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Biomedical subjects

L Laurent

Publications and source records attributed to L Laurent.

At least 19 recordsLinked to original sources

Microdisplacements induced by a local perturbation inside a granular packing.

The microdisplacements generated by a small localized overload at the free surface are visualized experimentally inside a packing of steel beads. For a triangular packing, beads rearrangements remain confined in two inverted triangles on both sides of the applied overload. This pattern disappears for stronger disorder. A simple model allows us to account for these observations and to relate them to the stress function response measured via photoelastic visualizations. This provides a different tool to probe the mechanical Green's function in weakly confined packings of rigid grains the description of which is the most challenged.

Journal Article↗

Multiscale clustering in granular surface flows.

We investigate steady granular surface flows in a rotating drum and demonstrate the existence of rigid clusters of grains embedded in the flowing layer. These clusters appear to be fractal and their size is power law distributed from the grain size scale up to the thickness of the flowing layer. The implications of the absence of a characteristic length scale on available theoretical models of dense granular flows are discussed. Finally, we suggest a possible explanation of the difference between velocity profiles observed in surface flows and in flows down a rough inclined plane.

Journal Article↗

[Hereditary neuropathy with pressure hypersensitivity or tomaculous neuropathy].

Hereditary neuropathy liability to pressure palsies is characterized by recurring accesses of painless paralysis at the level of various nerves likely to be compressed. This affection remains underdiagnosed because of its usually benign course, sometimes without any symptom. The diagnosis is supported by clinical and electrophysiological data associated with, in the majority of patients, a deletion of one of the alleles coding for protein PMP 22 on the level of the locus 17p11.2.

Adult↗

Human cytomegalovirus infection of bone marrow myofibroblasts enhances myeloid progenitor adhesion and elicits viral transmission.

Human cytomegalovirus (CMV) infection of bone marrow transplant recipients can cause pancytopenia, as well as life-threatening interstitial pneumonia. CMV replicates actively in bone marrow stromal cells, whereas it remains latent in hematopoietic progenitors. Our aim was to study the influence of CMV infection on adherence of CD34(+) cells to the myofibroblastic component of human bone marrow and examine transmission of virus from myofibroblasts to CD34(+) cells. We show that smooth actin, but not fibronectin, organization is markedly modified by CMV infection of bone marrow stromal myofibroblasts. Nonetheless, CMV infection led to increased adherence of the CD34(+) progenitor cell line, KG1a, relative to adherence to uninfected myofibroblasts from the same donors. Adherence of CD34(+) cells to infected bone marrow myofibroblasts resulted in transfer of virions and viral proteins through close cell-to-cell contacts. This phenomenon may play a role in the pathophysiology of CMV bone marrow infection and in eventual virus dissemination.

Actins↗

Human cytomegalovirus chemokine receptor gene US28 is transcribed in latently infected THP-1 monocytes.

The human cytomegalovirus (HCMV) US28 gene product, pUS28, is a G protein-coupled receptor that interacts with both CC and CX(3)C chemokines. To date, the role of pUS28 in immune evasion and cell migration has been studied only in cell types that can establish productive HCMV infection. We show that HCMV can latently infect THP-1 monocytes and that during latency US28 is transcribed. We also show that the transcription is sustained during differentiation of the THP-1 monocytes. Since cells expressing pUS28 were previously shown to adhere to immobilized CX(3)C chemokines (C. A. Haskell, M. D. Cleary, and I. F. Charo, J. Biol. Chem. 275:34183-34189, 2000), we hypothesize that latently infected circulating monocytes express pUS28, thereby enabling adhesion of these cells to CX(3)C-exposing endothelium. Consequently, the US28-encoded chemokine receptor may play an important role in dissemination of latent HCMV.

Antigens, Viral↗

Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells.

An in vitro model of human CMV infection of primary retinal pigment epithelial (RPE) cells was used to study the effects of cytokines on CMV replication in these cells, which are targets of CMV infection in vivo. IFN-gamma and IFN-beta were potent inhibitors of CMV replication in RPE cells, while TNF-alpha, IL-1beta, or TGF-beta2 did not affect viral replication. Inhibition by IFN-gamma, and to a lesser extent IFN-beta, was almost completely reversed by addition of L-tryptophan to the culture medium, strongly implicating the indoleamine 2,3 dioxygenase (IDO) pathway. Polyadenylated IDO mRNA accumulation was detected as early as 2 h after IFN stimulation. Furthermore, CMV blocked the production of nitric oxide by the inducible form of nitric oxide synthase. This inhibition depended on a functional viral genome. However, exogenous nitric oxide significantly inhibited viral protein expression in RPE cells. Thus, CMV infection blocks the inducible nitric oxide synthase pathway activated by IFN-gamma and IL-1beta, but cannot counteract the IFN-induced IDO pathway, which ultimately controls its replication in primary human RPE cells.

Antiviral Agents↗

Kinetics of transcription of human cytomegalovirus chemokine receptor US28 in different cell types.

In permissive cells, human cytomegalovirus encodes the protein US28, a functional CC chemokine receptor. US28 polyadenylated mRNA could be detected by RT-PCR as early as 2 h post-infection. US28 mRNA appeared after major IE1 transcripts (UL123), but before transcripts of the early genes pp65 (UL83) and gB (UL55), and the late gene pp150 (UL32). This temporal appearance indicates that US28 is transcribed earlier than previously reported. Furthermore, US28 mRNA could be detected in semi- and non-permissive cells.

Animals↗

Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells.

Human cytomegalovirus (HCMV), a betaherpesvirus, has developed several ways to evade the immune system, notably downregulation of cell surface expression of major histocompatibility complex class I heavy chains. Here we report that HCMV has devised another means to compromise immune surveillance mechanisms. Extracellular accumulation of both constitutively produced monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-superinduced RANTES (regulated on activation, normal T cell expressed and secreted) was downregulated in HCMV-infected fibroblasts in the absence of transcriptional repression or the expression of polyadenylated RNA for the cellular chemokine receptors CCR-1, CCR-3, and CCR-5. Competitive binding experiments demonstrated that HCMV-infected cells bind RANTES, MCP-1, macrophage inflammatory protein (MIP)-1beta, and MCP-3, but not MCP-2, to the same receptor as does MIP-1alpha, which is not expressed in uninfected cells. HCMV encodes three proteins with homology to CC chemokine receptors: US27, US28, and UL33. Cells infected with HCMV mutants deleted of US28, or both US27 and US28 genes, failed to downregulate extracellular accumulation of either RANTES or MCP-1. In contrast, cells infected with a mutant deleted of US27 continues to bind and downregulate those chemokines. Depletion of chemokines from the culture medium was at least partially due to continuous internalization of extracellular chemokine, since exogenously added, biotinylated RANTES accumulated in HCMV-infected cells. Thus, HCMV can modify the chemokine environment of infected cells through intense sequestering of CC chemokines, mediated principally by expression of the US28-encoded chemokine receptor.

Binding Sites↗

Molecular resolution of marine turtle stock composition in fishery bycatch: a case study in the Mediterranean.

Based on an extensive sampling regime from both nesting populations and bycatch, frequency analyses of mitochondrial (mt) DNA control region haplotypes in the Mediterranean were used to assess the genetic structure and stock composition of the loggerhead sea turtle, Caretta caretta, in different marine fisheries. The analyses show the following. (i) In drifting longline fisheries working in Mediterranean pelagic habitats 53-55% of turtles caught originated from the Mediterranean stock; (ii) In bottom-trawl fisheries all turtle bycatch is derived from this regional stock; (iii) This regional stock contribution to fishery bycatch suggests that the population size of the Mediterranean loggerhead nesting population is significantly larger than previously thought. This is consistent with a recent holistic estimate based on the discovery of a large rookery in Libya. (iv) Present impact of fishery-related mortality on the Mediterranean nesting population is probably incompatible with its long-term conservation. Sea turtle conservation regulations are urgently needed for the Mediterranean fisheries. (v) The significant divergence of mtDNA haplotype frequencies of the Turkish loggerhead colonies define this nesting population as a particularly important management unit. Large immature and adult stages from this management unit seem to be harvested predominantly by Egyptian fisheries. (vi) Combined with other data, our findings suggest that all the nesting populations in the Mediterranean should be considered as management units sharing immature pelagic habitats throughout the Mediterranean (and possibly the eastern Atlantic), with distinct and more localized benthic feeding habitats in the eastern basin used by large immatures and adults. (vii) Between the strict oceanic pelagic and the benthic stages, immature turtles appear to live through an intermediate neritic stage, in which they switch between pelagic and benthic foods.

Animals↗

Modulation of RANTES production by human cytomegalovirus infection of fibroblasts.

Chemokines play a major role in inflammatory responses and affect hematopoiesis both negatively and positively. We show that fresh isolates and laboratory strains (Towne and Ad-169) of human cytomegalovirus (HCMV) induce production of the CC chemokine RANTES in fibroblasts. Induction of extracellular RANTES production occurred as early as 8 h after infection, peaked around 24 h after infection, and was almost undetectable by 48 and 72 h. Upregulation occurred in the absence of viral DNA synthesis, suggesting that it was due to immediate-early-early HCMV gene expression. CMV infection stimulated RANTES transcription, since reverse transcription-PCR detected a sharp increase in RANTES RNA which persisted even when extracellular RANTES was no longer detected. Induction of RANTES in fibroblasts was not due to prior induction of tumor necrosis factor alpha or interleukin 1 beta. Down-regulation required an active viral genome. Decrease of RANTES in culture supernatants may be associated with the appearance of the HCMV CC chemokine receptor US28, since we show that this gene is transcribed as early as 8 h after infection. Modulation of CC chemokine production early during CMV infection might have a regulatory effect on viral replication, as well as affect immune surveillance.

Cells, Cultured↗

[Genetic studies of relationship between Mediterranean and Atlantic populations of loggerhead turtle Caretta caretta with mitochondrial marker].

The loggerhead turtle Caretta caretta is an endangered species in the Mediterranean. Therefore, the definition of the Mediterranean population, and their relationships to the Atlantic population is of fundamental importance. For this purpose, we have sequenced a portion of the mitochondrial cytochrome b gene to generate genetic markers. Results indicate that the Mediterranean nesting female population is genetically isolated from the Atlantic nesting female population, but loggerhead turtles of Atlantic origin were found in the West Mediterranean basin. This entry of Atlantic loggerheads in the Mediterranean confirms earlier speculations and presents special conservation problems. The Spanish swordfish longline fishery which incidentally captures large numbers of loggerheads in the West Mediterranean basin has therefore an impact on the Atlantic population. These data demonstrate the international nature of marine turtle conservation.

Animals↗