Middle Palaeolithic and Neolithic Occupations around Mundafan Palaeolake,Saudi Arabia: Implications for Climate Change and Human Dispersals

The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub’ al-Khali (the ‘Empty Quarter’), the world’s largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub’ al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources.     

Century‐long apparent decrease in intrinsic water‐use efficiency with no evidence of progressive nutrient limitation in African tropical forests

Forests exhibit leaf‐ and ecosystem‐level responses to environmental changes. Specifically, rising carbon dioxide (CO₂) levels over the past century are expected to have increased the intrinsic water‐use efficiency (iWUE) of tropical trees while the ecosystem is gradually pushed into progressive nutrient limitation. Due to the long‐term character of these changes, however, observational datasets to validate both paradigms are limited in space and time. In this study, we used a unique herbarium record to go back nearly a century and show that despite the rise in CO₂ concentrations, iWUE has decreased in central African tropical trees in the Congo Basin. Although we find evidence that points to leaf‐level adaptation to increasing CO₂—that is, increasing photosynthesis‐related nutrients and decreasing maximum stomatal conductance, a decrease in leaf δ¹³C clearly indicates a decreasing iWUE over time. Additionally, the stoichiometric carbon to nitrogen and nitrogen to phosphorus ratios in the leaves show no sign of progressive nutrient limitation as they have remained constant since 1938, which suggests that nutrients have not increasingly limited productivity in this biome. Altogether, the data suggest that other environmental factors, such as increasing temperature, might have negatively affected net photosynthesis and consequently downregulated the iWUE. Results from this study reveal that the second largest tropical forest on Earth has responded differently to recent environmental changes than expected, highlighting the need for further on‐ground monitoring in the Congo Basin.     

Differential ganciclovir-mediated cell killing by glutamine 125 mutants of herpes simplex virus type 1 thymidine kinase

The therapeutic combination of the herpesvirus simplex virus type 1 (HSV-1) thymidine kinase (TK) gene and the prodrug, ganciclovir (GCV), has found great utility for the treatment of many types of cancer. After initial phosphorylation of GCV by HSV-1 TK, cellular kinases generate the toxic GCV-triphosphate metabolite that is incorporated into DNA and eventually leads to tumor cell death. The cellular and pharmacological mechanisms by which metabolites of GCV lead to cell death are still poorly defined. To begin to address these mechanisms, different mutated forms of HSV-1 TK at residue Gln-125 that have distinct substrate properties were expressed in mammalian cell lines. It was found that expression of the Asn-125 HSV-1 TK mutant in two cell lines, NIH3T3 and HCT-116, was equally effective as wild-type HSV-1 TK for metabolism and sensitivity to GCV, bystander effect killing and induction of apoptosis. The major difference between the two enzymes was the lack of deoxypyrimidine metabolism in the Asn-125 TK-expressing cells. In HCT-116 cells expressing the Glu-125 TK mutant, GCV metabolism was greatly attenuated, yet at higher GCV concentrations, cell sensitivity to the drug and bystander effect killing were diminished but still effective. Cell cycle analysis, 4', 6'-diamidine-2'-phenylindoledihydrochloride staining, and caspase 3 activation assays indicated different cell death responses in the Glu-125 TK-expressing cells as compared with the wild-type HSV-1 TK or Asn-125 TK-expressing cells. A mechanistic hypothesis to explain these results based on the differences in GCV-triphosphate metabolite levels is presented.     

Human pregnancy: the role of chemokine networks at the fetal-maternal interface

Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. Similar events occur in pregnancy during development of the fetal-maternal interface, where there is extensive leukocyte trafficking and tissue morphogenesis, and this is accompanied by abundant chemokine expression. The relationship between chemokines, leukocytes and placental development is beginning to be delineated. During pregnancy a specialised population of maternal leukocytes infiltrates the implantation site. These leukocytes are thought to sustain the delicate balance between protecting the developing embryo/fetus and tolerating its hemiallogeneic tissues. A network of chemokine expression by both fetal and maternal components in the pregnant uterus functions in establishing this leukocyte population. Intriguingly, experiments investigating immune cell recruitment revealed the additional possibility that chemokines influence aspects of placental development. Specifically, cytotrophoblasts, the effector cells of the placenta, express chemokine receptors that can bind ligands found at key locations, implicating chemokines as regulators of cytotrophoblast differentiation and migration. Thus, as in other systems, at the fetal-maternal interface chemokines might regulate multiple functions.     

Ecological consequences of the phylogenetic and physiological diversities of acetogens

Acetogens reduce CO₂ to acetate via the acetyl-CoA pathway and have been classically thought of as obligately anaerobic bacteria. Nearly 100 acetogenic species from 20 different genera have been isolated to date. These isolates are able to use very diverse electron donors and acceptors, and it is thus very likely that the in situ activities of acetogens are very diverse and not restricted to acetogenesis. Since acetogens constitute a very phylogenetically diverse bacteriological group, it should be anticipated that they can inhabit, and have impact on, diverse habitats. Indeed, they have been isolated from a broad range of habitats, including oxic soils and other habitats not generally regarded as suitable for acetogens. Although the ecological impact of acetogens is determined by the in situ manifestation of their physiological potentials, assessing their in situ activities is difficult due to their physiological and phylogenetic diversities. This mini-review will highlight a few of the physiological and ecological realities of acetogens, and will focus on: (i) metabolic diversities and regulation, (ii) phylogenetic diversity and molecular ecology, and (iii) the capacity of acetogens to cope with oxic conditions under both laboratory and in situ conditions. This revised version was published online in August 2006 with corrections to the Cover Date.     

Acidovorax-like symbionts in the nephridia of earthworms

Dense accumulations of bacteria in the excretory organs, nephridia, were first described more than 75 years ago in members of the annelid family Lumbricidae (earthworms). These nephridial symbionts were assumed to play a role in the degradation of proteins in the excretory fluid for nitrogen recycling. In the present study, the phylogenetic affiliation of the nephridial bacteria of the earthworms Lumbricus terrestris, Aporrectodea tuberculata, Octolasion lacteum and Eisenia foetida was resolved. The 16S rRNA gene sequences of the symbionts formed a monophyletic cluster within the genus Acidovorax. Similarity between symbiont sequences from different host species was 95.5-97.6%, whereas similarity was> 99% between symbiont sequences from individuals of the same species. Densely packed bacteria were detected in the ampulla of the nephridia by fluorescence in situ hybridization (FISH) using Acidovorax-specific oligonucleotide probes. No other bacterial cells could be found by FISH, although a few sequences other than Acidovorax had been found by PCR and cloning. These results suggest that the Acidovorax-earthworm symbiosis is a stable, host-specific association that has evolved from a common bacterial ancestor. Given the close phylogenetic relationship of the symbionts to proteolytic, free-living Acidovorax species, they may indeed play a role in protein degradation during nitrogen excretion by earthworms.     

The production of recombinant pharmaceutical proteins in plants

Imagine a world in which any protein, either naturally occurring or designed by man, could be produced safely, inexpensively and in almost unlimited quantities using only simple nutrients, water and sunlight. This could one day become reality as we learn to harness the power of plants for the production of recombinant proteins on an agricultural scale. Molecular farming in plants has already proven to be a successful way of producing a range of technical proteins. The first plant-derived recombinant pharmaceutical proteins are now approaching commercial approval, and many more are expected to follow.     

Growth hormone hypersecretion in a girl with neurofibromatosis type 1 and an optic nerve glioma: resolution following chemotherapy

Growth hormone hypersecretion is extremely rare in childhood. We report a girl with neurofibromatosis type 1, an extensive optic nerve glioma and growth hormone hypersecretion. She was treated with chemotherapy to prevent further extension of her sight-threatening tumour. Three years after chemotherapy her growth hormone hypersecretion has resolved although she has gone on to develop precocious puberty.     

A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice

Previous studies have shown that the production of recombinant antibodies in plants is highly efficient and presents numerous therapeutic applications. It is, however, known that plant glycoproteins display different glycosylation patterns to those exhibited by mammalian glycoproteins. Thus, it is important to know if these plant recombinant antibodies could induce undesirable immune responses in mammal; and to date no report has documented the potential immunogenicity of parenterally administered plant recombinant antibodies in animals. In order to answer this question, mice were immunised subcutaneously with a recombinant mouse monoclonal antibody produced in tobacco plants, together with alum as adjuvant. Two control groups were immunised in the same way with either the original murine monoclonal antibody or horseradish peroxidase (a plant glycoprotein). Analyses by direct immunoassay, competition immunoassay and real-time surface plasmon resonance, showed undetectable levels of antibody directed against both the protein and the glycan part of the plant recombinant antibody. These results have a direct relevance for the application of plant recombinant proteins as therapeutic agents and vaccines in humans.     

Atomic force microscopy examination of the topography of a hydrated bacterial biofilm on a copper surface

A bacterium, designated CCI#8, that was isolated from a corroded copper coupon colonized both polished and unpolished copper surfaces under batch culture conditions. Atomic Force Microscopy (AFM) images revealed that the biofilm was heterogeneous in nature, both in depth and in cell distribution. Bacterial cells were shown to be associated with pits on the surface of the unpolished copper coupons. These observations support previous studies that CCI#8 is associated with the pitting corrosion of copper.