Interaction between the cytoplasmic domain of ICAM-1 and Pr55Gag leads to acquisition of host ICAM-1 by human immunodeficiency virus type 1

We have examined the molecular basis for the selective incorporation of the adhesion molecule ICAM-1 within human immunodeficiency virus type 1 (HIV-1). The process of ICAM-1 incorporation was investigated by using different ICAM-1 constructs in combination with virus capture and immunoprecipitation studies, Western blot and confocal microscopy analyses, and infectivity assays. Experiments conducted with viruses bearing a truncated version of ICAM-1 revealed that the cytoplasmic domain of ICAM-1 governs insertion of this adhesion molecule into HIV-1. Further experiments suggested that there is an association between ICAM-1 and the virus-encoded Pr55(Gag) polyprotein. This study represents the first demonstration that structural Gag polyproteins play a key role in the uptake of a host-derived cell surface by the virus entity. Taken together, our results indicate that interactions between viral and cellular proteins are responsible for the selective uptake of host ICAM-1 by HIV-1. This observation describes a new strategy by which HIV-1 can modulate its replicative cycle, considering that insertion of ICAM-1 within nascent virions has been shown to increase virus infectivity.     

Diminished dietary thermogenesis in exercise-trained human subjects

The influence of exercise-training on dietary-induced thermogenesis (DIT) was investigated in humans. The resting metabolic rate was identical in trained and non-trained subjects, but the response to a meal containing 1,636 kcal (6.9 MJ) was markedly lower in trained subjects. Mean dorsal skin temperature, as measured by thermography, was not influenced by training. A significant correlation was observed between postprandial RQ and DIT, which indicates that the reduced energy expenditure noted in trained subjects is related to a greater lipid oxidation. This sparing effect of exercise-training on energy utilization in the form of carbohydrate, is interpreted as adaptive in the sense that energy is preserved for the purpose of producing work.     

Adiposity and eating behaviors in patients under second generation antipsychotics

Background: Second generation antipsychotics (SGA) induce substantial weight gain but the mechanisms responsible for this phenomenon remain speculative. Objective: To explore eating behaviors among SGA‐treated patients and compare them with nonschizophrenic healthy sedentary individuals (controls). Methods and Procedures: Appetite sensations were recorded before and after a standardized breakfast using visual analog scales. Three hours after breakfast, a buffet‐type meal was offered to participants to document spontaneous food intake and food preferences. Satiety quotients (SQs) were calculated to determine the satiation of both meals and the Three‐Factor Eating Questionnaire (TFEQ) was used to document eating behaviors. Body composition and abdominal fat distribution were assessed. Results: Compared with controls (n = 20), SGA‐treated patients (n = 18) showed greater adiposity indices (P ≤ 0.04). Patients' degree of hunger was also higher following the standardized breakfast (P = 0.03). Moreover, patients had significantly higher cognitive dietary restraint, disinhibition, and susceptibility to hunger scores than the reference group (P ≤ 0.05). Disinhibition in the reference group was positively associated with hunger triggered by external cues (r = 0.48, P = 0.03) whereas internal cues seem to mainly regulate emotional susceptibility to disinhibition in patients (r = 0.56, P = 0.02). Higher strategic restraint behavior in patients was associated with decreased satiation right after the buffet‐type meal (r = ?0.56, P = 0.02). Discussion: These exploratory findings suggest that patients under SGA seem to develop disordered eating behaviors in response to altered appetite sensations and increased susceptibility to hunger, a factor which may influence the extent of body weight gain triggered by these drugs.     

Investing in early human development: Timing and economic efficiency

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.     

Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1

A variety of host factors, including membrane proteins acquired by human immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption onto host cells. Examples include the integrin intercellular adhesion molecule 1 (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based on the idea that these compounds have been shown to block ICAM-1-LFA-1 interactions. Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection.     

Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress

Protein-tyrosine phosphatase 1B (PTP-1B) is the prototypic tyrosine phosphatase whose function in insulin signaling and metabolism is well established. Although the role of PTP-1B in dephosphorylating various cell surface receptor tyrosine kinases is clear, the mechanisms by which it modulates receptor function from the endoplasmic reticulum (ER) remains an enigma. Here, we provide evidence that PTP-1B has an essential function in regulating the unfolded protein response in the ER compartment. The absence of PTP-1B caused impaired ER stress-induced IRE1 signaling. More specifically, JNK activation, XBP-1 splicing, and EDEM (ER degradation-enhancing alpha-mannosidase-like protein) gene induction, as well as ER stress-induced apoptosis, were attenuated in PTP-1B knock-out mouse embryonic fibroblasts in response to two ER stressors, tunicamycin and azetidine-2 carboxylic acid. We demonstrate that PTP-1B is not just a passive resident of the ER but on the contrary has an essential role in potentiating IRE1-mediated ER stress signaling pathways.     

Composition of nuclear dense bodies and nucleolus-associated bodies in interphase nuclei of the unicellular green alga Chlamydomonas reinhardtii

Summary— The interphase nucleus of the green alga, Chlamydomonas reinhardtii, displayed two types of bodies some of them, the dense bodies, lying apparently free in the nucleoplasm while the others were attached to the nucleolus and were, therefore, referred to as nucleolus-associated bodies (NABs). The presence of DNA, RNA and histones in dense bodies was investigated by means of post-embedding immunocytochemistry and cytochemistry using a monoclonal antibody to single and double stranded DNA, a polyclonal antibody to rye H3 histones and RNase A-gold complexes. The dense bodies were shown to contain significant amounts of RNA but neither DNA nor histones were detected; their composition was thus similar to that of the dense bodies described in higher plant cells. We propose that dense bodies might be implicated in the assembly of the 25 to 45 nm granules observed throughout the nucleoplasm of Chalamydomonas interphase nuclei. The composition of NABs was found to be distinct from that of the dense bodies since they were labeled by the antibody to DNA, specially in cryofixed and cryosubstituted specimens. The presence of DNA in NABs together with their intimate association to the nucleolus suggest that they may correspond to specific segments of chromosomes.     

Southern blot analysis with synthetic oligonucleotides. Application to prostatic protein genes.

1. An ethanol precipitation procedure was developed to purify radiolabeled DNA and oligonucleotide probes to be used in Southern blots. 2. The radiolabeled probes produced strong hybridization signals on a clear background on Southern blot analysis of single gene copies even after 5 days of exposure on X-ray films. 3. An oligonucleotide probe complementary to human glandular kallikrein-1 coding region (amino acids 161-167) detected a single DNA fragment after digestion with Bam H1, Hind III or Pst 1. 4. Another oligonucleotide probe coding for the same region of human prostate-specific antigen detected 3 DNA fragments on Southern blots by contrast to a 1.5 kb full length cDNA probe which detected the presence of only one strong hybridization signal. 5. Oligonucleotide probes appear to be excellent tools for gene mapping. Their sensitivity, specificity and limitations can be compared to the one of monoclonal antibodies used in epitope mapping of proteins.