Miracle-dz/UniFAR-FTUs huggingface dataset:
Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks

Abstract Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins.
Impulsivity, Painful and Provocative Events, and Suicide Intent: Testing the Interpersonal Theory of Suicide.

OBJECTIVE The Interpersonal Theory of Suicide (IPTS; Joiner, 2005. Why People Die by Suicide. Cambridge, MA: Harvard University Press) hypothesizes that repeated exposure to painful and provocative events (PPE) increases capability for suicide (CS), therefore facilitating the development of suicidal intent, and that impulsive individuals are more likely to experience these painful and provocative events, creating an indirect relationship between impulsivity and CS. Research to date largely supports this hypothesis but has not translated this theory to actual suicidal intent. METHOD The present study used data from the MacArthur Violence Risk Assessment Study to examine the relationship between PPE and intent, and the indirect relationship between impulsivity and intent among a sample of 245 recent suicide attempters, using the clinician-rated Suicide Intent Scale as an objective measure of intent. RESULTS Results supported the hypothesized direct relationship between PPE and intent, and the indirect relationship between impulsivity and intent through PPE. There was no direct relationship between impulsivity and intent, suggesting that the relationship between impulsivity and intent occurs entirely through exposure to PPE. CONCLUSIONS These findings suggest that assessing exposure to painful and provocative events is critical in evaluating risk of suicide, and that impulsivity itself does not confer an increased risk of lethal or nearly lethal attempts.
The impact of lipid accumulation product (LAP) and visceral adiposity index (VAI) on clinical, hormonal and metabolic parameters in lean women with polycystic ovary syndrome

Abstract This study was performed to assess the impact of lipid accumulation product (LAP) and visceral adiposity index (VAI) on clinical, hormonal, and metabolic parameters in lean women with PCOS. Retrospective analysis of 120 consecutive lean PCOS subjects was performed. Subjects were divided into two groups according to HOMA-IR, as IR + and IR−. A HOMA-IR value above 2.5 was used to indicate IR. Clinical, hormonal and metabolic parameters were compared between the two groups. Correlations between LAP and VAI and clinical, hormonal, metabolic features in women PCOS were analyzed. One hundred twenty lean PCOS subjects were enrolled, of which 39 were insulin resistant. Comparison of group means showed significantly higher values for TG levels, FAI, FGS, TG/HDL-c, TyG, LAP, and VAI indexes and lower values for glucose/insulin ratio and QUICKI in the IR + group. LAP and VAI were both found to be positively correlated with each other and with WC, FAI, FGS, TG, TC levels, lipid ratios, TyG index, and HOMA-IR and negatively correlated with Glucose/Insulin ratio, QUICKI, and HDL-c in lean women with PCOS. LAP and VAI may be promising in early identification of IR and cardiometabolic risk and may be useful for the assessment of hyperandrogenism in lean women with PCOS.
Cooperative spectrum estimation over large-scale cognitive radio networks

Spectrum sensing is a significant issue in cognitive radio networks which enables estimation of the frequency spectrum and hence provides frequency reuse. In the large-scale cognitive radio networks, secondary users cannot share a common spectrum since the coverage area of primary users is limited. In this study, the authors suggest a diffusion adaptive learning algorithm based on correntropy cooperation policy, which first categorises received data of secondary users into several groups, and then learns a common spectrum inside each group. The mean-square performance of proposed algorithm is analysed and supported by simulations. Experimental results show that, in a multitask cognitive network, the proposed algorithm can achieve a better mean-square deviation learning performance both in transient and steady-state regimes in comparison with other conventional algorithms.
Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis.

BACKGROUND Propofol can cause degeneration of developing brain cells and subsequent long-term learning or memory impairment. However, at the early stage of embryonic development, the molecular mechanism of propofol-induced inhibition in neural stem cells (NSCs) neurogenesis is still unclear. The aim of this study was to determine the role of propofol in NSCs neurogenesis and, more importantly, to explore the underlying mechanism. METHODS First, a single intraperitoneal injection of propofol was performed in pregnant mice, and 6 hours after administration of propofol, the hippocampus RNA and the protein of the embryos' brains was extracted to analyze the expression of neuron-specific markers. Second, the primary NSCs were isolated from the hippocampus of mouse embryonic brain and then treated with propofol for cell viability, immunostaining, and transwell assays; more importantly, we performed RNA sequencing (RNA-seq) and q-reverse transcription polymerase chain reaction assays to identify genes regulated by propofol; the Western blot, small interfering RNA (SiRNA), and luciferase reporter assays were used to study the effects of propofol on calmodulin-dependent protein kinase (CaMk) II/5' adenosine monophosphate-activated protein kinase (AMPK)/activating transcription factor 5 (ATF5) signaling pathway. RESULTS Our results indicated that propofol treatment could inhibit the proliferation, migration, and differentiation of NSCs. The results of RNA-seq assays showed that propofol treatment resulted in downregulation of a group of Ca-dependent genes. The following mechanism studies showed that propofol regulates the proliferation, differentiation, and migration of NSCs through the CaMkII/phosphorylation of serine at amino acid position 485 (pS485)/AMPK/ATF5 signaling pathway. CONCLUSIONS The results from study demonstrated that propofol inhibits the proliferation, differentiation, and migration of NSCs, and these effects are partially mediated by CaMkII/pS485/AMPK/ATF5 signaling pathway.
Glaucocalyxin B protects against oxygen‐glucose‐deprivation/reperfusion‐induced neuronal injury in PC‐12 cells

Oxidative stress has been implicated in the development of cerebral ischemia/reperfusion (I/R) injury. Glaucocalyxin B (GLB), one of five ent‐kauranoid diterpenoids, was reported to possess neuroprotective activity. However, the effect of GLB on oxygen‐glucose‐deprivation/reperfusion (OGD/R)‐induced cell injury in PC‐12 cells has not been explored. PC‐12 cells was treated with various concentrations of GLB (0, 2.5, 5 and 10 μM), and cell viability was detected using the MTT assay. PC‐12 cells were pretreated with the indicated concentration of GLB (2.5‐10 μM, 2 hours pretreatment), and were maintained under OGD for 3 hours, followed by 24 hours of reoxygenation. Cell viability was assessed using the MTT assay. The levels of superoxide dismutase, malondialdehyde, and glutathione peroxidase were detected using commercially available ELISA Kits. Intracellular reactive oxygen species level was measured using the fluorescent probe 2′,7′‐dichlorofluorescein diacetate. The levels of Bcl‐2, Bax, p‐Akt, Akt, p‐mTOR, mTOR were detected using Western blot. Our results revealed that GLB significantly protected PC12 cells against OGD/R‐induced cell injury. In addition, GLB efficiently inhibited oxidative stress and cell apoptosis in OGD/R‐stimulated PC‐12 cells. Mechanistic studies revealed that pretreatment with GLB could induce the activation of Akt/mTOR signaling pathway resulting in protection of OGD‐treated PC12 cells. In conclusion, our data indicate for the first time that GLB protects against OGD/R‐induced neuronal injury in PC‐12 cells. The mechanism of the protective effect of GLB is partially associated with activation of the Akt/mTOR signaling pathway. Thus, GLB may be a potential agent for protection against cerebral I/R injury.
Loss of perivascular aquaporin‐4 in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of dementia that may be successfully treated with cerebrospinal fluid (CSF) diversion. Recently, magnetic resonance imaging (MRI) using a MRI contrast agent as a CSF tracer revealed impaired clearance of the CSF tracer from various brain regions such as the entorhinal cortex of iNPH patients. Hampered clearance of waste solutes, for example, soluble amyloid‐β, may underlie neurodegeneration and dementia in iNPH. The goal of the present study was to explore whether iNPH is associated with altered subcellular distribution of aquaporin‐4 (AQP4) water channels, which is reported to facilitate CSF circulation and paravascular glymphatic drainage of metabolites from the brain parenchyma. Cortical brain biopsies of 30 iNPH patients and 12 reference individuals were subjected to AQP4 immunogold cytochemistry. Electron microscopy revealed significantly reduced density of AQP4 water channels in astrocytic endfoot membranes along cortical microvessels in patients with iNPH versus reference subjects. There was a significant positive correlation between density of AQP4 toward endothelial cells (perivascular) and toward parenchyma, but the reduced density of AQP4 toward parenchyma was not significant in iNPH. We conclude that perivascular AQP4 expression is attenuated in iNPH, potentially contributing to impaired glymphatic circulation, and waste clearance, and subsequent neurodegeneration. Hence, restoring normal perivascular AQP4 distribution may emerge as a novel treatment strategy for iNPH.
In vivo randomized trial of three marketed milk preparations enriched with calcium and vitamins (D and K) on bone mass and bone turnover markers from biological fluids in premenopausal Caucasian women.

INTRODUCTION osteoporosis is a metabolic bone disease that leads to increased bone fragility and increased risk of fracture. OBJECTIVES the aim of the present research was to determine the effectiveness of a diary intake of three different dairy products (250 ml) enriched with vitamins and calcium on decreasing bone mass. METHOS: the present study is a comparative trial of three dairy products fortified with calcium and vitamin D, parallel, randomized, double-blind andsingle-center. Bone mass content (BMC), bone mass density (BMD), T-score and Z-score were measured in different locations, besides biochemical markers along 18 months in premenopausal women. Two hundred and ten volunteers from all the three groups were submitted to the same monitoring procedures, consisting on blood extraction, urine collection and energy X-ray absorptiometry (DEXA) done in the laboratory. The monitoring was carried on three times, first at month 0 (baseline), the second at month 9 (in the middle of the treatment) and, finally, at month 18 (the end of the treatment). RESULTS the majority of anatomical locations showed both BMC and BMD decrease ranging between 0.5% and 1.5%. The T-score and the Z-scoreincreased in lumbar spine after the treatment with the dairy products. Moreover, the most noteworthy change on the biomarkers of bone resorption was showed by plasmatic tartrate-resistant acid phosphatase (TRAP), with and increase between 20.7% and 29.5% after the intake of the different products. CONCLUSIONS therefore, the intake of the three dairy products improves the bone mass in lumbar spine, leading to important changes in the concentration of biomarkers of bone resorption. Especially, tartrate-resistant acid phosphatase seems to be strongly influenced by the intake of every dairy product. However, no significant differences were found between the different dairy products used in the present study. Therefore, the intake of dairy product seems to be more determinant than micronutrients supplementation.
Postnatal changes in the development of rat submandibular glands in offspring of diabetic mothers: Biochemical, histological and ultrastructural study

Development and maturation of submandibular salivary glands are influenced by intrauterine diabetic environment. Several studies investigated the effects of diabetes on the salivary glands. However, the effects of maternal diabetes on the submandibular glands of the offspring was not properly examined. Therefore, the present study was designed to describe the changes in the development of the submandibular glands of the offspring of diabetic mothers. The submandibular glands of the offspring of Streptozotocin (STZ)-induced diabetic female rats were examined at two and four weeks after birth. Detection of mRNA demonstrated that maternal diabetes affects the level of different indicators. The reduction of expression of epidermal growth factor (EGF); a protein mitogen, cytokeratin 5 (CK5); an epithelial cell progenitor, CK7 and aquaporin 5 (AQP5); differentiation markers and B cell lymphoma 2 (Bcl2); an antiapoptotic marker were found. Increase in Bcl2-associated X protein (Bax); an apoptotic marker was detected. These changes indicate their effects on saliva secretion, glands tumorigenesis, growth of normal oral flora and oral microbes, with decreased protein synthesis and production of xerostomia and dental caries. Loss of normal glandular architecture, significant increase in fibrosis, by the detection of collagen fibers, and stagnation of secretory granules were found with atrophic changes in the acinar cells. Marked defect of polysaccharides in the acinar cells, denoting functional changes, was manifested by significant reduction of the intensity of periodic acid-Schiff (PAS) reaction. The positive immunoreactivity of caspase-3, denoting cellular apoptosis, and minimal reaction of alpha-smooth muscle actin (α SMA) and proliferating cell nuclear antigen (PCNA) were evident in the offspring of diabetic mothers. We conclude that maternal diabetes produces degenerative effects in the structure and function of the submandibular salivary glands of the offspring, reflecting possible influences on their secretory activity affecting oral and digestive health.
ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters

ABSTRACT Antigen recognition by the T cell receptor (TCR) directs the assembly of essential signaling complexes known as SLP-76 (also known as LCP2) microclusters. Here, we show that the interaction of the adhesion and degranulation-promoting adaptor protein (ADAP; also known as FYB1) with SLP-76 enables the formation of persistent microclusters and the stabilization of T cell contacts, promotes integrin-independent adhesion and enables the upregulation of CD69. By analyzing point mutants and using a novel phospho-specific antibody, we show that Y595 is essential for normal ADAP function, that virtually all tyrosine phosphorylation of ADAP is restricted to a Y595-phosphorylated (pY595) pool, and that multivalent interactions between the SLP-76 SH2 domain and its binding sites in ADAP are required to sustain ADAP phosphorylation. Although pY595 ADAP enters SLP-76 microclusters, non-phosphorylated ADAP is enriched in protrusive actin-rich structures. The pre-positioning of ADAP at the contact sites generated by these structures favors the retention of nascent SLP-76 oligomers and their assembly into persistent microclusters. Although ADAP is frequently depicted as an effector of SLP-76, our findings reveal that ADAP acts upstream of SLP-76 to convert labile, Ca2+-competent microclusters into stable adhesive junctions with enhanced signaling potential. Highlighted Article: During T cell activation, a cytoskeletal pool of ADAP enters nascent contacts in advance of other adaptors and enhances contact stability and TCR signaling by participating in multivalent signaling complexes.
Surface Modification of Magnetic Iron Oxide Nanoparticles

Functionalized iron oxide nanoparticles (IONPs) are of great interest due to wide range applications, especially in nanomedicine. However, they face challenges preventing their further applications such as rapid agglomeration, oxidation, etc. Appropriate surface modification of IONPs can conquer these barriers with improved physicochemical properties. This review summarizes recent advances in the surface modification of IONPs with small organic molecules, polymers and inorganic materials. The preparation methods, mechanisms and applications of surface-modified IONPs with different materials are discussed. Finally, the technical barriers of IONPs and their limitations in practical applications are pointed out, and the development trends and prospects are discussed.
Incontinence-Associated Dermatitis: State of the Science and Knowledge Translation

ABSTRACT This review of the literature updates and considers the evidence on incontinence-associated dermatitis (IAD). Best practice strategies for the management of skin damage from IAD (both prevention and treatment) are provided. A mnemonic to help clinicians translate IAD evidence into practice is introduced. Workplace experiences supplement this evidence synthesis. Approaches to assist in translation of this knowledge and evidence into practice are also provided.
State Estimation and Tracking Control for Hybrid Systems by Gluing the Domains

We study the design problems of state observers and tracking controllers for a class of hybrid systems whose state jumps. The idea is to utilize the well-known method of gluing the jump set (a part of domain where the jumps take place) onto its image, which converts the hybrid system into a continuous-time system whose state does not jump. Sufficient conditions for this idea to be implemented are listed and discussed with a few concrete examples. In particular, we present a structural condition for an observer design, and, for tracking control, we introduce a feedback to compensate residual discontinuity in the vector field after gluing. The benefits of the proposed approach include that the observer design does not require detection of the state jumps, and that the tracking control does not require the plant state jumps when the reference jumps.
Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

ABSTRACT Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.
Affective brain Computer Music Interfacing: a Case Study of Use by an Individualwith Huntington's disease

An affective brain-computer music interface (aBCMI), developed for use as an aid to music therapy, is trialled in a case study with an individual with Huntington’s disease. The aBCMI aims to detect a users current affective state and modulate music generated and played to that user in order to manipulate their affective state in a way that has potential therapeutic benefits. We have previously demonstrated the efficacy of this aBCMI on a population of healthy participants but it is unclear whether it could work with individuals with Huntington’s. Our case study demonstrates that there is some potential for aBCMI systems to be used by individuals with Huntington’s disease. However, we also highlight some key challenges that need to be overcome in adapting aBCMI systems to this user group. Specifically, we identify a need for more robust measures of ground truths of affective states to allow the aBCMI to be trained with this user group.
Can Determinacy Minimize Age of Information?

Age-of-information (AoI) is a newly proposed performance metric of information freshness. It differs from the traditional delay metric, because it is destination centric and measures the time that elapsed since the last received fresh information update was generated at the source. AoI has been analyzed for several queueing models, and the problem of optimizing AoI over arrival and service rates has been studied in the literature. We consider the problem of minimizing AoI over the space of update generation and service time distributions. In particular, we ask whether determinacy, i.e. periodic generation of update packets and/or deterministic service, optimizes AoI. By considering several queueing systems, we show that in certain settings, deterministic service can in fact result in the worst case AoI, while a heavy-tailed distributed service can yield the minimum AoI. This leads to an interesting conclusion that, in some queueing systems, the service time distribution that minimizes expected packet delay, or variance in packet delay can, in fact, result in the worst case AoI. This exposes a fundamental difference between AoI metrics and packet delay.
Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review

The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.