A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection.

The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN-related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN-related molecule is L-SIGN, liver/lymph node-specific ICAM-3-grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.

The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates.

The CD209 gene family that encodes C-type lectins in primates includes CD209 (DC-SIGN), CD209L (L-SIGN) and CD209L2. Understanding the evolution of these genes can help understand the duplication events generating this family, the process leading to the repeated neck region and identify protein domains under selective pressure. We compiled sequences from 14 primates representing 40 million years of evolution and from three non-primate mammal species. Phylogenetic analyses used Bayesian inference, and nucleotide substitutional patterns were assessed by codon-based maximum likelihood. Analyses suggest that CD209 genes emerged from a first duplication event in the common ancestor of anthropoids, yielding CD209L2 and an ancestral CD209 gene, which, in turn, duplicated in the common Old World primate ancestor, giving rise to CD209L and CD209. K(A)/K(S) values averaged over the entire tree were 0.43 (CD209), 0.52 (CD209L) and 0.35 (CD209L2), consistent with overall signatures of purifying selection. We also assessed the Toll-like receptor (TLR) gene family, which shares with CD209 genes a common profile of evolutionary constraint. The general feature of purifying selection of CD209 genes, despite an apparent redundancy (gene absence and gene loss), may reflect the need to faithfully recognize a multiplicity of pathogen motifs, commensals and a number of self-antigens.

[Morphology of acute lung injuries in mechanic trauma].

The lungs from 60 subjects who had died of polytrauma were studied morphologically. The heads of the corpses were not injuried. The aim of the study was investigation of characteristics and time of development of structural changes associated with lung injury. Early structural changes in trauma were disorders of circulation including microcirculation, acute emphysema, distelectases and atelectases, injury of bronchial and bronchiolar mucosa. Pulmonary edema and systemic inflammatory reaction emerge in the first hours after trauma.

The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts.

The ril gene encoding a LIM domain protein of an unknown function was previously identified by differential expression cloning as a candidate tumor suppressor gene in rat fibroblasts (Kiess, M., Scharm, B., Aguzzi, A., Hajnal, A., Klemenz, R., Schwarte-Waldhoff, I., Schafer, R., 1995. Expression of ril, a novel LIM domain gene, is down-regulated in HRAS-transformed cells and restored in phenotypic revertants. Oncogene 10, 61-68). Searching for novel genes on human chromosome 5q31.1 by the cDNA selection technique, we isolated a cDNA clone identical with the cDNA of the human RIL gene (GenBank Accession No. X93510). The human 5q31.1 region is of interest because it contains the cytokine gene cluster and is frequently deleted in the malignant cells of patients with myelodysplasia and myeloid leukemia. Using Southern blot analysis and restriction mapping of genomic YAC (yeast artificial chromosome) and cosmid clones, we located the human RIL gene 240-260 kb telomeric to the IRF1 gene and characterized its genomic structure. PCR analysis indicated the presence of two alternative RIL transcripts in human fetal brain mRNA. The major transcript is identical with the RIL cDNA previously deposited in GenBank and contains seven exons distributed over 14.5 kb of genomic DNA with the two last 3'-exons coding a LIM domain. The minor transcript lacks the sixth exon compared with the major transcript, which leads to the loss of the LIM domain. We also identified two putative transcription start points (tsp) and sequenced the 5'-flanking region of RIL to reveal potential binding sites for transcriptional factors.

Mutation S543N in the thumb subdomain of the Taq DNA polymerase large fragment suppresses pausing associated with the template structure.

Substitution of Asn for the conserved Ser543 in the thumb subdomain of the Taq DNA polymerase large fragment (Klentaq DNA polymerase) prevents pausing during DNA synthesis and allows the enzyme to circumvent template regions with a complex structure. The mutant enzyme (KlentaqN DNA polymerase) provides specific PCR amplification and sequencing of difficult templates, e.g. those with a high GC% content or strong secondary structure.