Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis

Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.     

The R- and AR-indices： Complementing the h-index

Based on the foundation laid by the h-index we introduce and study the R- and AR-indices. These new indices eliminate some of the disadvantages of the h-index, especially when they are used in combina-tion with the h-index. The R-index measures the h-core’s citation intensity, while AR goes one step further and takes the age of publications into account. This allows for an index that can actually in-crease and decrease over time. We propose the pair (h, AR) as a meaningful indicator for research evaluation. We further prove a relation characterizing the h-index in the power law model.     

Hirsch 指数研究的新进展

提出了离散Hirsch 指数（简称h 指数）的精确定义，引入了“Hirsch 核心”这一概念。不仅将h 指数推广到实数集，还介绍了其他相关的派生指数，g 指数和A 指数。只有h 指数和g 指数相结合，才能较全面地评价科学家的科研成就。     

On the history of the Euclidean Steiner tree problem

The history of the Euclidean Steiner tree problem, which is the problem of constructing a shortest possible network interconnecting a set of given points in the Euclidean plane, goes back to Gergonne in the early nineteenth century. We present a detailed account of the mathematical contributions of some of the earliest papers on the Euclidean Steiner tree problem. Furthermore, we link these initial contributions with results from the recent literature on the problem.     

Notes on the birds of Cold Spring Mountain, northwestern Colorado

Observations are presented on 117 bird species seen in a 250-km 2 area of northwestern Colorado adjacent to Utah and Wyoming. Three previously unreported species and seven status changes are listed for the Rangely, Colorado, latilong block.     

Selection of big sagebrush by sage grouse

Feeding sites of wintering sage grouse ( Centrocercus urophasianus ) were located, one each in stands of three subspecies of big sagebrush ( Artemisia tridentata : ssp. tridentata , basin; ssp. vaseyana , mountain; and ssp. Wyomingensis , Wyoming). Evidences of differential use of plants within subspecies were observed. Whole leaves from fed-on and nonfed-on big sagebrush plants were examined for intrasubspecies chemical comparisons of crude protein, phosphorus, in vitro digestibility, and monoterpenoids. No significant differences were detected except for in vitro digestibility of Wyoming fed-on and nonfed-on big sagebrush and monoterpenoid content of basin big sagebrush. Nutritive content of all three subspecies was high, which may in part help to explain wintering sage grouse weight gains.     

Bristlecone pine and Clark's Nutcracker: probable interaction in the White Mountains, California

Many bristlecone pines in the White Mountains, California, are members of multistem clumps. We propose that these clumps have arisen by multiple germinations from seed caches of Clark’s Nutcracker, as occurs in several other pine species. The commonness of nutcrackers and their caching of singleleaf pinyon seeds in the study area provide supporting evidence. Other vertebrates appear unlikely to be responsible for the stem clumps. Seed burial may be required to establish regeneration on these adverse sites where bristlecone pine attains great longevity.        

Additions to the vascular flora of Teton County, Wyoming

An annotated list of 125 taxa new to the flora of Teton County is presented, increasing the number of known species to 1043.