bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential representation of active and passive touch in mouse somatosensory thalamus
Authors: Sumser Anton , Isaías-Camacho Emilio Ulises , Mease Rebecca Audrey , Groh Alexander 
Published: July 2024

AbstractActive and passive sensing strategies are integral to an animal’s behavioral repertoire. Nevertheless, there is a lack of information regarding the neuronal circuitry that underpins these strategies, particularly at the thalamus level. We evaluated how active versus passive whisker deflections are represented in single neurons of the ventral posterior thalamus (VPM) and the posterior medial thalamus (POm) in awake mice. These are the first-and higher-order thalamic nuclei of the whisker system, respectively. VPM neurons robustly responded to both active and passive whisker deflections, while POm neurons showed a preference for passive deflections and responded poorly to active touches. This response disparity could not be explained by the animal’s voluntary whisking state or stimulus kinetics. In contrast, cortical activity significantly influenced POm’s responses to passive touch. Inhibition of the barrel cortex strongly attenuated whisker responses in POm and simultaneously increased the whisking phase coding. This suggests that POm receives touch information from the cortex and phase information from the brainstem. Together, these findings suggest two thalamic relay streams, where VPM robustly relays both active and passive deflection, while POm’s sensitivity requires top-down cortical involvement to signal salient events such as unexpected passive deflections.
Mechanism of auxin-dependent gene regulation through composite auxin response elements
Authors: Novikova Daria D. , Omelyanchuk Nadya , Korosteleva Anastasiia , Albrecht Catherine , Lavrekha Viktoriya V. , Weijers Dolf , Mironova Victoria 
Published: July 2024

AbstractThe plant signaling molecule auxin controls growth and development, largely through activating and repressing the expression of thousands of genes. Auxin-dependent transcriptional changes are mediated by DNA-binding Auxin Response Factors (ARF), whose AuxRE DNA binding sites are well-known. The identification of the first AuxRE showed this to be part of a composite element with a second motif. Indeed, systematic analysis showed other DNA motifs to be enriched in auxin-regulated promoters. Neither the basis for this enrichment nor the mechanisms for the activity of composite AuxRE’s is known. Here, we systematically mined Arabidopsis promoters for composite AuxRE elements enriched in auxin-responsive genes. We identified many and show that their presence is a reliable predictor of auxin response. Through mutating these elements and their higher-order modules, we demonstrate function in promoter activity. Lastly, we identified transcription factors (TFs) that bind AuxRE-associated motifs, showed their involvement in auxin response, and discovered that several of these TFs directly bind ARF proteins. We propose that ARF-TF complexes specifically bind compound motifs in promoters, and act as a source of diversification in auxin-dependent gene regulation.
ADToolbox: Incorporating Metagenomics Data for Improved Prediction of Anaerobic Digestion Dynamics
Authors: Ghadermazi Parsa , Rico Jorge L. , Rimmelman Ethan , Stenmark Siri , Reardon Kenneth F. , De Long Susan , Chan Siu Hung Joshua 
Published: July 2024

AbstractHandling the global food waste requires sustainable solutions. Anaerobic digestion (AD) is a common approach for waste remediation and bioenergy production which has been traditionally used mainly for methane production. Shifting the focus from methane to volatile fatty acids (VFAs), such as acetic, propionic, and butyric acids, offers promising alternatives due to their diverse applications and higher added value. Achieving desired AD product distributions requires a comprehensive understanding of factors like temperature, pH, feedstock composition, and the complex microbial dynamics inherent in AD. Various AD modeling approaches exist, from simple equations to complex flux balance analysis (FBA) and machine learning (ML) model. The Anaerobic Digestion Model No. 1 (ADM 1) is a commonly used kinetic model, striking a reasonable balance between parameter requirements and biochemical details involved in the model. Yet, it falls short in capturing specific VFAs like caproic acid and integrating microbial information directly. We present ADToolbox, a Python package for modeling AD metabolism. ADToolbox incorporates metagenomic information into an enhanced ADM model. The model accommodates a more detailed feedstock degradation model and VFA and methanogenesis metabolism. ADToolbox provides a variety of interfaces such as command line interface and an interactive web interface line interface, and a Python API, facilitating large-scale metagenomic analyses and modeling simulations. In this article we indicate that prioritizing the microbial aspect of AD enhances flexibility and predictive power in terms of VFA production accuracy, contributing to sustainable waste management strategies. Explore ADToolbox athttps://chan-csu.github.io/ADToolboxfor detailed documentation.
Cellulose synthesis in Arabidopsis by heterologous expression of lower plants CESA proteins
Authors: Kumar Manoj , Gomez Leonardo D. , Turner Simon 
Published: July 2024

AbstractCellulose is the most abundant component of plant cell walls where it plays a pivotal role in regulating plant cell size and shape. In addition, as a component of the woody secondary cell walls, cellulose represents an abundant renewable resource to produce materials and chemicals. In higher plants, cellulose is synthesised at the plasma membrane by a hexameric protein complex, known as the rosette, that is able to synthesise 18 glucose chains that bond together to form a microfibril. While this rosette structure is highly conserved, significant variation exists in the structure and physical properties of cellulose found in different cell types and synthesised by different species. In this study, we surveyed the ability of the catalytic subunits of the cellulose synthase complex (CESA proteins) from a range of lower plant species to synthesise cellulose in the Arabidopsis secondary cell walls. Several lower plant CESA proteins are able to function in higher plants in conjunction Arabidopsis CESAs. Additionally, two moss CESA proteins synthesised cellulose in absence of Arabidopsis CESAs but with reduced crystallinity, indicating that it is the structure of CESA proteins themselves and not the cellular environment that determines the properties of the cellulose synthesised.
Engineered NKG2C+NK-like T cells exhibit superior antitumor efficacy while mitigating cytokine release syndrome
Authors: Lupo Kyle B. , Panjwani M. Kazim , Shahid Sanam , Sottile Rosa , Lawry Clara , Kolk Gabryelle , Kontopolous Theodota , Daniyan Anthony F. , Chandran Smita S. , Klebanoff Christopher A. , Hsu Katharine C. 
Published: July 2024

AbstractEngineered T and NK cell therapies have widely been used to treat hematologic malignancies and solid tumors, with promising clinical results. Current chimeric antigen receptor (CAR) T cell therapeutics have, however, been associated with treatment-related adverse events such as cytokine release syndrome (CRS) and are prone to immunologic exhaustion. CAR-NK therapeutics, while not associated with CRS, have limited in vivo persistence. We now demonstrate that an NK-like TCRαβ+CD8 T cell subset, identified and expanded ex vivo through its expression of the activating receptor NKG2C (NKG2C+NK-like T cells), can be transduced to express a second-generation CD19 CAR (1928z), resulting in superior tumor clearance, longer persistence and decreased exhaustion compared to conventional 1928z CAR+CD8 T cells and 1928z CAR+ NK cells. Moreover, CAR-modified NKG2C+NK-like T cells resulted in significantly reduced CRS compared to conventional CAR+CD8 T cells. Similarly, NKG2C+NK-like T cells engineered with a TCR targeting the NY-ESO-1 antigen exhibit robust tumor control and minimal exhaustion compared to TCR-engineered conventional CD8 T cells. These data establish NKG2C+NK-like T cells as a robust platform for cell engineering, and offer a safer, more durable alternative to conventional CAR-T and CAR-NK therapies.
The role of YAP/TAZ signaling in dendritic cell-mediated pathogenesis of insulin resistance and non-alcoholic fatty liver disease
Authors: Schcolnik-Cabrera Alejandro , Lee Megan , Dzierlega Kasia , Basso Paulo , Strachan Erin , Zhu Mengyi , Akbari Masoud , Clemente-Casares Xavier , Tsai Sue 
Published: July 2024

AbstractObesity and insulin resistance (IR) are global health challenges linked to metabolic diseases, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). High-caloric intake, which is associated to NAFLD, induces adipocyte hypertrophy and inflammation, triggering dendritic cell (DC) activation and systemic inflammation. DC exacerbate inflammation by promoting pro-inflammatory responses, aggravating IR and NAFLD progression. NAFLD is characterized by liver fibrosis, which alters tissue stiffness that can trigger mechanosensing pathways such as the Hippo pathway in immune cell types. In this work we explored the roles of key mediators of the Hippo pathway, YAP and TAZ, in DCs within the context of liver fibrosis, obesity and IR, using a model of NAFLD induced by feeding a high fat high sucrose diet. Our findings indicate that specific deletion of YAP and/or TAZ in DCs had minimal impact on IR development and metabolic tissue inflammation. We conclude that YAP and TAZ have limited and possibly redundant roles in the immune pathophysiology of NAFLD and IR.
Identification of BLM’s Aggregation-Prone Nature and Its Similarity to Intrinsically Disordered Proteins: An In-silico Study
Authors: Sharma Sourav , Yadav Suresh Singh , Nair Rohini Ravindran 
Published: July 2024

AbstractBLM helicase is a member of the RecQ family of DNA helicases, enzymes that play a critical role in maintaining genome stability. The BLM protein is named after Bloom syndrome (BS), a rare genetic disorder caused by mutations in the helicase domain of BLM gene. BLM role has mostly been studied in DNA repair, replication, and recombination; however, a recent study has highlighted the RNA binding capability of the BLM protein. Several proteins, including TDP43, Tau, and alpha-synuclein, are known to play key roles in neurodegenerative diseases. These proteins possess residues prone to parallel aggregation and fibril formation, the key contributor to neurodegenerative disease development. We utilized various in-silico tools like PASTA 2.0, SIFT, PolyPhen 2, and PhD SNP, SNP&GO, Meta-SNP, and SNAP, etc., to identify the molecular signature of the BLM’s protein. Our in-silico analysis suggests that the BLM’s HRDC domain has ability of parallel aggregation and fibril formation. Moreover, structural similarity with proteins like α-synuclein, TDP-43, and Tau and its interactions with PARP1 suggests it may have a role in neurodegenerative diseases. Furthermore, we identified deleterious mutations in the HRDC domain of BLM protein that may compromise its stability and alter its function. Hence, these findings suggest that in addition to BLM’s well-known functions, the protein may have ability to form parallel aggregation and fibril formation and its role in neurodegenerative disease need to further be explored.Author SummaryThis paper higlights the importance of considering the structural and physical characteristics of the BLM protein, which may have been previously overlooked in the context of disease pathology. Through in-silico analyses, we identified that the BLM protein possesses residues within the HRDC domain that are prone to parallel aggregation and fibril formation. Moreover, the structural similarity of BLM to proteins such as α-synuclein, TDP-43, and Tau indicates a potential role for BLM in neurodegenerative processes. Additionally, we identified deleterious mutations within the HRDC domain that could compromise the stability of the protein. Furthermore, our findings suggest that the association between BLM and PARP1 may involve a regulatory mechanism that could significantly influence BLM’s function.
Classification of Variants of Reduced Penetrance in High Penetrance Cancer Susceptibility Genes: Framework for Genetics Clinicians and Clinical Scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK)
Authors: Garrett Alice , Allen Sophie , Durkie Miranda , Burghel George J , Robinson Rachel , Callaway Alison , Field Joanne , Frugtniet Bethan , Palmer-Smith Sheila , Grant Jonathan , Pagan Judith , McDevitt Trudi , Rowlands Charlie F. , McVeigh Terri , Hanson Helen , Turnbull Clare ,   CanVIG-UK
Published: July 2024

AbstractPurposeCurrent practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene (CSG) as though having equivalent penetrance, despite increasing evidence of inter-variant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants where reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance (VUS). We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.MethodsA series of surveys and live polls were conducted during and between CanVIG-UK monthly meetings on various scenarios potentially indicating reduced penetrance. These informed the iterative development of a framework for the classification of variants of reduced penetrance by the CanVIG-UK Steering and Advisory Group (CStAG) working group.ResultsCanVIG-UK recommendations for amendment of the 2015 ACMG/AMP variant interpretation framework were developed for variants where (i) Active evidence suggests a reduced penetrance effect size (e.g. from case-control or segregation data) (ii) Reduced penetrance effect is inferred from weaker/potentially-inconsistent observed data.ConclusionsCanVIG-UK propose a framework for the classification of variants of reduced penetrance in high-penetrance genes. These principles, whilst developed for CSGs, are potentially applicable to other clinical contexts.
Adoption of artificial intelligence and big data analytics: an organizational readiness perspective of the textile and garment industry in Bangladesh
Authors: Hossain Md Khalid , Srivastava Aashish , Oliver Gillian Christina , Islam Md Ekramul , Jahan Nayma Akther , Karim Ridoan , Kanij Tanjila , Mahdi Tanjheel Hasan 
Published: July 2024

PurposeThe purpose of this paper is to investigate the organizational readiness perspective of adopting artificial intelligence and big data analytics in the textile and garment industry in Bangladesh along with identifying the associated factors.Design/methodology/approachThe research uses a qualitative method using semi-structured interviews with representatives of business organizations and stakeholders of Bangladesh’s textile and garment industry.FindingsThe research reveals that the textile and garment industry in Bangladesh currently has low organizational readiness to adopt artificial intelligence and big data analytics. This is due to moderate knowledge- and leadership-readiness along with low human-, finance- and engagement-readiness of most of the business organizations. The readiness aspects interplay with each other and need to be improved holistically.Practical implicationsConsidering the significant global and national importance of Bangladesh’s textile and garment industry, gaining insights into the industry’s current state of readiness for adopting artificial intelligence and big data analytics would offer valuable assistance to both national and global economies and may enhance economic outcomes.Originality/valueSince no exploratory study was conducted to understand the organizational readiness aspects of adopting artificial intelligence and big data analytics of the globally significant textile and garment industry in Bangladesh, the paper analyzes five key aspects of such readiness and offers a basis for conducting similar studies in other emerging economies.
Cryo‐electron tomography elucidates annular intraluminal configurations in Caenorhabditis elegans microtubules
Authors: Zhu Hao , Li Ming , Li Meijing , Li Xueming , Ou Guangshuo 
Published: July 2024

AbstractBackground informationMicrotubules serve as integral components in cellular operations such as cell division, intracellular trafficking, and cellular architecture. Composed of tubulin protein subunits, these hollow tubular structures have been increasingly elucidated through advanced cryo‐electron microscopy (Cryo‐EM), which has unveiled the presence of microtubule inner proteins (MIPs) within the microtubular lumen.ResultsIn the present investigation, we employ a synergistic approach incorporating high‐pressure freezing, cryo‐focused ion beam milling, and Cryo‐electron tomography (Cryo‐ET) to interrogate the in situ architecture of microtubules in Caenorhabditis elegans larvae. Our Cryo‐ET assessments across neuronal cilia and diverse tissue types consistently demonstrate the formation of annular configurations within the microtubular lumen.ConclusionsIn concert with recently characterized MIPs, our in situ observations within a living organism corroborate the hypothesis that intricate luminal assemblages exist within microtubule scaffolds. These findings necessitate further exploration into the molecular constituents and functional ramifications of these internal microtubular configurations in both cellular physiology and pathophysiology.
The role of gastric mucins and mucin‐related glycans in gastric cancers
Authors: Arai Junya , Hayakawa Yoku , Tateno Hiroaki , Fujiwara Hiroaki , Kasuga Masato , Fujishiro Mitsuhiro 
Published: July 2024

AbstractGastric mucins serve as a protective barrier on the stomach's surface, protecting from external stimuli including gastric acid and gut microbiota. Their composition typically changes in response to the metaplastic sequence triggered by Helicobacter pylori infection. This alteration in gastric mucins is also observed in cases of gastric cancer, although the precise connection between mucin expressions and gastric carcinogenesis remains uncertain. This review first introduces the relationship between mucin expressions and gastric metaplasia or cancer observed in humans and mice. Additionally, we discuss potential pathogenic mechanisms of how aberrant mucins and their glycans affect gastric carcinogenesis. Finally, we summarize challenges to target tumor‐specific glycans by utilizing lectin‐drug conjugates that can bind to specific glycans. Understanding the correlation and mechanism between these mucin expressions and gastric carcinogenesis could pave the way for new strategies in gastric cancer treatment.
The neuroinflammatory role of microglia in Alzheimer's disease and their associated therapeutic targets
Authors: AmeliMojarad Melika , AmeliMojarad Mandana 
Published: July 2024

AbstractIntroductionAlzheimer's disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid‐β (Aβ) accumulation, hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain are considered to be the initiating factors of AD. However, this hypothesis falls short of explaining many aspects of AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role in the pathophysiology of AD and causes neurodegeneration by over‐activating microglia and releasing inflammatory mediators.MethodsPubMed, Web of Science, EMBASE, and MEDLINE were used for searching and summarizing all the recent publications related to inflammation and its association with Alzheimer's disease.ResultsOur review shows how inflammatory dysregulation influences AD pathology as well as the roles of microglia in neuroinflammation, the possible microglia‐associated therapeutic targets, top neuroinflammatory biomarkers, and anti‐inflammatory drugs that combat inflammation.ConclusionIn conclusion, microglial inflammatory reactions are important factors in AD pathogenesis and need to be discussed in more detail for promising therapeutic strategies.
Successful gall induction on wild roses by gall wasps under lab conditions
Authors: László Zoltán , Szilágyi Bálint , Macalik Borbála , Biró Mátyás , Iordache Constantin‐Teodor , Nicula Marco , Podar Dorina 
Published: July 2024

Abstract
Plant galls are unique outgrowths caused by various organisms, including insects, serving as nourishment for the inducer's larvae. Despite the taxonomists and ecologists attempts to elucidate the mechanisms behind plant gall formation, its understanding is still incomplete. Modern genetic techniques allow in‐depth analysis of the molecular processes, but variations across species entangle the analysis. Establishing laboratory‐friendly plant–gall inducer communities is crucial, yet past attempts have faced challenges.
Our study partly aimed to create a laboratory community involving wild roses (Rosa sp.) and rose gall wasps belonging to the genus Diplolepis as gall‐inducing insects. Controlled indoor conditions were optimized for plant growth. Wild roses were transplanted, then exposed to gall inducers, and monitored.
Successfully initialized gall growth was measured and analysed, revealing insights into the impact of plant vigour on gall size as a secondary aim.
Our study successfully established a novel laboratory community for further research on gall formation mechanisms.
Perceptions of undertaking a higher degree alongside dental specialty training: A cross‐sectional survey of UK dental specialty trainees
Authors: Haworth Jennifer A. , Jopson Jenifer L. , Harrison Jayne E. , Cobourne Martyn T. , Cunningham Susan J. , McIntyre Grant T. , Ireland Anthony J. 
Published: July 2024

AbstractIntroductionThe curricula for UK dental specialty training have recently been under review and until 2024, completion of a research component during training in Dental Public Health, Oral Microbiology and Orthodontics has been mandatory (with an alternative route for Orthodontics involving the submission of two scientific papers for those trainees not wishing to undertake a higher degree). Anecdotally, some trainees in other dental specialties choose to undertake higher degrees alongside specialty training.AimsThe aims were to investigate how many dental specialty registrars study for higher degrees alongside specialty training, and whether undertaking a higher degree alongside specialty training has an impact on completion of training, research skills, research experience, patient care and career opportunities.Materials and MethodsThis was a cross‐sectional study design, involving the distribution of an online, anonymous questionnaire‐based survey to UK dental specialty registrars in November and December 2022.ResultsIn total, 38 questionnaires were completed, representing a 7.7% response rate of the entire dental specialty registrar cohort in the UK and 42% of those who received it. Most respondents (76.3%) were either studying or had completed a clinically relevant higher degree prior to specialty training. Most respondents (76.3%) reported that the higher degree increased career opportunities and gave them additional skills.ConclusionsDental specialty trainees who responded to this survey perceived the higher degree to be beneficial in terms of preparing for exams, gaining skills in critical appraisal and for increasing future career opportunities.