Miracle-dz/UniFAR-FTUs huggingface dataset:
Giberellic Acid-Stimulated Transcript Proteins Evolved through Successive Conjugation of Novel Motifs and Their Subfunctionalization1

Exploration of GAST-like genes across the plant kingdom for their structure and evolution through acquisition of novel motifs and functional conservation uncovers possible roles in hormone signaling. Gibberellic Acid Stimulated Transcript (GAST)-like genes encode small polypeptides, some of which have been implicated in diverse biological processes regulating plant growth and development. However, the occurrence of GASTs among plants, their protein structures, and the mechanisms by which they evolved remain elusive. Here, using a customized workflow, we report genes encoding GAST proteins, identify novel motifs and evolutionary patterns contributing to the subfunctionalization of GAST domains, and explore functional conservation across diverse plant groups. We show that GAST-like sequences evolved initially in the vascular plant Selaginella moellendorffii, after the divergence from bryophytes, and later emerged in gymnosperms and angiosperms. GASTs in angiosperms are characterized by four conserved novel motifs; however, relatively fewer conserved motifs exist in pteridophytes and gymnosperms. Phylogenetic analysis revealed that the GAST-Cysteine Rich1 motif evolved early in the S. moellendorffii GAST, which further acquired subfunctionalization through successive conjugation of other motifs and remained conserved across plants, as supported by their collinearity. Functional characterization of two orthologs from the dicot Arabidopsis (Arabidopsis thaliana; Gibberellic Acid-Stimulated Arabidopsis 10) and the monocot rice (Oryza sativa; Gibberellic Acid Stimulated Transcript-Related 9) suggests hormonal regulation, novel roles in seed germination, and functional conservation among diverse plant groups. Computational modeling predicts that these GAST genes are regulated by several factors, including the phytohormones gibberellin and abscisic acid, through conserved cis-motifs present in their promoters, and that they might act as signaling molecules in a complex feedback loop. Thus, our study identifies GASTs and their encoded proteins, uncovers their structure, novel motifs, and evolutionary pattern among plants, and suggests their functional conservation.
Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: Mechanistic possibilities

We are facing a global epidemic of obesity and type 2 diabetes. Weight loss, in the context of obesity and type 2 diabetes, may improve glycaemic control and weight‐related comorbidities, and in some cases, induce diabetes remission. Although lifestyle‐based weight loss strategies may be initially successful, most are not effective long‐term. There is an increasing need to consider pharmacological approaches to assist weight loss in diabetes‐obesity. Older glucose‐lowering agents may cause weight gain, whereas the newer drug classes, sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide receptor agonists (GLP‐1 RAs), concomitantly target weight loss and glycaemic control. Clinical trial data suggest that both SGLT2i and GLP1 RAs cause a mean weight loss of approximately 2 to 3 kg but real‐world evidence and clinical experience suggests a significant heterogeneity in the magnitude of the weight loss (GLP‐1 RAs) or the magnitude of the actual weight loss is significantly less than anticipated (SGLT2i). Why do some individuals lose more weight than others in response to these pharmacological treatments? This review will first explore mechanisms by which body weight is regulated through control of energy balance and its dysregulation in obesity, and then consider how these mechanisms may be modulated therapeutically with SGLT2i and GLP1 RAs.
CD105 as a tool for assessing microvessel density in renal cell carcinoma

Background: Angiogenesis plays an essential role in both tumor growth and metastasis. CD105 expression was correlated with prognosis in many tumors, but its value in renal cell carcinoma (RCC) is still questionable. Materials and Methods: The aim of this study was to evaluate microvessel density (MVD) by using CD105 marker, in 95 cases of renal cell carcinoma. Results: CD105 showed positivity in 93 cases. The mean MVD value was significantly higher in clear cell carcinoma compared to papillary and chromophobe subtypes (P = 0.000). We noticed a significant correlation between MVD and ISUP grade (P = 0.007). The highest MVD value was observed in tumors with ISUP grade 1 and 2, while the lowest MVD value was noted in ISUP grade 3 tumors. A high vessel density was identified in tumors with a low Fuhrman grade, compared to those with a high grade (P = 0.010). MVD value was lower in tumors with a larger diameter, compared to small ones (P = 0.026). Conclusion: In conclusion, CD105 expression (MVD) is inversely related to tumor aggressiveness in clear cell RCC and can be used as a favorable prognosis marker. The vascularity differences between histological subtypes of RCCs could be useful for a better selection of patients that may benefit from anti-angiogenic therapies.
CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth

Inhibition of the CXXC5–DVL interaction is a potential therapeutic strategy for height enhancement of children with growth retardation. Longitudinal bone growth ceases with growth plate senescence during puberty. However, the molecular mechanisms of this phenomenon are largely unexplored. Here, we examined Wnt-responsive genes before and after growth plate senescence and found that CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt/β-catenin pathway, was gradually elevated with reduction of Wnt/β-catenin signaling during senescent changes of rodent growth plate. Cxxc5−/− mice demonstrated delayed growth plate senescence and tibial elongation. As CXXC5 functions by interacting with dishevelled (DVL), we sought to identify small molecules capable of disrupting this interaction. In vitro screening assay monitoring CXXC5–DVL interaction revealed that several indirubin analogs were effective antagonists of this interaction. A functionally improved indirubin derivative, KY19382, elongated tibial length through delayed senescence and further activation of the growth plate in adolescent mice. Collectively, our findings reveal an important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity.
Forecasting forecaster accuracy: Contributions of past performance and individual differences

A growing body of research indicates that forecasting skill is a unique and stable trait: forecasters with a track record of high accuracy tend to maintain this record. But how does one identify skilled forecasters effectively? We address this question using data collected during two seasons of a longitudinal geopolitical forecasting tournament. Our first analysis, which compares psychometric traits assessed prior to forecasting, indicates intelligence consistently predicts accuracy. Next, using methods adapted from classical test theory and item response theory, we model latent forecasting skill based on the forecasters’ past accuracy, while accounting for the timing of their forecasts relative to question resolution. Our results suggest these methods perform better at assessing forecasting skill than simpler methods employed by many previous studies. By parsing the data at different time points during the competitions, we assess the relative importance of each information source over time. When past performance information is limited, psychometric traits are useful predictors of future performance, but, as more information becomes available, past performance becomes the stronger predictor of future accuracy. Finally, we demonstrate the predictive validity of these results on out-of-sample data, and their utility in producing performance weights for wisdom-of-crowds aggregations.
Correlates of Discordance between Perceived and Objective Distances to Local Fruit and Vegetable Retailers

Background: Perceptions of neighbourhood attributes such as proximity of food retailers that are discordant with objective measures of the same are associated with poor health behaviours and weight gain. Factors associated with discordant perceptions are likely relevant to planning more effective interventions to improve health. Purpose: Analysis of cross-sectional relationships between individual and neighbourhood factors and overestimations of walking distances to local fruit/vegetable retailers (FVR). Methods: Perceived walking times, converted to distances, between participant residences and FVR were compared with objectively-assessed road network distances calculated with a Geographic Information System for n = 1305 adults residing in Adelaide, South Australia. Differences between perceived and objective distances were expressed as ‘overestimated’ distances and were analysed relative to perceptions consistent with objective distances. Cross-sectional associations were evaluated between individual socio-demographic, health, and area-level characteristics and overestimated distances to FVR using multilevel logistic regression. Results: Agreement between objective and perceived distances between participants’ residence and the nearest FVR was only fair (weighted kappa = 0.22). Overestimated distances to FVR were positively associated with mental well-being, and were negatively associated with household income, physical functioning, sense of community, and objective distances to greengrocers. Conclusions: Individual characteristics and features of neighbourhoods were related to overestimated distances to FVR. Sense of connectivity and shared identity may shape more accurate understandings of local resource access, and offer a focal point for tailored public health initiatives that bring people together to achieve improved health behaviour.
‘Tell Your Story’: a randomized controlled trial of an online intervention to reduce mental health stigma and increase help-seeking in refugee men with posttraumatic stress

Abstract Background Refugees report elevated rates of posttraumatic stress disorder (PTSD), but are relatively unlikely to seek help for their symptoms. Mental health stigma is a key barrier to help-seeking amongst refugees. We evaluated the efficacy of an online intervention in reducing self-stigma and increasing help-seeking in refugee men. Methods Participants were 103 refugee men with PTSD symptoms from Arabic, Farsi or Tamil-speaking backgrounds who were randomly assigned to either receive an 11-module online stigma reduction intervention specifically designed for refugees (‘Tell Your Story’, TYS) or to a wait-list control (WLC) group. Participants completed online assessments of self-stigma for PTSD and help-seeking, and help-seeking intentions and behaviors at baseline, post-intervention, and at a 1 month follow-up. Results Intent-to-treat analyses indicated that, compared to the WLC, TYS resulted in significantly smaller increases in self-stigma for seeking help from post-treatment to follow-up (d = 0.42, p = 0.008). Further, participants in the TYS conditions showed greater help-seeking behavior from new sources at follow-up (B = 0.69, 95% CI 0.19–1.18, p = 0.007) than those in the WLC. The WLC showed significantly greater increases in help-seeking intentions from post-intervention to follow-up (d = 0.27, p = 0.027), relative to the TYS group. Conclusions This is the first investigation of a mental health stigma reduction program specifically designed for refugees. Findings suggest that evidence-based stigma reduction strategies are beneficial in targeting self-stigma related to help-seeking and increasing help-seeking amongst refugees. These results indicate that online interventions focusing on social contact may be a promising avenue for removing barriers to accessing help for mental health symptoms in traumatized refugees.
Distinct and Specific Role of NlpC/P60 Endopeptidases LytA and LytB in Cell Elongation and Division of Lactobacillus plantarum

Peptidoglycan (PG) is an essential lattice of the bacterial cell wall that needs to be continuously remodeled to allow growth. This task is ensured by the concerted action of PG synthases that insert new material in the pre-existing structure and PG hydrolases (PGHs) that cleave the PG meshwork at critical sites for its processing. Contrasting with Bacillus subtilis that contains more than 35 PGHs, Lactobacillus plantarum is a non-sporulating rod-shaped bacterium that is predicted to possess a minimal set of 12 PGHs. Their role in morphogenesis and cell cycle remains mostly unexplored, except for the involvement of the glucosaminidase Acm2 in cell separation and the NlpC/P60 D, L-endopeptidase LytA in cell shape maintenance. Besides LytA, L. plantarum encodes three additional NlpC/P60 endopeptidases (i.e., LytB, LytC and LytD). The in silico analysis of these four endopeptidases suggests that they could have redundant functions based on their modular organization, forming two pairs of paralogous enzymes. In this work, we investigate the role of each Lyt endopeptidase in cell morphogenesis in order to evaluate their distinct or redundant functions, and eventually their synthetic lethality. We show that the paralogous LytC and LytD enzymes are not required for cell shape maintenance, which may indicate an accessory role such as in PG recycling. In contrast, LytA and LytB appear to be key players of the cell cycle. We show here that LytA is required for cell elongation while LytB is involved in the spatio-temporal regulation of cell division. In addition, both PGHs are involved in the proper positioning of the division site. The absence of LytA activity is responsible for the asymmetrical positioning of septa in round cells while the lack of LytB results in a lateral misplacement of division planes in rod-shaped cells. Finally, we show that the co-inactivation of LytA and LytB is synthetically affecting cell growth, which confirms the key roles played by both enzymes in PG remodeling during the cell cycle of L. plantarum. Based on the large distribution of NlpC/P60 endopeptidases in low-GC Gram-positive bacteria, these enzymes are attractive targets for the discovery of novel antimicrobial compounds.
Bone marrow characterization in sickle cell disease: inflammation and stress erythropoiesis lead to suboptimal CD34 recovery

Stress erythropoiesis and chronic inflammation in subjects with sickle cell disease (SCD) may have an impact on the bone marrow (BM) haematopoietic stem and progenitor cell (HSPC) quality and yield necessary for effective autologous, ex vivo HSPC gene therapy. BM from 19 subjects with SCD and five volunteers without SCD (non‐SCD) was collected in different anticoagulants and processed immediately (day 0) or the following day (day 1). Inflammatory, contamination and aggregation markers within the mononuclear layer, and CD34, CD45 and Glycophorin‐A (GPA) expression on HSPCs after CD34+ selection were analysed by conventional and imaging flow cytometry. Compared to non‐SCD BM, multiple markers of inflammation, contamination (red cells, P < 0·01; platelets, P < 0·01) and aggregates (platelet/granulocytes, P < 0·01; mononuclear/red cells, P < 0·01) were higher in SCD BM. Total CD34+ cell count was lower in SCD BM (P < 0·05), however CD34+ count was higher in SCD BM when collected in acid citrate dextrose‐A (ACDA) versus heparin (P < 0·05). Greater than 50% of CD34+ HSPCs from SCD BM are CD34dim due to higher erythroid lineage expression (P < 0·01) as single cell CD34+CD45+GPA+ (P < 0·01) and CD34+CD45−GPA+ (P < 0·01) HSPCs. SCD BM is characterized by increased inflammation, aggregation and contamination contributing to significant differences in HSPC quality and yield compared to non‐SCD BM.
High incidence of intended partner pregnancy among men living with HIV in rural Uganda: Implications for safer conception services.

BACKGROUND Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy (ART) in Uganda. METHODS Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men's sexual and reproductive health annually and repeated at time of reported pregnancy (2011-2015). We measured partner pregnancy incidence overall, by pregnancy intention, and by reported partner HIV-serostatus. We assessed viral suppression (≤400 copies/mL) during the peri-conception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy. RESULTS Among 189 men, baseline median age was 39.9 years [IQR:34.7,47.0], years on ART was 3.9 [IQR:0.0,5.1], and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence=16.0/100 person-years); 45% with HIV-serodifferent partners. By three years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV-serostatus (p=0.75). 69% of pregnancies were intended, 18% wanted but mis-timed, and 8% unwanted. 78% of men were virally suppressed prior to pregnancy report. Men who were younger (aHR:0.94/year;95%CI:0.89-0.99), had incomplete primary education (aHR:2.95;95%CI:1.36-6.40), and reported fertility desires (aHR:2.25;95%CI:1.04-4.85) had higher probability of partner pregnancy. CONCLUSION A high incidence of intended partner pregnancy highlights the need to address men's reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV and one-quarter of men were not virally suppressed during peri-conception. Safer conception care provides opportunity to support men's health and reproductive goals, while preventing HIV transmission to women and infants.
High Performance Bacteria Anchored by Nanoclay to Boost Straw Degradation

Generally, crop straw degrades slowly in soil, which is unfavorable for tillage and next crop growth. Thus, it is important to develop a promising technology to boost degradation of straw. Herein, a nanobiosystem has been developed by loading bacterial mixture in nanostructured attapulgite (ATP) and using it as a straw returning agent (SRA). Therein, ATP could effectively anchor bacteria to the surface of straw and greatly facilitate the adhesion and growth of bacteria. Consequently, this technology could effectively accelerate the degradation and transformation of straw into nutrients, including nitrogen (N), phosphorus (P), potassium (K), and organic matters (OM). Pot and field tests indicated that SRA displayed significant positive effects on the growth of the next crop. Importantly, SRA could effectively decrease greenhouse gas emissions from farmland, which is beneficial for the environment. Therefore, this work provides a facile and promising method to facilitate the degradation of straw, which might have a potential application value.
Pain during a marathon run: Prevalence and correlates in a cross-sectional study of 1251 runners

Background Science-based information about pain during a marathon run is scant. Based on related research it was hypothesized that: (i) most marathon runners would report moderate intensity pain, (ii) pain during the marathon would be associated with pain experienced while training as well as overall perceived exercise intensity, and (iii) females would experience pain earlier during the marathon and rate the pain intensity as higher after adjusting for expected sex-related differences in effort.Methods 1,251 runners, 550 females, ran in 252 different marathons and completed an online survey. Mile at which pain first occurred indicated pain threshold. Pain intensity was measured with a widely used 0–10 numerical graphical scale. Pearson and partial correlations examined the strength of associations. Sex-related differences in pain were tested using independent t-tests and, for the pain location data, z-scores for tests of two proportions. Effort ratings were added as a covariate in an ANCOVA to test if effort accounted for possible sex-related differences in pain.Results Most runners (99.8%) reported pain during a marathon, and most frequently in the thigh (17.1%), hamstring (10%) and calf (9.3%) body locations. The mean pain threshold occurred at 15.7 ± 6.1 miles; the mean overall pain intensity was 5.26 ± 2.45. No sex-related pain differences were found. Overall pain intensity during a marathon was significantly associated with: pain intensity of training runs (r = .39), percentage of training days with run-induced pain (r = .23), highest intensity pain ever experienced (r = .23), number of prior marathons (r = − .18) and intensity of effort (r = .11) (all P < 0.001). Conclusions Most runners experience moderate to very strong intensity pain during a marathon; the pain is independent of biological sex, and the pain is associated with marathon race experience, pain during training, race effort and the highest intensity of pain ever experienced.
Non-Enzymatic Impedimetric Sensor Based on 3-Aminophenylboronic Acid Functionalized Screen-Printed Carbon Electrode for Highly Sensitive Glucose Detection

A highly sensitive glucose sensor was prepared by a one-step method using 3-aminophenyl boronic acid as a unit of recognition and a screen-printed carbon electrode (SPCE) as an electrochemical transducer. Scanning Electron Microscopy confirmed the success of the functionalization of the SPCE due to the presence of clusters of boronic acid distributed on the carbon surface. In agreement with the Electrochemical Impedance Spectroscopy (EIS) tests performed before and after the functionalization, Cyclic Voltammetry results indicated that the electroactivity of the electrode decreased 37.9% owing to the presence of the poly phenylboronic acid on the electrode surface. EIS revealed that the sensor was capable to selectively detect glucose at a broad range of concentrations (limit of detection of 8.53 × 10−9 M), not recognizing fructose and sucrose. The device presented a stable impedimetric response when immediately prepared but suffered the influence of the storage time and some interfering species (dopamine, NaCl and animal serum). The response time at optimized conditions was estimated to be equal to 4.0 ± 0.6 s.