Genome-wide signatures of convergent evolution in echolocating mammals

Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10) although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised

Neutrino-electron scattering in noncommutative space

Neutral particles can couple with the $U(1)$ gauge field in the adjoint representation at the tree level if the space-time coordinates are noncommutative (NC). Considering neutrino-photon coupling in the NC QED framework, we obtain the differential cross section of neutrino-electron scattering. Similar to the magnetic moment effect, one of the NC terms is proportional to $\frac 1 T$, where $T$ is the electron recoil energy. Therefore, this scattering provides a chance to achieve a stringent bound on the NC scale in low energy by improving the sensitivity to the smaller electron recoil energy.Comment: 12 pages, 2 figure

Survival and hepatitis status among Asian Americans with hepatocellular carcinoma treated without liver transplantation

<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are established causes of HCC. HCC patients are often diagnosed late and receive palliative therapies, however, the survival of Asian American patients with HCC treated without transplantation has not been well studied. We reviewed our institution's experience to determine predictors and rates of survival in Asian American HCC patients treated without transplantation.</p> <p>Methods</p> <p>We identified Asian American patients with HCC referred to M. D. Anderson Cancer Center. Patients were tested for HBV and HCV. Survival curves were generated by Kaplan-Meier method. Multivariate Cox proportional hazards regression was used to test the relationship between prognostic factors and survival.</p> <p>Results</p> <p>Of 82 Asian American HCC patients, most had advanced disease (65%) and received treatment (68%); however, only 11% had surgical resection. 94% had positive anti-HBc and 61% had positive HBsAg. 20% had positive anti-HCV. There were no significant changes in the rates of HBV and HCV over time. Male gender, high alpha-fetoprotein levels, and stage IV disease were associated with shorter survival Overall median survival was 9.2 months (95% CI 6.5–11.9), and the survival of HCV and HBV patients was not statistically different.</p> <p>Conclusion</p> <p>The survival rate of Asian American patients with advanced HCC, for whom transplantation was not available, was low. Timely hepatitis screening and interventions by primary care physicians may be the most logical solution to reduce the burden of hepatitis-associated HCC among Asian Americans.</p

Localization of hRad9 in breast cancer

<p>Abstract</p> <p>Background</p> <p><it>hRad9 </it>is a cell cycle checkpoint gene that is up-regulated in breast cancer. We have previously shown that the mRNA up-regulation correlated with tumor size and local recurrence. Immunohistochemical studies were made to better define the role of <it>hRad9 </it>in breast carcinogenesis.</p> <p>Methods</p> <p>Localisation of hRad9 protein were performed on paired tumor and normal breast tissues. Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells.</p> <p>Results</p> <p>Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. This nuclear protein existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1 complex.</p> <p>Conclusion</p> <p>Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth.</p

Clinical Presentation of Hepatocellular Carcinoma (HCC) in Asian-Americans Versus Non-Asian-Americans

The incidence of HCC is rising worldwide. Studies on ethnicity-based clinical presentation of HCC remain limited. The aim is to compare the clinical presentation and stage of HCC between Asian-Americans and non-Asian-Americans. This retrospective study assessed ethnicity-based differences in HCC presentation, including demographics, laboratory results, diagnosis of underlying liver disease, and stage of HCC. Of 276 patients, 162 were Asian-Americans and 114 were non-Asian-Americans. Compared to non-Asian-Americans, Asian-Americans had a significantly higher incidence of history of hepatitis B virus (HBV) infection (55.0% vs. 4.9%, P < 0.001), family history of HBV infection (12.5% vs. 0.0%, P < 0.001) and HCC (15.2% vs. 2.9%, P = 0.002), but lower incidence of history of hepatitis C virus (HCV) infection (37.5% vs. 61.6%, P < 0.001). At diagnosis of HCC, Asian-American patients had a significantly lower frequency of hepatic encephalopathy (8.9% vs. 29.3%, P = 0.001), and ascites (26.7% vs. 57.3%, P < 0.001). Asian-Americans had lower Child-Pugh scores (class A: 62.0% vs. 31.4%, P < 0.001), and MELD scores (9.2 ± 4.4 vs. 12.0 ± 6.4, P = 0.02), and presented with a lower stage of HCC by Okuda staging (I: 43.8% vs. 22.8%, P = 0.001). Asian-American patients with HCC presented with a higher incidence of history and family history of HBV infection, lower incidence of hepatic decompensation, lower Child and MELD scores, and an early stage HCC disease

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres

Folding of the apolipoprotein A1 driven by the salt concentration as a possible mechanism to improve cholesterol trapping

The folding of the cholesterol trapping apolipoprotein A1 in aqueous solution at increasing ionic strength is studied using atomically detailed molecular dynamics simulations. We calculate various structural properties to characterize the conformation of the protein, such as the radius of gyration, the radial distribution function and the end to end distance. Additionally we report information using tools specifically tailored for the characterization of proteins, such as the mean smallest distance matrix and the Ramachandran plot. We find that two qualitatively different configurations of this protein are preferred, one where the protein is extended, and one where it forms loops or closed structures. It is argued that the latter promote the association of the protein with cholesterol and other fatty acids.Comment: 14 pages, 6 figures. To appear in "Selected Topics of Computational and Experimental Fluid Mechanics", Springer, J. Klapp, G. Ru\'iz, A. Medina, A. L\'opez & L. Di G. Sigalotti (eds.), 201

Transgenic CHD1L Expression in Mouse Induces Spontaneous Tumors

Background: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.published_or_final_versio

Centre of pressure characteristics in normal, planus and cavus feet

Background The aim of this study was to compare centre of pressure (COP) characteristics between healthy adults with normal, planus or cavus feet who were allocated to groups based on reliable foot posture measurement techniques. Methods Ninety-two healthy adult participants (aged 18 to 45) were recruited and classified as either normal (n = 35), pes planus (n = 31) or pes cavus (n = 26) based on Foot Posture Index, Arch Index and normalised navicular height truncated measurements. Barefoot walking trials were conducted using an emed®-x 400 plantar pressure system (Novel GmbH, Munich, Germany). Average, maximum, minimum and range (difference between maximum and minimum) values were calculated for COP velocity and lateral-medial force index during loading response, midstance, terminal stance and pre-swing phases of stance. The COP excursion index was also calculated. One-way analyses of variance were used to compare the three foot posture groups. Results The cavus foot exhibited the slowest average and minimum COP velocity during terminal stance, but this pattern was reversed during pre-swing, when the cavus foot exhibited the fastest maximum COP velocity. The planus foot exhibited the smallest lateral medial force index range during terminal stance. There were no differences between the groups for COP excursion index. Conclusion These findings indicate that there are differences in COP characteristics between foot postures, which may represent different mechanisms for generating force to facilitate forward progression of the body during the propulsive phases of gait

MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA