Miracle-dz/UniFAR-FTUs huggingface dataset:
Srsf1 and Elavl1 act antagonistically on neuronal fate choice in the developing neocortex by controlling TrkC receptor isoform expression

Abstract The seat of higher-order cognitive abilities in mammals, the neocortex, is a complex structure, organized in several layers. The different subtypes of principal neurons are distributed in precise ratios and at specific positions in these layers and are generated by the same neural progenitor cells (NPCs), steered by a spatially and temporally specified combination of molecular cues that are incompletely understood. Recently, we discovered that an alternatively spliced isoform of the TrkC receptor lacking the kinase domain, TrkC-T1, is a determinant of the corticofugal projection neuron (CFuPN) fate. Here, we show that the finely tuned balance between TrkC-T1 and the better known, kinase domain-containing isoform, TrkC-TK+, is cell type-specific in the developing cortex and established through the antagonistic actions of two RNA-binding proteins, Srsf1 and Elavl1. Moreover, our data show that Srsf1 promotes the CFuPN fate and Elavl1 promotes the callosal projection neuron (CPN) fate in vivo via regulating the distinct ratios of TrkC-T1 to TrkC-TK+. Taken together, we connect spatio-temporal expression of Srsf1 and Elavl1 in the developing neocortex with the regulation of TrkC alternative splicing and transcript stability and neuronal fate choice, thus adding to the mechanistic and functional understanding of alternative splicing in vivo.
Ice Shelf - Ocean Interaction in the Eastern Weddell Sea, Antarctica

This thesis investigates the interaction of the Antarctic ice shelves along the coast of Dronning Maud Land with the ocean circulation in the Eastern Weddell Sea. A set of direct oceanic observations below the Fimbul Ice Shelf, which were acquired during three Antarctic eld seasons in the austral summers 2009/10, 2010/11 and 2011/12, is a central element of the presented work. This new oceanographic dataset is complemented by a high-resolution state-of-the-art ice shelf ocean circulation model. The results provide an estimate of the amount of basal melting at the Fimbul Ice Shelf, and revise the physical processes that determine the ocean heat uxes over the East Antarctic continental slope. A major nding is that deep-ocean heat uxes towards the ice are much more constrained than predicted by previous ocean models, causing substantially lower rates of basal melting than earlier suggested. The predicted basal melting is consistent with mass balance estimates from satellite data and implicates that the Fimbul Ice Shelf is currently not subject to rapid basal mass loss. Furthermore, the complex interplay of the processes within the coastal, frontal system, and their respective role in transporting heat for melting towards the ice is examined. The results emphasize the importance of oceanic eddies within the coastal circulation for controlling the in ow of Warm Deep Water into the ice shelf cavities. A realistic representation of the e ect of the mesoscale eddy overturning is thus a crucial requirement in order to simulate basal melting along the Weddell Sea coast in the present and future climate. The results also imply that fresh, and solar-heated Antarctic Surface Water plays a central role for the ice shelf cavity exchange. Being produced by sea ice melting at the ocean surface, this water mass directly enters the cavity and increases the melting of shallow ice. Due to its buoyancy, the presence of Antarctic Surface Water also alters the coastal dynamics and regulates the in ow of warm water at depth, thus showing that a more detailed understanding of the role of this water mass for basal melting around Antarctica will need further attention. Finally, the results suggest a direct relationship between the simulated basal melting and only a few deterministic parameters of the coastal circulation, which is used to derive a simple parameterization of for basal melting at the Fimbul Ice Shelf.
Implications of 'peak oil' for atmospheric CO{sub 2} and climate - article no. GB3012

Unconstrained CO{sub 2} emission from fossil fuel burning has been the dominant cause of observed anthropogenic global warming. The amounts of 'proven' and potential fossil fuel reserves are uncertain and debated. Regardless of the true values, society has flexibility in the degree to which it chooses to exploit these reserves, especially unconventional fossil fuels and those located in extreme or pristine environments. If conventional oil production peaks within the next few decades, it may have a large effect on future atmospheric CO{sub 2} and climate change, depending upon subsequent energy choices. Assuming that proven oil and gas reserves do not greatly exceed estimates of the Energy Information Administration, and recent trends are toward lower estimates, we show that it is feasible to keep atmospheric CO{sub 2} from exceeding about 450 ppm by 2100, provided that emissions from coal, unconventional fossil fuels, and land use are constrained. Coal-fired power plants without sequestration must be phased out before midcentury to achieve this CO{sub 2} limit. It is also important to 'stretch' conventional oil reserves via energy conservation and efficiency, thus averting strong pressures to extract liquid fuels from coal or unconventional fossil fuels while clean technologies are being developed for the eramore » 'beyond fossil fuels'. We argue that a rising price on carbon emissions is needed to discourage conversion of the vast fossil resources into usable reserves, and to keep CO{sub 2} beneath the 450 ppm ceiling. « less
Arylidene and amino spacer‐linked rhodanine‐quinoline hybrids as upgraded antimicrobial agents

Antibiotic resistance associated with various microorganisms such as Gram‐positive, Gram‐negative, fungal strains, and multidrug‐resistant tuberculosis increases the risk of healthcare survival. Preliminary therapeutics becoming ineffective that might lead to noteworthy mortality presents a crucial challenge for the scientific community. Hence, there is an urgent need to develop hybrid compounds as antimicrobial agents by combining two or more bioactive heterocyclic moieties into a single molecular framework with fewer side effects and a unique mode of action. This review highlights the recent advances (2013–2023) in the pharmacology of rhodanine‐linked quinoline hybrids as more effective antimicrobial agents. In the drug development process, linker hybrids acquire the top position due to their excellent π‐stacking and Van der Waals interaction with the DNA active sites of pathogens. A molecular hybridization strategy has been optimized, indicating that combining these two bioactive moieties with an arylidene and an amino spacer linker increases the antimicrobial potential and reduces drug resistance. Moreover, the structure–activity relationship study is discussed to express the role of various functional groups in improving and decrementing antimicrobial activities for rational drug design. Also, a linker approach may accelerate the development of dynamic antimicrobial agents through molecular hybridization.
Impact of symptomatic menopausal transition on the occurrence of depression, anxiety, and sleep disorders: A real-world multi-site study

Abstract Background The menopause transition is a vulnerable period that can be associated with changes in mood and cognition. The present study aimed to investigate whether a symptomatic menopausal transition increases the risks of depression, anxiety, and sleep disorders. Methods This population-based, retrospective cohort study analysed data from five electronic health record databases in South Korea. Women aged 45–64 years with and without symptomatic menopausal transition were matched 1:1 using propensity-score matching. Subgroup analyses were conducted according to age and use of hormone replacement therapy (HRT). A primary analysis of 5-year follow-up data was conducted, and an intention-to-treat analysis was performed to identify different risk windows over 5 or 10 years. The primary outcome was first-time diagnosis of depression, anxiety, and sleep disorder. We used Cox proportional hazard models and a meta-analysis to calculate the summary hazard ratio (HR) estimates across the databases. Results Propensity-score matching resulted in a sample of 17,098 women. Summary HRs for depression (2.10; 95% confidence interval [CI] 1.63–2.71), anxiety (1.64; 95% CI 1.01–2.66), and sleep disorders (1.47; 95% CI 1.16–1.88) were higher in the symptomatic menopausal transition group. In the subgroup analysis, the use of HRT was associated with an increased risk of depression (2.21; 95% CI 1.07–4.55) and sleep disorders (2.51; 95% CI 1.25–5.04) when compared with non-use of HRT. Conclusions Our findings suggest that women with symptomatic menopausal transition exhibit an increased risk of developing depression, anxiety, and sleep disorders. Therefore, women experiencing a symptomatic menopausal transition should be monitored closely so that interventions can be applied early.
Home-based HIV testing strategies for middle-aged and older adults in rural South Africa

Objective: More than one in four adults over 40 years with HIV in South Africa are unaware of their status and not receiving antiretroviral therapy (ART). HIV self-testing may offer a powerful approach to closing this gap for aging adults. Here, we report the results of a randomized comparative effectiveness trial of three different home-based HIV testing strategies for middle-aged and older adults in rural South Africa. Design: Two thousand nine hundred and sixty-three individuals in the ‘Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI)’ cohort study were randomized 1 : 1 : 1 to one of three types of home-based and home-delivered HIV testing modalities: rapid testing with counseling; self-testing, and both rapid testing with counselling and self-testing. Method: In OLS regression analyses, we estimated the treatment effects on HIV testing and HIV testing frequency at about 1 year after delivery. Finally, we assessed the potential adverse effects of these strategies on the secondary outcomes of depressive symptom as assessed by the CESD-20, linkage to care, and risky sexual behavior. Results: There were no significant differences in HIV testing uptake or testing frequency across groups. However, respondents in the self-testing treatment arms were more likely to shift from testing at home and a facility [self-testing (HIVST), −8 percentage points (pp); 95% confidence interval (CI) −14 to −2 pp; self-testing plus rapid testing and counselling (ST+RT+C); −9 pp, 95% CI −15 to −3 pp] to testing only at home (HIVST 5 pp; 95% CI 2 to 9 pp; ST+RT+C: 5 pp, 95% CI 1 to 9 pp) – suggesting a revealed preference for self-testing in this population. We also found no adverse effects of this strategy on linkage to care for HIV and common comorbidities, recent sexual partners, or condom use. Finally, those in the self-testing only arm had significantly decreased depressive symptom scores by 0.58 points (95% CI −1.16 to −0.01). Conclusion: We find HIV self-testing to be a well tolerated and seemingly preferred home-based testing option for middle-aged and older adults in rural South Africa. This approach should be expanded to achieve the UNAIDS 95–95–95 targets.
Effectiveness of Continuing Post-Surgery Antibiotic Prophylaxis in Reducing Nosocomial Infections - A Literature Review.

Background: To prevent surgical site infection (SSI), antibiotic prophylaxis is frequently extended for one day or more following surgery. Post-operative, continuing antibiotic prophylaxis may not be advantageous compared to stopping it right away, as it exposes patients to the hazards of taking antibiotics. Although it is routinely recommended, post-procedural prophylaxis is sometimes not necessary. To optimize the effectiveness of antibiotic prophylaxis (AP) in preventing SSIs, healthcare providers should adhere to evidence-based guidelines, such as those provided by the World Health Organization (WHO) or the American Society of Health-System Pharmacists (ASHP). These guidelines provide recommendations on the appropriate selection, timing, and duration of antibiotic prophylaxis for various surgical procedures. In this literature review we looked if the data available support these recommendations. Methods: We searched PubMed database for articles written between 1st of January 2012 up to 31st of December 2022. We looked at randomized control trials (RCTs) of patients hospitalized in surgical departments, who were given postoperative antibiotic prophylaxis comparing them with those that did not receive it. Results: Out of a total of 566 randomized control trials, 15 were included in this literature review, totalling 11,728 patients. We found indications that in many cases it makes a significant difference in continuing antibiotic prophylaxis postoperatively. However, in some cases, this will result in a similar incidence of post-surgery nosocomial infections between the intervention and control groups. Conclusion: While antibiotic prophylaxis is an important strategy to prevent surgical site infections, the decision to extend antibiotic prophylaxis beyond the intraoperative period should be made on a case-by-case basis and led by guidelines.
Long noncoding RNA from Betula platyphylla, BplncSIR1, confers salt tolerance by regulating BpNAC2 to mediate reactive oxygen species scavenging and stomatal movement

Summary Long noncoding RNAs (lncRNAs) play an important role in abiotic stress tolerance. However, their function in conferring abiotic stress tolerance is still unclear. Herein, we characterized the function of a salt‐responsive nuclear lncRNA (BplncSIR1) from Betula platyphylla (birch). Birch plants overexpressing and knocking out for BplncSIR1 were generated. BplncSIR1 was found to improve salt tolerance by inducing antioxidant activity and stomatal closure, and also accelerate plant growth. Chromatin isolation by RNA purification (ChIRP) combined with RNA sequencing indicated that BplncSIR1 binds to the promoter of BpNAC2 (encoding NAC domain‐containing protein 2) to activate its expression. Plants overexpressing and knocking out for BpNAC2 were generated. Consistent with that of BplncSIR1, overexpression of BpNAC2 also accelerated plant growth and conferred salt tolerance. In addition, BpNAC2 binds to different cis‐acting elements, such as G‐box and ‘CCAAT’ sequences, to regulate the genes involved in salt tolerance, resulting in reduced ROS accumulation and decreased water loss rate by stomatal closure. Taken together, BplncSIR1 serves as the regulator of BpNAC2 to induce its expression in response to salt stress, and activated BpNAC2 accelerates plant growth and improves salt tolerance. Therefore, BplncSIR1 might be a candidate gene for molecular breeding to cultivate plants with both a high growth rate and improved salt tolerance.
Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
Microbial diversity and authigenic siderite mediation in sediments surrounding the Kedr‐1 mud volcano, Lake Baikal

The gas hydrate‐bearing structure—mud volcano Kedr‐1 (Lake Baikal, southern basin)—is located near the coal‐bearing sediments of the Tankhoy formation of Oligocene–Miocene age and can be an ideal source of gas‐saturated fluid. A significant amount of siderite minerals (FeCO3) were collected from sediments at depths ranging from 0.5 to 327 cm below the lake floor (cmblf). An important feature of these carbonate minerals is the extremely strong enrichment in the heavy 13C isotope, reaching values of +33.3‰ VPDB. The δ13C of the siderite minerals, as well as their morphology and elemental composition, and the δ13CDIC of the co‐existing pore water, differed across layers of the core, which implies at least two generations of siderite formation. Here, we leverage mineralogical and geochemical data with 16S rRNA data from the microbial communities in sediments surrounding layers containing siderite minerals. Statistical data reveal the formation of three clusters of microbial communities based on taxonomical composition, key taxa among bacteria and archaea, and environmental parameters. Diversity and richness estimators decrease with sediment depth, with several similar prevailing clades located at the bottom of the core. Most of the taxa in the deep sediments could be associated with putative metabolisms involving organotrophic fermentation (Bathyarchaeia, Caldatribacteriota, and Chloroflexota). Various groups of methanogens (Methanoregulaceae, Methanosaetaceae, and Methanomassiliicoccales) and methanotrophic (Methanoperedenaceae) archaea are present in the sediment at variable relative abundances throughout the sampled depth. Based on the physicochemical characteristics of the sediment, carbon isotope analysis of carbonate minerals and DIC, and phylogenetic analysis of individual taxa and their metabolic potential, we present several models for subsurface siderite precipitation in Lake Baikal sediments.
SEX/GENDER DIFFERENCES IN SERVICE USE PATTERNS, CLINICAL OUTCOMES AND MORTALITY RISK FOR ADULTS WITH ACQUIRED BRAIN INJURY: A RETROSPECTIVE COHORT STUDY (ABI-RESTART)

Objective To identify sex/gender differences in functional, psychosocial and service use patterns in community-based post-acute care for acquired brain injury. Design Retrospective cohort study. Subjects/patients Adults with acquired brain injury enrolled in post-acute neurorehabilitation and disability support in Western Australia (n = 1,011). Methods UK Functional Independence Measure and Functional Assessment Measure (FIM + FAM), Mayo-Portland Adaptability Inventory-4, goal attainment, length of stay (LOS), number of episodes of care and deaths were evaluated using routinely collected clinical and linked administrative data. Results At admission, women were older (p < 0.001) and displayed poorer functional independence (FIM + FAM; p < 0.05) compared with men. At discharge, there were no differences in goal attainment, psychosocial function or functional independence between men and women. Both groups demonstrated functional gains; however, women demonstrated clinically significant gains (+ 15.1, p < 0.001) and men did not (+ 13.7, p < 0.001). Women and men had equivalent LOS (p = 0.205). Aboriginal and/or Torres Strait Islander status predicted longer LOS for women but not for men. Being partnered predicted reduced LOS for women but not men. Women had a higher risk of multiple episodes of care (p < 0.001), but not death (p = 0.409), compared with that of men. Conclusion At admission to rehabilitation and disability support services for acquired brain injury, women have poorer functional independence and higher risk of multiple episodes of care, compared with men, suggesting greater disability in the community. By the time of discharge from these services, women and men make equivalent functional and psychosocial gains. The higher risk of multiple episodes of care for women relative to men suggest women may need additional post-discharge support, to avoid readmission. LAY ABSTRACT Acquired brain injury is associated with long-term consequences for health and wellbeing. Despite this, relatively little research has examined sex and gender differences in patterns of service use, functional and psychosocial outcomes, and risk of death in post-acute care for acquired brain injury. This study evaluates the admission and discharge characteristics of 1,011 adults with acquired brain injury. Findings indicate that, while women present with poorer functional independence at admission, post-acute care for acquired brain injury provides opportunities for equivalent functional and psychosocial gains for men and women. Women are at higher risk of requiring multiple episodes of care, compared with men, and women in some groups have a longer length of stay in post-acute care than men, although they are at no greater risk of death during care. This indicates that additional post-discharge support may be required for women with acquired brain injury, but that post-acute care supports both men and women to make meaningful functional improvements.
Investigating potential myopia risk factors, including chronotype, in Estonian adolescents

Purpose: To evaluate chronotype, lifestyle factors, and parental myopia in relation to myopia, and characterise the effect of cycloplegia on spherical equivalent refraction (SER) in Estonian secondary school students. Methods: One hundred twenty-three students aged between 15 and 17 years from three secondary schools in Estonia participated in the study. They underwent a comprehensive ocular examination, including cycloplegic refraction and ocular biometry. Chronotype was evaluated with the Morningness-Eveningness Questionnaire. Participants also completed a questionnaire about their daily activities, including time spent outdoors, time spent on near-work and mid-working distance activities, and parental myopia. Myopia was defined as cycloplegic SER [≤]-0.50 D. Logistic regression analysis was performed to assess the association of the studied factors with myopia. Results: In a multivariate regression model, having two myopic parents was associated with higher odds of myopia (OR 3.78, 95% CI 1.15-12.42). We found no association between myopia and chronotype. Notably, time spent outdoors, and doing near-work and mid-working distance activities, did not affect the likelihood of having myopia. Non-cycloplegic SER was significantly more myopic than cycloplegic SER on average by 0.86 D (p < 0.0001, Wilcoxon matched-pairs signed rank test). Conclusion: Consistent with previous reports, we identified parental myopia as a myopia risk factor. Chronotype was not associated with myopia in our study sample. Interestingly, there was no association between myopia and time spent outdoors or near work. Using non-cycloplegic refraction would lead to a significant overestimation of myopia.