bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown-resistance (kdr) mutations in IndianAedes aegyptipopulations: lack of recombination among haplotypes bearing V1016G, F1534C, and F1534Lkdralleles
Authors: Kaur Taranjeet , Kushwah Rajababu S. , Pradhan Sabyasachi , Das Manoj K. , Kona Madhavinadha P , Anushrita  , Weetman David , Dixit Rajnikant , Singh Om P. 
Published: December 2024

AbstractBackgroundKnockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene are a key mechanism of insecticide resistance in mosquitoes. In AsianAedes aegyptipopulations two main VGSC haplogroups withkdrmutations have been identified: one carrying the F1534C mutation and another with V1016G and/or S989P mutations. Functional studies have demonstrated that these three mutations on a single haplotype confer up to a 1100-fold increase in pyrethroid resistance, underscoring the need to monitor these triple mutations within distinct populations. This study investigates the prevalence ofkdrmutations in Indian populations and explores the linkage association between these mutations and two distinct conserved types of introns located between exons 20 and 21.MethodsAe. aegyptispecimens collected from eight different locations were genotyped forkdralleles and intron (between exons 20 and 21) haplotypes using PCR-based assays. Representative samples underwent DNA sequencing of VGSC regions.ResultsFivekdrmutations namely S989P, V1016G, T1520I, F1534C, and F1534L, were identified, each exhibiting varying distribution and frequencies across different geographical regions. Two distinct and stably-diverged intron haplotypes, designated as intron-A and intron-B, were identified between exons 20 and 21. Seven haplotypes, including two wild-type variants, were observed among Indian populations. Thekdr-bearing haplotypes can be classified into three distinct haplogroups: haplogroup G (V1016G with/or without S989P and with intron-A), haplogroup L (F1534L and intron-A), and haplogroup C (F1534C with/or without T1520I and with intron-B). Importantly, no evidence of recombination within Indian populations was detected among these three haplogroups.ConclusionsFivekdrmutations were identified in the VGSC of IndianAe. aegyptipopulations, each showing a definitive linkage with one of the two types of intron haplotypes. The lack of recombination among haplogroups bearing 1016G with 989P, 1534C and 1534L mutations suggests that the most potent insecticide resistance haplotype, bearing the triplekdrmutation, is currently absent. This finding has significant operational implications, as it may indicate that current vector control measures remain effective against these populations, potentially delaying the emergence of highly resistant phenotypes
Cell types associated with human brain functional connectomes and their implications in psychiatric diseases
Authors: Nie Pengxing , Zhan Yafeng , Chen Renrui , Qi Ruicheng , Liu Cirong , Wang Guang-Zhong 
Published: December 2024

AbstractCell types are fundamental to the functional organization of the human brain, yet the specific cell clusters contributing to functional connectomes remain unclear. Using human whole-brain single-cell RNA sequencing data, we investigated the relationship between cortical cell cluster distribution and functional connectomes. Our analysis identified dozens of cell clusters significantly associated with resting-state network connectivity, with excitatory neurons predominantly driving positive correlations and inhibitory neurons driving negative correlations. Many of these cell clusters are also conserved in macaques. Notably, functional network connectivity is predicted by cellular communication among these clusters. We further identified cell clusters linked to various neuropsychiatric disorders, with several clusters implicated in multiple conditions. Comparative analysis of schizophrenia and autism spectrum disorder revealed distinct expression patterns, highlighting disease-specific cellular mechanisms. These findings underscore the critical role of specific cell clusters in shaping functional connectomes and their implications for neuropsychiatric diseases.
Did Energy Costs of Walking Limit the Evolution of a Larger Human Birth Canal?
Authors: Stansfield Ekaterina , Egner Clara , Mitteroecker Philipp , Kainz Hans 
Published: December 2024

AbstractEnergetic disadvantages of a wider pelvis have long been central to explanations of the small human birth canal and the relatively risky birth process, iconic for antagonistic selection in evolution. While static mechanics predict such effects, recent empirical studies question this view. By altering a generic musculoskeletal model beyond modern human variation one parameter at a time and applying predictive forward modelling of human gait, we examined how body dimensions impact locomotion efficiency and inferred selective pressures on past morphologies. Our findings confirm that a wider pelvis increases abductor muscle demands, as lever mechanics suggest. However, dynamic walking compensates via other muscles, minimizing the total transport cost. Moreover, slightly longer legs easily offset the modest energetic costs of a larger birth canal. We propose that other factors, such as pelvic floor stability, likely constrained the evolution of the human birth canal, rather than energetic disadvantages alone.
Rapid Surge of Reassortant A(H1N1) Influenza Viruses in Danish Swine and their Zoonotic Potential
Authors: Ryt-Hansen Pia , George Sophie , Hjulsager Charlotte Kristiane , Trebbien Ramona , Krog Jesper Schak , Ciucani Marta Maria , Langerhuus Sine Nygaard , DeBeauchamp Jennifer , Crumpton Jeri Carol , Hibler Taylor , Webby Richard J. , Larsen Lars Erik 
Published: December 2024

AbstractIn 2018, a single detection of a novel reassortant swine influenza A virus (swIAV) was made in Denmark. The hemagglutinin (HA) of the virus was from the H1N1 pandemic 2009 (H1N1pdm09) lineage and the neuraminidase (NA) from the H1N1 Eurasian avian-like swine lineage (H1N1av). By 2022, the novel reassortant virus (H1pdm09N1av) constituted 27 % of swIAVs identified through the Danish passive swIAV surveillance program. Sequencing detected two H1pdm09N1av genotypes; Genotype 1 contained an internal gene cassette of H1N1pdm09 origin, Genotype 2 differed by carrying an NS gene segment of H1N1av origin. The internal gene cassette of Genotype 2 became increasingly dominant, not only in the H1pdm09N1av population, but also in other Danish enzootic swIAV subtypes. Phylogenetic analysis of the HA genes from H1pdm09N1av viruses revealed a monophyletic source, a higher substitution rate compared to other H1N1pdm09 viruses and genetic differences with human seasonal and other swine adapted H1N1pdm09 viruses. Correspondingly, H1pdm09N1av viruses were antigenically distinct from human H1N1pdm09 vaccine viruses. Both H1pdm09N1av genotypes transmitted between ferrets by direct contact, but only Genotype 1 was capable of efficient aerosol transmission. The rapid spread of H1pdm09N1av viruses in Danish swine herds is concerning for swine and human health. Their zoonotic threat is highlighted by the limited pre-existing immunity observed in the human population, aerosol transmission in ferrets and the finding that the internal gene cassette of Genotype 2 was present in the first two zoonotic infections ever detected in Denmark.
Calmodulin binding is required for calcium mediated TRPA1 desensitization
Authors: Sanders Justin H. , Taiwo Kehinde M. , Adekanye Glory A. , Bali Avnika , Zhang Yuekang , Paulsen Candice E. 
Published: December 2024

AbstractCalcium (Ca2+) ions affect nearly all aspects of biology. Excessive Ca2+entry is cytotoxic and Ca2+- mobilizing receptors have evolved diverse mechanisms for tight regulation that often include Calmodulin (CaM). TRPA1, an essential Ca2+-permeable ion channel involved in pain signaling and inflammation, exhibits complex Ca2+regulation with initial channel potentiation followed by rapid desensitization. The molecular mechanisms of TRPA1 Ca2+regulation and whether CaM plays a role remain elusive. We find that TRPA1 binds CaM best at basal Ca2+concentration, that they co-localize in resting cells, and that CaM suppresses TRPA1 activity. Combining biochemical, biophysical, modeling, NMR spectroscopy, and functional approaches, we identify an evolutionarily conserved, high-affinity CaM binding element in the distal TRPA1 C-terminus (DCTCaMBE). Genetic or biochemical perturbation of Ca2+/CaM binding to the TRPA1 DCTCaMBE yields hyperactive channels that exhibit drastic slowing of desensitization with no effect on potentiation. Ca2+/CaM TRPA1 regulation does not require the N-lobe, raising the possibility that CaM is not the Ca2+sensor,per se. Higher extracellular Ca2+can partially rescue slowed desensitization suggesting Ca2+/CaM binding to the TRPA1 DCTCaMBE primes an intrinsic TRPA1 Ca2+binding site that, upon binding Ca2+, triggers rapid desensitization. Collectively, our results identify a critical regulatory element in an unstructured TRPA1 region highlighting the importance of these domains, they reveal Ca2+/CaM is an essential TRPA1 auxiliary subunit required for rapid desensitization that establishes proper channel function with implications for all future TRPA1 work, and they uncover a mechanism for receptor regulation by Ca2+/CaM that expands the scope of CaM biology.
Effects of prey abundance and foliage structure in plant selection by insectivorous birds in the central Monte desert
Authors: Guerra-Navarro Carolina , Cueto Victor R. 
Published: December 2024

AbstractForaging behavior allows a direct examination of how birds use their habitats and provides the possibility to understand what environment factors can determine those patterns. We analyzed the woody plant selection, height and substrate use, and attack maneuver by Greater Wagtail-tyrant (Stigmatura budytoides), Grey-crowned Tyrannulet (Serpophaga griseicapilla) and Ringed Warbling-Finch (Microspingus torquata) in the main habitats of central Monte desert. The three bird species selectedProsopis flexuosatrees and avoided the most abundant shrub species:Larrea divaricataandLarrea cuneifoliain mesquite woodland and creosotebush habitats. The importance ofP. flexuosawas due because this plant constitute an abundant food patch of great diversity of arthropods. Our results about how bird species use their habitat and which factors were influencing these selection pattern are important to management and conservation of insectivorous birds in the central Monte desert.
Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines
Authors: Bangaru Sandhya , Jackson Abigail M. , Copps Jeffrey , Fernández-Quintero Monica L. , Torres Jonathan L. , Richey Sara T. , Nogal Bartek , Sewall Leigh M. , Torrents de la Peña Alba , Rehman Asma , Guebre-Xabier Mimi , Girard Bethany , Das Rituparna , Corbett-Helaire Kizzmekia S. , Seder Robert A. , Graham Barney S. , Edwards Darin K. , Patel Nita , Smith Gale , Ward Andrew B. 
Published: December 2024

SummaryCurrent COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors. Both vaccines induce diverse polyclonal antibody (pAb) responses to the N-terminal domain (NTD) in addition to the receptor-binding domain (RBD) of the Spike protein, with the NTD supersite being an immunodominant epitope. High-resolution cryo-EMPEM studies revealed extensive pAb responses to and around the supersite with unique angles of approach and engagement. NTD supersite pAbs were also the most susceptible to variant mutations compared to other specificities, indicating that ongoing Spike ectodomain-based vaccine design strategies should consider immuno-masking this site to prevent induction of these strain-specific responses.
Regulatory interactions between APOBEC3B N- and C-terminal domains
Authors: Braza Mac Kevin E. , Demir Özlem , Ahn Surl-Hee , Morris Clare K. , Calvó-Tusell Carla , McGuire Kelly L. , de la Peña Avalos Bárbara , Carpenter Michael A. , Chen Yanjun , Casalino Lorenzo , Aihara Hideki , Herzik Mark A. , Harris Reuben S. , Amaro Rommie E. 
Published: December 2024

AbstractAPOBEC3B (A3B) is implicated in DNA mutations that facilitate tumor evolution. Although structures of its individual N- and C-terminal domains (NTD and CTD) have been resolved through X-ray crystallography, the full-length A3B (fl-A3B) structure remains elusive, limiting understanding of its dynamics and mechanisms. In particular, the APOBEC3B C-terminal domain (A3Bctd) active site is frequently closed in models and structures. In this study, we built several new models of fl-A3B using integrative structural biology methods and selected a top model for further dynamical investigation. We compared dynamics of the truncated (A3Bctd) to the fl-A3B via conventional and Gaussian accelerated molecular dynamics (MD) simulations. Subsequently, we employed weighted ensemble methods to explore the fl-A3B active site opening mechanism, finding that interactions at the NTD-CTD interface enhance the opening frequency of the fl-A3B active site. Our findings shed light on the structural dynamics of fl-A3B, which may offer new avenues for therapeutic intervention in cancer.
Survivin modulates stiffness-induced vascular smooth muscle cell motility
Authors: Mousso Thomas , Rice Kalina , Tumenbayar Bat-Ider , Pham Khanh , Heo Yuna , Heo Su Chin , Lee Kwonmoo , Lombardo Andrew T , Bae Yongho 
Published: December 2024

ABSTRACTArterial stiffness is a key contributor to cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease, it has been characterized to be associated with the aberrant migration of vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms driving VSMC migration in stiff environments remain incompletely understood. We recently demonstrated that survivin, a member of the inhibitor of apoptosis protein family, is highly expressed in both mouse and human VSMCs cultured on stiff polyacrylamide hydrogels, where it modulates stiffness-mediated cell cycle progression and proliferation. However, its role in stiffness-dependent VSMC migration remains unknown. To assess its impact on migration, we performed time-lapse video microscopy on VSMCs seeded on fibronectin-coated soft and stiff polyacrylamide hydrogels, mimicking the physiological stiffness of normal and diseased arteries, with either survivin inhibition or overexpression. We observed that VSMC motility increased under stiff conditions, while pharmacologic or siRNA-mediated inhibition of survivin reduced stiffness-stimulated migration to rates similar to those observed under soft conditions. Further investigation revealed that cells on stiff hydrogels exhibited greater directional movement and robust lamellipodial protrusion compared to those on soft hydrogels. Interestingly, survivin-inhibited cells on stiff hydrogels showed reduced directional persistence and lamellipodial protrusion compared to control cells. We also examined whether survivin overexpression alone is sufficient to induce cell migration on soft hydrogels, and found that survivin overexpression modestly increased cell motility and partially rescued the lack of directional persistence compared to GFP-expressing control VSMCs on soft hydrogels. In conclusion, our findings demonstrate that survivin plays a key role in regulating stiffness-induced VSMC migration, suggesting that targeting survivin and its signaling pathways could offer therapeutic strategies for addressing arterial stiffness in cardiovascular diseases.
Long-read genomics reveal extensive nuclear-specific evolution and allele-specific expression in a dikaryotic fungus
Authors: Tam Rita , Möller Mareike , Luo Runpeng , Luo Zhenyan , Jones Ashley , Periyannan Sambasivam , Rathjen John P. , Schwessinger Benjamin 
Published: December 2024

AbstractPhased telomere to telomere (T2T) genome assemblies are revolutionising our understanding of long hidden genome biology “dark matter” such as centromeres, rDNA repeats, inter-haplotype variation, and allele specific expression (ASE). Yet insights into dikaryotic fungi that separate their haploid genomes into distinct nuclei is limited. Here we explore the impact of dikaryotism on the genome biology of a long-term asexual clone of the wheat pathogenic fungusPuccinia striiformisf. sp.tritici. We use Oxford Nanopore (ONT) duplex sequencing combined with Hi-C to generate a T2T nuclear-phased assembly with >99.999% consensus accuracy. We show that this fungus has large regional centromeres enriched in LTR retrotransposons, with a single centromeric dip in methylation that suggests one kinetochore attachment site per chromosomes. The centromeres of chromosomes pairs are most often highly diverse in sequence and kinetochore attachment sites are not always positionally conserved. Each nucleus carries a unique array of rDNAs with >200 copies that harbour nucleus-specific sequence variations. The inter-haplotype diversity between the two nuclear genomes is caused by large-scale structural variations linked to transposable elements. Nanopore long-read cDNA analysis across distinct infection conditions revealed pervasive allele specific expression for nearly 20% of all heterozygous gene pairs. Genes involved in plant infection were significantly enriched in ASE genes which appears to be mediated by elevated CpG gene body methylation of the lower expressed pair. This suggests that epigenetically regulated ASE is likely a previously overlooked mechanism facilitating plant infection. Overall, our study reveals how dikaryotism uniquely shapes key eukaryotic genome features.
NFAT2 drives both Orai3 transcription and protein degradation by harnessing the differences in epigenetic landscape
Authors: Raju Sharon , Sharma Akshay , Ranjan Gyan , Motiani Rajender K 
Published: December 2024

AbstractThe functional significance of any protein in physiological processes and pathological conditions is largely dependent on its expression profile. Therefore, nature has evolved several autonomous mechanisms to regulate protein expression such as transcription, translation, post-translational modifications and epigenetic changes. These processes are typically controlled by distinct molecular players with no overlapping roles. Here, we reveal that same transcription factor, NFAT2 regulates both transcription and lysosomal degradation of Orai3 oncochannel in a context dependent manner. We demonstrate that NFAT2 drives Orai3 transcription and thereby increases Orai3 levels in non-metastatic cancerous cells. While in invasive and metastatic cancerous cells, NFAT2 induces Orai3 lysosomal degradation by transcriptionally enhancing the levels of MARCH8 E3 ubiquitin ligase. Our biochemical and super-resolution microscopy data show that MARCH8 physically interacts with Orai3 eventually resulting in its degradation. Mechanistically, the dichotomy in regulation of Orai3 expression emerges from the differences in the epigenetic landscape of MARCH8. We uncover that the MARCH8 promoter is highly methylated in non-metastatic cancerous cells and hence NFAT2 does not induce MARCH8 mediated Orai3 degradation in these cells. Importantly, we demonstrate that MARCH8 restricts pancreatic cancer metastasis by targeting Orai3 degradation thereby highlighting pathophysiological importance of this signaling module. Taken together, we report a unique and clinically relevant scenario wherein nature has commissioned the same transcription factor to both enhance and curtail the expression of a target protein.Highlights➢ NFAT2 transcriptionally upregulates Orai3 Ca2+channel in non-metastatic cells➢ NFAT2 induces Orai3 lysosomal degradation via MARCH8 E3 ubiquitin ligase in metastatic cells➢ The dichotomy in NFAT2’s function is an outcome of differences in the methylation status of MARCH8 promoter➢ MARCH8 inhibits pancreatic cancer metastasis by driving Orai3 degradationGraphical Abstract
Effect of peer-group participation on Knowledge about condoms among adolescent girls in rural Eastern Ethiopia: a community-based repeated cross-sectional study
Authors: Fasil Nebiyou , Worku Alemayehu , Oljira Lemessa , Tadesse Amare Worku , Berhane Yemane 
Published: December 2024

AbstractAdolescent girls are at high risk of acquiring sexually transmitted infections (STIs), including the human immunodeficiency virus (HIV). Global evidence indicates significance of comprehensive sexual education in empowering adolescents with accurate knowledge regarding safe sexual practices. Adolescents living in rural areas, particularly have inadequately developed life skills; limited health promotion knowledge and are at risk of being coerced into sexual relationships. The study aimed to assess the effect of peer group participation on improving knowledge about condoms among adolescent girls in rural eastern Ethiopia. The study analyzed data from a repeated cross-sectional study involving 3186 and 3290 adolescent girls during the baseline period (2016) and the endline period (2019), respectively. The respondents were adolescent girls aged 13–17 years old. The study’s outcome was knowledge about condoms, which was assessed using 3-item questions. A weighted multivariable logistic regression analysis was used to examine the effect of peer group participation on improving knowledge about condoms by controlling for potential confounders. Statistical significance was set at a p-value <0.05. The magnitude of good knowledge about condoms among peer-group participants was 23% higher in the endline compared to the baseline. The odds of having good knowledge about condoms among girls who participated in an organized peer group were 2.15 times higher than those who didn’t participate (AOR: 2.15, 95% CI: 1.42, 3.26). Moreover, the odds of having good knowledge about condoms among those who reported high confidence in perceived communication skills were 1.68 times higher than those who reported no or little confidence (AOR: 1.68, 95% CI: 1.33, 2.13). Peer-group participation improved knowledge about condoms. Girls with high confidence in their perceived communication skills also had better knowledge about condoms. Peer-group education interventions have the potential to improve condom knowledge and thus improve sexual and reproductive health outcomes of adolescent girls. Further studies are needed in other contexts to inform intervention scale-up.