Template-directed synthesis of a genetic polymer in a model protocell

Contemporary phospholipid-based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel-to-liquid transition temperature, phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles that retain encapsulated oligonucleotides and are capable of growth and division. Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.     

Mellifluous matures to malodorous in musth

Male Asian elephants in musth--an annual period of heightened sexual activity and intensified aggression--broadcast odoriferous, behaviourally influential messages from secretions of the temporal gland. From our observations in the wild, together with instantaneous chemical sampling and captive-elephant playback experiments, we have discovered that young, socially immature males in musth signal their naivety by releasing honey-like odours to avoid conflict with adult males, whereas older musth males broadcast malodorous combinations to deter young males, facilitating the smooth functioning of male society. As elephant--human conflicts can upset this equilibrium, chemically modulating male behaviour may be one way to help the conservation of wild elephants.     

LKB1 modulates lung cancer differentiation and metastasis

Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.     

Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing

Mammalian ageing is associated with reduced regenerative capacity in tissues that contain stem cells. It has been proposed that this is at least partially caused by the senescence of progenitors with age; however, it has not yet been tested whether genes associated with senescence functionally contribute to physiological declines in progenitor activity. Here we show that progenitor proliferation in the subventricular zone and neurogenesis in the olfactory bulb, as well as multipotent progenitor frequency and self-renewal potential, all decline with age in the mouse forebrain. These declines in progenitor frequency and function correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibitor linked to senescence. Ageing p16INK4a-deficient mice showed a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis, and the frequency and self-renewal potential of multipotent progenitors. p16INK4a deficiency did not detectably affect progenitor function in the dentate gyrus or enteric nervous system, indicating regional differences in the response of neural progenitors to increased p16INK4a expression during ageing. Declining subventricular zone progenitor function and olfactory bulb neurogenesis during ageing are thus caused partly by increasing p16INK4a expression.     

Pattern of adult eclosion during interspecific competition

Summary During interspecific competition, eggs of the same age, of 2 different species, experience different speeds of development. In each mixed culture there exist 2 different peaks of adult emergence. Here is a mechanism ensuring that the maximum number of one of the competing species emerges first followed by the other. The possible implications of this are discussed. Thanks are due to Dr S.R. Ramesh and Iris Sedlak for their assistance in the preparation of the line drawings.     

Toxicity of Dithane M-45 onDrosophila melanogaster

Summary The toxicity of different concentrations of Dithane M-45 onDrosophila melanogaster was determined. The chemical was administered by larval feeding. It has been estimated that the LC₅₀ is 17.5 mg/100 ml food medium. The studies have suggested that Dithane M-45 has a pronounced effect on the rate of development and viability.Acknowledgments. The authors are grateful to Dr M.R. Rajasekarasetty, F.N.A., Professor and Head of the Department of Postgraduate Studies and Research in Zoology, Manasa Gangotri, University of Mysore, Mysore, for his constant encouragement and valuable suggestions. One of us (V.V.) is thankful to the UGC for the financial assistance.