Miracle-dz/UniFAR-FTUs huggingface dataset:
A panel of KSHV mutants in the polycistronic kaposin locus for precise analysis of individual protein products

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the cause of several human cancers including the endothelial cell (EC) malignancy, Kaposi’s sarcoma. Unique KSHV genes absent from other human herpesvirus genomes, the “K-genes”, are important for KSHV replication and pathogenesis. Among these, the kaposin transcript is highly expressed in all phases of infection, but its complex polycistronic nature has hindered functional analysis to date. At least three proteins are produced from the kaposin transcript: Kaposin A (KapA), B (KapB), and C (KapC). To determine the relative contributions of kaposin proteins during KSHV infection, we created a collection of mutant viruses unable to produce kaposin proteins individually or in combination. Kaposin-deficient latent iSLK cell lines displayed reduced viral genome copy number and often exhibited small LANA nuclear bodies; despite this, all were capable of progeny virion production. Primary infection with ΔKapB virus revealed decreased LANA expression and viral genome copy number, yet providing KapB protein in trans failed to complement these defects, suggesting a requirement for the kaposin locus in cis. Our previous work showed that KapB was sufficient to recapitulate the elevated proinflammatory cytokine transcripts associated with KS via the disassembly of RNA granules called processing bodies (PBs). We now show that KapB is necessary for PB disassembly during latent KSHV infection. These findings demonstrate that our panel of kaposin-deficient viruses enables precise analysis of the respective contributions of individual kaposin proteins to KSHV replication. Moreover, our mutagenesis approach serves as a guide for the functional analysis of other complex multicistronic viral loci. Importance Kaposi’s sarcoma-associated herpesvirus (KSHV) expresses high levels of the kaposin transcript during both latent and lytic phases of replication. Due to its repetitive, GC-rich nature and polycistronic coding capacity, until now no reagents existed to permit a methodical analysis of the role of individual kaposin proteins in KSHV replication. We report the creation of a panel of recombinant viruses and matched producer cell lines that delete kaposin proteins individually or in combination. We demonstrate the utility of this panel by confirming the requirement of one kaposin translation product to a key KSHV latency phenotype. This study describes a new panel of molecular tools for the KSHV field to enable precise analysis of the roles of individual kaposin proteins during KSHV infection.
Complete loss of mitochondrial complex I genes in mistletoes (Viscaceae) and evidence of polyadenylated mitochondrial transcripts shown by whole transcriptome sequencing

The profound absence of mitochondrial complex I (NADH-ubiquinone oxidoreductase) genes from the mitogenome of Viscum spp. and the rapid rates of molecular evolution characterizing most of their remaining mitochondrial genes raise questions regarding the possible transfer of the entire nad gene set to the nucleus, as well as for the functionality of the remaining highly divergent genes. Using whole transcriptome sequencing in three species of Viscaceae: V. album, V. crassulae, and Phoradendron leucarpum we were able to confirm transcription of all previously identified genes. However, we did not detect any nad gene transcripts, thus, providing further evidence of the complete loss of complex I in Viscaceae. The results from transcriptome sequencing also revealed that levels and patterns of RNA editing were not different from those found in autotrophic plant species. Hence, RNA editing is not a means of restoring conserved domains or folding sites of the proteins coded for by the divergent mitochondrial genes. Since we were able to recover mitochondrial genes transcripts following a sequencing protocol targeted towards polyadenylated mRNA molecules, it is suggested that mitochondrial genes undergo post-transcriptional polyadenylation in Viscaceae.
Prediction and Characterization of Disorder-Order Transition Regions in Proteins by Deep Learning

The biological functions of proteins are traditionally thought to depend on well-defined three-dimensional structures, but many experimental studies have shown that disordered regions lacking fixed three-dimensional structures also have crucial biological roles. In some of these regions, disorder–order transitions are also involved in various biological processes, such as protein-protein interaction and ligand binding. Therefore, it is crucial to study disordered regions and structural transitions for further understanding of protein functions and folding. Owing to the costs and time requirements of experimental identification of natively disordered or transitional regions, the development of effective computational methods is a key research goal. In this study, we used overall residue dependencies and deep representation learning for prediction and reused the obtained disordered regions for the prediction of disorder–order transitions. Two similar and related prediction tasks were combined. Firstly, we developed a novel deep learning method, Res-BiLstm, for residue-wise disordered region prediction. Our method outperformed other predictors with respect to almost all criteria, as evaluated using an independent test set. For disorder-order transition prediction, we proposed a transfer learning method, Res-BiLstm-NN, with an acceptable but unbalanced performance, yielding reasonable results. To grasp underlining biophysical principles of disorder-order transitions, we performed qualitative analyses on the obtained results and discovered that most transitions have strong disordered or ordered preferences, and more transitions are consistent with the ordered state than the disordered state, different from conventional wisdom. To the best of our knowledge, this is the first sizable-scale study of transition prediction. Availability https://github.com/Yanzziang/Transition_Disorder_Prediction Contact kengo@ecei.tohoku. ac.jp
Challenge based learning in third level education : A literature review

The application of Challenge Based Learning has increased in third level institutions, fostering student transversal competencies, knowledge of sociotechnical problems, and collaboration with industry and community actors. However, a broad range of different frameworks, hybrid approaches, and educational interventions are using this term to define their approach. This lack of standardization creates definitional and conceptual challenges for the domain. A review of CBL literature was conducted to examine key characteristics, challenges and benefits, and educational factors. A total of 100 articles were reviewed using a qualitative thematic matrix. Results describe how benefits of Challenge Based Learning are reported despite many institutional, practical and academic challenges remaining. Although there was much variability in CBL approaches, eight common characteristics of CBL emerged from the literature. This research can support future research and implementation of CBL by providing guiding characteristics and a preliminary classification of CBL approaches.
Electroacupuncture Pretreatment Mitigates Myocardial Ischemia/Reperfusion Injury via XBP1/GRP78/Akt Pathway

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.
What Do Survivors of Child Sexual Abuse Believe Will Facilitate Early Disclosure of Sexual Abuse?

The purpose of this study was to explore what adult survivors of child sexual abuse (CSA) believe will facilitate early disclosure of sexual abuse. We conducted semi-structured interviews with 12 adult survivors of CSA aged 18–57 years, and analyzed the transcripts using reflexive thematic analysis. Our analysis resulted in three main themes: Adults making it possible to tell; Adults daring to consider the unthinkable; and Conveying knowledge of CSA that facilitates understanding. The findings highlighted the importance of adults facilitating disclosure and making it possible for survivors to tell about their experiences, but also the responsibility adults have to dare to consider the possibility of CSA when children struggle. Another important finding was the significance of enhancing the general population's understanding of the complexity of CSA, including why disclosure is difficult, so adults are given the tools needed to understand and know what to do when they suspect CSA. The findings also have important implications for the planning and implementation of interventions to facilitate early disclosure of CSA.
Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
Diversity of Marine Macro-Algicolous Endophytic Fungi and Cytotoxic Potential of Biscogniauxia petrensis Metabolites Against Cancer Cell Lines

Hypersaline environments are known to support diverse fungal species from various orders. The production of secondary metabolites is one of the strategies that fungi adopt to thrive under such extreme environments, bringing up the stress tolerance response. Some such unique secondary metabolites also exhibit clinical significance. The increasing prevalence of drug resistance in cancer therapy demands further exploration of these novel bioactive compounds as cancer therapeutics. In the present study, a total of 31 endophytic fungi harboring inside red, green, and brown marine algae have been isolated and identified. The maximum likelihood analysis and diversity indices of fungal endophytes revealed the phylogenetic relationship and species richness. The genus Aspergillus was found to be the dominating fungus, followed by Cladosporium spp. All the isolated endophytic fungal extracts were tested for their cytotoxicity against HeLa and A431 cancer cell lines. Nine isolates were further analyzed for their cytotoxic activity from the culture filtrate and mycelia extract. Among these isolates, Biscogniauxia petrensis showed potential cytotoxicity with CC50 values of 18.04 and 24.85 μg/ml against HeLa and A431 cells, respectively. Furthermore, the media and solvent extraction optimization revealed the highest cytotoxic active compounds in ethyl acetate extract from the potato dextrose yeast extract broth medium. The compound-induced cell death via apoptosis was 50–60 and 45% when assayed using propidium iodide-live/dead and loss of mitochondrial membrane potential assay, respectively, in HeLa cells. Four bioactive fractions (bioassay-based) were obtained and analyzed using chromatography and spectroscopy. This study reports, for the first time, the cytotoxic activity of an endophytic fungal community that was isolated from marine macro-algae in the Rameswaram coastal region of Tamil Nadu, India. In addition, B. petrensis is a prominent apoptotic agent, which can be used in pharmaceutical applications as a therapeutic.
Use of Alcohol and Addictive Drugs During the COVID-19 Outbreak in Norway: Associations With Mental Health and Pandemic-Related Problems

Background: The outbreak of COVID-19 has had a major impact on people's daily life. This study aimed to examine use of alcohol and addictive drugs during the COVID-19 outbreak in Norway and examine their association with mental health problems and problems related to the pandemic. Methods: A sample of 4,527 persons responded to the survey. Use of alcohol and addictive drugs were cross-tabulated with sociodemographic variables, mental health problems, and problems related to COVID-19. Logistic regression analyses were used to examine the strength of the associations. Results: Daily use of alcohol was associated with depression and expecting financial loss in relation to the COVID-19 outbreak. Use of cannabis was associated with expecting financial loss in relation to COVID-19. Use of sedatives was associated with anxiety, depression, and insomnia. Use of painkillers was associated with insomnia and self-reported risk of complications if contracting the coronavirus. Conclusion: The occurrence of mental health problems is more important for an understanding of the use of alcohol and addictive drugs during the COVID-19 outbreak in Norway, compared to specific pandemic-related worries.
Improvement in the Prediction of Summer Precipitation in the North China−Hetao Region Using the Tropospheric Temperature Over the Tibetan Plateau in Spring

We investigated the relationship between the spring tropospheric temperature over the Tibetan Plateau (TPT) and summer precipitation in eastern China on an interannual timescale using the monthly mean ERA-Interim reanalysis dataset, the HadISST dataset and the daily mean precipitation dataset for China. We found that there is a significant positive correlation between the spring TPT and summer precipitation in the North China−Hetao region. The relationship is manifested in the context of the East Asia–Pacific pattern teleconnection. In the high spring TPT index years, the geopotential height anomalies over East Asia and the western North Pacific present a negative phase of the East Asia–Pacific pattern teleconnection in the subsequent summer. This circulation pattern is beneficial for the water vapor transport from the western Pacific to inland, which further transport to the North China−Hetao region from the Yangtze River–Yellow rivers region. Anomalous upward motion occurs in the North China–Hetao region, which increases precipitation. The East Asian subtropical westerly jet shifts further north and the South Asian high weakens and shrinks westward. These conditions all favor an increase in precipitation over the North China–Hetao region. The spring TPT plays an important part in the prediction of summer precipitation in the North China−Hetao region. The improvement in the use of the spring TPT to predict summer precipitation in the North China–Hetao region is examined by comparing the prediction equations with and without the prediction factor of the spring TPT on the basis of the sea surface temperatures in key regions. After considering the impact of the spring TPT, the explanatory variance of the prediction equation for precipitation in the North China–Hetao region increases by 17.3%.
A Novel Prognostic Signature Based on Metabolism-Related Genes to Predict Survival and Guide Personalized Treatment for Head and Neck Squamous Carcinoma

Metabolic reprogramming contributes to patient prognosis. Here, we aimed to reveal the comprehensive landscape in metabolism of head and neck squamous carcinoma (HNSCC), and establish a novel metabolism-related prognostic model to explore the clinical potential and predictive value on therapeutic response. We screened 4752 metabolism-related genes (MRGs) and then identified differentially expressed MRGs in HNSCC. A novel 10-MRGs risk model for prognosis was established by the univariate Cox regression analysis and the least absolute shrinkage and selection operator (Lasso) regression analysis, and then verified in both internal and external validation cohort. Kaplan-Meier analysis was employed to explore its prognostic power on the response of conventional therapy. The immune cell infiltration was also evaluated and we used tumor immune dysfunction and exclusion (TIDE) algorithm to estimate potential response of immunotherapy in different risk groups. Nomogram model was constructed to further predict patients’ prognoses. We found the MRGs-related prognostic model showed good prediction performance. Survival analysis indicated that patients suffered obviously poorer survival outcomes in high-risk group (p < 0.001). The metabolism-related signature was further confirmed to be the independent prognostic value of HNSCC (HR = 6.387, 95% CI = 3.281-12.432, p < 0.001), the efficacy of predictive model was also verified by internal and external validation cohorts. We observed that HNSCC patients would benefit from the application of chemotherapy in the low-risk group (p = 0.029). Immunotherapy may be effective for HNSCC patients with high risk score (p < 0.01). Furthermore, we established a predictive nomogram model for clinical application with high performance. Our study constructed and validated a promising 10-MRGs signature for monitoring outcome, which may provide potential indicators for metabolic therapy and therapeutic response prediction in HNSCC.
Investigation of a Hypoxia-Immune-Related Microenvironment Gene Signature and Prediction Model for Idiopathic Pulmonary Fibrosis

Background There is growing evidence found that the role of hypoxia and immune status in idiopathic pulmonary fibrosis (IPF). However, there are few studies about the role of hypoxia and immune status in the lung milieu in the prognosis of IPF. This study aimed to develop a hypoxia-immune-related prediction model for the prognosis of IPF. Methods Hypoxia and immune status were estimated with microarray data of a discovery cohort from the GEO database using UMAP and ESTIMATE algorithms respectively. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing hypoxia-immune-related genes. Cibersort was used to evaluate the difference of 22 kinds of immune cell infiltration. Three independent validation cohorts from GEO database were used for external validation. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by Quantitative reverse transcriptase-PCR (qRT-PCR) and flow cytometry from 22 clinical samples, including 13 healthy controls, six patients with non-fibrotic pneumonia and three patients with pulmonary fibrosis. Results Hypoxia and immune status were significantly associated with the prognosis of IPF patients. High hypoxia and high immune status were identified as risk factors for overall survival. CD8+ T cell, activated CD4+ memory T cell, NK cell, activated mast cell, M1 and M0 macrophages were identified as key immune cells in hypoxia-immune-related microenvironment. A prediction model for IPF prognosis was established based on the hypoxia-immune-related one protective and nine risk DEGs. In the independent validation cohorts, the prognostic prediction model performed the significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients. The preliminary clinical specimen validation suggested the reliability of most conclusions. Conclusions The hypoxia-immune-based prediction model for the prognosis of IPF provides a new idea for prognosis and treatment.
Energetics of Eddy-Mean Flow Interactions in the Amery Ice Shelf Cavity

Previous studies demonstrated that eddy processes play an important role in ice shelf basal melting and the water mass properties of ice shelf cavities. However, the eddy energy generation and dissipation mechanisms in ice shelf cavities have not been studied systematically. The dynamic processes of the ocean circulation in the Amery Ice Shelf cavity are studied quantitatively through a Lorenz energy cycle approach for the first time by using the outputs of a high-resolution coupled regional ocean-sea ice-ice shelf model. Over the entire sub-ice-shelf cavity, mean available potential energy (MAPE) is the largest energy reservoir (112 TJ), followed by the mean kinetic energy (MKE, 70 TJ) and eddy available potential energy (EAPE, 10 TJ). The eddy kinetic energy (EKE) is the smallest pool (5.5 TJ), which is roughly 8% of the MKE, indicating significantly suppressed eddy activities by the drag stresses at ice shelf base and bottom topography. The total generation rate of available potential energy is about 1.0 GW, almost all of which is generated by basal melting and seawater refreezing, i.e., the so-called “ice pump. ” The energy generated by ice pump is mainly dissipated by the ocean-ice shelf and ocean-bottom drag stresses, amounting to 0.3 GW and 0.2 GW, respectively. The EKE is generated through two pathways: the barotropic pathway MAPE→MKE→EKE (0.03 GW) and the baroclinic pathway MAPE→EAPE→EKE (0.2 GW). In addition to directly supplying the EAPE through baroclinic pathway (0.2 GW), MAPE also provides 0.5 GW of power to MKE to facilitate the barotropic pathway.