bluuebunny/crossref_metadata_2025_split huggingface dataset:
The small molecule ML233 is a direct inhibitor of tyrosinase function
Authors: Menard Romain , Baanannou Aissette , Halluin Caroline , Morse Dexter , Kuhn Sadie , Graber Joel H. , Strickland James , Madelaine Romain 
Published: February 2025

ABSTRACTMelanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. However, despite decades of research, currently there is no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report characterization of the ML233 chemical as a potent inhibitor of tyrosinase activityin vivoandin vitro. We demonstrate that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also predict that these effects are mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. Together, our results reveal that ML233 plays roles in both healthy and pathological skin cells via inhibition of melanin production. ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health.
Chemical diversity promotes ecosystem function
Authors: Fonvielle Jeremy A. , Sandor Sarah R. , Dittmar Thorsten , Tanentzap Andrew J. 
Published: February 2025

AbstractNature benefits people in many ways that rely on how microorganisms and abiotic processes interact with organic matter to influence ecosystem function (EF). Despite many studies evaluating how biodiversity affects EF, most variation in EF remains unexplained. Here, we tested how the variety of organic compounds in the environment, termed chemodiversity, influences EF. Using a laboratory experiment and 101-lake survey spanning Europe, we discovered that chemodiversity, not biodiversity, consistently explained variation in multiple functions related to carbon cycling and ecosystem metabolism. We attributed positive chemodiversity-ecosystem multifunctionality relationships to the accumulation of compounds that could be biochemically transformed in more diverse ways at higher chemodiversity. We estimated chemodiversity will decline by 2100 due to changes in organic matter sources, causing European lakes to emit, on average, 1.6-times more carbon. These findings reframe our understanding of ecosystem functioning and suggest chemodiversity is key to sustain the benefits that nature delivers to people.
VOYAGER: an international consortium investigating the role of human papilloma virus and genetics in oral and oropharyngeal cancer risk and survival
Authors: Gormley M , Adhikari A , Dudding T , Pring M , Hurley K , Macfarlane GJ , Lagiou P , Lagiou A , Polesel J , Agudo A , Alemany L , Ahrens W , Healy CM , Conway DI , Canova C , Holcatova I , Richiardi L , Znaor A , Olshan AF , Hung RJ , Liu G , Bratman S , Zhao X , Holt J , Cortez R , Gaborieau V , McKay JD , Waterboer T , Brennan P , Hayes N , Diergaarde B , Virani S 
Published: February 2025

AbstractHead and neck cancer (HNC) is the sixth most common cancer globally. Incidence and survival rates vary significantly across geographic regions and tumor subsites. This is partly due to differences in risk factor exposure, which includes tobacco smoking, alcohol consumption and human papillomavirus (HPV) infection, alongside detection and treatment strategies. The VOYAGER (human papillomaVirus, Oral and oropharYngeal cAncer GEnomic Research) consortium is a collaboration between five large North American and European studies which generated data on 10,530 participants (7,233 cases and 3,297 controls). The primary goal of the collaboration was to improve understanding of the role of HPV and genetic factors in oral cavity and oropharyngeal cancer risk and outcome. Demographic and clinical data collected by the five studies were harmonized, and HPV status was determined for the majority of cases. In addition, 999 tumors were sequenced to define somatic mutations. These activities generated a comprehensive biomedical resource that can be utilized to answer critical outstanding research questions to help improve HNC prevention, early detection, treatment, and surveillance.
Assessment of sexual dimorphismDesmodus rotundus(Chiroptera: Phyllostomidae), a rabies reservoir in Latin America
Authors: Cifuentes-Rincon Analorena , Sarmiento-Arias Karen D. , Soler-Tovar Diego , Rodríguez-Bolaños Abelardo , Bravo-Garcia Carlos , Reyes-Amaya Nicolas , Ávila-Vargas Laura , Escobar Luis E. 
Published: February 2025

AbstractMorphometric traits of a host have been used recently in disease ecology for a deeper understanding of the connection between phenotype and transmission rates. The common vampire bat,Desmodus rotundus,is the main reservoir of rabies in Latin America, one of the most lethal zoonotic diseases in the world. Comprehension of morphological variation inD. rotundusis insufficient, contradictory, and inconclusive. Due to this inconsistency, we explored sexual dimorphism inD. rotundus by combining different measuresto provide new knowledge that can contribute to the control of rabies. As a result, our study provides evidence of sexual dimorphism in D. rotundus with females generally larger than males in body and wing measurements.The statistical, as well as the principal components, and clusters analysis, confirm morphological differences between females and males, without observing a complete separation between the sexes, possibly due to environmental factors that change the specimens’ conditions or limitations with access to measures. Understanding the sexual dimorphism of the main transmitter of wild rabies in South America is essential since morphological variations between sexes could influence both the use of the habitat and the dispersion capacity of the bats, which are relevant to the epidemiology of rabies. Because our data originated primarily from lowland areas, we are unable to rule out the effects of elevation on sex dimorphism. Given the importance of rabies for global public health, investigating the morphological and behavioral aspects of rabies reservoirs could help us better understand how ecological aspects influence disease spread.
Actin contractility and endocytosis create apico-basal tension gradient in HeLa cells
Authors: Ghosh Tanmoy , Majhi Anisha , Kundu Avijit , Banerjee Ayan , Sinha Bidisha 
Published: February 2025

AbstractThe functions of the plasma membrane of a cell are coupled to its mechanical state. To understand the players that contribute to the tight regulation of membrane mechanics with its local heterogeneities, the tension of the cell membrane requires to be mapped out from the basal to the apical membrane. In this work, optical-trap-based tension measurements performed at two axial (z) planes per cell reveal an apico-basal gradient, that is understood better on comparison with basal membrane mechanics and membrane compaction measurements by a combination of high resolution microscopy (IRM) and fluorescence lifetime (Flipper-TR) measurements, respectively. While the apico-basal gradient in the apparent tension (low to high) was found to depend on an intact actin cytoskeleton, analysing the colocalization of the cortical actin with the motor protein myosin and the actin-membrane linker ezrin suggested that cytoskeleton contractility is a major determinant of the patterned tension. Tension-sensitive lifetime of Flipper-TR, validated the gradient but failed to catch the dependence on actin due to the dual and opposite effects of tension on lifetime. Finally, measurements utilizing fluorescently tagged transferrin (Tf) demonstrated that the functional state of the membrane also showed similar height dependence. Thus, planes where tension maximized showed a peak in accumulation of Tf colocalizing with clathrin indicative of the presence of more pits. This enabled us to demonstrate that cells exist in tightly regulated patterned tension states that is coupled to their cytoskeleton as well membrane functions like endocytosis.Significance StatementThe cell membrane is protective but also highly dynamic - performing a diverse set of functions usually via membrane shape changes. These functions affect membrane mechanics but are also mechano-regulated. Mapping the state of cell surface mechanics or tension of live cells is therefore of fundamental importance. Interestingly, recent works have suggested that membrane tension can be non-uniform. However, no single tension-measuring technique can truly reach every part of the cell. Our work addresses this issue where we map tension in live HeLa cells using multifarious approaches including the measurement of tether forces, membrane fluctuations, and lipid compaction. We show that at the top/apical surface, the membrane-tension is lower than that at the midplane. The observed gradient resembles that of the state of endocytosis and controlled acto-myosin contractility.
Adaptation to nighttime light via gene expression regulation inDrosophila suzukii
Authors: Takenaka Natsumi , Takahashi Yuma 
Published: February 2025

AbstractUrbanization causes environmental changes like habitat loss, fragmentation, and pollution, which reduce biodiversity. Urban organisms face stressors, such as heat islands, air and water pollution, and anthropogenic noise, all of which can disrupt their development, behavior, and physiology. While some species adapt to urban environments, their responses and the role of evolution in urbanization are limited, as most studies focus on phenotypic traits. Artificial light at night (ALAN), a common urban stressor, disrupts behaviors and physiological processes, including circadian rhythms, sleep, and reproduction. The present study examined ALAN’s effects on body size, survival, activity rhythms, and gene expression inDrosophila suzukii, a species found in urban and rural habitats. ALAN reduced wing and thorax sizes regardless of sex and origin, decreased survival in rural populations, and increased it in urban populations. ALAN elevated overall activity, especially in the early night, while urban females displayed reduced sensitivity regarding activity and sleep. The circadian rhythm length was disrupted in rural populations but not in urban populations. Transcriptomic analysis revealed ALAN-induced gene expression changes, particularly in urban females, with photoreceptor- and circadian rhythm-related genes responding differently between urban and rural populations. These results indicate that urban populations have evolved adaptive mechanisms to counter ALAN’s effects, likely mediated through gene regulation. This study highlights ALAN’s impact on diverse traits and its potential for adaptive evolution in urban environments. Evolutionary adaptations in traits related to urban stress responses may enhance the ecological success ofD. suzukiiin urban habitats.
Novel reporter of the PINK1-Parkin mitophagy pathway identifies its damage sensor in the import gate
Authors: Thayer Julia A. , Petersen Jennifer D. , Huang Xiaoping , Hawrot James , Ramos Daniel M. , Sekine Shiori , Li Yan , Ward Michael E. , Narendra Derek P. 
Published: February 2025

SummaryDamaged mitochondria can be cleared from the cell by mitophagy, using a pathway formed by the recessive Parkinson’s disease genes PINK1 and Parkin. How mitochondrial damage is sensed by the PINK1-Parkin pathway, however, remains uncertain. Here, using a Parkin substrate-based reporter in genome-wide screens, we identified that diverse forms of mitochondrial damage converge on loss of mitochondrial membrane potential (MMP) to activate PINK1. Consistently, the MMP but not the presequence translocase-associated motor (PAM) import motor provided the essential driving force for endogenous PINK1 import through the inner membrane translocase TIM23. In the absence of TIM23, PINK1 arrested in the translocase of the outer membrane (TOM) during import. The energy-state outside of the mitochondria further modulated the pathway by controlling the rate of new PINK1 synthesis. Our results identify separation of PINK1 from TOM by the MMP, as the key damage-sensing switch in the PINK1-Parkin mitophagy pathway.HighlightsMFN2-Halo is a quantitative single-cell reporter of PINK1-Parkin activation.Diverse forms of mitochondrial damage, identified in whole-genome screens, activate the PINK1-Parkin pathway by disrupting the mitochondrial membrane potential (MMP).The primary driving force for endogenous PINK1 import through the TIM23 translocase is the MMP with the PAM import motor playing a supporting role.Loss of TIM23 is sufficient to stabilize PINK1 in the TOM complex and activate Parkin.
Cortical substrates of perceptual confusion between pitch and timbre
Authors: Ou Yongtian , Allen Emily J. , Kay Kendrick N. , Oxenham Andrew J. 
Published: February 2025

AbstractPitch and timbre, two fundamental perceptual attributes of sound, are commonly regarded as distinct features, but can be confused when varied simultaneously. Here we combine human behavior and fMRI to demonstrate a neural substrate to explain the well-known perceptual confusion effects. We identify orderly mappings of both pitch and timbral brightness within auditory cortex and reveal two independent lines of evidence for cortical confusion between them. First, voxels’ preferred pitch decreases systematically as brightness increases, and vice versa, consistent with predictions based on perceptual confusion. Second, pitch and brightness mapping share a common high-low-high gradient across auditory cortex, implying a shared trajectory of cortical activation for changes in each dimension. The results provide a cortical substrate at both local and global scales for an established auditory perceptual phenomenon that is thought to reflect efficient coding of ubiquitous features in natural sound statistics.
From policies to programs: exploring the evolving landscape of science and technology in the Philippines
Authors: Custodio Raly James Perez 
Published: February 2025

Purpose
The Philippines has a long history of scientific and technological development from pre-colonial times through Spanish and American rule, marked by periods of both progress and neglect. In response to the growing importance of science and technology (S&T), the country established the National Science Development Board (NSDB) in 1958, which evolved into the Department of Science and Technology (DOST) in 1987. This transition facilitated significant advancements in research and technology through substantial investments. Despite these efforts and progress, challenges such as inadequate infrastructure, limited funding and insufficient human resources continue to hinder the sector’s growth and global competitiveness The purpose of this study is to analyze the evolution of S&T policies in the Philippines, assess innovation and research outputs, and identify key growth areas to provide insights that can guide policymakers in enhancing the country’s global competitiveness

Design/methodology/approach
This review analyzed available literature, government reports, policy documents and data from the Global Innovation Index (GII) and SCImago Journal and Country Ranking (SJR) to trace the evolution of S&T policies in the Philippines, identify growth areas and assess innovation and research outputs, providing insights to guide policymakers in enhancing the country’s global competitiveness.

Findings
The study highlights the challenges that remain in infrastructure, funding and human resources despite significant investments in S&T to enhance global competitiveness. The scarcity of skilled professionals such as scientists, researchers and engineers was particularly concerning, emphasizing the need for increased investment in education and training programs. It also underscored the importance of sustained support, funding and collaborations between government, academia and industry innovation, technological progress and sustainable growth in the global S&T sector.

Originality/value
The review provides a roadmap for advancing the Philippines’ S&T sector, emphasizing the need to overcome ongoing challenges. To fully realize its potential, the country should boost R&D investment, improve science education and strengthen the innovation ecosystem. Collaboration among policymakers, industry leaders and academic institutions is essential to build on past successes and develop a more dynamic and resilient S&T landscape for the future.
University police and mental health response: an exploratory examination of the use of co-responder teams on campus
Authors: Morabito Melissa S. , Sixbey Meggen Tucker , Burke Cameron 
Published: February 2025

PurposeThis study aims to provide foundational information about the nature and extent of calls responded to by a university co-responder team to better understand how these teams are utilized by the university community.Design/methodology/approachWe use data collected from the University of Florida Police Department (UFPD) co-responder program from 2022 to 2024.FindingsWe find that UFPD co-responder teams respond to a diverse population. Use of force and arrests are low frequency events.Originality/valueLittle is known about how campus police agencies adopt co-responder teams and how encounters involving people with mental illnesses are resolved.
Becoming a University President: An Accidental Meritocratic Career Trajectory
Authors: Baruch Yehuda , Nguyen Huong Thi Lan , Point Sébastien , Thomas Lisa 
Published: February 2025

AbstractAchieving top leadership positions is a career goal for many, including those in academia. Despite the increasing size and importance of the higher education sector, the literature on university presidents' careers remains scarce. We interviewed 48 university presidents in three academic models (UK, France, and Vietnam) to identify the ‘why’ and ‘how’ of their career trajectories. Whilst the academic career model reflects characteristics of ‘new careers’, our findings support and expand several career theories. We identified a multi‐stage career trajectory, where progression to the next stage is contingent on meeting certain requirements. It is only from having achieved prior levels that the move to an executive leadership role becomes a consideration. Progress is largely informal, partly ‘accidental’, and sponsored by existing leadership and/or other colleagues. Furthermore, we observed similarities and differences in the enablers and barriers across national systems. Finally, we reveal the almost complete lack of the involvement of human resource management in the process, providing implications for those responsible for people management in universities.
Research progress on the diversity, physiological and functional characteristics of lactic acid bacteria in the Nongxiangxing baijiu microbiome
Authors: Huang Xin , Liu Jie , Luo Huibo , Zou Wei 
Published: February 2025

AbstractNongxiangxing baijiu (NXXB) is one of the main types of Chinese Baijiu. Its unique flavor is formed during fermentation by the combined action of various microorganisms, with lactic acid bacteria (LAB) making a great contribution. Lactate fermentation produces the precursors of key flavor compounds, such as lactic acid, acetic acid, and other flavor compounds, which combine to produce the unique sensory characteristics of NXXB. This review focuses on the diversity of LAB species and their physiological and metabolic characteristics. These characteristics include key species involved at different fermentation stages, metabolite biosynthesis, acid‐tolerance mechanisms, interactions with yeasts, and factors influencing LAB community composition. It also discusses current challenges and future research directions for LAB in relation to NXXB production, aiming to advance understanding and potential future applications of these bacteria.
Lateral Ventricular Enlargement and Asymmetry and Myelin Content Imbalance in Individuals With Bipolar and Depressive Disorders: Clinical and Research Implications
Authors: Manelis Anna , Hu Hang , Miceli Rachel , Satz Skye , Lau Rachel , Iyengar Satish , Swartz Holly A. 
Published: February 2025

ABSTRACTBackgroundThe link between ventricular enlargement and asymmetry with other indices of brain structure remains underexplored in individuals with bipolar (BD) and depressive (DD) disorders. Our study compared the lateral ventricular size, ventricular asymmetry, and cortical myelin content in individuals with BD versus those with DD versus healthy controls (HC).MethodsWe obtained T1w and T2w images from 149 individuals (age = 27.7 (SD = 6.1) years, 78% female, BD = 38, DD = 57, HC = 54) using Magnetic Resonance Imaging (MRI). The BD group consisted of individuals with BD Type I (n = 11) and BD Type II (n = 27), while the DD group consisted of individuals with major depressive disorder (MDD, n = 38) and persistent depressive disorder (PDD, n = 19) Cortical myelin content was calculated using the T1w/T2w ratio. Elastic net regularized regression identified brain regions whose myelin content was associated with ventricular size and asymmetry. A post hoc linear regression examined how participants' diagnosis, illness duration, and current level of depression moderated the relationship between the size and asymmetry of the lateral ventricles and levels of cortical myelin in the selected brain regions.ResultsIndividuals with BD and DD had larger lateral ventricles than HC. Larger ventricles and lower asymmetry were observed in individuals with BD who had longer lifetime illness duration and more severe current depressive symptoms. A greater left asymmetry was observed in participants with DD than in those with BD (p < 0.01). Elastic net revealed that both ventricular enlargement and asymmetry were associated with altered myelin content in cingulate, frontal, and sensorimotor cortices. In BD, but not in other groups, ventricular enlargement was related to altered myelin content in the right insular regions.ConclusionsLateral ventricular enlargement and asymmetry are linked to myelin content imbalance, thus potentially leading to emotional and cognitive dysfunction in mood disorders.
Targeting LncRNA‐Vof16: A Novel Therapeutic Strategy for Neuropathic Pain Relief
Authors: He Xiuying , Mauki David H. , Zhao Xiaoming , Dai Songyu , Yang Huisi , Zheng Yuexiang , Xia Qingjie , Wang Rurong , Wang Tinghua 
Published: February 2025

ABSTRACTAimsNeuropathic pain (NP) is a debilitating condition characterized by chronic pain resulting from nerve damage or lesion. Despite the ongoing efforts of clinically defining NP, its distinctive mechanisms that lead to various NP phenotypes remain unresolved.MethodsUsing a spared nerve injury (SNI) model, we investigated the mechanisms underlying the development of NP caused by injury in the peripheral nerves. With CRISPR‐Cas9‐mediated knockout and virus‐mediated overexpression strategies, we investigated the role of LncRNA Vof16 (abbreviated as Vof16) during SNI‐induced NP.ResultsOur results revealed that SNI led to the downregulation of Vof16 expression in spinal dorsal horn (SDH) of lumbar enlargement. This was evidently confirmed when we disrupted the expression of Vof16 in SNI rats of which we observed exacerbation of hyperalgesia; while overexpressing it alleviated the pain.ConclusionOur findings suggest that Vof16 plays a crucial role in maintaining normal sensory function in healthy states and a protective shield against NP following peripheral nerve injury. We therefore propose Vof16 as a new therapeutic target for alleviating NP.