Modern humans in Sarawak, Malaysian Borneo, during Oxygen Isotope Stage 3: palaeoenvironmental evidence from the Great Cave of Niah

During recent reinvestigations in the Great Cave of Niah in Borneo, the ‘Hell Trench’ sedimentary sequence seen by earlier excavators was re-exposed. Early excavations here yielded the earliest anatomically-modern human remains in island Southeast Asia. Calibrated radiocarbon dates, pollen, algal microfossils, palynofacies, granulometry and geochemistry of the ‘Hell Trench’ sequence provide information about environmental and vegetational changes, elements of geomorphic history and information about human activity. The ‘Hell’ sediments were laid down episodically in an ephemeral stream or pool. The pollen suggests cyclically changing vegetation with forest habitats alternating with more open environments; indicating that phases with both temperatures and precipitation reduced compared with the present. These events can be correlated with global climate change sequences to produce a provisional dating framework. During some forest phases, high counts of Justicia, a plant which today colonises recently burnt forest areas, point to fire in the landscape. This may be evidence for biomass burning by humans, presumably to maintain forest-edge habitats. There is evidence from palynofacies for fire on the cave floor in the ‘Hell’ area. Since the area sampled is beyond the limit of plant growth, this is evidence for human activity. The first such evidence is during an episode with significant grassland indicators, suggesting that people may have reached the site during a climatic phase characterised by relatively open habitats ~50 ka. Thereafter, people were able to maintain a relatively consistent presence at Niah. The human use of the ‘Hell’ area seems to have intensified through time, probably because changes in the local hydrological regime made the area dryer and more suitable for human use.

A 50,000-year record of Late Pleistocene tropical vegetation and human impact in lowland Borneo.

There has been considerable uncertainty about the nature of Pleistocene environments colonised by the first modern humans in Island SE Asia, and about the vegetation of the Last Glacial Maximum (LGM) in the region. Here, the palynology from a series of exposures in the Great Cave of Niah, Sarawak, Malaysian Borneo, spanning a period from ca. 52,000 to 5000 BP is described. Vegetation during this period was climate-driven and often highly unstable. Interstadials are marked by lowland forest, sometimes rather dry and at times by mangroves. Stadials are indicated by taxa characteristic of open environments or, as at the LGM, by highly disturbed rather open forest. Stadials are also characterised by taxa now restricted to 1000-1600 m above sea level, suggesting temperature declines of ca 7-9 C relative to present, by comparison with modern lapse rates. The practice of biomass burning appears associated with the earliest human activity in the cave.

Cloning and characterization of the mouse homologue of the human dendritic cell maturation marker CD208/DC-LAMP

DC-LAMP, a member of the lysosomal-associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DC maturation. DC-LAMP is detected first in activated human DC within MHC class II molecules-containing compartments just before the translocation of MHC class II-peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC-LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC-LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2-B4 and 3q26) and conserved organization with the human DC-LAMP gene. Analysis of mouse DC-LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC-LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC-LAMP in human DC.

Major genetic marker of nidoviruses encodes a replicative endoribonuclease

Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the 30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn2+-dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2'-3' cyclic phosphate ends. 2'-O-ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2'-O-ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.