Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling DNA Opening in the Eukaryotic Transcription Initiation Complexes via Coarse-Grained Models

Recently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiation complex remain obscured. In this study, based on the three cryo-electron microscopic yeast structures for the closed, open, and initially transcribing complexes, we performed multiscale molecular dynamics (MD) simulations to model structures and dynamic processes of DNA opening. Combining coarse-grained and all-atom MD simulations, we first obtained the atomic model for the DNA bubble in the open complexes. Then, in the MD simulation from the open to the initially transcribing complexes, we found a previously unidentified intermediate state which is formed by the bottleneck in the fork loop 1 of Pol II: The loop opening triggered the escape from the intermediate, serving as a gatekeeper of the promoter DNA opening. In the initially transcribing complex, the non-template DNA strand passes a groove made of the protrusion, the lobe, and the fork of Rpb2 subunit of Pol II, in which several positively charged and highly conserved residues exhibit key interactions to the non-template DNA strand. Author Summary Transcription is fundamental phenomenon in all species, and its regulation of the initiation process is important. In eukaryotes, multiple proteins, which is not only RNA polymerase but also transcription factors, assemble on the promotor to form the complex. After that, this complex open the part of DNA duplex, leading to forming single-stranded region for transcription. Previous study, including structural analysis and biochemical experiments, obtained the information about single-stranded region, but the structure is incomplete, so the details of the mechanism remains unclear. In this study, by the calculation using structural information about the protein-DNA complex, we obtained the structure of the complex with complete single-stranded region. As the result of the calculation, it found that the size of single-stranded region was fluctuated, which is related the sequence of the region. Furthermore, we found the intermediate state during the extended process of single-stranded region, which has not been reported in previous study. In this state, we found that the particular region of RNA polymerase is relevant to the extension of single-stranded region. These founding may contribute the understanding about the regulation of transcription initiation.
The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance

Optic atrophy (OA) with autosomal inheritance is a form of optic neuropathy characterized by the progressive and irreversible loss of vision. In some cases, this is accompanied by additional, typically neurological, extra-ocular symptoms. Underlying the loss of vision is the specific degeneration of the retinal ganglion cells (RGCs) which form the optic nerve. Whilst autosomal OA is genetically heterogenous, all currently identified causative genes appear to be associated with mitochondrial organization and function. However, it is unclear why RGCs are particularly vulnerable to mitochondrial aberration. Despite the relatively high prevalence of this disorder, there are currently no approved treatments. Combined with the lack of knowledge concerning the mechanisms through which aberrant mitochondrial function leads to RGC death, there remains a clear need for further research to identify the underlying mechanisms and develop treatments for this condition. This review summarizes the genes known to be causative of autosomal OA and the mitochondrial dysfunction caused by pathogenic mutations. Furthermore, we discuss the suitability of available in vivo models for autosomal OA with regards to both treatment development and furthering the understanding of autosomal OA pathology.
Falling in Love With Work: The Effect of Enterprise Social Media on Thriving at Work

Using a survey of 300 employees in different types of enterprises and different positions, this study verified that the use of enterprise social media has a positive effect on employees’ work exuberance. The study separately examined the effects of social media applications for work tasks and social tasks. Both types of applications had a positive impact on employees’ work exuberance. The study also identified the mediating role of challenge and obstructive stressors in this relationship. Work-related social media applications enhanced employees’ exuberance by reducing obstructive stressors, and social-related social media applications enhanced employees’ exuberance by reducing challenge stressors. The implications of these findings are that managers should pay attention to the use of enterprise social media, especially for social tasks, as this can enhance employees’ sense of exuberance.
Pattern of Aeroallergen Sensitization and Quality of Life in Adult Thai Patients With Allergic Rhinitis

The prevalence of allergic rhinitis (AR) is steadily rising in the Thai population, causing a major impact on the quality of life (QoL). Enhancing knowledge on common aeroallergens in the local setting helps in the appropriate prevention and management of AR. In this study, the demographic characteristics, clinical data, aeroallergen sensitization pattern, allergic symptoms, visual analog scale (VAS) score, and QoL are described. We evaluated the association between VAS, QoL, and severity of symptoms, except the aeroallergen sensitization pattern. We retrospectively reviewed the medical records of adult AR patients with a positive skin prick test (SPT) for at least one aeroallergen from January 2018 to May 2020. Standard descriptive and inferential statistics were used for analysis. A total of 366 patients were enrolled. Indoor aeroallergen sensitization and outdoor aeroallergen sensitization were observed in 32% and 7.9% of patients, respectively. Mono-sensitization was noted in 16.9% of patients, while poly-sensitization was noted in 83.1% of patients. Mites (65%) and sedge (39.3%) were the most common indoor and outdoor allergens. Nasal obstruction (74.6%), runny nose (63.7%), and nasal itchiness (61.5%) were the primary symptoms affecting the QoL. The association between VAS and symptom scores showed a trend of association with AR severity (Allergic Rhinitis and its Impact on Asthma [ARIA] classification) and VAS. AR has a significant effect on QoL in all domains of the validated generic (short-form-36, SF-36) and specific (rhino-conjunctivitis QoL questionnaire, Rcq-36) questionnaires. Mite and sedge remain the most common indoor and outdoor aeroallergens. The pattern of sensitization and number of aeroallergens were not associated with AR based on the ARIA guidelines. Meanwhile, symptoms of patients affected the QoL and VAS scores, which can be used as a quick and reliable tool for monitoring and stepping up or stepping down the treatment according to the next-generation guidelines. AR has a significant impact on the QoL of adult Thai patients.
Self-Management in Anxiety and Depression: A Psychometric Evaluation of a Questionnaire

Objective: To examine the underlying factor structure and psychometric properties of the Assessment of Self-management in Anxiety and Depression (ASAD) questionnaire, which was specifically designed for patients with (chronic) anxiety and depressive disorders. Moreover, this study assesses whether the number of items in the ASAD can be reduced without significantly reducing its precision. Methods: The ASAD questionnaire was completed by 171 participants across two samples: one sample comprised patients with residual anxiety or depressive symptoms, while the other consisted of patients who have been formally diagnosed with a chronic anxiety or depressive disorder. All participants had previously undergone treatment. Both exploratory (EFA) and confirmatory factor analyses (CFA) were conducted. Internal consistency and test–retest reliability were also assessed. Results: Both EFA and CFA indicated three solid factors: Seeking support, Daily life strategies and Taking ownership [Comparative Fit Index = 0.80, Tucker Lewis Index = 0.78, Root Mean Square Error of Approximation = 0.09 (CI 0.08–1.00), Standardized Root Mean Square Residual = 0.09 (χ2 = 439.35, df = 168)]. The ASAD was thus reduced from 45 items to 21 items, which resulted in the ASAD-Short Form (SF). All sub-scales had a high level of internal consistency (> α = 0.75) and test–retest reliability (ICC > 0.75). Discussion: The first statistical evaluation of the ASAD indicated a high level of internal consistency and test–retest reliability, and identified three distinctive factors. This could aid patients and professionals’ assessment of types of self-management used by the patient. Given that this study indicated that the 21-item ASAD-SF is appropriate, this version should be further explored and validated among a sample of patients with (chronic or partially remitted) anxiety and depressive disorders. Alongside this, to increase generalizability, more studies are required to examine the English version of the ASAD within other settings and countries.
Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.
Higher Animal Protein Intake During the Second Trimester of Pregnancy Is Associated With Risk of GDM

Background and Aims: This study aimed to examine the associations between the total protein intake as well as types and sources of proteins with the gestational diabetes mellitus (GDM) risk. Method and Results: This was a prospective cohort study of the pregnant women in Malaysia. In this study, the total, animal, and plant protein intakes were assessed using a semi-quantitative food frequency questionnaire. Of the 452 women, 48 (10.62%) were diagnosed with GDM. From pre-pregnancy to second trimester, most of the women had 10–20% of energy intake from protein (88.9–90.3%) and ≥75% of recommended protein intake (74.6–86.5%). The women in the highest tertile (T3) of total animal protein intake [adjusted odds ratio (AOR) = 2.76, 95% CI = 1.27–6.04] and red meat protein (AOR = 2.69, 95% CI = 1.27–5.70), specifically in the second trimester, had significantly higher GDM risk compared with the women in the middle tertile of intake (T2). Interestingly, the women in the T3 of egg protein in the second trimester were significantly at lower GDM risk (AOR = 0.43, 95% CI = 0.18–0.91) compared with those in T2. Conclusion: The highest tertile of animal protein (≥42.15 g/day) intake, particularly red meat protein in the second trimester was positively associated with the GDM risk, whereas the highest tertile of egg protein was inversely associated with the GDM risk. Protein intake before or during early pregnancy was not associated with the GDM risk. These findings underscore the importance of sources and types of protein intake, particularly after the first trimester of pregnancy, in relation to GDM risk.
Association Between Migraine Complicated With Restless Legs Syndrome and Vitamin D

Background: This study aimed to evaluate the prevalence of restless legs syndrome (RLS) in patients with migraine and explore its association with vitamin D deficiency, aiming to provide biological support for the comorbidity of migraine with RLS, and shed new lights into clinical diagnosis and treatment. Methods: A case-control study was performed on 175 migraine patients and 151 non-headache controls. The information of all subjects concerning headache severity [visual analog scale (VAS) score], RLS, RLS severity [International Restless Legs Scale (IRLS) score], sleep quality [Pittsburgh sleep quality index (PSQI)], anxiety and depression symptoms [hospital anxiety and depression scale (HADS)], and demographic data were collected. At the same time, serum 25-(OH) D levels were also measured (concentration <20 ng/ml was defined deficiency). Afterward, the logistic regression model was adopted to explore the risk factors for RLS in patients with migraines. Results: Compared with control group, migraine group had lower vitamin D levels [(21.10 ± 6.58) vs. (16.42 ± 5.6) ng/ml, P < 0.001], a higher rate of vitamin D deficiency (45.03 vs. 72%, P <0001), higher prevalence of RLS (6.62 vs. 22.29%, P < 0.001). Compared with the pure RLS group, RLS with the migraine group had lower vitamin D levels and higher IRLS score (P < 0.05). Compared with pure migraine group, migraine with RLS group had lower vitamin D levels [(17.36 ± 5.56) vs. (13.15 ± 4.42) ng/ml, P < 0.001], higher incidence of vitamin D deficiency (66.18 vs. 92.31%, P = 0.001), higher frequency of headache attacks (P = 0.004). Thereafter, the multivariate logistic regression model was employed to adjust confounding factors such as age, gender, season, frequency of headache attacks, PSQI score, and HADS scores. According to the results vitamin D deficiency in patients with migraines was an independent risk factor for RLS (OR = 5.03, 95%CI: 1.2–21.16, P = 0.027). Conclusions: The prevalence of RLS in migraine patients was significantly higher than that in the non-headache population. Besides, vitamin D levels decreased, while the incidence of vitamin D deficiency increased in the migraine patients complicated with RLS. Finally, the occurrence of RLS in migraine patients was significantly related to vitamin D deficiency.
Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.
High-Quality Genome-Scale Reconstruction of Corynebacterium glutamicum ATCC 13032

Corynebacterium glutamicum belongs to the microbes of enormous biotechnological relevance. In particular, its strain ATCC 13032 is a widely used producer of L-amino acids at an industrial scale. Its apparent robustness also turns it into a favorable platform host for a wide range of further compounds, mainly because of emerging bio-based economies. A deep understanding of the biochemical processes in C. glutamicum is essential for a sustainable enhancement of the microbe's productivity. Computational systems biology has the potential to provide a valuable basis for driving metabolic engineering and biotechnological advances, such as increased yields of healthy producer strains based on genome-scale metabolic models (GEMs). Advanced reconstruction pipelines are now available that facilitate the reconstruction of GEMs and support their manual curation. This article presents iCGB21FR, an updated and unified GEM of C. glutamicum ATCC 13032 with high quality regarding comprehensiveness and data standards, built with the latest modeling techniques and advanced reconstruction pipelines. It comprises 1042 metabolites, 1539 reactions, and 805 genes with detailed annotations and database cross-references. The model validation took place using different media and resulted in realistic growth rate predictions under aerobic and anaerobic conditions. The new GEM produces all canonical amino acids, and its phenotypic predictions are consistent with laboratory data. The in silico model proved fruitful in adding knowledge to the metabolism of C. glutamicum: iCGB21FR still produces L-glutamate with the knock-out of the enzyme pyruvate carboxylase, despite the common belief to be relevant for the amino acid's production. We conclude that integrating high standards into the reconstruction of GEMs facilitates replicating validated knowledge, closing knowledge gaps, and making it a useful basis for metabolic engineering. The model is freely available from BioModels Database under identifier MODEL2102050001.
The Implications of Incumbent Intellectual Property Strategies for Open Source Software Success and Commercialization

This dissertation investigates how IPR enforcement by proprietary incumbents influences open source software (OSS) adoption and production. It suggests user interest and developer activity on OSS are negatively affected by IPR enforcement particularly for OSS projects technologically overlap with litigated OSS and business projects specific to a litigated OSS platform. Second, it examines how royalty-free patent pools contributed by incumbents affect OSS product entry. It finds the pools related to a software segment will facilitate OSS start-up entry into the same segment; this marginal effect is especially large in segments with high cumulativeness of innovation or high patent ownership concentration.
Development of Teachers’ Emotional Adjustment Performance Regarding Their Perception of Emotional Experience and Job Satisfaction During Regular School Operations, the First and the Second School Lockdown in Austria

Starting with the COVID-19 pandemic, research intensively investigated the effects of school lockdowns on involved stakeholders, such as teachers, students and parents. However, as research projects had to be hurriedly conducted, in-depth and longitudinal studies are lacking. Therefore, the current study uses data from a longitudinal study to investigate the well-being of Austrian in-service teachers during the COVID-19 pandemic. In total 256 teachers took part at both measurement waves and participated in an online survey. Standardized questionnaires were used to assess teachers’ perception of emotional experiences and job satisfaction before COVID-19 (retrospective, t1), during the first (in situ, t2) and during the second school lockdown (in situ, t3). The results indicated that the vast majority of teachers generally felt a high level of job satisfaction. However, teachers’ satisfaction decreased between regular teaching and school lockdowns. Similarly, positive emotional activation was reduced and negative activation increased. Further, results from a positive activation cross-lagged path model indicated that the lack of positive activation led to lower job satisfaction. For negative emotional activation, job satisfaction during the first school lockdown predicted negative activation at the second lockdown.
Association of Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Alarming Need for Human Papillomavirus 16 Screening in Cancer Patients

Background: The percentage of cancers of the tongue and palatine tonsils has continued to increase by 2%–4% among younger men. This increased prevalence of a subsection of oropharyngeal carcinoma can be associated with human papillomavirus (HPV). Among the head-and-neck cancers, a strong association with HPV infection is evident with oropharyngeal cancers, particularly tonsillar and basal tongue cancers. Objectives: Oral carcinoma, with an overall incidence of 16.1 adults per 100,000, is one of the leading malignancies worldwide, presenting a noticeable geographic variation in its distribution. Squamous cell carcinoma (SCC) being the most common of all oral malignancies, the objective of the study is to detect the HPV antigen p16 over-expression in patients with oral SCC using immunohistochemistry (IHC). Materials and Methods: Oral SCC (OSCC) diagnosed formalin-fixed-paraffin embedded blocks were processed for IHC. Results: Out of 50 cases, 3 were deferred due to insufficient tumor sample and 2/47 cases were p16 positive and the site was the lateral border of the tongue. Conclusion: The HPV antigen overexpression in patients with OSCC was investigated to detect the incidence of HPV in SCC of oral cavity. P16 was used as a marker for the detection of OSCC using IHC in HPV-induced OSCC. Positives were detected thus concluding the significance of studying HPV expression during diagnosis.