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41.
The X chromosome is found twice as often in females as males. This has led to an intuition that X‐linked genes for traits experiencing sexually antagonistic selection should tend to evolve toward the female optimum. However, this intuition has never been formally examined. In this paper, I present a simple mathematical model and ask whether the X chromosome is indeed biased toward effecting female‐optimal phenotypes. Counter to the intuition, I find that the exact opposite bias exists; the X chromosome is revealed to be a welcome spot for mutations that benefit males at the expense of females. Not only do male‐beneficial alleles have an easier time of invading and spreading through a population, but they also achieve higher equilibrium frequencies than comparable female‐beneficial alleles. The X chromosome is therefore expected over evolutionary time to nudge phenotypes closer to the male optimum. Consequently, the X chromosome should find itself engaged in perpetual intragenomic conflicts with the autosomes and the mitochondria over developmental outcomes. The X chromosome's male bias and the intragenomic conflicts that ensue bear on the evolution of gene regulation, speciation, and our concept of organismality. 相似文献
42.
Xiang J Ipek M Suri V Tam M Xing Y Huang N Zhang Y Tobin J Mansour TS McKew J 《Bioorganic & medicinal chemistry》2007,15(13):4396-4405
The design, synthesis, and biological evaluation of beta-keto sulfones as 11beta-HSD1 inhibitors and the mechanism of inhibition are described here. This class of compounds is not active against 11beta-HSD2 and therefore may have therapeutic potential for metabolic syndrome and type 2 diabetes. 相似文献
43.
Neuronal Apoptosis: BH3-Only Proteins the Real Killers? 总被引:2,自引:0,他引:2
At present there is a poor understanding of the events that lead up to neuronal apoptosis that occurs in neurodegenerative diseases and following acute ischemic episodes. Apoptosis is critical for the elimination of unwanted neurons within the developing nervous system. The Bcl-2 family of proteins contains pro- and anti-apoptotic proteins that regulate the mitochondrial pathway of apoptosis. There is increasing interest in a subfamily of the Bcl-2 family, the BH3-only proteins, and their pro-apoptotic effects within neurons. Recently ischemic and seizure-induced neuronal injury has been shown to result in the activation of the BH3-only protein, Bid. This protein is cleaved and the truncated protein (tBid) translocates to the mitochondria. The translocation of tBid to the mitochondria is associated with the activation of outer mitochondrial membrane proteins Bax/Bak and the release of cytochrome C from the mitochondria. ER stress also has been implicated as a factor for the induction of apoptosis in ischemic neuronal injury. The induction of ER stress in hippocampal neurons has been shown to activate expression of bb3/PUMA, a member of the BH3-only gene family. Activation of PUMA is associated with the activation and clustering of the pro-apoptotic Bcl-2 family member Bax and the loss of cytochrome C from the mitochondria. 相似文献
44.
Yiying Liu Irene de Bruijn Allison LH Jack Keith Drynan Albert H van den Berg Even Thoen Vladimir Sandoval-Sierra Ida Skaar Pieter van West Javier Diéguez-Uribeondo Menno van der Voort Rodrigo Mendes Mark Mazzola Jos M Raaijmakers 《The ISME journal》2014,8(10):2002-2014
Animals and plants are increasingly suffering from diseases caused by fungi and oomycetes. These emerging pathogens are now recognized as a global threat to biodiversity and food security. Among oomycetes, Saprolegnia species cause significant declines in fish and amphibian populations. Fish eggs have an immature adaptive immune system and depend on nonspecific innate defences to ward off pathogens. Here, meta-taxonomic analyses revealed that Atlantic salmon eggs are home to diverse fungal, oomycete and bacterial communities. Although virulent Saprolegnia isolates were found in all salmon egg samples, a low incidence of Saprolegniosis was strongly correlated with a high richness and abundance of specific commensal Actinobacteria, with the genus Frondihabitans (Microbacteriaceae) effectively inhibiting attachment of Saprolegniato salmon eggs. These results highlight that fundamental insights into microbial landscapes of fish eggs may provide new sustainable means to mitigate emerging diseases. 相似文献
45.
Hans-Georg König Markus Rehm Daniel Gudorf Stan Krajewski Atan Gross Manus W Ward Jochen HM Prehn 《BMC cell biology》2007,8(1):7
Background
Bcl-2 homology domain (BH) 3-only proteins are pro-apoptotic proteins of the Bcl-2 family that couple stress signals to the mitochondrial cell death pathways. The BH3-only protein Bid can be activated in response to death receptor activation via caspase 8-mediated cleavage into a truncated protein (tBid), which subsequently translocates to mitochondria and induces the release of cytochrome-C. Using a single-cell imaging approach of Bid cleavage and translocation during apoptosis, we have recently demonstrated that, in contrast to death receptor-induced apoptosis, caspase-independent excitotoxic apoptosis involves a translocation of full length Bid (FL-Bid) from the cytosol to mitochondria. We induced a delayed excitotoxic cell death in cultured rat hippocampal neurons by a 5-min exposure to the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 300 μM). 相似文献46.
The cellular fatty acids of 35 strains of Mycobacterium kansasii isolated from clinical material were analyzed to establish properties by which we could identify and characterize these acid-fast microorganisms. The fatty acids were extracted from cells grown in liquid synthetic media, and they were analyzed as methyl esters by gas-liquid chromatography. The fatty acid profiles of all strains were similar. They differed from fatty acid profiles of other mycobacteria by their content of a saturated fatty acid with a methyl group at C2. 相似文献
47.
Hu Y Cole D Denny RA Anderson DR Ipek M Ni Y Wang X Thaisrivongs S Chamberlain T Hall JP Liu J Luong M Lin LL Telliez JB Gopalsamy A 《Bioorganic & medicinal chemistry letters》2011,21(16):4758-4761
Synthesis, modeling and structure-activity relationship of indazoles as inhibitors of Tpl2 kinase are described. From a high throughput screening effort, we identified an indazole hit compound 5 that has a single digit micromolar Tpl2 activity. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk assay. 相似文献
48.
A closed depression is defined as a geomorphologic element where a sediment depository is encircled by hillslopes. Despite
the fact that closed depressions are often the only stagnant water points in many European landscapes, few ecological researches
on their plant assemblages have been done. The main goal of this study was to give first results of the environmental factors
responsible for the vegetation composition, richness and rarity in the closed depressions of the Lorraine biogeographical
district (Belgium, France and grand-duché de Luxembourg). We surveyed for plant presence 85 forest and 77 grassland closed
depressions. For each site, wetland area, local environmental factors and regional connectivities registered. For each species,
the Ellenberg values were compiled. To investigate the main source of variation in species composition and in species richness
(including richness in rare species), Non-metric Multidimensional Scaling analyses and Generalized Linear Models were respectively
used. Species pools in forest (forest and preforest species) and in grassland (bog plants, pioneers, helophytes) were quite
different. In both landscapes, a gradient from plants typical of basic high-productive soils to plants typical of acid low-productive
soils reflects a shared successional gradient. The accumulation of organic matter allowed the establishment of Sphagnum spp., which slowly acidified the soil and thus acted as ecosystem engineers for the arrival of bog plants. Moreover, the
species composition was additionally driven by the plant light tolerance in forests and by the plant water requirements in
grasslands. Mechanisms of species accumulation (increase in species richness) were different in forests and in grasslands:
respectively related to the plant light tolerance and to the wetland area. At the regional level, the averaged soil productivity
was negatively related to the richness in rare species. Indeed, perennial highly-competitive plants such as Glyceria spp., Iris pseudacorus or Urtica dioica impeded the establishment of smaller and rarer species. At the habitat level, isolated closed depressions (due to either
low connectivity or low grazing pressure) have more habitat rare species, giving evidences of dispersal limitation in plant
assemblages of closed depressions. 相似文献
49.
Xiang JS Hu Y Rush TS Thomason JR Ipek M Sum PE Abrous L Sabatini JJ Georgiadis K Reifenberg E Majumdar M Morris EA Tam S 《Bioorganic & medicinal chemistry letters》2006,16(2):311-316
Aggrecanases are recently discovered enzymes that cleave aggrecan, a key component of cartilage. Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis. The synthesis and evaluation of biphenylsulfonamidocarboxylic acid inhibitors of aggrecanase-1 are reported. Compound 24 demonstrated 89% inhibition of proteoglycan degradation at 10 microg/mL and has an oral bioavailability in rat of 35%. 相似文献
50.
A phosphoprotein phosphatase active towards casein, phosphorylase a and mRNP proteins has been detected in the cytosol of cryptobiotic gastrulae of Artemia sp. This phosphatase has a relative molecular mass (Mr) of 225,000 as measured by gel filtration on Sephadex G-200 and has been purified to near homogeneity by ion-exchange chromatography on different DEAE-substituted matrices, affinity chromatography on polylysine-agarose, histone-Sepharose 4B and protamine-agarose, hydrophobic chromatography on phenyl-Sepharose 4B and gel filtration on Sephadex G-200. Sodium dodecyl sulphate gel electrophoresis of the final purification step revealed that the enzyme contains two types of subunits, alpha and beta, with Mr of 40,000 and 75,000, respectively. These values, in conjunction with the native Mr and the molar ratios of the subunits estimated by densitometric analysis of the gel, suggested that the subunit composition of the enzyme is alpha 2 beta 2. When treated with 1.7% (v/v) 2-mercaptoethanol at -20 degrees C or with ethanol, the enzyme released the catalytic alpha subunit of Mr 40,000. The protein phosphatase was activated by basic proteins e.g. protamine (A 0.5 = 1 microM), histone H1 (A 0.5 = 1.6 microM) and polylysine (A 0.5 = 0.2 microM) and inhibited by ATP (I 0.5 = 12 microM), NaF (I 0.5 = 3.1 mM) and pyrophosphate (I 0.5 = 0.6 mM). The enzyme is a polycation-stimulated protein phosphatase. Purified mRNP proteins, phosphorylated by the mRNP-associated casein kinase type II, are among the substrates used by the enzyme. The function of reversible phosphorylation-dephosphorylation of mRNP as a regulatory mechanism in mRNP metabolism is discussed. 相似文献