Tibetan land use and change near khawa karpo, Eastern Himalayas

Collaborating Authors: Bee Gunn, Wayne Law, George Yatskievych, Wu Sugong, Fang Zhendong, Ma Jian, Wang Yuhua, Andrew Willson, Peng Shengjing, Zhang Chuanling, Sun Hongyan, Meng Zhengui, Liu Lin, Senam Dorji, Ana, Liqing Wangcuo, Sila Cili, Adu, Naji, Amu, Sila Cimu, Sila Lamu, Lurong Pingding, Zhima Yongzong, Loangbao, Bianma Cimu, Gerong Cili, Wang Kai, Sila Pingchu, Axima, and Benjamin Staver.TIBETAN LAND USE AND CHANGE NEAR KHAWA KARPO, EASTERN HIMALAYAS. Economic Botany 59(4):312-325, 2005. Tibetan land use near Khawa Karpo, Northwest Yunnan, China, incorporates indigenous forest management, gathering, pastoralism, and agriculture. With field-based GIS, repeat photography, and Participatory Rural Appraisal we quantitatively compare land use between higher and lower villages, and between villages with and without roads. Households in higher elevation (> 3,000 meters) villages cultivate more farmland (z = -5.387, P ≤ 0.001), a greater diversity of major crops (z = -5.760, P < 0.001), a higher percentage of traditional crops, and fewer cash crops (z = -2.430, P = 0.015) than those in lower elevation villages (< 2,500 meters). Villages with roads grow significantly more cash crops (z = -6.794, P ≤ 0.001). Both lower villages and villages with roads travel farther to access common property resources. Historical analyses indicate agricultural intensification in valleys, an increase in houses, new crop introduction, hillside aforestation, cessation of hunting, glacial retreat, and timberline advance within the past century. We suggest that Tibetan land use reveals trade-offs between high, remote villages and lower villages near roads. Higher villages offer abundant land and access to natural resources but short growing seasons and little market access; in contrast, lower villages have road and market access, an extended growing season, and modern technology, but limited access to land and many other natural resources.     

A hidden-state Markov model for cell population deconvolution.

Microarrays measure gene expression typically from a mixture of cell populations during different stages of a biological process. However, the specific effects of the distinct or pure populations on measured gene expression are difficult or impossible to determine. The ability to deconvolve measured gene expression into the contributions from pure populations is critical to maximizing the potential of microarray analysis for investigating complex biological processes. In this paper, we describe a novel approach called the multinomial hidden Markov model (MHMM) that produces: (i) a maximum a posteriori estimate of the fraction represented by each pure population and (ii) gene expression values for each pure population. Our method uses an unsupervised, probabilistic approach for handling missing data points and clusters genes based on expression in pure populations. MHMM, used with several yeast datasets, identified statistically significant temporal dynamics. This method, unlike the linear decomposition models used previously for deconvolution, can extract information from different types of data, does not require a priori identification of pure gene expression, exploits the temporal nature of time series data, and is less affected by missing data.     

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D₅R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D₅R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D₅R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D₅R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D₅R trafficking and that SNX1 depletion results in D₅R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension.     

Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase

Most currently available small molecule inhibitors of DNA replication lack enzymatic specificity, resulting in deleterious side effects during use in cancer chemotherapy and limited experimental usefulness as mechanistic tools to study DNA replication. Towards development of targeted replication inhibitors, we have focused on Mcm2-7 (minichromosome maintenance protein 2–7), a highly conserved helicase and key regulatory component of eukaryotic DNA replication. Unexpectedly we found that the fluoroquinolone antibiotic ciprofloxacin preferentially inhibits Mcm2-7. Ciprofloxacin blocks the DNA helicase activity of Mcm2-7 at concentrations that have little effect on other tested helicases and prevents the proliferation of both yeast and human cells at concentrations similar to those that inhibit DNA unwinding. Moreover, a previously characterized mcm mutant (mcm4chaos3) exhibits increased ciprofloxacin resistance. To identify more potent Mcm2-7 inhibitors, we screened molecules that are structurally related to ciprofloxacin and identified several that compromise the Mcm2-7 helicase activity at lower concentrations. Our results indicate that ciprofloxacin targets Mcm2-7 in vitro, and support the feasibility of developing specific quinolone-based inhibitors of Mcm2-7 for therapeutic and experimental applications.     

The mobilization of the ethnic vote: A thesis with some Scottish and Welsh evidence*

This article provides a historical and comparative analysis of post‐imperial migrations of ethnic unmixing. It examines the post‐Soviet migration of ethnic Russians to Russia in the light of the migrations of other once‐dominant ‘new minorities’ engendered by transitions from multinational empire to incipient nation‐states: Balkan Muslims during and after the disintegration of the Ottoman Empire, Hungarians after the collapse of the Habsburg Empire, and Germans after the collapse of the Habsburg Empire and the German Kaiserreich.     

Natural genetic variation in male reproductive genes contributes to nontransitivity of sperm competitive ability in Drosophila melanogaster

Female Drosophila melanogaster frequently mate with multiple males, and the success of a given male depends not only on his genotype but also on the genotype of his competitor. Here, we assess how natural genetic variation affects male–male interactions for traits influencing pre‐ and postcopulatory sexual selection. Males from a set of 66 chromosome substitution lines were competed against each other in a ‘round‐robin’ design, and paternity was scored using bulk genotyping. We observed significant effects of the genotype of the first male to mate, the second male to mate and an interaction between the males for measures of male mating rate and sperm utilization. We also identified specific combinations of males who show nontransitive patterns of reproductive success and engage in ‘rock‐paper‐scissors’ games. We then tested for associations between 245 polymorphisms in 32 candidate male reproductive genes and male reproductive success. We identified eight polymorphisms in six reproductive genes that associate with male reproductive success independent of the competitor (experimentwise P < 0.05). We also identified four SNPs in four different genes where the relative reproductive success of the alternative alleles changes depending on the competing males' genetic background (experimentwise P < 0.05); two of these associations include premature stop codons. This may be the first study that identifies the genes contributing to nontransitivity among males and further highlights that ‘rock‐paper‐scissors’ games could be an important evolutionary force maintaining genetic variation in natural populations.     

Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia

Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties.