Miracle-dz/UniFAR-FTUs huggingface dataset:
MARCH5-FUNDC1 axis fine-tunes hypoxia-induced mitophagy

ABSTRACT Mitophagy is responsible for removal of damaged mitochondria and is therefore a fundamental process in mitochondrial quality control. Both ubiquitin-dependent and receptor-dependent pathways are considered to mediate mitophagy. These distinct mechanisms may be activated in response to distinct mitochondrial stresses. An intriguing question is whether and how crosstalk occurs between the distinct pathways to coordinate mitophagy. We have uncovered a striking piece of evidence to demonstrate that the mitophagy receptor FUNDC1 is a substrate of MARCH5, a mitochondrially localized E3 ubiquitin ligase. In response to hypoxia, MARCH5 degrades redundant FUNDC1 to fine-tune hypoxia-induced mitophagy, whereas ablation of MARCH5 leads to accumulation of FUNDC1 and an exaggerated mitophagic phenotype. Mechanistic studies demonstrate that hypoxic insult enhances the interaction of FUNDC1 with MARCH5, which ubiquitinates FUNDC1 at lysine 119 for subsequent degradation. MARCH5-based ubiquitination and degradation of FUNDC1 circumvents injudicious removal of cellular mitochondria. However, severe hypoxic stress leads to dephosphorylation of FUNDC1, increasing mitophagic flux.
Coronary Calcifications in End-Stage Renal Disease Patients: A New Link between Osteoprotegerin, Diabetes and Body Mass Index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 ± 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca × P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-β1 (TGF-β1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0–7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-β1, OPG and days with Ca × P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.
An itchy vesiculobullous eruption in a patient with chronic lymphocytic leukaemia

Exaggerated reactions to insect bites are characteristic of patients with haemoproliferative disorders, particularly chronic lymphocytic leukaemia (CLL). Skin lesions usually appear after the diagnosis of leukaemia and seem unrelated to laboratory findings, disease course or therapy. Rarely, the eruption may precede the diagnosis of the haematologic malignancy. The patients usually do not recall of insect bites, and the diagnosis may require histological and laboratory investigations to exclude specific lesions or autoimmune bullous diseases. Lesions may run a chronic course and represent a therapeutic challenge. Here, we report an adult patient with CLL who developed itchy recurrent papulovesicular and bullous lesions. Differential diagnosis was made with cutaneous specific lesions of CLL, bullous pemphigoid and pemphigus vulgaris, but laboratory and histological investigations confirmed the diagnosis of an insect bite reaction. The patient was treated with oral H1 anti‐histamines and topical corticosteroids under occlusion, with marked improvement after 10 days.
Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK‐M

Abstract: Background/Aim: Biliary epithelial cells possess an innate immune system consisting of Toll‐like receptors (TLRs). Although the human bile contains lipopolysaccharide (LPS) in normal as well as diseased livers, LPS physiologically does not elicit an inflammatory response in the biliary tree. This absence of a response to LPS could be due to the ‘endotoxin tolerance’ speculated to maintain innate immune homeostasis in organs. Our aim here is to clarify the presence and molecular mechanisms of endotoxin tolerance of biliary epithelium.
Dissimilar mechanisms of Ca 2 1 response to bradykinin in different types of juxtamedullary glomerular arterioles

Dissimilar mechanisms of Ca 2 1 response to bradykinin in different types of juxtamedullary glomerular arterioles. Am. J. Physiol. 277 ( Renal Physiol. 46): F697– F705, 1999. —Bradykinin (BK)-induced changes in intracellular calcium level ([Ca 2 1 ] i ) were studied on fura 2-loaded afferent (AA) and efferent glomerular arterioles (EA) microdissected from juxtamedullary renal cortex. A distinction was made between thin and muscular EA. In AA and both types of EA, BK increased [Ca 2 1 ] i through activation of B 2 receptors located only on the endothelium. The responses were not affected by nifedipine (10 2 6 M) and were smaller in a Ca 2 1 free medium, providing evidence that BK opens voltage-independent Ca 2 1 channels and mobilizes intracellular Ca 2 1 . Thin EA differed from AA and muscular EA by a lower sensitivity to BK (EC 50 5 6.95 6 3.81 vs. 0.21 6 0.08 and 0.18 6 0.13 nM, respectively; P , 0.05), a higher maximal response (89 6 5 vs. 57 6 5 and 44 6 7 nM; P , 0.001), and a spontaneous return to basal Ca 2 1 level, even in the presence of BK. Genistein (10 2 4 M) and herbimycin A (25 3 10 2 6 M), speciﬁc inhibitors of tyrosine kinases, inhibited the [Ca 2 1 ] i responses exclusively in AA. Genistein reduced the peak and plateau phases of responses by 69 6 9 and 82 6 6%, respectively, in a medium with Ca 2 1 and the peak by 48 6 9% in a Ca 2 1 -free medium. Similar reductions were observed with herbimycin A. These results show that dissimilar signal transduction pathways are involved in BK effects on juxtamedullary arterioles and that a tyrosine kinase activity could participate in the regulation of BK effect onAAbut not on EA. tyrosine METHODS Microdissection of renal microvessels. Experiments were conducted on glomerular arterioles isolated from rat kidney by using a previously described protocol (10). Brieﬂy, male Sprague-Dawley rats (180–240 g) obtained from Iffa-Credo
Third law of black-hole dynamics: A formulation and proof.

It is shown that no continuous process in which the energy tensor of accreted matter remains bounded and satisfies the weak energy condition in a neighborhood of the apparent horizon can reduce the surface gravity of a black hole to zero within a finite advanced time. This gives a precise expression to the third law of black-hole mechanics.
Functionally relevant motions of haloalkane dehalogenases occur in the specificity‐modulating cap domains

One‐nanosecond molecular dynamics trajectories of three haloalkane dehalogenases (DhlA, LinB, and DhaA) are compared. The main domain was rigid in all three dehalogenases, whereas the substrate specificity‐modulating cap domains showed considerably higher mobility. The functionally relevant motions were spread over the entire cap domain in DhlA, whereas they were more localized in LinB and DhaA. The highest amplitude of essential motions of DhlA was noted in the α4′‐helix‐loop‐α4‐helix region, formerly proposed to participate in the large conformation change needed for product release. The highest amplitude of essential motions of LinB and DhaA was observed in the random coil before helix 4, linking two domains of these proteins. This flexibility is the consequence of the modular composition of haloalkane dehalogenases. Two members of the catalytic triad, that is, the nucleophile and the base, showed a very high level of rigidity in all three dehalogenases. This rigidity is essential for their function. One of the halide‐stabilizing residues, important for the catalysis, shows significantly higher flexibility in DhlA compared with LinB and DhaA. Enhanced flexibility may be required for destabilization of the electrostatic interactions during the release of the halide ion from the deeply buried active site of DhlA. The exchange of water molecules between the enzyme active site and bulk solvent was very different among the three dehalogenases. The differences could be related to the flexibility of the cap domains and to the number of entrance tunnels.
Pulmonary reflexes: neural mechanisms of pulmonary defense.

In his 1954 Harvey lecture on the functions of the lung, Comroe divided pulmonary reflexes into regulatory and defensive or protective (18). Char­ acteristically, regulatory reflexes are subject to a continuous input from low-threshold afferent endings whose impulse frequency waxes and wanes as their effective stimulus (e.g. volume or pressure) varies around a control or resting setpoint. Reflexes of this type exert a continuous control of ventilatory events (11) and promote the smooth interaction of the ventilatory and cardiovascular systems (13), their predominant function being to main­ tain the status quo. Defensive reflexes are a broader constellation of reflex responses evoked by stimuli that threaten lung function. These reflexes are the subject of the present review. Both regulatory and defensive reflexes are mediated predominantly by afferent fibers traveling to the medullary centers in the vagus nerves. The sensory innervation of the lower airways includes a component whose cell bodies are in the upper thoracic dorsal root ganglia and whose fibers travel to the spinal cord with branches of the sympathetic nerves. However, these so-called sympathetic afferents appear to play a relatively minor part in pulmonary defensive reflexes, and even powerful chemical stimuli applied to their endings cause little more than a brief disturbance of breathing (14, 19). Pulmonary defensive reflexes (or effects indistinguishable from them) are not only triggered by extrinsic agents such as irritant gases that pose a threat to the airways, but can be
Carbon dioxide correlation with oxidant air pollution in the San Bernardino mountains of California.

Ambient CO/sub 2/ concentrations in the San Bernardino Mountains fluctuate directly with the level of air pollution and are generally highest when O/sub 3/ levels are highest. Published laboratory studies employing unstressed plants and plants stressed by nitrogen and sulfur oxides have shown that CO/sub 2/ concentrations above normal ambient levels do have a stimulatory effect on net photosynthesis. This stimulatory effect can wholly or partially offset pollutant injury, depending on CO/sub 2/ and pollutant levels as well as other environmental conditions. Clearly this potential amelioration of pollutant effects must be taken into account in any attempt to understand and predict the effects of pollutants on plants.
Impact of organic polyelectrolytes on coagulation of source-separated black water

ABSTRACT Household wastewater is originated from common people's activities and has a potential harmful impact on the environment if discharged directly without proper treatment. Toilet wastewater or black water (BW) contains urine, faeces, toilet paper and flushing water and it contains the majority of pollutants obtained from a single household. In this study, the focus was on BW treatment using chemical methods. The main goal of current research was to define the possibility and applicability of conventional coagulants and flocculants in direct chemical treatment of vacuum-collected BW to remove particles, organic matter and phosphorous. After the definition of dosing ranges, based on the equivalent doses in conventional municipal and industrial wastewater treatment data, aluminium and iron coagulants, organic polyelectrolytes (polymers with anionic, neutral and cationic charge with different molecular weights) and their various combinations were tested using the well-known jar-test laboratory method to study aggregation and solid–liquid separation processes in raw BW. The most important process parameter during the coagulation was pH level, dependent on the type and doses of metal salts. Some side processes were found to occur while using iron-based coagulants. Dosing of either single coagulants or single polymers did not give satisfactory results, while a combination of aluminium salts and cationic polymers showed high removal rates in total suspended solids, total chemical oxygen demand and ortho-phosphates, reaching 97.8%, 92% and 98.6%, respectively, with the optimal doses of chemicals. Cationic polymers with the lowest molecular weight and highest charge density were the most efficient in combination with aluminium coagulants.
A hybrid test compression technique for efficient testing of systems-on-a-chip

One of the major challenges in testing a System-on-a-Chip (SOC) is dealing with the large test data size. To reduce the volume of test data, several efficient test data compression techniques have been recently proposed. In this paper, we propose hybrid test compression techniques that combine the Geometric-Primitives-Based compression technique with the frequency-directed run-length (FDR) and extended frequency-directed run-length (EFDR) coding techniques. Based on experimental results, we demonstrate the effectiveness of the proposed hybrid compression techniques in increasing the test data compression ratios over those obtained by the Geometric-Primitives-Based compression technique.
Predictors of parenting stress among Malaysian mothers of children with Down syndrome.

BACKGROUND Having children with intellectual disability can be stressful for most parents. Currently there are very few studies focusing on parenting stress among mothers of children with Down syndrome (DS) in Asia. The present study examined the level of parenting stress experienced by Malaysian mothers of children with DS and evaluated the child and maternal factors that contributed to parenting stress based on Hill's ABC-X Model (Hill 1949). METHODS We conducted a cross-sectional study of mothers of children with DS between the ages of 2-12 years during February-June 2008 in Kedah, a state in Peninsular Malaysia. We used self-administered questionnaires to gather data on parenting stress, child's birth history and current behavioural problems, as well as the maternal sociodemographic characteristics, coping styles and psychological well-being. Parental Stress Scale (PSS) was used to assess parenting stress. Measures of child's behavioural problem using Pediatric Symptom Checklist, mother's coping style using Carver et al. (1989) COPE inventory and their psychological well-being using Lovibond and Lovibond (1995) DASS21, a scale assessing depression, anxiety and stress were also carried out. RESULTS The 147 mothers who participated in the study had an average age of 43.1 years (SD = 7.6 years), of whom 94.6% were married, 57.1% had secondary level education and 28.6% were working outside their home. Based on PSS, mean parenting stress was 37.6 (SD = 8.1). Parenting stress was significantly higher among mothers who reported having children with behavioural problems. However, parenting stress was modified by positive coping styles and negative maternal psychological well-being. The final model based on hierarchical regression analysis identified maternal depression and lack of acceptance as significant predictors of parenting stress rather than child's behavioural problems. CONCLUSION Mean parenting stress among mothers of children with DS significantly differed by behavioural problems in their children. Parenting stress is also significantly correlated with frequent use of acceptance, religious and optimist coping styles, and presence of maternal depressive, anxiety and stress symptoms. However, hierarchical regression analysis identified maternal depression and lack of acceptance of having a child with DS as the most significant predictors of parenting stress in these mothers.
Crystallographic and Spectroscopic Studies of d(CCGGTACCGG)

The decanucleotide sequence d(CCGGTACCGG) crystallizes as a four-way junction at low cobalt ion concentrations (i.e., 1 mM). When the cobalt concentration in the crystallization solution is increased to 5 mM, the sequence crystallizes as resolved B-DNA duplexes. Gel retardation studies of the decamer show both a faint slow-moving band and a much thicker fast-moving band at low cobalt ion concentrations, and only the intense fast-moving band at higher ion concentration. Circular dichroism (CD) spectroscopy of the decamer indicates a structural transition as the cobalt ion concentration in the solution is increased, probably from B-type to A-type DNA. These studies revealed that the oligomer sequence has several conformations and structures accessible to it, in a manner dependent on sequence, ion concentration, and DNA concentration. [Supplementary materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids for the following free supplemental resources(s): Supplementary Figures 1, 2, and 3. ]
Screening and identification of a Bacillus thuringiensis strain S1/4 with large and efficient insecticidal activities

The bacterium Bacillus thuringiensis was recognized for its entomopathogenic activities related to Cry and Cyt proteins forming the δ‐endotoxins and some extracellular activities like the vegetative insecticidal proteins (VIP) and Cry1I. These activities may act specifically against diverse organisms and some of them typically characterize each strain. Here, we screened a set of 212 B. thuringiensis strains to search the higher insecticidal activities. These strains had bipyramidal and cubic crystal morphologies and 30% of them showed PCR amplification of vip3 internal region, from which five isolates (S1/4, S17, S122, S123, and S144) showed plasmid profile variability. These five strains contained the cry1I, cry1Aa and/or cry1Ac, cry1Ab and cry2 genes, and S1/4 harbored in addition the cry1C, vip1, and vip2 genes. They produced from 25 to 46 µg δ‐endotoxin per 107 spores. Their δ‐endotoxins displayed distinct lethal concentrations 50% against either Spodoptera littoralis or Ephestia kuehniella larvae with the lowest one for S1/4, which was also active against Tuta absoluta. Fortunately, the analysis of the culture supernatants revealed that S1/4 had the higher toxicity towards these lepidopteron but it did not show any toxicity against the Tribolium castaneum coleopteran larvae; additionally, S1/4 displayed an antibacterial activity. S1/4 is a good candidate for agricultural pest control, as it is more efficient than the reference strain HD1.
Ceftaroline fosamil use in hospitalized patients with acute bacterial skin and skin structure infections: Budget impact analysis from a hospital perspective.

PURPOSE The budgetary impact of adding ceftaroline fosamil to a hospital formulary for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) was evaluated. METHODS A three-year hospital budget impact model was constructed with three initial treatment options for ABSSSIs: ceftaroline fosamil, vancomycin plus aztreonam, and other vancomycin-containing regimens. The target population was hospitalized adult patients with an ABSSSI. Clinical cure rates with initial treatment were assumed to be similar to those from ceftaroline fosamil clinical trials. Patients who did not respond to initial treatment were assumed to be treated successfully with second-line antimicrobial therapy. Length of stay and cost per hospital day (by success or failure with initial treatment) were estimated based on a large database from more than 100 U.S. hospitals. Other model inputs included the annual number of ABSSSI admissions, projected annual case growth rate, proportion of ABSSSI target population receiving vancomycin-containing regimen, expected proportion of ABSSSI target population to be treated with ceftaroline fosamil, drug acquisition cost, cost of antibiotic administration, and cost of vancomycin monitoring. Sensitivity analysis using 95% confidence limits of clinical cure rates was also performed. RESULTS The estimated total cost of care for treating a patient with an ABSSSI was $395 lower with ceftaroline fosamil ($15,087 versus $15,482) compared with vancomycin plus aztreonam and $72 lower ($15,087 versus $15,159) compared with other vancomycin-containing regimens. CONCLUSION Model estimates indicated that adding ceftaroline fosamil to the hospital formulary would not have a negative effect on a hospital's budget for ABSSSI treatment.
Evaluation of in vivo genotoxicity induced by N‐ethyl‐N‐nitrosourea, benzo[a]pyrene, and 4‐nitroquinoline‐1‐oxide in the Pig‐a and gpt assays

The recently developed Pig‐a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor‐deficient red blood cells caused by a forward mutation in the Pig‐a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig‐a assay could be integrated into repeat‐dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig‐a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N‐ethyl‐N‐nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4‐nitroquinoline‐1‐oxide (4NQO, 50 mg/kg) in the Pig‐a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig‐a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7‐week terminal sacrifice. ENU increased both Pig‐a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig‐a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two‐ or threefold above control) were detected in the bone marrow in both the Pig‐a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig‐a mutation assay in order to use it as an alternative to the TGR mutation assay. Environ. Mol. Mutagen. 54:747–754, 2013. © 2013 Wiley Periodicals, Inc.
apple Watch 把苹果戴在手上

在市面上已有大量智能手表的情况下,作为全球最知名的数码产品生产商,苹果公司的智能手表自然拥有其独一无二之处 在最新出版的《VOGUE服饰与美容》中国版11月刊封面上,引人注意的除了超级名模刘雯,还有她手腕上佩戴的那块苹果手表。