RNAi-mediated gene silencing in non-human primates

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.     

沥青混合料水稳定性分析

根据沥青混合料的强度形成原理和破坏机理以及沥青混合料与水相互作用机理，着重从集料性质、沥青性质、混合料类型、集料粒径和面层压实层厚度等方面分析了影响沥青混合料水稳定性的因素，提出了应在集料选择、沥青选择、沥青混合料设计、加热与拌和、碾压工艺、环境等方面采取措施来改善沥青混合料的水稳定性。     

Variation in Lewsia kelloggii (Portulacaceae) with description of a new species endemic to Idaho

Lewisia kelloggii has been understood as a rare plant with a disjunct range in California and Idaho. Examination of herbarium specimens and analysis of isozymes in 6 Idaho and 7 California populations revealed consistent differences between plants of the 2 states. Fixed differences in alleles at 2 loci (AAT2 and PGI1) distinguished Idaho from California plants. Genetic identities based on isozymes between Idaho and California populations averaged 0.58, lower than the average for congeneric plant species. Idaho plants were smaller than most California plants, but California plants were variable. The most consistent morphological difference between Idaho and California specimens was the difference in the number of glands on the margins of bracts and sepals. Idaho plants had 0 (-5) pink glands on each margin of these organs, all on teeth near the tips. In California plants these organs had 12-25 glands on each margin, the distal ones elevated on teeth and the proximal ones sessile. We recognize the Idaho plants as a new species, L. sacajaweana , and retain the name L. kelloggii for the California populations.     

New Astragalus (Leguminosae) from the Goose Creek Drainage, Utah - Nevada

A new species, Astragalus anserinus Atwood, Goodrich, & Welsh, is described from specimens taken from tuffaceous outcrops in the Goose Creek drainage of Box Elder County, Utah and Elko County Nevada.        

Ecological studies of a regulated stream: Huntington River, Emery County, Utah

A 36.9x10 6 m 3 reservoir constructed on Huntington River, Emery County, Utah, resulted in changes in physical habitat, water quality, temperature, and flow regime. The greatest changes in physical habitat resulted from: (1) sediment additions from dam and road construction plus erosion of reservoir basin during filling; and (2) changing stream flow from a spring high runoff regime to a moderated flow regime. Elimination of spring nutrient concentration peaks and overall reduction of total dissolved nutrient availability in the river plus moderate reductions in pH were the most apparent water quality changes below the reservoir. Water temperature changes were an increased diurnal and seasonal constancy, summer depression, and winter elevation, generally limited to a 10–12 km reach below the dam. Physical and chemical changes altered macroinvertebrate community structure, with changes greatest near the dam and progressively less as distance downstream increased. Below the dam: (1) more environmentally tolerant taxa increased their dominance; (2) relative numbers of smaller sized individuals increased in relation to larger individuals; and (3) filter feeding, collector/gatherers, and scrapers gained an advantage over shredders. Insect taxa such as Rhithrogena robusta, Pteronarcella badia, and Ephemerella doddsi were eliminated from stream reaches near the dam, and other taxa such as Arctopsyche grandis, Chironomidae, and Simuliidae increased in numbers. Late spring to early summer egg hatch proved to be a disadvantage to Brachycentrus occidentalis, and B. americanus, with a fall hatch, was less impacted by altered river flow patterns. Macroinvertebrate taxa with small instar larvae present from late summer to early fall were negatively impacted by the unnaturally high July and August flows. The reservoir became a physical barrier to downstream larval drift and upcanyon and downcanyon immigration of adults, resulting in reduced numbers of several species above and below the reservoir.         

Terrestrial vertebrate fauna of the Kaiparowits Basin

This report includes data collected during an investigation by Brigham Young University personnel from 1971 to 1976, as well as a literature review. The fauna of the Kaiparowits Basin is represented by 7 species of amphibians (1 salamander, 5 toads, and 1 tree frog), 29 species of reptiles (1 turtle, 16 lizards, and 12 snakes), 183 species of birds (plus 2 hypothetical), and 74 species of mammals. Geographic distribution of the various species within the basin are discussed. Birds are categorized according to their population and seasonal status. Avian habitat relationships are discussed, and extensions of range are reported for 5 species of birds. Three threatened or endangered avian species occur in the basin. Four avian species seem to have declined significantly in numbers in recent years.     

Diversification within the Mexican vole ( Microtus mexicanus ) and the role of post-Pleistocene climate change

Normal 0 false false false MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} To examine the partitioning of genetic variation within the Mexican vole ( Microtus mexicanus ), we analyzed variation within the cytochrome b (cyt b, ca. 953 bp) from 44 samples of the Mexican vole from the mountains of the southwestern United States and Mexico. Phylogeographic analyses demonstrated strong support for a western clade and an eastern clade, corresponding to the Sierra Madre Occidental and mountains of the southwestern United States (western clade) and the Sierra Madre Oriental and the Sierra Madre del Sur (eastern clade). Levels of genetic distinctiveness among vole populations in Mexico and the southwestern United States support recognition of the Mogollon vole ( Microtus mogollonensis ). Estimates of lineage divergence suggested an older divergence for populations in Mexico and a more recent divergence for the presumptive M. mogollonensis. Ecological analyses demonstrated a distinct climate niche between vole lineages in the Southwest and Mexico, which indicated the possible role of environmental variation in diversification of the Mexican vole. A similar pattern of climatic separation was also demonstrated between clades of the codistributed taxa Sigmodon hispidus, Neotoma mexicana, and Peromyscus truei, suggesting a broader role for climatic variation in the origin and maintenance of the region’s biodiversity. Para examinar la distribución de la variación genética en el metorito mexicano, analizamos la variación en el citocromo b (cyt b, c. 953 pb ) en 44 muestras del metorito mexicano de las montañas de México y del suroeste de Estados Unidos. Los análisis filogeográficos demostraron fuerte apoyo para un clado occidental y un clado oriental, correspondientes a la Sierra Madre Occidental y las montañas del suroeste de Estados Unidos (oeste) y la Sierra Madre Oriental y la Sierra Madre del Sur (este). Los niveles de diferencia genética entre las poblaciones de metoritos en México y las del sur de Estados Unidos apoyan el reconocimiento del metorito Mogollon ( Microtus mogollonensis ) como especie. Las estimaciones de divergencia entre linajes indican una divergencia más remota para las poblaciones en México y una más reciente para el presunto M. mogollonensis. Los análisis ecológicos demuestran nichos climáticos distintos entre los linajes de metorito en el suroeste de Estados Unidos y en México, lo cual indica el posible papel de la variación ambiental en la diversificación del metorito mexicano. Un patrón similar de separación climática fue también demostrado entre clados de los taxones codistribuidos: Sigmodon hispidus, Neotoma mexicana y Peromysus truei, sugiriendo que la variación climática tiene un mayor papel en el origen y el mantenimiento de la biodiversidad de la región.