The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells

The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.     

Tumor necrosis factor-alpha inhibits hTERT gene expression in human myeloid normal and leukemic cells

Telomerase catalytic subunit (hTERT) has been shown to play a critical role not only in telomere homeostasis but also in cellular survival, DNA repair, and genetic stability. In a previous study, we described that tumor necrosis factor-xalpha (TNFxalpha) induced in the leukemic KG1 cells a senescence state characterized by decreased hTERT activity followed by prolonged growth arrest, increasedx beta-galactosidase activity, telomere shortening, and major chromosomal instability. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) abrogated all these events. In the present study, we show for the first time that TNFxalpha acts by inhibiting the hTERT gene in both normal CD34x+ cells and fresh leukemic cells. Using KG1 cells as a representative cellular model, we show that TNFxalpha induced sphingomyelin hydrolysis, ceramide production, and c-Jun N-terminal kinase (JNK) activation, all of which are critical components of TNFxalpha signaling, resulting in hTERT gene inhibition. Moreover, we provide evidence that the protective effect of GM-CSF is related to its capacity to interfere with both ceramide generation and ceramide signaling. Negative regulation of the hTERT gene may represent one mechanism by which TNFxalpha interferes with normal hemopoiesis.     

Twins after ART

From 1986 to 2002, 16,618 twin babies have been reported to FIVNAT. Mean length of gestation was 36.74 weeks. The mean weight was 2413 g and mean height 46 cm. The proportion of prematurity under 28 weeks of amenorrhea was 1.17% and under 33 weeks: 7.78%. These data are similar to those reported in the French AUDIPOG Report.     

Assisted Reproductive Technologies in HIV patients: a comprehensive review of indications, techniques and results

Assisted Reproductive Technologies (ART) are authorized in France in couples infected by the human immunodeficiency virus (HIV) since the French legislation of May 10th, 2001. The goals are to reduce the risk of viral transmission between partners and to treat an underlying infertility. The classical techniques are used: IUI, IVF or ICSI, but all of them must be done in specifically authorized laboratories. ART outcome is favourable when only the man is infected, but seems to be less favourable when the woman is infected. Management of pregnancy planning should first propose to women infected by HIV, self inseminations when possible, and if needed, a quick ART treatment as some studies showed ovarian function alterations in HIV women. When the man is infected, IUI would be first proposed. Thousands of HIV positive male partners have used ART in Europe and no contamination has been reported so far. Approximately half of couples with one or both partners infected can hope to have a child through the ART process.     

Impact of freezing/thawing technique on sperm DNA integrity in HIV-1 patients

Introduction  

According french legislation, sperm freezing/thawing procedures are used to prevent ART contaminations in couple with HIV-1 infected men. We determined sperm nuclear fragmentation rate before and after selection and freezing/thawing in HIV-1 14 patients.     

Transection of the brachial artery after closed posterior elbow dislocation

Although elbow dislocations are common orthopaedic lesions, vascular complications remain rare. We report the cases of three patients who presented with a rupture of the brachial artery after closed posterior dislocation, which is even more uncommon. Arteriograms were performed in all cases because of the persistent absence of pulses at the wrist after emergency reduction. In each patient, the treatment consisted of the insertion of reversed end-to-end saphenous bridges. None of them presented mid-term vascular complications (mean follow-up, 17 months). Brachial artery disruption can result from closed posterior elbow dislocation and responds well to vascular repair.     

Neuroligin-2 controls the establishment of fast GABAergic transmission in adult-born granule cells

GABAergic inhibition is critical for the precision of neuronal spiking and the homeostatic regulation of network activity in the brain. Adult neurogenesis challenges network homeostasis because new granule cells (GCs) integrate continuously in the functional dentate gyrus. While developing, adult-born GCs undergo a transient state of enhanced excitability due to the delayed maturation of perisomatic GABAergic inhibition by parvalbumin interneurons (PV-INs). The mechanisms underlying this delayed synaptic maturation remain unknown. We examined the morphology and function of synapses formed by PV-INs onto new GCs over a 2-month interval in young adult mice, and investigated the influence of the synaptic adhesion molecule neuroligin-2 (NL2). Perisomatic appositions of PV-IN terminals onto new GCs were conspicuous at 2 weeks and continued to grow in size to reach a plateau over the fourth week. Postsynaptic knockdown of NL2 by expression of a short-hairpin RNA (shNL2) in new GCs resulted in smaller size of synaptic contacts, reduced area of perisomatic appositions of the vesicular GABA transporter VGAT, and the number of presynaptic active sites. GCs expressing shNL2 displayed spontaneous GABAergic responses with decreased frequency and amplitude, as well as slower kinetics compared to control GCs. In addition, postsynaptic responses evoked by optogenetic stimulation of PV-INs exhibited slow kinetics, increased paired-pulse ratio and coefficient of variation in GCs with NL2 knockdown, suggesting a reduction in the number of active synapses as well as in the probability of neurotransmitter release (P_r). Our results demonstrate that synapses formed by PV-INs on adult-born GCs continue to develop beyond the point of anatomical growth, and require NL2 for the structural and functional maturation that accompanies the conversion into fast GABAergic transmission.