Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis

Introduction  

Increasing evidence support the regulatory role of leptin in osteoarthritis (OA). As high circulating concentrations of leptin disrupt the physiological function of the adipokine in obese individuals, the current study has been undertaken to determine whether the elevated levels of leptin found in the joint from obese OA patients also induce changes in the chondrocyte response to leptin.     

Les sites archéologiques plio-pléistocènes de la formation de Nachukui, Ouest-Turkana, Kenya : bilan synthétique 1997–2001

Plio-Pleistocene archaeological sites in the Nachukui Formation, West Turkana, Kenya: synthetic results 1997–2001. Stretched along the western side of the Turkana Basin, the Nachukui Formation preserves a large number of Plio-Pleistocene archaeological sites. Research carried out by the WTAP documents hominid behavioral evolution and technical diversity, through a time period ranging from 2.35 Myr to 0.7 Myr and within a relatively precise chronostratigraphic and paleoenvironmental frame. This work is based on comprehensive excavations conducted between 1997 and 2001 at the Late Pliocene and Early Pleistocene site complexes of the formation. To cite this article: H. Roche et al., C.R. Palevol 2 (2003).     

Azoospermias au Sénégal: quelle prise en charge à l’heure de l’ICSI?

Objective

to determine the place of azoospermia among the various causes of infertility in Senegal.

Material and methods

141 cases of azoospermia were identified from a series of 492 infertile patients. The clinical profile, laboratory results and outcome after management were studied.

Results

The mean age was 40.6 years. Testicular atrophy was detected in 34.75% of cases. Azoospermia was secretory in 71.69% of cases. A varicocele was associated in 56% of cases. Varicocele repair was performed in 32.62% and allowed an improvement of sperm parameters in 28.3% of cases. Testicular biopsy, performed in 53 cases, demonstrated 2 cases of Sertoli cell syndrome, 3 cases of arrested maturation, 8 cases of hypo spermatogenesis, and 25 cases of seminiferous tubules. Forty nine cases of azoospermia were associated with normal FSH levels. Only one patient was treated by assisted reproductive technologies (ART).     

Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship

Integrins are crucial for the ability of cells to sense mechanical perturbations and to transmit intracellular stress to their environment. We here review the more recently discovered role of integrins in activating the pleiotrophic cytokine transforming growth factor beta 1 (TGF-beta1). TGF-beta1 controls tissue homeostasis in embryonic and normal adult tissues and contributes to the development of fibrosis, cancer, autoimmune and vascular diseases when being mis-regulated. In most of these conditions, active TGF-beta1 is generated by dissociation from a large latent protein complex that sequesters latent TGF-beta1 in the extracellular matrix (ECM). Two main models are proposed how integrins contribute to latent TGF-beta1 activation: (1) In a protease-dependent mechanism, integrins alphavbeta8 and alphavbeta3 are suggested to simultaneously bind the latent TGF-beta1 complex and proteinases. This close vicinity at the cell surface improves enzymatic cleavage of the latent complex to release active TGF-beta1. (2) Integrins alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 appear to change the conformation of the latent TGF-beta1 complex by transmitting cell traction forces. This action requires association of the latent complex with a mechanically resistant ECM and is independent from proteolysis. Understanding that different integrins use different mechanisms to activate latent TGF-beta1 opens new possibilities to develop cell-specific therapeutic strategies for TGF-beta1-induced pathologies.     

Leaky scanning and scanning-independent ribosome migration on the tricistronic S1 mRNA of avian reovirus

The S1 genome segments of avian and Nelson Bay reovirus encode tricistronic mRNAs containing three sequential partially overlapping open reading frames (ORFs). The translation start site of the 3'-proximal ORF encoding the sigmaC protein lies downstream of two ORFs encoding the unrelated p10 and p17 proteins and more than 600 nucleotides distal from the 5'-end of the mRNA. It is unclear how translation of this remarkable tricistronic mRNA is regulated. We now show that the p10 and p17 ORFs are coordinately expressed by leaky scanning. Translation initiation events at these 5'-proximal ORFs, however, have little to no effect on translation of the 3'-proximal sigmaC ORF. Northern blotting, insertion of upstream stop codons or optimized translation start sites, 5'-truncation analysis, and poliovirus 2A protease-mediated cleavage of eIF4G indicated sigmaC translation derives from a full-length tricistronic mRNA using a mechanism that is eIF4G-dependent but leaky scanning- and translation reinitiation-independent. Further analysis of artificial bicistronic mRNAs failed to provide any evidence that sigmaC translation derives from an internal ribosome entry site. Additional features of the S1 mRNA and the mechanism of sigmaC translation also differ from current models of ribosomal shunting. Translation of the tricistronic reovirus S1 mRNA, therefore, is dependent both on leaky scanning and on a novel scanning-independent mechanism that allows translation initiation complexes to efficiently bypass two functional upstream ORFs.     

HIV/AIDS knowledge, women's education, epidemic severity and protective sexual behaviour in low- and middle-income countries

A fundamental public health strategy to reduce the risk of HIV/AIDS is to increase levels of awareness and knowledge about the disease. Although knowledge about HIV/AIDS and protective sexual behaviour are linked theoretically, relatively little is known about their empirical relationship. Using Demographic and Health Survey data from 23 low- and middle-income countries, this study used multilevel logistic regression models: to examine cross-national variability in the relationship between HIV/AIDS knowledge and protective behaviour (condom use and restricted sex); to investigate the moderating influences of women's educational attainment on this relationship; and to test the extent to which severity of the HIV/AIDS epidemic accounts for cross-national variability in the association between HIV/AIDS knowledge and protective behaviour. There was an association between increased knowledge of HIV/AIDS and condom use that varied in strength and form cross-nationally. This cross-national variation was accounted for partially by the socioeconomic characteristics of women resident in the study countries and between-country differences in the severity of the HIV epidemic. While education modified the association between HIV/AIDS knowledge and protective behaviour--stronger associations at lower levels of education--epidemic severity exerted a stronger influence on behaviour than any other characteristic. Finally, this study indicates that protective sexual practices are disturbingly low. In eight of 23 countries, overall levels of condom use to prevent STDs and HIV/AIDS were less than 5.0%. Waiting for the spread of HIV/AIDS infection to change sexual practices in low- and middle-income countries will result in dramatic unnecessary suffering.     

Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix

The conjunctive presence of mechanical stress and active transforming growth factor β1 (TGF-β1) is essential to convert fibroblasts into contractile myofibroblasts, which cause tissue contractures in fibrotic diseases. Using cultured myofibroblasts and conditions that permit tension modulation on the extracellular matrix (ECM), we establish that myofibroblast contraction functions as a mechanism to directly activate TGF-β1 from self-generated stores in the ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with Triton X-100 releases active TGF-β1 from the ECM. This process is inhibited either by antagonizing integrins or reducing ECM compliance and is independent from protease activity. Stretching myofibroblast-derived ECM in the presence of mechanically apposing stress fibers immediately activates latent TGF-β1. In myofibroblast-populated wounds, activation of the downstream targets of TGF-β1 signaling Smad2/3 is higher in stressed compared to relaxed tissues despite similar levels of total TGF-β1 and its receptor. We propose activation of TGF-β1 via integrin-mediated myofibroblast contraction as a potential checkpoint in the progression of fibrosis, restricting autocrine generation of myofibroblasts to a stiffened ECM.     

HIV infection among Quebec women giving birth to live infants.

This is the first anonymous unlinked seroprevalence study in Canada to use serum samples from newborns to determine the seroprevalence rate of human immunodeficiency virus (HIV) infection among childbearing women. Of the 68,808 samples tested 42 were confirmed as positive, for an overall crude seroprevalence rate of 6.1 per 10,000 live births (95% confidence interval [CI] 4.4 to 8.3), or 1 woman in 1638. Women who lived on Montreal island had an overall rate of 17.9 per 10,000 live births (95% CI 12.2 to 25.4), or 1 woman in 559. We observed a significant association between revenue index and seroprevalence; the rates were as high as 46.4 per 10,000 live births (95% CI 18.7 to 95.3), or 1 woman in 216, for Montreal island postal code areas with revenue indexes 20% or more below the provincial median. Extrapolation of the data suggested that 56 women with HIV infection gave birth to a live infant during 1989 in Quebec. Even though attempts to generalize the data from childbearing women to women of childbearing age have an inherent conservative bias, the results of our study suggest that 988 women (95% CI 713 to 1336) aged 15 to 44 years in Quebec had HIV infection in 1989. The actual number is likely substantially higher. The need for well-designed, creative interventions to prevent further HIV transmission to women is evident. Planning for the provision of medical and psychosocial services sensitive to specific needs of women who are already infected should start immediately.