Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

Background: Patients with Varicose veins (VV) show no obvious symptoms in the early stages, and it is a common and frequent clinical condition. DNA methylation plays a key role in VV by regulating gene expression. However, the molecular mechanism underlying methylation regulation in VV remains unclear. Methods: The mRNA and methylation data of VV and normal samples were obtained from the Gene Expression Omnibus (GEO) database. Methylation-Regulated Genes (MRGs) between VV and normal samples were crossed with VV-associated genes (VVGs) obtained by weighted gene co-expression network analysis (WGCNA) to obtain VV-associated MRGs (VV-MRGs). Their ability to predict disease was assessed using receiver operating characteristic (ROC) curves. Biomarkers were then screened using a random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). Next, gene set enrichment analysis (GSEA) was performed to explore the functions of biomarkers. Furthermore, we also predicted their drug targets, and constructed a competing endogenous RNAs (ceRNA) network and a drug target network. Finally, we verified their mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Total three VV-MRGs, namely Wnt1-inducible signaling pathway protein 2 (WISP2), Cysteine-rich intestinal protein 1 (CRIP1), and Odd-skipped related 1 (OSR1) were identified by VVGs and MRGs overlapping. The area under the curves (AUCs) of the ROC curves for these three VV-MRGs were greater than 0.8. RF was confirmed as the optimal diagnostic model, and WISP2, CRIP1, and OSR1 were regarded as biomarkers. GSEA showed that WISP2, CRIP1, and OSR1 were associated with oxidative phosphorylation, extracellular matrix (ECM), and respiratory system functions. Furthermore, we found that lncRNA MIR17HG can regulate OSR1 by binding to hsa-miR-21-5p and that PAX2 might treat VV by targeting OSR1. Finally, qRT-PCR results showed that the mRNA expression of the three genes was consistent with the results of the datasets. Conclusion: This study identified WISP2, CRIP1, and OSR1 as biomarkers of VV through comprehensive bioinformatics analysis, and preliminary explored the DNA methylation-related molecular mechanism in VV, which might be important for VV diagnosis and exploration of potential molecular mechanisms.
Productivity and nutrient removal by the microalga Chlamydopodium fusiforme grown outdoors in BG-11 and piggery wastewater

The objective of this work was to test the growth of the freshwater microalga Chlamydopodium fusiforme MACC-430 in diluted piggery wastewater (PWW) for biomass production which is a potential producer of biostimulating and antimicrobial compounds. The productivity and effectiveness in removing nitrogen and phosphorus by the cultures were tested outdoors in open ponds by comparing the mineral medium BG-11 medium (control) and piggery wastewater (PWW). Daily biomass yields were found 14.7 ± 4.6g m-2 d-1 in BG-11 and 17.6 ± 6.7g m-2 d-1 in 10-fold diluted wastewater (PWW10) with deionized water. Further increase in the biomass productivity yield (33.1 ± 5.6g m-2 d-1) was achieved with more concentrated PWW (5-fold dilution – PWW5). Nitrogen removal rate (N-NH4 +) reached 21.4 ± 2.9mg L-1 d-1 in cultures grown in PWW10 and increased to 38.4±16.3mg L-1 d-1 using the PWW5. The use of undiluted PWW strongly increased the bacterial load, which caused the loss of the culture. The photosynthetic performance measured as the maximum fluorescence yield Fv/Fm ratio in both the PWW10 and BG-11 cultures showed a cyclic behavior, as it decreased during the day and recovered at night. However, in the cultures grown in diluted PWW the Fv/Fm ratio slightly increased throughout the cultivation. Between PWW10 and BG-11, no significant differences were observed in photosynthetic oxygen evolution; on the contrary, PWW5 showed a 30% reduction compared to PWW10 and BG-11. Significantly lower chlorophyll and carotenoid contents were found in the cultures grown in PWW compared to BG-11. Biochemical composition showed a slightly higher protein content in biomass grown in PWW10 (53.4%) compared to BG-11 (52.7%). The protein content further increased (61.3%) when the more concentrated PWW5 was used. The biomass, particularly that produced on PWW, revealed antimicrobial activity against plant pathogens, including fungi, and oomycete, while rather weak biostimulant activity was determined for the C. fusiforme biomass independently of the cultivation medium. Results demonstrated that C. fusiforme is a robust strain suitable to be grown in diluted PWW outdoors with a high nutrient removal rate.
Mutational Analysis of Xist and the X-inactivation Center

Author(s): Goodrich, Leeanne | Advisor(s): Panning, Barbara | Abstract: In placental mammals, dosage compensation of the sex chromosomes isachieved through inactivation of one X chromosome in female cells. This Xchromosome inactivation (XCI) requires tight developmental regulation to ensure all butone X chromosome is silenced.At the center of this process is Xist, a long non-coding RNA. Upon differentiationof a female cell, Xist spreads in cis to coat and silence the inactive X chromosome.While upregulation of Xist, has been shown to be sufficient for X inactivation to occur,no one has thoroughly investigated whether Xist is necessary for the establishment of Xchromosome inactivation. In this thesis I provide evidence that Xist is not required fordosage compensation of the X chromosome during epiblast-like cell differentiation. Thisresult suggests Xist-independent silencing mechanisms for this essential process maybe in place.A 1-2 Mb region of the X chromosome, termed the X-inactivation center (Xic) isnecessary in two copies for XCI to occur, indicating it is necessary for cells to count thenumber of X chromosomes present. I delete one copy of the putative 2 Mb Xic in maleand female mouse embryonic stem cells and present evidence that this deletion is notwell tolerated, suggesting that this region requires finer resolution mapping to identifythe minimal element required for counting.Finally, I finish with a review which elaborates on studies that enlighten ourunderstanding of activators and repressors that control XCI. Our findings challengeexisting dogmas in the field and provide the foundation for future work focused onuncovering the molecular mechanisms behind Xist-independent silencing of the Xchromosome.
Musculoskeletal pain is prevalent in Chinese medical and dental students: A cross-sectional study

Objectives Musculoskeletal pain (MSP) is a major reason for consultation in primary care and is becoming increasingly prevalent among medical students. There is little research on the current situation of MSP among Chinese medical and dental students. Data on the analysis of risk factors related to MSP are also limited. The objectives of this study were to investigate the prevalence and characteristics of MSP among Chinese medical and dental students and to explore the risk factors for MSP and students' intent to seek medical treatment. Methods An anonymous, internet-based, cross-sectional, open survey was distributed to medical and dental students at Fujian Medical University, Fuzhou, China. Data on the demographic information and characteristics of MSP were collected and analyzed. In addition to descriptive statistics, logistic regression was used to analyze significant risk factors contributing to MSP. Results A total of 1,178 students responded to the survey (response rate = 79.6%), including 722 medical students and 456 dental students. The age ranged from 16 to 24. There were 553 male students and 625 female students. A total of 523 students reported neck pain (NP, 44.4%), 361 students reported low back pain (LBP, 30.6%), and 182 students reported joint pain (JP, 15.4%). Sixty-six students (5.6%) simultaneously suffered from NP, LBP, and JP. The prevalence of NP (49.1 vs. 41.4%, P = 0.01), LBP (34.6 vs. 28.1%, P = 0.02), and JP (20.2 vs. 12.5%, P < 0.001) was significantly higher in dental students than in medical students. The prevalence of MSP was significantly different among the academic years for NP and LBP (P = 0.02 and P < 0.001, respectively). Univariate and multivariate regression analyses demonstrated that female sex, PSS-10 score, and major of stomatology were risk factors for MSP. Medical and dental students' intention to seek treatment for MSP was low and was significantly associated with the severity of pain. Conclusions The prevalence of MSP in Chinese medical and dental students is high, especially for NP and LBP, and is significantly higher in dental students than in medical students. The prevalence of NP and LBP were significantly different among academic grades. Female sex, PSS-10 score, and major of stomatology were risk factors for MSP. Students' intent to seek treatment for MSP was very low and was determined by the severity of pain.
Rich polymorphic variants of alpha satellite 34mer higher order repeats in hg38 assembly of human chromosome Y

A challenging problem in human population genetics is related to the unique role of human Y chromosome, with properties that distinguish humans from other species. Centromeres in primate genomes are constituted of tandem repeats of ∼ 171 bp alpha satellite monomers, commonly organized into higher order repats (HORs). Because of gaps in DNA sequencing, HOR regions as genomic “black holes” have been understudied in spite of crucial importance. Only recently the sequencing of more complete satellite DNAs becomes accessible. In human Y chromosome the largest alpha satellite higher order repeat unit 34/36mer was found, but its polymorphic variants were not investigated. Here, we study the human Y chromosome centromeric genomic sequence from hg38 assembly using our novel ALPHAsub algorithm for simple identification of alpha satellite arrays and robust GRM algorithm for HOR identification in repeat sequences. We determine the monomer alignment scheme for alpha satellite HOR array based on canonical 34mer HOR, discovering a wealth of novel polymorphic variants which include the HOR-type monomer duplications, monomer deletions/insertions or rearrangements and non-HOR insertions. Author Summary The centromere is important for segregation of chromosomes during cell division in eukaryotes. Its destabilization results in chromosomal missegregation, aneuploidy, hallmarks of cancers and birth defects. In primate genomes centromeres contain tandem repeats of ∼ 171 bp alpha satellite DNA, commonly organized into higher order repeats (HORs). In this work, we used our bioinformatics algorithms to study the human Y chromosome centromeric genomic sequence and we discover a wealth of novel polymorphic variants which include the HOR-type monomer duplications, monomer deletions/insertions or rearrangements and non-HOR insertions. These results could help to understand the role of alpha satellites and alpha HOR structures in centromeric organization and function, in particular their role in creating a functional kinetochore that is crucial for chromosome segregation during cell division.
Folding latency of fluorescent proteins affects the mitochondrial localization of fusion proteins

The discovery of fluorescent proteins (FPs) has revolutionized cell biology. The fusion of targeting sequences to FPs enables the investigation of cellular organelles and their dynamics; however, occasionally, such fluorescent fusion proteins (FFPs) exhibit behavior different from that of the native proteins. Here, we constructed a color pallet comprising different organelle markers and found that FFPs targeted to the mitochondria were mislocalized when fused to certain types of FPs. Such FPs included several variants of Aequorea victoria green FP (aqGFP) and a monomeric variant of the red FP. Because the FFPs that are mislocalized include FPs with faster maturing or folding mutations, the increase in the maturation rate is likely to prevent their expected localization. Indeed, when we reintroduced amino acid substitutions so that the FP sequences were equivalent to that of wild-type aqGFP, FFP localization to the mitochondria was significantly enhanced. Moreover, similar amino acid substitutions improved the localization of mitochondria-targeted pHluorin, which is a pH-sensitive variant of GFP, and its capability to monitor pH changes in the mitochondrial matrix. Our findings demonstrate the importance of selecting FPs that maximize FFP function.
Architectural Components of Compact Growth Habits in Diploid Roses

Criteria to determine the horticultural quality of ornamental plants include plant architecture, flower characteristics, and resistance to biotic and abiotic stresses. The architecture of a rose (Rosa sp.) bush is linked to flower yield and ornamental value. The Texas A&M University (TAMU) Rose Breeding and Genetics program has the objective of developing garden rose cultivars that flower heavily and exhibit a compact full shape. To determine which architectural traits are key for the development of this desired shape, five rose seedlings with a desirable compact growth habit and five with an undesirable growth habit were selected from TAMU diploid rose breeding germplasm. This comparison indicated that the key traits for the selection of compact growth habit are the number of primary shoots followed by the number of secondary and tertiary shoots produced.
Large scale differential gene expression analysis identifies genes associated with Bipolar Disorder

Background Bipolar disorder (BD) remains one of the most common psychiatric disorders with high morbidity and mortality. Several polymorphisms have been found to be implicated in the pathogenesis of BD, however, these loci have small effect sizes that fail to explain the high heritability of the disease. Here, we attempt to better understand the genetic basis of bipolar disorder by identifying differentially expressed genes (DEG) in post-mortem brain tissues of patients with BD versus normal controls. Methods Nine publicly available gene expression data sets with 702 samples derived from human post-mortem brain tissues were used for differential expression analysis. 7 data sets were used for the discovery of the gene signature and the other two were left for independent validation. The multi-cohort analysis was performed using a random-effects model utilizing R and MetaIntegrator package. Results The analysis resulted in the identification of 13 up-regulated and 9 down-regulated genes in BD. The BD gene signature was further validated in two independent data sets and resulted in an Area Under the ROC Curve (AUC) of 0.74 and 0.73, respectively. Gene set enrichment analysis was performed and resulted in the identification of several biological processes and pathways related to BD including Ca transport, inflammation and DNA damage response. Conclusion Our findings support the previous findings that link BD pathogenesis to abnormalities in glial inflammation and calcium transport and also identify several other biological processes not previously reported to be associated with the development of BD. Such findings will improve our understanding of the genetic basis underlying BD and may have future clinical implications.
Type 1 interferon suppresses expression and glucocorticoid induction of glucocorticoid-induced leucine zipper (GILZ)

SLE is a systemic multi-organ autoimmune condition associated with reduced life expectancy and quality of life. Glucocorticoids (GC) are heavily relied on for SLE treatment but are associated with detrimental metabolic effects. Type 1 interferons (IFN) are central to SLE pathogenesis and may confer GC insensitivity. Glucocorticoid-induced leucine zipper (GILZ) mediates many effects of GC relevant to SLE pathogenesis, but the effect of IFN on GC regulation of GILZ is unknown. We performed in vitro experiments using human PBMC to examine the effect of IFN on GILZ expression. JAK inhibitors tofacitinib and tosylate salt were used in vivo and in vitro respectively to investigate JAK-STAT pathway dependence of our observations. ChiP was performed to examine glucocorticoid receptor (GR) binding at the GILZ locus. Several public data sets were mined for correlating clinical data. High IFN was associated with suppressed GILZ and reduced GILZ relevant to GC exposure in a large SLE population. IFN directly reduced GILZ expression and suppressed the induction of GILZ by GC in vitro in human leukocytes. IFN actions on GILZ expression were dependent on the JAK1/Tyk2 pathway, as evidenced by loss of the inhibitory effect of IFN on GILZ in the presence of JAK inhibitors. Activation of this pathway led to reduced GR binding in key regulatory regions of the GILZ locus. IFN directly suppresses GILZ expression and GILZ upregulation by GC, indicating a potential mechanism for IFN-induced GC resistance. This work has important implications for the ongoing development of targeted GC-sparing therapeutics in SLE.
Investigating effective testing strategies for the control of Johne's disease in western Canadian cow-calf herds using an agent-based simulation model

Johne's disease is an insidious infectious disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Johne's disease can have important implications for animal welfare and risks causing economic losses in affected herds due to reduced productivity, premature culling and replacement, and veterinary costs. Despite the limited accuracy of diagnostic tools, testing and culling is the primary option for controlling Johne's disease in beef herds. However, evidence to inform specific test and cull strategies is lacking. In this study, a stochastic, continuous-time agent-based model was developed to investigate Johne's disease and potential control options in a typical western Canadian cow-calf herd. The objective of this study was to compare different testing and culling scenarios that included varying the testing method and frequency as well as the number and risk profile of animals targeted for testing using the model. The relative effectiveness of each testing scenario was determined by the simulated prevalence of cattle shedding MAP after a 10-year testing period. A second objective was to compare the direct testing costs of each scenario to identify least-cost options that are the most effective at reducing within-herd disease prevalence. Whole herd testing with individual PCR at frequencies of 6 or 12 months were the most effective options for reducing disease prevalence. Scenarios that were also effective at reducing prevalence but with the lowest total testing costs included testing the whole herd with individual PCR every 24 months and testing the whole herd with pooled PCR every 12 months. The most effective method with the lowest annual testing cost per unit of prevalence reduction was individual PCR on the whole herd every 24 months. Individual PCR testing only cows that had not already been tested 4 times also ranked well when considering both final estimated prevalence at 10 years and cost per unit of gain. A more in-depth economic analysis is needed to compare the cost of testing to the cost of disease, taking into account costs of culling, replacements and impacts on calf crops, and to determine if testing is an economically attractive option for commercial cow-calf operations.
Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.
Consumer and Strategic Firm Response to Nutrition Shelf Labels

The display of nutrition facts is mandatory on virtually all packaged foods sold in the United States. Yet manufacturers and retailers add their own claims to differentiate their products and capture consumers' attention at point of sale. We implement experimental nutrition claims on shelf labels in a retail setting and test how consumers react to the display of these labels that express information reported on the Nutrition Facts Panel in a different format. We hypothesize that our labels either shift demand for the highlighted healthier products uniformly or trigger more complex demand rotations. Our estimated heterogeneous labeling effects suggest that consumers process nutrition information differently depending on which and how many claims are displayed and prefer products labeled with a single claim overall. When we simultaneously consider demand and supply responses under three price setting behaviors (competitive pricing, Bertrand‐Nash pricing, and monopoly pricing), we find that consumer surplus and overall welfare is highest when our labels display multiple nutrient claims and retailers are able to adjust prices across the entire product category. Firms' profits are highest when single nutrient claims are displayed, however. We conclude that firms with market power have little incentive to voluntarily display nutrition claims that maximize welfare.