bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of temperature on a ferroelectric interfaced negative capacitance double gate junctionless accumulation mode field effect transistor-compact model
Authors: Yadav Snehlata , Rewari Sonam , Pandey Rajeshwari 
Published: March 2023

Ferroelectric interfaced negative capacitance field effect transistors are gaining popularity for low power applications; however, as temperature is a constant influencing factor, further study is required to comprehend how these devices are influenced. Through a proposed compact model, this paper analytically investigates the influence of temperature on a ferroelectric interfaced negative capacitance double gate junctionless accumulation mode field effect transistor. This device integrates the benefits of negative capacitance with the junctionless accumulation mode structure. An extensive comparison of the proposed device is made with the existing structure to evaluate the benefits offered by the ferroelectric layer at different temperatures. The Landau–Khalatnikov equation and Pao–Sah integral are employed to obtain the surface potential and drain current model with temperature variation. Various key parameters of the device have been analysed extensively by varying the temperature from 200 to 500 K. It has been found that internal voltage amplification declines as temperature rises, but the sub-threshold swing increases from 46 to 72 mV decade
−1
with an increase in temperature. Additionally, with a progressive rise in temperature, the loss of gain and degradation of gate capacitance are observed.
Transcriptomic responses of sponge holobionts to in situ, seasonal anoxia and hypoxia
Authors: Strehlow Brian W. , Schuster Astrid , Francis Warren R. , Eckford-Soper Lisa , Kraft Beate , McAllen Rob , Nielsen Ronni , Mandrup Susanne , Canfield Donald E. 
Published: March 2023

AbstractDeoxygenation can be fatal for many marine animals; however, some sponge species are tolerant of hypoxia and anoxia. Indeed, two sponge species,Euryponsp. 2 andHymeraphia stellifera,survive seasonal anoxia for months at a time. To understand their tolerance mechanisms, we performed differential gene expression analyses on the sponges, their mitochondria and their microbial symbionts under in situ conditions of normoxia, hypoxia and anoxia. Each species possessed a unique microbiome, but the microbiomes of each species were dominated by a species-specificThaumarchaeonand aGammaproteobacterium. Holobiont gene expression was species-and oxygen-level dependent, though there were some shared interspecific responses to deoxygenation. In general, few changes occurred in the expression of sponge metabolic genes as a function of oxygenation level, indicating that they may remain metabolically active under anoxia. However, ATP synthesis genes were significantly upregulated under hypoxia when compared to normoxia, and genes for DNA replication were downregulated. Mitochondrial gene expression was effectively unchanged under both hypoxia and anoxia. Nevertheless, both anoxia and hypoxia caused upregulation of heat shock proteins (HSPs), indicating cellular level adaptations to deoxygenation stress. A meta-analysis demonstrated that sponge transcriptional responses to anoxia were distinct from those displayed by other invertebrates while dormant, and the hypothesis of sponge dormancy under anoxia was not supported.Thaumarchaeotasymbionts also upregulated stress response genes in hypoxia, while maintaining expression of oxygen-dependent metabolic pathways under hypoxia and anoxia.Gammaproteobacteriasymbionts showed relatively few noteworthy changes in gene expression in response to anoxia but decreased metabolic gene expression in hypoxia. There was no clear evidence of upregulated anaerobic respiration in the transcriptomes of the sponge holobionts under anoxia or hypoxia. The tolerance of some sponges to prolonged anoxia warrants further investigation and could give them an advantage in future oceans following climate change as well as in ancient oceans when oxygen concentrations were lower than at present.
Hypercholesterolemia aggravates in-stent restenosis in rabbits: a mitigating effect of stent surface modification with CD47-derived peptide
Authors: Fishbein Ilia , Inamdar Vaishali V , Alferiev Ivan S , Bratinov George , Zviman Menekhem M. , Yekhilevsky Anna , Nagaswami Chandrasekaran , Gardiner Kristin L. , Levy Robert J , Stachelek Stanley J 
Published: March 2023

AbstractBackgroundHypercholesterolemia (HC) has previously been shown to augment restenotic response in several animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our present studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model.Methods and ResultsPepCD47 was immobilized on metal foil coupons and stents using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. The relative abundance of the surface-associated cells on bare metal (BM) and pepCD47 foils exposed to whole rabbit blood showed a 40% inhibition of cell attachment on pepCD47-modified surfaces. Likewise, cytokine expression analyzed in buffy coat-derived cells cultured over the BM and pepCD47-derivatized foils demonstrated a M2/M1 increase with pepCD47 coating. Hypercholesterolemic and normocholesterolemic rabbit cohorts underwent bilateral implantation of BM and pepCD47 stents in the iliac location. Hypercholesterolemia increased neointimal growth in comparison with normocholesterolemic animals at 4 weeks post-stenting. These untoward outcomes were mitigated in the arteries of hypercholesterolemic rabbits treated with pepCD47-derivatized stents. Compared to NC animals, inflammatory cytokine immunopositivity and macrophage infiltration of peri-strut areas increased in HC group animals, and was attenuated in the arteries of hypercholesterolemic rabbits treated with pepCD47 stents.ConclusionsAugmented inflammatory responses triggered by HC underlie severe ISR morphology in hypercholesterolemic rabbits. Blockage of initial platelet and leukocyte attachment to stent struts through CD47 functionalization of stents mitigates pro-restenotic effects of HC.
TALE-based C-to-T base editor for multiple homologous genes with flexible precision
Authors: Hosoda Ayako , Nakazato Issei , Takanashi Hideki , Tsutsumi Nobuhiro , Arimura Shin-ichi 
Published: March 2023

AbstractRecently a cytidine deaminase-based method for highly efficient C-to-T targeted base editing was developed and has been used with CRISPR-mediated systems. It is a powerful method for genome engineering, although it is prone to off-target effects and has limited targeting scope. Transcription activator-like effector (TALE) -based tools which allow longer recognition sequences than do CRISPR/Cas9 systems, can also be used for targeted C-to-T base editing. Here, we describe a method that efficiently achieved targeted C-to-T substitutions inArabidopsisnuclear genes using cytidine deaminase fused to a TALE DNA-binding domain (TALECD). We used a single pair of TALEs with a novel TALE-repeat unit that can recognize all four DNA bases, especially to allow for variations in the third base of codons in homologous genes. This targeting strategy makes it possible to simultaneously base edit almost identical sites in multiple isoforms of a gene while suppressing off-target substitutions.
Atopic dermatitis complicated by recurrent eczema herpeticum is characterized by multiple, concurrent epidermal inflammatory endotypes
Authors: Jackson Nathan D. , Dyjack Nathan , Goleva Elena , Bin Lianghua , Montgomery Michael T. , Rios Cydney , Everman Jamie L. , Taylor Patricia , Bronchick Caroline , Richers Brittany N. , Leung Donald Y. , Seibold Max A. 
Published: March 2023

ABSTRACTBACKGROUNDA subgroup of atopic dermatitis (AD) patients suffer from recurrent, disseminated herpes simplex virus (HSV) skin infections, termed eczema herpeticum (EH), which can be life-threatening and contribute to AD morbidity. The pathobiology underlying ADEH is unknown.OBJECTIVETo determine transcriptional mechanisms of skin and immune system pathobiology that underlie ADEH disease.METHODSWe performed whole transcriptome RNA-sequencing of non-lesional skin samples (epidermis, dermis) of AD patients with (ADEH+, n=15) and without (ADEH-, n=13) recurrent EH history, and healthy controls (HC, n=15). We also performed RNA-sequencing on plasmacytoid dendritic cells (pDCs) collected from these participants and infectedin vitrowith HSV-1. Differential expression, gene set enrichment, and endotyping analyses were performed.RESULTSADEH+disease was characterized by dysregulation in skin gene expression, which was limited in dermis (differentially expressed genes [DEGs]=14) and widespread in epidermis (DEGs=129). ADEH+-upregulated epidermal DEGs were enriched in type 2 cytokine (T2) (IL4R, CCL22, CRLF2, IL7R), interferon (CXCL10, ICAM1, IFI44, andIRF7), and IL-36γ (IL36G) inflammatory pathway genes. At a person-level, all ADEH+participants exhibited T2 and interferon endotypes and 87% were IL36G-high. In contrast, these endotypes were more variably expressed among ADEH-participants. ADEH+patient skin also exhibited dysregulation in epidermal differentiation complex (EDC) genes within theLCE, S100, andSPRRfamilies, which are involved in skin barrier function, inflammation, and antimicrobial activities. pDC transcriptional responses to HSV-1 infection were not altered by ADEH status.CONCLUSIONSADEH+pathobiology is characterized by a unique, multi-faceted epidermal inflammation that accompanies dysregulation in the expression of EDC genes.Key MessagesAD patients with a history of recurrent EH exhibit molecular skin pathobiology that is similar in form, but more severe in degree, than in AD patients without this complication.Non-lesional skin of ADEH+patients concurrently exhibits excessive type 2 cytokine, interferon, and IL-36γ-driven epidermal inflammation.Expression of these inflammatory skin endotypes among ADEH+patients is associated with dysregulation in expression of epidermal differentiation complex genes involved in barrier function, inflammation, and antimicrobial activity.Capsule SummaryAD patients with a history of recurrent disseminated HSV-1 skin infections form a unique molecular skin endotype group that concurrently exhibits type 2 cytokine, interferon, and IL-36γ-driven skin inflammation, accompanied by dysregulation in expression of epidermal differentiation complex genes involved in barrier function, inflammation, and antimicrobial activity.
Tracking the intensity of the mechanism to produce antigenic diversity by subtelomeric ectopic recombination across the phylogeny ofPlasmodiumparasites
Authors: Martínez Carolina , Cárdenas Heiber , Cerón-Romero Mario A. 
Published: March 2023

1AbstractThe generation of antigenic diversity, key for parasite virulence, has been investigated in the genusPlasmodium, mainly inPlasmodium falciparum. Cytogenetic and molecular studies have revealed that its subtelomeres are rich in antigenic gene families and undergo ectopic recombination. As a result, these families are highly variable and even species-specific. More recent analyses focused on the phylogenetic mapping ofP. falciparumchromosomes with the bioinformatic tool PhyloChromoMap, showed that ectopic recombination of subtelomeres extends to all chromosomes. Although antigenic gene families have been described in subtelomeres of otherPlasmodiumspecies, the intensity of this mechanism in these species is still unclear. In this study, we investigated to what extent ectopic recombination of subtelomeres drives the generation of antigenic diversity in 19Plasmodiumspecies. To achieve this, we analyzed the profile of gene conservation in maps of all their chromosomes with PhyloChromoMap. Our results suggest that ectopic recombination of subtelomeres is more critical for the diversification ofpirorrif/stevorgenes than other antigenic gene families. Furthermore, its intensity varies among subgenera and was likely acquired and lost multiple times in the phylogeny ofPlasmodium.
The influence of Sex on microRNA expression in Human Skeletal Muscle
Authors: Hiam Danielle , Landen Shanie , Jacques Macsue , Voisin Sarah , Lamon Séverine , Eynon Nir 
Published: March 2023

AbstractIntroductionSex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the top tissues that underpin sex-based differences, yet there is limited research into whether there are sex differences in miRNA expression in skeletal muscle. Further, there is limited literature investigating potential differences between males and females in skeletal muscle miRNA expression following exercise, a well-known modulator of miRNA expression. Therefore, the aim of this study was to investigate the effect of sex on miRNA expression in skeletal muscle at baseline and after an acute bout of exercise.MethodsMiRNAs were measured using Taqman®miRNA arrays in skeletal muscle of 42 healthy participants from the GeneSMART study (24 males and 20 females aged 18-45 yrs). Differentially expressed miRNAs were identified using mixed linear models adjusted for age. Experimentally validated miRNA gene targets enriched in skeletal muscle were identified in-silico. Over representation analysis was conducted to identify enriched pathways. TransmiR V.2 was used to identify transcription factor (TF)-miR regulatory networks using CHIP-derived data. We further profiled the effects of two sex-biased miRNAs overexpressed in human primary muscle cells lines derived from male and female donors to understand the transcriptome targeted by these miRNAs and investigate and potential sex-specific effects.ResultsA total of 80 miRNAs were differentially expressed in skeletal muscle between the sexes, with 61 miRNAs responding differently to the exercise between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of the muscle cells and numerous metabolic pathways, suggesting that miRNAs are playing a role in programming sex differences in skeletal muscle. Over-expression of sex-biased miRNAs miRNA-30a and miRNA-30c resulted in profound changes to gene expression profiles that were partly specific to the sex of the cell donor in human primary skeletal muscle cells.ConclusionWe found sex-differences in the expression profile of skeletal muscle miRNAs at baseline and in response to exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism, suggesting that miRNAs play a profound but highly complex role in programming sex-differences in the skeletal muscle phenotype.
Identification of efflux substrates using a riboswitch-based reporter inPseudomonas aeruginosa
Authors: Urdaneta-Páez Verónica , Hamchand Randy , Anthony Karen , Crawford Jason , Sutherland Alan G. , Kazmierczak Barbara I. 
Published: March 2023

AbstractPseudomonas aeruginosais intrinsically resistant to many classes of antibiotics, reflecting the restrictive nature of its outer membrane and the action of its numerous efflux systems. However, the dynamics of compound uptake, retention and efflux in this bacterium remain incompletely understood. Here, we exploited the sensor capabilities of a Z-nucleotide sensing riboswitch to create an experimental system able to identify physicochemical and structural properties of compounds that permeate the bacterial cell, avoid efflux, and perturb the folate cycle orde novopurine synthesis. In a first step, a collection of structurally diverse compounds enriched in antifolate drugs was screened for ZTP riboswitch reporter activity in efflux-deficientP. aeruginosa, allowing us to identify compounds that entered the cell and disrupted the folate pathway. These initial hits were then rescreened using isogenic efflux-proficient bacteria, allowing us to separate efflux substrates from efflux avoiders. We confirmed this categorization by measuring intracellular levels of select compounds in the efflux-deficient and - proficient strain using high resolution LC-MS. This simple yet powerful method, optimized for high throughput screening, enables the discovery of numerous permeable compounds that avoid efflux and paves the way for further refinement of the physicochemical and structural rules governing efflux in this multi-drug resistant Gram-negative pathogen.ImportanceTreatment ofPseudomonas aeruginosainfections has become increasingly challenging. The development of novel antibiotics against this multi-drug resistant bacterium is a priority, but many drug candidates never achieve effective concentrations in the bacterial cell due due to its highly restrictive outer membrane and the action of multiple efflux pumps. Here, we develop a robust and simple reporter system inP. aeruginosato screen chemical libraries and identify compounds that either enter the cell and remain inside, or enter the cell and are exported by efflux systems. This approach enables developing rules of compound uptake and retention inP. aeruginosathat will lead to more rational design of novel antibiotics.
Whole Genome Sequencing based Identification of Human Tuberculosis caused by Animal-lineageMycobacterium orygis
Authors: Islam Md Rashedul , Sharma Meenu K. , KhunKhun Rupinder , Shandro Cary , Sekirov Inna , Tyrrell Gregory J. , Soualhine Hafid 
Published: March 2023

ABSTRACTA recently described member of theMycobacterium tuberculosiscomplex (MTBC) isMycobacterium orygis,which can cause disease primarily in animals but also in humans. AlthoughM. orygishas been reported from different geographic regions around the world, due to a lack of proper identification techniques, the contribution of this emerging pathogen to the global burden of zoonotic tuberculosis is not fully understood. In the present work, we report single nucleotide polymorphisms (SNPs) analysis using whole genome sequencing (WGS) that can accurately identifyM. orygisand differentiate it from other members of MTBC species. WGS-based SNPs analysis was performed for 61 isolates from different Provinces in Canada that were identified asM. orygis. A total of 56M. orygissequences from the public databases were also included in the analysis. Several unique SNPs ingyrB, PPE55, Rv2042c, leuS, mmpL6,andmmpS6genes were used to determine their effectiveness as genetic markers for the identification ofM. orygis. To the best of our knowledge, five of these SNPs,viz., gyrB277(A→G),gyrB1478(T→C),leuS1064(A→T),mmpL6486(T→C), andmmpS6334(C→G) are reported for the first time in this study. Our results also revealed several SNPs specific to other species within MTBC. The phylogenetic analysis shows that studied genomes were genetically diverse and clustered withM. orygissequences of human and animal origin reported from different geographic locations. Therefore, the present study provides a new insight into the high confidence identification ofM. orygisfrom MTBC species based on WGS data, which can be useful for reference and diagnostic laboratories.
Self-dyeing textiles grown from cellulose-producing bacteria with engineered tyrosinase expression
Authors: Walker Kenneth T. , Keane Jennifer , Goosens Vivianne J. , Song Wenzhe , Lee Koon-Yang , Ellis Tom 
Published: March 2023

AbstractEnvironmental concerns are driving interests in post-petroleum synthetic textiles produced from microbial and fungal sources. Bacterial cellulose is a promising sustainable leather alternative, on account of its material properties, low infrastructure needs and biodegradability. However, for alternative textiles like bacterial cellulose to be fully sustainable, alternative ways to dye textiles need to be developed alongside alternative production methods. To address this, we here use genetic engineering ofKomagataeibacter rhaeticusto create a bacterial strain that grows self-dyeing bacterial cellulose. Dark black pigmentation robust to material use is achieved through melanin biosynthesis in the bacteria from recombinant tyrosinase expression. Melanated bacterial cellulose production can be scaled up for the construction of prototype fashion products, and we illustrate the potential of combining engineered self-dyeing with tools from synthetic biology, via the optogenetic patterning of gene expression in cellulose-producing bacteria. With this work, we demonstrate that combining genetic engineering with current and future methods of textile biofabrication has the potential to create a new class of textiles.
LDHA maintains the growth and migration of vascular smooth muscle cells and promotes neointima formation via crosstalk between K5 crotonylation and K76 mono-ubiquitination
Authors: Chen Zhi-Huan , Cao Shan-Hu , Ren Zhi-Yan , Jiang Han-Mei , Hu Zhao-Kun , Dong Li-Hua 
Published: March 2023

AbstractPhenotypic plasticity of vascular smooth muscle cells (VSMCs) under stress is believed to be a key factor in neointima formation. Lactate dehydrogenase A (LDHA), a key enzyme for glycolysis, has been demonstrated to promote the proliferation and migration of VSMCs. However, the mechanism by which LDHA regulates this process is still unclear. Here we show that the crotonylation and mono-ubiquitination of LDHA are increased in platelet-derived growth factor (PDGF)-BB-induced proliferative VSMCs. Crotonylation at lysine 5 (K5) activates LDHA through tetramer formation to enhance lactate production and VSMCs growth. Mono-ubiquitination at K76 induces the translocation of LDHA into mitochondria, which promotes mitochondria fission and subsequent the formation of lamellipodia and podosomes, thereby enhancing VSMC migration and growth. Furthermore, the increase of crotonylation and ubiquitination were also observed in the carotid arteries of ligation injury mice. Deletion of LDHA K5 crotonylation or K76 mono-ubiquitination decreases ligation-induced neointima formation. Our study reveals a novel mechanism that combines VSMC metabolic reprogramming and behavioral abnormity through crosstalk between LDHA K5 crotonylation and K76 mono-ubiquitination.
A novel method for sampling subgingival microbiome - a comparative metatranscriptomic study
Authors: Demusaj Diana , Toma Ryan , Khan Tanveer , Hu Lan , Banavar Guruduth , Vuyisich Momchilo 
Published: March 2023

AbstractThe subgingival microbiome has been implicated in several oral and systemic diseases, such as periodontitis, arthritis, and Alzheimer’s disease. However, subgingival sampling is challenging and cannot be readily performed outside of primary care facilities. In order to support global, diverse, direct-to-participant clinical research studies, we developed a novel method of sampling the subgingival microbiome by rotationally swabbing the supragingival area, which we named subgingival-P (for proxy) samples. To validate this method, we sampled and metatranscriptomically analyzed subgingival and subgingival-P samples of three different teeth in 20 individuals. The subgingival-P samples were comparable to the subgingival samples in the relative abundances of microorganisms and microbial gene expression levels. Our data demonstrate that the novel method of collecting and analyzing the subgingival-P samples can act as a proxy for the subgingiva, paving the way for large and diverse studies investigating the role of the subgingival microbiome in health and disease.