Miracle-dz/UniFAR-FTUs huggingface dataset:
VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6

Hyperactivation of Wnt/β-catenin signaling pathway is a critical step in colorectal tumorigenesis. In this study, we identified that V-set and transmembrane domain containing 2A (VSTM2A) was a top-downregulated secreted protein that negatively regulated Wnt singling pathways in colorectal cancer (CRC). We investigated the functional mechanisms and clinical implication of VSTM2A in CRC. Methods: Function of VSTM2A was investigated in vitro and in vivo. VSTM2A binding partner was identified by mass spectrometry, immunoprecipitation and Western blot. The clinical impact of VSTM2A was assessed in 355 CRC patients and TCGA cohort. Results: VSTM2A protein was prominently silenced in CRC tumor tissues and cell lines mediated by its promoter hypermethylation. VSTM2A DNA promoter hypermethylation and VSTM2A protein downregulation was associated with poor survival of CRC patients. Ectopic expression of VSTM2A inhibited colon cancer cell lines and organoid growth, induced CRC cells apoptosis, inhibited cell migration and invasion, and suppressed growth of xenograft tumors in nude mice. VSTM2A was released from CRC cells through a canonical secretion pathway. Secreted VSTM2A significantly suppressed Wnt signaling pathway in colon cancer cells. Wnt signaling co-receptor LDL receptor related protein 6 (LRP6) was identified as a cell membrane binding partner of VSTM2A. Using deletion/mutation and immunoprecipitation, we demonstrated that VSTM2A bound to LRP6 E1-4 domain with its IgV domain. VSTM2A suppressed LRP6 phosphorylation in a time and dose dependent manner, and induced LRP6 endocytosis and lysosome-mediated degradation, which collectively contributing to the inactivation of Wnt signaling. Conclusions: VSTM2A is a novel antagonist of canonical Wnt signaling by directly binding to LRP6 and induces LRP6 endocytosis and degradation. VSTM2A is a potential prognostic biomarker for the outcome of CRC patients.
Salinity Tolerance and Recovery Attributes of Warm-season Turfgrass Cultivars

As population growth places greater pressures on potable water supplies, nonpotable recycled irrigation water is becoming widely used on turfgrass areas including golf courses, sports fields, parks, and lawns. Nonpotable recycled waters often have elevated salinity levels, and therefore turfgrasses must, increasingly, have good salinity tolerance to persist in these environments. This greenhouse study evaluated 10 commonly used cultivars representing warm-season turfgrass species of bermudagrass (Cynodon spp.), zoysiagrass (Zoysia spp.), st. augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze], and seashore paspalum (Paspalum vaginatum Swartz) for their comparative salinity tolerance at electrical conductivity (EC) levels of 2.5 (control), 15, 30, and 45 dS·m–1. Salinity treatments were imposed on the grasses for 10 weeks via subirrigation, followed by a 4-week freshwater recovery period. Attributes, including turf quality, the normalized difference vegetation index (NDVI), canopy firing, and shoot biomass reductions were evaluated before and after salinity stress, as well as after the 4-week freshwater recovery period. Results showed considerable differences in salinity tolerance among the cultivars and species used, with the greatest tolerance to elevated salinity noted within seashore paspalum cultivars and Celebration® bermudagrass. In comparison with growth in 2.5-dS·m–1 control conditions, increased shoot growth and turf quality were noted for many bermudagrass and seashore paspalum cultivars at 15 dS·m–1. However, st. augustinegrass and some zoysiagrass cultivars responded to elevated salinity with decreased growth and turf quality. No cultivars that had been exposed to 30- or 45-dS·m–1 salinity recovered to acceptable levels, although bermudagrass and seashore paspalum recovered to acceptable levels after exposure to 15-dS·m–1 salinity. More severe salinity stress was noted during year 2, which coincided with greater greenhouse temperatures relative to year 1.
Mesenchymal Stem Cells Alleviate DHEA-Induced Polycystic Ovary Syndrome (PCOS) by Inhibiting Inflammation in Mice

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Chronic inflammation is considered to be the cause of ovarian dysfunction. Increasing evidence in animal studies and in preliminary clinical trials has demonstrated that MSCs possess immunomodulatory effects via their interaction with immune cells. However, their contribution to PCOS remains unclear. In this study, we showed that the administration of hUC-MSCs could efficiently improve the pathological changes of PCOS mice induced by dehydroepiandrosterone (DHEA), including ovarian histopathology and function. Moreover, we found that the administration of MSCs significantly downregulated the expression of proinflammatory factors (TNF-α, IL-1β, and IFN-γ) and fibrosis-related genes (CTGF) in ovarian and uterus tissues and affected the systemic inflammatory response. The percentage of peripheral neutrophils, M1 macrophages, and B cells was significantly reduced, while M2 macrophages and regulatory T cells (Tregs) were increased in hUC-MSC-treated mice. In the spleen, the percentage of neutrophils, M1 macrophages, IFN-γ+CD19+B cell, IFN-γ+CD4+T cells (Th1), and IL-17+CD4+T cells (Th17) was significantly decreased in hUC-MSC-treated mice. These results suggested that hUC-MSC treatment could alleviate ovarian dysfunction by inhibiting ovarian local and systemic inflammatory responses.
Big‐Leaf Mahogany on CITES Appendix II: Big Challenge, Big Opportunity

On 15 November 2003, big-leaf mahogany (Swietenia macrophylla King, Meliaceae), the most valuable widely traded Neotropical timber tree, gained strengthened regulatory protection from its listing on Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). CITES is a United Nations-chartered agreement signed by 164 nations. Its objective is to ensure that international trade in animals and plants does not threaten species survival. Appendix II listing, the second-most stringent category of CITES protection, requires verification that internationally traded individuals or volumes of listed species have been harvested legally and in a manner that is not detrimental to their role in ecosystems where they naturally occur. This decision, made through a two-thirds majority vote at the twelfth Convention of Parties (CoP12) in November 2002, recognizes that international intervention is necessary to control illegal harvests and to maintain viable populations across mahogany’s natural range from Mexico through Central and South America as far south as Bolivia. What happens next? Can Appendix II listing solve the mahogany problem? The 12-month interval between the vote at CoP12 and official onset of Appendix II status in late 2003 suggests the degree of potential difficulty in implementation. No guidelines for making nondetriment findings (NDF) for timber species listed on CITES have been developed because none have been needed until now—the convention has historically focused on trade in wildlife. In October 2003 delegates from CITES Management and Scientific Authorities, representing 14 range and consumer nations, gathered to outline an implementation strategy at the second meeting of the Mahogany Working Group, convened by the CITES Secretariat and Brazil’s Ministry of the Environment. More re-
Hormonal and neural correlates of care in active versus observing poison frog parents

The occasional reversal of sex-typical behavior across species suggests that many of the neural circuits underlying behavior are conserved between males and females and can be activated in response to the appropriate social condition or stimulus. Most poison frog species (Family Dendrobatidae) exhibit male uniparental care, but flexible compensation has been observed in some species, where females can perform parental care duties when males disappear. Here, we investigated hormonal and neural mechanisms of sex-typical and sex-reversed parental care in a typically male uniparental species, the Dyeing Poison Frog (Dendrobates tinctorius). We first characterized hormone levels and whole brain gene expression across parental care stages during sex-typical behavior. Surprisingly, hormonal changes and brain gene expression differences associated with parental care in males were mirrored in their non-caregiving female partners. To further explore the disconnect between underlying neuroendocrine mechanisms and behavior, we characterized hormone levels and neural activity patterns in females performing sex-reversed parental care. In contrast to hormone and gene expression patterns, we found that patterns of neural activity were linked to the active performance of parental behavior, with sex-reversed tadpole transporting females exhibiting neural activity patterns more similar to those of transporting males than non-caregiving females. We suggest that parallels in hormones and brain gene expression in parental males and non-caregiving females are related to females’ ability to flexibly take over parental care in the absence of their male partners. Highlights Dendrobates tinctorius is a typically male uniparental species, but females will sometimes show parental care in the absence of their male mates. Testosterone decreases while cortisol increases in tadpole transporting males and their non-transporting female partners. Parental males and their non-caregiving female partners exhibit parallel patterns in brain gene expression across parental care stages. Neural activity in tadpole transporting females reflects transporting males more than non-transporting females. Patterns in active versus observing parents may relate to flexible compensation in parental behavior in D. tinctorius.
Histone deacetylase inhibitors reinforce the phenotypical markers of breast epithelial or mesenchymal cancer cells but inhibit their migratory properties

Introduction Histone deacetylase inhibitors (HDIs) are a group of compounds that exhibit anticancer activity, but their significance and usefulness in breast cancer (BC) treatment are still controversial. The ability of cancer cells to invade and migrate is augmented by the acquisition of a mesenchymal phenotype – a process known as epithelial-to-mesenchymal transition (EMT). Changes in the expression level of different cadherins, so-called cadherin switches, have been used to monitor the EMT process in development and tumor progression, in particular migration and invasion potential. The aim of this study was to analyze the influence of two HDIs – valproic acid (VPA) and vorinostat (SAHA) – on the migration potential of different BC cell types, as well as on EMT, or its reverse process – mesenchymal-to-epithelial transition, progression by means of shift in epithelial and mesenchymal marker expression. Methods HDI treatment-induced expression of E- and N-cadherin at the mRNA and protein levels was evaluated by qPCR, Western blotting and immunostaining methods, respectively. BC cell proliferation and migration were assessed by BrdU, xCELLigence system and wound-healing assay. Results VPA and SAHA inhibited the proliferation and migration in a dose- and time-dependent manner, regardless of the BC cell type. Unawares, BC cells having a more mesenchymal phenotype (MDA-MB-468) were found to overexpress N-cadherin, whereas BC lines having an epithelial phenotype (T47D, MCF7) responded to HDI treatment by a significant increase of E-cadherin expression. Discussion We suggest that HDAC inhibition results in a more relaxed chromatin concomitant to an increase in the expression of already expressing genes. Conclusion By using multiple cancer cell lines, we conclude that HDI induction or reversal of EMT is not a universal mechanism, yet inhibition of cell migration is, and thus EMT should not be considered as the only measurement for tumor aggressiveness.
Cross-Sectional and Longitudinal Validation of Serum Neurofilament Light Chain (NfL) as a Biomarker of Parkinson’s Disease Progression

Background Alterations in neurofilament light chain (NfL), reflecting axonal damage, have been proposed as a biomarker for neurological disorders including Parkinson’s disease (PD). Methods We measured NfL concentrations by immunoassay in (1) a set of longitudinal CSF samples from 82 PD, 14 other neurodegenerative disorders (OND), and 53 healthy controls (HC); (2) A cross-sectional cohort with paired CSF and serum samples from subjects with 151 PD, 344 OND, and 20 HC, and (3a) a large longitudinal validation cohort with serum samples from 375 PD, 178 HC, and 57 prodromal Lewy Body disorder with hyposmia or isolated REM sleep behaviour disorder (iRBD), (3b) 216 symptomatic and 298 asymptomatic LRRK2, GBA, and SNCA mutation carriers in the Parkinson’s Progression Markers Initiative (PPMI). Mean differences in serum NfL levels between diagnostic groups, and correlation with motor signs, cognitive measures and dopamine transporter imaging, were assessed. Linear mixed effects models were used to assess longitudinal changes in log10 (NfL) in relation to demographic, clinical, and imaging variables. Findings In the longitudinal cohort (1) NfL in CSF increased over time and was significantly positively correlated with MDS-UPDRS III motor and total scores in the PD group (p=0·0231 and 0·0081). In the cross-sectional cohort (2) the paired CSF and serum NfL samples were highly correlated (Spearman’s rank ). In the large validation cohort (3a) mean baseline serum NfL was higher in PD (13 ±7·2pg/ml), hyposmics (15±15·1pg/ml), and iRBD (17±8pg/ml) compared with HC (12±6·7pg/ml) but was highest in the seven OND cases (18±7pg/ml). In the genetic cohort (3b), serum NfL levels were lower in asymptomatic than in symptomatic mutation carriers. There was a significant (age-adjusted) longitudinal increase in serum NfL in PD compared with HC. Serum NfL values were significantly positively associated with longitudinal MDS-UPDRS motor and total scores, as well as age. Interpretation We identified NfL as the first blood-based PD progression biomarker. NfL levels in serum samples are increased in PD compared to HC, increase significantly over time in PD, and correlate with a clinical measure of disease severity. Although the specificity of NfL in PD is low and additional, more specific biomarkers are needed, serum NfL is the first blood-based biomarker candidate that could support disease stratification (PD vs. OND), track clinical progression, and might be used to assess responsiveness to neuroprotective treatments.
Validity of ICD-10 diagnoses of overweight and obesity in Danish hospitals

Purpose Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals. Patients and methods We linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m2 as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m2. Results Of all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m2, yielding a PPV of 87.6% (95% CI: 87.2–88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3–94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6–86.6). The PPV increased with higher patient age: from 75.3% (95% CI: 73.8–76.9) in those aged 18–29 years to 94.7% (95% CI: 92.6–96.9) in patients aged 80 years and above. Completeness of obesity/overweight diagnosis coding among patients recorded with BMI ≥25 kg/m2 was only 10.9% (95% CI: 10.8–11.0). Conclusion Our findings indicate a high validity of the ICD-10 code E66 for overweight/obesity when recorded; however, completeness of coding was low. Nonetheless, ICD-10 discharge codes may be a suitable source of data on overweight/obesity for epidemiological research.
Mechanisms that allow cortical preparatory activity without inappropriate movement

We reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEFSEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity evolves in FEFSEM during fixation in parallel with an objective measure of visual-motor gain. We propose that the use of FEFSEM output as a gain signal allows for preparation to progress in the pursuit system without causing movement. We also show that preparatory modulation of firing rate in FEFSEM progresses in a way that predicts movement, providing evidence against the “movement-null” space hypothesis of how preparatory activity can progress without movement. Finally, there is partial reorganization of FEFSEM population activity between preparation and movement. We propose that this reorganization allows for a directionally non-specific component of preparatory visual-motor gain enhancement in the pursuit system.
Conventional distance sampling versus strip transects and abundance indices for estimating abundance of greater gliders (Petauroides volans) and eastern ringtail possums (Pseudocheirus peregrinus)

Abstract Context. Accurate estimates of abundance are extremely useful for wildlife management and conservation. Estimates generated from distance sampling are typically considered superior to strip transects and abundance indices, as the latter do not account for probability of detection, thereby risking significant error. Aim. To compare density estimates generated from conventional distance sampling (CDS) of arboreal marsupials with strip transect density estimates and abundance indices. Methods. Off-track CDS and strip transects were used to estimate densities of P. volans and P. peregrinus across ∼2.6 km2 of remnant eucalypt forest at Mt Duval in north-eastern New South Wales. Key results. CDS density estimates for P. volans (1.36 ha−1, 95% confidence interval (CI) of 1.07–1.72 ha−1) and P. peregrinus (0.28 ha−1, 95% CI 0.22–0.35 ha−1) were consistent with densities reported in other studies conducted in open eucalypt forests. A strip transect width of 40 m for P. volans resulted in a collective set of values for density (1.35 ha−1), error (s.e. ± 0.14), precision (cv 0.10) and 95% CI (1.07–1.62 ha−1) closest to those associated with the CDS-generated density estimate (1.36 ha−1, s.e. ± 0.15, cv 0.10, 95% CI 1.07–1.72 ha−1). Strip widths of 10 to 40 m resulted in density estimates for P. peregrinus closest to those generated through CDS, but much less precise. Conclusions. Although a 40-m wide strip transect provided a robust density estimate for P. volans at Mt Duval, this is unlikely to be consistent across different study areas. Strip transects provided less precise density estimates, or underestimated P. peregrinus density at Mt Duval, when compared with CDS density estimates. CDS should be favoured over strip transects or abundance indices for estimating P. volans and P. peregrinus abundance, because it is capable of providing more meaningful and robust abundance estimates by accounting for the probability of detection from the transect line across different habitats. Implications. Researchers, conservation managers and decision makers should be aware that common methods for assessing arboreal marsupial abundance have serious potential weaknesses. Thus, it would be prudent to invest in studies that address imperfect detection to improve the quality of monitoring data.
Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective

With the accumulation of scientific knowledge of the genetic causes of common diseases and continuous advancement of gene-editing technologies, gene therapies to prevent polygenic diseases may soon become possible. This study endeavored to assess population genetics consequences of such therapies. Computer simulations were used to evaluate the heterogeneity in causal alleles for polygenic diseases that could exist among geographically distinct populations. The results show that although heterogeneity would not be easily detectable by epidemiological studies following population admixture, even significant heterogeneity would not impede the outcomes of preventive gene therapies. Preventive gene therapies designed to correct causal alleles to a naturally-occurring neutral state of nucleotides would lower the prevalence of polygenic early- to middle-age-onset diseases in proportion to the decreased population relative risk attributable to the edited alleles. The outcome would manifest differently for late-onset diseases, for which the therapies would result in a delayed disease onset and decreased lifetime risk, however the lifetime risk would increase again with prolonging population life expectancy, which is a likely consequence of such therapies. If gene therapies that prevent heritable diseases were to be applied on a large scale, the decreasing frequency of risk alleles in populations would reduce the disease risk or delay the age of onset, even with a fraction of the population receiving such therapies. With ongoing population admixture, all groups would benefit over generations.
Estimation of Genetic Parameters of Yield Traits in Crosses of Cowpea

The experiment was conducted in understanding and describing the nature and extent of genotypic and phenotypic variation, heritability, expected genetic advance, as well as gene effects between yield and yield components of cowpea. The experiments were conducted in the Department of Agricultural Technology, Federal College of Forestry, Jericho, Ibadan, Nigeria. Five generations (P 1 , P 2 , F 1 , F 2 and F 3 ) of three crosses from three cowpea lines ( TVu1xTVu14019, TVu1xTVu3629 and TVu3629xTVu14019). In days to flowering, there was no epistatic effect in the cross TVu3629 x TVu14019. All the crosses exhibited high broad sense heritability and moderate genetic advance as percentage of mean for pod length, number of seeds per pod and 100 seed weight while cross TVu1 x TVu14019 and TVu1 x TVu3629 also in seed yield per plant. There was significant complementary and duplicate epistatic gene effect in days to flowering, pod length, number of seeds per pod in the cross involving TVu1 with TVu3629 and TVu14019. There was significant epistasis gene effect in the cross of TVu3629 x TVu14019 in pod length, number of seeds per pod and 100 seed weight. High magnitude of broad sense heritability along with moderate to high genetic advance as percentage of mean recorded for days to flowering, pod length, number of seeds per pod, 100 seed weight and seed yield per plant indicated that these characters can be improved through selection in advanced generations. Since different gene effects were responsible for the inheritance of the same character in different crosses and for the different characters in the same cross specific handling of individual crosses for different characters would be advantageous for the improvement of these characters. The characters controlled by both additive and non-additive gene effects can be successfully improved by utilizing hybrid vigour or biparental mating method of breeding.