Miracle-dz/UniFAR-FTUs huggingface dataset:
An RNA-binding protein complex regulates the purine-dependent expression of a nucleobase transporter in trypanosomes

Abstract Post-transcriptional regulation of gene expression is particularly important in trypanosomatid protozoa. RNA-binding proteins (RBPs) regulate mRNA stability and translation, yet information about how RBPs are able to link environmental cues to post-transcriptional control is scarce. In Trypanosoma brucei, we have previously characterized a short RNA stem-loop cis-element (PuRE, Purine Responsive Element) within the 3′-UTR of the NT8 nucleobase transporter mRNA that is necessary and sufficient to confer a strong repression of gene expression in response to purines. In this study, we have identified a protein complex composed of two RNA-binding proteins (PuREBP1 and PuREBP2) that binds to the PuRE in vitro and to NT8 mRNA in vivo. Depletion of PuREBP1 by RNA interference results in the upregulation of just NT8 and the mRNAs encoding the amino acid transporter AATP6 paralogues. Moreover, we found that the PuREBP1/2 complex is associated with only a handful of mRNAs, and that it is responsible for the observed purine-dependent regulation of NT8 expression.
Identifying the Main Components of Substance-Related Addiction Recovery Groups

Abstract Objectives Mutual-aid groups are a central part of many individuals’ recovery journeys from substance addiction, and this research aimed to identify the key ingredients of a diverse range of recovery groups. Methods Individuals from 30 different substance addiction recovery groups across the UK (N = 151, 66% male, M age = 42.5 years) completed a survey, which asked participants to provide a narrative about their recovery group experiences. Participants were also asked to rate the extent to which theorized ingredients of addiction recovery groups were offered by their group, and how important each was to them. Both qualitative and quantitative data were collected and analyzed. Results The results indicated that the recovery group components suggested in previous literature were both present and rated as important. Component ratings did not differ depending on the type of group, the length of time the person had been in recovery, nor the length of time they had been involved in the group. The qualitative results identified other important components of recovery groups that had not been identified in the previous literature: presence of like-minded individuals and developing self-awareness and reflection skills. An updated list of recovery group components was thereby created. Conclusions Overall, the findings provide an in-depth, person-focused perspective on what makes an addiction recovery group successful. Asking group members directly about their experiences allowed us to refine and expand on previously theorized components. The updated components can be used as a template for developing future mutual-aid groups.
Cation ordering and phase transitions in feldspars along the join CaAl2Si2O8–SrAl2Si2O8: a TEM, IR and XRD investigation

Abstract Two feldspars of composition Ca0.3Sr0. 7Al2Si2O8 (An30SrF70) and Ca0.6Sr0. 4Al2Si2O8 (An60SrF40) were synthesized from gel and annealed at temperatures between 1150 and 1480°C for durations between 0.025 (1.5 min) and 1073 h. The An60SrF40 feldspar is triclinic for all annealing temperatures, whereas the An30SrF70 possesses, at room temperature, a monoclinic symmetry, C2/m in the shortest annealing runs and I2/c after slightly longer heating, and becomes triclinic after prolonged annealing. A TTT plot for the triclinic-monclinic transition shows an activation energy of 101±12 kcal, less than, but still close to, that observed for Al-Si order in anorthite. TEM investigation shows antiphase domains and Carlsbad twins the size of which increases with annealing. IR spectroscopy was performed on a series of samples of An30SrF70, annealed at T = 1350°C. The linewidth in hard mode is related to the spontaneous strain of the monoclinic-triclinic transition via ΔΓ ∝ qod2 ∝ Qod2 ∝ εss2. The evolution of the order parameter with time can be modelled as εss2 ∝ Qod2 ∝ lnt, as predicted in order-disorder processes at intermediate degrees of order. It is shown that even after the longest annealing runs in An30SrF70, equilibrium was not obtained whereas, under the same conditions, equilibrium Al-Si order can be obtained in anorthite and Sr-feldspar.
Identification of mutation resistance coldspots for targeting the SARS‐CoV2 main protease

Mutations in the novel coronavirus SARS‐CoV2 are the major concern as they might lead to drug/vaccine resistance. In the host cell, the virus largely depends on the main protease (Mpro) to regulate infection hence it is one of the most attractive targets for inhibitor design. However, >19,000 mutations in the Mpro have already been reported. The mutations encompassing 282 amino acid positions and these “hotspots” might change the Mpro structure, activity and potentially delay therapeutic strategies targeting Mpro. Thus, here we identified 24 mutational “coldspots” where mutations have not been observed. We compared the structure–function relationship of these coldspots with several SARS‐CoV2 Mpro X‐ray crystal structures. We found that three coldspot residues (Leu141, Phe185, and Gln192) help to form the active site, while seven (Gly2, Arg4, Tyr126, Lys137, Leu141, Leu286, and Leu287) contribute to dimer formation that is required for Mpro activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, most of the coldspots are found in three clusters and forms conserved patterns when compared with other coronaviruses. Importantly, several conserved coldspots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS‐CoV2 Mpro while avoiding mutation‐based drug resistance.
Understanding barriers and facilitators to HIV testing in Canada from 2009-2019: A systematic mixed studies review.

Background HIV testing is a core pillar of Canada's approach to sexually transmitted and blood-borne infection (STBBI) prevention and treatment and is critical to achieving the first Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target. Despite progress toward this goal, many Canadians remain unaware of their status and testing varies across populations and jurisdictions. An understanding of drivers of HIV testing is essential to improve access to HIV testing and reach the undiagnosed. Objective To examine current barriers and facilitators of HIV testing across key populations and jurisdictions in Canada. Methods A systematic mixed studies review of peer-reviewed and grey literature was conducted identifying quantitative and qualitative studies of barriers and facilitators to HIV testing in Canada published from 2009 to 2019. Studies were screened for inclusion and identified barriers and facilitators were extracted. The quality of included studies was assessed and results were summarized. Results Forty-three relevant studies were identified. Common barriers emerge across key populations and jurisdictions, including difficulties accessing testing services, fear and stigma surrounding HIV, low risk perception, insufficient patient confidentiality and lack of resources for testing. Innovative practices that could facilitate HIV testing were identified, such as new testing settings (dental care, pharmacies, mobile units, emergency departments), new modalities (oral testing, peer counselling) and personalized sex/gender and age-based interventions and approaches. Key populations also face unique sociocultural, structural and legislative barriers to HIV testing. Many studies identified the need to offer a broad range of testing options and integrate testing within routine healthcare practices. Conclusion Efforts to improve access to HIV testing should consider barriers and facilitators at the level of the individual, healthcare provider and policy and should focus on the accessibility, inclusivity, convenience and confidentiality of testing services. In addition, testing services must be adapted to the unique needs and contexts of key populations.
Secretory products of the corpus luteum and preeclampsia.

BACKGROUND Despite significant advances in our understanding of the pathophysiology of preeclampsia (PE), there are still many unknowns and controversies in the field. Women undergoing frozen-thawed embryo transfer (FET) to a hormonally prepared endometrium have been found to have an unexpected increased risk of PE compared to women who receive embryos in a natural FET cycle. The differences in risk have been hypothesized to be related to the absence or presence of a functioning corpus luteum (CL). OBJECTIVE AND RATIONALE To evaluate the literature on secretory products of the CL that could be essential for a healthy pregnancy and could reduce the risk of PE in the setting of FET. SEARCH METHODS For this review, pertinent studies were searched in PubMed/Medline (updated June 2020) using common keywords applied in the field of assisted reproductive technologies, CL physiology and preeclampsia. We also screened the complete list of references in recent publications in English (both animal and human studies) on the topics investigated. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized. OUTCOMES The CL is a major source of multiple factors regulating reproduction. Progesterone, estradiol, relaxin and vasoactive and angiogenic substances produced by the CL have important roles in regulating its functional lifespan and are also secreted into the circulation to act remotely during early stages of pregnancy. Beyond the known actions of progesterone and estradiol on the uterus in early pregnancy, their metabolites have angiogenic properties that may optimize implantation and placentation. Serum levels of relaxin are almost undetectable in pregnant women without a CL, which precludes some maternal cardiovascular and renal adaptations to early pregnancy. We suggest that an imbalance in steroid hormones and their metabolites and polypeptides influencing early physiologic processes such as decidualization, implantation, angiogenesis and maternal haemodynamics could contribute to the increased PE risk among women undergoing programmed FET cycles. WIDER IMPLICATIONS A better understanding of the critical roles of the secretory products of the CL during early pregnancy holds the promise of improving the efficacy and safety of ART based on programmed FET cycles.
Perspectives of Inpatients With Cirrhosis and Caregivers on Using Health Information Technology: Cross-sectional Multicenter Study

Background Health information technology (IT) interventions to decrease readmissions for cirrhosis may be limited by patient-associated factors. Objective The aim of this study was to determine perspectives regarding adoption versus refusal of health IT interventions among patient-caregiver dyads. Methods Inpatients with cirrhosis and their caregivers were approached to participate in a randomized health IT intervention trial requiring daily contact with research teams via the Patient Buddy app. This app focuses on ascites, medications, and hepatic encephalopathy over 30 days. Regression analyses for characteristics associated with acceptance were performed. For those who declined, a semistructured interview was performed with themes focused on caregivers, protocol, transport/logistics, technology demands, and privacy. Results A total of 349 patient-caregiver dyads were approached (191 from Virginia Commonwealth University, 56 from Richmond Veterans Affairs Medical Center, and 102 from Mayo Clinic), 87 of which (25%) agreed to participate. On regression, dyads agreeing included a male patient (odds ratio [OR] 2.08, P=.01), gastrointestinal bleeding (OR 2.3, P=.006), or hepatic encephalopathy admission (OR 2.0, P=.01), whereas opioid use (OR 0.46, P=.03) and alcohol-related etiology (OR 0.54, P=.02) were associated with refusal. Race, study site, and other admission reasons did not contribute to refusing participation. Among the 262 dyads who declined randomization, caregiver reluctance (43%), perceived burden (31%), technology-related issues (14%), transportation/logistics (10%), and others (4%), but not privacy, were highlighted as major concerns. Conclusions Patients with cirrhosis admitted with hepatic encephalopathy and gastrointestinal bleeding without opioid use or alcohol-related etiologies were more likely to participate in a health IT intervention focused on preventing readmissions. Caregiver and study burden but not privacy were major reasons to decline participation. Reducing perceived patient-caregiver burden and improving communication may improve participation. Trial Registration ClinicalTrials.gov NCT03564626; https://www.clinicaltrials. gov/ct2/show/NCT03564626
A Novel Sirolimus-eluting Biodegradable Magnesium-based Alloy Scaffold: Six-month Results In Porcine Peripheral Arteries.

PURPOSE Magnesium-based alloy scaffold is a promising biodegradable stent due to its intrinsic mechanical performance and biocompatibility. Based on our preliminary experiments, we designed a novel sirolimus-eluting magnesium-based alloy scaffold. This work aimed to assess its safety and degradation performance in vivo. METHODS The scaffolds were implanted in the lower limb arteries of Bama mini-pigs. Safety was defined as no immediate thrombosis or >30% residual stenosis, which was assessed with optical coherence tomography and digital subtraction angiography. Blood biochemical analyses were performed to evaluate hepatorenal toxicity. The degradation process of the scaffolds, the endothelialization, and lumen loss of the stented-vessels were detected with scanning electron microscopy, immunohistochemical, hematoxylin-eosin staining and optical coherence tomography. RESULTS Twenty-four scaffolds were successfully implanted in six pigs with no signs of immediate thrombosis or >30% residual stenosis. The scaffolds were covered by endothelium at one month and absolutely resorbed at six months post implantation. Blood analysis showed that the hepatorenal function except for alanine aminotransferase and γ-glutamyl transpeptidase was normal. Obvious intimal hyperplasia and lumen loss were found in the stented vessels at three months, while the diameters and inner lumen areas of stented segments had increased significantly at six months (p.
Detection of subclinical coronary artery lesions by Framingham risk score, peripheral artery atheromatosis and coronary artery calcium score: a pilot study in asymptomatic individuals living with HIV.

BACKGROUND The incidence of acute coronary events is increased among people living with HIV (PLWH) but there is no risk estimation score, nor a surrogate biomarker able to predict subclinical coronary artery disease (sCAD). We assessed the performance of: (i) Framingham risk score (FRMs), (ii) peripheral (carotid and femoral) artery atheromatosis, and (iii) coronary artery calcification score (CACs), to detect the presence of sCAD, in PLWH. METHODS In a cohort of PLWH free of CVD, we measured sCAD and CACs by computed tomography, calculated FRMs and assessed carotid/femoral plaques by ultrasound. RESULTS In 56 participants (age: 49± 10 years, men: 88%, FRMs: 7.2 ± 6.9; mean number of carotid/femoral plaques: 1.4±1.5; CACs>0 present in 59%, median CACs 0.9[(IQR 0-22]): (i) minimal sCAD (stenosis 1-24%; present in 30%) and mild sCAD (25-49%, 25%) were effectively detected by FRMs, number of plaques and CACs (AUC of CACs was better than that of both FRM and plaques, p<0.05); (ii) moderate sCAD (stenosis 50-69%; present in 8.9%) was detected by number of plaques and CACs, but similar AUC (0.969 vs 0.867, respectively, p=NS); (iii) severe sCAD (70-99%, present in only 3 [5.4%]) was detected only by CACs. CONCLUSIONS A high prevalence of sCAD in asymptomatic PLWH free of CVD was detected; CACs is a highly efficient biomarker to detect all grades of sCAD, however, the number of carotid/femoral plaques combined is also a very promising - lower cost and radiation free - surrogate biomarker. Future, larger studies are needed to verify these results.
Meat consumption and risk of incident dementia: cohort study of 493,888 UK Biobank participants

ABSTRACT Background Worldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Meat consumption has been cross-sectionally associated with dementia risk, but specific amounts and types related to risk of incident dementia remain poorly understood. Objective We aimed to investigate associations between meat consumption and risk of incident dementia in the UK Biobank cohort. Methods Meat consumption was estimated using a short dietary questionnaire at recruitment and repeated 24-h dietary assessments. Incident all-cause dementia comprising Alzheimer disease (AD) and vascular dementia (VD) was identified by electronic linkages to hospital and mortality records. HRs for each meat type in relation to each dementia outcome were estimated in Cox proportional hazard models. Interactions between meat consumption and the apolipoprotein E (APOE) ε4 allele were additionally explored. Results Among 493,888 participants included, 2896 incident cases of all-cause dementia, 1006 cases of AD, and 490 cases of VD were identified, with mean ± SD follow-up of 8 ± 1.1 y. Each additional 25 g/day intake of processed meat was associated with increased risks of incident all-cause dementia (HR: 1.44; 95% CI: 1.24, 1.67; P-trend < 0.001) and AD (HR: 1.52; 95% CI: 1.18, 1.96; P-trend = 0.001). In contrast, a 50-g/d increment in unprocessed red meat intake was associated with reduced risks of all-cause dementia (HR: 0.81; 95% CI: 0.69, 0.95; P-trend = 0.011) and AD (HR: 0.70; 95% CI: 0.53, 0.92; P-trend = 0.009). The linear trend was not significant for unprocessed poultry and total meat. Regarding incident VD, there were no statistically significant linear trends identified, although for processed meat, higher consumption categories were associated with increased risks. The APOE ε4 allele increased dementia risk by 3 to 6 times but did not modify the associations with diet significantly. Conclusion These findings highlight processed-meat consumption as a potential risk factor for incident dementia, independent of the APOE ε4 allele.
Tuning promoter boundaries improves regulatory motif discovery in nonmodel plants: the peach example

Abstract The identification of functional elements encoded in plant genomes is necessary to understand gene regulation. Although much attention has been paid to model species like Arabidopsis (Arabidopsis thaliana), little is known about regulatory motifs in other plants. Here, we describe a bottom-up approach for de novo motif discovery using peach (Prunus persica) as an example. These predictions require pre-computed gene clusters grouped by their expression similarity. After optimizing the boundaries of proximal promoter regions, two motif discovery algorithms from RSAT::Plants (http://plants.rsat.eu) were tested (oligo and dyad analysis). Overall, 18 out of 45 co-expressed modules were enriched in motifs typical of well-known transcription factor (TF) families (bHLH, bZip, BZR, CAMTA, DOF, E2FE, AP2-ERF, Myb-like, NAC, TCP, and WRKY) and a few uncharacterized motifs. Our results indicate that small modules and promoter window of [–500 bp, +200 bp] relative to the transcription start site (TSS) maximize the number of motifs found and reduce low-complexity signals in peach. The distribution of discovered regulatory sites was unbalanced, as they accumulated around the TSS. This approach was benchmarked by testing two different expression-based clustering algorithms (network-based and hierarchical) and, as control, genes grouped for harboring ChIPseq peaks of the same Arabidopsis TF. The method was also verified on maize (Zea mays), a species with a large genome. In summary, this article presents a glimpse of the peach regulatory components at genome scale and provides a general protocol that can be applied to other species. A Docker software container is released to facilitate the reproduction of these analyses.
Non-Algal Seston, Light, Nutrients and Chlorophyll in Missouri Reservoirs

ABSTRACT Limnological measurements were performed at five or six Missouri reservoirs in June-September 1992–1995 to examine the relation of light conditions and non-algal seston (NAS) to chlorophyll (CHL) and dissolved nutrient concentrations. NAS was estimated as the sum of non-volatile suspended solids and filterable (Whatman 934AH filter) suspended solids. Mean mixed layer irradiance (I mix ) varied ≈20 fold among observations, largely due to variation in light attenuation by NAS. In 42% of the observations, I mix was less than 7 E·m−2 d−1, a range where light limitation is likely. NAS comprised 15–96% (mean= 58%) of total seston and accounted for 89% of the temporal and inter-site variation in I mix . NAS was strongly correlated to total phosphorus (TP) and soluble reactive phosphorus (SRP) concentrations (r= 0.91 and r=0.84, respectively, p<0.0001). When NAS > 5 mg·L−1 or I mix was < 5 E m−2 d−1, SRP and dissolved inorganic N (DIN) were usually at concentrations capable of saturating algal nutrient uptake (SRP >3 μg·L−1, DIN >50 μg·L−1), suggesting light limitation replaced nutrient limitation under those conditions. Light limitation resulting from NAS in turbid lakes may alter the relationship of phytoplankton to phosphorus, yielding a CHL-TP relationship that is dome-shaped rather than asymptotic. Variation in the relation of NAS to TP will affect how CHL responds to nutrients in individual waterbodies.
One hundred years of inorganic crystal chemistry – a personal view

It was suspected by Leucippus (fifth century BCE) that atoms had to be ordered, but no relationship between atomic order and crystals has been handed down to us from antiquity. In modern times, beginning with Kepler, 1611, crystals were thought to be composed of ordered small particles, but not necessarily atoms. This changed with Dalton, ca. 1800. Barlow made in 1883 a successful prediction of alkali halide structures, while Alfred Werner understood in 1893 already coordination compounds and coordination numbers. By the time of the experiments of the Braggs, 1913, atomism was mostly accepted. The first important crystal chemistry paper was published in 1920 by W. Lawrence Bragg, the son: he found that interatomic distances in crystals obeyed an additivity rule. In 1926, Goldschmidt had amassed a large amount of crystal structure data and deduced from that what he called the laws of crystal chemistry, thus he became the founder of crystal chemistry. On the basis of W. L. Bragg's crystal structure determinations and of Goldschmidt's laws Machatschki unravelled in 1927, the principles of the constitution of the silicates, a problem that had vexed mineralogists and inorganic chemists during the nineteenth century. In 1928/1929, Pauling published his famous rules concerning the principles determining the structures of complex ionic crystals. His second rule, the electrostatic valence principle, which essentially says that the charges of the ions in a crystal structure are balanced locally, was particularly useful. The first book on crystal chemistry was published by Hassel in 1934. Wells showed beginning in 1954 in a series of papers and books that one could systematize crystal structures on the basis of three-dimensional periodic nets of bonds. After the 1950s, the increasing accuracy of crystal structure determinations made it possible to look for interpretations of bond length variations and distortions of coordination polyhedra. Bärnighausen constructed family trees of the group-subgroup relationships of topologically related crystal structures. A general method for predicting crystal structures of inorganic compounds from a knowledge of the chemical composition alone is not yet available. Empirical crystal chemistry remains a valuable tool for searching for methods of representing and classifying structures.