Inclusive fitness in evolution

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. For over fifty years, the evolution of social behaviour has been guided by the concept of inclusive fitness as a measure of evolutionary success. Nowak et al. argue that inclusive fitness should be abandoned. In so doing, however, they misrepresent the role that inclusive fitness has played in the theory of social evolution by which understanding social behaviour in a variety of disciplines has developed and flourished. By discarding inclusive fitness on the basis of its limitations, they create a conceptual tension which, we argue, is unnecessary, and potentially dangerous for evolutionary biology.     

Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B

Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.     

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.     

诺贝尔奖走过的一个世纪

最近 ,几位科学家看到了他们的名字已经与世人瞩目的成就、与永远不会失去的名誉相提并论。公众正探究着这些新出现的名人是怎样达到事业顶峰的 :他们克服了什么障碍、是站在什么人的肩膀上才看得如此之远。不计今年的得奖者 ,自诺贝尔在 1 0 0年前设奖至今 ,在 3个科学领域———物理学、化学和生理学或医学———中已经颁发了 2 80个奖项。艰苦的研究和献身未必能取得作为在这个独一无二的“俱乐部”中的一个成员的资格。斯德哥尔摩的诺贝尔博物馆馆长斯万特·林德奎斯特 (ＳｖａｎｔｅＬｉｎｄｑｖｉｓｔ)说 :“诺贝尔奖不是为终身的成就…     

Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling

The cellular machinery promoting phagocytosis of corpses of apoptotic cells is well conserved from worms to mammals. An important component is the Caenorhabditis elegans engulfment receptor CED-1 (ref. 1) and its Drosophila orthologue, Draper. The CED-1/Draper signalling pathway is also essential for the phagocytosis of other types of 'modified self' including necrotic cells, developmentally pruned axons and dendrites, and axons undergoing Wallerian degeneration. Here we show that Drosophila Shark, a non-receptor tyrosine kinase similar to mammalian Syk and Zap-70, binds Draper through an immunoreceptor tyrosine-based activation motif (ITAM) in the Draper intracellular domain. We show that Shark activity is essential for Draper-mediated signalling events in vivo, including the recruitment of glial membranes to severed axons and the phagocytosis of axonal debris and neuronal cell corpses by glia. We also show that the Src family kinase (SFK) Src42A can markedly increase Draper phosphorylation and is essential for glial phagocytic activity. We propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway. These Draper-Src42A-Shark interactions are strikingly similar to mammalian immunoreceptor-SFK-Syk signalling events in mammalian myeloid and lymphoid cells. Thus, Draper seems to be an ancient immunoreceptor with an extracellular domain tuned to modified self, and an intracellular domain promoting phagocytosis through an ITAM-domain-SFK-Syk-mediated signalling cascade.     

Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes

Mutation hotspots are commonly observed in genomic sequences and certain human disease loci, but general mechanisms for their formation remain elusive. Here we investigate the distribution of single-nucleotide changes around insertions/deletions (indels) in six independent genome comparisons, including primates, rodents, fruitfly, rice and yeast. In each of these genomic comparisons, nucleotide divergence (D) is substantially elevated surrounding indels and decreases monotonically to near-background levels over several hundred bases. D is significantly correlated with both size and abundance of nearby indels. In comparisons of closely related species, derived nucleotide substitutions surrounding indels occur in significantly greater numbers in the lineage containing the indel than in the one containing the ancestral (non-indel) allele; the same holds within species for single-nucleotide mutations surrounding polymorphic indels. We propose that heterozygosity for an indel is mutagenic to surrounding sequences, and use yeast genome-wide polymorphism data to estimate the increase in mutation rate. The consistency of these patterns within and between species suggests that indel-associated substitution is a general mutational mechanism.