Miracle-dz/UniFAR-FTUs huggingface dataset:
The kidneys and ANCA-associated vasculitis: from pathogenesis to diagnosis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of pauci-immune small vessel vasculitides that often affect the kidneys manifesting as rapidly progressive glomerulonephritis. Although the exact pathogenesis of AAV is not fully known, evidence from in vitro, in vivo and clinical studies all point to the involvement of ANCA in the pathogenesis of AAV. In this review, we highlight the contributory roles played by various factors (e.g. genetics, environment, B and T-regulatory cells, toll-like receptors, etc.) in the pathogenesis of AAV. Furthermore, we discuss renal involvement in AAV in terms of clinical features and the various histopathological classification patterns, which are also known to be of prognostic importance. We also present information on useful imaging techniques for localizing kidney and other organ system involvement in AAV, and also on novel laboratory methods and assays useful for rapid and more specific determination of patients' ANCA status. Finally, we demonstrate evidence on novel serum biomarkers that have been shown to correlate with disease activity in AAV.
Leptin Activates Hepatic 5′-AMP-activated Protein Kinase through Sympathetic Nervous System and α1-Adrenergic Receptor

Background: AMPK activation promotes glucose and lipid metabolism. Results: Hepatic AMPK activities were decreased in fatty liver from lipodystrophic mice, and leptin activated the hepatic AMPK via the α-adrenergic effect. Conclusion: Leptin improved the fatty liver possibly by activating hepatic AMPK through the central and sympathetic nervous systems. Significance: Hepatic AMPK plays significant roles in the pathophysiology of lipodystrophy and metabolic action of leptin. Leptin is an adipocyte-derived hormone that regulates energy homeostasis. Leptin treatment strikingly ameliorates metabolic disorders of lipodystrophy, which exhibits ectopic fat accumulation and severe insulin-resistant diabetes due to a paucity of adipose tissue. Although leptin is shown to activate 5′-AMP-activated protein kinase (AMPK) in the skeletal muscle, the effect of leptin in the liver is still unclear. We investigated the effect of leptin on hepatic AMPK and its pathophysiological relevance in A-ZIP/F-1 mice, a model of generalized lipodystrophy. Here, we demonstrated that leptin activates hepatic AMPK through the central nervous system and α-adrenergic sympathetic nerves. AMPK activities were decreased in the fatty liver of A-ZIP/F-1 mice, and leptin administration increased AMPK activities in the liver as well as in skeletal muscle with significant reduction in triglyceride content. Activation of hepatic AMPK with A769662 also led to a decrease in hepatic triglyceride content and blood glucose levels in A-ZIP/F-1 mice. These results indicate that the down-regulation of hepatic AMPK activities plays a pathophysiological role in the metabolic disturbances of lipodystrophy, and the hepatic AMPK activation is involved in the therapeutic effects of leptin.
Female common lizards (Lacerta vivipara) do not adjust their sex‐biased investment in relation to the adult sex ratio

Sex allocation theory predicts that facultative maternal investment in the rare sex should be favoured by natural selection when breeders experience predictable variation in adult sex ratios (ASRs). We found significant spatial and predictable interannual changes in local ASRs within a natural population of the common lizard where the mean ASR is female‐biased, thus validating the key assumptions of adaptive sex ratio models. We tested for facultative maternal investment in the rare sex during and after an experimental perturbation of the ASR by creating populations with female‐biased or male‐biased ASR. Mothers did not adjust their clutch sex ratio during or after the ASR perturbation, but produced sons with a higher body condition in male‐biased populations. However, this differential sex allocation did not result in growth or survival differences in offspring. Our results thus contradict the predictions of adaptive models and challenge the idea that facultative investment in the rare sex might be a mechanism regulating the population sex ratio.
Time-Varying Yield Curve Dynamics and Monetary Policy

The dynamics of the US economy are modelled using a time-varying structural vector autoregression that incorporates information from the yield curve. We find important changes in the dynamics of macroeconomic variables such as inflation and the federal funds rate. In addition our results suggest a change in the relationship between the yield curve and macroeconomic variables. The monetary policy shocks of the early 1980s explain a large portion of the persistence of inflation and the level of the yield curve. Shocks to the level of the yield curve account for the persistence of the federal funds rate. We use our time-varying model provides to revisit the evidence on the expectations hypothesis.
Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock

Global translation is inhibited in Saccharomyces cerevisiae cells under osmotic stress; nonetheless, osmostress-protective proteins are synthesized. We found that translation mediated by the mRNA cap-binding protein Cbc1 is stress-resistant and necessary for the rapid translation of osmostress-protective proteins under osmotic stress.
Tomato Bushy Stunt Virus Genomic RNA Accumulation Is Regulated by Interdependent cis-Acting Elements within the Movement Protein Open Reading Frames

ABSTRACT This study on Tomato bushy stunt virus identified and defined three previously unknown regulatory sequences involved in RNA accumulation that are located within the 3′-proximal nested movement protein genes p22 and p19. The first is a 16-nucleotide (nt) element termed III-A that is positioned at the very 3′ end of p22 and is essential for RNA accumulation. Approximately 300 nt upstream of III-A resides an ∼80-nt inhibitory element (IE) that is obstructive to replication only in the absence of a third regulatory element of ∼30 nt (SUR-III) that is positioned immediately upstream of III-A. Inspection of the nucleotide sequences predicted that III-A and SUR-III can form looped hairpins. A comparison of different tombusviruses showed, in each case, conservation for potential base pairing between the two predicted hairpin-loops. Insertion of a spacer adjacent to the predicted hairpins had no or a minimal effect on RNA accumulation, whereas an insertion in the putative III-A loop abolished genomic RNA multiplication. We conclude that the sequences composing the predicted III-A and SUR-III hairpin-loops are crucial for optimal RNA accumulation and that the inhibitory effect of IE surfaces when the alleged interaction between SUR-III and III-A is disturbed.
No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily Oral HIV Preexposure Prophylaxis

Objective Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior. Design and methods Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy. Results Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12). Conclusions There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.
Unique patterns of CpG island methylation in inflammatory bowel disease‐associated colorectal cancers

Background: CpG island (CGI) hypermethylation at discrete loci is a prevalent cancer‐promoting abnormality in sporadic colorectal carcinomas (S‐CRCs). We investigated genome‐wide CGI methylation in inflammatory bowel disease (IBD)‐associated CRCs (IBD‐CRCs). Methods: Methylation microarray analyses were conducted on seven IBD‐CRCs, 17 S‐CRCs, and eight normal control colonic tissues from patients without CRC or IBD. CGI methylator phenotype (CIMP), a surrogate marker for widespread cancer‐specific CGI hypermethylation, was examined in 30 IBD‐CRCs and 43 S‐CRCs. Results: The genome‐wide CGI methylation pattern of IBD‐CRCs was CIMP status‐dependent. Based on methylation array data profiling of all autosomal loci, CIMP+ IBD‐CRCs grouped together with S‐CRCs, while CIMP− IBD‐CRCs grouped together with control tissues. CIMP− IBD‐CRCs demonstrated less methylation than did age‐matched CIMP− S‐CRCs at autosomal CGIs (z‐score −0.17 vs. 0.09, P = 3 × 10−3) and CRC‐associated hypermethylation target CGIs (z‐score −0.43 vs. 0.68, P = 1 × 10−4). Age‐associated hypermethylation target CGIs were significantly overrepresented in CGIs that were hypermethylated in S‐CRCs (P = 1 × 10−192), but not in CGIs that were hypermethylated in IBD‐CRCs (P = 0.11). In contrast, KRAS mutation prevalence was similar between IBD‐CRCs and S‐CRCs. Notably, CIMP+ prevalence was significantly higher in older than in younger IBD‐CRC cases (50.0 vs. 4.2, P = 0.02), but not in S‐CRC cases (9.7 vs. 16.7, P = 0.92). Conclusions: Cancer‐specific CGI hypermethylation and age‐associated CGI hypermethylation are diminished in IBD‐CRCs relative to S‐CRCs, while the KRAS mutation rate is comparable between these cancers. CGI hypermethylation appears to play only a minor role in IBD‐associated carcinogenesis. We speculate that aging, rather than inflammation per se, promotes CIMP+ CRCs in IBD patients. (Inflamm Bowel Dis 2011;)
Emotional and behavioral problems in migrant children.

OBJECTIVES To assess emotional (depression, anxiety and self-esteem) and behavioural problems in migrant children and to compare them with non-migrant children. METHODS 526 students (60% boys, 40% girls) aged 11.23 +/- 1.05, at five schools in Adana, Turkey in areas with a high migrant population were included in this study. 182 children (35%) were migrants and 344 children (65%) were non-migrants. The Depression Inventory for Children (CDI), the State-Trait Anxiety Inventory for Children (STAI-C) and the Coopersmith Self-Esteem Inventory (CSEI) were administered to the pupils at their school and Rutter's Teachers Rating Scale (RTRS) was administered to their teachers. Sociodemographic variables were recorded on the basis of school records and the children's report. RESULTS In the migrant group, fathers were less educated and had more employment problems, homes were rented and the children were unsuccessful at school. Migrant children had significantly lower self-esteem with higher depression and anxiety. Behavioural symptoms on RTRS were not significant with regard to migration. No significant correlation was found between psychometric tests and father's education, duration of residence after migration or room density. CONCLUSIONS We found significant emotional but no behavioural problems in Turkish migrant children compared to Turkish non-migrant children. Further prospective studies are needed to clarify the long-term course of the various types of distress and the individual prognosis of migrant adjustment.
Cardiovascular Effects of Secondhand Smoke: Nearly as Large as Smoking

Background—Secondhand smoke increases the risk of coronary heart disease by ≈30%. This effect is larger than one would expect on the basis of the risks associated with active smoking and the relative doses of tobacco smoke delivered to smokers and nonsmokers. Methods and Results—We conducted a literature review of the research describing the mechanistic effects of secondhand smoke on the cardiovascular system, emphasizing research published since 1995, and compared the effects of secondhand smoke with the effects of active smoking. Evidence is rapidly accumulating that the cardiovascular system—platelet and endothelial function, arterial stiffness, atherosclerosis, oxidative stress, inflammation, heart rate variability, energy metabolism, and increased infarct size—is exquisitely sensitive to the toxins in secondhand smoke. The effects of even brief (minutes to hours) passive smoking are often nearly as large (averaging 80% to 90%) as chronic active smoking. Conclusions—The effects of secondhand smoke are substantial and rapid, explaining the relatively large risks that have been reported in epidemiological studies.
A catalogue quality audit tool

The current need for performance measurement and quality targets for services to users requires suitable performance indicators for libraries to use. This paper looks at the self‐assessment audit tool for catalogue quality developed by UKOLN in collaboration with Essex libraries. For the tool a checklist of errors was drawn up, which can then be used to assess the quality of records within a catalogue using a sample of library stock. The tool can be used to assess the quality of catalogue records for monographs and non‐book materials (but not serials), for complete collections or parts of collections and for records created at different periods. This paper describes the tool and the process of making the assessment and reports on the results of the pilot study carried out at the University of Bath library in 2000.
Decay of interspecific avian flock networks along a disturbance gradient in Amazonia

Our understanding of how anthropogenic habitat change shapes species interactions is in its infancy. This is in large part because analytical approaches such as network theory have only recently been applied to characterize complex community dynamics. Network models are a powerful tool for quantifying how ecological interactions are affected by habitat modification because they provide metrics that quantify community structure and function. Here, we examine how large-scale habitat alteration has affected ecological interactions among mixed-species flocking birds in Amazonian rainforest. These flocks provide a model system for investigating how habitat heterogeneity influences non-trophic interactions and the subsequent social structure of forest-dependent mixed-species bird flocks. We analyse 21 flock interaction networks throughout a mosaic of primary forest, fragments of varying sizes and secondary forest (SF) at the Biological Dynamics of Forest Fragments Project in central Amazonian Brazil. Habitat type had a strong effect on network structure at the levels of both species and flock. Frequency of associations among species, as summarized by weighted degree, declined with increasing levels of forest fragmentation and SF. At the flock level, clustering coefficients and overall attendance positively correlated with mean vegetation height, indicating a strong effect of habitat structure on flock cohesion and stability. Prior research has shown that trophic interactions are often resilient to large-scale changes in habitat structure because species are ecologically redundant. By contrast, our results suggest that behavioural interactions and the structure of non-trophic networks are highly sensitive to environmental change. Thus, a more nuanced, system-by-system approach may be needed when thinking about the resiliency of ecological networks.
The degrees of freedom region of the two-user MIMO broadcast channel with delayed CSIT

The degrees of freedom (DoF) region of the K-user MIMO (multiple-input multiple-output) Gaussian broadcast channel (BC) is studied under i.i. d. fading when there is delayed channel state information at the transmitter (CSIT). The general case of the MIMO BC is considered where each terminal has an arbitrary number of antennas. The delayed CSIT assumption is that the transmitter has perfect knowledge of ‘stale’ channel states (i.e., with some delay) but no knowledge of current CSI. An outer-bound to the DoF region is derived. This bound is shown to be tight in the 2-user case via an interference alignment scheme that optimally accounts for multiple and possibly distinct number of antennas at the two receivers.
Fabrication of copper-based microchannel devices and analysis of their flow and heat transfer characteristics

Metal-based microchannel heat exchangers (MHEs) offer potential solutions to high heat flux removal applications, such as cooling of high-performance microelectronic and energy-efficient lighting modules. Efficient fabrication of metal-based MHEs and quantitative flow and heat transfer measurements on them are critical for establishing the economic and technical feasibility of such devices. In this paper, all-Cu MHE prototypes were fabricated. Results of flow and heat transfer testing made on these Cu-based MHE prototypes are reported. Efficient fabrication of Cu-based high-aspect-ratio microscale structures (HARMSs) was achieved through direct molding replication using surface-engineered metallic mold inserts. Replicated Cu HARMSs were assembled through solid-state bonding to form all-Cu MHE prototypes. Flow and heat transfer testing of the Cu MHE prototypes was conducted to determine the average rate of heat transfer from the solid Cu body to water flowing within the enclosed microchannel array. Experimentally observed flow and heat transfer data are analyzed and shown to agree with known macroscale correlations once surface roughness and entrance length effects are taken into account.
Genetic contributions to the classification of renal cell cancer

The chromosomal pattern of thirty-one specimens of chromophilic renal cell cancer (RCC), selected according to the criteria mentioned in the classification of Thoenes and Störkel, is presented. A high male preponderance was found (8.7:1). Cytogenetic analysis revealed a typical pattern of numeric alterations specific for this subtype in the majority of cases (i.e. -Y, +7, +12, +16, +17, and/or +20) , which is different from the chromosomal patterns found in other subtypes of RCC. Gain of chromosome 20 as well as loss of the extra copy of chromosome 17 or loss of 17p was found to be related to the higher grade chromophilic carcinomas. None of the fourteen cases examined by SSCP analysis revealed mutations of the p53 gene, indicating that other genes at 17(p) might be important in the progression of this subtype of RCC.
Cardiac neural crest is dispensable for outflow tract septation in Xenopus

In vertebrate embryos, cardiac precursor cells of the primary heart field are specified in the lateral mesoderm. These cells converge at the ventral midline to form the linear heart tube, and give rise to the atria and the left ventricle. The right ventricle and the outflow tract are derived from an adjacent population of precursors known as the second heart field. In addition, the cardiac neural crest contributes cells to the septum of the outflow tract to separate the systemic and the pulmonary circulations. The amphibian heart has a single ventricle and an outflow tract with an incomplete spiral septum; however, it is unknown whether the cardiac neural crest is also involved in outflow tract septation, as in amniotes. Using a combination of tissue transplantations and molecular analyses in Xenopus we show that the amphibian outflow tract is derived from a second heart field equivalent to that described in birds and mammals. However, in contrast to what we see in amniotes, it is the second heart field and not the cardiac neural crest that forms the septum of the amphibian outflow tract. In Xenopus, cardiac neural crest cells remain confined to the aortic sac and arch arteries and never populate the outflow tract cushions. This significant difference suggests that cardiac neural crest cell migration into the cardiac cushions is an amniote-specific characteristic, presumably acquired to increase the mass of the outflow tract septum with the evolutionary need for a fully divided circulation.
ApoE genotypes in Australia: roles in early and late onset Alzheimer's disease and Down's syndrome

WE studied the apoE genotypes of 279 Australians in order to determine what relationships might exist in this group between apoE genotype and dementia associated with either early- or late-onset sporadic Alzheimer's disease (AD) or with Down's syndrome (DS). ApoE ϵ4 allele frequency was increased in Australians with either early-onset sporadic AD (p < 0.002) or late-onset sporadic AD (p < 0.0001) and apoE ϵ2 allele frequency was decreased in the late-onset sporadic AD group (p < 0.01). The apoE genotype distribution among patients with DS was not different from that of the control group. One individual with DS and an apoE ϵ4/ϵ4 genotype developed dementia at the earliest age of dementing DS patients, consistent with a role for apoE ϵ4 in determining age of onset of dementia in AD and DS. Another DS patient with an apoE ϵ2/ϵ3 genotype developed dementia within an age range similar to that of four demented DS patients with an apoE ϵ3/ϵ3 genotype, an observation which would appear inconsistent with the proposed protective effect of apoE ϵ2 to delay onset of dementia in DS. These results extend the evidence that the apoE genotype, particularly apoE ϵ4, modulates dementia in early- and late-onset sporadic AD and DS. The protective role of apoE ϵ2 in DS, however, may vary among different populations or ethnic groups.