bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Myostatin and Follistatin Levels in Patients With Dermatomyositis and Polymyositis
Authors: de Sordi Cintia M. , dos Reis-Neto Edgard T. , Keppeke Gerson D. , Shinjo Samuel K. , Sato Emília Inoue 
Published: November 2021

Background
Myostatin is a protein in the TGF-β family that negatively regulates muscle mass, and follistatin is a myostatin antagonist.

Objective
The aim of this study was to measure serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients and correlate these levels with muscle strength, fatigue, functional capacity, damage, and serum levels of muscle enzymes.

Methods
This was a multicenter cross-sectional study including 50 patients (34 dermatomyositis and 16 polymyositis [PM]) and 52 healthy individuals (control group [CG]). The disease status was evaluated according to the International Myositis Assessment & Clinical Studies. Fatigue was rated according to the Fatigue Severity Scale, and body composition was measured using dual-energy x-ray emission densitometry. Myostatin and follistatin were measured using enzyme-linked immunosorbent assays.

Results
Mean age was 50.9 ± 14.0 years, and mean disease duration was 89.2 ± 80.9 months. There were no differences in levels of myostatin (14.15 ± 9.65 vs. 10.97 ± 6.77 ng/mL; p = 0.131) or follistatin (0.53 ± 0.71 vs. 0.49 ± 0.60 ng/mL; p = 0.968) between patients and the CG. However, myostatin levels were higher in PM than CG (16.9 ± 12.1 vs. 11.0 ± 6.8 ng/mL; p = 0.036). There was no difference in serum myostatin among patients with and without low lean mass. Patients not treated with corticosteroids had higher serum levels of myostatin than the CG. There was a weak negative correlation between follistatin and Manual Muscle Testing and a Subset of Eight Muscles and a weak positive correlation between follistatin and Healthy Assessment Questionnaire.

Conclusions
Serum levels of myostatin and follistatin did not differ between dermatomyositis and PM patients and control subjects. The assessment of serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients seems not to be helpful in clinical practice.
Predicting Melanoma Staging using Targeted RNA Sequencing data using Machine Learning
Authors: Ahmed Fahad Shabbir , Irfan Furqan Bin 
Published: November 2021

ABSTRACTThe aim of this study is to use machine learning to predict tumor staging and metastasis in melanoma with differentially expressed genes. Machine has been used in different clinical setting to predict different outcomes. However, it has not been used to look at predicting the diagnostic aspect of tumor staging. We used the TCGA RNA-Sequencing data on melanomas to predict tumor staging nodal and/or metastasis using deep neural networks (DNN) and random forest classifier (RF). Results: We were able to predict tumor staging (lower vs higher stage, i.e. Tis / T1 / T2 vs T3 and higher), nodal metastasis and combined nodal or distant metastasis in patients with melanomas with high accuracies. However, we need to further validate these results.
Spread of Xanthomonas vasicola pv. musacearum within banana mats: implications for Xanthomonas wilt management
Authors: Ocimati Walter , Tazuba Anthony Fredrick , Blomme Guy 
Published: November 2021

AbstractXanthomonas wilt (XW) of banana caused by Xanthomonas vasicola pv. musacearum (Xvm) does not spread to all plants physically interconnected through the rhizome when one or a few are diseased. However, the factors behind this incomplete systemic spread of Xvm are not fully known yet could inform XW management. This study explored the effect of Xvm inoculum amounts, number and size of suckers, sucker positioning on mother plant corms and other mother plant corm attributes on sucker colonization. A shorter (p <0.05) incubation period (17.9 vs 21.1 days) and higher (p<.001) cumulative number of symptomatic leaves (5.2 vs 1.6 leaves) was observed when all (high inoculum) compared to two leaves (low inoculum) were inoculated. Xvm was recovered in corms at 29 days post inoculation (dpi) in both treatments with no differences (p >0.05) in proportions of corms with Xvm between the treatments. However, Xvm was recovered earlier and at a higher frequency in suckers when all leaves were inoculated. Lower Xvm recoveries occurred in the lower corm sections to which most suckers were attached relative to the middle and upper corm sections. Xvm incidence in corms increased with the number of attached maiden suckers, and the dpi while it declined with increasing mother plant and corm height. Thus, Xvm spread within mats is influenced by the amount of inoculum and the physiological stage (e.g., height) of the plant and attached suckers. The position of suckers, predominantly at the bottom of corms also protects them from infection. Measures that reduce Xvm inoculum build-up in mats are thus crucial for minimizing within mat XW spread.
SARS-CoV-2 infection in free-ranging white-tailed deer (Odocoileus virginianus)
Authors: Hale Vanessa L. , Dennis Patricia M. , McBride Dillon S. , Nolting Jaqueline M. , Madden Christopher , Huey Devra , Ehrlich Margot , Grieser Jennifer , Winston Jenessa , Lombardi Dusty , Gibson Stormy , Saif Linda , Killian Mary L. , Lantz Kristina , Tell Rachel , Torchetti Mia , Robbe-Austerman Suelee , Nelson Martha I. , Faith Seth A. , Bowman Andrew S. 
Published: November 2021

AbstractHuman-to-animal spillover of SARS-CoV-2 virus has occurred in a wide range of animals, but thus far, the establishment of a new natural animal reservoir has not been detected. Here, we detected SARS-CoV-2 virus using rRT-PCR in 129 out of 360 (35.8%) free-ranging white-tailed deer (Odocoileus virginianus) from northeast Ohio (USA) sampled between January-March 2021. Deer in 6 locations were infected with at least 3 lineages of SARS-CoV-2 (B.1.2, B.1.596, B.1.582). The B.1.2 viruses, dominant in Ohio at the time, spilled over multiple times into deer populations in different locations. Deer-to-deer transmission may have occurred in three locations. The establishment of a natural reservoir of SARS-CoV-2 in white-tailed deer could facilitate divergent evolutionary trajectories and future spillback to humans, further complicating long-term COVID-19 control strategies.One-Sentence SummaryA significant proportion of SARS-CoV-2 infection in free-ranging US white-tailed deer reveals a potential new reservoir.
Validation and invalidation of SARS-CoV-2 papain-like protease inhibitors
Authors: Ma Chunlong , Wang Jun 
Published: November 2021

AbstractSARS-CoV-2 encodes two viral cysteine proteases, the main protease (Mpro) and the papain-like protease (PLpro), both of which are validated antiviral drug targets. The PLprois involved in the cleavage of viral polyproteins as well as immune modulation through removing ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins. Therefore, targeting PLpromight be a two-pronged approach. Several compounds including YM155, cryptotanshinone, tanshinone I, dihydrotanshinone I, tanshinone IIA, SJB2-043, 6-thioguanine, and 6-mercaptopurine were recently identified as SARS-CoV-2 PLproinhibitors through high-throughput screening. In this study, we aim to validate/invalidate the reported PLproinhibitors using a combination of PLprotarget specific assays including enzymatic FRET assay, thermal shift binding assay (TSA), and the cell based FlipGFP assay. Collectively, our results showed that all compounds tested either did not show binding or led to denaturation of the PLproin the TSA binding assay, which might explain their weak enzymatic inhibition in the FRET assay. In addition, none of the compounds showed cellular inhibition of PLproas revealed by the FlipGFP assay. Therefore, more efforts are needed to search for specific and potent SARS-CoV-2 PLproinhibitors.
Brilacidin, a COVID-19 Drug Candidate, demonstrates broad-spectrum antiviral activity against human coronaviruses OC43, 229E and NL63 through targeting both the virus and the host cell
Authors: Hu Yanmei , Jo Hyunil , DeGrado William F. , Wang Jun 
Published: November 2021

AbstractBrilacidin, a mimetic of host defense peptides (HDPs), is currently in phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against SARS-CoV-2 by inactivating the virus. In this work, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, a HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.
Mutations in CSRP3/MLP, a Z-disc associated gene are functionally associated with dilated cardiomyopathy in Indian population
Authors: Giri Prerna , Dixit Ritu , Kumar Ashok , Mohapatra Bhagyalaxmi 
Published: November 2021

AbstractCSRP3 is a LIM domain containing protein, known to play an important role in cardiomyocyte development, differentiation and pathology. Mutations in CSRP3 gene are reported in both dilated and hypertrophic cardiomyopathy (DCM and HCM), however, the genotype-phenotype correlation still remains elusive. To investigate the pathogenic potential of CSRP3 variants in our DCM cohort, we have screened 100 DCM cases and 100 controls and identified 3 non-synonymous variations, of which two are missense variants viz., c.233 GGC>GTC, p.G78V; c.420 TGG>TGC, p.W140C, and the third one is a single nucleotide polymorphism (SNP) c.46 ACC>TCC, p.T16S. These variants were absent from 100 control individuals (200 chromosomes). In vitro functional analysis has revealed reduction of CSRP3 protein level in stably-transfected C2C12 cells with p.G78V or p.W140C variants. Immunostaining demonstrates both cytoplasmic and nuclear localization of the wild-type protein, however variants p.G78V and p.W140C cause obvious reduction in the cytoplasmic expression of CSRP3 protein which is more pronounced in case of p.W140C. Disarrayed actin cytoskeleton was also observed in mutants. Besides, the expression of target genes namely Ldb3, Myoz2, Tcap, Tnni3 and Ttn are also downregulated in response to these variants. GST-pulldown assay has also showed a diminished binding of CSRP3 protein with α-Actinin due to both variants p.G78V and p.W140C. Both 2D, 3D-modeling have shown confirmational changes. Most in silico tools predict these variants as deleterious. Taken together, all these results suggest the impaired gene function due to these deleterious variants in CSRP3, implicating its possible disease causing role in DCM.
Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts
Authors: Petropoulou-Vathi Lilian , Simitsi Athina , Valkimadi Politymi-Eleni , Kedariti Maria , Dimitrakopoulos Lampros , Koros Christos , Papadimitriou Dimitra , Papadimitriou Alexandros , Stefanis Leonidas , Alcalay Roy N. , Rideout Hardy J. 
Published: November 2021

AbstractDespite several advances in the field, pharmacodynamic outcome measures reflective of LRRK2 kinase activity in clinical biofluids remain urgently needed. A variety of targets and approaches have been utilized including assessments of LRRK2 itself (levels, phosphorylation), or its substrates (e.g. Rab10 or other Rab GTPases). We have previously shown that intrinsic kinase activity of LRRK2 isolated from PBMCs of G2019S carriers is elevated, irrespective of disease status. In the present study we find that phosphorylation of Rab10 is also elevated in G2019S carriers, but only those with PD. Additionally, phosphorylation of this substrate is also elevated in 2 separate idiopathic PD cohorts, but not in carriers of the A53T mutation in α-synuclein. In contrast, Rab29 phosphorylation was specifically reduced in urinary exosomes from A53T and idiopathic PD patients. Taken together, our findings highlight the need for the assessment of multiple complimentary targets for a more comprehensive picture of the disease.
Affinity sedimentation and magnetic separation with plant-made immunosorbent nanoparticles for therapeutic protein purification
Authors: McNulty Matthew J. , Schwartz Anton , Delzio Jesse , Karuppanan Kalimuthu , Jacobson Aaron , Hart Olivia , Dandekar Abhaya , Giritch Anatoli , Nandi Somen , Gleba Yuri , McDonald Karen A. 
Published: November 2021

SummaryThe virus-based immunosorbent nanoparticle is a nascent technology being developed to serve as a simple and efficacious agent in biosensing and therapeutic antibody purification. There has been particular emphasis on the use of plant virions as immunosorbent nanoparticle chassis for their diverse morphologies and accessible, high yield manufacturing via crop cultivation. To date, studies in this area have focused on proof-of-concept immunosorbent functionality in biosensing and purification contexts. Here we consolidate a previously reported pro-vector system into a singleAgrobacterium tumefaciensvector to investigate and expand the utility of virus-based immunosorbent nanoparticle technology for therapeutic protein purification. We demonstrate the use of this technology for Fc-fusion protein purification, characterize key nanomaterial properties including binding capacity, stability, reusability, and particle integrity, and present an optimized processing scheme with reduced complexity and increased purity. Furthermore, we present a coupling of virus-based immunosorbent nanoparticles with magnetic particles as a strategy to overcome limitations of the immunosorbent nanoparticle sedimentation-based affinity capture methodology. We report magnetic separation results which exceed the binding capacity of current industry standards by an order of magnitude.
Ancient genomes from the last three millennia support multiple human dispersals into Wallacea
Authors: Oliveira Sandra , Nägele Kathrin , Carlhoff Selina , Pugach Irina , Koesbardiati Toetik , Hübner Alexander , Meyer Matthias , Oktaviana Adhi Agus , Takenaka Masami , Katagiri Chiaki , Murti Delta Bayu , Putri Rizky Sugianto , Mahirta  , Higham Thomas , Higham Charles F. W. , O’Connor Sue , Hawkins Stuart , Kinaston Rebecca , Bellwood Peter , Ono Rintaro , Powell Adam , Krause Johannes , Posth Cosimo , Stoneking Mark 
Published: November 2021

AbstractPrevious research indicates that the human genetic diversity found in Wallacea - islands in present-day Eastern Indonesia and Timor-Leste that were never part of the Sunda or Sahul continental shelves - has been shaped by complex interactions between migrating Austronesian farmers and indigenous hunter-gatherer communities. Here, we provide new insights into this region’s demographic history based on genome-wide data from 16 ancient individuals (2600-250 yrs BP) from islands of the North Moluccas, Sulawesi, and East Nusa Tenggara. While the ancestry of individuals from the northern islands fit earlier views of contact between groups related to the Austronesian expansion and the first colonization of Sahul, the ancestry of individuals from the southern islands revealed additional contributions from Mainland Southeast Asia, which seems to predate the Austronesian admixture in the region. Admixture time estimates for the oldest individuals of Wallacea are closer to archaeological estimates for the Austronesian arrival into the region than are admixture time estimates for present-day groups. The decreasing trend in admixture times exhibited by younger individuals supports a scenario of multiple or continuous admixture involving Papuan- and Asian-related groups. Our results clarify previously debated times of admixture and suggest that the Neolithic dispersals into Island Southeast Asia are associated with the spread of multiple genetic ancestries.
A novel enhancer of Agouti contributes to parallel evolution of cryptically colored beach mice
Authors: Wooldridge T. Brock , Kautt Andreas F. , Lassance Jean-Marc , McFadden Sade , Domingues Vera S. , Mallarino Ricardo , Hoekstra Hopi E. 
Published: November 2021

AbstractIdentifying the genetic basis of repeatedly evolved traits provides a way to reconstruct their evolutionary history and ultimately investigate the predictability of evolution. Here, we focus on the oldfield mouse (Peromyscus polionotus), which occurs in the southeastern United States, where it exhibits considerable coat-color variation. Dorsal coats range from dark brown in mice inhabiting mainland habitat to near white on the white-sand beaches of the southeastern US, where light pelage has evolved independently on Florida’s Gulf and Atlantic coasts as an adaptation to visually hunting predators. To facilitate genomic analyses in this species, we first generated a high-quality, chromosome-level genome assembly of P. polionotus subgriseus. Next, in a uniquely variable mainland population that occurs near beach habitat (P. p. albifrons), we scored 23 pigment traits and performed targeted resequencing in 168 mice. We find that variation in pigmentation is strongly associated with a ~2 kb region approximately 5 kb upstream of the Agouti-signaling protein (ASIP) coding region. Using a reporter-gene assay, we demonstrate that this regulatory region contains an enhancer that drives expression in the dermis of mouse embryos during the establishment of pigment prepatterns. Moreover, extended tracts of homozygosity in this region of Agouti indicate that the light allele has experienced recent and strong positive selection. Notably, this same light allele appears fixed in both Gulf and Atlantic coast beach mice, despite these populations being separated by >1,000km. Given the evolutionary history of this species, our results suggest that this newly identified Agouti enhancer allele has been maintained in mainland populations as standing genetic variation and from there has spread to, and been selected in, two independent beach mouse lineages, thereby facilitating their rapid and parallel evolution.
Single cell RNA-seq uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19
Authors: Aznaourova Marina , Schmerer Nils , Janga Harshavardhan , Zhang Zhenhua , Pauck Kim , Hoppe Judith , Volkers Sarah M , Wendisch Daniel , Georg Philipp , Gündisch Margrit , Mack Elisabeth , Skevaki Chrysanthi , Keller Christian , Bauer Christian , Bertrams Wilhelm , Nist Andrea , Stiewe Thorsten , Gruber Achim D , Ruppert Clemens , Li Yang , Garn Holger , Sander Leif E , Schmeck Bernd , Schulte Leon N 
Published: November 2021

AbstractThe systemic immune response to viral infection is shaped by master transcription factors such as NFκB or PU.1. Although long non-coding RNAs (lncRNAs) have been suggested as important regulators of transcription factor activity, their contributions to the systemic immunopathologies observed during SARS-CoV-2 infection have remained unknown. Here, we employed a targeted single-cell RNA-seq approach to reveal lncRNAs differentially expressed in blood leukocytes during severe COVID-19. Our results uncover the lncRNA PIRAT as a major PU.1 feedback-regulator in monocytes, governing the production of the alarmins S100A8/A9 – key drivers of COVID-19 pathogenesis. Knockout and transgene expression, combined with chromatin-occupancy profiling characterized PIRAT as a nuclear decoy RNA, diverting the PU.1 transcription factor from alarmin promoters to dead-end pseudogenes in naïve monocytes. NFκB-dependent PIRAT down-regulation during COVID-19 consequently releases a transcriptional brake, fueling alarmin production. Our results suggest a major role of nuclear noncoding RNA circuits in systemic antiviral responses to SARS-CoV-2 in humans.
CALDERA: Finding all significant de Bruijn subgraphs for bacterial GWAS
Authors: Roux de Bézieux Hector , Lima Leandro , Perraudeau Fanny , Mary Arnaud , Dudoit Sandrine , Jacob Laurent 
Published: November 2021

AbstractGenome wide association studies (GWAS), aiming to find genetic variants associated with a trait, have widely been used on bacteria to identify genetic determinants of drug resistance or hypervirulence. Recent bacterial GWAS methods usually rely on k-mers, whose presence in a genome can denote variants ranging from single nucleotide polymorphisms to mobile genetic elements. Since many bacterial species include genes that are not shared among all strains, this approach avoids the reliance on a common reference genome. However, the same gene can exist in slightly different versions across different strains, leading to diluted effects when trying to detect its association to a phenotype through k-mer based GWAS. Here we propose to overcome this by testing covariates built from closed connected subgraphs of the De Bruijn graph defined over genomic k-mers. These covariates are able to capture polymorphic genes as a single entity, improving k-mer based GWAS in terms of power and interpretability. As the number of subgraphs is exponential in the number of nodes in the DBG, a method naively testing all possible subgraphs would result in very low statistical power due to multiple testing corrections, and the mere exploration of these subgraphs would quickly become computationally intractable. The concept of testable hypothesis has successfully been used to address both problems in similar contexts. We leverage this concept to test all closed connected subgraphs by proposing a novel enumeration scheme for these objects which fully exploits the pruning opportunity offered by testability, resulting in drastic improvements in computational efficiency. We illustrate this on both real and simulated datasets and also demonstrate how considering subgraphs leads to a more powerful and interpretable method. Our method integrates with existing visual tools to facilitate interpretation. We also provide an implementation of our method, as well as code to reproduce all results at https://github.com/HectorRDB/Caldera_Recomb.
ANI, Mash and Dashing equally differentiate between Klebsiella species
Authors: Hernández-Salmerón Julie E. , Moreno-Hagelsieb Gabriel 
Published: November 2021

ABSTRACTSpecies of the genus Klebsiella are among the most important multidrug resistant human pathogens, though they have been isolated from a variety of environments. Given the need for quickly and accurately classifying newly sequenced Klebsiella genomes, we compared 982 Klebsiella genomes using different species-delimiting measures: Average Nucleotide Identity (ANI), which is becoming a standard for species delimitation, as well as Mash, Dashing, and DNA compositional signatures, which can be run in a fraction of the time required to run ANI. ROC analyses showed equal quality in species delimitation for ANI, Mash and Dashing (AUC: 0.99), followed by DNA signatures (AUC: 0.96). The groups obtained at optimal cutoffs were largely in agreement with species designation. Using optimized cutoffs, we obtained 17 species-level groups using either ANI, Mash, or Dashing, all containing the same genomes, unlike DNA signatures which broke the dataset into 38 groups. Further use of Mash to map species after adding draft genomes to the dataset also showed excellent results (AUC: 0.99), producing a total of 28 Klebsiella species in the publicly available genome collection. The ecological niches of Klebsiella strains were found to neither be related to species delimitation, nor to protein functional content, suggesting that a single Klebsiella species can have a wide repertoire of ecological functions.