bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pericytes mediate neurovascular remodeling in chronic arterial hypertension
Authors: Morton Lorena , Garza Alejandra P. , Debska-Vielhaber Grazyna , Villafuerte Luis E. , Henneicke Solveig , Arndt Philipp , Meuth Sven G. , Schreiber Stefanie , Dunay Ildiko R. 
Published: May 2024

AbstractChronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated. Therefore, in this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat (SHRSP) model, emphasizing their phenotypic and metabolic transformation. Our results reveal an early transition in PDGFRß+pericytes toward increased NG2 and CD13 co-expressing subtypes, signaling enhanced pericyte reactivity in an effort to stabilize vascular structures and an inflammatory engagement within the vascular niche in response to hypertensive stress. Gene expression profiling of microvessels revealed altered expression within crucial pathways i.e., angiogenesis, blood-brain barrier integrity, hypoxia and inflammation. Furthermore, we detected that circulating extracellular vesicles from SHRSP alter pericyte mitochondrial membrane potential, highlighting their ability to transmit pathogenic signals that exacerbate vascular remodeling. Detailed metabolic analysis revealed a significant shift toward glycolytic metabolism in pericytes already in initial hypertension, alongside a dysregulation of ATP production pathways. These findings emphasize the transformative influence of hypertension on cerebral pericytes and the extensive consequences on cerebral vascular health.
Hyperactive mTORC1/4EBP1 Signaling Dysregulates Proteostasis and Accelerates Cardiac Aging
Authors: Zarzycka Weronika , Kobak Kamil A , King Catherine J , Peelor Frederick F , Miller Benjamin F , Chiao Ying Ann 
Published: May 2024

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) has a major impact on aging by regulation of proteostasis. It is well established that mTORC1 signaling is hyperactivated with aging and age-related diseases. Previous studies have shown that partial inhibition of mTOR signaling by rapamycin reverses the age-related decline in cardiac function and structure in old mice. However, the downstream signaling pathways involved in this protection against cardiac aging have not been established. TORC1 phosphorylates 4E-binding protein 1 (4EBP1) to promote the initiation of cap-dependent translation. The aim of this project is to examine the role of the mTORC1/4EBP1 axis in age-related cardiac dysfunction. We utilized a whole-body 4EBP1 KO mouse model, which mimics a hyperactive 4EBP1/eIF4E axis, to investigate the effects of hyperactive mTORC1/4EBP1 axis in cardiac aging. Echocardiographic measurements revealed that young 4EBP1 KO mice have no difference in cardiac function at baseline compared to WT mice. Interestingly, middle-aged (14–15-month-old) 4EBP1 KO mice show impaired diastolic function and myocardial performance compared to age-matched WT mice and their diastolic function and myocardial performance are at similar levels as 24-month-old WT mice, suggesting that 4EBP1 KO mice experience accelerated cardiac aging. Old 4EBP1 KO mice show further declines in systolic and diastolic function compared to middle-aged 4EBP1 KO mice and have worse systolic and diastolic function than age-matched old WT mice. Gene expression levels of heart failure markers are not different between 4EBP1 KO and WT mice at these advanced ages. However, ribosomal biogenesis and overall protein ubiquitination are significantly increased in 4EBP1 KO mice when compared to WT, which suggests dysregulated proteostasis. Together, these results show that a hyperactive 4EBP1/eIF4E axis accelerates cardiac aging, potentially by dysregulating proteostasis.
A Genome-Wide Association Study Reveals Novel Genetic Markers Associated with Human African Trypanosomiasis
Authors: Mulindwa Julius , Kimuda Magambo Phillip , Noyes Harry , Ilboudo Hamidou , Koffi Mathurin , Ahouty Bernadin , Nyangiri Oscar , Cooper Anneli , Clucas Caroline , Nambala Peter , Musaya Janelisa , Ngoyi Dieudonne ́ Mumba , Karume Kevin , Fataki Olivier , Simo Gustave , Ofon Elvis , Enyaru John , Nerima Barbara , Tait Andy , Marcello Lucio , Chisi John , Kabore Jacques , Kabore Justin Windingoudi , Kamoto Kelita , Simuunza Martin , Alibu Vincent P. , Jamonneau Vincent , Camera Marianne , Camara Mamadou , Bucheton Bruno , Hertz-Fowler Christiane , Macleod Annette , Matovu Enock ,   TrypanoGEN Research Group as members of The H3Africa Consortium
Published: May 2024

AbstractTrypanosoma brucei gambienseandTrypanosoma brucei rhodesiensecause human African trypanosomiasis (HAT), a neglected tropical disease that constitutes an important public health issue in sub-Saharan Africa. In the absence of a vaccine, only chemotherapy and vector control has been used to combat the disease. Environmental factors, such as exposure to infected tsetse files, and genetic factors such as variants in theAPOL1gene have been shown to contribute to the risk of developing HAT. However, the known factors only explain a small part of the risk of developing trypanosomiasis. We have undertaken a genome wide association study (GWAS) using 3813 samples fromT. b. gambienseandT.b. rhodesienseHAT foci in Guinea, Côte d’Ivoire, Cameroon, DRC, Malawi and Uganda. 2141 samples were genotyped on the H3Africa SNP chip followed by a genotyping a validation cohort of an additional 1,627 samples at candidate loci. After the primary and validation studies we identified a novel locus nearSMOC2with genome-wide significance. We also identified suggestive associations nearNXN, NTNG1andNCKAP5that have stronger associations with disease susceptibility than theAPOL1loci that has been previously identified by hypothesis driven approaches. These genes offer new entry points for future studies of the underlying genetic mechanisms of HAT.
Subcortical alterations in newly diagnosed epilepsy and associated changes in brain connectivity and cognition
Authors: de Bézenac Christophe E , Leek Nicola , Adan Guleed , Mohanraj Rajiv , Biswas Shubhabrata , Marson Anthony G , Keller Simon S 
Published: May 2024

AbstractObjectivesPatients with chronic focal epilepsy commonly exhibit subcortical atrophy, particularly of the thalamus. The timing of these alterations remains uncertain, though preliminary evidence suggests that observable changes may already be present at diagnosis. It is also not yet known how these morphological changes are linked to the coherence of white matter pathways throughout the brain, or to neuropsychological function often compromised before anti-seizure medication treatment. This study investigates localised atrophy in subcortical regions using surface shape analysis in individuals with newly diagnosed focal epilepsy (NDfE) and assesses their implications on brain connectivity and cognitive function.MethodsWe collected structural (T1w) and diffusion weighted MRI, as well as neuropsychological data from 104 patients with NDfE and 45 healthy controls (HC) matched for age, sex and education. A vertex-based shape analysis was performed on subcortical structures to compare patients with NDfE and HC, adjusting for age, sex and intracranial volume. The mean deformation of significance areas (pcor < 0.05) was used to identify white matter pathways associated with overall shape alterations in patients relative to controls using correlational tractography. Additionally, the relationship between significant subcortical shape values and neuropsychological outcomes was evaluated using a generalised canonical correlation approach.ResultsShape analysis revealed bilateral focal inward deformation (a proxy for localised atrophy) in anterior areas of the right and left thalamus and right pallidum in patients with NDfE compared to HC (FWE corrected). No structures showed areas of outward deformation in patients. The connectometry analysis revealed that fractional anisotropy (FA) was positively correlated with thalamic and pallidal shape deformation, i.e., reduced FA was associated with inward deformation in tracts proximal to and or connecting with the thalamus including the fornix, frontal, parahippocampal and corticothalamic pathways. Thalamic and pallidal shape changes were also related to with increased depression and anxiety, and reduced memory and cognitive function.DiscussionThese findings suggest that atrophy of the thalamus, which has previously been associated with the generation and maintenance of focal seizures, may present at epilepsy diagnosis and relate to alterations in both white matter connectivity and cognitive performance. We suggest that at least some alterations in brain structure and consequent impact on cognitive and affective processes are the result of early epileptogenic processes rather than exclusively due to the chronicity of longstanding epilepsy, recurrent seizures, and treatment with anti-seizure medication.
Prevalence and associated factors of gender-based violence for female: Evidence from school students in Nepal- a cross sectional study
Authors: Gautam Laxmi , Sha Manisha , Khadka Mishra Durga , Dahal Padam Kanta , Gautam Sujan 
Published: May 2024

AbstractBackgroundGender-based violence (GBV) is a major global public health challenge in 21stcentury that remains a serious impact on women’s health and well-being. Therefore, this study aimed to access the prevalence and factors associated with GBV among secondary school female students in Sarlahi district of Nepal.MethodsUsing a cross-sectional study, we collected data from 225 secondary school female students in Sarlahi district of Nepal. Data was collected by using a semi-structured, self-administered questionnaire. Probability proportionate and simple random sampling techniques were used for sampling. The association were explored by using chi-square test and binary logistic regression where a p value <0.05 was considered statistically significant.ResultsThe prevalence of GBV among the students during their lifetime was 45.33% followed by physical (16.89%), sexual (30.22%) and psychological (39.56%) violence respectively. The prevalence of physical violence from family members was 97.36%, followed by emotional violence (41.57%). Further, the prevalence of sexual violence from the non-family members was 91.17%. Type of family had a significant association with lifetime experience of GBV (p=0.003). Gender based discrimination in the family had a significant association with lifetime (p=0.001) as well as last 12 months (p=0.001) GBV experience. Experience of witnessing physical violence as a child was within last 12 months was associated with GBV (p=0.03).ConclusionGBV has been prevalent among the high school students, with limited level of awareness in that issue. This warrants the urgent need to establish preventive and responsive control measure within schools and communities to address the GBV effectively.
Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases
Authors: Langley Allison , Abeling-Wang Sarah , Wagner Erinn , Salogiannis John 
Published: May 2024

AbstractPeripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding along stable microtubules via molecular motors or attaching to the plus ends of dynamic microtubules through tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling ER tubules along microtubules. Previous research showed that ER hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do the same. In U2OS cells, we screened Rabs for their ability to cotransport with ER tubules and found that ER hitchhikes on post-Golgi vesicles marked by Rab6 (isoforms a and b). Rab6-ER hitchhiking occurs independently of ER-endolysosome contacts and TAC-mediated ER movement. Disrupting either Rab6 or the motility of Rab6-vesicles reduces overall ER movement. Conversely, relocating these vesicles to the cell periphery causes peripheral ER accumulation, indicating that Rab6-vesicle motility is crucial for a subset of ER movements. Proximal post-Golgi vesicles marked by TGN46 are involved in Rab6-ER hitchhiking, while other post-Golgi vesicles (Rabs 8/10/11/13/14) are not essential for ER movement. Our further analysis finds that ER to Golgi vesicles marked by Rab1 are also capable of driving a subset of ER movements. Taken together, our findings suggest that ER hitchhiking on Rab-vesicles is a significant mode of ER movement.SIGNIFICANCE STATEMENTPeripheral endoplasmic reticulum tubules move on microtubules by either attaching to motors (cargo adaptor-mediated), dynamic microtubule-plus ends (tip attachment complexes) or motile vesicles (hitchhiking) but the prevalence of each mode is not clearPost-Golgi vesicles marked by Rab6/TGN46 and ER to Golgi vesicles marked by Rab1 drive ER movementsER hitchhiking on multiple classes of vesicles (endolysosomal, post-Golgi and ER to Golgi) marked by Rabs plays a prominent role in ER movement
FlaHMM: unistrandflamenco-like piRNA cluster prediction inDrosophilaspecies using hidden Markov models
Authors: Trapotsi Maria-Anna , van Lopik Jasper , Hannon Gregory J , Nicholson Benjamin Czech , Bornelöv Susanne 
Published: May 2024

AbstractPIWI-interacting RNAs are a class of small non-coding RNAs that are essential for transposon control in animal gonads. InDrosophilaovarian somatic cells, piRNAs are transcribed from large genomic regions called piRNA clusters, which are enriched for transposon fragments and acts as a memory of past invasions. Despite being widely present acrossDrosophilaspecies, somatic piRNA clusters are notoriously difficult to identify and study due to their lack of sequence conservation and limited synteny. Current identification methods rely either on extensive manual curation or availability of high-throughput small RNA-seq data, limiting large-scale comparative studies. We now present FlaHMM, a hidden Markov model developed to automate genomic annotation offlamenco-like unistrand piRNA clusters inDrosophilaspecies without the need of experimental data beyond a genome assembly. FlaHMM uses transposable element content across 5 or 10 kb bins calculated from genome sequence alone and is thus able to detect candidate piRNA clusters without the need to obtain flies and experimentally perform small RNA sequencing. We show that FlaHMM performs on par with piRNA-guided or manual methods, and thus provides a scalable and efficient approach to piRNA cluster annotation in new genome assemblies. FlaHMM is freely available athttps://github.com/Hannon-lab/FlaHMMunder an MIT licence.
Longitudinal proteomic profiling of T cell differentiationin vivounveils dynamic proteome remodeling
Authors: Beusch Christian M. , Dawood Abdelhameed S. , Ozdilek Ahmet , Welbourn Sarah , Monaco Christopher M. , Flegle Alexandra S. , Malik Sakshi , Niavi Christina , Akhtar Akil , Roman Carly , Gavora Autumn A. , Gordon David E. , Abdel-Hakeem Mohamed S. 
Published: May 2024

AbstractT cell differentiation plays a pivotal role in orchestrating immune responses and is crucial for combating infection. Consequently, extensive studies on the cellular, transcriptional, and epigenetic levels have been conducted to deepen our understanding of T cell differentiation. Despite numerous studies revealing disparities between transcriptional and proteomic measurements of the same cells, there has been no direct ex-vivo proteomic profiling of antigen-specific T cell differentiation conducted thus far. In this study, we performed the first longitudinal proteomic profiling of T cell differentiationin vivo,utilizing the well-characterized lymphocytic choriomeningitis virus (LCMV) mouse model. We performedex-vivoprotein abundance profiling of effector to memory differentiation (TEFF/TMEM) and early to late exhausted T cell (TEX) differentiation following LCMV infection with the acute Armstrong and chronic Clone-13 strains, respectively. Our findings reveal dynamic alterations of the T cell proteome during differentiation that are either common or distinct for acute and chronic infection, recapitulating existing knowledge. Crucially, our proteomic analyses identify significant differences in the abundance of several proteins between cell states that were not previously highlighted through transcriptional profiling. Our study provides a comprehensive proteomics resource ofin vivoT cell differentiation within an antigen-specific context, complementing existing omics data and elucidating putative proteins with potential diagnostic and therapeutic relevance.
Tuning and functionalization of logic gates for time resolved programming of bacterial populations
Authors: Bäcker Leonard E. , Broux Kevin , Weckx Louise , Khanal Sadhana , Aertsen Abram 
Published: May 2024

AbstractIn order to increase our command over genetically engineered bacterial populations in bioprocessing and therapy, synthetic regulatory circuitry needs to enable the temporal programming of a number of consecutive functional tasks without external interventions. In this context, we have engineered a genetic circuit encoding an autonomous but chemically tunable timer inEscherichia coli, based on the concept of a transcription factor cascade mediated by the cytoplasmic dilution of repressors. As proof-of-concept, we used this circuit to impose a time-resolved two-staged synthetic pathway composed of a production-followed-by-lysis program, via a single input. Moreover, via a recombinase step, this synchronous timer was further engineered into an asynchronous timer in which the generational distance of differentiating daughter cells spawning off from a stem-cell like mother cell becomes a predictable driver and proxy for timer dynamics. Using this asynchronous timer circuit, a temporally defined population heterogeneity can be programmed in bacterial populations.Graphical abstract
Spontaneous Fluctuations in Pupil Size Shape Retinal Responses to Visual Stimuli
Authors: Mathôt Sebastiaan , Weiden Daria , Dimigen Olaf 
Published: May 2024

AbstractVisual perception is shaped at the earliest stage by the size of the eye’s pupil, which determines how much light enters the eye and how well this light is focused. But the exact role of pupil size in visual perception is still poorly understood. We recorded pupil size and electrical activity from the retina and brain while healthy human participants viewed full-screen flashes. We found that early retinal responses, which peaked ±25 ms after stimulus onset and predicted subsequent activity over visual cortex, were strongly affected by stimulus intensity. Importantly, pupil size, at least within the range of naturally occurring fluctuations, did not affect the amplitude of these early retinal responses, despite resulting in substantial changes in retinal light exposure. However, the direction of pupil-size change at the moment of stimulus presentation did modulate the amplitude of early retinal responses, which were enhanced during phases of dilation as compared to constriction. Based on these results, we suggest that fast-acting adaptation processes may normalize early retinal responses with respect to changes in retinal light exposure that result from spontaneous changes in pupil size: an initial form of brightness constancy. These results shed new light on, and raise important and previously unasked questions about, the role of pupil size in visual perception.
Unique RNA replication characteristics and nucleocapsid protein expression may explain differences in the replication capacity of SARS-COV-2 lineages
Authors: Corrêa Isadora Alonso , de Souza Marcos Romário Matos , da Silva Gustavo Peixoto Duarte , Pimentel Anna Beatriz Sampaio Vianna Macedo , Calil Pedro Telles , Cunha Marcela Sabino , Mariani Diana , de Moares Brindeiro Rodrigo , Costa Sara Mesquita , da Costa Simas Maria Clara , Ota Victor Akira , Pereira Elisa Cavalcante , Siqueira Marilda Mendonça , Resende Paola Cristina , Galliez Rafael Mello , Faffe Debora Souza , Silva Rosane , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar , da Costa Luciana Jesus 
Published: May 2024

SummaryCOVID-19 pandemic in Brazil was characterized by the sequential circulation of the SARS-CoV-2 lineages B.1.1.33, and variants Zeta (P.2), Gamma (P.1/P.1.*), Delta (B.1.617.2/AY.*), and Omicron (BA.*). Our research aimed to compare the biological traits of these lineages and variants by analyzing aspects of viral replication including binding, entry, RNA replication, and viral protein production. We demonstrated that the replication capacity of these variants varies depending on the cell type, with Omicron BA.1 exhibiting the lowest replication in the human pulmonary cells. Additionally, the nucleocapsid proteoforms generated during infection exhibit distinct patterns across variants. Our findings suggest that factors beyond the initial stages of virus entry influence the efficiency of viral replication among different SARS-CoV-2 variants. Thus, our study underscores the significance of RNA replication and the role of nucleocapsid proteins in shaping the replicative characteristics of SARS-CoV-2 variants.Author summaryThe COVID-19 pandemic was characterized by the emergence of different viral variants that presents specific properties such as response to antibodies, pathogenicity and detection by diagnostic tests. The circulation of these variants presented a particular pattern depending on the global geographic regions. Despite the cessation of the pandemic, as officially declared by the World Health Organization in 2023, new viral variants continue to emerge while aspects of the virus-cell interaction that contribute to the replication of these variants have not yet been completely understood. In our study, we compared the biological characteristics of SARS-CoV-2 variants that circulated in Brazil during the pandemic, verifying aspects of entry, viral replication and production of viral RNA and proteins. Our results indicate that Omicron BA.1 variant has reduced replication and protein production in human lung cells. We also observed that the viral nucleocapsid protein presents proteoforms that vary according to the variant. These differences could help to explain the differences observed in viral replication in human pulmonary cells.
A novel feeding mechanism: Sunbirds drink nectar via intralingual suction
Authors: Cuban David , Wang-Claypool Cynthia , Yohanna Yohanna , Downs Colleen T. , Bowie Rauri C. K. , Brau Fabian , Johnson Steven D. , Rico-Guevara Alejandro 
Published: May 2024

AbstractNectarivory has independently evolved many times among birds, yet little is known about the diversity of feeding mechanisms that enable specialized taxa to efficiently collect this energyrich resource. Multiple avian groups have converged on evolving elongated bills and tube-like tongues adapted for nectar extraction. Old World sunbirds (family Nectariniidae) stand out as having the greatest degree of convergence in bill and tongue morphology with the well-studied and highly-specialized New World hummingbirds (family Trochilidae) which fill their tongues via elastic filling. However, using museum specimens, high-speed video, and fluid modeling, we show that sunbirds use a previously undescribed and unique drinking mechanism not found in any other animal: intralingual suction through the inside of hollow tubular tongues, a remarkable feat for animals without lips or cheeks.