bluuebunny/crossref_metadata_2025_split huggingface dataset:
“How do we do this at a distance?!” A descriptive study of remote undergraduate research programs during COVID-19
Authors: Erickson Olivia A. , Cole Rebecca B. , Isaacs Jared M. , Alvarez-Clare Silvia , Arnold Jonathan , Augustus-Wallace Allison , Ayoob Joseph C. , Berkowitz Alan , Branchaw Janet , Burgio Kevin R. , Cannon Charles H. , Ceballos Ruben Michael , Cohen C. Sarah , Coller Hilary , Disney Jane , Doze Van A. , Eggers Margaret J. , Farina Stacy , Ferguson Edwin L. , Gray Jeffrey J. , Greenberg Jean T. , Hoffman Alexander , Jensen-Ryan Danielle , Kao Robert M. , Keene Alex C. , Kowalko Johanna E. , Lopez Steven A. , Mathis Camille , Minkara Mona , Murren Courtney J. , Ondrechen Mary Jo , Ordoñez Patricia , Osano Anne , Padilla-Crespo Elizabeth , Palchoudhury Soubantika , Qin Hong , Ramírez-Lugo Juan , Reithel Jennifer , Shaw Colin A. , Smith Amber , Smith Rosemary , Summers Adam P. , Tsien Fern , Dolan Erin L. 
Published: May 2021

ABSTRACTThe COVID-19 pandemic shut down undergraduate research programs across the U.S. Twenty-three sites offered remote undergraduate research programs in the life sciences during summer 2020. Given the unprecedented offering of remote research experiences, we carried out a study to describe and evaluate these programs. Using structured templates, we documented how programs were designed and implemented, including who participated. Through focus groups and surveys, we identified programmatic strengths and shortcomings as well as recommendations for improvements from the perspectives of participating students. Strengths included the quality of mentorship, opportunities for learning and professional development, and development of a sense of community. Weaknesses included limited cohort building, challenges with insufficient structure, and issues with technology. Although all programs had one or more activities related to diversity, equity, inclusion, and justice, these topics were largely absent from student reports even though programs coincided with a peak in national consciousness about racial inequities and structural racism. Our results provide evidence for designing remote REUs that are experienced favorably by students. Our results also indicate that remote REUs are sufficiently positive to further investigate their affordances and constraints, including the potential to scale up offerings, with minimal concern about disenfranchising students.
KmerKeys: a web resource for searching indexed genome assemblies and variants
Authors: Pavlichin Dmitri S. , Lee HoJoon , Greer Stephanie U. , Grimes Susan M. , Weissman Tsachy , Ji Hanlee P. 
Published: May 2021

ABSTRACTK-mers are short DNA sequences that are used for genome sequence analysis. Applications that use k-mers include genome assembly and alignment. Despite these current applications, the wider bioinformatic use of k-mers in has challenges related to the massive scale of genomic sequence data. A single human genome assembly has billions of these short sequences. The sheer amount of computation for effective use of k-mer information is enormous, particularly when involving multiple genome assemblies. To address these issues, we developed a new k-mer indexing data structure based on a hash table tuned for the lookup of k-mer keys. This web application, referred to as KmerKeys (https://kmerkeys.dgi-stanford.org/), provides performant, rapid query speeds for cloud computation on genome assemblies. We enable fuzzy as well as exact k-mer-based searches of assemblies. To enable robust and speedy performance, the website implements cache-friendly hash tables, memory mapping and massive parallel processing. Our method employs a scalable and efficient data structure that can be used to jointly index and search a large collection of human genome assembly information. One can include variant databases and their associated metadata such as the gnomAD population variant catalog. This feature enables the incorporation of future genomic information into sequencing analysis.
Skeletal Muscle Transcriptome Alterations Related to Physical Function Decline in Older Mice
Authors: Graber Ted G. , Maroto Rosario , Thompson Jill , Widen Steve , Man Zhaohui , Pajski Megan L. , Rasmussen Blake B. 
Published: May 2021

SummaryOne inevitable consequence of aging is the gradual deterioration of physical function and exercise capacity, driven in part by the adverse effect of age on muscle tissue. Our primary purpose was to determine the relationship between patterns of gene expression in skeletal muscle and this loss of physical function. We hypothesized that some genes changing expression with age would correlate with functional decline, or conversely with preservation of function. Male C57BL/6 mice (6-months old, 6m, 24-months, 24m, and 28+-months, 28m; all n=8) were tested for physical ability using acomprehensivefunctionalassessmentbattery (CFAB). CFAB is a composite scoring system comprised of five functional tests: rotarod (overall motor function), grip strength (fore-limb strength), inverted cling (4-limb strength/endurance), voluntary wheel running (activity rate/volitional exercise), and treadmill (endurance). We then extracted total RNA from the tibialis anterior muscle, analyzed with Next Generation Sequencing RNAseq to determine differential gene expression during aging, and compared these changes to physical function. Aging resulted in gene expression differences >│1.0│ log2 fold change (multiple comparison adjusted p<0.05) in219genes in the 24m and in6587genes in the 28m. Linear regression with CFAB determined253differentially expressed genes strongly associated (R>0.70) with functional status in the 28m, and22genes in the 24m. We conclude that specific age-related transcriptomic changes are associated with declines in physical function, providing mechanistic clues. Future work will establish the underlying cellular mechanisms and the physiological relevance of these genes to age-related loss of physical function.Graphical AbstractRNA sequencing of skeletal muscle from young and old mice were compared to physical function status obtained by performing a comprehensive functional assessment battery of tests. Between adulthood (6-months) and older age (28-months), 6707 genes were differentially expressed with 253 of these genes being significantly associated with physical function. Specific age-related changes to the skeletal muscle transcriptome are associated with a decline in physical function.
Mass Recovery following Caloric Restriction Reverses Lipolysis and Proteolysis, but not Gluconeogenesis, in Insulin Resistant OLETF Rats
Authors: Cornejo Manuel A. , Dhillon Jaapna , Nishiyama Akira , Nakano Daisuke , Ortiz Rudy M. 
Published: May 2021

AbstractCaloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.
Fluorinated oil-surfactant mixtures with the density of water: artificial cells for synthetic biology
Authors: Laos Roberto , Benner Steven 
Published: May 2021

AbstractThere is a rising interest in biotechnology for the compartmentalization of biochemical reactions in water droplets. Several applications, such as the widely used digital PCR, seek to encapsulate a single molecule in a droplet to be amplified. Directed evolution, another technology with growing popularity, seeks to replicate what happens in nature by encapsulating a single gene and the protein encoded by this gene, linking genotype with phenotype. Compartmentalizing reactions in droplets also allows the experimentalist to run millions of different reactions in parallel. Compartmentalization requires a fluid that is immiscible with water and a surfactant to stabilize the droplets. While there are fluids and surfactants on the market that have been used to accomplish encapsulation, there are reported concerns with these. Span® 80, for example, a commonly used surfactant, has contaminants that interfere with various biochemical reactions. Similarly, synthetic fluids distributed by the cosmetic industry allow some researchers to produce experimental results that can be published, but then other researchers fail to reproduce some of these protocols due to the unreliable nature of these products, which are not manufactured with the intent of being used in biotechnology. The most reliable fluids, immiscible with water and suitable for biochemical reactions, are fluorinated fluids. Fluorinated compounds have the peculiar characteristic of being immiscible with water while at the same time not mixing with hydrophobic molecules. This peculiar characteristic has made fluorinated fluids attractive because it seems to be the basis of their being biologically inert. However, commercially available fluorinated fluids have densities between 1.4 to 1.6 g/mL. The higher-than-water density of fluorinated oils complicates handling of the droplets since these would float on the fluid since the water droplets would be less dense. This can cause aggregation and coalescence of the droplets. Here, we report the synthesis, characterization, and use of fluorinated polysiloxane oils that have densities similar to the one of water at room temperature, and when mixed with non-ionic fluorinated surfactants, can produce droplets encapsulating biochemical reactions. We show how droplets in these emulsions can host many biological processes, including PCR, DNA origami, rolling circle amplification (RCA), and Taqman® assays. Some of these use unnatural DNA built from an Artificially Expanded Genetic Information System (AEGIS) with six nucleotide “letters”.
Genetic diversity and population structure of cowpea [Vigna unguiculata (L.) Walp.] accessions from Togo using SSR Markers
Authors: Dagnon Yao Dodzi , Palanga Koffi Kibalou , Bammite Damigou , Akabassi Ghislain Comlan , Tozo Koffi 
Published: May 2021

AbstractCowpea [Vigna unguiculata (L.) Walp.] is a crop with significant agronomic and nutritional potential. I is very appreciate by local people. It is the third food habit in Togo after maize and rice. However, several accessions of cowpea cultivated in Togo are now prone to extinction, creating a risk of genetic erosion. It is therefore urgent to assess the genetic diversity of accessions in order to set up a good conservation program. To achieve this, genetic diversity and phylogenetic relationships among 70 accessions of cowpea collected in the five (5) administrative regions of Togo were assessed using Simple Sequence Repeat (SSR) molecular markers. Twenty-eight out of the thirty-two (32) primer pairs screened for polymorphism were polymorphic, and a total of 164 alleles were detected for the 28 loci with an average of 5.82 alleles per locus. Polymorphic Information Content (PIC) values ranged from 0.18 to 0.895, with an average value of 0.67. Population structure analysis using model-based revealed that the cowpea germplasm was grouped into two subpopulations. The analysis of molecular variance (AMOVA) revealed that 85% of genetic variation existed among individuals within regions. The fixation index (Fst) value, which was 0.018, was low, indicating relatively low population differentiation. The Togolese cowpea germplasm collection was grouped into four groups independently of theirs origins. This study provides a foundation for a Togolese cowpea germplasm conservation program and can serve for the selection of parental material for further studies aimed at the genetic improvement of local germplasm.
Fusarium graminearumDICER-like-dependent sRNAs are required for the suppression of host immune genes and full virulence
Authors: Werner Bernhard , Koch Aline , Šečić Ena , Engelhardt Jonas , Jelonek Lukas , Steinbrenner Jens , Kogel Karl-Heinz 
Published: May 2021

AbstractIn filamentous fungi, gene silencing by RNA interference (RNAi) shapes many biological processes, including pathogenicity. Recently, fungal small RNAs (sRNAs) have been shown to act as effectors that disrupt gene activity in interacting plant hosts, thereby undermining their defence responses. We show here that the devastating mycotoxin-producing ascomyceteFusarium graminearum(Fg) utilizes DICER-like (DCL)-dependent sRNAs to target defence genes in two Poaceae hosts, barley (Hordeum vulgare Hv) andBrachypodium distachyon(Bd). We identified 104Fg-sRNAs with sequence homology to host genes that were repressed during interactions ofFgandHv, while they accumulated in plants infected by the DCL double knock-out (dKO) mutant PH1-dcl1/2. The strength of target gene expression correlated with the abundance of the correspondingFg-sRNA. Specifically, the abundance of three tRNA-derived fragments (tRFs) targeting immunity-relatedEthylene overproducer 1-like 1(HvEOL1)and three Poaceae orthologues ofArabidopsis thaliana BRI1-associated receptor kinase 1(HvBAK1, HvSERK2andBdSERK2) was dependent on fungal DCL. Additionally, RNA-ligase-mediated Rapid Amplification of cDNA Ends (RLM-RACE) identified infection-specific degradation products for the three barley gene transcripts, consistent with the possibility that tRFs contribute to fungal virulence via targeted gene silencing.Significance StatementFusarium graminearumis one of the most devastating fungal pathogens in cereals, while understanding the mechanisms of fungal pathogenesis is a prerequisite for developing efficient and environmentally friendly crop protection strategies. We show exploratory data suggesting that fungal small RNAs play a critical role in Fusarium virulence by suppressing plant immunity.
Comparative genomics reveals insights into phylogenomic taxonomy and potential algae-bacteria interactions of novel versatile Mameliella alba strain LZ-28 isolated from highly-toxic marine phycosphere
Authors: Zhu Wen-zhuo , Xu Fei-fei , Ye Yun , Yang Qiao , Zhang Xiao-ling 
Published: May 2021

AbstractPhycosphere harbors cross-kingdom interactions with significant ecological relevance for harmful algal blooms (HAB) and phycotoxins biosynthesis. Previously, a new red-pigmented bacterium designated as strain LZ-28 was isolated from phycosphere microbiota of typical HAB dinoflagellate Alexandrium catenella LZT09 which is a vitamin B12 auxotroph and produces high levels of paralytic shellfish poisoning toxins (PST). Strain LZ-28 exhibited obvious growth-promoting activity toward its algal host, along with the production of active bioflocculanting exopolysaccharides (EPS). But the phylogenetic affiliation and genomic potential of this versatile bacterium has not yet been elucidated. In this study, we carried out combined taxonomic and phylogenomic analysis to clarify the taxonomic classification of strain LZ-28. The obtained 16S rRNA phylogeny revealed close taxonomic relationship between strain LZ-28 and other Mameliella alba members. Additional calculations of key phylogenomic parameters, average nucleotide identity (ANI), the average amino acid identity (AAI) and the digital DNA-DNA hybridization (dDDH) values based on genomes of strain LZ-28 and type strain of Mameliella alba were all exceeded the limit of species circumscription. Collectively considering the phenotypic and biochemical characterizations, strain LZ-28 was therefore identified as a new member of Mameliella alba. Furthermore, based on the genomic evidence, potential algae-bacteria interactions of strain LZ-28 with host algae LZT09 were elucidated through the associations with photosynthetic and antioxidant carotenoids, supplying of bacterial VB12 to auxotroph host, and versatile EPS serving for bacterial colonization and nutrient exchange during their interactions, along with stress response systems to defense oxidative stress and quorum sensing (QS) signals benefited survival for bacteria in the symbiotic system. Comparative genomics shed light on similar genomic features between M. alba strains, revealed potential close associations of strain LZ-28 with its algae host, and further enriched the genomic repertoire of interactions between phycosphere microbiota and algal host LZT09.
Flexibility-aware graph-based algorithm improves antigen epitopes identification
Authors: Gao Chuang , Wang Yiqi , Luo Jie , Zhou Ziyi , Dong Zhiqiang , Zhao Liang 
Published: May 2021

AbstractEpitopes of an antigen are the surface residues in the spatial proximity that can be recognized by antibodies. Identifying such residues has shown promising potentiality in vaccine design, drug development and chemotherapy, thus attracting extensive endeavors. Although great efforts have been made, the epitope prediction performance is still unsatisfactory. One possible issue accounting to this poor performance could be the ignorance of structural flexibility of antigens. Flexibility is a natural characteristic of antigens, which has been widely reported. However, this property has never been used by existing models. To this end, we propose a novel flexibility-aware graph-based computational model to identify epitopes. Unlike existing graph-based approaches that take the static structures of antigens as input, we consider all possible variations of the side chains in graph construction. These flexibility-aware graphs, of which the edges are highly enriched, are further partitioned into subgraphs by using a graph clustering algorithm. These clusters are subsequently expanded into larger graphs for detecting overlapping residues between epitopes if exist. Finally, the expanded graphs are classified as epitopes or non-epitopes via a newly designed graph convolutional network. Experimental results show that our flexibility-aware model markedly outperforms existing approaches and promotes the F1-score to 0.656. Comparing to the state-of-the-art, our approach makes an increment of F1-score by 16.3%. Further in-depth analysis demonstrates that the flexibility-aware strategy contributes the most to the improvement. The source codes of the proposed model is freely available athttps://github.com/lzhlab/epitope.Author summaryEpitope prediction is helpful to many biomedical applications so that dozens of models have been proposed aiming at improving prediction efficiency and accuracy. However, the performances are still unsatisfactory due to its complicated nature, particularly the noteworthy flexible structures, which makes the precise prediction even more challenging. The existing approaches have overlooked the flexibility during model construction. To this end, we propose a graph model with flexibility heavily involved. Our model is mainly composed of three parts: i) flexibility-aware graph construction; ii) overlapping subgraph clustering; iii) graph convolutional network-based subgraph classification. Experimental results show that our newly proposed model markedly outperforms the existing best ones, making an increment of F1-score by 16.3%.
Compartmap enables inference of higher-order chromatin structure in individual cells from scRNA-seq and scATAC-seq
Authors: Johnson Benjamin K. , Fortin Jean-Philippe , Hansen Kasper D. , Shen Hui , Triche Timothy 
Published: May 2021

AbstractSingle-cell profiling of chromatin structure remains a challenge due to cost, throughput, and resolution. We introduce compartmap to reconstruct higher-order chromatin domains in individual cells from transcriptomic (RNAseq) and epigenomic (ATACseq) assays. In cell lines and primary human samples, compartmap infers higher-order chromatin structure comparable to specialized chromatin capture methods, and identifies clinically relevant structural alterations in single cells. This provides a common lens to integrate transcriptional and epigenomic results, linking higher-order chromatin architecture to gene regulation and to clinically relevant phenotypes in individual cells.
Moxidectin and ivermectin inhibit SARS-CoV-2 replication in Vero E6 cells but not in human primary airway epithelium cells
Authors: Kumar Nilima Dinesh , ter Ellen Bram M. , Bouma Ellen M. , Troost Berit , van de Pol Denise P. I. , van der Ende-Metselaar Heidi H. , van Gosliga Djoke , Apperloo Leonie , Carpaij Orestes A. , van den Berge Maarten , Nawijn Martijn C. , Stienstra Ymkje , Rodenhuis-Zybert Izabela A , Smit Jolanda M. 
Published: May 2021

AbstractAntiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 µM. These in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: “the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive”. It is speculated that the in vivo concentration of ivermectin is too low to exert a strong antiviral effect. Here, we performed a head-to head comparison of the antiviral activity of ivermectin and a structurally related, but metabolically more stable, moxidectin in multiple in vitro models of SARS-CoV-2 infection, including physiologically relevant human respiratory epithelial cells. Both moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Subsequent experiments revealed that the compounds predominantly act on a step after virus cell entry. Surprisingly, however, in human airway-derived cell models, moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection, even at a concentration of 10 µM. These disappointing results calls for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on Vero cells. Altogether, these findings suggest that, even by using a high-dose regimen of ivermectin or switching to another drug in the same class are unlikely to be useful for treatment against SARS-CoV-2 in humans.