Candidate Screening of the TRPC3 Gene in Cerebellar Ataxia

The hereditary cerebellar ataxias are a diverse group of neurodegenerative disorders primarily characterised by loss of balance and coordination due to dysfunction of the cerebellum and its associated pathways. Although many genetic mutations causing inherited cerebellar ataxia have been identified, a significant percentage of patients remain whose cause is unknown. The transient receptor potential (TRP) family member TRPC3 is a non-selective cation channel linked to key signalling pathways that are affected in cerebellar ataxia. Furthermore, genetic mouse models of TRPC3 dysfunction display cerebellar ataxia, making the TRPC3 gene an excellent candidate for screening ataxic patients with unknown genetic aetiology. Here, we report a genetic screen for TRPC3 mutations in a cohort of 98 patients with genetically undefined late-onset cerebellar ataxia and further ten patients with undefined episodic ataxia. We identified a number of variants but no causative mutations in TRPC3. Our findings suggest that mutations in TRPC3 do not significantly contribute to the cause of late-onset and episodic human cerebellar ataxias

Suppression of MMP-2 Attenuates TNF-α Induced NF-κB Activation and Leads to JNK Mediated Cell Death in Glioma

BACKGROUND: Abrogation of apoptosis for prolonged cell survival is essential in cancer progression. In our previous studies, we showed the MMP-2 downregulation induced apoptosis in cancer cell lines. Here, we attempt to investigate the exact molecular mechanism of how MMP-2 depletion leads to apoptosis in glioma xenograft cell lines. METHODOLOGY/PRINCIPAL FINDINGS: MMP-2 transcriptional suppression by MMP-2siRNA (pM) induces apoptosis associated with PARP, caspase-8 and -3 cleavage in human glioma xenograft cells 4910 and 5310. Western blotting and cytokine array showed significant decrease in the cellular and secreted levels of TNF-α with concomitant reduction in TNFR1, TRADD, TRAF2, RIP, IKKβ and pIκBα expression levels resulting in inhibition of p65 phosphorylation and nuclear translocation in pM-treated cells when compared to mock and pSV controls. In addition MMP-2 suppression led to elevated Fas-L, Fas and FADD expression levels along with increased p38 and JNK phosphorylation. The JNK-activity assay showed prolonged JNK activation in pM-transfected cells. Specific inhibition of p38 with SB203580 did not show any effect whereas inhibition of JNK phosphorylation with SP600125 notably reversed pM-induced cleavage of PARP, caspase-8 and -3, demonstrating a significant role of JNK in pM-induced cell death. Supplementation of rhMMP-2 counteracted the effect of pM by remarkably elevating TNF-α, TRADD, IKKβ and pIκBα expression and decreasing FADD, Fas-L, and phospho-JNK levels. The EMSA analysis indicated significant reversal of pM-inhibited NF-κB activity by rhMMP-2 treatment which rescued cells from pM-induced cell death. In vivo studies indicated that pM treatment diminished intracranial tumor growth and the immuno histochemical analysis showed decreased phospho-p65 and enhanced phospho-JNK levels that correlated with increased TUNEL-positive apoptotic cells in pM-treated tumor sections. CONCLUSION/SIGNIFICANCE: In summary, our study implies a role of MMP-2 in the regulation of TNF-α mediated constitutive NF-κB activation and Fas-mediated JNK mediated apoptosis in glioma xenograft cells in vitro and in vivo

Transcriptome Analysis of the Chinese White Wax Scale Ericerus pela with Focus on Genes Involved in Wax Biosynthesis

BACKGROUND: The Chinese white wax scale, Ericerus pela Chavannes is economically significant for its role in wax production. This insect has been bred in China for over a thousand years. The wax secreted by the male scale insect during the second-instar larval stage has been widespread used in wax candle production, wax printing, engraving, Chinese medicine, and more recently in the chemical, pharmaceutical, food, and cosmetics industries. However, little is known about the mechanisms responsible for white wax biosynthesis. The characterization of its larval transcriptome may promote better understanding of wax biosynthesis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, characterization of the transcriptome of E. pela during peak wax secretion was performed using Illumina sequencing technology. Illumina sequencing produced 41,839 unigenes. These unigenes were annotated by blastx alignment against the NCBI Non-Redundant (NR), Swiss-Prot, KEGG, and COG databases. A total of 104 unigenes related to white wax biosynthesis were identified, and 15 of them were selected for quantitative real-time PCR analysis. We evaluated the variations in gene expression across different development stages, including egg, first/second instar larvae, male pupae, and male and female adults. Then we identified five genes involved in white wax biosynthesis. These genes were expressed most strongly during the second-instar larval stage of male E. pela. CONCLUSION/SIGNIFICANCE: The transcriptome analysis of E. pela during peak wax secretion provided an overview of gene expression information at the transcriptional level and a resource for gene mining. Five genes related to white wax biosynthesis were identified

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Proteomic Analysis of Rta2p-Dependent Raft-Association of Detergent-Resistant Membranes in Candida albicans

In Candida albicans, lipid rafts (also called detergent-resistant membranes, DRMs) are involved in many cellular processes and contain many important proteins. In our previous study, we demonstrated that Rta2p was required for calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Here, we found that Rta2p was co-localized with raft-constituted ergosterol on the plasma membrane of C. albicans. Furthermore, this membrane expression pattern was totally disturbed by inhibitors of either ergosterol or sphingolipid synthesis. Biochemical fractionation of DRMs together with immunoblot uncovered that Rta2p, along with well-known DRM-associated proteins (Pma1p and Gas1p homologue), was associated with DRMs and their associations were blocked by inhibitors of either ergosterol or sphingolipid synthesis. Finally, we used the proteomic analysis together with immunoblot and identified that Rta2p was required for the association of 10 proteins with DRMs. These 5 proteins (Pma1p, Gas1p homologue, Erg11p, Pmt2p and Ali1p) have been reported to be DRM-associated and also that Erg11p is a well-known target of azoles in C. albicans. In conclusion, our results showed that Rta2p was predominantly localized in lipid rafts and was required for the association of certain membrane proteins with lipid rafts in C. albicans

Identified baryon and meson distributions at large transverse momenta from Au+Au collisions at sNN=200\sqrt{s_{_{NN}}} = 200 GeV

Transverse momentum spectra of $\pi^{\pm}$, $p$ and $\bar{p}$ up to 12 GeV/c at mid-rapidity in centrality selected Au+Au collisions at $\sqrt{s_{_{NN}}} = 200$ GeV are presented. In central Au+Au collisions, both $\pi^{\pm}$ and $p(\bar{p})$ show significant suppression with respect to binary scaling at $p_T >$ 4 GeV/c. Protons and anti-protons are less suppressed than $\pi^{\pm}$, in the range 1.5 $< p_{T} <$6 GeV/c. The $\pi^-/\pi^+$ and $\bar{p}/p$ ratios show at most a weak $p_T$ dependence and no significant centrality dependence. The $p/\pi$ ratios in central Au+Au collisions approach the values in p+p and d+Au collisions at $p_T >$ 5 GeV/c. The results at high $p_T$ indicate that the partonic sources of $\pi^{\pm}$, $p$ and $\bar{p}$ have similar energy loss when traversing the nuclear medium.Comment: 6 pages, 4 figure

Longitudinal double-spin asymmetry and cross section for inclusive jet production in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive midrapidity jet production in polarized proton collisions at sqrt(s)=200 GeV. The cross section data cover transverse momenta 5 < pT < 50 GeV/c and agree with next-to-leading order perturbative QCD evaluations. The A_LL data cover 5 < pT < 17 GeV/c and disfavor at 98% C.L. maximal positive gluon polarization in the polarized nucleon.Comment: 6 pages, 3 figures. Minor changes from review process in Phys. Rev. Lett. Plain text tables of data in STAR publications may be found at http://www.star.bnl.gov/central/publications

Neutral Kaon Interferometry in Au+Au collisions at sqrt(s_NN) = 200 GeV

We present the first statistically meaningful results from two-K0s interferometry in heavy-ion collisions. A model that takes the effect of the strong interaction into account has been used to fit the measured correlation function. The effects of single and coupled channel were explored. At the mean transverse mass m_T = 1.07 GeV, we obtain the values R = 4.09 +/- 0.46 (stat.) +/- 0.31 (sys) fm and lambda = 0.92 +/- 0.23 (stat) +/- 0.13 (sys), where R and lambda are the invariant radius and chaoticity parameters respectively. The results are qualitatively consistent with m_T systematics established with pions in a scenario characterized by a strong collective flow.Comment: 11 pages, 10 figure

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

BACKGROUND: Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. METHODS: A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China

Elliptic flow of electrons from heavy-flavor hadron decays in Au+Au collisions at sNN=\sqrt{s_{\rm NN}} = 200, 62.4, and 39 GeV

We present measurements of elliptic flow ($v_2$) of electrons from the decays of heavy-flavor hadrons ($e_{HF}$) by the STAR experiment. For Au+Au collisions at $\sqrt{s_{\rm NN}} =$ 200 GeV we report $v_2$, for transverse momentum ($p_T$) between 0.2 and 7 GeV/c using three methods: the event plane method ($v_{2}${EP}), two-particle correlations ($v_2${2}), and four-particle correlations ($v_2${4}). For Au+Au collisions at $\sqrt{s_{\rm NN}}$ = 62.4 and 39 GeV we report $v_2${2} for $p_T< 2$ GeV/c. $v_2${2} and $v_2${4} are non-zero at low and intermediate $p_T$ at 200 GeV, and $v_2${2} is consistent with zero at low $p_T$ at other energies. The $v_2${2} at the two lower beam energies is systematically lower than at $\sqrt{s_{\rm NN}} =$ 200 GeV for $p_T < 1$ GeV/c. This difference may suggest that charm quarks interact less strongly with the surrounding nuclear matter at those two lower energies compared to $\sqrt{s_{\rm NN}} = 200$ GeV.Comment: Version accepted by PR