Miracle-dz/UniFAR-FTUs huggingface dataset:
The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures

Clusterin is an extracellular chaperone present in all disease‐associated extracellular amyloid deposits, but its roles in amyloid formation and protein deposition in vivo are poorly understood. The current study initially aimed to characterize the effects of clusterin on amyloid formation in vitro by a panel of eight protein substrates. Two of the substrates (Alzheimer's beta peptide and a PI3‐SH3 domain) were then used in further experiments to examine the effects of clusterin on amyloid cytotoxicity and to probe the mechanism of clusterin action. We show that clusterin exerts potent effects on amyloid formation, the nature and extent of which vary greatly with the clusterin: substrate ratio, and provide evidence that these effects are exerted via interactions with prefibrillar species that share common structural features. Proamyloido‐genic effects of clusterin appear to be restricted to conditions in which the substrate protein is present at a very large molar excess;under these same conditions, clusterin coincorporates with substrate protein into insoluble aggregates. However, when clusterin is present at much higher but still substoichiometric levels (e.g., a molar ratio of clusterin:substrate = 1:10), it potently inhibits amyloid formation and provides substantial cytoprotection. These findings suggest that clus‐terin is an important element in the control of extracellular protein misfolding. —Yerbury, J. J., Poon, S. , Meehan, S. , Thompson, B. , Kumita, J. R. , Dobson, C. M. , Wilson, M. R. The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. FASEB J. 21, 2312–2322 (2007)
Progress in the Soviet Union on the theory and applications of bandlimited functions

An approach to the study of a wide class of linear systems and bandlimited signals is discussed. The mathematical method used is the applied branch of the well-developed theory of analytic entire functions of exponential type. The unified theory provides an adequate solution for problems, which are common to information theory, antenna pattern and filter design, optics, automatic control, and others. Sampling expansions are based on the entire function interpolating theory and are applied to the time discretizing and amplitude quantization. The synthesis problems are taken from the antenna synthesis theory and use the mean-square approximation with double orthogonal functions and also Chebyshev approximation with weighted polynomials. All synthesis problems are solved with a fixed parameter by which an implementation complexity is characterized. The reconstruction problems of the input from the linear system output is mixed with noise, of deconvolution, are discussed. The received results make the system resolution limit accurate. The problem of the finite control using mean-square metric is considered.
Neurochemical organization of chimpanzee inferior pulvinar complex

The pulvinar of primates, which connects with all visual areas, has been implicated in visual attention and in control of eye movements. Recently, five separate neurochemical subdivisions of a region termed the inferior pulvinar complex have been identified in monkeys (Gray et al. [ 1999 ] J Comp Neurol 409:452–468; Gutierrez et al. [ 1995 ] J Comp Neurol 363:545–562), and comparable subdivisions have been mapped in humans (Cola et al. [ 1999 ] NeuroReport 10:3733–3738). In the present study, we investigated the inferior pulvinar of the chimpanzee (Pan troglodytes), the closest evolutionary relative of humans, using cytochrome oxidase (CO) and acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for calbindin. Each staining method demarcated five histochemical zones corresponding, from medial to lateral, to the posterior (PIP), medial (PIM), central PIC), lateral (PIL), and the lateral‐shell (PIL‐S) divisions in monkeys. The PIP division stained darkly for calbindin and lightly for CO and AChE. The PIM division was characterized by less neuropil staining for calbindin, and by distinct, intensely stained patches of CO and AChE. PIC appeared lighter than adjacent divisions with CO and AChE histochemistry and was moderately stained with calbindin. PIL was moderately to darkly stained with each method and was adjoined by a lighter staining shell, PIL‐S. Thus, in the aspects of organization we examined, the inferior pulvinar of chimpanzees closely resembles that of humans and monkeys. This investigation provides a foundation for more detailed studies of the thalamic relationships of extrastriate cortex in apes and humans. J. Comp. Neurol. 484:299–312, 2005. © 2005 Wiley‐Liss, Inc.
Effect of whole saliva components on enamel demineralization in vitro.

The aim of the present study was to use an in vitro enamel demineralization model (1) to confirm that whole saliva pretreatment conferred acid resistance to dental enamel and (2) to determine whether this phenomenon was attributable to specific salivary proteins, minerals, lipids, or some combination of these. Crowns of human teeth, each with one exposed window, were prepared in groups of ten. They were each pretreated by immersion individually in 4 ml of either (1) clarified whole saliva for 18, 72, or 168 h, (2) dialyzed saliva (3500 MWCO membrane), (3) the "flow-through" fraction from a DEAE separation of whole saliva (neutral and basic proteins), (4) the "eluted" fraction of a DEAE separation of whole saliva (anionic proteins), or (5) a combination of salivary lipids and the DEAE "flow-through" fraction of whole saliva (neutral and basic proteins). Control groups were group 6 with no pretreatment, group 7 pretreated for 168 h in a borate buffer (5 mmol/l), and group 8 pretreated in a mineral solution containing calcium (0.7 mmol/l) and phosphate (2.6 mmol/l). The crowns were then demineralized for 7 d in vitro (0.1 mol/l acetate, 1 mmol/l Ca and phosphate, pH 5.0) to produce artificial caries-like lesions. Lesions were assessed by cross-sectional microhardness profiles, and mineral loss (delta Z, micron x vol% mineral) calculated. Mineral loss (delta Z) values decreased linearly with the square root of time of pretreatment by whole saliva, confirming a time-dependent protective effect of salivary pellicle against demineralization of enamel. (ABSTRACT TRUNCATED AT 250 WORDS)
Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M. tuberculosis Strains

Mycobacterium bovis causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of M. bovis named SP38, and performed comparative genomics of M. bovis genomes deposited in GenBank. M. bovis SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 M. bovis, 32 M. bovis BCG, and 23 Mycobacterium tuberculosis genomes available in GenBank were selected. M. bovis RDs (regions of difference) and Clonal Complexes (CC) were identified in silico. Genome dynamics of bacterial groups were analyzed by gene orthology and polymorphic sites identification. M. bovis polymorphic sites were used to construct a phylogenetic tree. Our RD analyses resulted in the exclusion of three genomes, mistakenly annotated as virulent M. bovis. M. bovis SP38 along with strain 35 represent the first report of CC European 2 in Brazil, whereas two other M. bovis strains failed to be classified within current CC. Results of M. bovis orthologous genes analysis suggest a process of genome remodeling through genomic decay and gene duplication. Quantification, pairwise comparisons and distribution analyses of polymorphic sites demonstrate greater genetic variability of M. tuberculosis when compared to M. bovis and M. bovis BCG (p ≤ 0.05), indicating that currently defined M. tuberculosis lineages are more genetically diverse than M. bovis CC and animal-adapted MTC (M. tuberculosis Complex) species. As expected, polymorphic sites annotation shows that M. bovis BCG are subjected to different evolutionary pressures when compared to virulent mycobacteria. Lastly, M. bovis phylogeny indicates that polymorphic sites may be used as markers of M. bovis lineages in association with CC. Our findings highlight the need to better understand host-pathogen co-evolution in genetically homogeneous and/or diverse host populations, considering the fact that M. bovis has a broader host range when compared to M. tuberculosis. Also, the identification of M. bovis genomes not classified within CC indicates that the diversity of M. bovis lineages may be larger than previously thought or that current classification should be reviewed.
Reduction of False-Negative Papillary Thyroid Carcinomas by the Routine Analysis of BRAFT1799A Mutation on Fine-Needle Aspiration Biopsy Specimens: A Prospective Study of 814 Thyroid FNAB Patients

Objectives:To evaluate prospectively the usefulness of the routine determination of BRAFT1799A mutation on thyroid fine-needle aspiration biopsy (FNAB) to detect cytopathology false negative papillary thyroid carcinomas (PTC) and, therefore, as a tool to improve the sensitivity of the preoperative cytopathological diagnosis of PTC in thyroid nodules. Background:FNAB is the most reliable diagnostic test to discriminate between malignant and benign thyroid nodules, but nondiagnostic results remain a clinical management dilemma. BRAFT1799A mutation is the most prevalent genetic alteration in thyroid cancers and is specific for PTC, characteristics that make it the most potentially helpful genetic tool to improve the diagnostic accuracy of FNAB. Methods:An exhaustive recruitment of all patients subjected to thyroid FNAB in our institution during 4 years was performed. BRAFT1799A mutation was determined on thyroid FNAB specimens by PCR and restriction fragment length polymorphism, plus direct sequencing in positive samples. Results:BRAFT1799A mutation on FNAB detected 47.2% (17/36) of PTC cases. It confirmed preoperatively 45.5% (5/11) of the PTC cases in the indeterminate category and decreased the rate of cytopathology false-negatives in 33.3% (6/18), improving the combined (BRAFT1799A mutation + cytopathological analysis) sensitivity of the detection of PTC on FNAB in 16.7%. Conclusions:BRAFT1799A mutation improves the diagnosis of PTC on FNAB, mainly because of the detection of cytopathology false-negatives, and it can be helpful in the routine analysis of thyroid nodules, especially in clinical settings with moderate sensitivity to detect PTC on FNAB.
Induction of apoptosis in lung‐cancer cells following bcl‐xL anti‐sense treatment

Over‐expression of the anti‐apoptotic protein bcl‐xL is frequently found in lung cancer where it potentially contributes to tumor development, progression and drug resistance. To override the apoptotic block in lung‐adenocarcinoma and small‐cell‐lung‐cancer (SCLC) cells caused by over‐expression of bcl‐xL, an anti‐sense oligodeoxynucleotide was designed targeting a sequence unique to the bcl‐xL coding region and not shared by the pro‐apoptotic splice variant bcl‐xS. Moreover, to improve the biophysical properties of the anti‐sense compound, 2`‐methoxy‐ethoxy modifications were made to selected deoxy‐ribose residues. The resulting gapmer oligonucleotide 4259 was tested on lung‐adenocarcinoma and SCLC cell lines in vitro. Treatment of the adenocarcinoma cell lines A549 and NCI‐H125 and the SCLC cell lines SW2 and NCI‐H69 with 600 nM 4259 reduced bcl‐xL levels by 70 to 90%. In the lung‐adenocarcinoma cell lines, apoptosis was induced, as indicated by caspase‐3‐like protease activation and nuclear condensation and fragmentation. In contrast, in the SCLC cell lines, no induction of apoptosis could be demonstrated. These findings imply that bcl‐xL is a more critical survival factor for lung adenocarcinomas than for SCLC, and suggest the use of oligonucleotide 4259 for therapy of this major sub‐type of lung cancer. Int. J. Cancer 86:570–576, 2000. © 2000 Wiley‐Liss, Inc.
How RNs View the Work Environment: Results of a National Survey of Registered Nurses

Objective To determine registered nurses' (RNs') views of the workplace environment. Background Numerous studies have shown relationships between work environment, RN satisfaction and retention, and patient safety and outcomes. In 2002, NurseWeek Publishing and the American Organization of Nurse Executives completed a national survey on the views of RNs on the nursing shortage, workplace environments, and their future career intentions, which revealed areas needing improvement. Results from the follow-up survey conducted in 2004 provide new information on RNs' views of the work environment and a comparison of results to the previous survey. Methods A nationally representative random sample of 3500 RNs licensed to practice in the United States was surveyed. Results In the views of RNs, there have been improvements in a number of aspects of the work environment of nurses. While there are no areas of decline, there are areas in which little or no progress is apparent. Conclusions/Implications Some strategies designed to improve the work environment have resulted in positive outcomes, but creative solutions must be continuously developed and implemented to build on recent successes. Results of this survey help identify areas for continued improvement efforts.
Do patients with traumatic brain injury learn a route in the same way in real and virtual environments?

An increasing number of studies address the use of virtual environments (VE) in the cognitive assessment of spatial abilities. However, the differences between learning in a VE and a real environment (RE) remain controversial. Purpose: To compare the topographical behavior and spatial representations of patients with traumatic brain injury navigating in a real environment and in a virtual reproduction of this environment. Methods: Twenty-seven subjects with moderate to severe traumatic brain injury were consecutively included and allocated to one of two groups. The subjects were taught the same route in either the virtual environment or the real environment and had to recall it twice immediately after learning the route and once after a delay. At the end of these sessions, the subjects were asked to complete three representational tests: a map test, a map recognition test recognition and a scene arrangement test. Results: No significant difference was found between the two groups with regards to demographics, severity of brain injury or episodic memory. As a main result, the number of error rates did not significantly differ between the real and virtual environment [F (1, 25) = 0.679; p = 0.4176)]. Scores on the scene arrangement test were higher in the real environment [U = 32.5; p = 0.01]. Conclusions: Although spatial representations probably differ between the real and virtual environment, virtual reality remains a trusty assessment tool for spatial abilities. Implications for Rehabilitation The transfer of cognitive skills and strategy acquired during rehabilitation programs into daily life situations remains a matter of debate. Virtual reality might provide ecological and rehabilitation scenarios that can be used to look at the daily functioning of patients. The route learning performance after traumatic brain injury shows no significant difference between the real environment and its virtual reproduction in this study.
ACCELERATED ENDOTHELIAL REGENERATION AND INTIMAL HYPERPLASIA FOLLOWING A REPEATED DENUDATION OF RABBIT CAROTID ARTERIES: MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES

1. We compared endothelial regeneration and intimal thickening after endothelial denudation between normal and sclerotic carotid arteries (CA). Endothelial denudation of the right CA of rabbits formed intimal thickening covered with regenerated endothelial cells (EC) in 6 weeks, which was considered as the sclerosis model. Both CA were then denuded. Morphological and immunohistochemical studies using antibodies for proliferating cell nuclear antigen (PCNA), von Willebrand factor and macrophages were performed.
The Repeatability of Corneal Thickness Measures

Purpose. To compare the repeatability of three measures of corneal thickness: Orbscan Slitscan pachymetry, ultrasound pachymetry, and optical pachymetry. Methods. Twenty normal subjects were tested on three occasions. Two occurred on the same day and the third was on a different day at approximately the same time of day as one of the first two visits. Central corneal thickness of the right eye was measured with a Haag-Streit optical pachymeter, a Humphrey Model 855 ultrasound pachymeter, and the Orbscan system. Day-to-day and same-day repeatability was assessed by calculating the difference between the values from two visits and determining the mean difference, the SD, and the 95% limits of agreement (LoA) (LoA = mean ± 1.96 SD). Results. Mean (±SD) central corneal thickness as measured by each instrument was as follows: 539 ± 33 &mgr;m for optical pachymetry, 542 ± 33 &mgr;m for ultrasound pachymetry, and 596 ± 40 &mgr;m for Orbscan pachymetry. For day-to-day comparisons, optical pachymetry showed the poorest repeatability with 95% LoA of −61 to +32 &mgr;m. Ultrasound pachymetry showed better repeatability with 95% LoA of −22 to +24 &mgr;m. The Orbscan showed the best repeatability centrally with 95% LoA of −10 to +17 &mgr;m. Peripheral Orbscan pachymetry was less repeatable than that measured centrally but still more repeatable than central optical pachymetry. Similar results were found with same-day comparisons. Conclusion. The Orbscan system is the most repeatable technique for measuring corneal thickness but shows a significant bias toward greater corneal thickness measures than both ultrasound and optical pachymetry.
Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study.

BACKGROUND Fe2+ released from tissue iron stores may accelerate lipid peroxidation by virtue of its pro-oxidant properties and thus promote early atherogenesis. METHODS AND RESULTS The present prospective survey addresses the potential association between serum ferritin concentrations and the 5-year progression of carotid atherosclerosis as assessed by ultrasonographic follow-up evaluations. The study population comprises a random sample of 826 men and women 40 to 79 years old. Serum ferritin was one of the strongest risk predictors of overall progression of atherosclerosis. The main part of this association appeared to act through modification of the atherogenic potential of LDL cholesterol (OR [95% CI] for a 1-SD unit increase in ferritin at LDL levels of 2.5, 3.6, and 4.9 mmol/L: 1.55 [1.30 to 1.85], 1.77 [1.40 to 2.24], and 2.05 [1.50 to 2.80]; P=.0012 for effect modification). Changes in iron stores during the follow-up period modified atherosclerosis risk, in that a lowering was beneficial and further iron accumulation exerted unfavorable effects. All these findings applied equally to incident atherosclerosis and the extension of preexisting atherosclerotic lesions. The significance of prominent iron stores in the development of carotid stenosis was clearly less pronounced. Finally, ferritin and LDL cholesterol showed a synergistic association with incident cardiovascular disease and death (n=59). CONCLUSIONS The present study provided strong epidemiological evidence for a role of iron stores in early atherogenesis and suggests promotion of lipid peroxidation as the main underlying pathomechanism. This hypothesis could in part explain the sex difference in atherosclerotic vascular disease.
Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease

Summary. Biological and clinical studies have shown that Hodgkin's disease (HD) can be divided into two major categories, termed nodular lymphocyte predominance HD (NLP HD) and classic HD (CHD). Within CHD four subtypes have been distinguished: nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion. To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma‐1/Interferon Regulatory Factor‐4), a lymphocyte‐specific member of the IRF family, that is expressed by late centrocytes and post‐germinal centre (GC) B cells. MUM1 reacted with Hodgkin's and Reed–Sternberg (HRS) cells of all CHD cases (75/75 cases), with a moderate to strong staining intensity. Conversely, lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD, were negative for MUM‐1 expression (9/13 cases) or displayed a weak reactivity for the antigen in < 10% neoplastic cells (4/13 cases). With respect to HD microenvironment, NLP HD displayed numerous MUM1‐positive T lymphocytes located in close proximity to L & H cells whereas, in CHD, MUM1‐positive T lymphocytes appeared to be distributed randomly with no specific relationship with HRS cells. Overall, this study shows that MUM1 expression differs in L & H cells versus HRS cells, corroborating the notion that NLP HD and CHD represent different stages of B‐cell differentiation. As MUM1‐positive T lymphocytes form rosettes around tumour cells of NLP HD, but not of CHD, these data point also to differences in the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1‐positive T lymphocytes with L & H cells.
Expression of B-type natriuretic peptide-45 (BNP-45) gene in the ventricular myocardial induced by systemic chronic hypoxia.

AIM To investigate the expression of B-type natriuretic peptide-45 (BNP-45) gene which was induced by systemic chronic hypoxia, and whether these changes would be different from BNP-45 protein in the plasma and its mRNA in the ventricular myocardial. This study also aimed to test the hypothesis that systemic chronic hypoxia may cause heart failure. METHODS Although clinical use of BNP as a biomarker in heart failure is increasing, the specificity of BNP for heart failure is not robust, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Plasma BNP levels were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. Thus, elevated BNP levels do not necessarily reflect heart failure but may also result from cardiac ischemia. Sprague-Dawley male rats, weighing 220-250 g at the time of recruitment were randomly divided into 7 groups (n = 4 per group), the control normoxia group was exposed to room air, while the hypoxia group were caged in a plexiglass hypoxic chamber (8%O2 and 92% N2) for 1, 3, 7, 14, 21, and 28 days, respectively. RESULTS Our data clearly showed that plasma BNP-45 and ventricular BNP-45 mRNA concentration were markedly increased which reached its peak on day 21 after treatment. CONCLUSION Regulation of BNP-45 gene expression occurred at transcription as well as post-transcription level. Systemic chronic hypoxia could result in heart failure, especially when the hypoxia is severe and prolonged.
Safety of rilpivirine plus nucleoside reverse-transcriptase inhibitors in HIV-infected Taiwanese with a higher prevalence of hepatitis virus infection

Combination antiretroviral therapy (cART) containing rilpivirine plus 2 NRTIs are effective antiretroviral (ARV) regimens for ARV‐naive HIV‐infected patients who had baseline plasma HIV RNA load (PVL) <5 log10 copies/mL and as switch therapy for those with viral suppression. In this study, we aimed to assess the short‐term safety of rilpivirine‐containing regimens among HIV‐infected patients who initiated or switched to rilpivirine plus two NRTIs in Taiwan.