Miracle-dz/UniFAR-FTUs huggingface dataset:
BAIAP3, a C2 domain–containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells

Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide–sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain–containing proteins are known to regulate Ca2+-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain–containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles. One of the latter, BAIAP3, is a secretory cell–specific Munc13-4 paralog of unknown function. BAIAP3 knockdown caused accumulation of fusion-incompetent DCVs in BON neuroendocrine cells and lysosomal degradation (crinophagy) of insulin-containing DCVs in INS-1 &bgr; cells. BAIAP3 localized to endosomes was required for Golgi trans-Golgi network 46 (TGN46) recycling, exhibited Ca2+-stimulated interactions with TGN SNAREs, and underwent Ca2+-stimulated TGN recruitment. Thus, unlike other Munc13 proteins, BAIAP3 functions indirectly in DCV exocytosis by affecting DCV maturation through its role in DCV protein recycling. Ca2+ rises that stimulate DCV exocytosis may stimulate BAIAP3-dependent retrograde trafficking to maintain DCV protein homeostasis and DCV function.
Anticoagulant therapy for ischemic stroke: A review of literature

For many years, anticoagulants have been used in the emergent treatment of patients with acute ischemic stroke. Anticoagulants are prescribed in an effort to prevent first or recurrent stroke, especially among patients with cardioembolism due to arterial fibrillation and large-artery atherosclerotic disease. Despite the widespread use, efficacy and safety of anticoagulants are controversial. Experts have given a broad spectrum of opinions. Surveys of practitioners have also demonstrated a lack of consensus on the use of anticoagulants for ischemic stroke. The uncertainty is due, in large part, to the lack of definitive clinical data. A review by the panel of the Stroke Council of the American Heart Association found no strong evidence for effectiveness of anticoagulants in treating acute ischemic stroke. Several clinical trials have suggested that utility of emergent anticoagulation has no significant effect in improving clinical outcomes for patients with acute ischemic stroke. In the present review, we have attempted to provide a framework for the emergent use of anticoagulants in acute ischemic stroke patients.
Carboxylated or Aminated Polyaniline—Multiwalled Carbon Nanotubes Nanohybrids for Immobilization of Cellobiose Dehydrogenase on Gold Electrodes

Polymer-multiwalled carbon nanotube (MWCNT) nanohybrids, which differ in surface charge have been synthesized to study the bioelectrocatalysis of adsorbed cellobiose dehydrogenase (CDH) from Phanerochaete sordida on gold electrodes. To obtain negatively charged nanohybrids, poly(3-amino-4-methoxybenzoic acid-co-aniline) (P(AMB-A)) was covalently linked to the surface of MWCNTs while modification with p-phenylenediamine (PDA) converted the COOH-groups to positively charged amino groups. Fourier transform infrared spectroscopy (FTIR) measurements verified the p-phenylenediamine (PDA) modification of the polymer-CNT nanohybrids. The positively charged nanohybrid MWCNT-P(AMB-A)-PDA promoted direct electron transfer (DET) of CDH to the electrode and bioelectrocatalysis of lactose was observed. Amperometric measurements gave an electrochemical response with KMapp = 8.89 mM and a current density of 410 nA/cm2 (15 mM lactose). The catalytic response was tested at pH 3.5 and 4.5. Interference by ascorbic acid was not observed. The study proves that DET between the MWCNT-P(AMB-A)-PDA nanohybrids and CDH is efficient and allows the sensorial detection of lactose.
Physical activity is not associated with spirometric indices in lung-healthy German youth

In lung disease, physical activity improves lung function and reduces morbidity. However, healthy populations are not well studied. We estimate the relationship between spirometric indices and accelerometric physical activity in lung-healthy adolescents. 895 nonsmoking German adolescents without chronic lung disease (45% male, mean±sd age 15.2±0.26 years) from the GINIplus and LISAplus cohorts completed questionnaires, spirometry, 7-day accelerometry and an activity diary. Physical activity was measured as minutes, quintiles and regularity of daily moderate, vigorous and moderate-to-vigorous physical activity (MVPA), participation in sport and active commuting to school. Primary outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow at 25–75% of FVC; they were separately correlated with physical activity and adjusted for confounders of respiratory function, including early-life exposures. Adolescents averaged 40 min MVPA per day, typical for European youth. 79% participated in sports and 51% commuted actively. An association was suggested between 3% higher FVC (∼100 mL) and either extreme MVPA quintile or percentage of days with >30 min MVPA (p<0.05). However, after Bonferroni correction all associations between spirometry, active lifestyle and physical activity were nonsignificant. Spirometric indices were not significantly associated with active lifestyle or measures of activity in lung-healthy adolescents after adjustment for confounding and multiple-comparison artefacts. In lung-healthy adolescents, spirometric indices were not associated with measures of physical activity http://ow.ly/YN4Nt
Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death

Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348–1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.
Effects of Carthamus tinctorius on Semen Quality and Gonadal Hormone Levels in Partially Sterile Male Rats

Purpose Traditional herbal medicine is just one of the many different approaches using plants in the remedy of diseases. Carthamus tinctorius (CT) or safflower is a popular plant that is used for coloring and flavoring in food industries. The effect of CT on spermatogenesis and sperm parameters has been reported in traditional medicine but has not yet been confirmed scientifically. Therefore, this study was designed to determine the effects of CT on spermatogenesis and the male reproductive system in an animal model. Materials and Methods Sixty male rats were divided into five groups. Four groups were injected with 5 mg/kg of busulfan as a model of partial infertility. Then, the experimental groups were treated with 10 mg/kg, 25 mg/kg, or 50 mg/kg of CT extract for 35 days. The control was treated with busulfan (infertile control) or distilled water only. After this period, the animals were sacrificed and blood samples were taken for hormonal assay. The semen was collected from the epididymis and the reproductive organs were assessed. Sperm count and motility were measured and smears were prepared for assessment of the other parameters. Results The results indicated that the percentage of sperm with good morphology, motility, and count increased significantly in the group treated with 10 mg/kg CT (p=0.002, p=0.03, and p=0.00001, respectively). The effects on hormonal changes and genital organ weights were also positive. Conclusions It is probable that the CT extract affects spermatogenesis and as a result sperm quality. Further studies are needed.
Repairing a bone defect with a three-dimensional cellular construct composed of a multi-layered cell sheet on electrospun mesh

In addition to providing maneuverability, electrospun nanofibrous meshes can make excellent supports for constructing flexible cell sheets to regulate cell behavior by nanofiber features. With the target of bone regeneration, herein composite nanofibers with two different fiber arrangements (nestlike, random) were electrospun from a blend solution containing poly(l-lactide) (PLLA) and gelatin (1:1 in weight ratio). Unlike the non-woven morphology in a random nanofibrous mesh, PLLA/gelatin composite nanofibers in the nestlike nanofibrous mesh displayed both non-woven and parallel morphologies. Both kinds of nanofibrous mesh were ∼50 μm thick as-prepared, and shrank to ∼30 μm after seeding with bone mesenchymal stromal cells (BMSCs). After 7 days of in vitro culture, cell sheets could form on both meshes (CSM) and on the culture plate. It was found that application of nanofibrous mesh promoted the osteogenic differentiation of BMSC sheets compared with the control. The nestlike mesh displayed slight superiority over the random mesh in enhancing osteogenic differentiation, but their different fiber arrangements did not cause much difference in cell proliferation. Three-dimensional multi-layered CSM constructs were built by stacking four mono-layered CSMs together. The CSM constructs (based on a nestlike or random nanofibrous mesh) were incubated in vitro for 3 days before being implanted into rat cranial defects. In comparison with the control group, there was significant formation of new calcified bone in both CSM construct-filled groups at 12 weeks’ post-operation. The nestlike group showed slightly better bone healing (based on both qualitative and quantitative analysis) than the random group, while showing insignificant differences. We showed that the concept of using a three-dimensional multi-layered CSM construct in enhancing bone regeneration was feasible. Future studies should take more nanofiber features (e.g. bioactive components) into account to further enhance osteogenesis.
An Investigation of Fecal Volatile Organic Metabolites in Irritable Bowel Syndrome

Diagnosing irritable bowel syndrome (IBS) can be a challenge; many clinicians resort to invasive investigations in order to rule out other diseases and reassure their patients. Volatile organic metabolites (VOMs) are emitted from feces; understanding changes in the patterns of these VOMs could aid our understanding of the etiology of the disease and the development of biomarkers, which can assist in the diagnosis of IBS. We report the first comprehensive study of the fecal VOMs patterns in patients with diarrhea-predominant IBS (IBS-D), active Crohn's disease (CD), ulcerative colitis (UC) and healthy controls. 30 patients with IBS-D, 62 with CD, 48 with UC and 109 healthy controls were studied. Diagnosis of IBS-D was made using the Manning criteria and all patients with CD and UC met endoscopic, histologic and/or radiologic criteria. Fecal VOMs were extracted by solid phase microextraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). 240 VOMs were identified. Univariate analysis showed that esters of short chain fatty acids, cyclohexanecarboxylic acid and its ester derivatives were associated with IBS-D (p<0.05), while aldehydes were more abundant in IBD (p<0.05). A predictive model, developed by multivariate analysis, separated IBS-D from active CD, UC and healthy controls with a sensitivity of 94%, 96% and 90%; and a specificity of 82%, 80% and 80% respectively (p<0.05). The understanding of the derivation of these VOMs may cast light on the etiology of IBS-D and IBD. These data show that fecal VOMs analyses could contribute to the diagnosis of IBS-D, for which there is no laboratory test, as well as IBD.
Hybrid procedure for total laryngectomy with a flexible robot‐assisted surgical system

Total laryngectomy is a standard procedure in head‐and‐neck surgery for the treatment of cancer patients. Recent clinical experiences have indicated a clinical benefit for patients undergoing transoral robot‐assisted total laryngectomy (TORS‐TL) with commercially available systems. Here, a new hybrid procedure for total laryngectomy is presented.
Odor Uniformity among Tomato Individuals in Response to Herbivore Depends on Insect Species

Plants produce specific volatile organic compound (VOC) blends in response to herbivory. Herbivore-induced blends may prime the plant for future attack or attract carnivorous insects; these responses have been considered adaptive for plants. If herbivores differentially modify the VOC emission among individuals within a group of plants they feed upon, then plant responses to herbivores will not only produce specific blends but also variation in odor among individuals, i.e. individuals smell the same, then having a uniform odor. We investigated the VOC emission variation or uniformity among tomato individuals (Solanum lycopersicum L. cv. Castlemart) in response to moderate wounding by (1) nymphs of the psyllid Bactericera cockerelli (Sulc.) (TP); (2) Lepidoptera chewing-feeding larvae of Fall Armyworm (Spodoptera frugiperda Smith) (FAW) and (3) of Cabbage Looper (Trichoplusia ni Hübner) (CL), and (4) mechanical damage (MD). We used a ratio-based analysis to compare the fold-change in concentration from constitutive to induced VOC emission. We also used size and shape analysis to compare the emission of damaged and non-damaged individuals. Aside of finding herbivore-specific blends in line with other studies, we found patterns not described previously. We detected constitutive and induced odor variation among individuals attacked by the same herbivore, with the induced odor uniformity depending on the herbivore identity. We also showed that the fold-change of VOCs from constitutive to induced state differed among individuals independently of the uniformity of the blends before herbivore attack. We discuss our findings in the context of the ecological roles of VOCs in plant-plant and plant-carnivore insects’ interactions.
Three-Year Follow-Up of Participants from a Self-Weighing Randomized Controlled Trial

Frequent self-weighing is associated with weight loss maintenance. Several years ago, we investigated frequent self-weighing's effect on weight loss and found the participants lost a significant amount of weight. Three years after this trial's end, participants were contacted for an update on their weight and self-weighing frequency. Weight change and self-weighing frequency since the end of the study were assessed. We hypothesized that participants who maintained frequent self-weighing behavior would have maintained their weight loss. Out of 98 participants enrolled in the RCT, 37% (n = 36) participated in this follow-up study. Total weight loss during the trial for the follow-up participants was 12.7 ± 19.4 lbs (p < 0.001). Three years after intervention, participants regained 0.9 ± 4.34 lbs, a value that was not statistically different from zero (p = 0.75). This did not differ by gender (p = 0.655). Over 75% of these participants continued to weigh themselves at least once a week. Frequent self-weighing may be an effective, low-cost strategy for weight loss maintenance. Future research should further investigate the role of self-weighing in long-term weight gain prevention.
Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation

ABSTRACT In normal cells, p53 is maintained at a low level by ubiquitin-mediated proteolysis, but after genotoxic insult this process is inhibited and p53 levels rise dramatically. Ubiquitination of p53 requires the ubiquitin-activating enzyme Ubc5 as a ubiquitin conjugation enzyme and Mdm2, which acts as a ubiquitin protein ligase. In addition to the N-terminal region, which is required for interaction with Mdm2, the C-terminal domain of p53 modulates the susceptibility of p53 to Mdm2-mediated degradation. To analyze the role of the C-terminal domain in p53 ubiquitination, we have generated p53 molecules containing single and multiple lysine-to-arginine changes between residues 370 and 386. Although wild-type (WT) and mutant molecules show similar subcellular distributions, the mutants display a higher transcriptional activity than WT p53. Simultaneous mutation of lysine residues 370, 372, 373, 381, 382, and 386 to arginine residues (6KR p53 mutant) generates a p53 molecule with potent transcriptional activity that is resistant to Mdm2-induced degradation and is refractory to Mdm2-mediated ubiquitination. In contrast to WT p53, transcriptional activity directed by the 6KR p53 mutant fails to be negatively regulated by Mdm2. Those differences are also manifest in HeLa cells which express the human papillomavirus E6 protein, suggesting that p53 C-terminal lysine residues are also implicated in E6-AP-mediated ubiquitination. These data suggest that p53 C-terminal lysine residues are the main sites of ubiquitin ligation, which target p53 for proteasome-mediated degradation.
Dynamic Mechanical Analysis in the Analysis of Polymers and Rubbers

Dynamic mechanical analysis (DMA) or dynamic mechanical thermal analysis is a thermal testing technique used extensively in the polymer and rubber industries. It involves applying an oscillatory force or deformation to a material and monitoring the response. This article summaries the theory and application of DMA to thermoplastics, rubber, thermosets, and composites. Keywords: DMA; damping; Tg; Modulus; Dynamic Mechanical
Adaptive Fuzzy Bounded Control for Consensus of Multiple Strict-Feedback Nonlinear Systems

This paper studies the adaptive fuzzy bounded control problem for leader–follower multiagent systems, where each follower is modeled by the uncertain nonlinear strict-feedback system. Combining the fuzzy approximation with the dynamic surface control, an adaptive fuzzy control scheme is developed to guarantee the output consensus of all agents under directed communication topologies. Different from the existing results, the bounds of the control inputs are known as a priori, and they can be determined by the feedback control gains. To realize smooth and fast learning, a predictor is introduced to estimate each error surface, and the corresponding predictor error is employed to learn the optimal fuzzy parameter vector. It is proved that the developed adaptive fuzzy control scheme guarantees the uniformly ultimate boundedness of the closed-loop systems, and the tracking error converges to a small neighborhood of the origin. The simulation results and comparisons are provided to show the validity of the control strategy presented in this paper.
Modeling the Distribution of Geodia Sponges and Sponge Grounds in the Northwest Atlantic

Deep-sea sponge grounds provide structurally complex habitat for fish and invertebrates and enhance local biodiversity. They are also vulnerable to bottom-contact fisheries and prime candidates for Vulnerable Marine Ecosystem designation and related conservation action. This study uses species distribution modeling, based on presence and absence observations of Geodia spp. and sponge grounds derived from research trawl catches, as well as spatially continuous data on the physical and biological ocean environment derived from satellite data and oceanographic models, to model the distribution of Geodia sponges and sponge grounds in the Northwest Atlantic. Most models produce excellent fits with validation data although fits are reduced when models are extrapolated to new areas, especially when oceanographic regimes differ between areas. Depth and minimum bottom salinity were important predictors in most models, and a Geodia spp. minimum bottom salinity tolerance threshold in the 34.3-34.8 psu range was hypothesized on the basis of model structure. The models indicated two currently unsampled regions within the study area, the deeper parts of Baffin Bay and the Newfoundland and Labrador slopes, where future sponge grounds are most likely to be found.
Solid-gel interactions in geopolymers

Mineral binders are inorganic polymers that possess bonding properties towards a number of materials such as natural rocks, crushed stones, synthetic mineral wastes and glass wastes. Although the use of mineral binders has dated thousands of years since the Neolithic times (ca. 7000 B.C.), the ‘ultimate’ mineral binder still remains illusive. This is partly because the requirements for such an ultimate material change with people’s perception about its properties as well as its environmental impact. Thus, the once-believed ultimate Portland cement binder is now becoming unacceptable for a number of reasons including poor durability as well as severe environmental impact during production. Thus, an improved mineral binder is required by modern society to serve the same purposes as the existing Portland cement binder, as well as to reduce the current environmental impact caused by Portland cement production. Geopolymerisation is such a ‘green’ technology capable of turning both natural ‘virgin’ aluminosilicates and industrial aluminosilicate wastes, such as fly ash and blast furnace slag, into mechanically strong and chemically durable construction materials. However, the source materials for geopolymer synthesis are less reactive than Portland cement clinkers and the chemical compositions of these source materials can vary significantly. Consequently, product quality control is a major engineering challenge for the commercialisation of geopolymers. This thesis is therefore devoted to the mechanistic understanding of the interfacial chemical interactions between a number of natural and industrial aluminosilicates and the various activating solutions, which govern the reactivity of the aluminosilicate source materials. The effects of activating solution alkalinity, soluble silicate dosage and anionic contamination on the reactivity of the aluminosilicate source materials to produce geopolymeric binders, as well as their bonding properties to natural siliceous aggregates for concrete making, are examined. In particular, a new set of novel ‘realistic’ reaction models has been developed for such purposes. These reaction models have been further utilised to develop a novel analytical procedure, which is capable of studying geopolymerisation on ‘real’ geopolymers in situ and in real time. This novel procedure is invaluable for the total understanding of geopolymerisation, which is in turn vital for effective geopolymer mix designs.