bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral degradation
Authors: Sitron Cole S , Trinkaus Victoria A , Galesic Ana , Garhammer Maximilian , Yuste Checa Patricia , Dransfeld Ulrich , Feigenbutz Dennis , Zhang Jiuchun , Dudanova Irina , Harper J Wade , Hartl F Ulrich 
Published: January 2025

SUMMARYα-Synuclein aggregation is a hallmark of Parkinson’s disease and related synucleinopathies. Extracellular α-synuclein fibrils enter naïve cells via endocytosis, followed by transit into the cytoplasm to seed endogenous α-synuclein aggregation. Intracellular aggregates sequester numerous proteins, including subunits of the ESCRT-III system for endolysosome membrane repair, but the toxic effects of these events remain poorly understood. Using cellular models and in vitro reconstitution, we found that α-synuclein fibrils interact with an α-helix common to ESCRT-III proteins. This interaction results in sequestration of ESCRT-III subunits and triggers their proteasomal destruction in a process of “collateral degradation.” These twin mechanisms deplete the available ESCRT-III pool, initiating a toxic feedback loop. The ensuing loss of ESCRT function compromises endolysosome membranes, thereby facilitating escape of aggregate seeds into the cytoplasm, which in turn increases aggregation and ESCRT-III sequestration. We suggest that collateral degradation and triggering of self-perpetuating systems could be general mechanisms of sequestration-induced proteotoxicity.HIGHLIGHTSα-Synuclein fibrils bind and sequester ESCRT-III endolysosome repair proteinsAn α-helical segment common to ESCRT-III mediates fibril-selective interactionFibril-bound ESCRT-III subunits undergo “collateral degradation” via the proteasomeESCRT-III depletion damages endolysosomes and worsens α-synuclein aggregation
GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration
Authors: Albers Dan , Novikova Sofya , Vieyto-Nuñez Julio , Almeida-Hernández Yasser , Pastorio Chiara , Klassen Florian , Weiss Dana , von Maltitz Pascal , Jaikishan Janeni , Datta Moumita , Jumaa Hassan , Jebaraj Billy , Stilgenbauer Stephan , Kumar Manish , Maity Palash Chandra , Buske Christian , Stifel Ulrich , Zinngrebe Julia , Fischer-Posovszky Pamela , Chevigné Andy , Kirchhoff Frank , Sanchez-Garcia Elsa , Münch Jan , Harms Mirja 
Published: January 2025

AbstractGPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. This study investigates the effects of GPR15LG on the signaling and downstream functions of C-X-C chemokine receptor type 4 (CXCR4), which plays a critical role in immune cell trafficking and cancer metastasis. The results demonstrate that GPR15LG binds to the orthosteric site of CXCR4, modulating downstream signaling in a context-dependent manner. Specifically, GPR15LG enhances CXCL12-mediated CXCR4 signaling synergistically, promoting wound healing and cell migration across various cell types, including CD4+ T cells and cancer cells. These findings underscore the role of GPR15LG in inflammation and metastasis, offering potential therapeutic avenues for CXCR4-mediated diseases.TeaserGPR15LG binds CXCR4 thereby modulating CXCL12/CXCR4 signaling and immune and cancer cell trafficking.
Neuron type-specific mRNA translation programs provide a gateway for memory consolidation
Authors: Oliveira Mauricio M. , Mosto Olivia , Carney Robert , Liu Wendy , Makinde Emmanuel , Lu Emily H. , Ruiz Karen S.A. , Carew Thomas , Klann Eric 
Published: January 2025

SummaryLong-term memory consolidation is a dynamic process that requires a heterogeneous ensemble of neurons, each with a highly specialized molecular environment. Considerable effort has been placed into understanding how the molecular mechanisms in specific neuron types are modified in memory, but these studies are often undertaken hours or days after training, when memory is already consolidated. Studies have shown that protein synthesis is elevated during the early stages of consolidation, but there is limited information as to how it impacts neuronal function. We hypothesize that mRNAs being translated during the early stages of consolidation could provide clues as to how diverse neurons involved in memory formation restructure their molecular architecture to support memory formation. Here, we generate a landscape of the translatome of three neuron types in the dorsal hippocampus during the first hour of contextual memory consolidation. Our results show that these neurons share a common backbone of readily translated mRNAs. However, excitatory neurons undergo deep reconfiguration of proteostatic control, whereas interneurons modify their synaptic transmission. We demonstrate that the translational control in these neurons requires GADD34, which promotes translation initiation. Finally, we show that the differential expression of mRNAs by neurons during early consolidation can be explained by features hard coded in the mRNA, suggesting ubiquitous mechanisms controlling activity-dependent neuronal translation. Altogether, our work uncovers previously unknown checkpoints controlling activity-dependent translation in neurons and provides a large, readily available resource for further investigations of memory formation in health and disease.
Weak and tunable adhesion-clutch drives rapid cell migration and glioblastoma motility
Authors: Baba Kentarou , Fukushi-Kumagaya Ami , Morisaki Megumi , Takeuchi Ryosuke , Xiao Zhize , Nagashima Yoshikazu , Sakai Mizuki , Higashiguchi Yasuna , Katsuno-Kambe Hiroko , Katsuma Asako , Ueda Yoshihiro , Kamioka Yuji , Kawauchi Daisuke , Kinashi Tatsuo , Kanemura Yonehiro , Inagaki Naoyuki 
Published: January 2025

SUMMARYTo move forward, migrating cells must exert backward forces against the extracellular environment. Recent studies have highlighted the importance of integrin-independent forces for cell migration; but the molecular machinery that exerts forces remains unclear. Here, we show that the clutch-linker molecule shootin1 and the cell adhesion molecule L1 transmit the backward force of treadmilling actin filaments to the adhesive environment for rapid dendritic cell migration. Notably, shootin1 and L1 transmit weak traction forces, ∼100 times weaker than integrin-based forces, by constituting an integrin-independent slippery adhesion-clutch. This adhesion-clutch system is tunable in response to the chemoattractant CCL19 and the adhesive ligand laminin and mediates chemotaxis through its polarized activation within cells. Furthermore, its aberrant activity enhances glioblastoma cell motility. Our results show that the weak adhesion-clutch is well-suited for rapid cell migration, without forming strong adhesions that impede cell motility, and provides a potential target for inhibiting abnormal cell motility.
Residual flavor symmetries at the modular self-dual point and constraints on neutrino masses and mixing
Authors: Kashav Monal , Patel Ketan M. 
Published: January 2025

We explore the implications of symmetries that remain unbroken at the self-dual point τ=i in modular invariant theories. Assuming that (a) the three generations of lepton doublets transform as an irreducible representation of a finite modular group ΓN, and (b) the light neutrino masses arise from the Weinberg operator and are in modular form, we demonstrate that this setup yields a unique residual flavor symmetry or antisymmetry for the neutrinos, depending on the modular weight. In the antisymmetric case, one neutrino is always massless, and the other two can be degenerate if the mass matrix is real. These findings are independent of the level N. If the charged leptons are arranged to exhibit an appropriate residual symmetry from the same ΓN, they determine a column of the leptonic mixing matrix, leading to specific correlations between the mixing angles and the Dirac CP phase. The presence of residual (anti)symmetries enables the application of standard flavor symmetry techniques to derive these predictions, and we scan all possible ΓN satisfying condition (a). Most solutions yield O(1) entries in the fixed column, favoring relatively large lepton mixing.

Published by the American Physical Society
2025
Dynamic nature of leadership – the case of university management
Authors: Jaiswal Mayank 
Published: January 2025

Research methodology
The case was motivated after listening to Dr Heather Westphal’s leadership journey as a President of State University of North State (SUNS), Somerville. Several subsequent interviews were conducted with Heather, and she also became the chief protagonist of the case. Heather provided multiple quotes and anecdotes. The protagonist Heather and the focal organization (SUNS, Somerville) are disguised. However, the material facts of the case are authentic. Data were collected from public sources and SUNS, Somerville administration. Some of the data have been jittered to maintain anonymity yet keep the authenticity of the lesson.

Case overview/synopsis
The case exposes students to a female leader of a higher education institution in the USA. Various aspects a high-level executive must consider when deciding on career moves have been explored. Furthermore, the case draws attention to some extra particulars women leaders must consider during career transitions. The case study then dives into how a leader sets goals, executes them and repeats the process to set new goals. Two types of situations are covered – the first is where planning is followed by execution and the other is a crisis where not much planning can be done. Students will also get a glimpse into how leaders remain fit physically and mentally, as they conduct their duties in high-stress situations. Exposure to mental fitness is especially pertinent in today’s day and age where mental fatigue and issues because of work-related strain are a significant concern. Finally, the case presents students with a decision the leader is facing regarding the direction of the institution – Should she keep it traditional, go nontraditional (online) or become a hybrid?

Complexity academic level
This case is designed to target undergraduate juniors or seniors in strategy and leadership courses. The course could also be suitable for strategy students of nonprofit and not-for-profit management. It could be taught in the latter half of the course after the basic concepts have been covered. Students will be able to apply the knowledge of the core courses of management and strategy in this case. Hence, this case can act as an integrative case that brings together multiple disciplines and focuses on the leadership of a large institution.
Plague in Small Mammals From an Endemic Focus of the Malagasy Central Highlands: A Longitudinal Survey With a Special Reference on Black Rats (Rattus rattus)
Authors: Parany Mamionah Noro Jully , Stenseth Nils Christian , Rasoamalala Fanohinjanaharinirina , Rahelinirina Soanandrasana , Rahajandraibe Soloandry , Andrianaivoarimanana Voahangy , Dobigny Gauthier , Gorgé Olivier , Valade Eric , Fell Henry , Ramasindrazana Beza , Rajerison Minoarisoa 
Published: January 2025

ABSTRACTPlague, a zoonotic disease caused by Yersinia pestis, remains a major public health threat in several parts of the world, including Madagascar. Factors underlying long‐term persistence and emergence of the pathogen remain poorly understood. We implemented a longitudinal survey to provide insights into plague reservoir ecology within an endemic focus. Six trapping sessions (TS) were conducted in six different localities of the Ankazobe district from 2018 to 2020 in order to monitor small mammal communities. A total of 2762 individuals composed of six species (Rattus rattus, Rattus norvegicus, Mus musculus, Setifer setosus, Suncus murinus and Tenrec ecaudatus) were caught over the six successive TS. R. rattus represented 88% of all captures, with the highest relative abundances observed during the dry season (June to August 2019). None of the micromammals tested positive for the presence of Y. pestis, neither with qPCR nor bacterial culture. However, 11 seropositive individuals (6 R. rattus, 2 M. musculus and 3 S. murinus) were retrieved following ELISA, thus leading to a global seroprevalence of 0.4%. Our study highlighted the significant influence of climatic data on the seasonal variations of R. rattus abundance and suggest that black rat control should be conducted before the dry season, that is, during high reproduction period of rats, in order to reduce the number of reproducing animals and prevent subsequent increase in abundance. As three S. murinus and two M. musculus plague seropositive were identified in the present study, their potential role in plague eco‐epidemiology in Madagascar should be explored further.
Assessing the Role of Data in Operational Decisions and Risk Planning for Water Permit Holders
Authors: Whateley Sarah , Josset Laureline , Gibson Catherine , Lowrie Stuart , Schuler George 
Published: January 2025

ABSTRACTWater data are evolving rapidly, driven by the expansion of diverse data platforms and the implementation of new policy frameworks. Despite advancements, the utilization of water data by water users remains uncertain. We surveyed 173 water permit holders across New York State to understand what water data are collected and for what purpose across geography, sector, and withdrawal volume. This study reveals that water data primarily serve regulatory purposes and play little role in permittees' operational, sustainability, or risk management decisions. To unlock the full potential of water data for users, we recommend educational initiatives such as training programs for data‐driven assessments, alongside technological advancements like developing web data portals that support risk and impact assessments. These recommendations aim to foster collaboration for navigating the complexities of stressors and achieving a more informed and adaptable approach to water usage.
Hypomethylating agents for patients with VEXAS without myelodysplastic syndrome: Clinical outcome and longitudinal follow‐up of vacuolization and UBA1 clonal dynamics
Authors: Álamo Jose R. , Torres Lucía Mont‐de , Castaño‐Díez Sandra , Mensa‐Vilaró Anna , Mónica López‐Guerra M. , Zugasti Ines , Díaz Johana , Jiménez‐Vicente Carlos , Plaza Susana , Fabregat Virginia , de Landazuri Iñaki Ortiz , Yagüe Jordi , Espinosa Gerard , Sanmartí Raimon , Rozman Maria , Guijarro Francesca , Cortes Albert , Triguero Ana , Cardús Aina , Cuartas Adriana , Cornejo Marina , Esteve Jordi , Aróstegui Juan I. , Díaz‐Beyá Marina 
Published: January 2025

SummaryVEXAS syndrome is a haemato‐inflammatory disease caused by somatic UBA1 mutations and characterized by cytoplasmic vacuoles in myeloid and erythroid precursor cells. Although there is currently no standard treatment algorithm for VEXAS, patients are generally treated with anti‐inflammatory therapies focused on symptom management, with only partial effectiveness. Hypomethylating agents (HMA) have shown promise in VEXAS patients with concomitant myelodysplastic syndrome (MDS), while the efficacy of HMA in VEXAS patients without MDS is largely unknown. Furthermore, the usefulness of monitoring the variant allele frequency (VAF) of UBA1 or vacuolization in precursor cells over the course of treatment has not been extensively investigated. We have evaluated the efficacy of HMA in four VEXAS patients without MDS and performed longitudinal analyses of the VAF of UBA1 and vacuolization during treatment. HMA treatment led to overall clinical improvement, a dramatic reduction in the VAF of UBA1, normalization of haematological and inflammatory markers and a quantifiable decrease in vacuolization, leading us to speculate that unlike anti‐inflammatory therapies, HMA may well act as a disease‐modifying treatment. If these findings are confirmed in further studies, it could lead to the early use of HMA in the treatment of all VEXAS patients—with or without MDS.
The Performance of Ankle‐ and Waist‐Based Accelerometry in Quantifying Physical Activity Intensity Among 6‐ to 24‐Month‐Year‐Olds: A Semistructured Laboratory Study
Authors: Dorris Hannah J. , Carlson Delaina D. , Ballarino Grace A. , Lopez Nanette V. , Emond Jennifer A. 
Published: January 2025

ABSTRACTObjectivesWe aim to quantify the performance of accelerometry in objectively measuring physical activity (PA) intensity among infants and toddlers.MethodsThirty‐eight 6‐ to 24‐month‐olds participated in a 30‐min, semistructured lab visit. Twenty‐three (61%) children could walk independently. Children engaged in a variety of activities while wearing accelerometers on each ankle and at the waist. Visits were video recorded, and study team members independently coded the first three 5‐s epochs of each minute for PA intensity using a 5‐level scale ranging from 1 = completely sedentary to 5 = moderate‐to‐high intensity. Interrater agreement for PA classifications was excellent (median kappa per child = 0.85). A series of logistic regression models were fit to find the vector magnitude threshold per 5‐s epoch that differentiated activity intensity above each PA level with ≥ 80% sensitivity.ResultsAnalyses included 3191 epochs; a median of 88 epochs per child. The classification performance applying all thresholds concurrently for the five PA intensity levels was poor for each wear location (agreement < 50%, kappa < 0.25). Classification improved when concatenating intensity levels, with the best performance comparing sedentary (levels 1–2) to nonsedentary (levels 3–5) and using data from the left ankle device: agreement ≥ 77.6%, kappa ≥ 0.44. Applying those novel thresholds to predict the total time spent in level 3–5 activities over all coded epochs using linear regression performed as well as using the sum of vector magnitude across epochs when using data from the left ankle device. Overall, the performance of the left ankle wear location was similar to the right ankle wear location and superior to the waist location.ConclusionsAnkle‐worn accelerometry had adequate validity to classify in‐the‐moment nonsedentary behaviours and total time spent nonsedentary over a time interval among this sample of infants and toddlers. While caution is warranted when generalizing these lab‐based findings to naturalistic settings, findings provide insight into objective measures of PA for this age range.
Functional Characterization and In Silico Prediction Tools Improve the Pathogenicity Prediction of Novel Bile Acid Transporter Variants
Authors: Peng Ziyue , Wang Xin , Li Ying , Ren Yaqiong , Meng Yuhuan , Sun Liwei , Zhang Zitong , Song Yue , Xia Yang , Shi Lei , Yu Shihui , Cheng Liang , Zhang Xue 
Published: January 2025

ABSTRACTThe pathogenicity of cholestatic liver diseases (CLDs) remains insufficiently characterized, hindering definitive diagnosis and timely treatment. The aim of this study was to improve the pathogenicity prediction of novel bile acid (BA) transporter variants in patients with CLDs. We analyzed the clinical characteristics and genetic profiles of a CLD cohort (n = 57) using multiple in silico tools and in vitro functional assays. We identified 78 unique variants in four BA transporter genes. The predominant defects were associated with ABCC2 (57/78, 73.1%), with the most frequent being missense variants (39/78, 50.0%). Using in silico tools, we identified 47 novel variants: 12 mis‐splicing, 21 deleterious missense, and 23 with altered protein stability. Of the 34 novel variants in ABCC2 identified through in vitro functional assays, seven incurred aberrant splicing, 11 missense variants resulted in MRP2 reduction, 9 missense variants resulted in abnormal N‐glycosylation, 18 variants altered MRP2 localization, and 26 variants reduced organic anion transport activity. These findings indicate that a multidisciplinary approach, integrating bioinformatics and experimental data, significantly enhances the accuracy of genetic‐based CLD diagnosis. It serves as a foundational study for BA transport variants pathogenicity reclassification and expands the mutation spectrum of CLDs in China.
Real‐Time Nail‐Biting Detection on a Smartwatch Using Three CNN Models Pipeline
Authors: Alesmaeil Abdullah , Şehirli Eftal 
Published: January 2025

ABSTRACTNail‐biting (NB) or onychophagia is a compulsive disorder that affects millions of people in both children and adults. It has several health complications and negative social effects. Treatments include surgical interventions, pharmacological medications, or additionally, it can be treated using behavioral modification therapies that utilize positive reinforcement and periodical reminders. Although it is the least invasive, such therapies still depend on manual monitoring and tracking which limits their success. In this work, we propose a novel approach for automatic real‐time NB detection and alert on a smartwatch that does not require surgical intervention, medications, or manual habit monitoring. It addresses two key challenges: First, NB actions generate subtle motion patterns at the wrist that lead to a high false‐positives (FP) rate even when the hand is not on the face. Second, is the challenge to run power‐intensive applications on a power‐constrained edge device like a smartwatch. To overcome these challenges, our proposed approach implements a pipeline of three convolutional neural networks (CNN) models instead of a single model. The first two models are small and efficient, designed to detect face‐touch (FT) actions and hand movement away (MA) from the face. The third model is a larger and deeper CNN model dedicated to classifying hand actions on the face and detecting NB actions. This separation of tasks addresses the key challenges: decreasing FPs by ensuring NB model is activated only when the hand on the face, and optimizing power usage by ensuring the larger NB model runs only for short periods while the efficient FT model runs most of the time. In addition, this separation of tasks gives more freedom to design, configure, and optimize the three models based on each model task. Lastly, for training the main NB model, this work presents further optimizations including developing NB dataset from start through a dedicated data collection application, applying data augmentation, and utilizing several CNN optimization techniques during training. Results show that the model pipeline approach minimizes FPs significantly compared with the single model for NB detection while improving the overall efficiency.
HN1 Functions in Protein Synthesis Regulation via mTOR‐RPS6 Axis and Maintains Nucleolar Integrity
Authors: Özduman Gülseren , Javed Aadil , Akçaöz Alasar Azime , Akgül Bünyamin , Korkmaz Kemal Sami 
Published: January 2025

ABSTRACTHaematological and Neurological Expressed 1 (HN1) is an oncogene for various cancers and previously has been linked with centrosome clustering and cell cycle pathways. Moreover, HN1 has recently been reported to activate mTOR signalling, which is the regulator of ribosome biogenesis and maintenance. We explored the role of HN1 in mTOR signalling through various gain‐ and loss‐of‐function experiments using biochemical approaches in different cell lines. We demonstrated for the first time that HN1 is required for nucleolar organiser region (NOR) integrity and function. Immunoprecipitation‐based association and colocalization studies demonstrated that HN1 is an important component of the mTOR‐RPS6 axis, and its depletion results with reduced mRNA translation in mammalian cancer cell lines. This study also demonstrated that the depletion of HN1 leads to the irregular distribution of nucleolar structures, potentially leading to cell cycle deregulation as reported previously. Accordingly, components of the translation machinery aggregate with a distinct speckled pattern, lose their essential interactions and ultimately impair mRNA translation efficiency when the HN1 is depleted. These results suggest that HN1 is an essential component of the nucleolus, required for ribosome biogenesis as well as global mRNA translation.