bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity
Authors: Safra Modi , Tamari Zvi , Polak Pazit , Shiber Shachaf , Matan Moshe , Karameh Hani , Helviz Yigal , Levy-Barda Adva , Yahalom Vered , Peretz Avi , Ben-Chetrit Eli , Brenner Baruch , Tuller Tamir , Gal-Tanamy Meital , Yaari Gur 
Published: December 2022

AbstractThe success of the human body in fighting SARS-CoV-2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance. We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV-2 compared with uninfected controls. In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients. These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.
Nature and biological irrelevance of mixed-type enzyme inhibition
Authors: Pesaresi Alessandro 
Published: December 2022

AbstractMixed-type enzyme inhibitors were originally envisaged to decrease the enzyme affinity for the substrates and the maximum turnover rate by simultaneously targeting two distinct protein sites, i.e., the active site and an allosteric site. After a century from the first formulation of this hypothesis, the consensus on its validity is still unanimous, although several of its implications are in open conflict with the current knowledge on molecular recognition mechanisms. In particular, there is no plausible explanation for the experimental evidence that mixed-type inhibitors bind the enzyme active sites always more effectively than the allotopic sites. In an attempt to solve this controversy, it was found that the preference of mixed inhibitors for active sites emerges as an inevitable numerical artifact that is implicit in the equations used to model the apparent mixed inhibition caused under certain circumstances by active site-bound competitive inhibitors. Hence, proving that the consolidated model of mixed inhibition is incorrect and, more generally, strongly pointing to the biological irrelevance of mixed-type inhibition.
CEP signaling coordinates plant immunity with nitrogen status
Authors: Rzemieniewski Jakub , Leicher Henriette , Lee Hyun Kyung , Broyart Caroline , Nayem Shahran , Wiese Christian , Maroschek Julian , Camgöz Zeynep , Lalun Vilde Olsson , Djordjevic Michael Anthony , Corina Vlot A. , Hückelhoven Ralph , Santiago Julia , Stegmann Martin 
Published: December 2022

AbstractPlant endogenous signaling peptides shape growth, development and adaptations to biotic and abiotic stress. Here, we identified C-TERMINALLY ENCODED PEPTIDEs (CEPs) as novel immune-modulatory peptides (phytocytokines) inArabidopsis thaliana. Our data reveals that CEPs induce immune outputs and are required to mount resistance against the leaf-infecting bacterial pathogenPseudomonas syringaepv. tomato. We show that effective immunity requires CEP perception by tissue-specific CEP RECEPTOR 1 (CEPR1) and CEPR2. Moreover, we identified the related RECEPTOR-LIKE KINASE 7 (RLK7) as a novel CEP4-specific CEP receptor contributing to CEP-mediated immunity, suggesting a complex interplay of multiple CEP ligands and receptors in different tissues during biotic stress. CEPs have a known role in the regulation of root growth and systemic nitrogen (N)-demand signaling. We now provide evidence that CEPs and their receptors promote immunity in an N status-dependent manner, suggesting a previously unknown molecular crosstalk between plant nutrition and cell surface immunity. We propose that CEPs and their receptors are central regulators for the adaptation of biotic stress responses to plant-available resources.
Effect of flavonoids hydroxygenkwanin on vascular smooth muscle cell proliferation, migration, and neointimal formation
Authors: Chen Chin-Chuan , Lin Mao-Shin , Chen Pin-Yu , Leu Yann-Lii , Wang Shu-Huei 
Published: December 2022

AbstractBackgroundRestenosis and atherosclerosis are chronic inflammatory disease. Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to evaluate and elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia.MethodsTo determine the therapeutic effects of HGK in PDGF-BB- or TNF-α-treated VSMCs, MTT assays, Western blotting analysis, cell cycle analysis, BrdU incorporation assay, wound healing assay and adhesion assay were performed in vitro. A docking assay was also used to elucidate the mechanism underlying the regulatory effect of HGK. Histological and immunohistochemical staining of denuded femoral arteries was conducted to elucidate the therapeutic effect of HGK in an in vivo assay.ResultsHGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice.ConclusionsIn the present study, HGK decreased the PDGF-BB- or TNF-α-induced abnormal proliferation, migration and inflammation in VSMCs and improved re-endothelialization and neointimal hyperplasia in denuded femoral arteries. These results provide a novel potential treatment for restenosis in the future.Graphic abstractHGK decreases VSMC abnormal proliferation, migration and inflammation through PDK1/AKT/mTOR/S6K inhibition and promotes EPC chemotaxis and reendothelialization. HGK is a potential therapeutic candidate for intimal hyperplasia and restenosis.
Host reverse transcriptase is required to maintain persistent dengue virus infections in C6/36 insect cells
Authors: Gangnonngiw Warachin , Flegel Timothy W. , Kanthong Nipaporn 
Published: December 2022

ABSTRACTIt has been long known that C6/36 cells challenged with Dengue virus serotype 2 (DENV-2) show initial cytopathic effects (CPE) but overcome these within 3 split passages to resume normal growth and morphology. It is also known that establishment of persistent infections requires combined action of host reverse-transcriptase (RT) activity and RNA-mediated interference (RNAi). We hypothesized that RT inhibition in C6/36 cells would also prevent persistent infections with DENV-2 and that treatment of stable, grossly normal C6/36 cells persistently infected with DENV-2, even after long passaging, would revert to CPE and die under continuous exposure to the RT inhibitor tenofovir disoproxil fumarate (TDF). Toxicity tests using TDF with naive C6/36 cells revealed limited effects at 0.1 mM but challenge with DENV-2 in its presence resulted in death, as expected based on previous reports. However, TDF treatment of stable, grossly normal C6/36 cell cultures persistently infected with DENV-2 for up to 30 split passages also induced severe CPE and death. The results indicate a key role of host RT not only in the establishment of persistent infections but also in their long-term maintenance. Persistent infections in shrimp and insects are sometimes characterized with low to very low levels of viral infection that are not detectable by routine histological analysis,in situhybridization, immunohistochemistry or even by very sensitive PCR. Our results suggest that treatment of grossly normal insects or crustaceans with TDF may be a simple approach to induce higher replication by accommodated viruses. This could improve detection by histological or molecular methods and provide a way to invoke a disease state. It could also be used to increase viral quantities for purification purposes.
Genome editing of thevermilionlocus generates a visible eye color marker forOncopeltus fasciatus
Authors: Reding Katie , Lê Minh , Pick Leslie 
Published: December 2022

AbstractInsects display a vast array of eye and body colors. Genes encoding products involved in biosynthesis and deposition of pigments are ideal genetic markers, contributing, for example, to the power ofDrosophilagenetics.Oncopeltus fasciatusis an emerging model for hemimetabolous insects, a member of the piercing-sucking feeding order Hemiptera, that includes pests and disease vectors. To identify candidate visible markers forO. fasciatus, we used parental and nymphal RNAi to identify genes that altered eye or body color while having no deleterious effects on viability. We selectedOf-vermilionfor CRISPR/Cas9 genome editing, generating three independent loss-of-function mutant lines. These studies mappedOf-vermilionto the X-chromosome, the first assignment of a gene to a chromosome in this species.Of-vermilionhomozygotes have bright red, rather than black, eyes and are fully viable and fertile. We used these mutants to verify a role forOf-xdh1, ortholog ofDrosophila rosy, in contributing to red pigmentation after RNAi. Rather than wild-type-like red bodies, bugs lacking bothvermilionandxdh1have bright yellow bodies, suggesting that ommochromes and pteridines contribute toO. fasciatusbody color. Our studies generated the first gene-based visible marker forO. fasciatusand expanded the genetic toolkit for this model system.
Post-secretory synthesis of a natural analog of iron-gall ink in the black nectar ofMelianthusspp.
Authors: Magner Evin T. , Roy Rahul , Saxhaug Katrina Freund , Zambre Amod , Bruns Kaitlyn , Snell-Rood Emilie C. , Hampton Marshall , Hegeman Adrian D. , Carter Clay J. 
Published: December 2022

SUMMARYThe black nectar ofMelianthusflowers is thought to serve as a visual attractant to pollinators, but the chemical identity and synthesis of the black pigment are unknown. Here we report that the black nectar contains a natural analog of iron-gall ink, which humans have used since medieval times. Specifically, dark black nectar at anthesis contains high levels of ellagic acid and iron; synthetic solutions of ellagic acid and iron(III) recapitulate the black color of the nectar. Conversely, lightly colored nectars before and after anthesis contain significantly lower levels of ellagic acid and iron, but higher levels of gallic acid. We then explored the possibility of post-secretory synthesis of ellagic acid from gallic acid. Indeed,Melianthusnectar contains a peroxidase that oxidizes gallic acid to form ellagic acid. Reactions containing the nectar peroxidase, gallic acid, hydrogen peroxide, and iron can fully recreate the black color of the nectar. Visual modeling indicates that the black color is both visible and conspicuous to birds within the context of the flower. In summary, the black nectar ofMelianthusis derived from an ellagic acid-Fe complex analogous to iron-gall ink and is likely involved in the attraction of passerine bird pollinators.
HIGHLY PHAGOCYTIC LIPID-ASSOCIATED MACROPHAGES (LAMs) ARE INCREASED IN COLONIC LAMINA PROPRIA IN OBESITY
Authors: Castoldi Angela , Sanin David E , van Teijlingen Bakker Nikki , Aguiar Christiane F , de Brito Monteiro Lauar , Rana Nisha , Grzes Katarzyna M , Kabat Agnieszka M , Curtis Jonathan , Cameron Alanna M , Caputa George , de Souza Tiago Antônio , O Souto Fabrício , Buescher Joerg M , Edwards-Hicks Joy , Pearce Erika L , Pearce Edward J , Saraiva Camara Niels Olsen 
Published: December 2022

AbstractLittle is known about the effects of high fat diet (HFD)-induced obesity on resident colonic lamina propria (LP) macrophages (LPMs) function and metabolism. Here, we report that obesity and diabetes resulted in increased macrophage infiltration in the colon. These macrophages exhibited the residency phenotype CX3CR1hiMHCIIhi, and were CD4−TIM4−. During HFD, resident colonic LPM exhibited a lipid metabolism gene expression signature that overlapped that used to define lipid associated macrophages (LAMs). Via single cell RNA sequencing, we identified a sub-cluster of macrophages, increased in HDF, that were responsible for the LAM signature. Compared to other macrophages in the colon, these cells were characterized by elevated glycolysis, phagocytosis and efferocytosis signatures. CX3CR1hiMHCIIhicolonic resident LPMs had fewer lipid droplets (LD) and decreased triacylglycerol (TAG) content compared to equivalent cells in lean mice, and exhibited increased phagocytic capacity, suggesting that HFD induces adaptive responses in LPMs to limit bacterial translocation.
Spatial-temporal evolution characteristics of land use and its driving factor analysis during the period of 2000-2020 in Putian City, Fujian Province
Authors: Zhang Jinshan , Wu Dongqing , Peng Qingxia , Lin Zhimin , Lin Wenxiong , Su Kai 
Published: December 2022

AbstractExploring the spatial and temporal evolution characteristics of land use and its driving force can provide scientific basis for the construction of regional ecological civilization. Based on the remote sensing cloud computing platform of Google Earth Engine (GEE), the study took the remote sensing images of the three periods of 2000, 2010 and 2020 as the basic data and interpreted them to obtain the basic land use data of Putian city and its five districts and counties. The land-use change characteristics of Putian city in those periods were systematically analyzed by using the methods of single land-use dynamics and Geo-informatic Tupu, so as to reveal the Tupu characteristics of land-use transfer and the spatial-temporal evolution pattern in the past 20 years. Then social and economic development indicators were selected to further explore the key driving force of land-use evolution in the study area by canonical correspondence analysis. The results showed that: 1) the land use structure of Putian city was mainly composed of cultivated land and forest land, and the other land types were embedded in them and the built-up land continued to expand outward. 2) The spatial distribution of Tupu units of land use transfer in Putian city was significantly different, change types of land use were diversified and the areas of cultivated land and grassland transferred out were the most obvious. Different degrees of cultivated land abandonment had occurred in various regions. Putian city was facing great challenges in ensuring food security and curbing the non-agricultural and non grain of cultivated land. 3) The macro-economic development in a specific period, especially the urban expansion and the development of the secondary industry caused by the merger of cities and counties, were the key factors driving the spatial and temporal evolution of land use and the differential distribution pattern in Putian city. The author suggested that land resources should be used efficiently in addition to optimizing the layout of land use and carrying out the renovation of abandoned land. Therefore, the study proposed to strengthen the scientific planning and effective regulation of land use, combine spatial and temporal resources of cultivated land with agriculture, culture and tourism, and build ecological barriers and ecological corridors to ensure the coordinated and sustainable development of regional ecology and economy.
Transposable element and host silencing activity in gigantic genomes
Authors: Wang Jie , Yuan Liang , Tang Jiaxing , Liu Jiongyu , Sun Cheng , Itgen Michael W. , Chen Guiying , Sessions Stanley K. , Zhang Guangpu , Mueller Rachel Lockridge 
Published: December 2022

AbstractTransposable elements (TEs) and the silencing machinery of their hosts are engaged in a germline arms-race dynamic that shapes TE accumulation and, therefore, genome size. In animal species with extremely large genomes (>10 Gb), TE accumulation has been pushed to the extreme, prompting the question of whether TE silencing also deviates from typical conditions. To address this question, we characterize TE silencing via two pathways — the piRNA pathway and KRAB-ZFP transcriptional repression — in the male and female gonads ofRanodon sibiricus, a salamander species with a ∼21 Gb genome. We quantify 1) genomic TE diversity, 2) TE expression, and 3) small RNA expression and find a significant relationship between the expression of piRNAs and TEs they target for silencing in both sexes. We also quantified TE silencing pathway gene expression inR. sibiricusand 14 other vertebrates with genome sizes ranging from 1 – 130 Gb and find no association between pathway expression and genome size. Taken together, our results reveal that the giganticR. sibiricusgenome includes at least 19 putatively active TE superfamilies, all of which are targeted by the piRNA pathway in proportion to their expression levels, suggesting comprehensive piRNA-mediated silencing. Males have higher TE expression than females, suggesting that they may contribute more to the species’ high genomic TE load. We posit that apparently conflicting interpretations of TE silencing and genomic gigantism in the literature, as well as the absence of a correlation between TE silencing pathway gene expression and genome size, can be reconciled by considering whether the TE community or the host is currently “on the attack” in the arms race dynamic.
Dissecting Complexity: The Hidden Impact of Application Parameters on Bioinformatics Research
Authors: Cashman Mikaela , Cohen Myra B. , Marsh Alexis L. , Cottingham Robert W. 
Published: December 2022

AbstractBiology is a quest; an ongoing inquiry about the nature of life. How do the different forms of life interact? What makes up an ecosystem? How does a tiny bacterium work? To answer these questions biologists turn increasingly to sophisticated computational tools. Many of these tools are highly configurable, allowing customization in support of a wide range of uses. For example, algorithms can be tuned for precision, efficiency, type of inquiry, or for specific categories of organisms or their component subsystems. Ideally, configurability provides useful flexibility. However, the complex landscape of configurability may be fraught with pitfalls. This paper examines that landscape in bioinformatics tools. We propose a methodology, SOMATA, to facilitate systematic exploration of the vast choice of application parameters, and apply it to three different tools on a range of scientific inquires. We further argue that the tools themselves are complex ecosystems. If biologists explore these, ask questions, and experiment just as they do with their biological counterparts, they will benefit by both finding improved solutions to their problems as well as increasing repeatability and transparency. We end with a call to the community for an increase in shared responsibility and communication between tool developers and the biologists that use them in the context of complex system decomposition.
Choice of Parcellation Atlas Might Not be Too Critical for Connectomic Analysis
Authors: Nesbit Steven C. , Parker Drew , Verma Ragini , Osmanlıoğlu Yusuf 
Published: December 2022

ABSTRACTConnectomics has been a rapidly growing discipline in neuroimaging and neuroscience that evolved our understanding of the brain. Connectomics involves representing the brain as a network of regions, where the parcellation of the brain into regions using a template atlas is an integral part of the analysis. Over developmental and young adult cohorts of healthy individuals, we investigated how choosing parcellation atlases at certain resolutions affect sex classification and age prediction tasks performed using deep learning on structural connectomes. Datasets were processed on a total of 35 parcellations, where the only significant difference was observed for age prediction on the developmental cohort with a slight improvement on higher resolutions. This indicates that choice of parcellation scheme is generally not critical for deep learningbased age prediction and sex classification. Therefore, results between studies using different parcellation schemes could be comparable and repeating analyses on multiple atlases might be unnecessary.
Inhibition of pyrimidine synthesis in murine skin wounds induces a pyoderma gangrenosum-like neutrophilic dermatosis accompanied by spontaneous gut inflammation
Authors: Jatana Samreen , Ponti András K. , Johnson Erin E. , Rebert Nancy A. , Smith Jordyn L. , Fulmer Clifton G. , Maytin Edward V. , Achkar Jean-Paul , Fernandez Anthony P. , McDonald Christine 
Published: December 2022

AbstractPyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ∼40% of patients that present with PG have underlying IBD, suggesting shared but unknown pathogenesis mechanisms. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concurrent intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) and pro-inflammatory cellular as well as soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating immature low-density IL-1β primed granulocytes that undergo enhanced NETosis at inflamed tissue sites supported by increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.