Enhancement of infectivity of a non-syncytium inducing HIV-1 by sCD4 and by human antibodies that neutralize syncytium inducing IIIV-1

Enhancement of virus infectivity after sCD4 treatment has been documented for SIVagm and HIV-2. It has been suggested that a similar phenomenon may play a role in HIV-1 infection. In the present study we have analysed biological activities of virus neutralizing polyclonal and monoclonal human antibodies and of sCD4, towards HIV-1 chimeras with envelope proteins derived from one donor, which display different biological phenotypes. The antibodies, which recognize the V3 and/or the CD4 binding domains of the glycoproteins of these viruses and also sCD4 showed different levels of virus neutralizing activity toward the syncytium inducing HIV-1 strains. In contrast, they all dramatically enhanced the infectivity of an HIV-1 chimera with an envelope glycoprotein displaying the non-syncytium-inducing phenotype. Given the relatively conserved nature of non-syncytium-inducing HIV-1 surface glycoproteins early after infection, these data suggest a major role for antibody mediated enhancement of virus infectivity in the early pathogenesis of HIV-1 infection

Modeling relaxation and jamming in granular media

We introduce a stochastic microscopic model to investigate the jamming and reorganization of grains induced by an object moving through a granular medium. The model reproduces the experimentally observed periodic sawtooth fluctuations in the jamming force and predicts the period and the power spectrum in terms of the controllable physical parameters. It also predicts that the avalanche sizes, defined as the number of displaced grains during a single advance of the object, follow a power-law, $P(s)\sim s^{-\tau}$, where the exponent is independent of the physical parameters

A single amino acid substitution in hypervariable region 5 of the envelope protein of feline immunodeficiency virus allows escape from virus neutralization.

We infected a specific-pathogen-free cat (cat 14) with molecularly cloned feline immunodeficiency virus clone 19k1 (FIV19k1 [K. H. J. Siebelink, I. Chu, G. F. Rimmelzwaan, K. Weijer, A. D. M. E. Osterhaus, and M. L. Bosch, J. Virol. 66:1091-1097, 1992]). Serum of this cat obtained 22 weeks postinfection (serum 1422) neutralized FIV19k1 but not FIV19k32, which is 99.3% identical to FIV19k1 in the envel

Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study

BACKGROUND: Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. METHODS AND RESULTS: We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. CONCLUSIONS: The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events

A determinant of feline immunodeficiency virus involved in Crandell feline kidney cell tropism.

Viral progeny of the molecular clone 19k1 of feline immunodeficiency virus (FIV) can infect feline T-cells but not Crandell feline kidney (CrFK) cells. In contrast, the biological isolate FIV-AM6c, which was CrFK adapted by co-cultivation of FIV-AM6 infected thymocytes with CrFK cells, can infect both thymocytes and CrFK cells. The envelope gene of FIV-AM6c was amplified by polymerase chain reaction using DNA from infected CrFK cells, an

Widespread mitochondrial depletion via mitophagy does not compromise necroptosis

Programmed necrosis (or necroptosis) is a form of cell death triggered by the activation of receptor interacting protein kinase-3 (RIPK3). Several reports have implicated mitochondria and mitochondrial reactive oxygen species (ROS) generation as effectors of RIPK3-dependent cell death. Here, we directly test this idea by employing a method for the specific removal of mitochondria via mitophagy. Mitochondria-deficient cells were resistant to the mitochondrial pathway of apoptosis, but efficiently died via tumor necrosis factor (TNF)-induced, RIPK3-dependent programmed necrosis or as a result of direct oligomerization of RIPK3. Although the ROS scavenger butylated hydroxyanisole (BHA) delayed TNF-induced necroptosis, it had no effect on necroptosis induced by RIPK3 oligomerization. Furthermore, although TNF-induced ROS production was dependent on mitochondria, the inhibition of TNF-induced necroptosis by BHA was observed in mitochondria-depleted cells. Our data indicate that mitochondrial ROS production accompanies, but does not cause, RIPK3-dependent necroptotic cell death

Highly water-stable rare ternary Ag-Au-Se nanocomposites as long blood term X-rays computed tomography contrast agents

X-ray computed tomography (CT) is a powerful and widely used medical non-invasive technique that requires intravenously administration of contrast agents to enhance the sensitivity and visualization of soft tissues. In this work, we have developed a novel CT contrast agent based on ternary Ag-Au-Se chalcogenide nanoparticles. A facile and gentle ligand exchange by using a 3 kDa PEGylated ligand with a dithiol dihydrolipoic as an anchor resulted in highly water-soluble and monodisperse nanoparticles. Moreover, the injected PEGylated ternary NPs presented excellent characteristics as a CT contrast agent with high bioavailability, low cytotoxicity and long blood circulation times with slow uptake by the mononuclear phagocyte system, thus being ideal for in vivo imaging

A model for cascading failures in complex networks

Large but rare cascades triggered by small initial shocks are present in most of the infrastructure networks. Here we present a simple model for cascading failures based on the dynamical redistribution of the flow on the network. We show that the breakdown of a single node is sufficient to collapse the efficiency of the entire system if the node is among the ones with largest load. This is particularly important for real-world networks with an highly hetereogeneous distribution of loads as the Internet and electrical power grids.Comment: 4 pages, 4 figure

Peripheral arterial disease in the elderly: The Rotterdam Study

To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC

Transient neurological attacks in the general population. Prevalence, risk factors, and clinical relevance

BACKGROUND AND PURPOSE: Patients with typical transient ischemic attacks (TIAs) have a higher risk of stroke but a lower risk of cardiac events than patients with nonspecific transient neurological symptoms. We assessed the prevalences of typical TIAs and nonspecific transient neurological attacks (TNAs) and their determinants in the general population because such data are virtually absent. METHODS: The Rotterdam Study is a population-based cohort study of 7983 subjects, aged 55 years and over, conducted in a district of Rotterdam, the Netherlands. At baseline examination, a history of episodes of disturbances in sensibility, strength, speech, and vision that lasted less than 24 hours and occurred within the preceding 3 years was determined by a trained physician. When such a history was present, information on time of onset, duration, and disappearance of symptoms and a detailed description of the symptoms (in ordinary language) were obtained. Subjects were classified by a neurologist as typical TIA or nonspecific TNA. RESULTS: Prevalence of TNAs was 1.9% in subjects aged 55 to 64 years, 3.5% in subjects aged 65 to 74 years, 4.3% in subjects aged 75 to 84 years, and 5.1% in subjects aged 85 years or over. Prevalence figures for typical TIA were 0.9%, 1.7%, 2.3%, and 2.2% and for nonspecific TNA 1.0%, 1.8%, 2.0%, and 2.9%, respectively. Clinical parameters such as number of attacks, onset, duration, and disappearance of symptoms were similar for typical TIA and nonspecific TNA. Increased age, male sex, diabetes mellitus, low HDL cholesterol, Q-wave myocardial infarction on electrocardiogram, and carotid atherosclerosis were related to typical TIA, whereas increased age, hypertension, low HDL cholesterol, smoking, and angina pectoris were associated with nonspecific TNA. CONCLUSIONS: About half of the subjects with a TNA had symptoms that were not entirely typical for a TIA. Differences in associations with risk factors between typical TIA and nonspecific TNA point toward different underlying mechanisms of symptoms and may lead to different ancillary investigations and possibly treatment