Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation

Many members of the AAA+ ATPase family function as hexamers that unfold their protein substrates. These AAA unfoldases include spastin, which plays a critical role in the architecture of eukaryotic cells by driving the remodeling and severing of microtubules, which are cytoskeletal polymers of tubulin subunits. Here, we demonstrate that a human spastin binds weakly to unmodified peptides from the C-terminal segment of human tubulin α1A/B. A peptide comprising alternating glutamate and tyrosine residues binds more tightly, which is consistent with the known importance of glutamylation for spastin microtubule severing activity. A cryo-EM structure of the spastin-peptide complex at 4.2 Å resolution revealed an asymmetric hexamer in which five spastin subunits adopt a helical, spiral staircase configuration that binds the peptide within the central pore, whereas the sixth subunit of the hexamer is displaced from the peptide/substrate, as if transitioning from one end of the helix to the other. This configuration differs from a recently published structure of spastin from Drosophila melanogaster, which forms a six-subunit spiral without a transitioning subunit. Our structure resembles other recently reported AAA unfoldases, including the meiotic clade relative Vps4, and supports a model in which spastin utilizes a hand-over-hand mechanism of tubulin translocation and microtubule remodeling.
Neutralization sites of human papillomavirus-6 relate to virus attachment and entry phase in viral infection

ABSTRACT Human papillomavirus type 6 (HPV6) is the major etiologic agent of genital warts and recurrent respiratory papillomatosis. Although the commercial HPV vaccines cover HPV6, the neutralization sites and mode for HPV6 are poorly understood. Here, we identify the HPV6 neutralization sites and discriminate the inhibition of virus attachment and entry by three potent neutralizing antibodies (nAbs), 5D3, 17D5, and 15F7. Mutagenesis assays showed that these nAbs predominantly target surface loops BC, DE, and FG of HPV6 L1. Cryo-EM structures of the HPV6 pseudovirus (PsV) and its immune complexes revealed three distinct binding modalities – full-occupation-bound to capsid, top-center-bound-, and top-rim-bound to pentamers – and illustrated a structural atlas for three classes of antibody-bound footprints that are located at center-distal ring, center, and center-proximal ring of pentamer surface for 5D3, 17D5, and 15F7, respectively. Two modes of neutralization were identified: mAb 5D3 and 17D5 block HPV PsV from attaching to the extracellular matrix (ECM) and the cell surface, whereas 15F7 allows PsV attachment but prohibits PsV from entering the cell. These findings highlight three neutralization sites of HPV6 L1 and outline two antibody-mediated neutralization mechanisms against HPV6, which will be relevant for HPV virology and antiviral inhibitor design. Highlights Major neutralization sites of HPV6 were mapped on the pseudovirus cryo-EM structure mAb 15F7 binds HPV6 capsid with a novel top-rim binding modality and confers a post-attachment neutralization mAb 17D5 binds capsid in top-centre manner but unexpectedly prevents virus from attachment to cell surface
Serum Procollagen Type I N-Terminal Propeptide and Osteocalcin Levels in Korean Children and Adolescents

Purpose Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents. Materials and Methods The participants (290 boys and 290 girls, age range 0–18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer. Results Significant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity. Conclusion We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.
Momilactones A, B, and Tricin in Rice Grain and By-Products are Potential Skin Aging Inhibitors

We previously reported the inhibitory potentials of momilactones A (MA) and B (MB) against key enzymes related to type 2 diabetes and obesity. In this study, antioxidant and anti-skin-aging activities of MA and MB were investigated and compared with tricin, a well-known antioxidant and antiaging flavonoid in rice. MA, MB, and tricin were purified from rice husk by column chromatography and their biological activities were subsequently assayed by in vitro trials. The contents of MA, MB, and tricin of different commercial rice cultivars in Japan were quantified and confirmed by ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) and high-performance liquid chromatography (HPLC) analyses. The antioxidant assays revealed a synergistic activity of the mixture MA and MB (MAB, 1:1, v/v). In addition, in 2,2'-azino-bis (ABTS) assay, IC50 values of MAB (0.3 mg/mL) and tricin (0.3 mg/mL) was 4-fold and 9-fold greater than that of individual MB (1.3 mg/mL) or MA (2.8 mg/mL), respectively. The in vitro enzymatic assays on pancreatic elastase and tyrosinase indicated that MA and MB were potential to relief skin wrinkles and freckles. In detail, MA exerted higher inhibition on both enzymatic activities (30.9 and 37.6% for elastase and tyrosinase inhibition, respectively) than MB (18.5 and 12.6%) and MAB (32.0 and 19.7%) at a concentration of 2.0 mg/mL. Notably, MA and the mixture MAB exhibited stronger inhibitions on elastase and tyrosinase in comparison with tricin and vanillin. MA, MB, and tricin in rice are potential to develop cosmetics as well as supplements for skin aging treatments.
Environmental Enrichment Partially Repairs Subcortical Mapping Errors in Ten-m3 Knock-Out Mice during an Early Critical Period

Abstract Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.
In pursuit of meaningful occupation: Employment and occupational outcomes for older Irish adults with an intellectual disability.

BACKGROUND Adults with an intellectual disability (ID) have much lower rates of employment than their counterparts without intellectual disability, which increases their risk of poverty and social exclusion. Differential treatment of people with intellectual disability in welfare and training policies suggests an expectation they will be passive welfare recipients rather than productive employees. METHODS This paper aims to examine occupational activities by older people with intellectual disability in Ireland, exploring factors influencing outcomes using data from the IDS-TILDA study (n = 708). RESULTS Most people were unemployed but engaged in regular occupational activity. Occupational activity was associated with better emotional/mental health. Activities of Daily Living (ADL) functioning was associated with an active occupational status, while social supports most strongly predicted high occupational engagement across a range of activities. CONCLUSIONS A focus on the individual meaning derived from a broad range of engagement may better support people with intellectual disabilities to benefit from regular occupational activity.
Gonadotropins in Keratoconus: The Unexpected Suspects

Keratoconus (KC) is the most common ectatic corneal disease with a significant visual acuity burden. The actual burden is intangible given that KC can disrupt daily activities (reading, driving, and various career paths). Despite decades of research and clinical studies, the etiology, onset, and pathobiology of KC remain a mystery. The purpose of this study was to investigate the role of gonadotropins in KC. We recruited 86 KC patients (63 males, 23 female), and 45 healthy controls (22 male, 23 female). Plasma samples were collected and analyzed using an enzyme-linked immunosorbent assay. Corneal stromal cells from KC and healthy controls, and human epithelial corneal cells, were also investigated for gonadotropin-related markers. Our results show significant alterations of LH/FSH in KCs, compared to healthy controls. Our data also reveals, for the first time, the existence of gonadotropins and their receptors in KC. Our study is the first to demonstrate the role of LH/FSH in KCs, and expand the list of organs known to express gonadotropins, or their receptors, to include the human cornea. Our findings suggest that the human cornea is capable of responding to gonadotropins, and propose an intriguing mechanism for the onset and/or progression of KC.
Mobile Health Apps for Self-Management of Rheumatic and Musculoskeletal Diseases: Systematic Literature Review

Background Although the increasing availability of mobile health (mHealth) apps may enable people with rheumatic and musculoskeletal diseases (RMDs) to better self-manage their health, there is a general lack of evidence on ways to ensure appropriate development and evaluation of apps. Objective This study aimed to obtain an overview on existing mHealth apps for self-management in patients with RMDs, focusing on content and development methods. Methods A search was performed up to December 2017 across 5 databases. For each publication relevant to an app for RMDs, information on the disease, purpose, content, and development strategies was extracted and qualitatively assessed. Results Of 562 abstracts, 32 were included in the analysis. Of these 32 abstracts, 11 (34%) referred to an app linked to a connected device. Most of the apps targeted rheumatoid arthritis (11/32, 34%). The top three aspects addressed by the apps were pain (23/32, 71%), fatigue (15/32, 47%), and physical activity (15/32, 47%). The development process of the apps was described in 84% (27/32) of the articles and was of low to moderate quality in most of the cases. Despite most of the articles having been published within the past two years, only 5 apps were still commercially available at the time of our search. Moreover, only very few studies showed improvement of RMD outcome measures. Conclusions The development process of most apps was of low or moderate quality in many studies. Owing to the increasing RMD patients’ willingness to use mHealth apps for self-management, optimal standards and quality assurance of new apps are mandatory.
Detecting Pulmonary Oxygen Toxicity Using eNose Technology and Associations between Electronic Nose and Gas Chromatography–Mass Spectrometry Data

Exposure to oxygen under increased atmospheric pressures can induce pulmonary oxygen toxicity (POT). Exhaled breath analysis using gas chromatography–mass spectrometry (GC–MS) has revealed that volatile organic compounds (VOCs) are associated with inflammation and lipoperoxidation after hyperbaric–hyperoxic exposure. Electronic nose (eNose) technology would be more suited for the detection of POT, since it is less time and resource consuming. However, it is unknown whether eNose technology can detect POT and whether eNose sensor data can be associated with VOCs of interest. In this randomized cross-over trial, the exhaled breath from divers who had made two dives of 1 h to 192.5 kPa (a depth of 9 m) with either 100% oxygen or compressed air was analyzed, at several time points, using GC–MS and eNose. We used a partial least square discriminant analysis, eNose discriminated oxygen and air dives at 30 min post dive with an area under the receiver operating characteristics curve of 79.9% (95%CI: 61.1–98.6; p = 0.003). A two-way orthogonal partial least square regression (O2PLS) model analysis revealed an R² of 0.50 between targeted VOCs obtained by GC–MS and eNose sensor data. The contribution of each sensor to the detection of targeted VOCs was also assessed using O2PLS. When all GC–MS fragments were included in the O2PLS model, this resulted in an R² of 0.08. Thus, eNose could detect POT 30 min post dive, and the correlation between targeted VOCs and eNose data could be assessed using O2PLS.
A neural circadian signal essential for ovulation is generated in the suprachiasmatic nucleus during each stage of the oestrous cycle

What is the central question of this study? Is the suprachiasmatic nucleus the structure that generates the neural circadian signals that occur during every stage of the oestrous cycle, not only pro‐oestrus, and are these signals essential for proper regulation of ovulation? What is the main finding and its importance? Transient inhibition of Na+‐dependent action potentials in the suprachiasmatic nucleus by tetrodotoxin microinjection at 14.00 h inhibits ovulation irrespective of the stage of the oestrous cycle at which the procedure is performed. Microinjection of saline solution into the suprachiasmatic nucleus has a disruptive effect on ovulation that depends on the stage of the cycle at which it is administered.
Nanostructured and Photochromic Material for Environmental Detection of Metal Ions

Compared to conventional spectroscopy or chromatography analysis, chemical sensing based on colorimetric changes offers an alternative to monitor potential metal hazards in aqueous environment through rapid and low-cost colorimetric changes which can be easily interpreted. In this work poly(ethylene glycol) (PEG 2000) was modified with a carboxylic acid spiropyran (SPCOOH) derivate by Steglich esterification (PEGSP2). PEGSP2 was incorporated into a poly(ε-caprolactone) (PCL) polymer matrix by electrospinning technique to produce nanofibers with photochromic properties. Spectroscopic analysis, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to characterize PEGSP2. Drop shape analysis (DSA) and scanning electronic microscopy (SEM) were used to characterize the electrospun (ES) nanofibers morphology. Several metal ions solutions relevant to environmental hazards were prepared to be spotted on the surface of ES nanofibers for photochromatic sensing. Among them, Mg2+, Ca2+, Zn2+, Cd2+, La3+, and Er3+ demonstrated orange fluorescence when exposed to UV light. ES nanofibers also presented higher wettability when compared to a pure PCL polymer matrix, which is critical for sensitivity. Eighteen metals ions could be detected on the electrospun material. Additionally, among all metal ions Fe3+ was the most sensitive one in solution, in a µmol L−1 range.
Development of Nontoxic Biodegradable Polyurethanes Based on Polyhydroxyalkanoate and L-lysine Diisocyanate with Improved Mechanical Properties as New Elastomers Scaffolds

A nontoxic and biodegradable polyurethane was prepared, characterized, and evaluated for biomedical applications. Stretchable, biodegradable, and biocompatible polyurethanes (LPH) based on L-lysine diisocyanate (LDI) with poly(ethylene glycol) (PEG) and polyhydroxyalkanoates(PHA) of different molar ratios were synthesized. The chemical and physical characteristics of the LPH films are tunable, enabling the design of mechanically performance, hydrophilic, and biodegradable behavior. The LPH films have a Young’s modulus, tensile strength, and elongation at break in the range of 3.07–25.61 MPa, 1.01–9.49 MPa, and 102–998%, respectively. The LPH films demonstrate different responses to a change of temperature from 4 to 37 °C, with the swelling ratio for the same sample at equilibrium varying from 184% to 151%. In vitro degradation tests show the same LPH film has completely different degradation morphologies in pH of 3, 7.4, and 11 phosphate buffered solution (PBS). In vitro cell tests show feasibility that some of the LPH films are suitable for culturing rat bone marrow stem cells (rBMSCs), for future soft-tissue regeneration. The results demonstrate the feasibility of the LPH scaffolds for many biomedical applications.
Biochanin A Provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury by Nrf2-Mediated Inhibition of Oxidative Stress and Inflammation Signaling Pathway in Rats

Background Oxidative stress and neuroinflammation are 2 pivotal mechanisms in the progression of cerebral ischemia/reperfusion injury. Biochanin A, a natural phytoestrogen, has been reported to protect against ischemic brain injury in animal experiments, but the possible pharmacological mechanisms of its neuroprotection remain elusive. In this research, we sought to investigate the neuroprotective effects of biochanin A in experimental stroke rats and the probable mechanisms underlying oxidative stress and inflammation signaling pathways. Material/Methods An ischemic stroke model was induced by inserting thread into the middle cerebral artery. Rats were pre-administered intraperitoneally with a vehicle solution or biochanin A (10, 20, or 40 mg·kg·d−1) for 14 days prior to ischemic stroke. Neurological score, infarct volume, and cerebral edema were assessed after 2 h of ischemia and 24 h of reperfusion. The activities of SOD and GSH-Px and MDA content were measured. The expressions of Nrf2, HO-1, and NF-κB and the activity of phosphor-IκBα were detected by Western blotting. Results Biochanin A pretreatment significantly improved neurological deficit and decreased infarct size and brain edema. Biochanin A also enhanced SOD and GSH-Px activities and suppressed the production of MDA. Additionally, biochanin A promoted Nrf2 nuclear translocation, promoted the expression of HO-1, and inhibited NF-κB activation in ischemic brain injury. Conclusions The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NF-κB pathway may contribute to the neuroprotective effects of biochanin A.
Spotlight on avian pathology: aspergillosis

ABSTRACT Aspergillosis is a disease of domestic and free-living birds caused by infection with a fraction of fungi within the genus Aspergillus. Species can be identified by colony morphology and microscopic characterization of conidia and conidiophores or by PCR, and isolates can be typed by microsatellite typing. Serodiagnostic options for testing are limited to antibody and antigen detection methods. The sensitivity of these tests can be enhanced through the use of protein electrophoresis. In many countries, no systemic antifungal drugs are registered for use in food-producing birds and resistance to antifungal drugs has been reported in Aspergillus strains derived from birds. The most important prevention strategy against aspergillosis is keeping the infection pressure low by adequate ventilation as well as cleaning and disinfection. Open questions about avian aspergillosis that research needs to address are related to epidemiology and serodiagnosis, as well as therapy and prevention.
Genetic variation in the Chinese soft-shell turtles (Pelodiscus spp.) revealed by sequences of mitochondrial Cytb gene

Abstract Genetic diversity is an important component of biodiversity and investigating and protecting the wild genetic diversity of species has always been an important research topic in conservation biology. Due to habitat destruction and over catching, wild Chinese soft-shell turtles (Pelodiscus spp.) have been severely damaged, resulting in the species being listed on the IUCN Red List of Threatened Species in 2000. However, only few studies with contradictory results on the genetic diversity of Pelodiscus turtles have been reported. To investigate the genetic diversity and population structure of Pelodiscus turtles, 123 specimens were collected from five localities in East Asia, and their genetic variation was analyzed on the basis of a 922-bp partial sequence of the mitochondrial cytb gene. Forty-nine polymorphic sites were detected, revealing 56 haplotypes. A pattern of high haplotype diversity (Hd = 0.994) and nucleotide diversity (π = 0.01655) was found in the examined range. A maximum likelihood phylogenetic tree and median-joining network analyses indicated that the Pelodiscus turtles divided in four populations throughout East Asia, and the Pelodiscus turtles probably originate from the Yangtze River and was introduced to Yellow River, Taiwan, and Japan through Xijiang River. These results served a helpful resource for conservation of Pelodiscus turtles.
The Multifaceted Roles of Plant Hormone Salicylic Acid in Endoplasmic Reticulum Stress and Unfolded Protein Response

Different abiotic and biotic stresses lead to the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER), resulting in ER stress. In response to ER stress, cells activate various cytoprotective responses, enhancing chaperon synthesis, protein folding capacity, and degradation of misfolded proteins. These responses of plants are called the unfolded protein response (UPR). ER stress signaling and UPR can be regulated by salicylic acid (SA), but the mode of its action is not known in full detail. In this review, the current knowledge on the multifaceted role of SA in ER stress and UPR is summarized in model plants and crops to gain a better understanding of SA-regulated processes at the physiological, biochemical, and molecular levels.