Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenovirus Exploits the Cellular Aggresome Response To Accelerate Inactivation of the MRN Complex

ABSTRACT Results reported here indicate that adenovirus 5 exploits the cellular aggresome response to accelerate inactivation of MRE11-RAD50-NBS1 (MRN) complexes that otherwise inhibit viral DNA replication and packaging. Aggresomes are cytoplasmic inclusion bodies, observed in many degenerative diseases, that are formed from aggregated proteins by dynein-dependent retrograde transport on microtubules to the microtubule organizing center. Viral E1B-55K protein forms aggresomes that sequester p53 and MRN in transformed cells and in cells transfected with an E1B-55K expression vector. During adenovirus infection, the viral protein E4orf3 associates with MRN in promyelocytic leukemia protein nuclear bodies before MRN is bound by E1B-55K. Either E4orf3 or E4orf6 is required in addition to E1B-55K for E1B-55K aggresome formation and MRE11 export to aggresomes in adenovirus-infected cells. Aggresome formation contributes to the protection of viral DNA from MRN activity by sequestering MRN in the cytoplasm and greatly accelerating its degradation by proteosomes following its ubiquitination by the E1B-55K/E4orf6/elongin BC/Cullin5/Rbx1 ubiquitin ligase. Our results show that aggresomes significantly accelerate protein degradation by the ubiquitin-proteosome system. The observation that a normal cellular protein is inactivated when sequestered into an aggresome through association with an aggresome-inducing protein has implications for the potential cytotoxicity of aggresome-like inclusion bodies in degenerative diseases.
Interactions of 2,3‐benzodiazepines and cydothiazide at AMPA receptors: patch clamp recordings in cultured neurones and area CA1 in hippocampal slices

1 The 2,3‐benzodiazepines GYKI 52466, GYKI 53405 and GYKI 53655 antagonized AMPA‐induced currents in cultured superior colliculus neurones in a non use‐dependent manner (steady state IC50S: GYKI 52466 9.8±0.6 μm; GYKI 53405 3.1±0.6 μm; GYKI 53655 0.8±0.1 μm). 2 Higher concentrations of all three antagonists slowed the onset kinetics and quickened the offset kinetics of AMPA‐induced currents indicative of an allosteric interaction with the AMPA recognition site. 3 Cydothiazide (3–300 μm) dramatically slowed desensitization of AMPA‐induced currents and potentiated steady state currents (EC50 10.0±2.5 μm) to a much greater degree than peak currents. Both τon and τoff were also increased by cydothiazide in a concentration‐dependent manner (EC50: τon 42.1±4.5 μm; τoff 31.6±6.6 μ.M). 4 Cydothiazide (10–100 μ.M) shifted the concentration‐response curves of the 2,3‐benzodiazepines to the right. For example, with 10 μm cydothiazide the IC50S of GYKI 52466 and GYKI 53405 on steady‐state AMPA‐induced currents were 57.9±9.5 and 41.6±1.5 μm respectively. 5 GYKI 53405 and GYKI 52466 concentration‐dependently reversed the effects of cydothiazide (100 μm) on offset kinetics (GYKI 53405 IC50 16.6±4.2 μm). However, the 2,3‐benzodiazepines were unable to reintroduce desensitization in the presence of cydothiazide and even concentration‐dependently slowed the onset kinetics of AMPA responses further (GYKI 53405 EC50 8.0±2.8 μm). 6 GYKI 52466 decreased the peak amplitude of hippocampal area CA1 AMPA receptor‐mediated exdtatory postsynaptic currents (e.p.s.cs) (IC50 10.8±0.8 μm) with no apparent effect on response kinetics. Cydothiazide prolonged the decay time constant of AMPA receptor‐mediated e.p.s.cs (EC50 35.7±6.5 μm) with less pronounced effects in slowing e.p.s.c. onset kinetics and increasing e.p.s.c. amplitude. 7 Cydothiazide (330 μm) shifted the concentration‐response curve for the effects of GYKI 52466 on AMPA receptor‐mediated e.p.s.c. peak amplitude to the right (GYKI 52466 IC50 26.9±9.4 μm). Likewise, GYKI 52466 (30–100 μm)) shifted the concentration‐response curve for the effects of cydothiazide on AMPA receptor‐mediated e.p.s.c. decay time constants to the right. 8 In conclusion, cydothiazide and the 2,3‐benzodiazepines seem to bind to different sites on AMPA receptors but exert strong allosteric interactions with one another and with other domains such as the agonist recognition site. The interactions of GYKI 52466 and cydothiazide on AMPA receptor‐mediated e.p.s.cs in area CA1 of hippocampal slices provide evidence that the decay time constant of these synaptic events are not governed by desensitization.
The effect of aging on glutathione peroxidase-i knockout mice-resistance of the lens to oxidative stress.

Populations of control, C, and glutathione peroxidase-1 (GPx-1) knockout mice, K, were studied over a period of 2 years. No significant difference was observed between the C and K populations with respect to longevity, vitality, weight, lens biochemistry or morphology based on light and electron microscopy. It was concluded that under normal animal room barrier facilities, GPx-1 is not required. Furthermore, C and K lenses placed in organ culture and observed over a 24 hr period were indistinguishable. Organ cultured C lenses degraded medium H(2)O(2)levels at only a slightly greater rate than K lenses and this did not appear to change with age. However, tertiary butyl hydroperoxide (TBHP) was degraded less effectively by K lenses and this deficiency increased with age. No indication of change in redox non-protein SH (equivalent to GSH) status was observed between C and K whole lenses or epithelial cell fractions. With H(2)O(2)stress, the drop in C and K non-protein SH was comparable and there was little change with age. Examination of the impact of photochemical stress with 1.5 microM riboflavin and 4% O(2)upon choline transport indicated considerable damage with both C and K lenses, but little difference between the two populations until 1 or 2 years of age when the K lenses appear more vulnerable. With TBHP, the detrimental effect on the K lenses is greater and is observed earlier than with photochemical stress suggesting that the K lens membrane function is more susceptible to phospholipid hydroperoxide stress than are C lenses. Light and electron microscopy of the oxidative stressed lenses indicates significant damage which was generally somewhat greater in the K lenses. TBHP was a more potent oxidant than photochemically generated oxidants particularly at the anterior pole. The overall results suggest that under normal conditions, at any age, the lens does not require the presence of GPx-1 but depending on the type of oxidative stress, the enzyme may significantly contribute to its defense and this dependency may increase with age.
Nutritional Regulation of Lignin Degradation by Phanerochaete chrysosporium

Previous studies have shown that a lignin-degrading system appears in cultures of the white rot fungus Phanerochaete chrysosporium in response to nitrogen starvation, apparently as part of secondary metabolism. We examined the influence of limiting carbohydrate, sulfur, or phosphorus and the effect of varying the concentrations of four trace metals, Ca2+, and Mg2+. Limitation of carbohydrate or sulfur but not limitation of phosphorus triggered ligninolytic activity. When only carbohydrate was limiting, supplementary carbohydrate caused a transient repression of activity. In carbohydrate-limited cultures, ligninolytic activity appeared when the supplied carbohydrate was depleted, and this activity was associated with a decrease in mycelial dry weight. The amount of lignin degraded depended on the amount of carbohydrate provided, which determined the amount of mycelium produced during primary growth. Carbohydrate-limited cultures synthesized only small amounts of the secondary metabolite veratryl alcohol compared with nitrogen-limited cultures. l-Glutamate sharply repressed ligninolytic activity in carbohydrate-starved cultures, but NH4+ did not. Ligninolytic activity was also triggered in cultures supplied with 37 μM sulfur as the only limiting nutrient. The balance of trace metals, Mg2+, and Ca2+ was important for lignin degradation.
Narrative review of yoga intervention clinical trials including weight-related outcomes.

CONTEXT Medical authorities have identified obesity as a causal factor in the development of diabetes, hypertension, and cardiovascular disease (CVD), and more broadly, of metabolic syndrome/insulin resistance syndrome. To provide solutions that can modify this risk factor, researchers need to identify methods of effective risk reduction and primary prevention of obesity. Research on the effectiveness of yoga as a treatment for obesity is limited, and studies vary in overall quality and methodological rigor. OBJECTIVE This narrative review assessed the quantity and quality of clinical trials of yoga as an intervention for weight loss or as a means of risk reduction or treatment for obesity and diseases in which obesity is a causal factor. This review summarized the studies' research designs and evaluated the efficacy of yoga for weight loss via the current evidence base. DESIGN The research team evaluated published studies to determine the appropriateness of research designs, comparability of programs' intervention elements, and standardization of outcome measures. The research team's literature search used the key terms yoga and obesity or yoga and weight loss in three primary medical-literature databases (PubMed, PsychInfo, and Web of Science). The study excluded clinical trials with no quantitative obesity related measure. Extracted data included each study's (1) design; (2) setting and population; (3) nature, duration, and frequency of interventions; (4) comparison groups; (5) recruitment strategies; (6) outcome measures; (7) data analysis and presentation; and (8) results and conclusions. The research team developed an overall evaluation parameter to compare disparate trials. OUTCOME MEASURES The research team reviewed each study to determine its key features, each worth a specified number of points, with a maximum total of 20 points. The features included a study's (1) duration, (2) frequency of yoga practice, (3) intensity of (length of) each practice, (4) number of yogic elements, (5) inclusion of dietary modification, (6) inclusion of a residential component, (7) the number of weight-related outcome measures, and (8) a discussion of the details of the yogic elements. RESULTS Overall, therapeutic yoga programs are frequently effective in promoting weight loss and/or improvements in body composition. The effectiveness of yoga for weight loss is related to the following key features: (1) an increased frequency of practice; (2) a longer intervention duration (3) a yogic dietary component; (4) a residential component; (5) the comprehensive inclusion of yogic components; (5) and a home-practice component. CONCLUSIONS Yoga appears to be an appropriate and potentially successful intervention for weight maintenance, prevention of obesity, and risk reduction for diseases in which obesity plays a significant causal role.
Production of hydrolytic enzymes by Trichoderma isolates with antagonistic activity against Crinipellis perniciosa, the causal agent of witches' broom of cocoa

Two isolates of Trichoderma, which reduce the incidence of witches'broom disease caused in cocoa by Crinipellis perniciosa, were evaluated for their potential to produce hydrolases in liquid medium. Very low or no hydrolytic activity was produced in the absence of any substrate. The activities of chitinase, N-acetylglucosaminidase, b-1,3-glucanase, total cellulase, endoglucanase, aryl- b-glucosidase, b-glucosidase, protease and amylase increased dramatically within 72-120 h of growth in the presence of specific substrates. Except for N-acetylglucosaminidase and b-glucosidase Trichoderma harzianum isolate 1051 produced the largest amounts of hydrolases. The possible involvement of these enzymes in the antagonistic interaction between Trichoderma and C. perniciosa is discussed.
An improved accuracy version of the method of auxiliary sources for computational electromagnetics

The method of auxiliary sources (MAS) is normally applicable to electromagnetic problems involving structures of significant thickness, so that an adequately large distance between source and collocation points is guaranteed. For thin or open geometries the accuracy of the method is depleted, due to numerical instabilities caused by the highly singular terms of the dyadic Green's function (DGF). In this paper a modified MAS (MMAS) is developed to circumvent this particular difficulty. Higher order terms of the DGF are numerically calculated by introducing a canonical grid, where derivatives can be accurately computed via a discrete scheme, unlike standard MAS, where the DGF analytical, problematic expression is invoked instead. This procedure is equivalent to the involvement of auxiliary currents and charges in the solution, instead of the elementary source fields used in standard MAS.
Carbon nanotube-based hierarchical composites: a review

The introduction of carbon nanotubes (CNTs) into conventional fibre-reinforced polymer composites creates a hierarchical reinforcement structure and can significantly improve composite performance. This paper reviews the progress to date towards the creation of fibre reinforced (hierarchical) nanocomposites and assesses the potential for a new generation of advanced multifunctional materials. Two alternative strategies for forming CNT-based hierarchical composites are contrasted, the dispersion of CNTs into the composite matrix and their direct attachment onto the primary fibre surface. The implications of each approach for composite processing and performance are discussed, along with a summary of the measured improvements in the mechanical, electrical and thermal properties of the resulting hierarchical composites.
Immunological studies on human antithrombin 3. Influence of age, sex and use of oral contraceptives on serum concentration.

Isolation of what is probably the main thrombin inhibitor antithrombin III (At-III) made the preparation of specific antisera for immunochemical analysis possible. When immunoelectrophoresis of At III against anti At III and anti whole human serum was performed a single precipitation arc was formed in the alpha 2-globulin region. When thrombin was added the apparent concentration of At III decreased. Serum concentration of At III is probably influenced by sex hormones since women of childbearing age have lower serum concentrations of At III. They are further decreased by oral contraceptive implying a relationship between the low At III levels and the tendency to thrombosis in women using oral contraceptives.
Regulation of the differentiation‐related gene Drg‐1 during mouse skin carcinogenesis

Differentiation‐related gene‐1 (Drg‐1) has been identified as a gene whose expression is increased in several processes related to differentiation, but its function is currently unknown. In this report, we show that Drg‐1 was expressed in keratinocytes, this expression being rapidly increased as a result of induction by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) or the presence of an activating form of Ha‐ras. Induction by TPA occurred both in cultured cell lines and primary keratinocytes as well as in mouse skin after a single TPA application. Overexpression of Drg‐1 was also observed in TPA‐induced hyperplastic skin. In agreement, mouse skin papillomas and carcinomas also overexpressed Drg‐1. In addition, Drg‐1 was induced when keratinocytes were forced to differentiate by calcium switch or serum starvation. Analysis of the expression of Drg‐1 during the keratinocyte cell cycle demonstrated relatively high levels of Drg‐1 mRNA in G0, which increased in early G1 and decreased afterwards in late G1/S. In situ analysis showed an accumulation of Drg‐1 in the suprabasal layers of the skin, as well as in the more differentiated areas of mouse skin papillomas. These results suggest that, in addition to being upregulated during keratinocyte differentiation, the Drg‐1 gene might have a complex function in skin tumorigenesis. © 2001 Wiley‐Liss, Inc.
Spermatogenic activity of rhizomes of Curculigo orchioides Gaertn in male rats

ethanolic extract of rhizomes was evaluated for its effect on orientation behavior and spermatogenesis in albino rats. A change in orientation behavior was assessed by orientation towards female, towards environment, towards self and type of mobility. Administration of 100 mg/Kg b. w. of ethanolic extract had pronounced effect on orientation of male towards the female rats. Males treated with the extract displayed more frequent and vigorous anogenital sniffing and mounting as compared to untreated animals. The increased spermatogenesis in treated group was confirmed by change in histoarchitecture as evidenced by increase in number of spermatocyte and spermatids. These findings support the folk use of this plant as aphrodisiac. Industrial relevance: Study proposes to elucidate and demarcate the potential of Rasayan herbs in the treatment as well as uprooting the causes of disease; which is the underlying principle of Rasayana therapy. This leads to discovery of newer phytoconstituents with better activities and provide source of new biomolecules for biotechnologists to work on. The study explore the utilization of Rasyana herbs for effective management of sexual dysfunction. It brings out a competent literature on rasayana, validating their utilization. It gives a larger platform for the herbal cultivators by providing scientific support and data to the traditional unvalidated herbal drugs as rejuvenative tonics.
Genetics of ulcerative colitis: the come-back of interleukin 10

Crohn’s disease and ulcerative colitis are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract, affecting up to 0.4% of the population in Western countries.1 They are considered complex multifactorial polygenic diseases. While dramatic progress has been made in deciphering the genetic architecture of Crohn’s disease, ulcerative colitis was somewhat left behind, with virtually no relevant studies published until very recently. Although both disorders are considered to belong to the same spectrum of pathologies, the first gene clearly associated with Crohn’s disease ( CARD-15 )2 3 did not seem to predispose to ulcerative colitis in any cohort in which it was tested. This finding highlighted some pathogenic differences between the two diseases, and reminded geneticists working on inflammatory bowel diseases (IBDs) of the more modest contribution of genetics to the predisposition to ulcerative colitis, reflected in a lower ratio of disease concordance between monozygotic and dizygotic twins.4 The lower heritability of ulcerative colitis also accounts for the fact that most of the linkage studies performed in the 1990s did not include sufficient ulcerative colitis-affected sib pairs to disclose ulcerative colitis-related loci. With few exceptions,5 6 7 reports of associations with candidate genes have not been confirmed. Recently, major advances in cataloguing common genetic variants in humans combined with the development of high-throughput single nucleotide polymorphism (SNP) genotyping capacity, have made large-scale, genome-wide association studies (GWASs) with hundreds of thousands of common SNPs feasible. These have dramatically increased the list of loci shown to be associated with Crohn’s disease,8 9 10 11 12 13 and now also with ulcerative colitis14 15 16 17 (table 1). View this table: Table 1 Single nucleotide polymorphisms (SNPs) significantly associated with ulcerative colitis, identified through genome-wide association studies15 16 17 or systematic testing after significant association with Crohn’s disease in genome-wide association studies14 …
N-terminal and C-terminal cytosine deaminase domain of APOBEC3G inhibit hepatitis B virus replication.

AIM To investigate the effect of human apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G (APOBEC3G) and its N-terminal or C-terminal cytosine deaminase domain-mediated antiviral activity against hepatitis B virus (HBV) in vitro and in vivo. METHODS The mammalian hepatoma cells HepG2 and HuH7 were cotransfected with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vector and 1.3-fold-overlength HBV DNA as well as the linear monomeric HBV of genotype B and C. For in vivo study, an HBV vector-based mouse model was used in which APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vectors were co-delivered with 1.3-fold-overlength HBV DNA via high-volume tail vein injection. Levels of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in the media of the transfected cells and in the sera of mice were determined by ELISA. The expression of hepatitis B virus core antigen (HBcAg) in the transfected cells was determined by Western blot analysis. Core-associated HBV DNA was examined by Southern blot analysis. Levels of HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by quantitative PCR and quantitative RT-PCR analysis, respectively. RESULTS Human APOBEC3G exerted an anti-HBV activity in a dose-dependent manner in HepG2 cells, and comparable suppressive effects were observed on genotype B and C as that of genotype A. Interestingly, the N-terminal or C-terminal cytosine deaminase domain alone could also inhibit HBV replication in HepG2 cells as well as Huh7 cells. Consistent with in vitro results, the levels of HBsAg in the sera of mice were dramatically decreased, with more than 50 times decrease in the levels of serum HBV DNA and core-associated RNA in the liver of mice treated with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain as compared to the controls. CONCLUSION Our findings provide probably the first evidence showing that APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain could suppress HBV replication in vitro and in vivo.
Characterization of Mumps Virus Isolated in Saitama Prefecture, Japan, by Sequence Analysis of the SH Gene

Mumps virus (MuV) strains isolated from cerebrospinal fluid and throat swabs from patients in Saitama Prefecture and Tokyo, Japan, from 1997 to 2000 were examined by analyzing the SH gene nucleotide sequence (316‐nt). Eighteen of the 20 strains studied were divided into three genotypes, recognized as B, G, and H in previous reports. Two genotypes (G and H) are believed to be new in Japan. Two of the 20 strains belonged to none of the previously reported genotypes (A–I), but were closely related to two known strains, MP94‐H and Lougl/UK97. We propose that the two strains identified in this study together with the previously reported strains, MP94‐H and Lougl/UK97, form a new genotype, designated J, based on the divergence of the SH gene nucleotide sequences between these four strains and other strains reported (genotypes A–I). Our results also suggest that more than two genotypes circulated in Saitama Prefecture from 1997 to 1999, but only one, genotype G, was in evidence in 2000. Genotype B was earlier reported as the predominant strain in Japan, but it became undetectable by the year 2000. These results provide important epidemiological data on mumps in Japan.