Miracle-dz/UniFAR-FTUs huggingface dataset:
t‐loops at trypanosome telomeres

Mammalian telomeres form large duplex loops (t‐loops) that may sequester chromosome ends by invasion of the 3′ TTAGGG overhang into the duplex TTAGGG repeat array. Here we document t‐loops in Trypanosoma brucei, a kinetoplastid protozoan with abundant telomeres due to the presence of many minichromosomes. These telomeres contained 10–20 kb duplex TTAGGG repeats and a 3′ TTAGGG overhang. Electron microscopy of psoralen/UV cross‐linked DNA revealed t‐loops in enriched telomeric restriction fragments and at the ends of isolated minichromosomes. In mammals, t‐loops are large (up to 25 kb), often comprising most of the telomere. Despite similar telomere lengths, trypanosome t‐loops were much smaller (∼1 kb), indicating that t‐loop sizes are regulated. Coating of non‐cross‐linked minichromosomes with Escherichia coli single‐strand binding protein (SSB) often revealed 3′ overhangs at both telomeres and several cross‐linked minichromosomes had t‐loops at both ends. These results suggest that t‐loops and their prerequisite 3′ tails can be formed on the products of both leading and lagging strand synthesis. We conclude that t‐loops are a conserved feature of eukaryotic telomeres.
Reliable secret key generation from physical unclonable functions under varying environmental conditions

Two methods are proposed to extract secret keys from ring oscillator (RO) physical unclonable functions (PUFs) under varying environmental conditions. A discrete cosine transform (DCT)-based RO PUF scheme that gives good results under nominal conditions is used in combination with these two methods, which are shown to be highly robust to environmental variations. The proposed methods significantly improve the secret-key size, reliability, uniqueness, and randomness results of existing RO PUF schemes under varying temperature and voltage conditions.
Alcohol abuse in a metropolitan city in China: a study of the prevalence and risk factors.

AIMS To investigate the prevalence of alcohol abuse in modern China and to explore the risk factors that may be associated with alcohol abuse. DESIGN A face-to-face interview was carried out in a random sample with 2327 respondents. SETTING Respondents were selected randomly from Wuhan City, Hubei Province, China, between May and June 2002. Participants Fifteen-65-year-old urban Chinese adults. MEASUREMENTS Scores for alcohol abuse and related risk factors were the main measures. FINDINGS (1) Nearly 15% of urban Chinese adults aged 15-65 were alcohol abusers. (2) Deviant drinking habits of mother, schoolmates, colleagues or friends all had a negative impact on the respondent's alcohol drinking behaviours, and higher economic status, current smokers, being male and being older were identified as risk factors related to alcohol abuse. In particular, if a drinker's mother used alcohol frequently then this drinker was more likely to become an alcohol abuser than those drinkers whose mothers did not use alcohol frequently (P = 0.0001). Fathers' drinking behaviours do not have a significant impact on the alcohol abusers. CONCLUSIONS In addition to common risk factors such as economic status, deviant peers' and fellows' drinking behaviours and negative attitudes to alcohol drinking, maternal alcohol drinking habit influenced significantly the offspring's drinking habits. Therefore, efficient intervention and education of healthy drinking habits in early motherhood is necessary for Chinese women.
ADAMTS-13 Metalloprotease Interacts with the Endothelial Cell-derived Ultra-large von Willebrand Factor*

Thrombotic thrombocytopenic purpura is caused by congenital or acquired deficiency of ADAMTS-13, a metalloprotease that cleaves the endothelium-derived ultra-large multimers of von Willebrand factor (ULVWF). The proteolysis converts hyper-reactive and thrombogenic ULVWF into smaller and less adhesive plasma forms. Activity of ADAMTS-13 is usually measured in a static system under non-physiological conditions that require protein denaturation and prolonged incubation. We have demonstrated previously that ULVWF multimers, upon release from endothelial cells, form plateletdecorated string-like structures that are rapidly cleaved by ADAMTS-13. Here we report the direct interaction between ADAMTS-13 and VWF under both static and flowing conditions. ADAMTS-13-coated beads adhered to both immobilized VWF and ULVWF strings presented by stimulated endothelial cells. These beads adhered to VWF under both venous (2.5 dynes/cm2) and arterial (30 dynes/cm2) shear stresses. We then demonstrated that ADAMTS-13 beads adhered to immobilized recombinant VWF-A1 and -A3 domains, but soluble metalloprotease bound preferentially to the A3 domain, suggesting that the VWF A3 domain may be the primary docking site for the metalloprotease. We suggest that tensile stresses imposed by fluid shear stretch endothelial bound ULVWF multimers to expose binding sites within the A domains for circulating ADAMTS-13. The bound enzyme then cleaves within the A2 domain that lies in close proximity and releases smaller VWF multimers into the plasma. Once released, these cleaved VWF fragments become inaccessible for the metalloprotease to prevent further cleavage.
The Development of Obesity Begins at an Early Age in Captive Common Marmosets (Callithrix jacchus)

Animal models to study the causes and consequences of obesity during infancy in humans would be valuable. In this study, we examine the patterns of fat mass gain from birth to 12 months in common marmosets (Callithrix jacchus). Lean and fat mass was measured by quantitative magnetic resonance at 1, 2, 6, and 12 months for 31 marmosets, 15 considered Normal and 16 considered Fat (>14% body fat) at 12 months. Animals were fed either the regular colony diet mix or a high‐fat variation. Subjects classified as Fat at 12 months already had greater lean mass (198.4 ± 6.2 g vs. 174.0 ± 6.8 g, P = 0.013) and fat mass (45.5 ± 5.0 g vs. 24.9 ± 3.4 g, P = .002) by 6 months. Body mass did not differ between groups prior to 6 months, however, by 1 month, Fat infants had greater percent body fat. Percent body fat decreased between 1 and 12 months in Normal subjects; in Fat subjects, it increased. The high‐fat diet was associated with body fat >14% at 6 months (P = 0.049), but not at 12 months. This shift was due to three subjects on the normal diet changing from Normal to Fat between 6 and 12 months. Although maternal prepregnancy adiposity did not differ, overall, between Normal and Fat subjects, the subjects Normal at 6 and Fat at 12 months all had Fat mothers. Therefore, diet and maternal obesity appear to have potentially independent effects that may also vary with developmental age. Although birth weight did not differ between groups, it was associated with fat mass gain from 1 to 6 months in animals with >14% body fat at 6 months of age (r = 0.612, P = 0.026); but not in 6‐month‐old animals with <14% body fat (r = –0.012, P = 0.964). Excess adiposity in captive marmosets develops by 1 month. Birth weight is associated with adiposity in animals vulnerable to obesity.
Long-term exposure to air pollution and asthma hospitalisations in older adults: a cohort study

Background Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether long-term exposure to air pollution can lead to asthma onset or progression in adulthood. Objectives The authors studied the effect of exposure to traffic-related air pollution over 35 years on the risk for asthma hospitalisation in older people. Methods 57 053 participants in the Danish Diet, Cancer and Health cohort, aged 50–65 years at baseline (1993–1997), were followed up for first hospital admission for asthma until 2006, and the annual nitrogen dioxide (NO2) levels were estimated as a proxy of the exposure to traffic-related air pollution at the residential addresses of the participants since 1971. The association between NO2 and hospitalisation for asthma was modelled using Cox regression, for the full cohort and in people with and without previous hospitalisations for asthma, and the effect modification by comorbid conditions was assessed. Results During 10.2 years' median follow-up, 977 (1.9%) of 53 695 eligible people were admitted to hospital for asthma: 821 were first-ever admissions and 176 were readmissions. NO2 levels were associated with risk for asthma hospitalisation in the full cohort (HR and 95% CI per IQR, 5.8 μg/m3: 1.12; 1.04–1.22), and for first-ever admissions (1.10; 1.01–1.20), with the highest risk in people with a history of asthma (1.41; 1.15–2.07) or chronic obstructive pulmonary disease (COPD) (1.30; 1.07–1.52) hospitalisation. Conclusions Long-term exposure to traffic-related air pollution increases the risk for asthma hospitalisation in older people. People with previous asthma or COPD hospitalisations are most susceptible.
Visual functions of mental imagery

Bright zinc plate is obtained from alkaline, cyanide-free zinc plating baths containing at least one linear polyamine obtained by condensing an aliphatic diamine with an aliphatic dihalide. Especially good results are obtained if the bath also contains at least one substituted pyridine compound in the form of a free base or as a quaternised derivative. A brightener composition containing both the linear polyamine and the pyridine compound can be added to alkaline, cyanide-free zinc plating baths.
Self-injurious behaviour in autism spectrum disorder

Background: Self-injury is reported to be common in autism spectrum disorder (ASD). However, there are limited robust data detailing the prevalence, persistence, associated person characteristics and operant function of self-injury in ASD. Method: Three large scale survey studies were employed to establish the prevalence, persistence and risk markers for self-injury in ASD compared to contrast groups. Experimental functional analyses were conducted, including a fine grained temporal analysis of behaviours associated with self-injury. Results: Self-injury was displayed by 50% of the ASD sample and was persistent over three years in 77.8% of the group. Self-injury was associated with higher levels of autistic behaviour in individuals without idiopathic autism. Self-injury was associated with higher levels of impulsivity, hyperactivity, painful health conditions, repetitive behaviours and lower levels of adaptive behaviour. ‘ASD weighted’ operant functions for self-injury were identified for the majority of children with ASD. Conclusions: Self-injury is prevalent and persistent in ASD. The presence of ASD phenomenology is a risk marker for self-injury. There is a role for repetitive behaviours, pain and impaired behavioural inhibition in the development and persistence of self-injury. Self-injury is likely to be maintained by operant reinforcement in many individuals with ASD, through ‘ASD weighted’ reinforcement contingencies.
Possible effects of global environmental changes on Antarctic benthos: a synthesis across five major taxa

Because of the unique conditions that exist around the Antarctic continent, Southern Ocean (SO) ecosystems are very susceptible to the growing impact of global climate change and other anthropogenic influences. Consequently, there is an urgent need to understand how SO marine life will cope with expected future changes in the environment. Studies of Antarctic organisms have shown that individual species and higher taxa display different degrees of sensitivity to environmental shifts, making it difficult to predict overall community or ecosystem responses. This emphasizes the need for an improved understanding of the Antarctic benthic ecosystem response to global climate change using a multitaxon approach with consideration of different levels of biological organization. Here, we provide a synthesis of the ability of five important Antarctic benthic taxa (Foraminifera, Nematoda, Amphipoda, Isopoda, and Echinoidea) to cope with changes in the environment (temperature, pH, ice cover, ice scouring, food quantity, and quality) that are linked to climatic changes. Responses from individual to the taxon-specific community level to these drivers will vary with taxon but will include local species extinctions, invasions of warmer-water species, shifts in diversity, dominance, and trophic group composition, all with likely consequences for ecosystem functioning. Limitations in our current knowledge and understanding of climate change effects on the different levels are discussed.
Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease

Hepatic steatosis is caused by metabolic imbalances that could be explained in part by an increase in de novo lipogenesis that results from increased sterol element binding protein 1 (SREBP-1) activity. The nuclear receptor liver receptor homolog 1 (LRH-1) is an important regulator of intermediary metabolism in the liver, but its role in regulating lipogenesis is not well understood. Here, we have assessed the contribution of LRH-1 SUMOylation to the development of nonalcoholic fatty liver disease (NAFLD). Mice expressing a SUMOylation-defective mutant of LRH-1 (LRH-1 K289R mice) developed NAFLD and early signs of nonalcoholic steatohepatitis (NASH) when challenged with a lipogenic, high-fat, high-sucrose diet. Moreover, we observed that the LRH-1 K289R mutation induced the expression of oxysterol binding protein-like 3 (OSBPL3), enhanced SREBP-1 processing, and promoted de novo lipogenesis. Mechanistically, we demonstrated that ectopic expression of OSBPL3 facilitates SREBP-1 processing in WT mice, while silencing hepatic Osbpl3 reverses the lipogenic phenotype of LRH-1 K289R mice. These findings suggest that compromised SUMOylation of LRH-1 promotes the development of NAFLD under lipogenic conditions through regulation of OSBPL3.
New process for production of fermented black table olives using selected autochthonous microbial resources

Table olives represent one important fermented product in Europe and, in the world, their demand is constantly increasing. At the present time, no systems are available to control black table olives spontaneous fermentation by the Greek method. During this study, a new protocol for the production of black table olives belonging to two Italian (Cellina di Nardò and Leccino) and two Greek (Kalamàta and Conservolea) cultivars has been developed: for each table olive cultivar, starter-driven fermentations were performed inoculating, firstly, one selected autochthonous yeast starter and, subsequently, one selected autochthonous LAB starter. All starters formulation were able to dominate fermentation process. The olive fermentation was monitored using specific chemical descriptors able to identify a first stage (30 days) mainly characterized by aldehydes; a second period (60 days) mainly characterized by higher alcohols, styrene and terpenes; a third fermentation stage represented by acetate esters, esters and acids. A significant decrease of fermentation time (from 8 to 12 months to a maximum of 3 months) and an significant improvement in organoleptic characteristics of the final product were obtained. This study, for the first time, describes the employment of selected autochthonous microbial resources optimized to mimic the microbial evolution already recorded during spontaneous fermentations.
Nuclear localization of Semliki Forest virus-specific nonstructural protein nsP2

About 50% of Semliki Forest virus-specific nonstructural protein nsP2 is associated with the nuclear fraction in virus-infected BHK cells. Transport into the nucleus must be specific, since only trace amounts of nsP3 and nsP4 and about 13% of nsP1, all derived from the same polyprotein, were found in the nucleus. Subfractionation of [35S]methionine-labeled Semliki Forest virus-infected cells showed that 80 to 90% of the nuclear nsP2 was associated with the nuclear matrix. Indirect immunofluorescence, with anti-nsP2 antiserum, showed the most intensive staining of structures which by Nomarski optics appeared to be nucleoli. In the presence of 1 to 5 micrograms of dactinomycin per ml the nuclei were stained evenly and no nucleoli could be found. Transport of nsP2 into the nucleus occurred early in infection and was fairly rapid. A cDNA encoding the complete nsP2 was isolated by the polymerase chain reaction technique and ligated into a simian virus 40 expression vector derivative. When BHK cells were transfected with this pSV-NS2 vector by the lipofection procedure, nsP2 was expressed in about 1 to 5% of the cells, as shown by indirect immunofluorescence. In positively transfected cells the immunofluorescence stain was most intensive in the nucleoli. Thus, Semliki Forest virus-specific nsP2 must have information which directs it into the nuclear matrix and, more specifically, into the nucleoli.
Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron‐specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15‐MKL1 fusion gene.
TNF Receptors Differentially Signal and Are Differentially Expressed and Regulated in the Human Heart

Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild‐type (WTC57BL/6), TNFR1‐knockout (KO), TNFR2KO, TNFR1/2KO mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal‐regulating kinase‐1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co‐expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In WTC57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF‐treated TNFR1KO myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2KO myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1‐mediated cell death and TNFR2‐mediated repair.
Conquering Neutrophils

Neutrophils are the most abundant innate immune cells, making up 50%–70% of all leukocytes. Neutrophils are the “first responders” of host defense, preventing infections by deploying sophisticated antimicrobial strategies acting in concert. As neutrophils are short-living cells, they are continuously produced and released from the bone marrow in abundance (>10 per day). Circulating neutrophils are terminally differentiated, fully equipped with pre-stored antimicrobial molecules [1], and also contribute to shaping adaptive immune responses, as reviewed recently [2]. Neutrophils present challenges and limitations to experimentation, as they are short-lived, non-dividing, and genetically non-modifiable. Furthermore, no adequate cell lines exist that fully recapitulate the cellular and physiological functions of neutrophils, and murine neutrophils differ in number and (re)activity from their human counterparts. On the plus side, neutrophils can be relatively easily and quickly purified in large quantities from the blood of healthy human volunteers. In this article, we discuss the suite of mechanisms employed by neutrophils to clear bacterial infections and the corresponding counterattack mounted by bacterial pathogens. Focusing primarily on the host response, we illustrate how a single human-specific pathogen, Streptococcus pyogenes (group A Streptococcus [GAS]), has developed an impressive range of strategies to thwart neutrophil clearance [3]. This capacity correlates to an estimated 700 million infections and 150,000 deaths annually from GAS disease, a “top 10” cause of infection-related mortality worldwide [4].
Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review.

IMPORTANCE Ischemic heart disease is the leading cause of death globally. Coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) are the revascularization options for ischemic heart disease. However, the choice of the most appropriate revascularization modality is controversial in some patient subgroups. OBJECTIVE To summarize the current evidence comparing the effectiveness of CABG surgery and PCI in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease (CAD), diabetes, or left ventricular dysfunction (LVD). EVIDENCE REVIEW A search of OvidSP MEDLINE, EMBASE, and Cochrane databases between January 2007 and June 2013, limited to randomized clinical trials (RCTs) and meta-analysis of trials and/or observational studies comparing CABG surgery with PCI was performed. Bibliographies of relevant studies were also searched. Mortality and major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause mortality, myocardial infarction, stroke, and repeat revascularization) were reported wherever possible. FINDINGS Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with ULMD, multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX ≤22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies. CONCLUSIONS AND RELEVANCE Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise.
Soft-decision decoding of RS codes

By introducing a few simplifying assumptions we derive a simple condition for successful decoding using the Koetter-Vardy algorithm for soft-decision decoding of RS codes. We show that the algorithm has a significant advantage over hard decision decoding when the code rate is low, when two or more sets of received symbols have substantially different reliabilities, or when the number of alternative transmitted symbols is very small