Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease

Background and Objectives We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field. Methods We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0–1) and high-grade (2–3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed. Results MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08–3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05–0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47–6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02–0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77–6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28–5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28–10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36–0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19–0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11–4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18–1.59]; p<0.001). During follow-up (1.79 [0.94–2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome. Conclusions MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.
Impact of Vital Status Investigation Procedures on Estimates of Survival in Cohorts of HIV-Infected Patients From Sub-Saharan Africa

In HIV cohorts in sub-Saharan Africa, documenting vital status of patients lost to follow-up is a major challenge. The effect of specific vital status investigation procedures (VSIPs) on the number of known deaths has never been shown. We assessed the effects of VSIP on survival estimates in a 4-year prospective cohort study in Abidjan, Côte d'Ivoire. As of June 2000, 545 HIV-infected adults had been followed for 1186 person-years, of whom 233 were documented as deceased. Forty-eight percent of deaths were known through scheduled VSIPs, including reading of the newspaper obituaries (2%), telephone calls to relatives (10%), and home visits (36%). Survival probability at 1, 2, and 3 years was estimated to be 0.79, 0.65, and 0.56, respectively. Without VSIP, survival at 1, 2, and 3 years would have been estimated to be 11, 23, and 30% higher, respectively. In this large African capital city, survival estimates closely depended on VSIPs, mainly home visits. We suggest that the percentage of deaths known through VSIPs would be a useful indicator to be added when reporting survival data from urban HIV cohort studies in sub-Saharan Africa.
Endocytosis Resumes during Late Mitosis and Is Required for Cytokinesis*

Recent work has underscored the importance of membrane trafficking events during cytokinesis. For example, targeted membrane secretion occurs at the cleavage furrow in animal cells, and proteins that regulate endocytosis also influence the process of cytokinesis. Nonetheless, the prevailing dogma is that endosomal membrane trafficking ceases during mitosis and resumes after cell division is complete. In this study, we have characterized endocytic membrane trafficking events that occur during mammalian cell cytokinesis. We have found that, although endocytosis ceases during the early stages of mitosis, it resumes during late mitosis in a temporally and spatially regulated pattern as cells progress from anaphase to cytokinesis. Using fixed and live cell imaging, we have found that, during cleavage furrow ingression, vesicles are internalized from the polar region and subsequently trafficked to the midbody area during later stages of cytokinesis. In addition, we have demonstrated that cytokinesis is inhibited when clathrin-mediated endocytosis is blocked using a series of dominant negative mutants. In contrast to previous thought, we conclude that endocytosis resumes during the later stages of mitosis, before cytokinesis is completed. Furthermore, based on our findings, we propose that the proper regulation of endosomal membrane traffic is necessary for the successful completion of cytokinesis.
Induction of CaSR expression circumvents the molecular features of malignant CaSR null colon cancer cells

We recently reported on the isolation and characterization of calcium sensing receptor (CaSR) null human colon cancer cells (Singh et al., Int J Cancer 2013; 132: 1996–2005). CaSR null cells possess a myriad of molecular features that are linked to a highly malignant and drug resistant phenotype of colon cancer. The CaSR null phenotype can be maintained in defined human embryonic stem cell culture medium. We now show that the CaSR null cells can be induced to differentiate in conventional culture medium, regained the expression of CaSR with a concurrent reversal of the cellular and molecular features associated with the null phenotype. These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil. Other features include the expression of epithelial mesenchymal transition linked molecules and transcription factors, oncogenic miRNAs and tumor suppressive molecule and miRNA. With the exception of cancer stem cell markers, the reversal of molecular features, upon the induction of CaSR expression, is directly linked to the expression and function of CaSR because blocking CaSR induction by shRNA circumvented such reversal. We further report that methylation and demethylation of the CaSR gene promoter underlie CaSR expression. Due to the malignant nature of the CaSR null cells, inclusion of the CaSR null phenotype in disease management may improve on the mortality of this disease. Because CaSR is a robust promoter of differentiation and mediates its action through diverse mechanisms and pathways, inactivation of CaSR may serve as a new paradigm in colon carcinogenesis.
Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease--results of the renal Hope-2 study.

BACKGROUND Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases. Plasma homocysteine increases in chronic kidney disease (CKD) and could contribute to the increased cardiovascular risk in CKD. METHODS Participants aged 55 years or older with CKD, defined as estimated GFR<60 ml/min and at high cardiovascular risk, were randomly assigned to the combination of folic acid, 2.5 mg, vitamin B6, 50 mg and vitamin B12, 1 mg (n = 307) or placebo (n = 312) daily for 5 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction and stroke. RESULTS Mean baseline plasma homocysteine was 15.9 +/- 7.3 micromol/l in the active treatment group and 15.7 +/- 5.7 micromol/l in placebo group and decreased to 11.9 +/- 3.3 micromol/l (P < 0.001) on active treatment (15.5 +/- 4.5 on placebo). Primary outcome events occurred in 90 participants (29.3%) on active therapy and in 80 (25.6%) on placebo (relative risk, 1.19; 95% confidence interval, 0.88-1.61; P = 0.25). There were no significant treatment benefits on death from cardiovascular causes (1.24; 0.84-1.83), myocardial infarction (1.10; 0.76-1.61) and stroke (1.00; 0.54-1.85). More participants in the active treatment group were hospitalized for heart failure (1.98; 1.21-3.26; P = 0.007) and for unstable angina (1.70; 1.02-2.83; P = 0.04). Incidence of primary outcome increased with decreasing GFR. CONCLUSIONS Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk.
Loss of circadian rhythm and light‐induced suppression of pineal melatonin levels in Cry1 and Cry2 double‐deficient mice

Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm expression and acute light‐induced suppression of pineal melatonin was assessed using Cry1 and Cry2 double‐deficient mice (Cry1−/−/Cry2−/−) developed from the C3H strain that synthesizes melatonin. We examined the circadian variation of pineal melatonin under a 12:12‐h light–dark (LD) cycle and constant darkness (DD). Light suppression of pineal melatonin concentration was analyzed by subjecting a 30‐min light pulse at the peak phase of melatonin concentration. Wild‐type mice showed significant rhythmicity in pineal melatonin concentration with the highest level at Zeitgeber time 22 (ZT22, where time of light on was defined as ZT0) under LD or ZT18 on the first day of DD. In contrast, Cry1−/−/Cry2−/− mice did not show significant circadian rhythmicity, with only a small peak observed at ZT22 in LD. Nevertheless, a significant daily variation could be observed under DD, with a small increase at ZT6 and ZT18 h. Melatonin concentration was significantly suppressed by acute light pulse at ZT22 in wild‐type mice but not in Cry1−/−/Cry2−/− mice. The present results suggest that Cry genes are required for regulating pineal melatonin synthesis via circadian and photic signals from the suprachiasmatic nucleus of the hypothalamus (SCN).
Activation of a local tissue angiotensin system in podocytes by mechanical strain.

BACKGROUND Glomerular capillary hypertension, a common denominator in various forms of progressive glomerular disease, results in mechanical distention of the capillary tuft, and subsequent injury of the overlying podocyte layer. The mechanisms by which elevated intraglomerular pressure is translated into a maladaptive podocyte response remain poorly understood. Angiotensin II plays a central role in the pathogenesis of chronic renal injury, largely through its actions on the subtype 1 receptor. Accordingly, we have tested the hypothesis that mechanical strain up-regulates local angiotensin II in podocytes, thereby resulting in a progressive reduction in podocyte number. METHODS Conditionally immortalized mouse podocytes were subjected to cyclical stretch of 10% amplitude. Nonstretched podocytes served as controls. Angiotensin II levels were measured in whole cell lysate by competitive enzyme-linked immunosorbent assay (ELISA). Expression of angiotensin II receptors (AT1R, AT2R) was measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. Apoptosis was measured by Hoechst staining. Immunostaining for AT1R was performed in tissue sections from rats with 5/6 remnant kidney disease, a model of glomerular hypertension. RESULTS Mechanical strain increased angiotensin II production in podocytes at 24, 48, and 72 hours (P < 0.05 vs. nonstretched controls). Stretching podocytes resulted in a fivefold increase in AT1R mRNA expression at 24 hours and a twofold increase in protein levels vs. controls (P < 0.05), and also an increase in transforming growth hormone-beta (TGF-beta) mRNA expression. AT1R staining was increased in a podocyte distribution in the 5/6 remnant kidney, consistent with our in vitro findings. Mechanical strain resulted in a 2.5-fold increase in apoptosis (P < 0.001 vs. nonstretched controls) in an angiotensin II-dependent fashion. CONCLUSION Mechanical strain leads to up-regulation of the AT1R and increased angiotensin II production in conditionally immortalized podocytes. The resulting activation of a local tissue angiotensin system leads to an increase in podocyte apoptosis, mainly in an AT1R-mediated fashion.
Hybrid Procedures for Complex Thoracoabdominal Aortic Aneurysms: Early Results and Secondary Interventions

Background: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have been previously described as an attractive alternative to open reconstruction. Patients and Methods: Between 1999 and 2009, 16 patients with a median age of 67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present, with previous aortic surgery in 56% of the patients; elective/urgent repair was done in 10 and emergent surgery in 6 patients. Results: Primary technical success was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10) and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2 patients died and 2 patients had to undergo secondary interventions. Conclusion: In high-risk patients especially after prior aortic surgery hybrid repair of TAAA is feasible. However, due to high mortality rates especially in the emergent situation this procedure should be reserved only for decidedly selected patients.
The Ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats after transient, middle cerebral artery occlusion in conditions of unprevented, ischemia‐induced fever

There is much biochemical evidence, but very few studies in animal models of stroke in vivo, to suggest that Ginkgo biloba (EGb 761) may offer neuroprotection against regional, ischemic brain damage; additional investigations are needed to ensure future clinical trials. This study reports the effects of EGb 761 given acutely or chronically before ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and the brain infarct size was assessed 24 h later. Dipyrone (100 mg/kg, i.p.) was injected 30 min before ischemia, and 2.5 and 5.5 h after ischemia, to reduce ischemia‐induced fever. EGb 761 (Tebonin®) was given acutely (200 mg/kg, p.o., 60 min before ischemia) or chronically (100 mg/kg, p.o., once daily, for 14 days before ischemia). Acute or chronic treatment with EGb 761, either alone or in combination with dipyrone, did not reduce the infarct size compared with saline alone (p > 0.05). Dipyrone failed to prevent ischemia‐induced fever during the intra‐ischemic period (p > 0.05 vs saline; p < 0.001 vs sham). In the reperfusion phase, dipyrone reduced fever to normothermic levels in the group treated acutely with EGb 761 (p < 0.01 vs saline, p > 0.05 vs sham) but not after chronic EGb 761 (p < 0.01 vs sham), indicating possible pharmacokinetic interaction. In conclusion, within the context of unprevented, ischemia‐induced fever, the present results demonstrate that EGb 761 has no significant effect on brain infarct size. Copyright © 2006 John Wiley & Sons, Ltd.
Extracellular Hippocampal Acetylcholine Level Controls Amygdala Function and Promotes Adaptive Conditioned Emotional Response

Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.
S‐acylation of LCK protein tyrosine kinase is essential for its signalling function in T lymphocytes

LCK is a non‐receptor protein tyrosine kinase required for signal transduction via the T‐cell antigen receptor (TCR). LCK N‐terminus is S‐acylated on Cys3 and Cys5, in addition to its myristoylation on Gly2. Here the role of S‐acylation in LCK function was examined. Transient transfection of COS‐18 cells, which express a CD8‐ζ chimera on their surface, revealed that LCK mutants that were singly S‐acylated were able to target to the plasma membrane and to phosphorylate CD8‐ζ. A non‐S‐acylated LCK mutant did not target to the plasma membrane and failed to phosphorylate CD8‐ζ, although it was catalytically active. Fusion of non‐S‐acylated LCK to a transmembrane protein, CD16:7, allowed its plasma membrane targeting and also phosphorylation of CD8‐ζ when expressed in COS‐18 cells. Thus S‐acylation targets LCK to the plasma membrane where it can interact with the TCR. When expressed in LCK‐negative JCam‐1.6 T cells, delocalized, non‐S‐acylated LCK was completely non‐functional. Singly S‐acylated LCK mutants, which were expressed in part at the plasma membrane, efficiently reconstituted the induced association of phospho‐ζ with ZAP‐70 and intracellular Ca2+ fluxes triggered by the TCR. Induction of the late signalling proteins, CD69 and NFAT, was also reconstituted, although at reduced levels. The transmembrane LCK chimera also supported the induction of tyrosine phosphorylation and Ca2+ flux by the TCR in JCam‐1.6 cells. However, induction of ERK MAP kinase was reduced and the chimera was incapable of reconstituting induced CD69 or NFAT expression. These data indicate that LCK must be attached to the plasma membrane via dual acylation of its N‐terminus to function properly in TCR signalling.
Capacity analysis for multi-antenna dual-hop AF system with random co-channel interference

In this work, the performance of a dual-hop amplify-and-forward (AF) multi-antenna relaying system over Rayleigh fading channels with random co-channel interference (CCI) is investigated. Three receiving strategies such as the maximal-ratio combining (MRC), zero-forcing (ZF) and minimum mean square error (MMSE) are employed in the relay to mitigate the impact of CCI which follows a Poisson point process. In second hop, the relay forwards the signal to the destination by using maximum ratio transmission (MRT). Specifically, we derive the asymptotic expressions of the capacities for this system. The simulation and analytical results show that the MMSE/MRT scheme always provides significant improvement on capacity compared with MRC/MRT and ZF/MRT schemes. Furthermore, the MRC/MRT scheme gives almost the same performance as the MMSE/MRT scheme when the density of CCI sources is high.
Single‐strand conformation polymorphism analysis by capillary zone electrophoresis in neutral pH buffer

Sensitivity of single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products was reported to be lower in capillary zone electrophoresis (CZE) compared to conventional slab gel electrophoresis. We examined the effects of buffer ion type, pH, and temperature in an attempt to improve the mutation detectability in the SSCP‐CZE mode. It was noted that, by utilizing short‐chain polyacrylamide as sieving media while simultaneously lowering the temperature, there was no improvement of conformer detectability. On the contrary, there was a large increment in conformers' resolution by running samples in a lower‐pH buffer system. The effects of different buffering ions and pH values were investigated. By using a new buffer system, consisting of 35 mM 2‐(N‐morpholino)propanesulfonic acid (MES), 30 mM tris(hydroxymethyl)aminomethane (Tris), 1 mM ethylene diaminetetraacetic acid (EDTA), pH 6.8, and keeping constant all the other conditions, such as temperature, sieving, applied voltage, capillary length, and inner diameter (ID), there was a remarkable improvement in resolution and the sensitivity became comparable to that of slab gel systems.
Paramyxovirus strategies for evading the interferon response

Two genera, the Respirovirus (Sendai virus (SeV) and human parainfluenza virus (hPIV3) and the Rubulavirus (simian virus (SV) 5, SV41, mumps virus and hPIV2), of the three in the subfamily Paramyxovirinae inhibit interferon (IFN) signalling to circumvent the IFN response. The viral protein responsible for the inhibition is the C protein for respirovirus SeV and the V protein for the rubulaviruses, both of which are multifunctional accessory proteins expressed from the P gene. SeV suppresses IFN‐stimulated tyrosine phosphorylation of signal transducers and activators of transcription (STATs) at an early phase of infection and further inhibits the downstream signalling without degrading any of the signalling components in most cell lines. On the contrary, the Rubulavirus V protein targets Stat1 or Stat2 for degradation. Proteasome‐mediated degradation appears to be involved in most cases. Studies on the molecular mechanisms by which paramyxoviruses evade the IFN response will offer important information for modulating the JAK‐STAT pathway, designing novel antiviral drugs and recombinant live vaccines, and improving paramyxovirus expression vectors for gene therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Impacts and kinematic adjustments during an exhaustive run.

PURPOSE To examine the kinematic adjustments that runners make during an exhaustive run and to look at the effects these adjustments have on shock and shock attenuation. METHODS Ten recreational runners ran to volitional exhaustion on a treadmill at a velocity equal to their average 3200-m running velocity at maximal effort (average time: 15.7 +/- 1.7 min). Head and leg accelerometers, a knee electrogoniometer, and a rearfoot electrogoniometer were attached to each subject. The data were sampled at 1000 Hz at the start, middle, and end of the run. RESULTS The knee became significantly more flexed at heel impact (start: 164.9 +/- 2.3 degrees; end: 160.5 +/- 2.9 degrees; P < 0.05). The rearfoot angle became more inverted at impact (start: 12.2 +/- 1.6 degrees; end: 13.6 +/- 1.9 degrees; P < 0.05). These kinematic changes resulted in a lower extremity that that had a lower effective mass during the impact. This decreased effective mass allowed the leg to accelerate more easily; thus, peak leg impact accelerations (start: 6.11 +/- 0.96 g; end: 7.38 +/- 1.05 g; P < 0.05) and impact attenuation (start: 74.5 +/- 5.4%; end: 77.5 +/- 4.1%; P < 0.05) increased during the progression of the run. CONCLUSIONS The increase in peak impact accelerations at the leg was not considered an increased injury risk because of the decreased effective mass. The altered kinematics may have resulted in increased metabolic costs during the latter stages of the exhaustive run.