bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic actin network assembly on lipid bilayer uncovers the network density-dependent functions of actin-binding proteins
Authors: Yamamoto Kei , Miyazaki Makito 
Published: December 2024

AbstractThe actin cytoskeleton forms a mesh-like network that drives cellular deformations. The network property is defined by the network density and the species of the actin-binding proteins. However, the relationship between the actin network density, the penetration ability of actin-binding proteins into the network, and resulting network dynamics remains elusive. Here, we report anin vitrooptogenetic system, named OptoVCA, which induces Arp2/3-mediated actin network assembly on a lipid membrane. By changing the illumination power, duration, and pattern, the OptoVCA flexibly manipulates the density, thickness, and shape of the actin network. Taking these advantages, we examine the effects of the network density on the two representative actin-binding proteins, myosin and ADF/cofilin. We find that the penetration of myosin filaments into the network is strictly inhibited by only a several-fold increase in network density due to the steric hindrance. Furthermore, penetrated myosin filaments induce directional actin flow when the network has a density gradient. On the other hand, ADF/cofilin penetrates into the network regardless of network density, however, network disassembly is dramatically inhibited by only a several-fold increase in network density. Thus, the OptoVCA contributes to understanding cell mechanics through the examination of the network density-dependent effect on the actin-binding proteins.
Osteoporosis with different causation exhibits different changes in bone tissue mineral and organic matrix
Authors: Lin Jing-Yu , Guo Xu , Sun Ming-Hui , Zhang Yifeng , Lu Jun-Xia 
Published: December 2024

AbstractOsteoporosis (OP) which is a common skeletal disease with different causation is prevalent in aging population. Postmenopause women generally suffer from OP with bone loss due to estrogen deficiency. Diabetes are also associated with OP by complex metabolic mechanisms. Bone qualities of OP caused by aging were compared with the ovariectomy (OVX) model and the Type 2 diabetic model using Sprague-Dawley (SD) rats in our study. Combining with micro-computed tomography (μ-CT) and solid-state NMR (SSNMR) methods, this research studied bone changes in SD rats from tissue level to the molecular level. The studies revealed bone loss was most significant for cancellous bones, but not for cortical bones in OP rats. However, at the molecular level, the content of HAP in cortical bone increased with aging, contributing to the brittleness of the bone. Triglyceride, as a senescence maker of osteocyte in cortical bone, was also identified to be closely associated with OP in aging and OVX rats, but not in diabetic rats. This research suggests differing bone qualities in molecular level of OP with various causes more objectively reflect the bone tissue reconstruction rather than bone loss inμ-CT analysis.
Mechanistic studies of PFKFB2 reveals a novel inhibitor of its kinase activity
Authors: Eyster Craig , Matsuzaki Satoshi , Pranay Atul , Giorgione Jennifer R. , Faakye Anna , Ahmed Mostafa , Humphries Kenneth M. 
Published: December 2024

ABSTRACTThe 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) family of proteins are bifunctional enzymes that are of clinical relevance because of their roles in regulating glycolysis in insulin sensitive tissues and cancer. Here, we sought to express recombinant PFKFB2 and develop a robust protocol to measure its kinase activity. These studies resulted in the unexpected finding that bacterially expressed PFKFB2 is phosphorylatedin situon Ser483 but is not a result of autophosphorylation. Recombinant PFKFB2 was used to develop an enzymatic assay to test a library of molecules selected by the Atomwise AtomNet® AI platform. This resulted in the identification of a new inhibitor, B2, that inhibits PFKFB2 (IC503.29 μM) and PFKFB3 (IC5011.89 μM). A-498 cells, which express both PFKFB2 and PFKFB3, were treated with B2. Seahorse XFe analysis revealed B2 inhibited cellular glycolysis and glycolytic capacity. Targeted LC/MS analysis showed B2 decreased fructose-1,6-bisphosphate and downstream glycolytic intermediates but increased fructose-6-phosphate levels, which is consistent with an inhibitory effect on PFK-1 activity. The LC/MS metabolic profile of A-498 cells treated under identical conditions with the known PFKFB3 inhibitor, PFK158, was distinct from that induced by B2. These results thus demonstrate the identification and validation of a new PFKFB kinase inhibitor.
Contribution of glutamatergic projections to neurons in the nonhuman primate lateral substantia nigra pars reticulata for the reactive inhibition
Authors: Yoshida Atsushi , Hikosaka Okihide 
Published: December 2024

AbstractThe basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, most likely from the subthalamic nucleus, drive the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinson’s disease.Significance StatementUnderstanding how the basal ganglia facilitate desired actions while suppressing unwanted ones is fundamental to neuroscience. This study shows that neurons in the primate substantia nigra pars reticulata (SNr) bidirectionally modulate activity to control action, decreasing firing rates to facilitate movements and increasing rates to suppress them. Importantly, we provide causal evidence that glutamatergic inputs to the lateral SNr mediate action suppression. These findings reveal a conserved mechanism of action control in primates and highlight the role of excitatory inputs in behavioral inhibition. This advances our understanding of basal ganglia function and has significant implications for treating movement disorders like Parkinson’s disease.
XhetRel: A Pipeline for X Heterozygosity and Relatedness Analysis in Sequencing Data
Authors: Salman Barış , Bebek Nerses , Uğur İşeri Sibel 
Published: December 2024

AbstractMotivationChecking sample sex is one of the preliminary controls performed in genetic studies. Comparing multiple individuals and families in terms of sex and relatedness allows us to eliminate systematic errors in downstream analyses. While developing the pipeline we further delved into the origins of X heterozygosity by analysing the chromosome X variants from the 1000 Genomes Project.ResultWe created an accessible and user-friendly notebook application for X heterozygosity analysis. XhetRel can serve as an initial quality control step in sequencing projects.Further investigating the source of X heterozygosity reveals the limitations of sequencing and variant calling methods in heterozygosity analysis. Our findings point to specific pseudogenes and gene clusters, such asSLC25A5andGAGEcluster, as key contributors to erroneous variant allele fractions.Availability and implementationSource code is availablehttps://github.com/barslmn/XhetRel.Collab notebook can be accessed athttps://colab.research.google.com/drive/1ep69JvXLwK5ndHUQ8qIGTWvauzsTW9fi.
Seroprevalence and cross-reactivity of neutralizing antibodies to six types of adenoviruses
Authors: Zubkova O.V. , Ozharovskaia T.A. , Popova O. , Vavilova I.V. , Zrelkin D.I. , Goldovskaya P.P. , Voronina D.V. , Dolzhikova I.V. , Grousova D.M. , Shcheblyakov D.V. , Logunov D.Y. , Gintsburg A.L. 
Published: December 2024

AbstractBackgroundThe use of adenoviral vector vaccines is an effective way to induce an antiviral immune response. Most vaccines used worldwide are based on human adenovirus type 5 (Ad5). Pre-existing natural immunity to Ad5 is a limitation to the frequent use of Ad5-based vectors in gene therapy and vaccination. In the present study, we assessed the seroprevalence and cross-reactivity of neutralizing antibodies to six adenovirus types: Ad1, Ad2, Ad5, Ad19, Ad26, and Ad37.MethodsThe study used immunological and virological research methods. Adenovirus vectors encoding the enhanced green fluorescent protein (EGFP) were developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology. For seroprevalence and cross-neutralation study we used a panel of sera from 101 volunteers.ResultsThe conducted correlation analysis showed a strong relationship between seropositivity and the geometric mean titer of neutralizing antibodies to adenovirus. An increase in antibody titers indicates the formation of a humoral immune response and population immunity. We determined that there is no cross-reactivity between NtAbs to Ad1, Ad2, Ad5 and Ad26.ConclusionsBased on the presented data, we assume that Ad1 or Ad2 should be considered the most promising alternative candidates for the development of vaccine vectors.
How suitable are clustering methods for functional annotation of proteins?
Authors: Busi Rakesh , Machingal Pranav , Hemachandra Nandyala , Balaji Petety V. 
Published: December 2024

AbstractThe advent of affordable high-throughput genome sequencing has drastically expanded protein sequence databases, necessitating the development of computational tools to predict protein function from sequence data. Current methods, such as BLASTp and profile HMMs, while effective, are limited by difficulties in detecting remote homologs and uncertainties in multiple sequence alignments. To address this, we explore the use of clustering algorithms for unsupervised protein function annotation, using pseudo-amino acid composition (PAAC) as features.In this study, we evaluated nine clustering algorithms for their ability to segregate protein sequences based on functional differences using the PAAC feature. Using intrinsic metrics, particularly the silhouette coefficient (SC), we determined the optimal number of clusters (k) for each algorithm. We observed that agglomerative clustering produced results resembling phylogenetic relationships; even k-means clustering, Gaussian mixture model(GMM), and spectral clustering do so but occasionally merge datapoints from distinct original clusters at higherkvalues.Our findings reveal that k-means clustering, GMM, and agglomerative clustering effectively segregate distinct protein functional families, but effectiveness decreases when distinguishing fine-grained functional differences. Notably, spectral clustering underperformed relative to other methods. Affinity propagation clustering, while effective in some cases, generated more clusters than expected and is prone to false positives. Overall, we find that some of the clustering algorithms are suitable for functional annotation of protein sequences using PAAC as a feature set, even when the number of ground-truth sequences is limited.The implementation of the clustering method for protein sequences is available in the GitHub repository linked below. It provides comprehensive steps for preprocessing, feature extraction, clustering, and evaluation. All results are presented in a Jupyter Notebook.https://github.com/RakeshBusi/Clustering
Transcontinental patterns in floral pigment frequencies among animal-pollinated species
Authors: Narbona Eduardo , Del Valle Jose C. , Whittall Justen B. , León-Osper Melissa , Buide M. Luisa , Pulgar Iñigo , Camargo Maria Gabriela Gutierrez , Morellato Leonor Patricia Cerdeira , Rodríguez-Castañeda Nancy , Rossi Victor , Conrad Katie , Hernandez-Mena Joey , Ortiz Pedro L. , Arista Montserrat 
Published: December 2024

AbstractFlower coloration arises primarily from pigments that serve dual functions: attracting pollinators and mitigating environmental stresses. Among major flower pigment groups, anthocyanins and UV-absorbing phenylpropanoids are particularly notable for fulfilling both roles. Their importance suggests that both pigment types should be widespread in flowers. Here, we analyze the UV-Vis absorption profiles of major floral pigments to assess their potential protective role against UV radiation and demonstrate that this protection is largely confined to UV-absorbing phenylpropanoids. We also analyzed the floral pigment composition of 926 animal-pollinated species from California, southern Spain, and southeastern Brazil. UV-absorbing phenylpropanoids were ubiquitous, while anthocyanins occurred in ∼56% of species, carotenoids in ∼37%, and chlorophylls in ∼17%. Pigment frequencies varied with abiotic and biotic factors, such as light environment in Spain, and pollinator type, such as insect versus hummingbird, in California. Despite these local differences, our findings reveal a consistent regional distribution of floral pigments.
“Comparative analysis of red blood cell under real and simulated microgravity conditions”
Authors: Hinge Sarika , Dixit Jyotsana , Vidyasagar Pandit , Kulkarni Gauri 
Published: December 2024

AbstractRed blood cell is an important role model of microcirculation, gas exchange, drug carrier, and related diseases. There has been an increasing interest in understanding the biochemical and structural changes in Red blood cells (RBC) due to simulated microgravity conditions. In the present work, isolated human red blood cells were exposed to simulated microgravity (SMG) conditions using 2D clinostat. Comparative analysis of normal RBC and RBC in simulated microgravity conditions was performed using UV-visible spectroscopy, FTIR spectroscopy, and single-beam optical tweezer. The change in position of the Soret band absorption peak is observed after the exposure to simulated microgravity. However, biochemical functional groups of RBCs were studied using FTIR spectroscopy with a change in % Transmittance. Power spectrum density (PSD) variations in optically trapped control and SMG exposed single RBC are obtained from position signals acquired by Thorlabs’s OTKBFM-CAL data acquisition software. Microgravity (SMG)-induced stress is responsible for a reduction in haematocrit, haemolysis, change in the morphology, and rigidity of red blood cells. These investigation of the physicochemical properties of RBC in simulated microgravity is useful for improving the health of astronauts during space missions.
Critical look at the cosmological neutrino mass bound
Authors: Naredo-Tuero Daniel , Escudero Miguel , Enrique Fernandez-Martinez  , Marcano Xabier , Poulin Vivian 
Published: December 2024

Cosmological neutrino mass bounds are becoming increasingly stringent. The latest limit within ΛCDM from Planck 2018+ACT lensing+DESI is ∑mν<0.072  eV at 95% CL, very close to the minimum possible sum of neutrino masses (∑mν>0.06  eV), hinting at vanishing or even “negative” cosmological neutrino masses. In this context, it is urgent to carefully evaluate the origin of these cosmological constraints. In this paper, we investigate the robustness of these results in three ways: (i) we check the role of potential anomalies in Planck CMB and DESI BAO data; (ii) we compare the results for frequentist and Bayesian techniques, as very close to physical boundaries subtleties in the derivation and interpretation of constraints can arise; (iii) we investigate how deviations from ΛCDM, potentially alleviating these anomalies, can alter the constraints. From a profile likelihood analysis, we derive constraints in agreement at the ∼10% level with Bayesian posteriors. We find that the weak preference for negative neutrino masses is mostly present for Planck 18 data, affected by the well-known “lensing anomaly.” It disappears when the new Planck 2020 HiLLiPoP is used, leading to significantly weaker constraints. Additionally, the pull toward negative masses in DESI data stems from the z=0.7 bin, which contains a BAO measurement in ∼3σ tension with Planck expectations. Without this bin, and in combination with HiLLiPoP, the bound relaxes to ∑mν<0.11  eV at 95% CL. The recent preference for dynamical dark energy alleviates this tension and further weakens the bound. As we are at the dawn of a neutrino mass discovery from cosmology, it will be very exciting to see if this trend is confirmed by future data.

Published by the American Physical Society
2024
W
-boson exotic decay into three charged leptons at the LHC
Authors: Fei Yifan , Li Peiran , Liu Zhen , Lyu Kun-Feng , Pospelov Maxim 
Published: December 2024

We investigate the W boson’s exotic decay channel, W→ℓℓℓν, at the LHC. Although the four-body final states suppress the decay branching ratio, the large production of W bosons makes detecting and precisely measuring this decay probability entirely feasible. Our simulation study indicates that this tiny branching ratio can be measured with subpercent precision at the HL-LHC. This decay channel can also constrain Standard Model extensions. Using the Lμ−Lτ model as a benchmark, we find that the current bound on the gauge coupling for Z′ mass in the range of [4, 75] GeV can significantly improve.

Published by the American Physical Society
2024
Strong Limits on keV-Scale Galactic Sterile Neutrino Dark Matter with Stray Light from
NuSTAR
after 11 Years of Operation
Authors: Krivonos R. A. , Barinov V. V. , Mukhin A. A. , Gorbunov D. S. 
Published: December 2024

Using tremendous photon statistics gained with the stray light aperture of the telescope over 11 years of operation, we set strong limits on the emission of close to monochromatic photons from the radiative decays of putative dark matter sterile neutrinos in the Milky Way. In the energy range of 3–20 keV covered by the , the obtained limits reach the bottom edge of theoretical predictions of realistic models where sterile neutrinos are produced in the early Universe. Only a small region is left to explore, if the sterile neutrinos form the entire dark matter component.

Published by the American Physical Society
2024
Useful or not? A review filtering system based on hybrid methods
Authors: Kim Jiho , Jang Youngjun , Seo Wongyeom , Lee Hongchul 
Published: December 2024

PurposeInformation filtering systems serve as robust tools in the ongoing difficulties associated with overwhelming volumes of data. With constant generation and accumulation of reviews in online communities, the ability to distill and provide valuable insights to assist customers in their search for relevant information is of considerable significance. This study devised an effective review filtering system for a popular online physical experience review site.Design/methodology/approachThis study entailed an investigation of a hybrid approach for a review filtering system augmented with various text mining-based operational variables to extract the linguistic signals of online reviews. Moreover, we devised three ensemble models based on multiple machine learning and deep learning algorithms to build a high-performance review filtering system.FindingsThe main findings confirm the effectiveness of using the derived operational variables when reviewing filtering systems. We found that the reviewer’s tendency and history macros, as well as the readability and sentiment of the reviews, contribute significantly to the filtering performance. Furthermore, the proposed three ensemble frameworks demonstrated good efficiency with an average accuracy of 89.39%.Originality/valueThis study provides a methodological blueprint for operationalizing variables in online reviews, covering both structured and unstructured datasets. Incorporating different variables enhances the efficiency of the algorithm and provides a more comprehensive understanding of user-generated content. Furthermore, the study affords a strategic perspective and integrated guidelines for developers seeking to create advanced review filtering systems.
Unequally prepared: a distributive equity study of local emergency management funding in Virginia, USA
Authors: Louis-Charles Hans , Derakhshan Sahar , Kalokoh Amidu , Brown Curtis , Starke Anthony 
Published: December 2024

PurposeRecent US federal executive orders have prioritized equity within the federal government, and the Federal Emergency Management Agency (FEMA) has declared equity as a foundational pillar in their 2022–2026 Strategic Plan. This research study investigates the distributive equity of the most locally disseminated FEMA grant, the Emergency Management Performance Grant (EMPG).Design/methodology/approachThe Commonwealth of Virginia was selected for our research study due to its exposure to natural hazards, recent disaster losses, variance among local emergency management programs, and high-profile political disputes against diversity, equity and inclusion (DEI) initiatives. EMPG data from 2020 to 2023 were analyzed for correlations with social vulnerability (SoVI®), community resilience (BRIC), previous disaster losses (SHELDUS), and the National Risk Index (NRI). A difference of means test was conducted on the jurisdictions that opted out of participation in the EMPG.FindingsVirginia’s current EMPG funding is allocated disproportionately to wealthier local jurisdictions with lower social vulnerability, higher community resilience, and lower previous disaster losses. Jurisdictions that opted-out or received the minimum amounts had a disproportionately higher amount of total disaster losses.Originality/valueThis study provides a novel approach to evaluating the equity of public funding dedicated to local disaster preparedness. The findings are instructive to federal lawmakers, state governments and global initiatives in climate resilience with a similar allocation process focused solely on population sizes. The framework of this research study is easily replicable, and the metrics are publicly available for future researchers.