Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.     

Systematic identification of genomic markers of drug sensitivity in cancer cells

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.     

First dairying in green Saharan Africa in the fifth millennium BC

In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities. The remarkable rock art found widely across the region depicts cattle herding among early Saharan pastoral groups, and includes rare scenes of milking; however, these images can rarely be reliably dated. Although the faunal evidence provides further confirmation of the importance of cattle and other domesticates, the scarcity of cattle bones makes it impossible to ascertain herd structures via kill-off patterns, thereby precluding interpretations of whether dairying was practiced. Because pottery production begins early in northern Africa the potential exists to investigate diet and subsistence practices using molecular and isotopic analyses of absorbed food residues. This approach has been successful in determining the chronology of dairying beginning in the 'Fertile Crescent' of the Near East and its spread across Europe. Here we report the first unequivocal chemical evidence, based on the δ(13)C and Δ(13)C values of the major alkanoic acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium bc. Interpretations are supported by a new database of modern ruminant animal fats collected from Africa. These findings confirm the importance of 'lifetime products', such as milk, in early Saharan pastoralism, and provide an evolutionary context for the emergence of lactase persistence in Africa.     

NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10(-/-) mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and -independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4(+) T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.     

应用于服装与人体之间的压力传感器

开发了一种微薄型压力传感器.传感器精确测量所穿服装施加在人体上的压力,并且将其作为一种方法用来决定在各种不同款式的服装中所需要的适当的放松量的大小.实验结果显示,传感器可以测试在不同变化姿势时服装的压力.