Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive aging is associated with redistribution of synaptic weights in the hippocampus

Significance A longstanding question in the field of the neurobiology of learning and memory is why some aged individuals perform comparably to young adults in learning and memory tasks, whereas others show impairments that resemble the performance of those with hippocampal damage. Answers to this question have been critical for advancing our understanding of, and our ability to treat, aging-related cognitive impairments. Here, we have exploited the exquisite organization of the hippocampal circuit to reveal that “unsuccessful” cognitive aging is associated with a breakdown of young adult-like circuit organization, and provide a remarkably straightforward potential cellular substrate for the well-documented dysfunction in neuronal encoding of hippocampal CA1 and CA3 pyramidal neurons in aged learning-impaired rats. Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others’ lifespans outlast their “mindspans. ”
Effect of Pretreatments on Drying and Rehydration Kinetics and Color of Sweet Potato Slices

The effect of air temperature and pretreatments (KMS: citric acid) on drying kinetics of sweet potato slices was investigated. Drying experiments were performed in a tray dryer. In falling rate period, moisture transfer from sweet potato slices was described by applying the unsteady-state Fickian diffusion model, and the rate constant (k) were calculated. The effect of temperature on k could be interpreted according to Arrhenius law. Drying rate and therefore k values were found to be affected by pretreatments. Rehydration rates of dried sweet potato slices at 25, 40, 80°C were also determined and found to be independent of drying conditions and rehydration temperature. The ΔE value was found to be the highest for slices treated at 50°C with 0.5:1.0% KMS and citric acid.
Automated Rational Strain Construction Based on High-Throughput Conjugation

Molecular cloning is the core of Synthetic Biology, as it comprises the assembly of DNA and its expression in target hosts. At present, however, cloning is most often a manual, time-consuming and repetitive process that highly benefits from automation. The automation of a complete rational cloning procedure, i.e., from DNA part creation to expression in the target host, involves the integration of different operations and machines. Examples of such workflows are sparse, especially when the design is rational (i.e., the DNA sequence design is fixed, and not based on randomized libraries) and the target host is less genetically tractable (e.g., not sensitive to heat-shock transformation). In this study, an automated workflow for the rational construction of plasmids and their subsequent conjugative transfer into the biotechnological platform organism Corynebacterium glutamicum is presented. The whole workflow is accompanied by a custom-made software tool. As an application example, a rationally designed library of transcription factor biosensors based on the regulator Lrp was constructed and characterized. A sensor with an improved dynamic range was obtained, and insights from the screening provided evidence for a dual regulator function of C. glutamicum Lrp.
ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor–activated cancer

Significance The multiple-domain protein ZMYND8 is well known as a chromatin reader that recognizes methylated, acetylated, and/or mutated histones. Here we report that ZMYND8 is overexpressed in human ccRCC, and that it preferentially binds T487-phosphorylated EZH2. We show that in hypoxia-stimulated or von Hippel–Lindau–deficient cells, ZMYND8 binding of EZH2 is important for maintenance of EZH2 phosphorylation level, inhibition of PRC2 complex formation, and enhanced interaction between EZH2 and FOXM1. Our results reveal a reader function of ZMYND8 in recognizing a phosphorylation “code” on a nonhistone protein. Our findings also identify ZMYND8 binding as a facet of regulation and function of EZH2 phosphorylation in the Polycomb-dependent to -independent switch of EZH2/PRC2 activities. Both gene repressor (Polycomb-dependent) and activator (Polycomb-independent) functions of the Polycomb protein enhancer of zeste homolog 2 (EZH2) are implicated in cancer progression. EZH2 protein can be phosphorylated at various residues, such as threonine 487 (T487), by CDK1 kinase, and such phosphorylation acts as a Polycomb repressive complex 2 (PRC2) suppression “code” to mediate the gene repressor-to-activator switch of EZH2 functions. Here we demonstrate that the histone reader protein ZMYND8 is overexpressed in human clear cell renal cell carcinoma (ccRCC). ZMYND8 binds to EZH2, and their interaction is largely enhanced by CDK1 phosphorylation of EZH2 at T487. ZMYND8 depletion not only enhances Polycomb-dependent function of EZH2 in hypoxia-exposed breast cancer cells or von Hippel–Lindau (VHL)-deficient ccRCC cells, but also suppresses the FOXM1 transcription program. We further show that ZMYND8 is required for EZH2–FOXM1 interaction and is important for FOXM1-dependent matrix metalloproteinase (MMP) gene expression and EZH2-mediated migration and invasion of VHL-deficient ccRCC cells. Our results identify a previously uncharacterized role of the chromatin reader ZMYND8 in recognizing the PRC2-inhibitory phosphorylation “code” essential for the Polycomb-dependent to -independent switch of EZH2 functions. They also reveal an oncogenic pathway driving cell migration and invasion in hypoxia-inducible factor–activated (hypoxia or VHL-deficient) cancer.
Climate control on terrestrial biospheric carbon turnover

Significance Terrestrial organic-carbon reservoirs (vegetation, soils) currently consume more than a third of anthropogenic carbon emitted to the atmosphere, but the response of this “terrestrial sink” to future climate change is widely debated. Rivers export organic carbon sourced over their watersheds, offering an opportunity to assess controls on land carbon cycling on broad spatial scales. Using radiocarbon ages of biomolecular tracer compounds exported by rivers, we show that temperature and precipitation exert primary controls on biospheric-carbon turnover within river basins. These findings reveal large-scale climate control on soil carbon stocks, and they provide a framework to quantify responses of terrestrial organic-carbon reservoirs to past and future change. Terrestrial vegetation and soils hold three times more carbon than the atmosphere. Much debate concerns how anthropogenic activity will perturb these surface reservoirs, potentially exacerbating ongoing changes to the climate system. Uncertainties specifically persist in extrapolating point-source observations to ecosystem-scale budgets and fluxes, which require consideration of vertical and lateral processes on multiple temporal and spatial scales. To explore controls on organic carbon (OC) turnover at the river basin scale, we present radiocarbon (14C) ages on two groups of molecular tracers of plant-derived carbon—leaf-wax lipids and lignin phenols—from a globally distributed suite of rivers. We find significant negative relationships between the 14C age of these biomarkers and mean annual temperature and precipitation. Moreover, riverine biospheric-carbon ages scale proportionally with basin-wide soil carbon turnover times and soil 14C ages, implicating OC cycling within soils as a primary control on exported biomarker ages and revealing a broad distribution of soil OC reactivities. The ubiquitous occurrence of a long-lived soil OC pool suggests soil OC is globally vulnerable to perturbations by future temperature and precipitation increase. Scaling of riverine biospheric-carbon ages with soil OC turnover shows the former can constrain the sensitivity of carbon dynamics to environmental controls on broad spatial scales. Extracting this information from fluvially dominated sedimentary sequences may inform past variations in soil OC turnover in response to anthropogenic and/or climate perturbations. In turn, monitoring riverine OC composition may help detect future climate-change–induced perturbations of soil OC turnover and stocks.
Comparison between two preventive treatments for hyperketonaemia carried out pre-partum: effects on non-esterified fatty acids, β-hydroxybutyrate and some biochemical parameters during peripartum and early lactation

Abstract The objective of this study was to compare the effect of two different preventive protocols, on serum β-hydroxybutyrate (BHB) concentration and liver health indices pre-partum and during early-lactation in high-yielding Holstein dairy cows. One hundred cows were randomly divided into three groups: control group (CTRL, n = 20, without preventive treatment), second group (SUPP, n = 40 animals treated with a compound based on acetyl-methionine, inositol, cyanocobalamin, l-alanine, l-arginine, l-threonine, l-glutamic acid supplementation and α-lipoic acid) and third group (MON, n = 40 animals treated with monensin). Blood samples were collected from all cows at on 3 occasions pre-partum and 3 occasions post-partum. Body condition (BCS) score was evaluated and glucose, non-esterified fatty acids (NEFA), BHB, triglycerides, total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin, total proteins, globulins, albumin and urea concentrations were assessed. Two-way repeated measures analysis of variance was applied. Statistically significant differences among the three experimental groups were found in the values of all studied parameters (P < 0.05). Our results confirm the established beneficial effect of MON treatment in decreasing BHB levels and increasing glucose availability after calving. Serum biochemical analysis revealed the expected post-partum alterations attributable to adaptations that influenced the metabolism and liver function in CTRL, whereas these alterations were reduced or absent in SUPP and MON. Results from the present study suggest that both preventive protocols, but in particular SUPP, could positively affect selected indicators of energy metabolism reducing the risk of hyperketonaemia and increase of liver function in Holstein dairy cows, both pre- and post-partum.
Extrahippocampal contributions to spatial navigation in humans: A review of the neuroimaging evidence

Spatial navigation is a crucial everyday skill, which when impaired leads to a significant decrease in quality of life. In humans, functional magnetic resonance imaging (fMRI) has provided extensive insights into the neural underpinnings of navigation skills. Whereas the hippocampus has been recognized as the prime region underpinning navigation abilities, by providing a cognitive map of the environment, imaging studies have also implicated a range of other brain regions. In this review, we provide an overview of the fMRI evidence for extrahippocampal contributions to spatial navigation. We show that the parahippocampal cortex, retrosplenial cortex, dorsal striatum, and the posterior parietal cortex provide important complementary functions, and ultimately form part of a functional network that regulates successful way‐finding behavior.
Effects of Whey Protein on Skeletal Muscle Microvascular and Mitochondrial Plasticity Following 10-Weeks of Exercise Training in Men with Type-2 Diabetes.

Skeletal muscle microvascular dysfunction and mitochondrial rarefaction feature in type-2 diabetes mellitus (T2DM) linked to low tissue glucose disposal rate (GDR). Exercise training and milk protein supplementation independently promote microvascular and metabolic plasticity in muscle associated with improved nutrient delivery, but combined effects are unknown. In a randomised-controlled trial, 24 men (55.6 y, SD5.7) with T2DM ingested whey protein drinks (protein/carbohydrate/fat: 20/10/3 g; WHEY) or placebo (carbohydrate/fat: 30/3 g; CON) before/after 45 mixed-mode intense exercise sessions over 10 weeks, to study effects on insulin-stimulated (hyperinsulinemic clamp) skeletal-muscle microvascular blood flow (mBF) and perfusion (near-infrared spectroscopy), and histological, genetic, and biochemical markers (biopsy) of microvascular and mitochondrial plasticity. WHEY enhanced insulin-stimulated perfusion (WHEY-CON 5.6%; 90%CI -0.1, 11.3), while mBF was not altered (3.5%; -17.5, 24.5); perfusion, but not mBF, associated (regression) with increased GDR. Exercise training increased mitochondrial (range of means: 40-90%) and lipid density (20-30%), enzyme activity (20-70%), capillary:fiber ratio (~25%), and lowered systolic (~4%) and diastolic (4-5%) blood pressure, but without WHEY effects. WHEY dampened PGC1α -2.9% (90%CI -5.7, -0.2) and NOS3 -6.4% (-1.4, -0.2) expression, but other mRNA were unclear. Skeletal muscle microvascular and mitochondrial exercise adaptations were not accentuated by whey protein ingestion in men with T2DM. Clinical Trial Registration Number: ACTRN12614001197628 Novelty Bullets: • Chronic whey ingestion in T2DM with exercise altered expression of several mitochondrial and angiogenic mRNA. • Whey added no additional benefit to muscle microvascular or mitochondrial adaptations to exercise. • Insulin-stimulated perfusion increased with whey but was without impact on glucose disposal.
Trichoderma reesei Rad51 tolerates mismatches in hybrid meiosis with diverse genome sequences

Significance Sexual eukaryotes fall into two groups with respect to their RecA-like recombinases. The first group possesses Rad51 (ubiquitous) and Dmc1 (meiosis-specific), which cooperate to conduct interhomolog recombination in zygotes with high sequence heterogeneity. Interestingly, Dmc1 was lost from the second group of eukaryotic organisms. Here we used the industrial workhorse fungus Trichoderma reesei to address if and how Rad51-only eukaryotes carry out hybrid meiosis. We show that T. reesei Rad51 (TrRad51) is indispensable for interhomolog recombination during meiosis and that TrRad51, like Saccharomyces cerevisiae Dmc1, possesses a better mismatch tolerability than S. cerevisiae Rad51. Our results indicate that the ancestral TrRad51 evolved to acquire Dmc1-like properties by adopting multiple structural variations in the L1 and L2 DNA-binding loops. Most eukaryotes possess two RecA-like recombinases (ubiquitous Rad51 and meiosis-specific Dmc1) to promote interhomolog recombination during meiosis. However, some eukaryotes have lost Dmc1. Given that mammalian and yeast Saccharomyces cerevisiae (Sc) Dmc1 have been shown to stabilize recombination intermediates containing mismatches better than Rad51, we used the Pezizomycotina filamentous fungus Trichoderma reesei to address if and how Rad51-only eukaryotes conduct interhomolog recombination in zygotes with high sequence heterogeneity. We applied multidisciplinary approaches (next- and third-generation sequencing technology, genetics, cytology, bioinformatics, biochemistry, and single-molecule biophysics) to show that T. reesei Rad51 (TrRad51) is indispensable for interhomolog recombination during meiosis and, like ScDmc1, TrRad51 possesses better mismatch tolerance than ScRad51 during homologous recombination. Our results also indicate that the ancestral TrRad51 evolved to acquire ScDmc1-like properties by creating multiple structural variations, including via amino acid residues in the L1 and L2 DNA-binding loops.
The effect of cereal type and α-tocopherol supplementation on selective quality and processability parameters of milk from late lactation grazing dairy cows

Abstract This research communication addressed the hypothesis that late lactation cows offered an oat-grain-based supplement or a high level of α-TOC supplementation at pasture would have improved milk composition and processability. Over a grazing period of 49 d, 48 Holstein Friesian dairy cows were randomly assigned to one of four dietary treatments. The dietary treatments were: control, pasture only (CTRL), pasture + 2.65 kg DM barley-based concentrate + 350 IU α-TOC/kg (BARLO), pasture + 2.65 kg DM oat-based concentrate + 350 IU α-TOC/kg (OATLO) and pasture + 2.65 kg DM oat-based concentrate + 1050 IU α-TOC/kg (OATHI). Within this randomised complete block design experiment cows were blocked on days in milk (DIM) and balanced for parity, milk yield and composition. Rennet coagulation time (RCT) was reduced in milk from cows offered OATHI compared to CTRL cows and OATLO. Concentration of conjugated linoleic acid (CLA) was increased by OATHI compared to OATLO and in OATLO compared to CTRL. Supplementation with OATHI reduced individual saturated fatty acids (SFAs) in milk compared to OATLO. In conclusion, supplementing grazing dairy cows with an oat-based supplement improved total milk CLA concentration compared to pasture only. Offering a high level of α-TOC (2931 IU/d) to dairy cows reduced RCT, individual SFA and increased total CLA concentration of milk compared to a lower α-TOC level (738 IU α-TOC/d).
Short-term IL-15 priming leaves a long-lasting signalling imprint in mouse NK cells independently of a metabolic switch

NK cell reactivity is dynamically regulated by IL-15, and NK cells do not need more than a few minutes of exposure to remember the cytokine for several hours. IL-15 priming of NK cells is a broadly accepted concept, but the dynamics and underlying molecular mechanisms remain poorly understood. We show that as little as 5 min of IL-15 treatment in vitro, followed by removal of excess cytokines, results in a long-lasting, but reversible, augmentation of NK cell responsiveness upon activating receptor cross-linking. In contrast to long-term stimulation, improved NK cell function after short-term IL-15 priming was not associated with enhanced metabolism but was based on the increased steady-state phosphorylation level of signalling molecules downstream of activating receptors. Inhibition of JAK3 eliminated this priming effect, suggesting a cross talk between the IL-15 receptor and ITAM-dependent activating receptors. Increased signalling molecule phosphorylation levels, calcium flux, and IFN-γ secretion lasted for up to 3 h after IL-15 stimulation before returning to baseline. We conclude that IL-15 rapidly and reversibly primes NK cell function by modulating activating receptor signalling. Our findings suggest a mechanism by which NK cell reactivity can potentially be maintained in vivo based on only brief encounters with IL-15 trans-presenting cells.
Availability of adequately iodized salt at the household level in Ethiopia: A systematic review and meta-analysis

Background Iodine deficiency disorder (IDD) is a global, regional, and national public health problem that is preventable. Universal salt iodization is a worldwide accepted strategy to prevent IDD. The level of iodine in the salt should be adequate at the household level (≥15ppm). Though there was fragmented evidence on the proportion of adequately iodized salt at the household level in Ethiopia, the national level proportion of adequately iodized salt at the household level was remaining unknown. Therefore, this systematic review and meta-analysis estimated the pooled proportion of adequately iodized salt at the household level in Ethiopia from 2013–2020. Method We systematically searched the databases: PubMed/MEDLINE, Google Scholar, and Science Direct for studies conducted in Ethiopia on the availability of adequately iodized salt at the household level since 2013. We have included observational studies, which were published between January first, 2013, and 10 August 2020. The report was compiled according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of included studies was scored based on the Newcastle Ottawa quality assessment scale adapted for cross-sectional studies. The data were extracted in Microsoft excel and analyzed using Stata version 14.1 software. We employed a random-effects model to estimate the pooled proportion of adequately iodized salt at the household level in Ethiopia. The presence of statistical heterogeneity within the included studies was evaluated using the I-squared statistic. We used Egger’s regression test to identify evidence of publication bias. The pooled proportion with a 95% confidence interval (CI) was presented using tables and forest plots. Results We screened a total of 195 articles. Of these, 28 studies (with 15561 households) were included in the final systematic review and meta-analysis. In Ethiopia, the pooled proportion of adequately iodized salt at the household level was 37% (95% CI: 28, 46%). The subgroup analyses of 28 studies by residence revealed that the pooled proportion of adequately iodized salt at the household level was 32% (95% CI: 29, 35%) and 48% (95% CI: 31, 66%) in rural and urban areas, respectively. Based on geographic location, the highest proportion was found in Addis Ababa (81%; 95%CI: 78, 83), and the lowest proportion found in Dire Dawa (20%; 95%CI: 17, 22). Besides, the proportion of adequately iodized salt at the household level was significantly increased during 2017–2020 (42%; 95% CI: 30, 53%) as compared with 2013–2016 (27%; 95% CI: 17, 39%). Conclusions In Ethiopia, the pooled proportion of adequately iodized salt at the household level was very low as compared to the world health organization’s recommendation. Thus, the Federal Ministry of Health of Ethiopia and different stakeholders should give more attention to improve the proportion of adequately iodized salt at the household level.