Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of KAP1/TRIM28 Requirements for HIV-1 Transcription Activation

HIV-1 latency maintenance and reactivation are regulated by several viral and host factors. One such factor is Krüppel-associated box (KRAB)-associated protein 1 (KAP1: also named TRIM28 or TIF1β). While initial studies have revealed KAP1 to be a positive regulator of latency reversal in transformed and primary CD4+ T cells, subsequent studies have proposed KAP1 to be a repressor required for latency maintenance. Given this discrepancy, in this study, we re-examine KAP1 transcription regulatory functions using a chemical genetics strategy to acutely deplete KAP1 expression to avoid the accumulation of indirect effects. Notably, KAP1 acute loss partially decreased HIV-1 promoter activity in response to activating signals, a function that can be restored upon complementation with exogenous KAP1, thus revealing that KAP1-mediated activation is on target. By combining comprehensive KAP1 domain deletion and mutagenesis in a cell-based reporter assay, we genetically defined the RING finger domain and an Intrinsically Disordered Region as key activating features. Together, our study solidifies the notion that KAP1 activates HIV-1 transcription by exploiting its multi-domain protein arrangement via previously unknown domains and functions.
Recent Approaches to the Formulation, Uses, and Impact of Edible Coatings on Fresh Peach Fruit

Peaches are among the most well-known fruits in the world due to their appealing taste and high nutritional value. Peach fruit, on the other hand, has a variety of postharvest quality issues like chilling injury symptoms, internal breakdown, weight loss, decay, shriveling, and over-ripeness, which makes a challenging environment for industries and researchers to develop sophisticated strategies for fruit quality preservation and extending shelf life. All over the world, consumers prefer excellent-quality, high-nutritional-value, and long-lasting fresh fruits that are free of chemicals. An eco-friendly solution to this issue is the coating and filming of fresh produce with natural edible materials. The edible coating utilization eliminates the adulteration risk, presents fruit hygienically, and improves aesthetics. Coatings are used in a way that combines food chemistry and preservation technology. This review, therefore, examines a variety of natural coatings (proteins, lipids, polysaccharides, and composite) and their effects on the quality aspects of fresh peach fruit, as well as their advantages and mode of action. From this useful information, the processors could benefit in choosing the suitable edible coating material for a variety of fresh peach fruits and their application on a commercial scale. In addition, prospects of the application of natural coatings on peach fruit and gaps observed in the literature are identified.
Evaluation of the Effects of an Undenatured Collagen Type-2-Based Nutraceutical (ARTHROSHINE® HA²) on Recovery Time after TPLO in Dogs: A Prospective, Randomized Study with Objective Gait Analysis as the Primary Outcome Measure

Simple Summary Undenatured collagen type 2 is considered a promising treatment for osteoarthritis in both humans and animals. Osteoarthritis, a degenerative joint disease, is often associated with cranial cruciate ligament rupture in dogs, which frequently necessitates Tibial Plateau Leveling Osteotomy (TPLO). Despite the generally successful outcomes of TPLO, dogs frequently experience postoperative pain and ongoing joint degeneration. To address these concerns, our study delved into the effects of oral supplementation with a high-concentration undenatured collagen type 2 dietary supplement (ARTHROSHINE® HA²) post-TPLO surgery. Employing a prospective, randomized design, we utilized treadmill analysis and a validated owner questionnaire to objectively gauge the nutraceutical supplement’s influence on limb function, overall activity level, and pain. The results are highly encouraging. Gait analysis revealed a significant reduction in the duration of postoperative rehabilitation, enabling complete recovery within just 12 weeks after the procedure, compared to the 24 weeks required without the supplement. This research underscores the potential of undenatured collagen type 2 as an adjunctive therapy for alleviating lameness following TPLO surgery. Notably, subjective owner perceptions did not differ between the groups. Abstract This randomized, prospective clinical trial investigates the impact of a novel undenatured collagen type 2 (T2NDC)-based nutraceutical, ARTHROSHINE® HA² (AS), on postoperative rehabilitation following Tibial Plateau Leveling Osteotomy (TPLO) in 50 dogs with unilateral cranial cruciate ligament rupture (CCLR). The patients were randomly allocated to either group A, receiving AS once daily for 24 weeks post-TPLO surgery, or group B, without any supplementation. Frequency matching was applied to enhance group comparability. Assessment of outcomes included computerized gait analysis and a validated owner questionnaire. AS supplementation was well received, without any reported side effect. Consistently, patients in group A exhibited significantly higher peak vertical force values during all follow-up assessments. By the 12-week mark, gait analysis indicated a return to a physiological gait pattern in group A, while group B achieved this normalization only by the 24-week point. The administration of AS post-TPLO surgery demonstrates promise in enhancing limb function, leading to faster restoration of a physiological gait pattern. The inclusion of AS, a T2NDC-based nutraceutical, in the post-TPLO rehabilitation protocol may contribute to improved limb function and an expedited recovery, potentially facilitating a quicker return to normalcy. It is noteworthy that subjective owner perceptions did not differ between the two groups.
Lessons from the Past: Unfolding the Dynamics among Climate, Balkan Landscapes, and Humans over the Past Millennium

This study presents the first, well-dated, high-resolution record of vegetation and landscape change from Serbia, which spans the past 500 years. Biological proxies (pollen, spores, and charcoal), geochemical analysis through X-ray Fluorescence (XRF), and a detailed chronology based on AMS C dating from a western Serbian sinkhole core suggest complex woodlandgrassland dynamics and strong erosional signals throughout the Little Ice Age (LIA). An open landscape with prominent steppe vegetation (e.g. Poaceae, Chenopodiaceae) and minor woodland exists during 1540-1720 CE (early LIA), while the late LIA (1720-1850 CE) in this record shows higher tree percentages possibly due to increased moisture availability. The post LIA Era (18502012 CE) brings a disturbed type of vegetation with the presence of weedy genera and an increase in regional woodland. Anthropogenic indicators for agricultural, pastoral and fire practices in the region together attest to the dominant role of humans in shaping this Balkan landscape throughout the interval. The changing nature of human interference, potentially as a response to underlying climatic transitions, is evident through large-scale soil depletion resulting from grazing and land clearance during the early LIA and stabilization of arable lands during the late and post-LIA eras.
Galactosylceramide Upregulates the Expression of the BCL2 Gene and Downregulates the Expression of TNFRSF1B and TNFRSF9 Genes, Acting as an Anti-Apoptotic Molecule in Breast Cancer Cells

Simple Summary Galactosylceramide (GalCer) increases the resistance of breast cancer to anti-cancer drugs by acting as an anti-apoptotic molecule. This glycosphingolipid was found to specifically downregulate the levels of the pro-apoptotic TNFRSF1B and TNFRSF9 genes and upregulate the levels of the anti-apoptotic BCL2 gene, suggesting that GalCer regulates their expression at the transcriptional level. Consistent with this hypothesis, (1) MDA-MB-231 and MCF7 cell lines with increased GalCer content showed low activity of the TNFRSF1B and TNFRSF9 promoters; (2) in such MCF7 cells, the activity of the BCL2 promoter was high. However, no differences in BCL2 promoter activity were observed between MDA-MB-231 cells with low and high GalCer contents. Instead, GalCer increased the stability of Bcl-2 mRNA in the latter cells. The regulatory protein that simultaneously increases the expression of the TNFRSF1B and TNFRSF9 genes and decreases the expression of the BCL2 gene and the stability of Bcl-2 transcripts is most likely P53, the expression of which is GalCer dependent. Abstract Galactosylceramide (GalCer) increases the resistance of breast cancer cells to doxorubicin, paclitaxel, and cisplatin by acting as an anti-apoptotic molecule. GalCer was found to specifically downregulate the levels of the pro-apoptotic TNFRSF1B and TNFRSF9 genes and upregulate the levels of the anti-apoptotic BCL2 gene, suggesting that this glycosphingolipid regulates their expression at the transcriptional level. Consistent with this hypothesis, MDA-MB-231 and MCF7 breast cancer cells with high levels of GalCer showed lower activity of the TNFRSF1B and TNFRSF9 promoters than cells lacking GalCer. In contrast, the activity of the BCL2 promoter was higher in MCF7 cells overproducing GalCer than in MCF7 cells without GalCer. However, no difference in BCL2 promoter activity was observed between MDA-MB-231 cells with high and no GalCer content. Instead, we found that high levels of GalCer increased the stability of Bcl-2 mRNA. Subsequent studies showed that breast cancer cells with high levels of GalCer are characterized by significantly lower expression of P53. Importantly, inhibition of P53 expression by siRNA in MCF7 and MDA-MB-231 cells lacking GalCer resulted in decreased expression and promoter activity of the TNFRS1B and TNFRSF9 genes. On the other hand, increased expression and promoter activity of the BCL2 gene was found in such MCF7 cells, and increased stability of Bcl-2 transcripts was observed in such MDA-MB-231 cells. Taken together, these data strongly suggest that the regulatory protein that simultaneously increases the expression of the TNFRSF1B and TNFRSF9 genes and decreases the expression of the BCL2 gene and the stability of Bcl-2 transcripts is most likely P53, the expression of which is GalCer dependent.
Genetic Dissection of BDNF and TrkB Expression in Glial Cells

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL) as well as a lower level of truncated TrkB (TrkB.T). However, there are conflicting reports regarding the expression of BDNF and TrkB in glial cells, particularly microglia. In this study, we employed a sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent reporter mice to label BDNF- or TrkB-expressing cells with soma-localized EGFP. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB-expressing microglia in examined CNS regions, including the somatomotor cortex, hippocampal CA1, and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the hippocampus of adult brains. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF in the hippocampus, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the hippocampus of adult mice. These results not only clarify the expression of BDNF and TrkB in glial cells but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in astrocytes and oligodendrocytes.
The 2.6 Å Structure of a Tulane Virus Variant with Minor Mutations Leading to Receptor Change

Human noroviruses (HuNoVs) are a major cause of acute gastroenteritis, contributing significantly to annual foodborne illness cases. However, studying these viruses has been challenging due to limitations in tissue culture techniques for over four decades. Tulane virus (TV) has emerged as a crucial surrogate for HuNoVs due to its close resemblance in amino acid composition and the availability of a robust cell culture system. Initially isolated from rhesus macaques in 2008, TV represents a novel Calicivirus belonging to the Recovirus genus. Its significance lies in sharing the same host cell receptor, histo-blood group antigen (HBGA), as HuNoVs. In this study, we introduce, through cryo-electron microscopy (cryo-EM), the structure of a specific TV variant (the 9-6-17 TV) that has notably lost its ability to bind to its receptor, B-type HBGA—a finding confirmed using an enzyme-linked immunosorbent assay (ELISA). These results offer a profound insight into the genetic modifications occurring in TV that are necessary for adaptation to cell culture environments. This research significantly contributes to advancing our understanding of the genetic changes that are pivotal to successful adaptation, shedding light on fundamental aspects of Calicivirus evolution.
Polymeric Binder Design for Sustainable Lithium-Ion Battery Chemistry

The design of binders plays a pivotal role in achieving enduring high power in lithium-ion batteries (LIBs) and extending their overall lifespan. This review underscores the indispensable characteristics that a binder must possess when utilized in LIBs, considering factors such as electrochemical, thermal, and dispersion stability, compatibility with electrolytes, solubility in solvents, mechanical properties, and conductivity. In the case of anode materials, binders with robust mechanical properties and elasticity are imperative to uphold electrode integrity, particularly in materials subjected to substantial volume changes. For cathode materials, the selection of a binder hinges on the crystal structure of the cathode material. Other vital considerations in binder design encompass cost effectiveness, adhesion, processability, and environmental friendliness. Incorporating low-cost, eco-friendly, and biodegradable polymers can significantly contribute to sustainable battery development. This review serves as an invaluable resource for comprehending the prerequisites of binder design in high-performance LIBs and offers insights into binder selection for diverse electrode materials. The findings and principles articulated in this review can be extrapolated to other advanced battery systems, charting a course for developing next-generation batteries characterized by enhanced performance and sustainability.
How dialectical behavioral-based intervention affects nursing college students' hope, somatic symptoms, and negative thoughts during COVID-19.

INTRODUCTION During the COVID-19 pandemic, the mental health of college students was typically poor; somatic symptoms, depression, negative thoughts, and hopelessness were widespread issues that should have been addressed through therapy and intervention. OBJECTIVE To examine the effect of dialectical behavioral-based Intervention (DBBI) on female nursing college students' hope, somatic symptoms, and negative thoughts during COVID-19. METHODOLOGY In the quasi-experimental study, 28 female nursing college students were treated with DBBI (intervention group). This group was compared to 28 students who received no intervention (the control group). The somatic self-rating scale, the adult hope questionnaire, and the automatic thought questionnaire 30 were used to assess changes in students' somatic symptoms, hope, and negative thoughts. RESULTS The DBBI group's value-added total score of student`s hope and negative thoughts were both considerably higher than the control group (t = 2.53, p = 0.01 and t = 2.36, p = 0.03, respectively), while the value added of the total score of somatic symptoms was not statistically significant (t = 0.93, p = 0.36). The depression subscale's value-added score was significantly higher in the DBBI group than in the control group (t = 2.23, p = 0.02). CONCLUSIONS Dialectical behavioral-based intervention is advised to develop knowledge and empower students against depression and its components because of its effectiveness in lowering negative thoughts and raising the level of hope.
Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study

Background More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. Methods and findings Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. Conclusions The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.
The Traumatic Inoculation Process Affects TSPO Radioligand Uptake in Experimental Orthotopic Glioblastoma

Background: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma. Methods: Serial [18F]GE-180 and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET scans were performed at day 7/8 and day 14/15 after the inoculation of GL261 mouse glioblastoma cells (n = 24) or saline (sham, n = 6) into the right striatum of immunocompetent C57BL/6 mice. An additional n = 25 sham mice underwent [18F]GE-180 PET and/or autoradiography (ARG) at days 7, 14, 21, 28, 35, 50 and 90 in order to monitor potential reactive processes that were solely related to the inoculation procedure. In vivo imaging results were directly compared to tissue-based analyses including ARG and immunohistochemistry. Results: We found that the inoculation process represents an immunogenic event, which significantly contributes to TSPO radioligand uptake. [18F]GE-180 uptake in GL261-bearing mice surpassed [18F]FET uptake both in the extent and the intensity, e.g., mean target-to-background ratio (TBRmean) in PET at day 7/8: 1.22 for [18F]GE-180 vs. 1.04 for [18F]FET, p < 0.001. Sham mice showed increased [18F]GE-180 uptake at the inoculation channel, which, however, continuously decreased over time (e.g., TBRmean in PET: 1.20 at day 7 vs. 1.09 at day 35, p = 0.04). At the inoculation channel, the percentage of TSPO/IBA1 co-staining decreased, whereas TSPO/GFAP (glial fibrillary acidic protein) co-staining increased over time (p < 0.001). Conclusion: We identify the inoculation-driven immune response to be a relevant contributor to the PET signal and add a new aspect to consider for planning PET imaging studies in orthotopic glioblastoma models.
Empirically derived portion sizes from the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study for 4- to 18-year-old children and adolescents to simplify analysis of dietary data using FFQ

Objective: To apply FFQ, knowledge about portion sizes is relevant. According to increased energy and nutrient requirements, average portion sizes of foods are supposed to increase during growth. We provide empirically derived portion sizes for 4- to 18-year-olds in different age groups to facilitate analyses of FFQ data in children and adolescents. Design: Using data from the dynamic DOrtmund Nutritional and Anthropometric Longitudinally Designed cohort study, quantile regression for smoothing percentiles was used to derive portion sizes as a function of age from which age- and food group-specific portion sizes were calculated as median food group intake (g). Setting: Dortmund, Germany. Participants: Data from 3-day weighed dietary records (WDR) of 1,325 participants (♀: 653) were analysed. Participants provided in total 9,828 WDR (on average 7·5 per participant) between 1985 and 2022. WDR were grouped into five age groups, whereby each age group covered 3 years of age. Results: In total, 11 955 food items were reported and categorised into sixteen major food groups with seventy-one sub-groups. Portion sizes tended to increase with age, except for milk- and plant-based alternatives. Comparing 4- to 6-year-olds to 16- to 18-year-olds, portion size increased between 22·2 % (processed meat: 18 g v. 22 g) and 173·3 % (savoury snacks: 15 g v. 41 g). Conclusion: We provide empirically derived portion sizes for children and adolescents. These data are useful to establish dietary assessment methods based on estimates of portion sizes, such as FFQ, for children and adolescents.