Electrical and infrared properties of thin niobium microbolometers near T(sub c)

Niobium microbolometers approximately 1 micron wide x 2 micron long x 10 nm thick have been integrated at the feeds of equiangular spiral antennas made of 200 nm thick Nb. The device's current-voltage characteristics and infrared responsivity as a function of DC bias voltage were measured over a range of temperature spanning approximately plus or minus 2 percent around T(sub c). The greatest voltage responsivity occurs well below T(sub c), in a regime where the I-V curve is significantly hysteretic due to self-heating and resembles the I-V curve of a superconducting microbridge

A role for GPx3 in activity of normal and leukemia stem cells

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs

Analysis of Blood Stem Cell Activity and Cystatin Gene Expression in a Mouse Model Presenting a Chromosomal Deletion Encompassing Csta and Stfa2l1

The cystatin protein superfamily is characterized by the presence of conserved sequences that display cysteine protease inhibitory activity (e.g., towards cathepsins). Type 1 and 2 cystatins are encoded by 25 genes of which 23 are grouped in 2 clusters localized on mouse chromosomes 16 and 2. The expression and essential roles of most of these genes in mouse development and hematopoiesis remain poorly characterized. In this study, we describe a set of quantitative real-time PCR assays and a global expression profile of cystatin genes in normal mouse tissues. Benefiting from our collection of DelES embryonic stem cell clones harboring large chromosomal deletions (to be reported elsewhere), we selected a clone in which a 95-kb region of chromosome 16 is missing (Del16qB3Δ/+). In this particular clone, 2 cystatin genes, namely Csta and Stfa2l1 are absent along with 2 other genes (Fam162a, Ccdc58) and associated intergenic regions. From this line, we established a new homozygous mutant mouse model (Del16qB3Δ/16qB3Δ) to assess the in vivo biological functions of the 2 deleted cystatins. Stfa2l1 gene expression is high in wild-type fetal liver, bone marrow, and spleen, while Csta is ubiquitously expressed. Homozygous Del16qB3Δ/16qB3Δ animals are phenotypically normal, fertile, and not overtly susceptible to spontaneous or irradiation-induced tumor formation. The hematopoietic stem and progenitor cell activity in these mutant mice are also normal. Interestingly, quantitative real-time PCR expression profiling reveals a marked increase in the expression levels of Stfa2l1/Csta phylogenetically-related genes (Stfa1, Stfa2, and Stfa3) in Del16qB3Δ/16qB3Δ hematopoietic tissues, suggesting that these candidate genes might be contributing to compensatory mechanisms. Overall, this study presents an optimized approach to globally monitor cystatin gene expression as well as a new mouse model deficient in Stfa2l1/Csta genes, expanding the available tools to dissect cystatin roles under normal and pathological conditions

Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring protein-coding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.National Science Foundation (U.S.) (Postdoctoral Research Fellowship in Biology DBI-0905973

The Tug1 locus is essential for male fertility

Background: Several long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge. Results: We previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities - two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential. Conclusions: Our results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci

Human Papilloma Virus vaccine and cervical cancer screening acceptability among adults in Quebec, Canada

<p>Abstract</p> <p>Background</p> <p>The Pap test has been used for cervical cancer screening for more than four decades. A human papillomavirus (HPV) vaccine has been approved for use in Canada and is commercially available now. These two preventive interventions should be considered simultaneously. General population support is an important factor for the successful combination of these interventions. The study had two objectives: 1) To assess practices, beliefs, and attitudes regarding Pap test screening and HPV immunization; 2) To identify socio-demographic factors for Pap screening and vaccine acceptability.</p> <p>Methods</p> <p>In 2006, 500 adults were invited to participate in a telephone survey in the region of Quebec City (urban and rural population, 600 000), Canada. Some neutral and standardized information on Pap test and HPV was provided before soliciting opinions.</p> <p>Results</p> <p>471 adults (18–69 year-olds) answered the questionnaire, the mean age was 45 years, 67% were female, and 65% had college or university degree. Eighty-six percent of women had undergone at least one Pap-test in their life, 55% in the last year, and 15% from 1 to 3 years ago. Among screened women, the test had been performed in the last three years in 100% of 18–30 year-olds, but only in 67% of 60–69 year-olds (P < 0.0001). Only 15% of respondents had heard of HPV. Eighty-seven percent agreed that HPV vaccines could prevent cervical cancer, 73% that the vaccine has to be administered before the onset of sexual activity, 89% would recommend vaccination to their daughters and nieces. Among respondents < 25 years, 91% would agree to receive the vaccine if it is publicly funded, but only 72% would agree to pay $100/dose.</p> <p>Conclusion</p> <p>There is an important heterogeneity in cervical cancer screening frequency and coverage. Despite low awareness of HPV infection, the majority of respondents would recommend or are ready to receive the HPV vaccine, but the cost could prevent its acceptability.</p

Feasibility and impact of providing feedback to vaccinating medical clinics: evaluating a public health intervention

<p>Abstract</p> <p>Background</p> <p>Vaccine coverage (VC) at a given age is a widely-used indicator for measuring the performance of vaccination programs. However, there is increasing data suggesting that measuring delays in administering vaccines complements the measure of VC. Providing feedback to vaccinators is recognized as an effective strategy for improving vaccine coverage, but its implementation has not been widely documented in Canada. The objective of this study was to evaluate the feasibility of providing personalized feedback to vaccinators and its impact on vaccination delays (VD).</p> <p>Methods</p> <p>In April and May 2008, a one-hour personalized feedback session was provided to health professionals in vaccinating medical clinics in the Quebec City region. VD for vaccines administered at two and twelve months of age were presented. Data from the regional vaccination registry were analysed for participating clinics. Two 12-month periods before and after the intervention were compared, namely from April 1^st, 2007 to March 31^st, 2008 and from June 1^st, 2008 to May 31^st, 2009.</p> <p>Results</p> <p>Ten medical clinics out of the twelve approached (83%), representing more than 2500 vaccinated children, participated in the project. Preparing and conducting the feedback involved 20 hours of work and expenses of $1000 per clinic. Based on a delay of one month, 94% of first doses of DTaP-Polio-Hib and 77% of meningococcal vaccine doses respected the vaccination schedule both before and after the intervention. Following the feedback, respect of the vaccination schedule increased for vaccines planned at 12 months for the four clinics that had modified their vaccination practices related to multiple injections (depending on the clinic, VD decreased by 24.4%, 32.0%, 40.2% and 44.6% respectively, p < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>The present study shows that it is feasible to provide personalized feedback to vaccinating clinics. While it may have encouraged positive changes in practice concerning multiple injections, this intervention on its own did not impact vaccination delays of the clinics visited. It is possible that feedback integrated into other types of effective interventions and sustained over time may have more impact on VD.</p

Cryptic Haploid Stages in the Life Cycle of Leathesia marina (Chordariaceae, Phaeophyceae) Under In Vitro Culture

We evaluated the life cycle of Leathesia marina through molecular analyses, culture studies, morphological observations, and ploidy measurements. Macroscopic sporophytes were collected from two localities in Atlantic Patagonia and were cultured under long-day (LD) and short-day (SD) conditions. Molecular identification of the microscopic and macroscopic phases was performed through the cox3 and rbcL genes and the phylogeny was assessed on the basis of single gene and concatenated datasets. Nuclear ploidy of each phase was estimated from the DNA contents of individual nuclei through epifluorescence microscopy and flow cytometry. Molecular results confirmed the identity of the Argentinian specimens as L. marina and revealed their conspecificity with L. marina from New Zealand, Germany, and Japan. The sporophytic macrothalli (2n) released mitospores from plurilocular sporangia, which developed into globular microthalli (2n), morphologically similar to the sporophytes but not in size, constituting a generation of small diploid thalli, with a mean fluorescent nuclei cross-sectional area of 3.21 ± 0.7 μm2. The unilocular sporangia released meiospores that developed two morphologically different types of microthalli: erect branched microthalli (n) with a nuclear area of 1.48 ± 0.07 µm2 that reproduces asexually, and prostrate branched microthalli (n) with a nuclear area of 1.24 ± 0.10 µm2 that reproduces sexually. The prostrate microthalli released gametes in LD conditions, which merged and produced macroscopic thalli with a nuclear cross-sectional area of 3.45 ± 0.09 µm2. Flow cytometry confirmed that the erect and prostrate microthalli were haploid and that the globular microthalli and macrothalli were diploid.Fil: Poza, Ailen Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Santiañez, Wilfred John E.. Hokkaido University; Japón. University of the Philippines Diliman; FilipinasFil: Croce, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Gauna, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Kogame, Kazuhiro. Hokkaido University; JapónFil: Parodi, Elisa Rosalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentin