bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the relationship between gut microbiota, immune characteristics, and female genital tract polyps using genetic evidence
Authors: Jia Ran , Fu Yuhang , Xue Miaomiao , Zhou Cheng , Jin Jie
Published: December 2024

The study investigates the causal relationship between gut microbes and female genital tract polyps, exploring the potential mediating role of immune cells via Mendelian randomization (MR) analysis. Our MR study was designed following the STROBE-MR guidelines. We combined data from a large-scale GWAS meta-analysis, including 731 immune profiles and female genital tract polyps, with gut microbiology data sourced from the MiBioGen consortium. Univariate Mendelian randomization was employed to identify gut microbes and immune profiles significantly associated with female genital tract polyps causally. A 2-step MR analysis was utilized to investigate the potential mediating role of immune cells. Furthermore, we utilized the multivariable MR approach based on Bayesian model averaging (MR-BMA) to further assess the prioritization of gut microbiota vs immune characteristics in the development of female genital tract polyps. Through univariate MR analysis, we identified a significant causal link between 12 gut microbiota, 31 immune features, and female genital tract polyps. Four causal pathways involving gut microbiota, immune cells, and polyps were identified among them. MR-BMA analysis indicated marginal inclusion probability (MIP) values exceeding 0.1 for 5 gut microbiota groups: Victivallaceae (model-averaged causal estimate [MACE] = 0.060, MIP = 0.581, P = .0089), Ruminococcus gautreuii (MACE = 0.052, MIP = 0.346, P = .0640), Lachnoclostrium (MACE = 0.0380, MIP = 0.225, P = .1875), Alphaprobacter (MACE = 0.0186, MIP = 0.140, P = .3934), and Fusicatenibacter (MACE = 0.013, MIP = 0.110, P = .5818). Six immune features exhibit high priority, with MIP values exceeding 0.5, including HLA DR on CD33+ HLA DR+ CD14dim (MACE = −0.015, MIP = 0.753, P = .0853), HVEM on naive CD4+ T cell (MACE = 0.024, MIP = 0.737, P = .0053), CD80 on CD62L+ plastic cytoplasmic dendritic cell (MACE = 0.024, MIP = 0.721, P = .0228), CD28 on activated and secret CD4 regulatory T cell (MACE = 0.0054, MIP = 0.706, P = .3245), HLA DR on CD14+ CD16 monocyte (MACE = −0.0003, MIP = 0.520, P = .7927), HLA DR on CD14+ monocyte (MACE = −0.0029, MIP = 0.509, P = .5576). Our research indicates that gut microbiota exerts an independent causal influence on female genital tract polyps, potentially impacting them via various immune cells.
Large uterine fibroid causing DVT and PE: Successful management with mechanical aspiration thrombectomy and hysterectomy: A case report and literature review
Authors: Qammar Asfia , Raja Sandesh , Raja Adarsh , Chaulagain Aayush , Moshayedi Poupak , East Cara
Published: December 2024

Rationale:

Uterine leiomyomas, though commonly benign, can occasionally lead to serious complications, including deep vein thrombosis (DVT) and pulmonary embolism (PE). This study aims to highlight the uncommon yet serious association between large uterine leiomyomas and thromboembolism, which is often overlooked in patients without traditional risk factors. It emphasizes the need for awareness, early diagnosis, and timely intervention to prevent complications in patients presenting with unexplained symptoms and pelvic masses.

Patient concern:

A 38-year-old gravida 5, para 2 woman presented to the emergency room with left lower extremity swelling, pain, and discoloration, accompanied by dyspnea. She had no prior history of DVT or PE and did not have any known risk factors for venous thromboembolism.

Diagnosis:

The patient was diagnosed with DVT and PE, confirmed by venous duplex ultrasound and abdominal and pelvic computed tomography, which revealed thrombus extension to the left iliac vein. Chest computed tomography angiography confirmed a partially occlusive thrombus in the pulmonary arteries.

Intervention:

The patient underwent mechanical aspiration thrombectomy, followed by placement of a left iliac stent. Anticoagulation therapy with heparin was initiated post-thrombectomy. On the third day, a right supracervical hysterectomy was successfully performed. After surgery, anticoagulation was continued with heparin, and the patient was later discharged on apixaban for ongoing therapy.

Outcomes:

The patient made full recovery with no recurrence of thromboembolic events at 11 months posttreatment.

Lessons:

This case highlights the rare but serious complication of DVT and PE in patients with uterine leiomyomas. Timely intervention with thrombectomy, stent placement, and hysterectomy was effective in resolving the thromboembolic events.
Therapeutic Efficacy of Tirofiban Combined With Thrombus Aspiration and Stent Thrombectomy in the Treatment of Large Vessel Occlusion Ischemic Stroke
Authors: Jiao Yang , Wang Xiaoli , Guan Yaxin , Wang Xinxin , Li Zhaosheng , Xiang Xiuzhi , Zhang Zhongmin
Published: December 2024

Objective:

This research aimed to ascertain the effects of tirofiban combined with thrombus aspiration and stent thrombectomy on large vessel occlusion ischemic stroke (LVO-IS).

Methods:

Sixty patients with acute ischemic stroke (AIS) caused by LVO were randomized into the control group and the intervention group (n=30). Patients in the control group received thrombus aspiration combined with stent thrombectomy, while those in the intervention group were treated with tirofiban combined with thrombus aspiration and stent thrombectomy. General data, perioperative-related indicators, cerebral blood flow perfusion, coagulation function indicators, and neurological function indicators were collected, and the prognosis was observed after 3-month treatment.

Results:

A comparison of symptomatic cerebral hemorrhage rate and hospital mortality rate between the 2 groups displayed no significant difference (P>0.05). The rate of revascularization in the intervention group (90.00%) was higher versus the control group (66.67%). After treatment, the mean blood flow and cerebral blood volume of the intervention group were higher and the time to peak cerebral blood flow was less versus the control group. The prothrombin time, activated partial thromboplastin time, and prothrombinogen time of the intervention group were higher, and fibrinogen was lower versus the control group. A lower National Institutes of Health Stroke Scale score was observed in the intervention group versus the control group.

Conclusions:

Tirofiban combined with thrombus aspiration and stent thrombectomy has good efficacy in LVO-IS patients.
Comparison of the Effect of Delay Phenomenon and Quercetin Application on the Viability of Dorsal Skin Island Flaps in Rats
Authors: Bi Kübra , Livaoğlu Murat
Published: December 2024

Background

Surgical delay is any surgical intervention performed 7–14 days before flap elevation, separating part of flap from its vascular bed and aiming to decrease flap necrosis. However, delay surgery needs to be planned and performed as a separate surgical operation. Quercetin is a flavonoid with anti-inflammatory, and vasodilator effects. This study compares the effects of quercetin and surgical delay on flap survival.

Materials and Methods

The study included 32 male Wistar rats divided into four groups: control group (group 1), surgical delay group (group 2), quercetin group (group 3), and both surgical delay and quercetin group (group 4). All dorsal skin island flaps were elevated based on deep circumflex iliac artery and 7 days were selected as waiting period after flap elevation, 50 mg/kg (0.5 mL) intraperitoneal quercetin administration period, and surgical delay period. Macroscopically flap necrosis rates were calculated and histopathological examination was performed to evaluate number of vessels, vessel lumen diameters, inflammation, epidermal damage, and dermal fibrosis scores. All rats were euthanized.

Results

Flap necrosis rates, inflammation, epidermal damage, and dermal fibrosis scores of group 3 and 4 were found to be lower than group 1 and 2 (P < 0.05). Vascular lumen diameter of group 2, 3, and 4 were found to be higher than group 1 (P < 0.05) but no statistically significant difference was found for this parameter between group 2, 3, and 4 (P > 0.05). The number of vessels were found to be higher in group 2, group 3, and group 4 compared with group 1, but this difference was not to be found statistically significant (P = 0.534).

Conclusions

This study shows that quercetin application is more effective in reducing flap necrosis rates and anti-inflammatory effect than surgical delay and also has superior effect in terms of vasodilation.
Mapping the Void
Authors: Harris Chelsea A. , Vastardis Andrew , Jobin Chad , Dossett Lesly
Published: December 2024

Objective:

To delineate how identity-based bias exposure evolves with rank and/or context among health care workers, and assess their attitudes toward existing diversity, equity, and inclusion (DEI) education.

Background:

Although DEI training is widely mandated for health care workers, few studies examine how clinicians’ needs evolve across a career, how context impacts recipients’ ability to respond, or how well existing programs adapt to individual contexts.

Methods:

A 54-question electronic survey was distributed during Morbidity and Mortality conferences beginning in December 2020. Descriptive statistics were performed regarding respondents’ bias exposure across rank, perceptions regarding existing training’s fidelity to recipients’ lived experience, and ability to confer useful response strategies.

Results:

This study included 648 individuals (65.6% White; 50.2% women) practicing in mostly academic medical centers (70.6%). Respondents affirmed that discrimination was common, with half (320, 49.4%) reporting that they experienced bias at least monthly. Among people of color, the proportion reporting monthly exposure decreased with rank. Women of color experienced the biggest drop (74% as residents/fellows down to 11% in late career). Broadly, participants reported the greatest discomfort in addressing subtle bias from patients or high-ranked individuals, and this did not uniformly improve with seniority. Finally, although 478 (73.8%) individuals reported receiving DEI training, 51.3% of respondents reported online DEI modules had little utility. Shortcomings included that training focused on individual rather than structural solutions and that it did not confer response strategies users could reliably employ.

Conclusions:

Identity and context strongly influence both clinicians’ exposure and ability to respond to bias in the hospital environment, independent of seniority. Existing DEI training fails to account for this nuance, ultimately diminishing its utility to clinicians.
Differences in embodied cognition between the arrow-orientation and the arrow-position recognition tasks: evidence from event-related potentials
Authors: Qi WenJing , Gong Jin , Sui Li
Published: December 2024

Embodied cognition is known to play a role in verbal semantic processing. However, its involvement in nonverbal semantic elements, such as arrows, is less understood. Two spatial recognition tasks, specifically arrow-orientation recognition and arrow-position recognition, were employed using directional arrows in various spatial arrangements as visual stimuli. Stimuli were categorized into congruent (where orientation and position align), incongruent 1 (where orientation and position are directly opposing), and incongruent 2 (where orientation and position are unrelated) groups for both tasks. To investigate neural processes, event-related potentials (ERPs) were recorded and analyzed during task performance. Additionally, standardized low-resolution electromagnetic tomography (sLORETA) was utilized to examine brain electrical activity during ERP intervals. The analysis revealed significant ERP component differences between congruent and incongruent conditions across both spatial tasks, highlighting a Stroop-like interference effect. Notably, the arrow-orientation task showed marked enhancements in P3 and N400 components, as well as heightened brain activity in the frontal lobe, anterior cingulate cortex, and insula, compared with the arrow-position task. These findings suggest that embodied cognition is involved in both spatial arrow recognition tasks. The unique role of embodied cognition in these contexts is primarily reflected in the modulation of the P3-N400 complex, indicating differentiated cognitive processing.
Genome resource of chitin-degrading bacterium Brevibacillus formosus YSY-2.2
Authors: TRAN Dinh Minh , Huynh To Uyen , Nguyen Dinh Sy , Pentekhina Iuliia
Published: December 2024

This work announced the whole genome resource of Brevibacillus formosus YSY-2.2, a chitin-degrading bacterium possessing antifungal activity and producing phytohormones previously isolated from Yok Don National Park, Vietnam. The genome contained 6,191,946 bp with 47.3% GC content, 5,791 CDSs, 116 RNAs, 101 CAZymes, and 13 BGCs. It showed the highest values of both ANI (95.07%) and dDDH (72.6%) to those of B. formosus NF2 (CP018145). The genome sequence will provide useful information for further studies on the functional gene and application of B. formosus YSY-2.2.
A murine model of cardiovascular-kidney-metabolic syndrome demonstrates compromised limb function in the ischemic hind limb
Authors: Lotfollahzadeh Saran , Paul Herreet , Bonifacio Joshua , Almiron Ricardo , Hockestra Isaac , Prezkop Kylla , Yamamoto Trent , Piqueras Maria Carmen , Yin Wenqing , Malikova Marina , Siracuse Jeffrey J. , Belghasem Mostafa , Cabral Howard , Sayed Nazish , Chitalia Vipul
Published: December 2024

Abstracts

Background

Cardiovascular-Kidney-metabolic (CKM) syndrome is a public health problem involving > 90% of the US and results in premature CVD at a relatively preserved GFR. The molecular mediators of CKM are poorly understood, partly due to the lack of a reliable animal model. We set out to generate an animal model with renal and metabolic dysfunctions, using PAD as a CKM manifestation.

Methods

A group of C57BL/6 mice was randomized into four groups-a normal diet (ND), a 0.2% adenine diet (AD, a CKD model), a high-fat diet (HFD, a metabolic model), and a combination of HFD+AD (a potential CKM model). Mice underwent a hind limb ischemia surgery. An array of structural (capillary density, soleus muscle evaluation), and functional assays were performed.

Results

Compared to ND mice, AD mice showed loss of weight (40%) and GFR (90%) (P<0.001). The HFD+AD mice had 23-50% higher weight and GFR than the AD group (P = 0.003). The kidneys of HFD+AD showed tubular atrophy, tubulointerstitial fibrosis, immune infiltration, glomerulomegaly, consistent with glomerular hyperperfusion, hypercholesterolemia, impaired glucose tolerance, and adipophilin in the liver, an early marker of hepatic steatosis, and myocardial fibrosis. Compared to ND mice, the AD and HFD+AD mice showed similar reductions in the hind limb perfusion ratios, microcapillary density, Type II muscle fibers, and increased muscle fibrosis, immune infiltration, and lowest cross-sectional muscle area. Compared to AD, HFD+AD mice showed a lower flux ratio and grip strength, all at a GFR double that of the AD group.

Conclusion

A combination of HFD+AD in mice displays features of CKD (loss of GFR, renal fibrosis), dysfunctional obesity (dyslipidemia, impaired glucose tolerance, hepatic steatosis and glomerulomegaly), and cardiovascular disease (myocardial fibrosis and PAD) at a higher GFR, consistent with the features of CKM. This model can be explored to probe the mechanisms of CKM syndrome.
Biological Database Mining for LLM-Driven Alzheimer’s Disease Drug Repurposing
Authors: Schmitt Rico Andre , Buelau Konstantin , Martin Leon , Huettl Christoph , Schirner Michael , Stefanovski Leon , Ritter Petra
Published: December 2024

INTRODUCTION

The synergy of structured knowledge and large language models (LLMs) may contribute to identifying drugs for Alzheimer’s disease (AD) drug repurposing (DR). This paper developed a software pipeline that uses LLMs to translate knowledge stored in natural language (such as in scientific texts) to an applicable DR information structure.

METHODS

AD-related entries in Gene Ontology and DrugBank were integrated into a Knowledge Graph database to inform LLM prompts. Based on the biological process impact, the LLM provided a suitability rating for DR, taking into account the inhibitory effect of drugs on AD driving processes..

RESULTS

Drugs with a high potential for DR were identified and manually reviewed, also considering adverse effects. Ripretinib and Pertuzumab (both kinase inhibitors) had the highest DR applicable rating across all iterations.

DISCUSSION

We propose retrospective analyses, considering the high-rated drugs and their effect on AD patients as a starting point for further (prospective) research.
CASSIA allows for robust, automated cell annotation in single-cell RNA-sequencing data
Authors: Xie Elliot , Cheng Lingxin , Shireman Jack , Cai Yujia , Liu Jihua , Mohanty Chitrasen , Dey Mahua , Kendziorski Christina
Published: December 2024

Numerous methods are available to assign cell type to subpopulations of cells profiled using single-cell RNA-sequencing. Most require a combination of computational and domain-specific expertise, and they frequently yield inconsistent results that can be challenging to interpret. Large language models have the potential to expand accessibility while reducing manual input and improving accuracy, but existing approaches suffer from hyperconfidence, hallucinations, and lack of interpretation. To address these limitations, we developed CASSIA for automated, accurate, and interpretable cell annotation of single-cell RNA-sequencing data.
Yeast Knowledge Graphs Database for ExploringSaccharomyces cerevisiaeandSchizosaccharomyces pombe
Authors: Kumar Mani R , Arulprakasam Karthick Raja , Kutevska An-Nikol , Mutwil Marek , Thibault Guillaume
Published: December 2024

Biomedical literature contains an extensive wealth of information on gene and protein function across various biological processes and diseases. However, navigating this vast and often restricted-access data can be challenging, making it difficult to extract specific insights efficiently. In this study, we introduce a high-throughput pipeline that leverages OpenAI’s Generative Pre-Trained Transformer Model (GPT) to automate the extraction and analysis of gene function information. We applied this approach to 84,427 publications onSaccharomyces cerevisiaeand 6,452 publications onSchizosaccharomyces pombe, identifying 3,432,749 relationships for budding yeast and 421,198 relationships forS. pombe. This resulted in a comprehensive, searchable online Knowledge Graph database, available atyeast.connectome.toolsandspombe.connectome.tools, which offers users extensive access to various interactions and pathways. Our analysis underscores the power of integrating artificial intelligence with bioinformatics, as demonstrated through key insights into important nodes like Hsp104 and Atg8 proteins. This work not only facilitates efficient data extraction in yeast research but also presents a scalable model for similar studies in other biological systems.

HIGHLIGHTS

Generated Yeast Knowledge Graphs from full-text research articles.

Analyzed over 90,000 publications forSaccharomycesandSchizosaccharomycesspecies.

Extracted millions of relationships using GPT-based natural language processing.

Yeast Knowledge Graphs accessible through interactive web platforms and APIs.

Advanced tool enabling insights into gene networks and functional interactions.

Abstract Figure
Uncovering the signaling networks of disseminated glioblastoma cellsin vivowith INSIGHT
Authors: Ahn Ryuhjin , D’Souza Alicia D. , Long Lawrence , Cui Yufei , Burgenske Danielle , Bakken Katrina K. , Ott Lauren L. , Carlson Brett L. , Zhou Grace , Yaron-Barir Tomer M. , Kohale Ishwar N. , Whittaker Charles A. , Flower Cameron T. , Wyckoff Jeffrey , Tuma Ann , Johnson Jared L. , Sarkaria Jann , White Forest M.
Published: December 2024

Dysregulation of intracellular signaling networks underpins cancer. However, a systems-level elucidation of how signaling networks within distinct cell subpopulations drive cancer progressionin vivohas been unattainable due to technical limitations. We developed INSIGHT (INvestigating SIGnaling network of specific cell subpopulation in Heterogeneous Tissue), a new platform technology combining fluorescence-activated cell sorting with ultra-sensitive mass spectrometry to enable phosphoproteomic characterization of rare and discrete cell subpopulations from fixed tissues. We demonstrated the broad utility of INSIGHT by analyzing the oligodendroglial cell-specific signaling network in the mouse brain. We then applied INSIGHT to investigate the rare, disseminated tumor cell subpopulation in glioblastoma patient-derived xenograft models. INSIGHT uncovered a global rewiring of signaling networks with tumor cell dissemination, marked by a transition from proliferation-associated signaling in the primary tumor cells to signaling associated with postsynapse, neuronal migration, and ion homeostasis in disseminated tumor cells. We reveal interconnections between signaling circuitries within the networks, with numerous proteins, including GluA2, exhibiting altered phosphorylation without protein expression changes, emphasizing the role of post-translational modifications in glioblastoma dissemination. We validated key phosphorylation changes and inferred differentially active kinases with tumor spread to offer new systems-level insights into glioblastoma dissemination mechanismsin vivo. INSIGHT is generally applicable to a wide range of biological systems without genetic engineering and provides quantitative phosphorylation and protein expression data for selected cell subpopulations from heterogeneous tissues.
Unveiling the diversity, transmission, and zoonotic potential of microbes in true insectivores
Authors: Li Hongfeng , Huang Zheng Y.X. , Lan Jie , Hu Li , Wei Xuemin , Wang Yuhao , Li Xiujun , Li Yang , Becker Daniel J. , Wei Fuwen , Xu Yifei
Published: December 2024

The Eulipotyphla (true insectivores) is the third largest mammalian order, comprising over 500 species, and could be an important source of human infectious diseases. However, relatively little is known about the diversity of microbes in insectivores and the contribution of insectivores to virus transmission more specifically among wild hosts. In this study, we compiled a comprehensive dataset containing over 400,000 records of insectivores and their associated microbes from 1903 to 2023. Our analyses showed that insectivores host a wide spectrum of 941 microbes, 60% of which are viruses and are predominantly found in the shrew and hedgehog families. Notably, human-associated viruses harbored by shrews and hedgehogs were phylogenetically closely related to those found in humans, suggesting potential bidirectional transmission between insectivores and humans. Moreover, virus-sharing networks revealed that insectivores held the second-most central position for virus sharing, just second to bats, among all mammalian orders. Insectivores had a high proportion of cross-order transmitted viruses, including many human-associated viruses. Dietary diversity, habitat diversity, and distributional traits (e.g. geographical range size, mean latitude, and urban adaptation status) emerged as the key ecological factors contributing to this cross-species virus transmission. Our findings highlight the microbial diversity present in insectivores, indicating this order may act as potential incubators for novel viruses capable of infecting mammals and spreading viruses of public health concern.
OMAnnotator: a novel approach to building an annotated consensus genome sequence
Authors: Bates Sadé , Dessimoz Christophe , Nevers Yannis
Published: December 2024

Motivation

Advances in sequencing technologies have enabled researchers to sequence whole genomes rapidly and cheaply. However, despite improvements in genome assembly, genome annotation (i.e. the identification of protein-coding genes) remains challenging, particularly for eukaryotic genomes: it requires combining several approaches (typicallyab initio, transcriptomics, and homology search), each with its own pros and cons. Deciding which gene models to retain in a consensus is far from trivial, and automated approaches tend to lag behind laborious manual curation efforts in accuracy.

Results

Here, we present OMAnnotator, a novel approach to building a consensus annotation. OMAnnotator repurposes the OMA algorithm, originally designed to elucidate evolutionary relationships among genes across species, to integrate predictions from different annotation sources, using evolutionary information as a tie-breaker. We validated OMAnnotator by reannotating theDrosophila melanogasterreference genome and comparing it with the expert-curated reference and results from the automated pipelines BRAKER2 and EvidenceModeller. OMAnnotator produced a consensus annotation that outperformed each individual input and surpassed the existing pipelines. Finally, when applied to three recently published genomes, OMAnnotator gave substantial improvements in two cases, and mixed results in the third, which had already benefited from extensive expert curation.

Conclusion

We introduce an original, flexible, and effective approach to annotating genomes by integrating multiple lines of evidence. The method’s robustness is underlined by its successful implementation in re-annotating recently published genomes, opening up new avenues in eukaryotic genome annotation.
Meiotic Sex Chromosome Inactivation: conservation across theDrosophilagenus
Authors: Avelino Camila C. , Mendonca Carolina A. , Goldstein Gabriel , Bernardo Carvalho A. , Vibranovski Maria D.
Published: December 2024

The inherent difference between sex chromosomes in males and females drives conflicts in gene expression, leading to adaptations such as Meiotic Sex Chromosome Inactivation (MSCI). In this study, we explore the evolutionary dynamics of MSCI within theDrosophilagenus by analyzing transcriptomes across different stages of spermatogenesis inD. melanogasterand its progressively more distant relatives,D. simulans,D. willistoni, andD. mojavensis. Stage-specific bulk RNA sequencing, showing a strong correlation in spermatogenic gene expression patterns among these species, revealed that MSCI dates back to the early evolution of theDrosophilagenus, impacting the regulation of both coding and long non-coding RNAs. Notably, for newly evolved genes, X-linked genes show higher expression levels than autosomal genes during mitosis and meiosis, indicating that MSCI predominantly regulates older genes. In contrast, newly evolved autosomal genes exhibit a gradual increase in expression throughout spermatogenesis, reaching their peak in the post-meiotic phase. During this phase, the expression of X-linked new genes decreases, eventually aligning with that of autosomal genes. This expression pattern suggests that haploid selection plays a crucial role in the regulation of new genes, with monoallelic expression of the X chromosome providing an advantage across all stages of germline development, while autosomal gene expression gains a selective edge primarily in the post-meiotic phase. Together, these findings provide new insights into the evolution of sex chromosomes and highlight the critical role of MSCI in shaping gene expression profiles inDrosophila.
Nanobactericides Derived from Cinnamon Bark Extract: Phytochemical Profiling and Antibacterial Efficacy Against Bacterial Panicle Blight in Rice
Authors: Naji Qamar Mohammed , Zulperi Dzarifah Mohamed , Ahmad Khairulmazmi , Hata Erneeza Mohd
Published: December 2024

Bacterial panicle blight (BPB), caused by the Gram-negative aerobic bacteriumBurkholderia glumae (B.glumae), poses a significant threat to global rice production. Cinnamon bark extract (CBE) has demonstrated potent antioxidant and antimicrobial properties due to its high concentration of bioactive compounds, including eugenol and cinnamaldehyde. To enhance the efficacy and stability of these volatile compounds, this study employed nanotechnology and encapsulation techniques. The objective was to develop a CBE-based nanoformulation to inhibitB. glumaeand control BPB in rice. CBE-chitosan (CBE-CS) nanoformulations were synthesized using ionic cross-linking between chitosan and trisodium phosphate (TPP) at various concentrations (0%, 0.5%, 1%, 2%, and 4% TPP). More than 15 active compounds were identified in CBE, including (Z)-3-Phenylacrylaldehyde, 2-Propenoic acid, 3-(2-hydroxyphenyl), cinnamaldehyde dimethyl acetal, and hexadecanoic acid. Bacterial membrane damage was significantly greater in treatments with CBE compared to untreated controls. The synthesized nanoparticles ranged in size from 43.66 nm to 106.1 nm, with encapsulation efficiencies between 48.65% and 48.78%, and loading capacities between 25.65% and 33.9%. Scanning electron microscopy (SEM) revealed spherical and homogeneous nanoparticles, while FTIR and XRD analysis confirmed the successful encapsulation of CBE in the chitosan nanoparticles. The antibacterial activity of the nanoformulations showed inhibition zones ranging from 7.5 to 11.8 mm, with the CBE-CS formulation containing 0.5% TPP demonstrating the highest efficacy (MIC = 15.6 μmol/ml; MBC = 31.25 μmol/ml).
FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment
Authors: Li Mengdie , Yang Yating , Chen Tangcong , Luo Yueyang , Zhang Yingqian , Liu Huanzhong , Maes Michael
Published: December 2024

Abstract

Background

The demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging is a risk factor for synaptic plasticity damage in the brain and leads to neurocognitive dysfunctions. However, whether FTO is associated with susceptibility to depression in different age groups remains unknown.

Methods

We subjected 3-and 12-month-old C57BL/6J male mice to 6 weeks of chronic unpredictable mild stress (CUMS) and 3 weeks of hippocampal injection of FTO knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 male mice in each 3-month-old and 12-month-old groups were divided into three groups (n=12): Sham, CUMS, and FTO-KD. After 6 weeks, we assessed behavioral deficits (depressive and anxiety-like behaviors and cognitive impairment) by behavioral tests and hippocampal neuronal damage (dendritic spine density, neuronal atrophy, and expression of proteins associated with synaptic plasticity) by molecular biochemical experiments.

Results

The results showed that 12-month-old C57BL/6J mice were more likely to develop depression-like behavior and spatial learning and memory impairment induced by CUMS than 3-month-old mice. Chronic stress-induced depression-like behavior and cognitive impairment worsened after the FTO-KD intervention. In the hippocampus of 3-and 12-month-old mice, CUMS induced the downregulation of FTO, nerve growth factor (NGF), reelin, and synaptic plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density of dendritic spines, and an increased number of neuronal pyknotic nuclei, leading to neuronal disarray, which was more significant in 12-month-old animals. FTO deficiency accelerated neuronal damage in the hippocampus of 12-month-old CUMS mice.

Conclusions

This study provides rodent evidence that FTO deficiency may increase the susceptibility to depression in older adults by impairing hippocampal neuronal function and neuronal synaptic plasticity in an age-dependent manner. This suggests that the development of FTO activators may be an effective treatment for depression in older adults.
Shared and distinct adaptations to early-life exercise training based on inborn fitness
Authors: Sadler Daniel G. , Treas Lillie , Barre Mary , Ross Taylor , Sikes James D. , Zhong Ying , Britton Steven L. , Koch Lauren G. , Wankhade Umesh , Børsheim Elisabet , Porter Craig
Published: December 2024

Background

Low cardiorespiratory fitness due to genetics increases the risk for cardiometabolic disease. Endurance exercise training promotes cardiorespiratory fitness and improves cardiometabolic risk factors, but with great heterogeneity. Here, we tested the hypothesis that the metabolic phenotype imparted by low parental (inborn) cardiorespiratory fitness would be overcome by early-life exercise training, and that exercise adaptations would be influenced in part by inborn fitness.

Methods

At 26 days of age, male and female rat low-capacity runners (LCR,n=20) and high-capacity runners (HCR,n=20) generated by artificial selection were assigned to either sedentary control (CTRL,n=10) or voluntary wheel running (VWR,n=10) for 6 weeks. Post-intervention, whole-body metabolic phenotyping was performed, and the respiratory function of isolated skeletal muscle and liver mitochondria assayed. Transcriptomics and proteomics were performed on skeletal muscle and liver tissue using RNA-sequencing and mass spectrometry, respectively.

Results

Daily VWR volume was 1.8-fold higher in HCR-VWR compared to LCR-VWR. In LCR, VWR reduced adiposity and enhanced glucose tolerance, coincident with elevated total energy expenditure. While intrinsic skeletal muscle mitochondrial respiratory function was unaffected by VWR, estimated skeletal muscle oxidative capacity increased in VWR groups owing to greater mitochondrial content. In the liver, both maximal oxidative capacity and ATP-linked respiration were higher in HCR-VWR than HCR-CTRL. Transcriptomic and proteomic profiling revealed extensive remodeling of skeletal muscle and liver tissue by VWR, elements of which were both shared and distinct based on inborn fitness.

Early-life exercise training partially overcomes the metabolic phenotype imparted by low inborn cardiorespiratory fitness. However, molecular adaptations to VWR are partly influenced by inborn fitness, which may have implications for personalized exercise medicine.
Effects of Spatial Constraints of Inhibitory Connectivity on the Dynamical Development of Criticality in Spiking Networks
Authors: Kern Felix Benjamin , Date Takahisa , Chao Zenas C.
Published: December 2024

Neural systems are hypothesized to operate near criticality, enhancing their capacity for optimal information processing, transmission and storage capabilities. Criticality has typically been studied in spiking neural networks and related systems organized in random or full connectivity, with the balance of excitation and inhibition being a key determinant of the critical point of the system. However, given that neurons in the brain are spatially distributed, with their distances significantly influencing connectivity and signal timing, it is unclear how the spatial organization of excitatory and inhibitory connectivity influences the network’s self-organization towards criticality. Here, we systematically constrain the distance and density of inhibitory connectivity in two-dimensional spiking networks and allow synaptic weights to self-organize with activity-dependent excitatory and inhibitory plasticity in the presence of a low level of stochastic intrinsic activity. We then investigate the relationship between inhibitory connectivity, synaptic weights, and the resulting network activity during and after development. We find that networks with longer-range inhibitory synapses tend towards more supercritical behavior compared to networks with a similar number of shorter-range inhibitory synapses. We show that this distance dependence is a consequence of weaker long-range synapses after development due to the presence of synaptic delays, which shift most spike pairs outside of the potentiation window of the inhibitory learning rule.
Vasoinhibin is Generated by the Renin-Angiotensin System
Authors: Núñez Francisco Freinet , Siqueiros-Marquez Lourdes , Adán-Castro Elva , Zamora Magdalena , Robles Juan Pablo , Ruiz-Herrera Xarubet , Bertsch Thomas , Triebel Jakob , Martínez de la Escalera Gonzalo , Clapp Carmen
Published: December 2024

Vasoinhibin is a fragment of the hormone prolactin (PRL) that inhibits angiogenesis, vasopermeability, and vasodilation. Cathepsin D (CTSD) cleaves the N-teminal of PRL to generate vasoinhibin in the retina of neonate mice as revealed by the CTSD inhibitor, pepstatin A (PA). However, PA also inhibits renin. Because renin is expressed in the retina and the renin-angiotensin system (RAS) gives rise to peptides with positive and negative effects on blood vessel growth and function, we investigated whether renin cleaves PRL to vasoinhibin in the newborn mouse retina and in the circulation. Newborn mouse retinal extracts from wild-type and CTSD-null newborn mice cleaved PRL to a 14 kDa vasoinhibin and such cleavage was prevented by heat-inactivation, PA, and the selective renin inhibitor VTP-27999 suggesting the contribution of renin. In agreement, recombinant renin cleaved different species PRLs to the expected 14 kDa vasoinhibin, a mass consistent with a consensus renin cleavage site located at Leu124-Leu125 in rat and mouse PRLs and at Leu126-Leu127 in human, bovine, and ovine PRLs. Dehydration and rehydration (D/R) in rats increased the levels of renin and PRL in plasma. Further increase in PRL circulating levels by the dopamine D2 receptor blocker, sulpiride, enabled detection of 14 kDa vasoinhibin in D/R rats. Moreover, the incubation of PRL with plasma from D/R rats generated a 14 kDa vasoinhibin that was prevented by VTP-27999. These findings add renin to the list of PRL-cleaving proteases and introduce vasoinhibin as a RAS-mediated mechanism for regulating blood vessel growth and function.
Top-down attention and Alzheimer's pathology impact cortical selectivity during learning, influencing episodic memory in older adults
Authors: Sheng Jintao , Trelle Alexandra N , Romero America , Park Jennifer , Tran Tammy T , Sha Sharon , Andreasson Katrin , Wilson Edward N. , Mormino Elizabeth , Wagner Anthony D
Published: December 2024

Human aging affects the ability to remember new experiences, in part, because of altered neural function during memory formation. One potential contributor to age-related memory decline is diminished neural selectivity -- i.e., a decline in the differential response of cortical regions to preferred vs. non-preferred stimuli during event perception -- yet the factors driving variability in neural selectivity with age remain unclear. We examined the impact of top-down attention and preclinical Alzheimer's disease (AD) pathology on neural selectivity during memory encoding in 156 cognitively unimpaired older participants who underwent fMRI while performing a word-face and word-scene associative memory task. Neural selectivity in face- and place-selective cortical regions was greater during events that were later remembered compared to forgotten. Critically, neural selectivity during learning positively scaled with memory-related variability in top-down attention, whereas selectivity negatively related to early AD pathology, evidenced by elevated plasma pTau181. Path analysis revealed that neural selectivity at encoding mediated the effects of age, top-down attention, and pTau181 on associative memory. Collectively, these data reveal multiple pathways that contribute to memory differences among older adults -- AD-independent reductions in top-down attention and AD-related pathology alter the precision of cortical representations of events during experience, with consequences for remembering.
Solar UVB Radiation for the Synthesis of Vitamin D3in Four Skin Types – Model Propagation Studies
Authors: Pasricha Pradeep K. , Upadhayaya Arun K.
Published: December 2024

The study presents model computations of the wavelength of absorption of radiation energy in the ultraviolet (UV) band in the epidermis cells keratinocytes for four skin types: White-skin, Pale Yellow-skin, Brown-skin and Black-skin. Keratinocytes cells are idealized as spherical dielectric microcavities, with central melanin granule and a layer of keratin molecules surrounding the cell. Refractive indices of epidermis tissue, melanin and keratin are obtained from the published data. The size distribution of keratinocytes in the epidermis is obtained with the conjecture that the differentiated keratinocytes grow exponentially in the process of cell differentiation. The mole concept is used to calculate the size of melanin granules, one each for four skin types, using the published data of melanin content of the four skin types. The thickness of keratin layer around the cell keratinocyte does not occur in the model computations. In White-skin, the model solar UVB radiation wavelength range of 296 – 300 nm is close to the maximal range of 295 – 300 nm, of the range 290 – ∼317 nm, of the synthesis of vitamin D3 by the compound 7-dehydrocholesterol in skin cells. In Pale Yellow-skin, Brown-skin and Black-skin, the model solar UVB/(limited UVA) radiation wavelength ranges for the synthesis of vitamin D3are 290 – 295 nm, 290 – 297 nm and 307 – 314 nm, and 313 – ∼317 nm, respectively. The solar UVB radiation synthesizes vitamin D3to the maximum in White-skin and the least in Black-skin. The synthesis of vitamin D3is to a lesser extent in Pale Yellow-skin compared to White-skin. The solar UVB radiation synthesizes ample levels of vitamin D3in the pigmented Brown-skin. The solar UVB radiation is more effective to synthesize vitamin D3in Pale Yellow-skin compared to Brown-skin, since the Brown-skin is prone to pigmentation. The UVA radiation wavelength ranges that cause tanning of skin are analyzed. In Brown-skin, in particular, the wavelength range is 315 – 342 nm. Also, the physical mechanism of the UVA-caused tanning is similar to that of the UVB-caused tanning of skin. The UVA radiation phototherapies toward tanning of skin may be applied in the wavelength range of 340 – 370 nm. A sunscreen gel, in Brown-skin, in particular, may have the formulation to absorb the effective solar UVB and UVA radiation of wavelengths of 290 – 310 nm and 315 – 340 nm, respectively. The UVB radiation phototherapies to synthesize vitamin D3, especially for individuals allergic to medicinal vitamin D3, have varied model wavelength ranges for the four skin types. The study emphasizes the specific role of UV radiation toward synthesis of vitamin D3and therapeutic use in skin tanning for different skin types. The preparation of a sunscreen gel for skin protection may vary with skin type.
Cardiomyocyte STIM1 downregulation exacerbates post-Myocardial Infarction remodeling by dysregulating mitochondrial ultrastructure and metabolic signaling
Authors: Cacheux Marine , Velasco Juan , Wu Xiaohong , Strauss Benjamin , Akar Fadi G.
Published: December 2024

Background

Loss of stromal interaction molecule 1 (STIM1) expression in smooth muscle cells protects against ischemia-reperfusion (I/R) injury. Whether and how decreased STIM1 expression in cardiomyocytes (CM) impacts cardiac remodeling in response to I/R injury remains unknown.

Objective

To examine mechanisms by which decreased CM-STIM1 expression in the adult heart modulates cardiac function before and after I/R injury.

Methods

8-week old mice underwent cardiotropic AAV9-mediated gene transfer of shRNA directed against STIM1 (shSTIM1). Control (Ctrl) mice underwent shRNA luciferase or PBS injections. Ctrl and shSTIM1 mice were then challenged by 30-min coronary occlusion to induce MI,in-vivo. Mechanical, structural and electrophysiological (EP) properties were compared 1-week following MI. In a second cohort of mice, the impact of CM-STIM1 knockdownper seon upstream metabolic signaling, mitochondrial ultrastructure, and electrophysiological properties were studied.

Results

CM-STIM1 expression was markedly decreased in shSTIM1 vs Ctrl hearts. Challenge within-vivoI/R injury resulted in more pronounced (p<0.0001) LV dysfunction indexed by % drop in fractional shortening in shSTIM1 (44.3%) vs Ctrl (12.2%) hearts 1-week post-MI. Similarly, post-MI structural remodeling and the extent of fibrosis were more severe in shSTIM1 vs Ctrl despite comparable infarct size (p=0.514). Consistently, shSTIM1 exhibited greater impairment in post-MI EP function including predisposition to spatially-discordant action potential alternans. To understand mechanisms underlying this differential remodeling, we examined the impact of CM-STIM1 downregulation on mitochondrial ultrastructure and regulation by metabolic signaling. Quantification of mitochondrial morphology revealed smaller, more rounded mitochondria caused by CM-STIM1 downregulationper se. Underlying these changes was a marked (by 55%, p=0.0057) increase in phosphorylated (p)DRP1 at S616 along with reduced OPA1 expression. Mitochondrial alterations were associated with significant decreases in AMPK downstream signaling with loss of phosphorylated-to-total Raptor and ACC expression in shSTIM1-vs-Ctrl hearts consistent with impaired fatty acid oxidation. These MI-independent metabolic alterations coincided with higher pro-arrhythmic vulnerability under conditions of elevated heart rate.

Conclusions

Our findings reveal that decreased CM-STIM1 expression exacerbates post-MI remodeling likely by altering metabolic processes and mitochondrial network dynamics.

Functionally, STIM1-dependent mitochondrial alterations impact EP function during conditions of elevated heart rate even without the confounding influence of MI.
Development of the “EASY-HSV (Efficient And Simple high-Yield Herpes Simplex virus Vector) system” based on HSV-1 genome-maintaining HEK293 cells
Authors: Maeda Fumio , Adachi Shungo , Natsume Tohru
Published: December 2024

Herpes simplex virus (HSV) amplicon vector is a promising molecular tool with a large transgene capacity of 150 kb. However, the conventional vector production method is labor-intensive and expensive, limiting its application. Here, we generated HEK293 cells harboring the HSV genome (293/HSV) and developed an EASY-HSV (Efficient And Simple high-Yield Herpes Simplex virus Vector) system in which 293/HSV cells are transfected with only two plasmids.
Bridging species boundaries: eDNA and genetic analysis reveal hybrid settlement at the very end of American eel distribution
Authors: Jacobsen Magnus Wulff , Nygaard Rasmus , Frankowski Jens , Buur Tengstedt Aja Noersgaard , Nielsen Julius , Hansen Michael M. , Hedeholm Rasmus , Retzel Anja , Hedal Ida , Urban Paulina , Jørgensen Casper Gundelund , Larsen Rasmus Stenbak , Maggini Sara , Rask Peter , Nielsen Einar Eg
Published: December 2024

Documenting species distributions and hybridization patterns is paramount for elucidating biogeography and understanding speciation processes. Here we combined genetic specimen analysis and environmental DNA (eDNA) to investigate the presence of American eel (Anguilla rotrata) and American × European eel (Anguilla anguilla) hybrids in Greenland freshwater. We further tested the use of eDNA to document hybridization by using European eel mtDNA as a proxy for hybrid occurrence. Overall, eDNA analysis detected mainly American eel but also European eel mtDNA. This finding was validated by DNA sequencing, which identified 3 out of 26 captured eels (14.3%) carrying European eel mtDNA. Five eels (19.2%), including all three with European mtDNA, were heterozygous for species-specific nuclear gene variants, supporting a hybrid ancestry. Further, eDNA successfully identified eels in lakes where they were caught by fyke net fishing, extending their confirmed northern range by 40 km, and indicated eel presence >200km further north. The study provides an empirical demonstration of the use of eDNA to document hybrid occurrence and extends the reported northern distribution of eels in Greenland significantly beyond previous observations. Further, the existence of hybrid eels in Greenland may be key for understanding the complex mechanisms of hybridization between American and European eels.