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81.
82.
It is unclear when, where and how novel pathogens such as human immunodeficiency virus (HIV), monkeypox and severe acute respiratory syndrome (SARS) will cross the barriers that separate their natural reservoirs from human populations and ignite the epidemic spread of novel infectious diseases. New pathogens are believed to emerge from animal reservoirs when ecological changes increase the pathogen's opportunities to enter the human population and to generate subsequent human-to-human transmission. Effective human-to-human transmission requires that the pathogen's basic reproductive number, R(0), should exceed one, where R(0) is the average number of secondary infections arising from one infected individual in a completely susceptible population. However, an increase in R(0), even when insufficient to generate an epidemic, nonetheless increases the number of subsequently infected individuals. Here we show that, as a consequence of this, the probability of pathogen evolution to R(0) > 1 and subsequent disease emergence can increase markedly. 相似文献
83.
植物生长调节剂BAS-125-10W对梨枝条生长控制效应的研究 总被引:1,自引:0,他引:1
就新型植物生长调节剂BAS-125-10W对梨枝条生长控制效应进行了研究.结果表明,随着喷施浓度、喷施次数的增加,枝条生长可得到较好控制.适时早期喷施效果较好.在喷施浓度、喷施次数和喷施时期不同处理下,各品种间均表现出显著性差异. 相似文献
84.
Maser RS Choudhury B Campbell PJ Feng B Wong KK Protopopov A O'Neil J Gutierrez A Ivanova E Perna I Lin E Mani V Jiang S McNamara K Zaghlul S Edkins S Stevens C Brennan C Martin ES Wiedemeyer R Kabbarah O Nogueira C Histen G Aster J Mansour M Duke V Foroni L Fielding AK Goldstone AH Rowe JM Wang YA Look AT Stratton MR Chin L Futreal PA DePinho RA 《Nature》2007,447(7147):966-971
Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome. 相似文献
85.
Polarized traffic in epithelial cells depends on well-organized pathways that direct secretory cargo to the apical or basolateral
plasma membrane. In MDCK cells, apical trafficking can be further divided into a lipid raft-dependent and a raft-independent
route, which separate biosynthetic cargo in a post-Golgi endosomal compartment. We have now identified KIF5C as a kinesin
motor for apical trafficking of both raft-associated sucrase isomaltase and raft-independent neurotrophin receptor. KIF5C
was identified by mass spectrometry in vesicle enriched fractions and on immunoisolated post-Golgi vesicles carrying apical
cargo. The amount of vesicle-associated KIF5C was highest on material isolated directly after trans-Golgi network release
and declined thereafter. Altogether, our data suggest that KIF5C is involved in the passage of apical cargo molecules to a
post-Golgi endosomal compartment, where further segregation into distinct vesicle populations proceeds. 相似文献
86.
Paternoster L Standl M Chen CM Ramasamy A Bønnelykke K Duijts L Ferreira MA Alves AC Thyssen JP Albrecht E Baurecht H Feenstra B Sleiman PM Hysi P Warrington NM Curjuric I Myhre R Curtin JA Groen-Blokhuis MM Kerkhof M Sääf A Franke A Ellinghaus D Fölster-Holst R Dermitzakis E Montgomery SB Prokisch H Heim K Hartikainen AL Pouta A Pekkanen J Blakemore AI Buxton JL Kaakinen M Duffy DL Madden PA Heath AC Montgomery GW Thompson PJ Matheson MC Le Souëf P;Australian Asthma Genetics Consortium 《Nature genetics》2012,44(2):187-192
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis. 相似文献
87.
Eoin P. Cummins Andrew C. Selfridge Peter H. Sporn Jacob I. Sznajder Cormac T. Taylor 《Cellular and molecular life sciences : CMLS》2014,71(5):831-845
The capacity of organisms to sense changes in the levels of internal and external gases and to respond accordingly is central to a range of physiologic and pathophysiologic processes. Carbon dioxide, a primary product of oxidative metabolism is one such gas that can be sensed by both prokaryotic and eukaryotic cells and in response to altered levels, elicit the activation of multiple adaptive pathways. The outcomes of activating CO2-sensitive pathways in various species include increased virulence of fungal and bacterial pathogens, prey-seeking behavior in insects as well as taste perception, lung function, and the control of immunity in mammals. In this review, we discuss what is known about the mechanisms underpinning CO2 sensing across a range of species and consider the implications of this for physiology, disease progression, and the possibility of developing new therapeutics for inflammatory and infectious disease. 相似文献
88.
Aitman TJ Critser JK Cuppen E Dominiczak A Fernandez-Suarez XM Flint J Gauguier D Geurts AM Gould M Harris PC Holmdahl R Hubner N Izsvák Z Jacob HJ Kuramoto T Kwitek AE Marrone A Mashimo T Moreno C Mullins J Mullins L Olsson T Pravenec M Riley L Saar K Serikawa T Shull JD Szpirer C Twigger SN Voigt B Worley K 《Nature genetics》2008,40(5):516-522
The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research. 相似文献
89.
Guryev V Saar K Adamovic T Verheul M van Heesch SA Cook S Pravenec M Aitman T Jacob H Shull JD Hubner N Cuppen E 《Nature genetics》2008,40(5):538-545
The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease. 相似文献
90.
Mueller JL Mahadevaiah SK Park PJ Warburton PE Page DC Turner JM 《Nature genetics》2008,40(6):794-799
According to the prevailing view, mammalian X chromosomes are enriched in spermatogenesis genes expressed before meiosis and deficient in spermatogenesis genes expressed after meiosis. The paucity of postmeiotic genes on the X chromosome has been interpreted as a consequence of meiotic sex chromosome inactivation (MSCI)--the complete silencing of genes on the XY bivalent at meiotic prophase. Recent studies have concluded that MSCI-initiated silencing persists beyond meiosis and that most genes on the X chromosome remain repressed in round spermatids. Here, we report that 33 multicopy gene families, representing approximately 273 mouse X-linked genes, are expressed in the testis and that this expression is predominantly in postmeiotic cells. RNA FISH and microarray analysis show that the maintenance of X chromosome postmeiotic repression is incomplete. Furthermore, X-linked multicopy genes exhibit a similar degree of expression as autosomal genes. Thus, not only is the mouse X chromosome enriched for spermatogenesis genes functioning before meiosis, but in addition, approximately 18% of mouse X-linked genes are expressed in postmeiotic cells. 相似文献