Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Maltose and Trehalose Transport in Corynebacterium glutamicum

Zur Produktion von Aminosauren mit dem kommerziell bedeutsamen Bakterium Corynebacterium glutamicum kann aus Starkehydrolysat gewonnene Maltose als gute und gunstige Kohlenstoffquelle dienen. In der vorliegenden Arbeit wurde das Maltose/Maltodextrin Aufnahme-System MusIFGK2-E von C. glutamicum identifiziert und charakterisiert; ein ABC Transporter mit einem Km von 1,2 ± 0,2 μM und Vmax von 26,2 ± 1,0 nmol/(min*mg TG). Es konnte gezeigt werden, dass das System kein Operon bildet und dass es von dem transkriptionellen Regulator RamA reguliert wird. Zusatzlich konnte eine regulatorische Verbindung zur Phosphotransferase System vermittelten Glukose Verstoffwechslung aufgezeigt werden. Weitere Analysen identifizierten das Protein MusI, welches zwar fur die Aufnahme von Maltose essentiell, dessen Funktion aber noch unbekannt ist. Neben der Bedeutung als Aminosaureproduzent ist C. glutamicum ein wichtiger Modellorganismus fur die Zellwand und deren Synthese innerhalb der Corynebacterineae. In diesem Zusammenhang spielt Trehalose als Komponente von Mycolaten, wichtigen Bausteinen der Zellwand von Corynebakterien and Mycobakterien, eine bedeutende Rolle. In dieser Arbeit konnte zum ersten Mal gezeigt werden, dass C. glutamicum, im Gegensatz zu bereits publizierten Daten, mit einem Trehalose Aufnahme-System ausgestattet ist. Die Aufnahme wird uber den ABC Transporter TusFGK2-E mit einem Km von 0,16 ± 0,02 μM und Vmax von 2,5 ± 0,1 nmol/(min*mg TG) vermittelt. Trehalose kann anschliesend durch TreS in Maltose umgewandelt werden und dann uber den Maltose Abbauweg verstoffwechselt werden. Beachtenswerterweise konnte in dieser Arbeit ein zweiter Abbauweg fur Trehalose / Maltose identifiziert werden. Dieser Weg beinhaltet die TreS vermittelte Umwandlung von Trehalose in Maltose, TreX vermittelte Maltose-1- Phosphate und anschliesende α-Glucan Synthese durch GlgE, vergleichbar zu einem Abbauweg in M. tuberculosis (Kalscheuer et al., 2010a). Diese Ergebnisse stellten die Hypothese von Tropis et al., 2005 in Frage, dass man zur Synthese von Trehalose-Mycolaten Biosynthese und Export von Trehalose benotigt. Mit Hilfe einer vierfach-Deletionsmutante, die weder fahig ist Trehalose zu synthetisieren noch aufzunehmen, konnte gezeigt werden, dass die Synthese von Trehalose-Mycolaten durch externe Zugabe des Zuckers, auch ohne die vorherige Aufnahme von Trehalose moglich ist. Dies zeigte dass die Trehalose Export Hypothese weiterhin Gultigkeit besitzt und dass das Trehalose Export-System von C. glutamicum noch zu identifizieren ist.
Accurate prediction of protein structures and interactions using a 3-track neural network

Deep learning takes on protein folding In 1972, Anfinsen won a Nobel prize for demonstrating a connection between a protein's amino acid sequence and its three-dimensional structure. Since 1994, scientists have competed in the biannual Critical Assessment of Structure Prediction (CASP) protein-folding challenge. Deep learning methods took center stage at CASP14, with DeepMind's Alphafold2 achieving remarkable accuracy. Baek et al. explored network architectures based on the DeepMind framework. They used a three-track network to process sequence, distance, and coordinate information simultaneously and achieved accuracies approaching those of DeepMind. The method, RoseTTA fold, can solve challenging x-ray crystallography and cryo–electron microscopy modeling problems and generate accurate models of protein-protein complexes. Science, abj8754, this issue p. 871 Protein structure modeling enables the rapid solution of protein structures and provides insights into function. DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo–electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.
Neighbourhood Social Determinants of Health and Geographical Inequalities in Premature Mortality in Taiwan: A Spatiotemporal Approach

Geographical inequalities in premature mortality and the role of neighbourhood social determinants of health (SDOH) have been less explored. This study aims to assess the geographical inequalities in premature mortality in Taiwan and how neighbourhood SDOH contribute to them and to examine the place-specific associations between neighbourhood SDOH and premature mortality. We used township-level nationwide data for the years 2015 to 2019, including age-standardized premature mortality rates and three upstream SDOH (ethnicity, education, and income). Space-time scan statistics were used to assess the geographical inequality in premature mortality. A geographical and temporal weighted regression was applied to assess spatial heterogeneity and how neighbourhood SDOH contribute to geographic variation in premature mortality. We found geographical inequality in premature mortality to be clearly clustered around mountainous rural and indigenous areas. The association between neighbourhood SDOH and premature mortality was shown to be area-specific. Ethnicity and education could explain nearly 84% variation in premature mortality. After adjusting for neighbourhood SDOH, only a handful of hotspots for premature mortality remained, mainly consisting of rural and indigenous areas in the central-south region of Taiwan. These findings provide empirical evidence for developing locally tailored public health programs for geographical priority areas.
Age- and sex-related profiles for macro, macro/micro and microvascular reactivity indexes: Association between indexes and normative data from 2609 healthy subjects (3-85 years)

Vascular reactivity (VR), defined as blood vessels’ capability to actively modify the diameter and flow resistances can be non-invasively assessed analyzing vascular response to forearm occlusion. Several VR indexes can be quantified: (i) ´microvascular´, which consider variables that depend almost exclusively on changes in distal resistances, (ii)´ macrovascular´, that evaluate the changes in brachial artery (BA) diameter, adjusting for blood flow stimulus, and (iii) ´macro/micro´, whose values depend on the micro and macrovascular response without discriminating each one´s contribution. VR indexes could not be associated. Many VR indexes have been used without availability of adequate normative data (reference intervals, RIs). Aims: (1) to evaluate macro, macro/micro and micro VR indexes obtained in a cohort of healthy children, adolescents and adults, (2) to evaluate the association between VR indexes, (3) to determine the need for age and/or sex-specific RIs, and (4) to define RIs for VR indexes. Methods: Ultrasound (B-mode/Doppler) and automatic computerized analysis were used to assess BA diameter, blood flow velocity and distal resistances, at rest and in conditions of decreased and increased blood flow. Macro, macro/micro and micro VR indexes were quantified (n = 3619). RIs-subgroups were defined according to European Reference Values for Arterial Measurements Collaboration Group (n = 1688, 3–84 years) and HUNT3-Fitness Study Group (n = 2609, 3–85 years) criteria. Mean value and standard deviation equations were obtained for VR indexes. The need for age or sex-specific RIs was analyzed. Percentile curves were defined and data were compared with those obtained in other populations. Conclusion: Macro and macro/micro VR indexes showed no association (or it was very weak) with microvascular indexes. Age- and sex-related profiles and RIs for macro, macro/micro and micro VR indexes were defined in a large population of healthy subjects (3–85 y). Equations for mean, standard deviation and percentiles values (year-to-year) were included in text and spreadsheet formats.
Monitoring Immune Activation with Whole-Body Fluorodeoxyglucose–Positron-Emission Tomography in Simian Immunodeficiency Virus–Infected Rhesus Macaques

This study aimed to assess immune activation in tissues by measuring glucose metabolism with 18F-fluorodeoxyglucose (FDG) and investigate the associations of various peripheral markers of disease progression with initiation and interruption of combination antiretroviral therapy in SIV-infected rhesus macaques (Macaca mulatta). Mixed-effect linear models revealed a significant inverse association of peripheral blood CD4+ T cell counts (p < 0.01) and a direct association of plasma viral load (p < 0.01) with the FDG uptake in the spleen, bone marrow, and most clusters of lymph nodes. In contrast, no significant associations were found for the liver and the bowel FDG uptake. We also found no association of the fraction of proliferating peripheral blood T and B lymphocytes with FDG uptake in any analyzed tissues. The bowel FDG uptake of uninfected animals was heterogeneous and reached levels as high as those seen in the bowel or the clusters of lymph nodes or the spleen of high viremic SIV-infected animals, suggesting that factors beyond SIV-induced immune activation dominate the gut FDG uptake.
Sex Differences in Angiotensin II-Induced Hypertension and Kidney Injury: Role of AT1a Receptors in The Proximal Tubule of The Kidney.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wild-type and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female wild-type and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic pump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24 h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than wild-type controls (P<0.01) without significant sex differences between different strains. Both male and female wild-type and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female wild-type and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female wild-type and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.
Investigating pig survival in different production phases using genomic models

Abstract Pig survival is an economically important trait with relevant social welfare implications, thus standing out as an important selection criterion for the current pig farming system. We aimed to estimate (co)variance components for survival in different production phases in a crossbred pig population as well as to investigate the benefit of including genomic information through single-step genomic best linear unbiased prediction (ssGBLUP) on the prediction accuracy of survival traits compared with results from traditional BLUP. Individual survival records on, at most, 64,894 crossbred piglets were evaluated under two multi-trait threshold models. The first model included farrowing, lactation, and combined postweaning survival, whereas the second model included nursery and finishing survival. Direct and maternal breeding values were estimated using BLUP and ssGBLUP methods. Furthermore, prediction accuracy, bias, and dispersion were accessed using the linear regression validation method. Direct heritability estimates for survival in all studied phases were low (from 0.02 to 0.08). Survival in preweaning phases (farrowing and lactation) was controlled by the dam and piglet additive genetic effects, although the maternal side was more important. Postweaning phases (nursery, finishing, and the combination of both) showed the same or higher direct heritabilities compared with preweaning phases. The genetic correlations between survival traits within preweaning and postweaning phases were favorable and strong, but correlations between preweaning and postweaning phases were moderate. The prediction accuracy of survival traits was low, although it increased by including genomic information through ssGBLUP compared with the prediction accuracy from BLUP. Direct and maternal breeding values were similarly accurate with BLUP, but direct breeding values benefited more from genomic information. Overall, a slight increase in bias was observed when genomic information was included, whereas dispersion of breeding values was greatly reduced. Combined postweaning survival presented higher direct heritability than in the preweaning phases and the highest prediction accuracy among all evaluated production phases, therefore standing out as a candidate trait for improving survival. Survival is a complex trait with low heritability; however, important genetic gains can still be obtained, especially under a genomic prediction framework.
Marital Adjustment in Patients with Cancer: Association with Psychological Distress, Quality of Life, and Sleep Problems

Marital adjustment plays a key role in the physical and psychosocial wellbeing. We conducted a cross-sectional study to evaluate marital adjustment and its association with psychological distress, suicidal ideation, sleep problems, and quality of life in patients with cancer. We collected demographic and clinical information using a structured survey. We assessed marital adjustment, quality of life, psychological distress profile, and sleep problems of participants using validated instruments: the Locke and Wallace Marital Adjustment Test (LWMAT), the Short-Form Health Survey-12, the Beck’s Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the Insomnia Severity Index (ISI). Suicidal ideation was assessed with item nine of the BDI. Of the 130 patients (52.3% females, mean age 57.9 ± 12.4 years) enrolled, 20 (15%) were classified as experiencing poor marital adjustment. Moderate to severe depression, anxiety, and insomnia were found in 25.4%, 34.6%, and 24.7% of participants, respectively. Positive suicidal ideation was documented in 13.8% of participants. We found a significant association between poor marital adjustment and depression, anxiety, suicidal ideation, and poor sleep. Our study confirms the relevance of marital adjustment in relation to the psychological wellbeing of patients with cancer. Depression, anxiety, and poor sleep were found to be significantly associated with poor marital adjustment.
Quantifying Age-Related Changes in Brain and Behavior: A Longitudinal versus Cross-Sectional Approach

Abstract Cross-sectional versus longitudinal comparisons of age-related change have often revealed differing results. In the current study, we used within-subject task-based fMRI to investigate changes in voxel-based activations and behavioral performance across the life span in the Reference Ability Neural Network cohort, at both baseline and 5 year follow-up. We analyzed fMRI data from between 127 and 159 participants (20–80 years) on a battery of tests relating to each of four cognitive reference abilities. We applied a Gaussian age kernel to capture continuous change across the life span using a 5 year sliding window centered on each age in our participant sample, with a subsequent division into young, middle, and old age brackets. This method was applied separately to both cross-sectional approximations of change and real longitudinal changes adopting a comparative approach. We then focused on longitudinal measurements of neural change to identify regions expressing peak changes and fluctuations of sign change across our sample. Our results revealed several regions expressing divergence between cross-sectional and longitudinal measurements in each domain and age bracket; behavioral comparisons between measurements showed differences in change curves for all four domains, with processing speed displaying the steepest declines. In the longitudinal change measurement, we found lack of support for age-related frontal increases across analysis types, instead finding more posterior regions displaying peak increases in activation, particularly in the old age bracket. Our findings encourage greater focus on longitudinal measurements of age-related changes, which display appreciable differences from cross-sectional approximations.
Physical Activity and Quality of Life in High School Students: Proposals for Improving the Self-Concept in Physical Education

Adolescence is a critical period for the acquisition of health-related behaviors that will transcend later psychological well-being in adulthood. The present study presents a theoretical model whose objective is to analyze how physical activity predicts an adequate quality of life through self-concept and subjective happiness among adolescents. A total of 452 students aged 12 to 15 (M = 13.8; SD = 0.77) from four Compulsory Secondary Education institutes of the Autonomous Community of Extremadura participated, including boys (n = 258) and girls (n = 194). The students reported information on the following variables: physical activity, body mass index, self-concept, subjective happiness, and quality of life. The results show acceptable fit indices for the proposed theoretical model, which showed the importance of physical activity through self-concept and subjective happiness in quality of life: MRLχ2 = 67.533, p < 0.05, CFI = 0.93, TLI = 0.90, SRMR = 0.05, and RMSA = 0.07. Likewise, the model presented a better fit index for males than females. This study draws conclusions on the importance of physical activity as a predictor of quality of life mediated by the perception of self-concept and mood in adolescents.
Systematic Review of Psychosocial Smoking Cessation Interventions for People with Serious Mental Illness

Abstract Objective Tobacco smoking is a major driver of premature mortality in people with serious mental illness (SMI; e.g., schizophrenia, bipolar disorder). This systematic literature review described randomized control trials of psychosocial smoking cessation interventions for people with SMI, rated their methodological rigor, evaluated the inclusion of racial/ethnic and sexual/gender minorities, and examined smoking cessation outcomes. Methods: Eligible studies included peer-reviewed articles published between 2009 and 2020 that examined psychosocial smoking cessation interventions in people with SMI. We used the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines to conduct our review and the Methodological Quality Rating Scale to evaluate methodological rigor. Results: Eighteen studies were included. Ten were categorized as high methodological rigor given their study characteristics (e.g., longer follow-up) and eight as lower methodological rigor based on their characteristics (e.g., not intent-to-treat). Racial/ethnic and sexual/gender minorities were under-represented in these studies. A range of psychosocial interventions were examined including motivational enhancements, smoking cessation education, cognitive behavioral strategies, and contingency management. Most studies also provided smoking cessation medications (e.g., NRT, bupropion), although provision was not always uniform across treatment conditions. Three studies found the intervention condition achieved significantly higher abstinence from smoking compared to the comparison group. Seven studies found the intervention condition achieved significantly higher reductions in smoking compared to the comparison group. Conclusions: Studies finding significant differences between the intervention and comparison groups shared common evidenced-based components, including providing smoking cessation medications (e.g., NRT, bupropion), motivational enhancement techniques, and cessation education and skills training, but differed in intensity (e.g., number and frequency of sessions), duration, and modality (e.g., group, individual, technology). Methodological limitations and a small number of studies finding significant between-group differences prevent the identification of the most effective psychosocial smoking cessation interventions. Clinical trial designs (e.g., SMART, factorial) that control for the provision of psychosocial medications and allow for the identification of optimal psychosocial treatments are needed. Future studies should also ensure greater inclusion of racial/ethnic and sexual/gender minorities and should be culturally/linguistically adapted to improve treatment engagement and study outcomes.
Covalent immobilization of trypsin onto thermo‐sensitive poly(N‐isopropylacrylamide‐co‐acrylic acid) microspheres with high activity and stability

Poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AA)) microspheres with a high copolymerized AA content were fabricated using rapid membrane emulsification technique. The uniform size, good hydrophilicity, and thermo sensitivity of the microspheres were favorable for trypsin immobilization. Trypsin molecules were immobilized onto the microspheres surfaces by covalent attachment. The effects of various parameters such as immobilization pH value, enzyme concentration, concentration of buffer solution, and immobilization time on protein loading amount and enzyme activity were systematically investigated. Under the optimum conditions, the protein loading was 493 +/- 20 mgg(-1) and the activity yield of immobilized trypsin was 155%+/- 3%. The maximum activity (V-max) and Michaelis constant (K-m) of immobilized enzyme were found to be 0.74 Ms-1 and 0.54 mM, respectively. The immobilized trypsin showed better thermal and storage stability than the free trypsin. The enzyme-immobilized microspheres with high protein loading amount still can show a thermo reversible phase transition behavior. The research could provide a strategy to immobilize enzyme for application in proteomics. (c) 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43343.
SUSTAINABLE INNOVATION OF CHEMICALS: USING LCA AS A METRICS IN ADVANCING AND SCALING UP GREEN CHEMISTRY RESEARCH

The concept of Green Chemistry was coined in the 1990s and can be briefly defined as applying the pollution prevention approach to chemistry. LCA is a technique to assess environmental impacts associated with all the stages of a product's life from-cradle-to-grave. If this method is applied in the form of a gate-to-gate LCA it provides the environmental profile, or footprint, of a chemical or material composed of multiple chemicals. A criticism to the 12 green chemistry principles as a tool is their qualitative nature. Using two examples, this paper shows how LCA can help evaluating the 12 principles in concrete cases of advancing green chemistry research towards the sustainable innovation of chemicals. Emphasis is made to show the potential for using LCA as a metrics in scaling up this research.