The molecular basis of thalassaemia in Sri Lanka

Blood samples from over 1600 schoolchildren revealed a prevalence of both trait and HbE trait, averaging 2.3% and 0.8% respectively. With the present popUlation estimate at 18.6 million, it is predicted that approximately 2650 patients with l3-thalassaemia major and 956 with HbE/I3-thalassaemia should consume >5% of the current health budget for treatment of these patients. Patients with the phenotype of severe thalassaemia, from seven centres, were analysed to understand the molecular basis of the disease. Twenty-four l3-globin gene mutations were identified with three mutations accounting for 84.4% of the 1234 alleles: IVSI-5 (G--7C) 56.1 %; IVSI-l (G--7A) 15.2% and HbE 13.1 %. Sixteen mutations have previously been described on the Indian subcontinent and demonstrate close regional links between the popUlations, especially North East India, and were supported by haplotype association. The IVSI-l (G--7A) mutation occurs commonly in countries around the Mediterranean but very rarely on the Indian subcontinent. In Sri Lanka it is associated with a different 3' haplotype, suggesting a multicentric origin. Three new mutations were found; a frameshift codon 6-10 IVSI-129 (A--7C) in the consensus splice site and a second frame shift, CD55 (-A). Four a-gene arrangements were demonstrated. An allele frequency of the a+-thalassaemia gene deletions were 6.5% and 1.1% for the _a3.7 deletion and the _a4.2 deletion, respectively. Cord blood analysis of Hb Bart's levels confirmed an estimated level of 7.1 % for a single a-gene nonexpression. Extra a-genes are common and the first instance of homozygosity for the aaaa arrangement was observed. No aOthalassaemia was revealed and only a single polymorphism was associated with a possible extremely mild a-thalassaemia allele. The phenotype associated with the various l3-globin genotypes was found to be extremely variable. Within the many factors that modify this phenotype the Xmn-I polymorphism was significantly associated with the level of haemoglobin expressed. A +1+ genotype appeared to be a good indicator of a milder outcome. The incidence of a-gene deletions was low in patients with HhElI3-thalassaemia and thus proposed this as a strong modifier for a mild phenotype. Other factors were associated with specific complications

Sub-Alfvenic Non-Ideal MHD Turbulence Simulations with Ambipolar Diffusion: I. Turbulence Statistics

Most numerical investigations on the role of magnetic fields in turbulent molecular clouds (MCs) are based on ideal magneto-hydrodynamics (MHD). However, MCs are weakly ionized, so that the time scale required for the magnetic field to diffuse through the neutral component of the plasma by ambipolar diffusion (AD) can be comparable to the dynamical time scale. We have performed a series of 256^3 and 512^3 simulations on supersonic but sub-Alfvenic turbulent systems with AD using the Heavy-Ion Approximation developed in Li, McKee, & Klein (2006). Our calculations are based on the assumption that the number of ions is conserved, but we show that these results approximately apply to the case of time-dependent ionization in molecular clouds as well. Convergence studies allow us to determine the optimal value of the ionization mass fraction when using the heavy-ion approximation for low Mach number, sub-Alfvenic turbulent systems. We find that ambipolar diffusion steepens the velocity and magnetic power spectra compared to the ideal MHD case. Changes in the density PDF, total magnetic energy, and ionization fraction are determined as a function of the AD Reynolds number. The power spectra for the neutral gas properties of a strongly magnetized medium with a low AD Reynolds number are similar to those for a weakly magnetized medium; in particular, the power spectrum of the neutral velocity is close to that for Burgers turbulence.Comment: 37 pages, 11 figures, 4 table

Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer

BACKGROUND: Long intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive. RESULTS: Here we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation. CONCLUSIONS: Our systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0429-8) contains supplementary material, which is available to authorized users

The Midlands LGBT Needs Assessment Community Report

Health disparities research seeks to understand specific health-related needs and outcomes for groups of people, particularly minority groups. In 2011, the Institutes of Medicine (IOM) released a report commissioned by the National Institutes of Health entitled The Health of Lesbian, Gay, Bisexual, and Transgender (LGBT) People: Building a Foundation for Understanding. For the first time, research on the health and well-being of LGBT persons has been prioritized by research funders at the highest levels

On the Hydrodynamic Interaction of Shock Waves with Interstellar Clouds. II. The Effect of Smooth Cloud Boundaries on Cloud Destruction and Cloud Turbulence

The effect of smooth cloud boundaries on the interaction of steady planar shock waves with interstellar clouds is studied using a high-resolution local AMR technique with a second-order accurate axisymmetric Godunov hydrodynamic scheme. A 3D calculation is also done to confirm the results of the 2D ones. We consider an initially spherical cloud whose density distribution is flat near the cloud center and has a power-law profile in the cloud envelope. When an incident shock is transmitted into a smooth cloud, velocity gradients in the cloud envelope steepen the smooth density profile at the upstream side, resulting in a sharp density jump having an arc-like shape. Such a ``slip surface'' forms immediately when a shock strikes a cloud with a sharp boundary. For smoother boundaries, the formation of slip surface and therefore the onset of hydrodynamic instabilities are delayed. Since the slip surface is subject to the Kelvin-Helmholtz and Rayleigh-Taylor instabilities, the shocked cloud is eventually destroyed in $\sim 3-10$ cloud crushing times. After complete cloud destruction, small blobs formed by fragmentation due to hydrodynamic instabilities have significant velocity dispersions of the order of 0.1 $v_b$, where $v_b$ is the shock velocity in the ambient medium. This suggests that turbulent motions generated by shock-cloud interaction are directly associated with cloud destruction. The interaction of a shock with a cold HI cloud should lead to the production of a spray of small HI shreds, which could be related to the small cold clouds recently observed by Stanimirovic & Heiles (2005). The linewidth-size relation obtained from our 3D simulation is found to be time-dependent. A possibility for gravitational instability triggered by shock compression is also discussed.Comment: 62 pages, 16 figures, submitted to Ap

Generation of mice with a conditional Foxp2 null allele

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12–14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the loxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain. genesis 45:440–446, 2007. Published 2007 Wiley-Liss, Inc

Sexting and sexual behaviour in Australian adolescents

BACKGROUND: Previous studies have tried to determine the relationship between sexting and risky behaviour to discover whether sexting fits into a deviance or normalcy discourse. This study investigated the relationship between sexting and sexual risk behaviours, contraception use and gender. METHODS: The design was a cross-sectional analysis of data from the sixth National Survey of Secondary Student and Adolescent Sexual Health, collected in 2018. There were 8263 Australian adolescents (aged 14-18years). Participants were fairly evenly split by gender, and 73% identified as heterosexual. Participants were asked a series of questions about their engagement in sexting, sexual behaviour and sexual health behaviours. RESULTS: A total of 52% of participants had sent a sext in the previous 2months, with most being text-based sexts. Sexters were 3.29times more likely to have engaged in anal or vaginal intercourse, and 2.88times more likely to have gotten pregnant than non-sexters. Sexters (M =2.76) had significantly more partners than non-sexters (M =2.35), t (3763)=-10.99, P X 2 (1)=0.38, P =0.535, or contraceptive use based on sexting status. CONCLUSIONS: Sexters are more likely to have engaged in sexual intercourse and have more partners than non-sexters. Sexting is not strongly associated with other risky behaviours. Evidence for differences between sexters and non-sexters in protecting against STIs and pregnancy was not found, as there were no significant differences in contraceptive use

Temporally and Spatially Resolved Plasma Spectroscopy in Pulsed Laser Deposition of Ultra-Thin Boron Nitride Films

Physical vapor deposition (PVD) has recently been investigated as a viable, alternative growth technique for two-dimensional materials with multiple benefits over other vapor deposition synthesis methods. The high kinetic energies and chemical reactivities of the condensing species formed from PVD processes can facilitate growth over large areas and at reduced substrate temperatures. In this study, chemistry, kinetic energies, time of flight data, and spatial distributions within a PVD plasma plume ablated from aboron nitride (BN) target by a KrF laser at different pressures of nitrogen gas were investigated. Time resolved spectroscopy and wavelength specific imaging were used to identify and track atomic neutral and ionized species including B+, B*, N+, N*, and molecular species including N2*, N2 +, and BN. Formation and decay of these species formed both from ablation of the target and from interactions with the background gas were investigated and provided insights into fundamental growth mechanisms of continuous, amorphous boron nitride thin films. The correlation of the plasma diagnostic results with film chemical composition and thickness uniformity studies helped to identify that a predominant mechanism for BN film formation is condensation surface recombination of boron ions and neutral atomic nitrogen species. These species arrive nearly simultaneously to the substrate location, and BN formation occurs microseconds before arrival of majority of N+ ions generated by plume collisions with background molecular nitrogen. The energetic nature and extended dwelling time of incident N+ ions at the substrate location was found to negatively impact resulting BN film stoichiometry and thickness. Growth of stoichiometric films was optimized at enriched concentrations of ionized boron and neutral atomic nitrogen in plasma near the condensation surface, providing few nanometer thick films with 1:1 BN stoichiometry and good thicknesses uniformity over macroscopic areas