Antibacterial agents based on the cyclic D,L-alpha-peptide architecture

The rapid emergence of bacterial infections that are resistant to many drugs underscores the need for new therapeutic agents. Here we report that six- and eight-residue cyclic d,l-alpha-peptides act preferentially on Gram-positive and/or Gram-negative bacterial membranes compared to mammalian cells, increase membrane permeability, collapse transmembrane ion potentials, and cause rapid cell death. The effectiveness of this class of materials as selective antibacterial agents is highlighted by the high efficacy observed against lethal methicillin-resistant Staphylococcus aureus infections in mice. Cyclic d,l-alpha-peptides are proteolytically stable, easy to synthesize, and can be derived from a potentially vast membrane-active sequence space. The unique abiotic structure of the cyclic peptides and their quick bactericidal action may also contribute to limit temporal acquirement of drug resistant bacteria. The low molecular weight d,l-alpha-peptides offer an attractive complement to the current arsenal of naturally derived antibiotics, and hold considerable potential in combating a variety of existing and emerging infectious diseases.     

多项式微分系统的不变直线的不同斜率的最大个数

本文证明了公式β（ｎ）＝σ（ｎ－１）＋１其中α（ｎ－１）是ｎ－１次多项式微分系统的不为直线的最多条数，βｎ）是ｎ次多项式微分系统的不变直线的不同斜率的最大个数。这里假设所讨论的多项式系统只有限条不变直线。     

Reconstructing Native American population history

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.     

Ca-efflux,from direct membrane injury by CCl4, is elicited by amphiphilic vehicles in vitro

Direct membrane injury by CCl₄, in situations excluding metabolic activation, was evaluated in saponin-permeabilized hepatocytes and in microsomes by measuring immediate Ca²⁺ efflux. A good correlation appears between the Ca²⁺ efflux and the level of CCl₄ in the membrane and also the variations in fluidity. Mixtures of CCl₄ with water-soluble vehicles were used to improve the dispersion of CCl₄ in the medium. The mixtures varied in their ability to elicit the membrane effects of CCl₄. The performance of ethanol and, to a lesser degree, other alcohols, suggests the existence of a water stable structural organization between CCl₄ and these amphiphilic vehicles, facilitating the transfer of CCl₄ to the membrane.