its interfered with dynamic of formation of hnRNPA/B like Protein 2 dimers, whereas possibly involved disulfide bounds and postranslations modification in a distinct stage of dimers formation. An understanding of the molecular and biochemical mechanisms involved in the stability of the dimeric form, and the regulation of the transition between monomeric and dimeric forms may bring insights into evolution of several neurodegenerative diseases.

Highlights

We identified monomeric (p37) and dimeric (p65) forms of squid hnRNPA/B-like Protein 2 in squid optic lobes

Our data indicate a conserved structure and cellular properties of squid hnRNPA/B-like Protein 2 and human hnRNPA1 protein colocalizing with PABP into stress granules (SGs)

The stability of hnRNPA/B-like dimers involved the squid RNAs and disulfide bonds to promote higher SDS-stable dimers formation

An understanding of the transition between monomeric and dimeric forms of squid hnRNPA/B-like Protein 2 may give clues to misfolding processes in neuropathologies
The role of organizational culture and voluntariness in the adoption of artificial intelligence for disaster relief operations
Authors: Behl Abhishek , Chavan Meena , Jain Kokil , Sharma Isha , Pereira Vijay Edward , Zhang Justin Zuopeng
Published: July 2021

Purpose

The study explores the readiness of government agencies to adopt artificial intelligence (AI) to improve the efficiency of disaster relief operations (DRO). For understanding the behavior of state-level and national-level government agencies involved in DRO, this study grounds its theoretical arguments on the civic voluntarism model (CVM) and the unified theory of acceptance and use of technology (UTAUT).

Design/methodology/approach

We collected the primary data for this study from government agencies involved in DRO in India. To test the proposed theoretical model, we administered an online survey questionnaire to 184 government agency employees. To test the hypotheses, we employed partial least squares structural equation modeling (PLS-SEM).

Findings

Our findings confirm that resources (time, money and skills) significantly influence the behavioral intentions related to the adoption of AI tools for DRO. Additionally, we identified that the behavioral intentions positively translate into the actual adoption of AI tools.

Research limitations/implications

Our study provides a unique viewpoint suited to understand the context of the adoption of AI in a governmental context. Companies often strive to invest in state-of-the-art technologies, but it is important to understand how government bodies involved in DRO strategize to adopt AI to improve efficiency.

Originality/value

Our study offers a fresh perspective in understanding how the organizational culture and perspectives of government officials influence their inclinations to adopt AI for DRO. Additionally, it offers a multidimensional perspective by integrating the theoretical frameworks of CVM and UTAUT for a greater understanding of the adoption and deployment of AI tools with organizational culture and voluntariness as critical moderators.
Discussing adapted physical education during IEP meetings: First‐hand parent experiences and a supporting tool
Authors: McNamara Scott W.T. , Lieberman Lauren , Weiner Brad , McMullen Brock
Published: July 2021

Physical education (PE) has long been neglected throughout the individualized education programme (IEP) process. Parents often feel unprepared to advocate for PE services within the IEP process. Aim: Thus, the purpose of this study was to outline the development of an advocacy checklist to help parents address PE within the IEP process and to examine parents’ experiences discussing PE during IEP meetings. A qualitative descriptive approach was used to drive interviews that were conducted with seven parents of children with visual impairments (VI). Three interrelated themes were constructed using an inductive category development approach: (1) ‘It’s [PE] basically a check mark, It’s, he was there. He didn’t go to sleep’, (2) ‘I’d say it’s [PE] one of our most important pieces… we believe in as a family’ and (3) ‘This is a perfect checklist of what they [IEP team] need to be going over’. The current study revealed multiple barriers that intervene with appropriate documentation of PE services during the IEP meeting. As voiced by the parents in this study, the checklist outlined in this study offers a practical and user‐friendly PE advocacy checklist to guide all parties on the IEP team towards making informed decisions regarding these services.
Overexpression of SlERF3b and SlERF5 in transgenic tomato alters fruit size, number of seeds and promotes early flowering, tolerance to abiotic stress and resistance to Botrytis cinerea infection
Authors: Álvarez‐Gómez Tania Belen , Ramírez‐Trujillo José Augusto , Ramírez‐Yáñez Mario , Suárez‐Rodríguez Ramón
Published: July 2021

Ethylene response factors (ERFs) are a large family of plant‐specific transcription factors that have been implicated in positively regulating stress responses. The aim of this work was to study the expression pattern of ethylene response factors SlERF1, SlERF3b and SlERF5 in Solanum lycopersicum cv. Ailsa Craig, when subjected to different stress conditions, as well as to determine the overexpression effect in transgenic tomato when exposed to abiotic and biotic stress conditions. Here we report that SlERF1, SlERF3b and SlERF5 genes are differentially upregulated in tomato wild‐type plants grown under either simulated biotic (when trehalose was applied exogenously) and abiotic stress. SlERF5 and SlERF3b are mainly induced under dehydration and salinity conditions; SlERF1 and SlERF5 are upregulated in response to exogenous trehalose, while SlERF3b is downregulated. These results suggest that SlERF3b could be involved in modulating defence responses to abiotic and biotic stresses. The overexpression of SlERF3b and SlERF5 in transgenic tomato plants promotes abiotic stress tolerance as a result of upregulating genes involved to confer stress tolerance such as P5CS and APx, triggering a major cell membrane‐mediated protection against oxidative stress and avoiding chlorophyll degradation under salinity and drought conditions. Transgenic plants overexpressing SlERF3b positively regulates fruit development, seed production and early flowering; however, germination seeds are more sensitive to osmotic stress as compared to saline stress, while SlERF5 transgenic line has better germination rate in saline stress compared to osmotic stress. On the other hand, overexpression of SlERF5 and SlERF3b plays an important role in regulating the immune response against the pathogenic fungus Botrytis cinerea, by positively regulating JA/ET signalling pathways.
From the saltpan to the plate: An evaluation of the use of the edible halophyteSalicornia ramosissimain catering
Authors: Cardoso Mariana , Silva Helena , Patinha Carla , Costa Natália , Nunes Susana , Cunha Ângela
Published: July 2021

The halophyte speciesSalicornia ramosissimahas long been consumed as food and is currently regarded as a high‐value gourmet item. However, given that these plants grow in estuarine areas, often impacted by pollution, and are prone to the accumulation of ions, the risks associated with food borne pathogens or toxic metals has to be carefully considered. The objective of this work was to gather evidence thatS. ramossissimaharvested locally in an estuarine system (Ria de Aveiro, Portugal) can be safely consumed as a healthy and catering‐amenable food. Fresh shoots, taken as green vegetables, and dried powdered shoots (green salt) intended as seasoning, were analysed for total aerobic bacteria, total coliforms,Escherichia coli,Bacillus cereusand fungi (yeasts and moulds). The nutritional profile and the concentration of macro and micro elements, including potential toxic elements, was also established. Fresh shoots and green salt were incorporated in catering meals (soup and a meat dish) and subjected to sensory analyses. The microbiological quality of fresh shoots and green salt was compliant with the guidelines for salad greens and herbs and spices, respectively. The nutritional and elemental profile revealed that fresh shoots have a high content in fibre and NaCl. From the concentration of Na determined in green salt, a daily dose of 7 g was estimated as corresponding to the recommended daily dietary intake Na. None of the other elements was present in concentrations that could exceed the dietary intake limits. In the sensory tests, fresh shoots were well accepted as salad greens but green salt, used as seasoning, was considered as insufficient in terms of saltiness and does not completely substitute cooking salt. The results confirm the nutritional and sensory value ofS. ramossisimaand represent a promising prospect for the incorporation of locally harvested or crop cultivated plants in catering meals.
Egyptian Scarabs Discovered on Kuwait’s Failaka Island and Similar Finds from the Gulf Region
Authors: Mahfouz El‐Sayed , Al‐Duweish Sultan , Saied Ahmed
Published: July 2021

Over the course of the last three decades, Ancient Egyptian scarabs have been discovered on Failaka Island off Kuwait, as well as at other sites in the Arabian Gulf. A scarab is the most expressive amulet of the cultural identity of ancient Egypt, revealing its influence and its cultural diffusion in the ancient world. Therefore, this paper discusses the reasons for the presence of such exotic products on the island and also answers the question about their origin. Were Failaka scarabs locally manufactured? What is their connection to the Levant? Are they a testimony to the interconnection between ancient Egypt and Arabia?
The value‐added creation effect of industry position in global value chains: implications for Asia‐Pacific economies
Authors: Park Soonchan , Park Innwon
Published: July 2021

We analyse the value‐added creation effect of global value chain (GVC) participation activities of APEC member economies, using a fixed‐effects regression model analysis based on country–industry data from Organisation for Economic Co‐operation and Development (OECD) Inter‐country Input–Output Tables. We find that forward participation in GVCs is more desirable than backward participation for creating domestic value‐added and that the industry position in the middle stages of the production line creates higher domestic value‐added per output unit. These results hold regardless of the application of standard Ordinary Least Squares (OLS) or fractional logit for panel data and of the characteristics of the interconnected countries in GVCs (APEC member vs. non‐APEC member economies, Asian APEC vs. non‐Asian APEC members, developed vs. developing countries). This implies that the conventional firm‐ or product‐specific U‐shaped ‘smile curve hypothesis’ is not applicable at the economy‐wide, country–industry level. This finding suggests that depending on the product type, manufacturing industries can be a major driving force for less‐developed APEC member economies to climb the development ladder. Since GVC participation gains are diversified across industries and upgrading country–industry positions in GVCs are challenging for APEC member economies, we strongly recommend that they construct effective domestic value chains and coordinate with other members while upgrading their GVC participation.