bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of keratin and keratin associated proteins are linked with hair loss condition in spontaneously mutated inbred mice
Authors: Chilukoti Neeraja , Pavuluri Sivapriya , Kumar Satish 
Published: July 2024

AbstractHair loss condition is heritable and is influenced by multifactorial inheritance. In the present study, spontaneously mutated mice showed hair loss phenotype with defect in the first cycle of hair follicle formation leading to cyclic alopecia. These mutant mice follow autosomal recessive inheritance pattern. The transcriptomic profile and differential gene expression analysis of skin tissues by RNA-sequencing at different stages of hair cycle formation was performed. The genes with significant differential genes expression levels in each stage of hair cycle formation were identified and most of these genes were shown to be associated with keratinization process and hair follicle formation. Transcriptome profiling followed by QPCR validation revealed that mRNA levels ofKrt16,Alox15,Fetub(upregulated) andMsx2(downregulated) were significantly differentially expressed in mutant skin tissues during late anagen and catagen stages.Krt6bmRNA and protein levels were significantly higher in the mutant mice during all stages of first hair cycle formation. The present study provides basis for understanding the differential gene expression of hair-related genes, including keratinization-associated proteins and its relevance. These mutant mice can serve as a model for studying hair loss condition that can be further used in the identification, evaluation and treatment strategies for alopecia condition.
The discovery of phages in the Substantia Nigra and its implication for Parkinson’s Disease
Authors: Zhao Yun , Xiong Changxian , Wang Bingwei , Li Daotong , Liu Jiarui , Wei Shizhang , Hou Yujia , Zhou Yuan , Zheng Ruimao 
Published: July 2024

AbstractBackground:A century ago, a mystery between virus and Parkinson’s disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly-developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantial nigra (SN), and whether symbiotic viruses underlie PD pathogenesis remain unknown.Methods:We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands and Switzerland. We used bioinformatic approaches including viruSITE and the Virus-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson’s correlation analysis was used to examine the association between the viral RNA fragment counts (VRFC) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN.Findings:We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A significant correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified three bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174 and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the UK, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken cGAS-STING function.Interpretation:This is the first study to discover the involvement of phages in PD pathogenesis. A life-long low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phages-human symbiosis.
Maintenance of long-term transposable element activity through regulation by nonautonomous elements
Authors: Omole Adekanmi Daniel , Czuppon Peter 
Published: July 2024

AbstractTransposable elements are DNA sequences that can move and replicate within genomes. Broadly, there are two types: autonomous elements, which encode the necessary enzymes for transposition, and nonautonomous elements which rely on the enzymes produced by autonomous elements for their transposition. Nonautonomous elements have been proposed to regulate the numbers of transposable elements, which is a possible explanation for the persistence of transposition activity over long evolutionary times. However, previous modeling studies indicate that interactions between autonomous and nonautonomous elements usually result in the extinction of one type. Here, we study a stochastic model that allows for the stable coexistence of autonomous and nonautonomous retrotransposons. We determine the conditions for this coexistence and derive an analytical expression for the stationary distribution of their copy numbers, showing that nonautonomous elements regulate stochastic fluctuations and the number of autonomous elements in stationarity. We find that the stationary variances of each element can be expressed as a function of the average copy numbers and their covariance, enabling data comparison and model validation. These results suggest that continued transposition activity of transposable elements, regulated by nonautonomous elements, is a possible evolutionary outcome that could for example explain the long co-evolutionary history of autonomousLINE1and nonautonomousAluelement transposition in the human ancestry.
JAK2/STAT3 signaling pathway mediates methylmercury toxicity in mouse astrocyte neuronal C8-D1A cell line
Authors: Ahmed Aafia , Aschner Michael , Ferrer Beatriz 
Published: July 2024

AbstractMethylmercury (MeHg) is an environmental pollutant. Consumption of contaminated fish is the main exposure route in humans, leading to severe neurological disorders. Upon ingestion MeHg reaches the brain and selectively accumulates in astrocytes disrupting glutamate and calcium homeostasis and increasing oxidative stress. Despite extensive research, the molecular mechanisms underlying MeHg neurotoxicity remain incompletely understood. The induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role activating antioxidant responses during MeHg-induced oxidative injury have garnered significant attention as a potential therapeutic target against MeHg toxicity. However, recent studies indicate that the Nrf2 signaling pathway alone may not be sufficient to mitigate MeHg-induced damage, suggesting the existence of other protective mechanisms. The signal transducer and activator of transcription 3 (STAT3) plays a crucial role in cell growth and survival. Several studies have also highlighted its involvement in regulating redox homeostasis, thereby preventing oxidative stress through mechanisms that involve modulation of nuclear genes that encode electron transport complexes (ETC) and antioxidant enzymes. These characteristics suggest that STAT3 could serve as a viable mechanism to mitigate MeHg toxicity, either in conjunction with or as an alternative to Nrf2 signaling. Our previous findings demonstrated that MeHg activates the STAT3 signaling pathway in the GT1-7 hypothalamic neuronal cell line, suggesting its potential role in promoting neuroprotection. Here, to elucidate the role of the STAT3 signaling pathway in MeHg neurotoxicity, we pharmacologically inhibited STAT3 using AG490 in the C8D1A astrocytic cell line exposed to 10 µM MeHg. Our data demonstrated that pharmacological inhibition of STAT3 phosphorylation exacerbates MeHg-induced mortality, antioxidant responses, and ROS production, suggesting that STAT3 may contribute to neuroprotection against MeHg exposure in astrocytes.
Towards a Rosetta Stone to Decipher the Survival Networks of Senescence
Authors: Olascoaga Samael , López-Diazguerrero Norma Edith 
Published: July 2024

AbstractCellular senescence, an irreversible state of cell cycle arrest in response to various stressors that can damage cells, is a key player in developing and progressing multiple chronic degenerative diseases associated with aging. Over the years, these senescent cells accumulate in organs and tissues, it is thought that the accumulation of these cells results from their capacity to evade programmed cell death by developing and activating Senescent Cell Anti-apoptotic Pathways (SCAPs); however, numerous aspects of the development and activation of these SCAPs are still unknown. In this study, we analyzed the variations in the expression levels and co-expression patterns of 39 SCAPs genes across 33 tissues from young and elderly individuals. Surprisingly, we did not observe a consistent increase in SCAPs gene expression with age in any tissue. Instead, we found tissue-specific variations in gene expression levels, changes in the strength of gene coordination, and the wiring and rewiring of gene co-expression networks that depend on the tissue. Our results suggest that the development and activation of SCAPs are far more complex than previously understood; merely increasing the expression of specific survival genes would not adequately explain the anti-apoptotic capabilities of senescent cells. We suggest that the formation and triggering of SCAPs entail a complex interplay of factors, encompassing distinct alterations in expression levels alongside shifts in the intensity and configurations of gene interactions, moreover, these modifications are unique to individual tissues. Our results deepen our understanding of how senescent cells evade programmed cell death and are essential for developing targeted pharmacological therapies that can selectively and safely eliminate senescent cells more effectively.
Androgen receptor plays critical role in regulating cervical cancer cell migration
Authors: Bose Sarpita , Das Subhrangshu , Maity Sebabrata , Chakrabarti Oishee , Chakrabarti Saikat 
Published: July 2024

AbstractCervical cancer (CC) is the second most common cancer among women in India and the fourth worldwide. While major genes and pathways have been studied, further research is needed to identify candidates for targeted therapy in metastatic disease. This study used a network biology approach to identify key genes in disease progression. Stage-specific cervical cancer protein-protein interaction networks (PPIN) were constructed by overlaying stage-specific, patient-derived transcriptomics data onto a human protein-protein interaction network (HPPIN). Graph-theory-based network analysis identified important interacting proteins (IIPs) with maximum connectivity, high centrality scores, and significant global and local network perturbation scores. Among the identified IIPs, the Androgen receptor (AR) emerged as one of the crucial yet understudied regulator in cervical cancer. Patient samples and in vitro experiments showed significant downregulation in cervical cancer. Ligand-dependent overexpression of AR reduced cancer cell migration while failed to induce apoptosis in CC cell lines. Downregulation of mesenchymal markers and restoration of epithelial markers suggested AR’s potential in reversing invasive properties of cervical cancer cells. AR overexpression upregulated its downstream target PTEN and restored GSK3β activity by interfering with AKT phosphorylation, probably leading to degradation of mesenchymal markers. Further studies showed AR reduced cell motility by hindering focal adhesion formation and Actin filament assembly. An increased G-Actin ratio suggested AR disrupted cytoskeletal dynamics through the RhoA/ROCK1/LIMK1/CFL1 pathway, impeding cervical cancer cell spread.
Drug resistant pancreatic cancer cells exhibit altered biophysical interactions with stromal fibroblasts in imaging studies of 3D co-culture models
Authors: Struth Eric , Labaf Maryam , Karimnia Vida , Liu Yiran , Cramer Gwendolyn , Dahl Joanna B. , Slack Frank J. , Zarringhalam Kourosh , Celli Jonathan P. 
Published: July 2024

AbstractInteractions between tumor and stromal cells are well known to play a prominent roles in progression of pancreatic ductal adenocarcinoma (PDAC). As knowledge of stromal crosstalk in PDAC has evolved, it has become clear that cancer associated fibroblasts can play both tumor promoting and tumor suppressive roles through a combination of paracrine crosstalk and juxtacrine interactions involving direct physical contact. Another major contributor to dismal survival statistics for PDAC is development of resistance to chemotherapy drugs. Though less is known about how the acquisition of chemoresistance impacts upon tumor-stromal crosstalk. Here, we use 3D co-culture geometries to recapitulate juxtacrine interactions between epithelial and stromal cells. In particular, extracellular matrix (ECM) overlay cultures in which stromal cells (pancreatic stellate cells, or normal human fibroblasts) are placed adjacent to PDAC cells (PANC1), result in direct heterotypic cell adhesions accompanied by dramatic fibroblast contractility which leads to highly condensed macroscopic multicellular aggregates as detected using particle image velocimetry (PIV) analysis to quantify cell velocities over the course of time lapse movie sequences. To investigate how drug resistance impacts these juxtacrine interactions we contrast cultures in which PANC1 are substituted with a drug resistant subline (PANC1-OR) previously established in our lab. We find that heterotypic cell-cell interactions are highly suppressed in drug-resistant cells relative to the parental PANC1 cells. To investigate further we conduct RNA-seq and bioinformatics analysis to identify differential gene expression in PANC1 and PANC1-OR, which shows that negative regulation of cell adhesion molecules, consistent with increased epithelial mesenchymal transition (EMT), is also consistent with loss of hetrotypic cell-cell contact necessary for the contractile behavior observed in drug naïve cultures. Overall these findings elucidate the role of drug-resistance in inhibiting an avenue of stromal crosstalk which is associated with tumor suppression and also help to establish cell culture conditions useful for further mechanistic investigation.
Towards Reliable Diabetes Prediction: Innovations in Data Engineering and Machine Learning Applications
Authors: Talukder Md. Alamin , Islam Md. Manowarul , Uddin Md Ashraf , Kazi Mohsin , Khalid Majdi , Akhter Arnisha , Moni Mohammad Ali 
Published: July 2024

AbstractObjectiveDiabetes is a metabolic disorder that causes the risk of stroke, heart disease, kidney failure, and other long-term complications because diabetes generates excess sugar in the blood. Machine learning (ML) models can aid in diagnosing diabetes at the primary stage. So, we need an efficient machine learning model to diagnose diabetes accurately.MethodsIn this paper, an effective data preprocessing pipeline has been implemented to process the data and random oversampling to balance the data, handling the imbalance distributions of the observational data more sophisticatedly. We used four different diabetes datasets to conduct our experiments. Several ML algorithms were used to determine the best models to predict diabetes faultlessly.ResultsThe performance analysis demonstrates that among all ML algorithms, RF surpasses the current works with an accuracy rate of 86% and 98.48% for dataset-1 and dataset-2; XGB and DT surpass with an accuracy rate of 99.27% and 100% for dataset-3 and dataset-4 respectively. Our proposal can increase accuracy by 12.15% compared to the model without preprocessing.ConclusionsThis excellent research finding indicates that the proposed models might be employed to produce more accurate diabetes predictions to supplement current preventative interventions to reduce the incidence of diabetes and its associated costs.
OPTIMIZATION OFRECOVERABLE CLEAR PLASTIC POT(rCPP) METHOD AND VALIDATION OF MOLECULAR MARKS FOR THE SCREENING OF DEEP ROOTING OF RICE (Oryza sativaL.)
Authors: Pratama Mukhlis Syahril , Basunanda Panjisakti , Wulandari Rani Agustina , Widyawan Muhammad Habib 
Published: July 2024

AbstractThe generally of Rice plants have shallow roots and require large amounts of water for cultivation. However, water resources are becoming increasingly limited due to climate change. Therefore, efforts are needed to improve rice genetics in order to produce stable crop production in drought-prone areas. One strategy to avoid drought stress is to change the architecture of deeper rooting. The identification can be done by screening the root morphology. Most of the screening methods for deep rooting ability in rice are stilldestructive, so the proposed activity in this study is the optimization of theRecoverable Clear Plastic Pot(rCPP) method that can detect deep rooting ability in rice early andnon-destructively. The method was further validated using InDel and SSR-based molecular markers designed based on theDRO1gene. TheDRO1gene plays a role in increasing the root growth angle, so that the roots grow in a deeper vertical direction. The results showed thatRecoverable Clear Plastic Pot(rCPP) optimization was able to show good screening ability for plant root charactersnon-destructively. Mayangan is the best drought-tolerant genotype based on deep rooting characters that have root distribution centered on theinner circle. The relationship between deep rooting screening using the DRO1 marker provides results that are in line with deep rooting screening through theRecoverable Clear Plastic Pot(rCPP) method.HighlightThis research is part of an effort to improve rice genetics in order to produce stable crop production in drought-prone areas.The research activities used the optimizationRecoverable Clear Plastic Pot(rCPP) method.The rCPP method was validated using InDel and SSR-based molecular markers designed based on theDRO1gene.Optimization of rCPP shows good screening ability for plant rooting characters in anon-destructive manner.
Two mechanisms of photoenergy regulation revealed by kinetic behaviors of chlorophyll fluorescence during light adaptation
Authors: Chen Junqing , Fu Lijiang , Guo Ya , Tan Jinglu 
Published: July 2024

AbstractPhotochemical reactions were analyzed and modeled to observe photoenergy regulation mechanisms in PSII from measured chlorophyll fluorescence (ChlF) kinetics. Two pH-driven mechanisms were revealed: One is the PsbS-mediated non-photochemical quenching (NPQ) of activated antennae (A*), as commonly understood, and the other is a disruption of energy transfer from A* to P680. Representing the latter with a conformational change from complex formation of zeaxanthin and lutein with antennae closely described measured ChlF from initially dark-adapted state to light-adapted state and measured NPQ variations. Analysis based on the model indicates that zeaxanthin and lutein lead to slow protracted reductions in P680* and ChlF via the second mechanism without strong influence by pH or PsbS. Protonation of PsbS plays a major role via the first mechanism in responding to fast changes in illumination. The research provides insights into the mechanisms for photoenergy regulation in PSII and a kinetic model with broadened applicability.
Loss ofMEF2Cfunction by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice
Authors: Yousefian-Jazi Ali , Kim Suhyun , Choi Seung-Hye , Chu Jiyeon , Nguyen Phuong Thi-Thanh , Park Uiyeol , Lim Kayeong , Hwang Hongik , Lee Kyungeun , Kim Yeyun , Hyeon Seung Jae , Rhim Hyewhon , Ryu Hannah L. , Lim Grewo , Stein Thor D. , Ryu Hoon , Lee Junghee 
Published: July 2024

AbstractGenetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region ofMEF2C(rs304152), residing in a putative enhancer element, using convolutional neural network. The enhancer mutation ofMEF2Creduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of theMEF2Cenhancer decreases expression of mitochondria-encoded genes. Moreover,MEF2Cmutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress.MEF2Cdeficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits. Together,MEF2Cdysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.
Understanding the physical determinants of pressure denaturation: Exploring the unfolding pathways of Yfh1 at different temperatures with High-Pressure NMR
Authors: Roumestand Christian , Dudas Erika , Puglisi Rita , Calió Antonino , Barthe Philippe , Temussi Piero Andrea , Pastore Annalisa 
Published: July 2024

AbstractProteins unfold under different environmental insults, among which are heat, cold, high pressure and chaotropic agents. Understanding the mechanisms that determine unfolding under each of these conditions is an important problem that directly relates to the physical forces that determine the three-dimensional structure of a protein. Here, we studied a residue-specific description of the unfolding transitions of the marginally stable yeast protein Yfh1 using high-pressure nuclear magnetic resonance. We compared the cold, heat and pressure unfolded states and demonstrated what has up to now been only a hypothesis: the pressure-unfolded spectrum shares features in common with that at low but not at high temperature and room pressure, suggesting a tighter similarity of the mechanisms and a similar role of hydration in these two processes. By exploring the phase diagram of the protein and mapping unfolding onto the three-dimensional structure of the protein, we also show that the pressure-induced unfolding pathways at low and high temperatures differ, suggesting a synergic mechanism between pressure- and temperature-induced denaturation. Our observations help us to reconstruct the structural events determining unfolding and distinguish the mechanisms that rule the different processes of unfolding.