bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient receptor potential vanilloid channel 2 contributes to multi-modal endoplasmic reticulum and perinuclear space dilations that can also be observed in prion-infected mice
Authors: Zhao Wenda , Eid Shehab , Sackmann Chris , Williams Declan , Wang Xinzhu , Ouyang Yunqing , Zerbes Thomas , Schmitt-Ulms Gerold 
Published: December 2024

ABSTRACTOur recent work on the prion protein and Na+,K+-ATPases (NKAs) led us to revisit data from over 50 years ago, which suggested a similarity between vacuolation phenotypes in rodents poisoned with cardiac glycosides (CGs) and spongiform degeneration in prion disease. At that time, this hypothesis was dismissed because the vacuolation observed in prion diseases affects neurons, whereas CG poisoning in rodent brains led to swellings of the endoplasmic reticulum (ER) in astrocytes. We speculated that this difference might be specific to rodents and document here that the vacuolation shifts to neurons in mice expressing a humanized NKA α1 subunit. Next, we investigated the molecular mechanisms that could cause similar ER vacuolation in human cellsin vitro. We found that certain stressors—such as overexpression of NKA α subunits and exposure to specific toxins known to trigger the unfolded protein response—can induce a phenotype characterized by profound ER dilation that is most strikingly observed for the perinuclear space (PNS). The ion imbalance typically caused by functional NKAs does not contribute to this phenotype. In fact, it can occur even with the overexpression of catalytically inactive NKAs. Several lines of evidence, generated with pharmacological agents, ion-specific dyes, antagonists, and truncated expression constructs, suggest a calcium leak channel in the ER, known as transient receptor potential vanilloid 2 (TRPV2), plays a role in this ER and PNS dilation. Additionally, we observed that the formation of these vacuoles coincides with a decrease in steady-state levels of the lipid kinase PIKFYVE, which is recognized for its role in endolysosomal fission and fusion processes. Finally, we found evidence of vacuoles in cryo-sectioned brains of prion-infected mice that can be filled with a fluorescent marker targeted to the ER and PNS. This raises the possibility that this vacuolation phenomenon contributes to spongiform degeneration seen in prion diseases.
Timing of Menarche and Menopause and Epigenetic Aging among U.S. Adults: Results from the National Health and Nutrition Examination Survey 1999-2002
Authors: Daredia Saher , Khodasevich Dennis , Gladish Nicole , Shen Hanyang , Nwanaji-Enwerem Jamaji C. , Bozack Anne K. , Needham Belinda L. , Rehkopf David H. , Deardorff Julianna , Cardenas Andres 
Published: December 2024

ABSTRACTReproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N=1,033) and menopause (N=658) with epigenetic aging in a nationally representative sample of women ≥50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation (B= -0.10 years, 95% CI: -0.19, -0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.
Racial disparities in continuous glucose monitoring-based 60-min glucose predictions among people with type 1 diabetes
Authors: Thomsen Helene Bei , Li Livie Yumeng , Isaksen Anders A. , Lebiecka-Johansen Benjamin , Bour Charline , Fagherazzi Guy , van Doorn William P. T. M. , Varga Tibor V. , Hulman Adam 
Published: December 2024

AbstractNon-Hispanic white (White) populations are overrepresented in medical studies. Potential healthcare disparities can happen when machine learning models, used in diabetes technologies, are trained on data from primarily White patients. We aimed to evaluate algorithmic fairness in glucose predictions. This study utilized continuous glucose monitoring (CGM) data from 101 White and 104 Black participants with type 1 diabetes collected by the JAEB Center for Health Research, US. Long short-term memory (LSTM) deep learning models were trained on 11 datasets of different proportions of White and Black participants and tailored to each individual using transfer learning to predict glucose 60 minutes ahead based on 60-minute windows. Root mean squared errors (RMSE) were calculated for each participant. Linear mixed-effect models were used to investigate the association between racial composition and RMSE while accounting for age, sex, and training data size.A median of 9 weeks (IQR: 7, 10) of CGM data was available per participant. The divergence in performance (RMSE slope by proportion) was not statistically significant for either group. However, the slope difference (from 0% White and 100% Black to 100% White and 0% Black) between groups was statistically significant (p=0.02), meaning the RMSE increased 0.04 [0.01, 0.08] mmol/L more for Black participants compared to White participants when the proportion of White participants increased from 0 to 100% in the training data. This difference was attenuated in the transfer learned models (RMSE: 0.02 [-0.01, 0.05] mmol/L, p=0.20).The racial composition of training data created a small statistically significant difference in the performance of the models, which was not present after using transfer learning. This demonstrates the importance of diversity in datasets and the potential value of transfer learning for developing more fair prediction models.
Bottom-up design of calcium channels from defined selectivity filter geometry
Authors: Liu Yulai , Weidle Connor , Mihaljević Ljubica , Watson Joseph L. , Li Zhe , Yu Le Tracy , Majumder Sagardip , Borst Andrew J. , Carr Kenneth D. , Kibler Ryan D. , Gamal El-Din Tamer M. , Catterall William A. , Baker David 
Published: December 2024

AbstractNative ion channels play key roles in biological systems, and engineered versions are widely used as chemogenetic tools and in sensing devices1,2. Protein design has been harnessed to generate pore-containing transmembrane proteins, but the capability to design ion selectivity based on the interactions between ions and selectivity filter residues, a crucial feature of native ion channels3, has been constrained by the lack of methods to place the metal-coordinating residues with atomic-level precision. Here we describe a bottom-up RFdiffusion-based approach to construct Ca2+channels from defined selectivity filter residue geometries, and use this approach to design symmetric oligomeric channels with Ca2+selectivity filters having different coordination numbers and different geometries at the entrance of a wide pore buttressed by multiple transmembrane helices. The designed channel proteins assemble into homogenous pore-containing particles, and for both tetrameric and hexameric ion-coordinating configurations, patch-clamp experiments show that the designed channels have higher conductances for Ca2+than for Na+and other divalent ions (Sr2+and Mg2+). Cryo-electron microscopy indicates that the design method has high accuracy: the structure of the hexameric Ca2+channel is nearly identical to the design model. Our bottom-up design approach now enables the testing of hypotheses relating filter geometry to ion selectivity by direct construction, and provides a roadmap for creating selective ion channels for a wide range of applications.
Recombinant Pichinde reporter virus as a safe and suitable surrogate for high-throughput antiviral screening against highly pathogenic arenaviruses
Authors: Sacramento Carolina Q. , Bott Ryan , Huang Qinfeng , Eaton Brett , Postnikova Elena , Sabir Ahmad J. , Argade Malaika D. , Ratia Kiira , Anantpadma Manu , Carlier Paul R , Ly Hinh , Liang Yuying , Rong Lijun 
Published: December 2024

ABSTRACTSeveral arenaviruses, such as the Old World (OW) Lassa virus (LASV) and the New World (NW) Junin virus (JUNV), can cause severe and lethal viral hemorrhagic fevers in humans. Currently, no vaccines or specific antiviral therapies are FDA-approved for treating arenavirus infections. One major challenge for the development of new therapeutic candidates against these highly pathogenic viruses is that they are BSL-3/4 pathogens that need to be handled in high biocontainment laboratories. In this work, a recombinant non-pathogenic New World arenavirus, Pichinde virus (rPICV), was used for the development of a high-throughput screening (HTS) assay in the BSL-2 laboratory for the screening and identification of small molecule inhibitors against arenaviruses. The rPICV is a replication-competent virus expressing the firefly luciferase reporter gene in the infected cells proportionally to the infection rate. rPICV infection was optimized for an automated HTS in 384-well format with robust Z′ scores, high signal-to-background ratios, and low intrinsic variance. Screening an established library allowed for the identification of five top hit compounds, which included ribavirin, a known inhibitor of arenaviral RNA synthesis, showing good potency and selectivity in inhibiting rPICV replication. The antiviral activity of the top hit compounds was further validated against another recombinant arenavirus, the OW lymphocytic choriomeningitis virus (rLCMV) and against laboratory strains of LASV (Josiah) and JUNV (Romero). The use of rPICV in the HTS-based antiviral assay under BSL-2 condition has proven to be safe and suitable for the identification of broad-spectrum small molecule inhibitors against highly pathogenic arenaviruses.
Capturing Dynamic Neuronal Responses to Dominant and Subordinate Social Hierarchy Members with catFISH
Authors: Dwortz Madeleine F. , Curley James P. 
Published: December 2024

AbstractDominance hierarchies are key to social organization in group-living species, requiring individuals to recognize their own and others’ ranks. This is particularly complex for intermediate-ranking animals, who navigate interactions with higher- and lower-ranking individuals. Using in situ hybridization, we examined how the brains of intermediate-ranked mice in hierarchies respond to dominant and subordinate stimuli by labeling activity-induced immediate early genes and neuronal markers. We show that distinct neuronal populations in the amygdala and hippocampus respond differentially across social contexts. In the basolateral amygdala, glutamatergic Slc17a7+ neurons, particularly dopamine-receptive Slc17a7+Drd1+ neurons, show elevated IEG expression in response to social stimuli, with a higher response to dominant over subordinate animals. Similar patterns are observed among Slc17a7+Oxtr+ neurons in the dorsal endopiriform nucleus and GABAergic Slc32a+ neurons in the medial amygdala. We also identified distinct neural ensembles selectively active in response to dominant and subordinate hierarchy members. We find a higher degree of reactivation among Slc17a7+Oxtr+ ensembles in the dorsal endopiriform nucleus in animals repeatedly presented with the same hierarchy member, as opposed to those presented with a dominant and subordinate member. We observe a similar pattern among Oxtr+ neurons in the dentate gyrus hilus, while the inverse is observed among Slc17a7+ Avrp1b+Oxtr+ neurons in the distal CA2CA3 region. Collectively, our findings reveal how social context is associated with activity changes in social, olfactory, and memory systems in the brain at the neuronal cell type level. This work lays the foundation for further precise cell-type investigation into how the brain processes social information.
The Chromosome Periphery is an Essential Compartment of Oocyte Chromosomes
Authors: Simpson Eva L , Wetherall Ben , Byrska Aleksandra , Cheeseman Liam P , Mendonca Tania , Xing Xiaomeng , Beckett Alison J , Maiato Helder , Sarginson Alexandra , Prior Ian A , Hartshorne Geraldine M , McAinsh Andrew D , Madgwick Suzanne , Booth Daniel G. 
Published: December 2024

SUMMARYChromosomes and their constituent compartments are core elements of the cell division machinery. In mammalian oocytes, defects in the structure or composition of chromosomes are a leading cause of aberrant or failed meiosis, and by extension, can cause miscarriage and infertility. The underlying mechanisms are poorly understood, but are critical for development of novel diagnostics and treatments.The chromosome periphery, the least understood chromosome compartment, has recently emerged as an essential component of mitotic chromosomes and somatic cell division. However, in female meiosis it remains completely unexplored.This study provides the first comprehensive survey of a meiotic chromosome periphery compartment in both human and mouse oocytes. Using a combination of time-lapse microscopy, super-resolution imaging and 3DCLEM we show that removing the chromosome periphery, via Ki67 depletion, has substantial negative impact on chromosome structure, spatial organization and positional awareness, with many oocytes stalling and arresting in meiosis I. Importantly, we also reveal key differences between the mitotic and oocyte meiotic chromosome periphery compartments, most remarkably in the retention of Ki67 in the oocyte through anaphase I, where unwanted chromosomes are stripped of Ki67 before being ejected from the oocyte.This work presents the discovery of an exciting new pathway operating during female meiosis and a provides a platform for future work exploring the meiotic chromosome periphery for therapeutic vulnerabilities.
A comprehensive spatiotemporal map of dystrophin isoform expression in the developing and adult human brain
Authors: Catapano Francesco , Alkharji Reem , Chambers Darren , Singh Simran , Aghaeipour Arta , Malhotra Jyoti , Ferretti Patrizia , Phadke Rahul , Muntoni Francesco 
Published: December 2024

AbstractMutations in the dystrophin gene (DMD)cause the severe muscle-wasting disease Duchenne Muscular Dystrophy (DMD). Additionally, there is a high incidence of intellectual disability and neurobehavioural comorbidities in individuals with DMD. Similar behavioural abnormalities are found inmdxdystrophic mouse models. Unlike muscle, several dystrophin isoforms are expressed in the human brain, but a detailed map of regional and cellular localisation of dystrophin isoforms is missing. This is crucial in understanding the neuropathology of DMD individuals, and for evaluating the translatability of pre-clinical findings in DMD mouse models receiving genetic therapy interventions. Here, we provide a comprehensive dystrophin expression profile in human brains from early development to adulthood. We reveal expression ofdp427p2,dp427c,dp427manddp40isoforms in embryonic brains, not previously reported.Dp427p2anddp140were greatly downregulated in adult brains, although the latter continued to be expressed across several regions. Importantly, we demonstrate for the first-time expression ofDMDtranscripts in human motor neurons and co-expression of different dystrophin isoforms within single neurons in both developing and adult brains. Finally, we show localisation ofDMDtranscripts withGAD1+ GABAergic-associated transcripts in neurons including cerebellar Purkinje cells and interneurons, as well as in the majority of neocortical and hippocampalSLC17A7+ glutamatergic neurones, suggesting a role for dystrophin in signalling at the neuronal inhibitory and excitatory synapses.Graphical Abstract
The Soil Microbiome of the Caatinga Drylands in Brazil
Authors: Tacca Luísa Mayumi Arake de , Lima Rayane Nunes , Oliveira Marco Antônio de , Pascoal Patrícia Verdugo , Bambil Deborah , Rosinha Grácia Maria Soares , Signor Diana , Freire Marcelo , Rech Elibio 
Published: December 2024

ABSTRACTDrylands represent a significant part of the Earth’s surface and include essential and vulnerable ecosystems for the global ecological balance. The Caatinga, with its unique biodiversity adapted to the extreme conditions of this semi-arid region, offers a valuable opportunity to expand our knowledge about these ecosystems. Here, this work reveals the high microbial diversity in the soil and rhizosphere of the Caatinga, with the roots presenting more specialized communities. Bacteria such asBacilli,AlphaproteobacteriaandFirmicutesexcelled in critical functions such as nutrient cycling. Interplant differences suggested the influence of root exudates. The metagenomic study of interactions between microorganisms in the rhizosphere of selected plants revealed microbial biodiversity and contributed to our understanding of nutrient cycling, plant growth and resistance to water stress. In addition, they demonstrate biotechnological potential to address global challenges such as desertification and food security.
LC3 forms functional nanocluster on autophagosome
Authors: Fatihi Saman , Khushalani Deepak M. , Kar Joydipta , Mohan Nitin , Thukral Lipi 
Published: December 2024

AbstractAutophagosome biogenesis relies on the intricate coordination of proteins and lipids, with LC3B proteins persistently anchored to the double-membraned autophagosomes through a lipid anchor. However, little is known about how LC3B is organized in high concentration, its spatial distribution, and the mechanisms underlying its protein-mediated tethering on membranes. Using molecular dynamics simulations and super-resolution microscopy, we demonstrate that LC3B self-assembles to form higher-order clusters, averaging 150 nm in size. Interestingly, simulations provided cue for LC3B and phosphatidylinositol lipid specificity, and STORM imaging confirmed a clear overlap of LC3B-enriched regions with phosphatidylinositol-3-phosphate lipids. Together, LC3B nanoclusters on these lipids form spatially distinct “islands” on the autophagosome. Additionally, molecular analysis of 296 clusters revealed that clustering is driven by a unique rear binding pocket in Loop6 defined by alternating hydrophobic and polar residues. We generated four mutants to disrupt the characteristic self-assembly motif, with all four mutants resulting in aberrant cluster formation and impaired autophagosome motility. These findings highlight that LC3B self-assembly is crucial for autophagy and suggest a spatiotemporal mechanism regulating LC3B function.
Integrating or tailoring? Optimizing touchpoints for enhanced omnichannel customer experience
Authors: Yin Chin-Ching 
Published: December 2024

PurposeTo successfully implement omnichannel strategies, companies are required to use physical and online touchpoints effectively. This research aims to explore how consumers interact with various omnichannel touchpoints and identify the positive outcomes for firms.Design/methodology/approachDrawing on the perspective of MRT and UGT, this study developed a comprehensive framework based on hypotheses and employed structural equation modeling to test it in Study 1. To further examine the effects of omnichannel touchpoints on customer experience and shopping behavior intentions, Study 2 used a between-subjects experimental design.FindingsThe results reveal that particular touchpoints positively influence specific dimensions of customer experience, affecting brand attitude, purchase intention and experience sharing. Findings also indicate that product types moderate the relationship between omnichannel touchpoints and customer experience, as well as the relationship between customer experience and brand attitude.Originality/valueThis research enriches interactive marketing literature on customer experience and omnichannel shopping, providing companies seeking omnichannel touchpoint design with solid theoretical insights and empirical evidence.
Linking effect traits of soil fauna to processes of organic matter transformation
Authors: Bonfanti Jonathan , Potapov Anton M. , Angst Gerrit , Ganault Pierre , Briones Maria J. I. , Calderón‐Sanou Irene , Chen Ting‐Wen , Conti Erminia , Degrune Florine , Eisenhauer Nico , Ferlian Olga , Hackenberger Davorka , Hauer Amelie , Hedde Mickaël , Hohberg Karin , Krogh Paul Henning , Mulder Christian , Perez‐Roig Camila , Russell David , Shelef Oren , Zhou Zheng , Zuev Andrey G. , Berg Matty P. 
Published: December 2024

Abstract

Soil organic matter (SOM) transformation processes are regulated by the activities of plants, microbes, and fauna. Compared with plants and microbes, effects of soil fauna are less understood because of their high taxonomic and functional diversity, and mix of direct and indirect effect mechanisms. Trait‐based approaches offer a generic perspective to quantify mechanistic relationships between soil fauna and SOM transformations, including decomposition, translocation, and stabilisation of organic carbon. Yet, at present, we lack a consensus concerning relevant key effect traits of soil fauna (i.e. those affecting ecosystem functioning).

Here, we address this knowledge gap by focusing on relationships between soil fauna effect traits and SOM transformations. Based on existing literature, we identify key processes linked to SOM transformations, and fauna effect traits universally applicable across taxa and soil types, and discuss the process‐trait links.

We define eight SOM transformation processes that are directly affected by soil fauna: (i) litter mass loss, (ii) litter fragmentation, (iii) SOM aggregation in faeces, (iv) SOM aggregation in soil mineral particles, (v) decomposition of faeces, (vi) SOM and mineral translocation, (vii) pore space creation and maintenance and (viii) SOM stabilisation. We link these processes to general effect traits classified into four categories: (a) food selection and ingestion, (b), digestion and excretion, (c) mobility, and (d) body mass and metabolic rate. We also propose proxies when effect trait measurements are laborious.

The proposed links between effect traits and SOM transformation processes need to be validated in targeted experiments. We urge researchers to obtain quantitative experimental data, together with metabolic approaches, to integratively quantify soil fauna contributions to soil functioning.

Read the free Plain Language Summary for this article on the Journal blog.