bluuebunny/crossref_metadata_2025_split huggingface dataset:
S100A1ct: a synthetic peptide derived from human S100A1 protein improves cardiac contractile performance and survival in pre-clinical heart failure models
Authors: Kehr Dorothea , Ritterhoff Julia , Glaser Manuel , Jarosch Lukas , Salazar Rafael E. , Spaich Kristin , Varadi Karl , Birkenstock Jennifer , Egger Michael , Gao Erhe , Koch Walter J. , Katus Hugo A. , Frey Norbert , Jungmann Andreas , Busch Cornelius , Mather Paul J. , Ruhparwar Arjang , Völkers Mirko , Wade Rebecca C. , Most Patrick 
Published: March 2023

AbstractBackgroundThe EF-hand Ca2+sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. S100A1’s ability to recognize and modulate the activity of targets such as SERCA2a and RyR2 in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminalα-helix (residues 75-94).Objective:We therefore hypothesized that a synthetic peptide consisting of residues 75-94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.Methods and Results:Applying an integrative translational research pipeline, ranging from computational molecular modeling to large animal cardiac disease models, we characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardiumin vitroandin vivo. This activity translates into improved contractile performance and survival in pre-clinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. Mechanistically, S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca2+cycling and prevents ß-adrenergic receptor triggered Ca2+imbalances by targeting SERCA2a and RyR2 activity. Modeling suggests that S100A1ct may stimulate SERCA2a by interacting with the sarcoplasmic transmembrane segments of the multi-span integral membrane Ca2+pump. Incorporation of a cardiomyocyte targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potencyin vitroandin vivo.Conclusion:S100A1ct peptide is a promising lead for the development of a novel peptide-based therapeutic against heart failure with reduced ejection fraction.
Inferring B-cell derived T-cell receptor induced multi epitope-based vaccine candidate against enterovirus 71 (EV 71): A reverse vaccinology approach
Authors: Swain Subrat Kumar , Panda Subhasmita , Sahu Basanta Pravas , Mahapatra Soumya Ranjan , Dey Jyotirmayee , Misra Namrata , Sarangi Rachita 
Published: March 2023

AbstractIn addition to Coxsackie virus (CV), another pathogen that causes Hand-foot and mouth disease (HFMD), Enterovirus 71 (EV 71) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in paediatric patients with blister like sores or rashes on the hand, feet and mouth. Not withstanding the significant burden of the disease, few treatments are currently available, and there is no authorised vaccine available for the disease prevention. Several vaccinations based on attenuated and inactivated vaccines have previously been identified, however they become worthless over time owing to changes in the viral genome. As a result, the goal of the study is to create an immunoinformatics and reverse vaccinology pipeline for predicting a multi epitope vaccine. A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein and found the induction of possible immune response, in order to boost the immune system, aBeta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. The immunogenicity of the designed, refined, and verified prospective 3D- structure of multi-epitope vaccine was found to be quite high with non-allergen, and antigenic property. The vaccine candidates bound to the TLR-3 in a molecular docking analysis and the efficacy of the potential vaccine to generate a strong immune response was assessed by means of an in silico immunological simulation. Computational analysis has shown that the proposed multi epitope vaccine possibility safe for use in humans and elicit an immune response, making it a promising tool against HFMD viral genome.
Sexual Dimorphic Gene Expression Profile of Perirenal Adipose Tissue in Ovine Fetuses with Growth Restriction
Authors: Blomberg Jack , Luna Ramirez Rosa I. , Goyal Dipali , Limesand Sean W. , Goyal Ravi 
Published: March 2023

AbstractWorldwide, fetal growth restriction (FGR) affects 7 to 10% of pregnancies, or roughly 20.5 million infants, each year. FGR not only increases neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR “programs” an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus,we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from male and female near-term FGR and normal-weight fetal lambs (N=4 in each group, 16 total), examined the preadipocytes’ differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have lower cellular density compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.
Mapping cell types in the tumor microenvironment from tissue images via deep learning trained by spatial transcriptomics of lung adenocarcinoma
Authors: Na Kwon Joong , Koh Jaemoon , Choi Hongyoon , Kim Young Tae 
Published: March 2023

AbstractProfiling heterogeneous cell types in the tumor microenvironment (TME) is important for cancer immunotherapy. Here, we propose a method and validate in independent samples for mapping cell types in the TME from only hematoxylin and eosin (H&E)-stained tumor tissue images using spatial transcriptomic data of lung adenocarcinoma. We obtained spatial transcriptomic data of lung adenocarcinoma from 22 samples. The cell types of each spot were estimated using cell type inference based on a domain adaptation algorithm with single-cell RNA-sequencing data. They were used to train a convolutional neural network with a corresponding H&E image patch as an input. Consequently, the five predicted cell types estimated from the H&E images were significantly correlated with those derived from the RNA-sequencing data. We validated our model using immunohistochemical staining results with marker proteins from independent lung adenocarcinoma samples. Our resource of spatial transcriptomics of lung adenocarcinoma and proposed method with independent validation can provide an annotation-free and precise profiling method of tumor microenvironment using H&E images.
BuTT-Seq: a new method for facile profiling of transcription
Authors: Yu Albert D. , Rosbash Michael 
Published: March 2023

SummaryA wide range of sequencing methods have been developed to assess nascent RNA transcription and resolve the single-nucleotide position of RNA polymerase genome-wide. These techniques are often burdened with high input material requirements and lengthy protocols. We leveraged the template-switching properties of thermostable group II intron reverse transcriptase (TGIRT) and developed BuTT-Seq (BUlk analysis of nascent Transcript Termini sequencing), which can produce libraries from purified nascent RNA in 6 hours and from as few as 10,000 cells – an improvement of at least 25-fold over existing techniques. BuTT-Seq shows that inhibition of the superelongation complex (SEC) causes promoter-proximal pausing to move upstream in a fashion correlated with subnucleosomal fragments. To address transcriptional regulation in a tissue, BuTT-Seq was used to measure the circadian regulation of transcription from fly heads. All the results indicate that BuTT-Seq is a simple and powerful technique to analyze transcription at a high level of resolution.
Application of DNA forensic to identify a problem leopard and its implications for human-leopard conflict mitigation
Authors: Manandhar Prajwol , Manandhar Ajaya , Joshi Jyoti , Karmacharya Dibesh 
Published: March 2023

AbstractAttacks on humans by leopardsPanthera pardusoften escalate human-leopard conflict, influence extreme negative tolerance and encourage retaliatory killings. In the rural hilly region of Arghakhanchi district, mid-western Nepal, a leopard killed a child in November 2018. Government authorities captured a leopard a week later which was immediately killed by the villagers. We collected the predator’s salivary DNA from the victim’s bite wound and compared its DNA fingerprint profile with the killed leopard’s profile to resolve the case using 13 microsatellite markers for leopard individualization. Our genetic analysis confirmed that the leopard persecuted by the villagers was the same leopard that had killed the victim. We urge the government to devise dedicated policy and guidelines for human-leopard conflict management and mitigation in Nepal, and to incorporate protocols, including leopard individualization microsatellite panel we have standardized, that mandate correct identification of captured leopard before any interventions such as persecutions and translocations are attempted. We also recommend steering community programs to proactively safeguard children, people and livestock to avoid conflicts and to influence positive tolerance towards leopards. This will benefit leopard conservation and save human lives and livelihoods leading to a healthy coexistence.
Leaf hydration status under drought is predominantly linked to stomatal regulation and leaf roll but not osmotic adjustment in Canadian hard red spring wheat (Triticum aestivum) cultivars
Authors: Sharma G , Brar GS , Knipfer T 
Published: March 2023

ABSTRACTFor wheat (Triticum aestivum), sustained crop yield at limited soil water has been linked to osmotic adjustment (OA) as one of the main drivers to minimize drought-induced reductions in leaf hydration status and growth. Canada Western Red Spring (CWRS) cultivars are typically grown in rainfed areas in northern regions with milder climates, but ongoing climate change has increased the frequency and intensity of drought event questioning how successful they are in tolerating drought. The extent of OA and its relation to stomatal behavior, leaf roll, and kernel development under periods of drought remain elusive for CWRS. For several commercially used Canada Western Red Spring (CWRS) wheat cultivars (‘Superb’, ‘Stettler’, ‘AAC Viewfield’), OA was not found to be a mechanism contributing to drought tolerance. In contrast, we found that sustained kernel weight during periods of relatively low soil water content was linked to ‘tight’ stomatal behavior (i.e., efficient transition from onset to full stomatal closure) and ‘early’ leaf roll (i.e., reductions in flag leaf width). Moreover, leaf hydration status (ΘRWC) marked the onset of drought-induced losses in kernel weight in all three cultivars. In conclusion, CWRS wheat lacks OA but leaf stomatal behavior and leaf rolling aid in securing leaf hydration status and kernel weight under drought.One-sentence summarySelect wheat cultivars maintain leaf hydration status and yield by early leaf roll and rapid stomatal closure in the absence of osmotic adjustment and isohydric behavior.
Cryopreservation and revival of Hawaiian stony corals via isochoric vitrification
Authors: Powell-Palm Matthew J. , Henley E. Michael , Consiglio Anthony N. , Lager Claire , Chang Brooke , Perry Riley , Fitzgerald Kendall , Daly Jonathan , Rubinsky Boris , Hagedorn Mary 
Published: March 2023

ABSTRACTCorals are under siege by both local and global threats, creating a wordwide reef crisis. Cryopreservation is an important intervention measure and a vital component of the modern coral conservation toolkit, but preservation techniques are currently limited to sensitive reproductive materials that can only be obtained a few nights per year during spawning. Here, we report the first successful cryopreservation and revival of cm-scale coral fragments via mL-scale isochoric vitrification. We demonstrate coral viability at 24h post-thaw using a calibrated oxygen-uptake respirometry technique, and further show that the method can be applied in a passive, electronics-free configuration. Finally, we detail a complete prototype coral cryopreservation pipeline, which provides a platform for essential next steps in modulating postthaw stress and initiating long-term growth. These findings pave the way towards an approach that can be rapidly deployed around the world to secure the biological genetic diversity of our vanishing coral reefs.
An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease
Authors: Zhu Yuying , Xue Xiaoou , Li Jun , Long Zilin , Zhang Jiawei , Zhao Baohua 
Published: March 2023

AbstractPurposeTo explore the possible pharmacological mechanisms of Danbai Granules (DBG) against sequelae of pelvic inflammatory disease (SPID) by the method of network pharmacology and molecular docking combined with experimental validation.MethodsFirstly, biologically active compounds, targets of DBG, and related targets of SPID were collected from public databases. The protein– protein interaction (PPI) network, Gene GO and KEGG enrichment analysis were carried out via R language to find the potential biological processes and pathways of DBG against SPID. Subsequently, molecular docking was used to calculate the affinity between the top six targets and the top ten compounds, respectively. Finally, the above analysis results were verified by in vivo experiments.ResultsA total of 106 crossover genes were selected from 220 potential medicine genes and 952 SPID-related genes. PPI network analysis indicated that IL-6, IL-1β, VEGFA, CASP3, PTGS2, JUN, etc., were core targets. GO and KEGG enrichment analysis revealed that PI3K-Akt, AGE–RAGE, IL-17, TNF, HIF-1 and Toll-like receptors signaling pathways were the main signaling pathways. Molecular docking showed that 15 pairs of target-ingredient combinations have good binding activity. The animal experiments showed that DBG administration inhibited the expression of TLR4/MyD88/NF-κB p65 signaling pathway-related proteins expression, altered the high expression of IL-6, IL-1β, and low level of IL-4, IL-10, thereby relieving the pelvic inflammation of SPID.ConclusionThrough the network pharmacology and molecular docking, our findings predicted the active ingredients and potential targets of DBG in treating SPID. The experimental verification preliminarily revealed that DBG may inhibit the inflammatory response of SPID rats by regulating the TLR4/MyD88/NF-κB p65 signaling pathway. which provides a theoretical basis for the study of the pharmacodynamic material basis and mechanism of DBG against SPID at the comprehensive level.
Deep neural generation of neuronal spikes
Authors: Nakajima Ryota , Shirakami Arata , Tsumura Hayato , Matsuda Kouki , Nakamura Eita , Shimono Masanori 
Published: March 2023

AbstractIn the brain, many regions work in a network-like association, yet it is not known how durable these associations are in terms of activity and could survive without structural connections. To assess the association or similarity between brain regions with a new “generating” approach, this study evaluated the similarity of activities of neurons at the cellular level within each region after disconnecting between regions. To this end, a multi-layer LSTM (Long-Short Term Memory) model was used. Surprisingly, the results revealed that generation of activity from one region to other regions that had been disconnected was possible with similar reproduction accuracy as generation between the same regions in many cases. Notably, not only firing rates but also synchronization of firing between neuron pairs, which is often used as neuronal representations, could be reproduced with considerable precision. Additionally, their accuracies were associated with the relative distance between brain regions and the strength of the structural connections that initially connected them. This outcome not only enables us to look into principles in neuroscience based on the potential to generate new informative data, but also creates neural activity that has not been measured in adequate amounts and could potentially lead to reduced animal experiments.
Mainly Heterosexual, Bisexual, or Other?: the measurement of sexual minority status and its impact on analytic sample, demographic distribution and health outcomes
Authors: Tabor Evangeline , Kneale Dylan , Patalay Praveetha 
Published: March 2023

AbstractBackgroundSexual orientation has been measured in a wide variety of ways which reflect both theoretical and practical considerations. However, choice of sexual orientation measure and recoding strategy can impact analytic sample, as well as demographic and health profiles, in analyses of sexual minority populations. We aimed to examine how choice of sexual orientation dimension and recoding decisions impact estimates in the sexual minority population in two population-based studies in the UK.MethodsWe used data collected at age 17 (2018) in the UK Millennium Cohort Study and at wave six (2012-13) and eight (2017-18) of the English Longitudinal Study of Ageing. Descriptive statistics were used to examine the impact of choice of sexual orientation dimension (i.e. identity, attraction and experience) and recoding decisions on achieved analytic sample and composition by selected demographic and health measures within and between datasets.ResultsDimension choice and recoding decisions resulted in variation in analytic sample. For example, more respondents reported some same-sex sexual attraction than reported a non-heterosexual identity (adolescents: 20.77% vs 8.97%, older adults: 4.77% vs 1.04%). Demographic distributions varied, but not substantially by dimension choice or recoding strategy. Overall, in both datasets sexual minority respondents were more likely to be White and in the highest quintiles for income and education than heterosexual respondents. Health status did not vary substantially by dimension choice or recoding strategy, however sexual minority respondents reported worse health than their heterosexual peers.ConclusionsThis study explores a range of practical and theoretical considerations when analysing sexual minority respondents using survey data. We highlight the impact recoding decisions may have on the numbers of sexual minority respondents identified within a dataset and demographic and health distributions in this understudied population. We also demonstrate the benefits of including multiple dimensions for capturing mechanisms of interest in elucidating ambiguous responses and exploring sexual diversity.
Bone marrow from focal segmental glomerulosclerosis displays activation of inflammatory pathway
Authors: Rashmi Priyanka , Boada Patrick , Soni Arvind , Sigdel Tara K , Rychkov Dmitry , Hahm Eunsil , Da Silva Andrea Alice , Damm Izabella , Paul Rohan , Vincenti Flavio , Ye Jimmie , Reiser Jochen , wolf Jeffrey , Sarwal Minnie M. 
Published: March 2023

AbstractCirculating factors resulting from immune dysfunction have been proposed as one of the causes for increased risk of graft loss associated with recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplant. However, the precise identity of the circulating factors and their sources remain incompletely characterized.In vivostudies in mouse models have implicated a role for immature bone marrow cells in the development of FSGS. Using single-cell RNA sequencing we have profiled >50,000 cells from bone marrow of FSGS patients with or without recurrence after kidney transplant and controls including healthy individuals and patients with end-stage renal disease due to non-FSGS causes. Bone marrow mononuclear cells from patients with recurrence of FSGS after transplant display an inflammatory phenotype with activation of cytokine and interferon signaling in neutrophils, T cells and B cells. We also observe a dramatically depleted B cell population in R-FSGS patients. Conditioned media from BMNCs of R-FSGS patients have higher levels of pro-inflammatory cytokine MIP-1α/CCL3, reduced anti-inflammatory chemokine CCL22 and cause injury in a human podocyte cell culture model. Our studies provide evidence for the role of bone marrow cells in FSGS associated inflammatory milieu and elucidate the transcriptional changes associated with the disease.
Assessment of Erectile Dysfunction in Patients with Benign Prostate Hyperplasia Using the Sexual Function Index at Muhimbili National Hospital, Dar es Salaam, Tanzania
Authors: Mawji Said Ali , Mkony Charles , Nyongole Obadia , Msinde Peter , Mahenda Deogratius 
Published: March 2023

AbstractBackgroundErectile dysfunction (ED) is the inability to achieve and maintain a steady erection for sexual performance. Erectile dysfunction (ED) is becoming more common in the general population, particularly among elderly men with lower urinary tract symptoms and those with benign prostatic hyperplasia. This rise in erectile dysfunction has also been attributed by several other etiologies, which includes inflammatory, mechanical, psychological, occlusive vascular, trauma, endocrine, neurologic, chemical and extra factors (prostatectomy, old age). The purpose of the study was to assess erectile dysfunction in patients with benign prostate hyperplasia before treatment using international index of erectile function (IIEF) tool.MethodologyHospital-based cross-sectional study from March 2021 to June 2022, which involved 188 patients clinically diagnosed with benign prostatic enlargement. Convenient sampling method was used to recruit participants and structured questionnaires were used to attain social demographic characteristics. The international prostate symptom score (IPSS) was used to assess, diagnose patients with BPH as well as the severity of LUTS and international index of erectile function (IIEF) was used to assess erectile dysfunction. Data was analyzed using SPSS software version 27.ResultsThe proportion of ED in patients with benign prostate hyperplasia/LUTS using IIEF tool was found to be 154(82%) and those with no erectile dysfunction was 34(18%). The factors that were statistically associated with erectile dysfunction were age, marital status, cigarette smoking, and diabetes mellitus.ConclusionErectile dysfunction is very common in men who have Benign Prostate Hyperplasia. The prevalence and severity of ED increased with age, diabetes, cigarette smoking, lower urinary tract symptoms, and hypertension, according to the study.