bluuebunny/crossref_metadata_2025_split huggingface dataset:
Existence of solutions for stress-rate type strain-limiting viscoelasticity in Gevrey spaces
Authors: Bachmann L. , De Anna F. , Schlömerkemper A. , Şengül Y. 
Published: November 2023

In this work, we deal with a one-dimensional stress-rate type model for the response of viscoelastic materials, in relation to the strain-limiting theory. The model is based on a constitutive relation of stress-rate type. Unlike classical models in elasticity, the unknown of the model under consideration is uniquely the stress, avoiding the use of the deformation. Here, we treat the case of periodic boundary conditions for a linearized model. We determine an optimal function space that ensures the local existence of solutions to the linearized model around certain steady states. This optimal space is known as the Gevrey-class3/2, which characterizes the regularity properties of the solutions. The exponent3/2in the Gevrey-class reflects the specific dispersion properties of the equation itself.This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’.
A certain counterpart in dissipative setting of the Noether theorem with no dissipation pseudo-potentials
Authors: Mariano Paolo Maria 
Published: November 2023

We look at a mechanical dissipation inequality differing from the standard one by what we call a relative power, a notion that is appropriate in the presence of material mutations. We prove that a requirement of structural invariance for such an inequality under the action of diffeomorphism-based changes of observers (covariance) implies (i) the representation of contact actions in terms of the first Piola–Kirchhoff stress, (ii) local balances of standard and configurational actions, (iii)
a priori
constitutive restrictions in terms of free energy, and (iv) a representation of viscous-type stress components.

This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’.
Augmentation of growth media for extreme iron-limitation in Escherichia coli
Authors: Southwell James W , Wilson Keith S , Thomas Gavin H , Duhme-Klair Anne-Kathrin 
Published: November 2023

Iron is an essential nutrient for microbial growth and bacteria have evolved numerous routes to solubilise and scavenge this biometal, which is often present at very low concentrations in host tissue. We recently used a MOPS-based medium to induce iron limitation in Escherichia coli K-12 during the characterisation of novel siderophore conjugated antibiotics. In this study we confirm that growth media derived from commercially-available M9 salts are unsuitable for studies of iron-limited growth, likely through the contamination of the sodium phosphate buffer components with over 100 µM iron. In contrast, MOPS-based media that are treated with metal-binding Chelex® resin, allow the free iron concentration to be reduced to growth-limiting levels. Despite these measures a small amount of E. coli growth is still observed in these iron-depleted media. By growing E. coli in conditions that theoretically increase the demand for iron-dependent enzymes, namely by replacing the glucose carbon source for acetate and by switching to a microaerobic atmosphere, we can reduce background growth even further. Finally, we demonstrate that by adding an exogeneous siderophore to the growth media which is poorly used by E. coli, we can completely prevent growth, perhaps mimicking situation in host tissue. In conclusion, this short study provides practical experimental insight into low iron media and how to augment the growth conditions of E. coli for extreme iron-limited growth.
Nuclear localization of HD-Zip IV transcription factor GLABRA2 is driven by Importin α
Authors: Ahmad Bilal , Lerma-Reyes Ruben , Mukherjee Thiya , Nguyen Hieu V. , Weber Audra L. , Schulze Waltraud X. , Comer Jeffrey R. , Schrick Kathrin 
Published: November 2023

ABSTRACTGLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor (TF) fromArabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a putative monopartite nuclear localization sequence (NLS) partially overlapping with its homeodomain (HD). We demonstrate that NLS deletion or alanine substitution of its basic residues (KRKRKK) affects nuclear localization and results in a loss-of-function phenotype. Fusion of the predicted NLS (GTNKRKRKKYHRH) to the fluorescent protein EYFP is sufficient for its nuclear localization in roots and trichomes. The functional NLS is evolutionarily conserved in a distinct subset of HD-Zip IV members including PROTODERMAL FACTOR2 (PDF2). Despite partial overlap of the NLS with the HD, genetic dissection of the NLS from PDF2 indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plant tissues followed by mass spectrometry-based proteomics identified Importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Split-ubiquitin cytosolic yeast two-hybrid assays suggest interaction between GL2 and four IMPα isoforms fromArabidopsis.Direct interactions were verified in vitro by co-immunoprecipitation with recombinant proteins. IMPα triple mutants (impα- 1,2,3) exhibit defects in EYFP:GL2 nuclear localization in trichomes but not in roots, consistent with tissue-specific and redundant functions of IMPα isoforms inArabidopsis. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 and other HD-Zip IV TFs in plants.One sentence summaryGLABRA2, a representative HD-Zip IV transcription factor fromArabidopsis, contains an evolutionarily conserved monopartite nuclear localization sequence that is recognized by Importin α for translocation to the nucleus, a process that is necessary for cell-type differentiation of the epidermis.
Increasing equity in science requires better ethics training: a course by trainees, for trainees
Authors: Patel Roshni A. , Ungar Rachel A. , Pyke Alanna L. , Adimoelja Alvina , Chakraborty Meenakshi , Cotter Daniel J. , Freund Malika , Goddard Pagé , Gomez-Stafford Justin , Greenwald Emily , Higgs Emily , Hunter Naiomi , MacKenzie Tim M. G. , Narain Anjali , Martschenko Daphne O. 
Published: November 2023

SummaryDespite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we – a group of predominantly human genetics trainees – developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines. Our curriculum positions human genetics within its historical and societal context and encourages students to evaluate how societal norms and structures impact the conduct of scientific research. We demonstrate the utility of this course via surveys of enrolled students and provide resources and strategies for others hoping to teach a similar course. We conclude by arguing that if we are to work towards rectifying the inequities and injustices produced by our field, we must first learn to view our own research as impacting and being impacted by society.
Whole Genome Sequencing and Assembly of the House Sparrow,Passer domesticus
Authors: Kumar Vikas , Sharma Gopesh , Sharma Sankalp , Prasad Samvrutha , Vaishnoi Toral , Vishnudasan Dalia , Maheswaran Gopinathan , Tyagi Kaomud , Tyagi Inderjeet , Desai Shailesh , PB Kavi Kishor , Chaubey Gyaneshwer , Suravajhala Prashanth 
Published: November 2023

AbstractThe common house sparrow,Passerdomesticus is a small bird belonging to the family Passeridae. Here, we provide high-quality whole genome sequence data along with assembly for the house sparrow. The final genome assembly was made using Shovill/SPAdes/MASURCA/BUSCO which consisted of contigs spanning 268193 bases coalescing 922 MB. We employed rigorous statistical thresholds to check the coverage as the Passer genome showed considerable similarity toGallus gallus(chicken) andTaeniopygia guttata(Zebra finch) genomes providing a functional annotation. This new annotated genome assembly will be a valuable resource as a reference for comparative and population genomic analyses of passerine, avian, and vertebrate evolution.SignificanceAvian evolution has been of great interest in the context of extinction. Annotating the genomes such as passerines would be of significant interest as we could understand the behavior/foraging traits and further explore their evolutionary landscape. In this work, we provide a full genome sequence of Indian house sparrow,viz. Passer domesticuswhich will serve as a useful resource in understanding the adaptability, evolution, geography, allee effects and circadian rhythms.
An Alzheimer’s disease-associated common regulatory variant in a PTK2B intron alters microglial function
Authors: Bello Erica , Long Kathleen , Iwama Sho , Steer Juliette , Cooper Sarah , Alasoo Kaur , Kumasaka Natsuhiko , Schwartzentruber Jeremy , Panousis Nikolaos I , Bassett Andrew 
Published: November 2023

SummaryGenome-wide association studies (GWAS) are revealing an ever-growing number of genetic associations with disease, but identifying and functionally validating the causal variants underlying these associations is very challenging and has only been done for a vanishingly small number of variants. Here we validate a single nucleotide polymorphism (SNP) associated with an increased risk of Alzheimer’s disease (AD) in an intronic enhancer of thePTK2Bgene, by engineering it into human induced pluripotent stem cells (hiPSCs). Upon differentiation to macrophages and microglia, this variant shows effects on chromatin accessibility of the enhancer and increased binding of the transcription factor CEBPB but only subtle effects on PTK2B or CLU expression. Nevertheless, this variant also results in global changes to the transcriptome and phenotype of these cells. Expression of interferon gamma responsive genes including chemokine transcripts and their protein products are altered, and chemotaxis of the resulting microglial cells is affected. This variant thus causes disease-relevant transcriptomic and phenotypic changes, and we propose that it acts by altering microglia reactivity, consistent with the role of these cells in progression of AD.
Anesthetic oxygen use and sex are critical factors in the FLASH sparing effect
Authors: Tavakkoli Armin D. , Clark Megan A. , Kheirollah Alireza , Sloop Austin M. , Soderholm Haille E. , Daniel Noah J. , Petusseau Arthur F. , Huang Yina H. , Thomas Charles R. , Jarvis Lesley A. , Zhang Rongxiao , Pogue Brian W. , Gladstone David J. , Hoopes P. Jack 
Published: November 2023

AbstractIntroductionUltra-high dose-rate (UHDR) radiation has been reported to spare normal tissue compared to conventional dose-rate (CDR) radiation. However, reproducibility of the FLASH effect remains challenging due to varying dose ranges, radiation beam structure, and in-vivo endpoints. A better understanding of these inconsistencies may shed light on the mechanism of FLASH sparing. Here, we evaluate whether sex and/or use of 100% oxygen as carrier gas during irradiation contribute to the variability of the FLASH effect.MethodsC57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm2diameter area of the right leg skin using the Mobetron linear accelerator. The primary post-radiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female) skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions.ResultsIn the UHDR group, time to ulceration was significantly shorter in mice that received 100% oxygen compared to room air, and amongst them female mice ulcerated sooner compared to males. However, no significant difference was observed between male and female UHDR mice that received room air. Oxygen measurements showed significantly higher tissue oxygenation using 100% oxygen as the anesthesia carrier gas compared to room air, and female mice showed higher levels of tissue oxygenation compared to males under 100% oxygen.ConclusionThe FLASH sparing effect is significantly reduced using oxygen during anesthesia compared to room air. The FLASH sparing was significantly lower in female mice compared to males. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect.
PEFT-SP: Parameter-Efficient Fine-Tuning on Large Protein Language Models Improves Signal Peptide Prediction
Authors: Zeng Shuai , Wang Duolin , Xu Dong 
Published: November 2023

AbstractSignal peptides (SP) play a crucial role in protein translocation in cells. The development of large protein language models (PLMs) provides a new opportunity for SP prediction, especially for the categories with limited annotated data. We present a Parameter-Efficient Fine-Tuning (PEFT) framework for SP prediction, PEFT-SP, to effectively utilize pre-trained PLMs. We implanted low-rank adaptation (LoRA) into ESM-2 models to better leverage the protein sequence evolutionary knowledge of PLMs. Experiments show that PEFT-SP using LoRA enhances state-of-the-art results, leading to a maximum MCC2 gain of 0.372 for SPs with small training samples and an overall MCC2 gain of 0.048. Furthermore, we also employed two other PEFT methods, i.e., Prompt Tunning and Adapter Tuning, into ESM-2 for SP prediction. More elaborate experiments show that PEFT-SP using Adapter Tuning can also improve the state-of-the-art results with up to 0.202 MCC2 gain for SPs with small training samples and an overall MCC2 gain of 0.030. LoRA requires fewer computing resources and less memory compared to Adapter, making it possible to adapt larger and more powerful protein models for SP prediction.
Chronic thromboembolic pulmonary hypertension in UAE: the first reported seven year outcomes from a tertiary center in UAE
Authors: Saleh Khaled , Mallat Jihad , Dougherty Kelly , Ghanem Mohannad , Ghorab Ahmed , Alsaadi Reem , Agrawal Manyoo , Salim Simi , Abdalla Sara , Khan Naureen , Sabbour Hani 
Published: November 2023

AbstractBackgroundThe aim of the study was to present the first United Arab Emirates (UAE) Chronic Thromboembolic Pulmonary Hypertension registry of patients’ clinical characteristics, hemodynamic parameters, and treatment outcomes.MethodsThis was a retrospective study describing all adult patients who were diagnosed with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) between January 2015 and April 2022 in a tertiary referral center in Abu Dhabi, United Arab Emirates (UAE).Ethics StatementIRB and Research Ethics Committee approval was obtained under REC number A-2017-030. Researchers had access to the anonymized electronic medical records with fully anonymized data for analysis of retrospective data collected from July 2015 till April 2022. IRB and REC waived the requirement for informed consent.ResultsA total of 39 consecutive patients were diagnosed with CTEPH during the seven years of the study. Two patients who had pulmonary artery balloon angioplasty (BPA) were not included in the analysis. Twelve out of the 37 patients (56%) had pulmonary thrombo-endarterectomy (PTE) and were designated as the surgical group, the rest were designated the medical group. The patients were followed for a median of 11 months [IQR: 6-22.5]. Most of the patients in the medical group were started on dual then subsequently escalated to triple combination therapy. Most of the patients in the surgical group stopped the vasodilator therapy. The 1-, 3- and 5-year medical group survival rates were 80%, 68% and 68%, respectively. None of the patients in the surgical group died.ConclusionThis is the first registry of CTEPH patients from a single tertiary referral center in UAE. Our cohort was younger than ones reported in the Western World but similar to the one reported in Saudi Arabia. The medical group mortality is comparable to other major registries. The recent introduction of PTE program in our center is likely to increase number of surgical patients.
Role of Walking Energetics and Perceived Fatigability on Mobility Differ by Walking Speed: The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Moffit Reagan E. , Blackwell Terri , Forman Daniel E. , Coen Paul M. , Nicklas Barbara J. , Qiao Yujia (Susanna) , Cawthon Peggy M. , Toledo Frederic G. S. , Goodpaster Bret H. , Cummings Steven R. , Newman Anne B. , Glynn Nancy W. 
Published: November 2023

AbstractBackgroundSlow gait speed is a risk factor for poor health outcomes among older adults and may be driven by decreased energy availability and increased fatigability.ObjectiveExamine walking energetics and perceived physical fatigability with gait speed among slower and faster walkers and understand whether fatigability statistically mediates the association between energetics and gait speed.MethodsPerceived physical fatigability was assessed using the Pittsburgh Fatigability Scale (PFS) Physical score (range 0-50, higher=greater). A three-phase cardiopulmonary exercise treadmill test collected peak oxygen consumption (VO2peak mL/kg/min), energetic cost of walking per distance travelled (ECW, mL/kg/meter), and cost-capacity ratios (VO2/VO2peak, %). Gait speed was determined by 4m walk; slower (<1.01m/s) vs faster (≥1.01m/s) walkers were classified using median 4m gait speed. Linear regressions and statistical mediation analyses were conducted.ResultsSlower walkers had lower VO2peak, higher ECWat preferred walking speed (PWS), and greater PFS Physical score compared to faster walkers (all p<0.05) (N=849). One standard-deviation higher increment of VO2peak, ECWat PWS, cost-capacity ratios at PWS and slow walking speed (SWS), and PFS Physical score were associated with 0.1m/s faster (VO2peak only) or 0.02-0.09m/s slower gait speed. PFS Physical score was a significant statistical mediator in the associations between VO2peak (15.2%), cost-capacity ratio (15.9%), and ECWat PWS (10.7%) with gait speed, and stronger among slower walkers.ConclusionsFitness and fatigability are associated with slower gait speed yet contributions may differ among slower and faster walkers. Future interventions may consider targeting fatigability among slower walkers and fitness among faster walkers.
Large language models implicitly learn to straighten neural sentence trajectories to construct a predictive representation of natural language
Authors: Hosseini Eghbal A. , Fedorenko Evelina 
Published: November 2023

AbstractPredicting upcoming events is critical to our ability to effectively interact with our environment and conspecifics. In natural language processing, transformer models, which are trained on next-word prediction, appear to construct a general-purpose representation of language that can support diverse downstream tasks. However, we still lack an understanding of how a predictive objective shapes such representations. Inspired by recent work in vision neuroscience Hénaff et al. (2019), here we test a hypothesis about predictive representations of autoregressive transformer models. In particular, we test whether the neural trajectory of a sequence of words in a sentence becomes progressively more straight as it passes through the layers of the network. The key insight behind this hypothesis is that straighter trajectories should facilitate prediction via linear extrapolation. We quantify straightness using a 1-dimensional curvature metric, and present four findings in support of the trajectory straightening hypothesis: i) In trained models, the curvature progressively decreases from the first to the middle layers of the network. ii) Models that perform better on the next-word prediction objective, including larger models and models trained on larger datasets, exhibit greater decreases in curvature, suggesting that this improved ability to straighten sentence neural trajectories may be the underlying driver of better language modeling performance. iii) Given the same linguistic context, the sequences that are generated by the model have lower curvature than the ground truth (the actual continuations observed in a language corpus), suggesting that the model favors straighter trajectories for making predictions. iv) A consistent relationship holds between the average curvature and the average surprisal of sentences in the middle layers of models, such that sentences with straighter neural trajectories also have lower surprisal. Importantly, untrained models don’t exhibit these behaviors. In tandem, these results support the trajectory straightening hypothesis and provide a possible mechanism for how the geometry of the internal representations of autoregressive models supports next word prediction.
Evolutionary origin and structural ligand mimicry by the inserted domain of alpha-integrin proteins
Authors: Hollis Jeremy A. , Chan Matthew C. , Malik Harmit S. , Campbell Melody G. 
Published: November 2023

AbstractHeterodimeric integrin proteins transmit signals through conformational changes upon ligand binding between their alpha (α) and beta (β) subunits. Early in chordate evolution, some α subunits acquired an “inserted” (I) domain, which expanded their ligand binding capacity but simultaneously obstructed the ancestral ligand-binding pocket. While this would seemingly impede conventional ligand-mediated integrin activation, it was proposed that the I domain itself could serve both as a ligand replacement and an activation trigger. Here, we provide compelling evidence in support of this longstanding hypothesis using high-resolution cryo-electron microscopy structures of two distinct integrin complexes: the ligand-free and E-cadherin-bound states of the αEβ7 integrin with the I domain, as well as the α4β7 integrin lacking the I domain in both a ligand-free state and bound to MadCAM-1. We trace the evolutionary origin of the I domain to an ancestral collagen-collagen interaction domain. Our analyses illuminate how the I domain intrinsically mimics an extrinsic ligand, enabling integrins to undergo the canonical allosteric cascade of conformational activation and dramatically expanding the range of cellular communication mechanisms in vertebrates.
Cross-Dataset Identification of Human Disease-Specific Cell Subtypes Enabled by the Gene Print-based Algorithm--gPRINT
Authors: Yan Ruojin , Fan Chunmei , Gu Shen , Wang Tingzhang , Yin Zi , CHEN Xiao 
Published: November 2023

AbstractDespite extensive efforts in developing cell annotation algorithms for single cell RNA sequencing results, most algorithms fail to achieve cross-dataset mapping of cell subtypes due to factors such as batch effects between datasets. This limitation is particularly evident when rapidly annotating disease-specific cell subtypes across multiple datasets. In this study, we present gPRINT, a machine learning tool that utilizes the unique one-dimensional “gene print” expression patterns of individual cells. gPRINT is capable of automatically predicting cell types and annotating disease-specific cell subtypes. The development of gPRINT involved curation and harmonization of public datasets, algorithm validation within and across datasets, and the annotation of disease-specific fibroblast subtypes across various disease subgroups and datasets. Additionally, we created a preliminary single-cell atlas of human tendinopathy fibroblasts and successfully achieved automatic prediction of disease-specific cell subtypes in tendon disease. Furthermore, we conducted an exploration of key targets and related drugs specific to this subtype in tendon disease. The proposed approach offers an automated and unified method for identifying disease-specific cell subtypes across datasets, serving as a valuable reference for annotating fibroblast-specific subtypes in different disease states and facilitating the exploration of therapeutic targets in tendon disease.