Reinvestigation of the Saccharomyces cerevisiae genome annotation by comparison to the genome of a related fungus: Ashbya gossypii

BACKGROUND: The recently sequenced genome of the filamentous fungus Ashbya gossypii revealed remarkable similarities to that of the budding yeast Saccharomyces cerevisiae both at the level of homology and synteny (conservation of gene order). Thus, it became possible to reinvestigate the S. cerevisiae genome in the syntenic regions leading to an improved annotation. RESULTS: We have identified 23 novel S. cerevisiae open reading frames (ORFs) as syntenic homologs of A. gossypii genes; for all but one, homologs are present in other eukaryotes including humans. Other comparisons identified 13 overlooked introns and suggested 69 potential sequence corrections resulting in ORF extensions or ORF fusions with improved homology to the syntenic A. gossypii homologs. Of the proposed corrections, 25 were tested and confirmed by resequencing. In addition, homologs of nearly 1,000 S. cerevisiae ORFs, presently annotated as hypothetical, were found in A. gossypii at syntenic positions and can therefore be considered as authentic genes. Finally, we suggest that over 400 S. cerevisiae ORFs that overlap other ORFs in S. cerevisiae and for which no homolog can be detected in A. gossypii should be regarded as spurious. CONCLUSIONS: Although, the S. cerevisiae genome is rightly considered as one of the most accurately sequenced and annotated eukaryotic genomes, we have shown that it still benefits substantially from comparison to the completed sequence and syntenic gene map of A. gossypii, an evolutionarily related fungus. This type of approach will strongly support the annotation of more complex genomes such as the human and murine genomes

Reverberation Mapping of the Kepler-Field AGN KA1858+4850

KA1858+4850 is a narrow-line Seyfert 1 galaxy at redshift 0.078 and is among the brightest active galaxies monitored by the Kepler mission. We have carried out a reverberation mapping campaign designed to measure the broad-line region size and estimate the mass of the black hole in this galaxy. We obtained 74 epochs of spectroscopic data using the Kast Spectrograph at the Lick 3-m telescope from February to November of 2012, and obtained complementary V-band images from five other ground-based telescopes. We measured the H-beta light curve lag with respect to the V-band continuum light curve using both cross-correlation techniques (CCF) and continuum light curve variability modeling with the JAVELIN method, and found rest-frame lags of lag_CCF = 13.53 (+2.03, -2.32) days and lag_JAVELIN = 13.15 (+1.08, -1.00) days. The H-beta root-mean-square line profile has a width of sigma_line = 770 +/- 49 km/s. Combining these two results and assuming a virial scale factor of f = 5.13, we obtained a virial estimate of M_BH = 8.06 (+1.59, -1.72) x 10^6 M_sun for the mass of the central black hole and an Eddington ratio of L/L_Edd ~ 0.2. We also obtained consistent but slightly shorter emission-line lags with respect to the Kepler light curve. Thanks to the Kepler mission, the light curve of KA1858+4850 has among the highest cadences and signal-to-noise ratios ever measured for an active galactic nucleus; thus, our black hole mass measurement will serve as a reference point for relations between black hole mass and continuum variability characteristics in active galactic nuclei

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Identifying Archaeological Bone via Non-Destructive ZooMS and the Materiality of Symbolic Expression: Examples from Iroquoian Bone Points.

Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology

Meaningful cognitive decline is uncommon in virally suppressed HIV, but sustained impairment, subtle decline and abnormal cognitive aging are notResearch in context

Summary: Background: High antiretroviral therapy (ART) coverage and viral suppression among people with HIV (PWH) in Australia provide a unique context to study individual cognitive trajectories, cognitive aging and factors associated with longitudinal cognitive function during chronic and stable HIV disease. Methods: Participants from the Predictors of Adherence to Antiretroviral Therapy study (n = 457, recruited between September 2013 and November 2015, median age = 52 years, and all with HIV RNA 0.5). Meaningful cognitive change was statistically defined (decline or improvement versus stability, i.e., 90% CI, that is p < 0.05, 2-tailed) using a novel evidence-based change score: the linear mixed-effect regression (LMER)-based GZS change score. A separate LMER model with a top-down variable selection approach identified the independent effects of age and other demographic, HIV disease characteristics, socioeconomic and health-related factors on the demographically corrected GZS. The combined definitions of change and cross-sectional impairment enabled the identification of cognitive trajectories. Findings: At Month-12 and Month-24, 6% and 7% showed meaningful cognitive decline and 4% and 3% improved respectively. Only 1% showed sustained decline. Incident impairment due to subtle cognitive decline (i.e., below the threshold of meaningful cognitive decline) was 31% and 25% at Month-12 and Month-24, while 14% showed sustained impairment (i.e., cognitively impaired at all study visits). Older age (≥50 years) and time interaction was associated with lower demographically corrected GZS (β = −0.31, p < 0.001). Having a regular relationship, excellent English proficiency, and perceived stigma (avoidance) were associated with higher GZS (all p < 0.05). Relying on government subsidy, severe depression, and lower belief in ART necessity and higher concerns were associated with lower GZS (all p < 0.05). No HIV disease characteristics had a significant effect. Interpretations: Meaningful cognitive decline was not different from normal expectation in chronic stable HIV disease. Despite this, subtle cognitive decline, sustained cognitive impairment, and greater than normative-age cognitive aging were evident. Funding: Funding for the PAART study was provided in part by unrestricted educational grants from Gilead Sciences (www.gilead.com) (Grant Number: IN-AU-264- 0131), the Balnaves Foundation (www.balnavesfoundation.com), the Victorian Department of Health and Human Services (Australia) (www.dhs.vic.gov.au/home), Western Australia Health (www.health.wa.gov.au), the ACT Ministry of Health (Australia) (www.health.act.gov.au), and in-kind support from the Queensland Department of Health (Australia) (www.health.qld.gov.au), and NHMRC Partnership grant APP1058474 (PI: Carr, Andrew)

Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

BACKGROUND: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS: Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. RESULTS: We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004), reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012). CONCLUSIONS: In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support

Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

BACKGROUND: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS: Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. RESULTS: We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004), reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012). CONCLUSIONS: In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support

Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

<div><p>Background</p><p>Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings.</p><p>Methods</p><p>Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression.</p><p>Results</p><p>We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2–6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2–4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5–7.3], p = 0.004), reaching the “Medicare safety net” (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1–4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0–6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0–18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1–5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3–7.0], p = 0.012).</p><p>Conclusions</p><p>In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support.</p></div