Miracle-dz/UniFAR-FTUs huggingface dataset:
Onset of coeliac disease: a prospective longitudinal study

Aim: To make a prospective assessment of close family members of patients with coeliac disease (CD) by testing their endomysium (EMA) and antigliadin antibodies once a year over a period of 12 y and to investigate whether and when they would develop a positive serology for CD while on a gluten‐containing diet. Methods: Since first‐degree relatives of CD patients have a high prevalence of CD, we screened 92 children and adolescents, all first‐degree relatives of coeliac patients, for EMA and total IgA antibodies, once a year. Results: Among 11 relatives, at the time of the first screening, 6 already had a positive serology and histology for CD, while 5 became positive only after a period of 2 to 5 y of negative testing. The jejunal mucosa biopsy of these five relatives with retarded positive serology for CD showed a flat mucosa in four of them and a partial villous atrophy in one. They were all HLA DQ2 positive and clinically silent for CD.
Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer's Disease-Related Pathology

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that selectively attenuates proinflammatory cytokine production at low doses. MW-151 was tested in an APP/PS1 knock-in mouse model that exhibits increases in AD-relevant pathology progression with age, including increases in proinflammatory cytokine levels. Drug was administered during two distinct but overlapping therapeutic time windows of early stage pathology development. MW-151 treatment attenuated the increase in microglial and astrocyte activation and proinflammatory cytokine production in the cortex and yielded improvement in neurologic outcomes, such as protection against synaptic protein loss and synaptic plasticity impairment. The results also demonstrate that the therapeutic time window is an important consideration in efficacy studies of drugs that modulate glia biological responses involved in pathology progression and suggest that such paradigms should be considered in the development of new therapeutic regimens that seek to delay the onset or slow the progression of AD.
Rat whisker motor cortex is subdivided into sensory-input and motor-output areas

Rodent whisking is an exploratory behavior that can be modified by sensory feedback. Consistent with this, many whisker-sensitive cortical regions project to agranular motor [motor cortex (MI)] cortex, but the relative topography of these afferent projections has not been established. Intracortical microstimulation (ICMS) evokes whisker movements that are used to map the functional organization of MI, but no study has compared the whisker-related inputs to MI with the ICMS sites that evoke whisker movements. To elucidate this relationship, anterograde tracers were placed in posterior parietal cortex (PPC) and in the primary somatosensory (SI) and secondary somatosensory (SII) cortical areas so that their labeled projections to MI could be analyzed with respect to ICMS sites that evoke whisker movements. Projections from SI and SII terminate in a narrow zone that marks the transition between the medial agranular (AGm) and lateral agranular (AGl) cortical areas, but PPC projects more medially and terminates in AGm proper. Paired recordings of MI neurons indicate that the region between AGm and AGl is highly responsive to whisker deflections, but neurons in AGm display negligible responses to whisker stimulation. By contrast, AGm microstimulation is more effective in evoking whisker movements than microstimulation of the transitional region between AGm and AGl. The AGm region was also found to contain a larger concentration of corticotectal neurons, which could convey whisker-related information to the facial nucleus. These results indicate that rat whisker MI is comprised of at least two functionally distinct subregions: a sensory processing zone in the transitional region between AGm and AGl, and a motor-output region located more medially in AGm proper.
Reduced Activity of Anabolizing Enzymes in 5‐Fluorouracil‐resistant Human Stomach Cancer Cells

The mechanism of resistance to 5‐fluorouracil (5‐FU) was studied with NUGC‐3/5FU/L, a human stomach cancer cell line which had acquired resistance as a consequence of repeated 5‐day exposures to stepwise‐increasing concentrations of 5‐FU in vitro. NUGC‐3/5FU/L was 200‐fold and over 16‐fold resistant to 96‐h and 1‐h exposures to 5‐FU, respectively. NUGC‐3/5FU/L incorporated less 5‐FU into RNA, indicating resistance to the RNA‐directed action of 5‐FU. On the other hand, NUGC‐3/5FU/L also showed resistance to in situ thymidylate synthase (TS) inhibition by 5‐FU. Polymerase chain reaction‐single‐strand conformation polymorphism analysis of TS cDNA and a FdUMP ligand binding assay showed that quantitative and qualitative alterations of TS are not responsible for this resistance. In contrast, the ability to metabolize 5‐FU to its active metabolites, FUTP and FdUMP, was reduced in NUGC‐3/5FU/L. We found that not only the activities of uridine phosphorylase/kinase and orotate phosphoribosyl‐transferase (OPRT), but also the level of phosphoribosyl pyrophosphate, a cosubstrate for OPRT, were significantly lower in NUGC‐3/5FU/L than in the parent NUGC‐3. These results indicated that resistance to 5‐FU in NUGC‐3/5FU/L is due to reduced activities of 5‐FU‐anabolizing enzymes, but not to an alteration of TS. 2′‐Deoxyinosine effectively enhanced TS inhibition by 5‐FU in the resistant cells, thus markedly sensitizing them to 5‐FU.
The effect of chronic treadmill exercise and acetaminophen on collagen and cross-linking in rat skeletal muscle and heart.

UNLABELLED The purpose of this study was to determine whether exercise and/or acetaminophen (APAP) alter collagen and cross-linking in the rat gastrocnemius muscle, soleus muscle, and heart. Male Wistar rats (n = 50; 8 wk old) were divided into placebo (PLA) or APAP groups and sedentary (SED) or exercised (RUN) groups. APAP (200 mg/kg) was administered daily by oral gavage. Exercised groups ran on a treadmill 5 days/wk for 8 wk with progression to 60 min/day, 20 m/min, and 8° incline. Tissues were assayed for collagen (hydroxyproline) and hydroxylyslpyridinoline (HP) and lysylpyridinoline (LP) cross-links by HPLC. Collagen content (μg/mg dry weight) was greater in both the gastrocnemius (SED-PLA: 114 ± 16 vs. RUN-PLA 244 ± 32; P < 0.001) and soleus (SED-PLA: 51 ± 7 vs. RUN-PLA 99 ± 27; P = 0.005) of exercised animals. In contrast, collagen content was not significantly greater in exercised animals treated with APAP (SED-APAP: 113 ± 16 vs. RUN-APAP 145 ± 21) and soleus (SED-APAP: 55 ± 8 vs. RUN-APAP 57 ± 10). HP cross-linking (mmol/mol collagen) in the gastrocnemius (SED-PLA: 126 ± 28, RUN-PLA: 50 ± 7, SED-APAP: 41 ± 7, and RUN-APAP 30 ± 4) and soleus muscles (SED-PLA: 547 ± 107, RUN-PLA: 318 ± 92, SED-APAP: 247 ± 64, and RUN-APAP 120 ± 17) was lower in exercised rats compared with sedentary rats (P < 0.05). Cross-linking was further reduced in animals treated with APAP (P < 0.05). Neither heart collagen nor cross-linking was influenced by exercise or APAP (P > 0.05). Our findings suggest that exercise and APAP have tissue-specific effects on muscle collagen. Given the widespread use of APAP as an analgesic and antipyretic, further work in humans is warranted.
Immunobiological Characterization of Cancer Stem Cells Isolated from Glioblastoma Patients

Purpose: Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy. Experimental Design: GBM CSC lines and their fetal bovine serum (FBS)–cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively. Results: Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines. Conclusions: These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell–mediated immune response. Clin Cancer Res; 16(3); 800–13
A Spectrophotometric Study of Plumage Color in the Eared Dove (Zenaida auriculata), the Most Abundant South American Columbiforme

For birds, plumage color perception is critical in social interactions such as courtship, in both monochromatic and dichromatic species. In the Eared Dove (Zenaida auriculata), perhaps the most abundant South American Columbiforme, the plumage of males and females looks alike and both sexes share the same melanistic coloration with gray and pink tones. The aim of this study was therefore to determine whether evident sexual dichromatism exists in the plumage of the Eared Dove using a spectrophotometry technique in the avian-visible range (300–700 nm). The results of the classic colorimetric variables analysis (hue, chroma and brightness) show that males are in general brighter and have higher UV chroma values than females. The avian visual model points to differences in achromatic and chromatic levels between males and females in body regions possibly involved in sexual selection (e.g. the crown). The model also indicates chromatic or achromatic differences in body regions not subject to sexual selection such as the black spots on the wing coverts and white tail bands, both of which may be involved in intra- or inter-gender-specific communication.
Selective Subcarrier Pairing and Power Allocation for Decode-and-Forward OFDM Relay Systems

This paper investigates a Decode-and-Forward (DF) two-hop relaying system in which Orthogonal Frequency Division Multiplexing (OFDM) is used. The relay forwards the message received from the source on a subset of available subchannels in the second time slot. Firstly, a pairing and selecting algorithm is proposed. Then, power will be allocated to the both base station and relay station under individual power constraints in order to maximize the capacity. The pairing and selecting algorithm and resource allocation is based on instantaneous channel state information (ICSI). Finally, the simulation results show that selective relaying combined with subcarrier pairing and power allocation will improve the system capacity to a considerable extent.
Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis.

BACKGROUND Several clinical trials have investigated the impact of glucomannan on plasma lipids, body weight, fasting blood glucose (FBG), and blood pressure (BP), but have yielded conflicting results and had only modest sample sizes. OBJECTIVE The objective was to perform a meta-analysis of randomized controlled trials of glucomannan to better characterize its impact on plasma lipids, FBG, body weight, and BP. DESIGN A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through November 2007. A random-effects model was used to calculate the weighted mean difference (WMD) and 95% CIs as the difference between the mean for the glucomannan and control groups. Standard methods for assessing statistical heterogeneity and publication bias were used. RESULTS Fourteen studies (n = 531) met the inclusion criteria. The use of glucomannan significantly lowered total cholesterol [weighted mean difference (WMD): -19.28 mg/dL; 95% CI: -24.30, -14.26], LDL cholesterol (WMD: -15.99 mg/dL; 95% CI: -21.31, -10.67), triglycerides (WMD: -11.08 mg/dL; 95% CI: -22.07, -0.09), body weight (WMD: -0.79 kg; 95% CI: -1.53, -0.05), and FBG (WMD: -7.44 mg/dL; 95% CI: -14.16, -0.72). The use of glucomannan did not appear to significantly alter any other study endpoints. Pediatric patients, patients receiving dietary modification, and patients with impaired glucose metabolism did not benefit from glucomannan to the same degree. CONCLUSIONS Glucomannan appears to beneficially affect total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG, but not HDL cholesterol or BP.
European Conference on Information Systems ( ECIS ) 2007 Cooperation Technology and Timeliness of Information : Comparing Travelbooks , Wikis and Online Communities

Based on an information systems metaphor for virtual communities this paper discusses up-todateness as one crucial factor of travel information quality. Two empirical studies are presented which show that the up-to-dateness of information in travelbooks, wikis and in forum communities does not differ systematically. Based on this empirical evidence we focus on understanding the factors influencing the up-to-dateness of the three media. We propose a framework with three determining factors: 1) the initial up-to-dateness at the time the information is first available for the user 2) the information volatility in a certain domain and 3) the length of the revision cycles. From these factors we hypothesize a) that the initial up-to-dateness is best in travelbooks and worst in forums and b) that the revision cycle is shortest in forums and longest in travelbooks. Since wikis come close the initial up-to-dateness of travelbooks and its revision cycle is almost as short as in forums, we finally argue why we believe wikis to be the most up-to-date medium in the long run.
On the Improvement of Free-Energy Calculation from Steered Molecular Dynamics Simulations Using Adaptive Stochastic Perturbation Protocols

The potential of mean force (PMF) calculation in single molecule manipulation experiments performed via the steered molecular dynamics (SMD) technique is a computationally very demanding task because the analyzed system has to be perturbed very slowly to be kept close to equilibrium. Faster perturbations, far from equilibrium, increase dissipation and move the average work away from the underlying free energy profile, and thus introduce a bias into the PMF estimate. The Jarzynski equality offers a way to overcome the bias problem by being able to produce an exact estimate of the free energy difference, regardless of the perturbation regime. However, with a limited number of samples and high dissipation the Jarzynski equality also introduces a bias. In our previous work, based on the Brownian motion formalism, we introduced three stochastic perturbation protocols aimed at improving the PMF calculation with the Jarzynski equality in single molecule manipulation experiments and analogous computer simulations. This paper describes the PMF reconstruction results based on full-atom molecular dynamics simulations, obtained with those three protocols. We also want to show that the protocols are applicable with the second-order cumulant expansion formula. Our protocols offer a very noticeable improvement over the simple constant velocity pulling. They are able to produce an acceptable estimate of PMF with a significantly reduced bias, even with very fast perturbation regimes. Therefore, the protocols can be adopted as practical and efficient tools for the analysis of mechanical properties of biological molecules.
Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells

We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.
Heritable variation in the timing of spermatophore removal, a mechanism of post‐copulatory female choice in crickets

Female crickets can exert post‐copulatory mating preferences by prematurely removing a male’s spermatophore after copulation, which terminates sperm transfer. Although most models of sexual selection assume that female mating preferences are heritable, there has been little work addressing genetic variation underlying post‐copulatory mate choice. We used a paternal half‐sib design, in which different males were randomly assigned as mates to several females to create half‐sib families, to determine the heritability of spermatophore retention time in female house crickets, Acheta domesticus. There was significant additive genetic variance in the timing of spermatophore removal by females [h2 = 0.50 ± 0.19 (± SE)], suggesting that the timing of spermatophore removal is determined, in part, by the female’s own genotype independent of the quality of her mate. The relatively high heritability of spermatophore retention time may be reflective of the absence of strong selection on this trait, consistent with previous work showing no difference in the fitness of females permitted to freely remove the spermatophore of their mates and those forced to accept complete ejaculates.
A Reanalysis of the 1911–20 Atlantic Hurricane Database

Abstract A reanalysis of the Atlantic basin tropical storm and hurricane database (“best track”) for the period of 1911–20 has been completed. This reassessment of the main archive for tropical cyclones of the North Atlantic Ocean, Caribbean Sea, and Gulf of Mexico was necessary to correct systematic biases and random errors in the data as well as to search for previously unrecognized systems. A methodology for the reanalysis process for revising the track and intensity of tropical cyclone data is provided in detail. The dataset now includes several new tropical cyclones, excludes one system previously considered a tropical storm, makes generally large alterations in the intensity estimates of most tropical cyclones (both toward stronger and weaker intensities), and typically adjusts existing tracks with minor corrections. Average errors in intensity and track values are estimated for both open ocean conditions as well as for landfalling systems. Finally, highlights are given for changes to the more signi.
Evidence of involvement of GIRK 1 / GIRK 4 in long-term desensitization of cardiac muscarinic K 1 channels

Shui, Zhigang, Tomoko Takahashi Yamanushi, and Mark R. Boyett. Evidence of involvement of GIRK1/GIRK4 in long-term desensitization of cardiac muscarinic K channels. Am J Physiol Heart Circ Physiol 280: H2554–H2562, 2001. —The cardiac M2 muscarinic receptor/G protein/K channel system was studied in neonatal rat atrial cells cultured with and without 10 mM carbachol (CCh) for 24 h. Channel activity in CCh-pretreated cells was substantially reduced as a result of long-term desensitization regardless of whether the channel was activated by ACh in cell-attached patches or GTP in inside-out patches. Channel activity in CCh-pretreated cells was also low when the receptor was bypassed and the G protein and channel were directly activated by [g-S]GTP or both the receptor and G protein were bypassed and the channel was directly activated by trypsin. Finally, in CCh-pretreated cells, the whole cell K current was low when the channel was activated via the independent adenosine receptor. This suggests that the channel is involved in long-term desensitization. However, in CCh-pretreated cells, although the receptor was internalized, there was no internalization of the channel. We suggest that the function of the muscarinic K channel declines in long-term desensitization of the cardiac M2 muscarinic receptor/G protein/K channel system.
In Vitro Comparison of the Activity Requirements and Substrate Specificity of Human and Triboleum castaneum PINK1 Orthologues

Mutations in the gene encoding the mitochondrial kinase PINK1 cause early-onset familial Parkinson’s disease. To understand the biological function of PINK1 and its role in the pathogenesis of Parkinson’s disease, it is useful to study its kinase activity towards substrates both in vivo and in vitro. For in vitro kinase assays, a purified Triboleum castaneum PINK1 insect orthologue is often employed, because it displays higher levels of activity when compared to human PINK1. We show, however, that the activity requirements, and more importantly the substrate specificity, differ between both orthologues. While Triboleum castaneum PINK1 readily phosphorylates the PINKtide peptide and Histone H1 in vitro, neither of these non-physiological substrates is phosphorylated by human PINK1. Nonetheless, both Tc and human PINK1 phosphorylate Parkin and Ubiquitin, two physiological substrates of PINK1. Our results show that the substrate selectivity differs among PINK1 orthologues, an important consideration that should be taken into account when extrapolating findings back to human PINK1.