A molecular cell biology toolkit for the study of meiosis in the silkworm Bombyx mori

Meiosis is usually described as 4 essential and sequential processes: (1) homolog pairing; (2) synapsis, mediated by the synaptonemal complex; (3) crossing over; and (4) segregation. In this canonical model, the maturation of crossovers into chiasmata plays a vital role in holding homologs together and ensuring their segregation at the first meiotic division. However, Lepidoptera (moths and butterflies) undergo 3 distinct meiotic processes, only one of which is canonical. Lepidoptera males utilize 2 meiotic processes: canonical meiosis that produces nucleated fertile sperm, and a noncanonical meiosis that produces anucleated nonfertile sperm which are nonetheless essential for reproduction. Lepidoptera females, which carry heteromorphic sex chromosomes, undergo a completely achiasmate (lacking crossovers) meiosis, thereby requiring an alternative mechanism to ensure proper homolog segregation. Here, we report that the development of a molecular cell biology toolkit designed to properly analyze features of meiosis, including the synaptonemal complex structure and function, in the silkworm Bombyx mori. In addition to standard homology searches to identify Bombyx orthologs of known synaptonemal complex encoding genes, we developed an ortholog discovery app (Shinyapp) to identify Bombyx orthologs of proteins involved in several meiotic processes. We used this information to clone genes expressed in the testes and then created antibodies against their protein products. We used the antibodies to confirm the localization of these proteins in normal male spermatocytes, as well as using in vitro assays to confirm orthologous interactions. The development of this toolkit will facilitate further study of the unique meiotic processes that characterize meiosis in Lepidoptera.</p

Randomised Trial to Evaluate the Effectiveness and Impact of Offering Postvisit Decision Support and Assistance in Obtaining Physician-Recommended Colorectal Cancer Screening: The e-Assist: Colon Health Study - A Protocol Study

INTRODUCTION: How to provide practice-integrated decision support to patients remains a challenge. We are testing the effectiveness of a practice-integrated programme targeting patients with a physician recommendation for colorectal cancer (CRC) screening. METHODS AND ANALYSIS: In partnership with healthcare teams, we developed \u27e-assist: Colon Health\u27, a patient-targeted, postvisit CRC screening decision support programme. The programme is housed within an electronic health record (EHR)-embedded patient portal. It leverages a physician screening recommendation as the cue to action and uses the portal to enrol and intervene with patients. Programme content complements patient-physician discussions by encouraging screening, addressing common questions and assisting with barrier removal. For evaluation, we are using a randomised trial in which patients are randomised to receive e-assist: Colon Health or one of two controls (usual care plus or usual care). Trial participants are average-risk, aged 50-75 years, due for CRC screening and received a physician order for stool testing or colonoscopy. Effectiveness will be evaluated by comparing screening use, as documented in the EHR, between trial enrollees in the e-assist: Colon Health and usual care plus (CRC screening information receipt) groups. Secondary outcomes include patient-perceived benefits of, barriers to and support for CRC screening and patient-reported CRC screening intent. The usual care group will be used to estimate screening use without intervention and programme impact at the population level. Differences in outcomes by study arm will be estimated with hierarchical logit models where patients are nested within physicians. ETHICS AND DISSEMINATION: All trial aspects have been approved by the Institutional Review Board of the health system in which the trial is being conducted. We will disseminate findings in diverse scientific venues and will target clinical and quality improvement audiences via other venues. The intervention could serve as a model for filling the gap between physician recommendations and patient action. TRIAL REGISTRATION NUMBER: NCT02798224; Pre-results

DAS181 treatment of severe lower respiratory tract parainfluenza virus infection in immunocompromised patients: A phase 2 randomized, placebo-controlled study

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877

A Systematic Evaluation of Websites Offering Information on Chronic Kidney Disease

In this study, we described the content and characteristics of 40 non-proprietary websites offering information about chronic kidney disease (CKD) and evaluated their information quality using the DISCERN scale and readability using Flesch Reading Ease and Flesch-Kincaid grade level. The areas in which the websites scored the lowest on the DISCERN scale were whether the website discussed knowledge gaps, presented balanced information, and was clear about the information source. Websites that rated higher quality on the DISCERN scale were more difficult to read. The quality and readability of many websites about CKD to be used as meaningful educational resources for patients who desire to learn more about CKD and treatment options remain inadequate

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Absence of RIP140 Reveals a Pathway Regulating glut4-Dependent Glucose Uptake in Oxidative Skeletal Muscle through UCP1-Mediated Activation of AMPK

Skeletal muscle constitutes the major site of glucose uptake leading to increased removal of glucose from the circulation in response to insulin. Type 2 diabetes and obesity are often associated with insulin resistance that can be counteracted by exercise or the use of drugs increasing the relative proportion of oxidative fibers. RIP140 is a transcriptional coregulator with a central role in metabolic tissues and we tested the effect of modulating its level of expression on muscle glucose and lipid metabolism in two mice models. Here, we show that although RIP140 protein is expressed at the same level in both oxidative and glycolytic muscles, it inhibits both fatty acid and glucose utilization in a fiber-type dependent manner. In RIP140-null mice, fatty acid utilization increases in the extensor digitorum longus and this is associated with elevated expression of genes implicated in fatty acid binding and transport. In the RIP140-null soleus, depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with no change in Akt activity. AMPK phosphorylation/activity is inhibited in the soleus of RIP140 transgenic mice and increased in RIP140-null soleus. This is associated with increased UCP1 expression and mitochondrial uncoupling revealing the existence of a signaling pathway controlling insulin-independent glucose uptake in the soleus of RIP140-null mice. In conclusion, our findings reinforce the participation of RIP140 in the maintenance of energy homeostasis by acting as an inhibitor of energy production and particularly point to RIP140 as a promising therapeutic target in the treatment of insulin resistance

LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in Hepatocytes.

Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Racial/ethnic differences in job loss for women with breast cancer

IntroductionWe examined race/ethnic differences in treatment-related job loss and the financial impact of treatment-related job loss, in a population-based sample of women diagnosed with breast cancer.MethodsThree thousand two hundred fifty two women with non-metastatic breast cancer diagnosed (August 2005-February 2007) within the Los Angeles County and Detroit Metropolitan Surveillance Epidemiology and End Results registries, were identified and asked to complete a survey (mean time from diagnosis = 8.9&nbsp;months). Latina and African American women were over-sampled (n = 2268, eligible response rate 72.1%).ResultsOne thousand one hundred eleven women (69.6%) of working age (&lt;65&nbsp;years) were working for pay at time of diagnosis. Of these women, 10.4% (24.1% Latina, 10.1% African American, 6.9% White, p &lt; 0.001) reported that they lost or quit their job since diagnosis due to breast cancer or its treatment (defined as job loss). Latina women were more likely to experience job loss compared to White women (OR = 2.0, p = 0.013)), independent of sociodemographic factors. There were no significant differences in job loss between African American and White women, independent of sociodemographic factors. Additional adjustments for clinical and treatment factors revealed a significant interaction between race/ethnicity and chemotherapy (p = 0.007). Among women who received chemotherapy, Latina women were more likely to lose their job compared to White women (OR = 3.2, p &lt; 0.001), however, there were no significant differences between Latina and White women among those who did not receive chemotherapy. Women who lost their job were more likely to experience financial strain (e.g. difficulty paying bills 27% vs. 11%, p &lt; 0.001).ConclusionJob loss is a serious consequence of treatment for women with breast cancer. Clinicians and staff need to be aware of aspects of treatment course that place women at higher risk for job loss, especially ethnic minorities receiving chemotherapy