Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales

Most of the matter in the universe is not luminous and can be observed directly only through its gravitational effect. An emerging technique called weak gravitational lensing uses background galaxies to reveal the foreground dark matter distribution on large scales. Light from very distant galaxies travels to us through many intervening overdensities which gravitationally distort their apparent shapes. The observed ellipticity pattern of these distant galaxies thus encodes information about the large-scale structure of the universe, but attempts to measure this effect have been inconclusive due to systematic errors. We report the first detection of this ``cosmic shear'' using 145,000 background galaxies to reveal the dark matter distribution on angular scales up to half a degree in three separate lines of sight. The observed angular dependence of this effect is consistent with that predicted by two leading cosmological models, providing new and independent support for these models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex errors and typos.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm(2), n = 319) and high (> 1.11 g/cm(2), n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm(2)) and 138 females with high (>1.04 g/cm(2)) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis

PPARγ agonists inhibit growth and expansion of CD133+ brain tumour stem cells

Brain tumour stem cells (BTSCs) are a small population of cells that has self-renewal, transplantation, multidrug resistance and recurrence properties, thus remain novel therapeutic target for brain tumour. Recent studies have shown that peroxisome proliferator-activated receptor gamma (PPARγ) agonists induce growth arrest and apoptosis in glioblastoma cells, but their effects on BTSCs are largely unknown. In this study, we generated gliospheres with more than 50% CD133+ BTSC by culturing U87MG and T98G human glioblastoma cells with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In vitro treatment with PPARγ agonist, 15-Deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) or all-trans retinoic acid resulted in a reversible inhibition of gliosphere formation in culture. Peroxisome proliferator-activated receptor gamma agonists inhibited the proliferation and expansion of glioma and gliosphere cells in a dose-dependent manner. Peroxisome proliferator-activated receptor gamma agonists also induced cell cycle arrest and apoptosis in association with the inhibition of EGF/bFGF signalling through Tyk2-Stat3 pathway and expression of PPARγ in gliosphere cells. These findings demonstrate that PPARγ agonists regulate growth and expansion of BTSCs and extend their use to target BTSCs in the treatment of brain tumour

PPARγ agonists inhibit growth and expansion of CD133+ brain tumour stem cells

Brain tumour stem cells (BTSCs) are a small population of cells that has self-renewal, transplantation, multidrug resistance and recurrence properties, thus remain novel therapeutic target for brain tumour. Recent studies have shown that peroxisome proliferator-activated receptor gamma (PPARγ) agonists induce growth arrest and apoptosis in glioblastoma cells, but their effects on BTSCs are largely unknown. In this study, we generated gliospheres with more than 50% CD133+ BTSC by culturing U87MG and T98G human glioblastoma cells with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In vitro treatment with PPARγ agonist, 15-Deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) or all-trans retinoic acid resulted in a reversible inhibition of gliosphere formation in culture. Peroxisome proliferator-activated receptor gamma agonists inhibited the proliferation and expansion of glioma and gliosphere cells in a dose-dependent manner. Peroxisome proliferator-activated receptor gamma agonists also induced cell cycle arrest and apoptosis in association with the inhibition of EGF/bFGF signalling through Tyk2-Stat3 pathway and expression of PPARγ in gliosphere cells. These findings demonstrate that PPARγ agonists regulate growth and expansion of BTSCs and extend their use to target BTSCs in the treatment of brain tumour

Soil water-holding capacity and monodominance in Southern Amazon tropical forests

Background and aims: We explored the hypothesis that low soil water-holding capacity is the main factor driving the monodominance of Brosimum rubescens in a monodominant forest in Southern Amazonia. Tropical monodominant forests are rare ecosystems with low diversity and high dominance of a single tree species. The causes of this atypical condition are still poorly understood. Some studies have shown a relationship between monodominance and waterlogging or soil attributes, while others have concluded that edaphic factors have little or no explanatory value, but none has accounted for soil-moisture variation other than waterlogging. This study is the first to explicitly explore how low soil water-holding capacity influences the monodominance of tropical forests. Methods: We conducted in situ measurements of vertical soil moisture using electrical resistance collected over 1 year at 0–5; 35–40 and 75–80 cm depths in a B. rubescens monodominant forest and in an adjacent mixed-species forest in the Amazon-Cerrado transition zone, Brazil. Minimum leaf water potential (Ψmin) of the seven most common species, including B. rubescens, and soil water-holding capacity for both forests were determined. Results: The vertical soil moisture decay pattern was similar in both forests for all depths. However, the slightly higher water availability in the monodominant forest and Ψmin similarity between B. rubescens and nearby mixed forest species indicate that low water-availability does not cause the monodominance. Conclusions: We reject the hypothesis that monodominance of B. rubescens is primarily determined by low soil water-holding capacity, reinforcing the idea that monodominance in tropical forests is not determined by a single factor

Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects

<p>Abstract</p> <p>Background</p> <p>Although much progress has been made on antipsychotic drug development, precise mechanisms behind the action of typical and atypical antipsychotics are poorly understood.</p> <p>Methods</p> <p>We performed genome-wide expression profiling to study effects of typical antipsychotics and atypical antipsychotics in the postmortem liver of schizophrenia patients using microarrays (Affymetrix U133 plus2.0). We classified the subjects into typical antipsychotics (n = 24) or atypical antipsychotics (n = 26) based on their medication history, and compared gene expression profiles with unaffected controls (n = 34). We further analyzed individual antipsychotic effects on gene expression by sub-classifying the subjects into four major antipsychotic groups including haloperidol, phenothiazines, olanzapine and risperidone.</p> <p>Results</p> <p>Typical antipsychotics affected genes associated with nuclear protein, stress responses and phosphorylation, whereas atypical antipsychotics affected genes associated with golgi/endoplasmic reticulum and cytoplasm transport. Comparison between typical antipsychotics and atypical antipsychotics further identified genes associated with lipid metabolism and mitochondrial function. Analyses on individual antipsychotics revealed a set of genes (151 transcripts, FDR adjusted p < 0.05) that are differentially regulated by four antipsychotics, particularly by phenothiazines, in the liver of schizophrenia patients.</p> <p>Conclusion</p> <p>Typical antipsychotics and atypical antipsychotics affect different genes and biological function in the liver. Typical antipsychotic phenothiazines exert robust effects on gene expression in the liver that may lead to liver toxicity. The genes found in the current study may benefit antipsychotic drug development with better therapeutic and side effect profiles.</p

Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.https://nsuworks.nova.edu/hpd_medsci_faculty_books/1002/thumbnail.jp

The evolution of a highly variable sex chromosome in Gehyra purpurascens (Gekkonidae)

A karyotypic survey of the gekkonid lizard Gehyra purpurascens revealed a distinctive sex chromosome system. G-banding showed that the Z Chromosome of males is derived from a tandem fusion of two acrocentric chromosomes of a presumed ancestral Gehyra with 2n=44. Through the application of G-; N- and C-banding, a total of six morphs of the W chromosome were identified. These differ by paracentric and pericentric inversions and, in one case, by a centric shift. The possible reasons for such extensive variation in the W chromosome are considered, and it is suggested that increased mutability of the W chromosome may be a causal factor. In contrast to earlier speculations, this example demonstrates that sex chromosomes can evolve without significant changes in the amount of C-band heterochromatin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47361/1/412_2004_Article_BF00292447.pd