Miracle-dz/UniFAR-FTUs huggingface dataset:
The histone chaperone FACT modulates nucleosome structure by tethering its components

The histone chaperone FACT functions by tethering partial components of the nucleosome, thereby assisting nucleosome disassembly and reassembly during transcription. Human FAcilitates Chromatin Transcription (hFACT) is a conserved histone chaperone that was originally described as a transcription elongation factor with potential nucleosome assembly functions. Here, we show that FACT has moderate tetrasome assembly activity but facilitates H2A–H2B deposition to form hexasomes and nucleosomes. In the process, FACT tethers components of the nucleosome through interactions with H2A–H2B, resulting in a defined intermediate complex comprising FACT, a histone hexamer, and DNA. Free DNA extending from the tetrasome then competes FACT off H2A–H2B, thereby promoting hexasome and nucleosome formation. Our studies provide mechanistic insight into how FACT may stabilize partial nucleosome structures during transcription or nucleosome assembly, seemingly facilitating both nucleosome disassembly and nucleosome assembly.
Effectiveness of Secondary School Conceptual Physical Education: A 20-Year Longitudinal Study.

BACKGROUND Previous research findings from Project Active Teen demonstrated the effectiveness of high school conceptual physical education (CPE) in promoting active lifestyles. METHOD This study followed Project Active Teen participants 20 years after graduation from high school and 24 years after taking a CPE class. Physical activity behaviors were assessed using the same procedures as previous Project Active Teen studies. Activity patterns were compared with patterns while in high school and shortly after high school graduation. Activity patterns were also compared with a national sample of age-equivalent adults. RESULTS Twenty years after high school graduation, former CPE students were less likely to be inactive and more likely to be moderately active than when in high school and were less likely to be inactive and more likely to be moderately active than national sample age-equivalent peers. They were typically not more vigorously physically active than comparison groups. CONCLUSION Results support the long-term effectiveness of CPE in reducing inactive behavior and promoting moderate physical activity later in life.
Osteoinductive effects of tantalum and titanium on bone mesenchymal stromal cells and bone formation in ovariectomized rats.

OBJECTIVE Although Tantalum (Ta) exhibits better osteoinductivity in healthy subjects when compared with titanium (Ti), the relative effects in osteoporosis remain unknown. MATERIALS AND METHODS In this study, bone mesenchymal stromal cells of ovariectomized rats (OVX-rBMSCs) were seeded on Ta and Ti substrates for in vitro evaluation of cell viability, reactive oxygen species (ROS) production, alkaline phosphatase (ALP) activity, extracellular mineralization osteogenic gene and protein expression involved in bone morphogenetic protein (BMP2)/small mothers against decapentaplegic homologs 1 (Smad1) pathway. For in vivo assessment, Ta and Ti implants were embedded in femur defects of ovariectomized rats, followed by sequential fluorochrome labeling and histological staining. RESULTS Compared to Ti, the Ta substrates demonstrated higher viable cell percentages (96.5 ± 0.26 vs. 88.17 ± 2.23%), lower ROS levels (65% vs. Ti), and enhanced ALP activity and extracellular matrix calcification. Reverse Transcription-Polymerase Chain Reaction and Western blot assays validated the better osteoinductive effect of Ta regarding small mothers against decapentaplegic homologs 1 (Smad1), runt-related transcription factor 2, bone morphogenetic protein (BMP2), and ALP expression at both the mRNA (1.5-2-fold) and protein (1.2-1.8-fold) levels. BMP2/Smad1 signaling over-expression or knockdown yielded significantly enhanced or deteriorated OVX-rBMSC osteogenesis on the two surfaces. In addition, the Ta group revealed more new bone formation (1.3-1.5-fold vs. Ti) and slightly better bone-implant contact (31.82 ± 4.07 vs. 25.2-3.84% at 8 weeks post-implantation, p = 0.052) without the contribution of specific surface structures. CONCLUSIONS In comparison to Ti, Ta reveals better biocompatibility and osteoinductivity to OVX-rBMSCs, and the preferential Ta osteoinductivity may reflect its greater potential to trigger the BMP2/Smad1 cascade. Thus," in front of "Ta". Ta appears preferable to Ti as a bone-implant surface material under osteoporosis conditions.
Audiological follow-up in a risk-based newborn hearing screening programme: An exploratory study of the influencing factors

Background Follow-up return rate in Early Hearing Detection and Intervention (EHDI) programmes is of specific importance as it ensures that benchmarks are met and that no child with suspected hearing loss is left unidentified. Objectives The aim of this study was to determine the factors influencing audiological follow-up of high-risk infants in a risk-based newborn hearing screening programme. Method A non-experimental, exploratory, qualitative research design was employed. Purposive sampling was used. The study was conducted at a secondary level hospital in the public health care sector in South Africa. Participants comprised 10 caregivers (age range 26–40 years) of infants who had been enrolled in a risk-based newborn hearing screening programme, and returned for follow-up appointments. Data were collected using semi-structured interviews. Responses were recorded by the researcher and a colleague to ensure rigour and trustworthiness of findings. Data were analysed using thematic analysis for open-ended questions and descriptive statistics for the closed-ended questions. Results The most common positive contributors that facilitated participants’ attendance at follow-up appointments were: having friendly audiologists; a clear line of communication between caregiver and audiologist and a reminder of the appointment. The most significant perceived challenge that participants described in returning for the follow-up appointment was living in far proximity from the hospital. Conclusion Findings of the study revealed that influencing factors on follow-up return rate are demographic, socio-economic, and interpersonal in nature and further suggested the need for an all-inclusive appointment day. It may be of importance to not only look at what is being done to improve the follow-up return rate but also how it should be done in terms of professional-to-patient communication and interactions.
The Benefits of Closed-Loop Transcranial Alternating Current Stimulation on Subjective Sleep Quality

Background: Poor sleep quality is a common complaint, affecting over one third of people in the United States. While sleep quality is thought to be related to slow-wave sleep (SWS), there has been little investigation to address whether modulating slow-wave oscillations (SWOs) that characterize SWS could impact sleep quality. Here we examined whether closed-loop transcranial alternating current stimulation (CL-tACS) applied during sleep impacts sleep quality and efficiency. Methods: CL-tACS was used in 21 participants delivered at the same frequency and in phase with endogenous SWOs during sleep. Sleep quality was assessed in the morning following either verum or sham control stimulation during sleep, with order counterbalanced within participants. Results: Higher sleep quality and efficiency were found after verum stimulation nights compared to control. The largest effects on sleep quality were found immediately following an adaptation night in the laboratory for which sleep quality was reduced. Conclusions: Applying CL-tACS at the same frequency and phase as endogenous SWOs may offer a novel method to improve subjective sleep quality after a night with poor quality sleep. CL-tACS might be helpful for increasing sleep quality and efficiency in otherwise healthy people, and in patients with clinical disorders that involve sleep deficits.
Metabolomic Response to Acute Hypoxic Exercise and Recovery in Adult Males

Metabolomics is a relatively new “omics” approach used to characterize metabolites in a biological system at baseline and following a diversity of stimuli. However, the metabolomic response to exercise in hypoxia currently remains unknown. To examine this, 24 male participants completed 1 h of exercise at a workload corresponding to 75% of pre-determined O2max in hypoxia (Fio2 = 0.16%), and repeated in normoxia (Fio2 = 0.21%), while pre- and post-exercise and 3 h post-exercise metabolites were analyzed using a LC ESI-qTOF-MS untargeted metabolomics approach in serum samples. Exercise in hypoxia and in normoxia independently increased metabolism as shown by a change in a combination of twenty-two metabolites associated with lipid metabolism (p < 0.05, pre vs. post-exercise), though hypoxia per se did not induce a greater metabolic change when compared with normoxia (p > 0.05). Recovery from exercise in hypoxia independently decreased seventeen metabolites associated with lipid metabolism (p < 0.05, post vs. 3 h post-exercise), compared with twenty-two metabolites in normoxia (p < 0.05, post vs. 3 h post-exercise). Twenty-six metabolites were identified as responders to exercise and recovery (pooled hypoxia and normoxia pre vs. recovery, p < 0.05), including metabolites associated with purine metabolism (adenine, adenosine and hypoxanthine), the amino acid phenylalanine, and several acylcarnitine molecules. Our novel data provides preliminary evidence of subtle metabolic differences to exercise and recovery in hypoxia and normoxia. Specifically, exercise in hypoxia activates metabolic pathways aligned to purine and lipid metabolism, but this effect is not selectively different from exercise in normoxia. We also show that exercise per se can activate pathways associated with lipid, protein and purine nucleotide metabolism.
Ecophysiology of Layered Macroalgal Assemblages: Importance of Subcanopy Species Biodiversity in Buffering Primary Production

Shallow coastal rocky reefs worldwide have faced large-scale loss of biodiversity, yet little is known about the contributions of highly diverse multi-layered autotrophic species to ecosystem function over long periods. In this study we tested the role of functional diversity on net primary productivity (NPP) of macroalgal assemblages in one-off, and multi-year experiments. We removed canopy (perennial fucoid), mid-canopy and basal algae (turfing and encrusting algae) in intertidal assemblages and used in situ photorespirometry to measure recovery of NPP over 2 years. Experimental removal of the canopy caused a >50% decline in NPP, which remained significantly lower than undisturbed assemblages for up to 24 months. Removal of midcanopy and basal algae reduced NPP by >25%, but converged with controls after just 6-12 months. Canopy loss greatly reduced NPP for long periods and productivity began recovering only after the recruitment of the canopy-forming species. Subcanopy species composition varied with experimental disturbance treatment and through time, but consistently contributed to total assemblage NPP. High irradiance in the shallow intertidal zone may be vital to a maximizing the efficiency of light harvesting, and the spatial and temporal variations in species composition may play a critical role in buffering carbon fixation of macroalgal assemblages.
Natural Killer Cell Dysfunction in Hepatocellular Carcinoma: Pathogenesis and Clinical Implications

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying human NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.
Scaffolding the Design Process using Parsons Problems

The design process for solving a problem requires recollection of previously learned strategies to identify and organise tasks for implementation. With minimal background knowledge in software design, novices might spend less time designing, potentially leading to misunderstandings about the problem's goals and a lower rate of completed tasks. Novices could benefit from explicit support in the design process, supporting them in gaining design experience to develop internal knowledge and skills in identifying and organising tasks. We present preliminary results experimenting with Parsons Problems as a scaffolding tool to provide CS1 students with design guidance. Findings reveal that students who do not complete the activity receive lower assessment grades, but additional analysis is required to realise methods to measure the impact when Parsons Problems are used to support design knowledge and skills.
Nonclinical safety assessment of a human interleukin‐22FC IG fusion protein demonstrates in vitro to in vivo and cross‐species translatability

Although Interleukin‐22 (IL‐22) is produced by various leukocytes, it preferentially targets cells with epithelial origins. IL‐22 exerts essential roles in modulating various tissue epithelial functions, such as innate host defense against extracellular pathogens, barrier integrity, regeneration, and wound healing. Therefore, IL‐22 is thought to have therapeutic potential in treating diseases associated with infection, tissue injury or chronic tissue damage. A number of in vitro and in vivo nonclinical studies were conducted to characterize the pharmacological activity and safety parameters of UTTR1147A, an IL‐22 recombinant fusion protein that links the human cytokine IL‐22 with the Fc portion of a human immunoglobulin. To assess the pharmacological activity of UTTR1147A, STAT3 activation was evaluated in primary hepatocytes isolated from human, cynomolgus monkey, minipig, rat, and mouse after incubation with UTTR1147A. UTTR1147A activated STAT3 in all species evaluated, demonstrating that all were appropriate nonclinical species for toxicology studies.
Crystal structure of the catalytic domain from GH74 enzyme PoGH74 from Paenibacillus odorifer, apoenzyme

Paenibacillus odorifer produces a single multimodular enzyme containing a glycoside hydrolase (GH) family 74 module (AIQ73809). Recombinant production and characterization of the GH74 module (PoGH74cat) revealed a highly specific, processive endo-xyloglucanase that can hydrolyze the polysaccharide backbone at both branched and unbranched positions. X-ray crystal structures obtained for the free enzyme and oligosaccharide complexes evidenced an extensive hydrophobic binding platform - the first in GH74 extending from subsites -4 to +6 - and unique mobile active-site loops. Site-directed mutagenesis revealed that glycine-476 was uniquely responsible for the promiscuous backbone-cleaving activity of PoGH74cat; replacement with tyrosine, which is conserved in many GH74 members, resulted in exclusive hydrolysis at unbranched glucose units. Likewise, systematic replacement of the hydrophobic platform residues constituting the positive subsites indicated their relative contributions to the processive mode of action. Specifically, W347 (+3 subsite) and W348 (+5 subsite) are essential for processivity, while W406 (+2 subsite) and Y372 (+6 subsite) are not strictly essential, but aid processivity.
The Mid‐Fusiform Sulcus (sulcus sagittalis gyri fusiformis)

In the human brain, the mid‐fusiform sulcus (MFS; sulcus sagittalis gyri fusiformis) divides the fusiform gyrus (FG) into lateral and medial partitions. Recent studies show that the MFS is identifiable in every hemisphere and is a landmark that identifies (a) cytoarchitectonic transitions among four areas of the FG, (b) functional transitions in many large‐scale maps, and (c) the location of fine‐scale functional regions. Thus, simply identifying the MFS in a person's brain provides researchers with knowledge regarding: (a) how cells are organized across layers within a particular cortical location, (b) how functional representations will be laid out in cortex, and (c) the precise location of functional regions from cortical folding alone. The predictive power of the MFS can guide future studies examining the anatomical‐functional organization of the FG, as well as the development of translational applications for different patient populations. Nevertheless, progress has been slow in incorporating the MFS into the broader anatomical community and into neuroanatomical reference sources. For example, even though the MFS is a rare structural–functional landmark in human association cortex as just described, it is not recognized in the recently published Terminologia Neuroanatomica (TNA). In this review, I collate the anatomical and functional details of the MFS in one place for the first time. Together, this article serves as a comprehensive reference regarding the anatomical and functional details of the MFS, as well as provides a growing number of reasons to include the MFS as a recognized neuroanatomical structure in future revisions of the TNA. Anat Rec, 302:1491–1503, 2019. © 2018 American Association for Anatomy
Effects of the Extracts from Fruit and Stem of Camellia japonica on Induced Pluripotency and Wound Healing

Small molecules that improve reprogramming, stem cell properties, and regeneration can be widely applied in regenerative medicine. Natural plant extracts represent an abundant and valuable source of bioactive small molecules for drug discovery. Natural products themselves or direct derivatives of them have continued to provide small molecules that have entered clinical trials, such as anticancer and antimicrobial drugs. Here, we tested 3695 extracts from native plants to examine whether they can improve induced pluripotent stem cell (iPSC) generation using genetically homogeneous secondary mouse embryonic fibroblasts (MEFs) harboring doxycycline (dox)-inducible reprograming transgenes. Among the tested extracts, extracts from the fruit and stem of Camellia japonica (CJ) enhanced mouse and human iPSC generation and promoted efficient wound healing in an in vivo mouse wound model. CJ is one of the best-known species of the genus Camellia that belongs to the Theaceae family. Our findings identified the natural plant extracts from the fruit and stem of CJ as novel regulators capable of enhancing cellular reprogramming and wound healing, providing a useful supplement in the development of a more efficient and safer method to produce clinical-grade iPSCs and therapeutics.
The impact of steatosis on liver regeneration

Abstract Alcoholic and non-alcoholic fatty liver diseases are the leading causes of cirrhosis in Western countries. These chronic liver diseases share common pathological features ranging from steatosis to steatohepatitis. Fatty liver is associated with primary liver graft dysfunction, a higher incidence of complications/mortality after surgery, in correlation with impaired liver regeneration. Liver regeneration is a multistep process including a priming phase under the control of cytokines followed by a growth factor receptor activation phase leading to hepatocyte proliferation. This process ends when the initial liver mass is restored. Deficiency in epidermal growth factor receptor (EGFR) liver expression, reduced expression of Wee1 and Myt1 kinases, oxidative stress and alteration in hepatocyte macroautophagy have been identified as mechanisms involved in the defective regeneration of fatty livers. Besides the mechanisms, we will also discuss in this review various treatments that have been investigated in the reversal of the regeneration defect, for example, omega-3 fatty acids, pioglitazone, fibroblast growth factor (FGF)19-based chimeric molecule or growth hormone (GH). Since dysbiosis impedes liver regeneration, targeting microbiota could also be an interesting therapeutic approach.
Modulating Effects of Contextual Emotions on the Neural Plasticity Induced by Word Learning

Recently, numerous studies have investigated the neurocognitive mechanism of learning words in isolation or in semantic contexts. However, emotion as an important influencing factor on novel word learning has not been fully considered in the previous studies. In addition, the effects of emotion on word learning and the underlying neural mechanism have not been systematically investigated. Sixteen participants were trained to learn novel concrete or abstract words under negative, neutral, and positive contextual emotions over 3 days; then, fMRI scanning was done during the testing sessions on day 1 and day 3. We compared the brain activations in day 1 and day 3 to investigate the role of contextual emotions in learning different types of words and the corresponding neural plasticity changes. Behaviorally, the performance of the words learned in the negative context was lower than those in the neutral and positive contexts, which indicated that contextual emotions had a significant impact on novel word learning. Correspondingly, the functional plasticity changes of the right angular gyrus (AG), bilateral insula, and anterior cingulate cortex (ACC) induced by word learning were modulated by the contextual emotions. The insula also was sensitive to the concreteness of the learned words. More importantly, the functional plasticity changes of the left inferior frontal gyrus (left IFG) and left fusiform gyrus (left FG) were interactively influenced by the contextual emotions and concreteness, suggesting that the contextual emotional information had a discriminable effect on different types of words in the neural mechanism level. These results demonstrate that emotional information in contexts is inevitably involved in word learning. The role of contextual emotions in brain plasticity for learning is discussed.
State of the Art in Fair ML: From Moral Philosophy and Legislation to Fair Classifiers

Machine learning is becoming an ever present part in our lives as many decisions, e.g. to lend a credit, are no longer made by humans but by machine learning algorithms. However those decisions are often unfair and discriminating individuals belonging to protected groups based on race or gender. With the recent General Data Protection Regulation (GDPR) coming into effect, new awareness has been raised for such issues and with computer scientists having such a large impact on peoples lives it is necessary that actions are taken to discover and prevent discrimination. This work aims to give an introduction into discrimination, legislative foundations to counter it and strategies to detect and prevent machine learning algorithms from showing such behavior.