Comparative Efficacy of Mayaro Virus-Like Particle Vaccines Produced in Insect or Mammalian Cells.

Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes often debilitating rheumatic disease in tropical Central and South America. There are currently no licensed vaccines or antiviral drugs available for MAYV disease. Here, we generated Mayaro virus-like particles (VLPs) using the scalable baculovirus-insect cell expression system. High-level secretion of MAYV VLPs in the culture fluid of Sf9 insect cells was achieved, and particles with a diameter of 64 to 70 nm were obtained after purification. We characterize a C57BL/6J adult wild-type mouse model of MAYV infection and disease and used this model to compare the immunogenicity of VLPs from insect cells with that of VLPs produced in mammalian cells. Mice received two intramuscular immunizations with 1 µg of nonadjuvanted MAYV VLPs. Potent neutralizing antibody responses were generated against the vaccine strain, BeH407, with comparable activity seen against a contemporary 2018 isolate from Brazil (BR-18), whereas neutralizing activity against chikungunya virus was marginal. Sequencing of BR-18 illustrated that this virus segregates with genotype D isolates, whereas MAYV BeH407 belongs to genotype L. The mammalian cell-derived VLPs induced higher mean neutralizing antibody titers than those produced in insect cells. Both VLP vaccines completely protected adult wild-type mice against viremia, myositis, tendonitis, and joint inflammation after MAYV challenge. IMPORTANCE Mayaro virus (MAYV) is associated with acute rheumatic disease that can be debilitating and can evolve into months of chronic arthralgia. MAYV is believed to have the potential to emerge as a tropical public health threat, especially if it develops the ability to be efficiently transmitted by urban mosquito vectors, such as Aedes aegypti and/or Aedes albopictus. Here, we describe a scalable virus-like particle vaccine against MAYV that induced neutralizing antibodies against a historical and a contemporary isolate of MAYV and protected mice against infection and disease, providing a potential new intervention for MAYV epidemic preparedness.

Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1-55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1-5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene-bearing strains, and 3 had nontoxigenic tox gene-bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

Are the Relevant Risk Factors Being Adequately Captured in Empirical Studies of Smoking Initiation? A Machine Learning Analysis Based on the Population Assessment of Tobacco and Health Study.

INTRODUCTION: Cigarette smoking continues to pose a threat to public health. Identifying individual risk factors for smoking initiation is essential to further mitigate this epidemic. To the best of our knowledge, no study today has used machine learning (ML) techniques to automatically uncover informative predictors of smoking onset among adults using the Population Assessment of Tobacco and Health (PATH) study. AIMS AND METHODS: In this work, we employed random forest paired with Recursive Feature Elimination to identify relevant PATH variables that predict smoking initiation among adults who have never smoked at baseline between two consecutive PATH waves. We included all potentially informative baseline variables in wave 1 (wave 4) to predict past 30-day smoking status in wave 2 (wave 5). Using the first and most recent pairs of PATH waves was found sufficient to identify the key risk factors of smoking initiation and test their robustness over time. The eXtreme Gradient Boosting method was employed to test the quality of these selected variables. RESULTS: As a result, classification models suggested about 60 informative PATH variables among many candidate variables in each baseline wave. With these selected predictors, the resulting models have a high discriminatory power with the area under the specificity-sensitivity curves of around 80%. We examined the chosen variables and discovered important features. Across the considered waves, two factors, (1) BMI, and (2) dental and oral health status, robustly appeared as important predictors of smoking initiation, besides other well-established predictors. CONCLUSIONS: Our work demonstrates that ML methods are useful to predict smoking initiation with high accuracy, identifying novel smoking initiation predictors, and to enhance our understanding of tobacco use behaviors. IMPLICATIONS: Understanding individual risk factors for smoking initiation is essential to prevent smoking initiation. With this methodology, a set of the most informative predictors of smoking onset in the PATH data were identified. Besides reconfirming well-known risk factors, the findings suggested additional predictors of smoking initiation that have been overlooked in previous work. More studies that focus on the newly discovered factors (BMI and dental and oral health status,) are needed to confirm their predictive power against the onset of smoking as well as determine the underlying mechanisms.

The evolution of age-specific smoking cessation rates in the United States from 2009 to 2017: a Kalman filter based approach.

BACKGROUND: Tracking the US smoking cessation rate over time is of great interest to tobacco control researchers and policymakers since smoking cessation behaviors have a major effect on the public's health. Recent studies have employed dynamic models to estimate the US cessation rate through observed smoking prevalence. However, none of those studies has provided annual estimates of the cessation rate by age group. Hence, the primary objective of this study is to estimate annual smoking cessation rates specific to different age groups in the US from 2009 to 2017. METHODS: We employed a Kalman filter approach to investigate the annual evolution of age-group-specific cessation rates, unknown parameters of a mathematical model of smoking prevalence, during the 2009-2017 period using data from the 2009-2018 National Health Interview Surveys. We focused on cessation rates in the 25-44, 45-64 and 65 + age groups. RESULTS: The findings show that cessation rates followed a consistent u-shaped curve over time with respect to age (i.e., higher among the 25-44 and 65 + age groups, and lower among 45-64-year-olds). Over the course of the study, the cessation rates in the 25-44 and 65 + age groups remained nearly unchanged around 4.5% and 5.6%, respectively. However, the rate in the 45-64 age group exhibited a substantial increase of 70%, from 2.5% to 2009 to 4.2% in 2017. The estimated cessation rates in all three age groups tended to converge to the weighted average cessation rate over time. CONCLUSIONS: The Kalman filter approach offers a real-time estimation of cessation rates that can be helpful for monitoring smoking cessation behavior.

Integration of Interbull's multiple across-country evaluation approach breeding values into the multiple-trait single-step random regression test-day genetic evaluation for yield traits of Australian Red breeds.

Interbull's multiple across-country evaluaftion provides national breeding organizations with breeding values for internationally used bulls, which integrate performance data obtained in different breeding populations, environments, and production systems. However, breeding value-based selection decisions on domestic individuals born to foreign sires can only benefit from Interbull breeding values if they are integrated such that their information can contribute to the breeding values of all related domestic animals. For that purpose, several methods have been proposed which either model Interbull breeding values as prior information in a Bayesian approach, as additional pseudo data points, or as correlated traits, where these methods also differ in their software and parameterization requirements. Further, the complexity of integration also depends on the traits and genetic evaluation models. Especially random regression models require attention because of the dimensionality discrepancy between the number of Interbull breeding values and the number of modeled genetic effects. This paper presents the results from integrating 16,063 Interbull breeding values into the domestic single-step random regression test-day model for milk, fat, and protein yield for Australian Red dairy cattle breeds. Interbull breeding values were modeled as pseudo data points with data point-specific residual variances derived within animal across traits, ignoring relationships between integrated animals. Results suggest that the integration was successful with regard to alignment of Interbull breeding values with their domestic equivalent as well as with regard to the individual and population-wide increase in reliabilities. Depending on the relationship structure between integration candidates, further work is required to account for those relationships in a computationally feasible manner. Other traits with separate parity effects nationally could use a similar approach, even if not modeled with a test-day model.

A unique genetic variation with respect to blast (Pyricularia oryzae Cavara) resistance in rice (Oryza sativa L.) varieties in Vietnam.

A unique genetic variation with respect to blast resistance was clarified in 201 rice accessions from Vietnam. These accessions were classified into three clusters-A, B1, and B2-based on their reactions to 26 standard differential blast isolates selected in Vietnam. Cluster A was the dominant cultivar group in Vietnam and the most susceptible of the three clusters. Cluster B1 was the smallest group and the most resistant. Cluster B2 was the second-most dominant group and of intermediate resistance between clusters A and B1. The percentages of accessions comprising each cluster varied by region and area. Accessions in cluster A were distributed widely throughout Vietnam and had the highest frequencies in both the Central and North regions. Accessions in cluster B2 were found with highest frequencies in the mountainous and intermediate areas of the North region. Accessions in cluster B1 were found with highest frequencies in the Central region and Red River Delta area (North region). These results suggest that rice accessions in Vietnam were basically susceptible (cluster A) or of intermediate resistance (cluster B2), and that high-resistance cultivars were mainly distributed in the low altitude areas, such as the Red River Delta area and Central region.

Presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies Among Vietnamese Healthcare Workers by Dosing Interval for ChAdOx1 nCoV-19 Vaccine.

BACKGROUND: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). METHODS: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2. RESULTS: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%). CONCLUSIONS: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.

Monitoring the Increase in the U.S. Smoking Cessation Rate and Its Implication for Future Smoking Prevalence.

INTRODUCTION: We calculate the U.S. adult smoking cessation rate for 2014-2019, compare it to the historical trend, and estimate the implication for future smoking prevalence. METHODS: We repeated an earlier analysis, which examined the cessation rate from 1990 to 2014, extending the period to 2019. Employing National Health Interview Survey (NHIS) and National Survey on Drug Use and Health (NSDUH) data, we estimated the adult cessation rate in 6-year intervals, using weighted nonlinear least squares. We then employed a meta-regression model to test whether the cessation rate has increased beyond expectation. We used cessation rate estimates and smoking initiation rate estimates to project smoking prevalence in 2030 and eventual steady-state prevalence. RESULTS: The annual cessation rate increased 29% using NHIS data (from 4.2% in 2008-2013 to 5.4% in 2014-2019) and 33% with NSDUH data (4.2%-5.6%). The cessation rate increase accounts for 60% of a smoking prevalence decline in the most recent period exceeding the 1990-2013 predicted trend. The remaining 40% owes to declining smoking initiation. With current initiation and cessation rates, smoking prevalence should fall to 8.3% in 2030 and eventually reach a steady state of 3.53%. CONCLUSIONS: The smoking cessation rate continued to increase during 2014-2019. NHIS and NSDUH results are practically identical. The larger share (60%) of the smoking prevalence decrease, beyond expectation, attributable to the increased cessation rate is encouraging since the positive health effects of cessation occur much sooner than those derived from declining initiation. IMPLICATIONS: The smoking cessation rate in the United States continues to increase, accelerating the decline in smoking prevalence. This increase suggests that the Healthy People 2030 goal of 5% adult smoking prevalence, while ambitious, is attainable. Our findings can be used in simulation and statistical models that aim to predict future prevalence and population health effects due to smoking under various scenarios.

Stigma experienced by people living with HIV who are on methadone maintenance treatment and have symptoms of common mental disorders in Hanoi, Vietnam: a qualitative study.

BACKGROUND: Stigma around human immunodeficiency virus (HIV), injection drug use (IDU), and mental health disorders can be co-occurring and have different impacts on the well-being of people living with HIV (PWH) who use drugs and have mental health disorders. This stigma can come from society, health professionals, and internalized stigma. A person who has more than one health condition can experience overlapping health-related stigma and levels of stigma which can prevent them from receiving necessary support and healthcare, serving to intensify their experience with stigma. This study investigates HIV, drug use, and mental health stigmas in three dimensions (social, internalized, and professional) around PWH on methadone maintenance treatment (MMT) who have common mental disorders (CMDs) including depression, anxiety, and stress-related disorders in Hanoi, Vietnam.Please check and confirm whether corresponding author's email id is correctly identified.The cooresponding author's email is correct METHODS: We conducted semi-structured, in-depth interviews (IDIs) (n = 21) and two focus group discussions (FGDs) (n = 10) with PWH receiving MMT who have CMD symptoms, their family members, clinic health care providers, and clinic directors. We applied thematic analysis using NVIVO software version 12.0, with themes based on IDI and FGD guides and emergent themes from interview transcripts. RESULTS: The study found evidence of different stigmas towards HIV, IDU, and CMDs from the community, family, health care providers, and participants themselves. Community and family members were physically and emotionally distant from patients due to societal stigma around illicit drug use and fears of acquiring HIV. Participants often conflated stigmas around drug use and HIV, referring to these stigmas interchangeably. The internalized stigma around having HIV and injecting drugs made PWH on MMT hesitant to seek support for CMDs. These stigmas compounded to negatively impact participants' health. CONCLUSIONS: Strategies to reduce stigma affecting PWH on MMT should concurrently address stigmas around HIV, drug addiction, and mental health. Future studies could explore approaches to address internalized stigma to improve self-esteem, mental health, and capacities to cope with stigma for PWH on MMT. TRIAL REGISTRATION: NCT04790201, available at clinicaltrials.gov.

The association between smoking behaviors and prices and taxes per cigarette pack in the United States from 2000 through 2019.

OBJECTIVE: The conclusions on how tax and price increases affect smoking behaviors are mixed. This work is devoted to re-evaluating the relationship between cigarette prices and taxes and smoking behaviors. METHODS: Using 2000-2019 Behavioral Risk Factor Surveillance System data, we employed linear mixed-effect models to re-examine the impact of cigarette prices and taxes on smoking prevalence and the proportion of current smokers having tried to quit smoking in the past 12 months. All the analyses were conducted for the general population, then by age group, gender, race/ethnicity, and income level. RESULTS: The results indicate that higher cigarette prices and taxes were associated with a decrease in smoking prevalence and an increased likelihood of quitting smoking. Cigarette tax and price increases produced the most powerful impact on the smoking prevalence of 18- to 24-year-olds. The estimates also show that males tended to be more price-sensitive than females. Raising cigarette prices and taxes was estimated to be more effective in reducing the smoking prevalence among non-Hispanic Blacks and Hispanics when compared to non-Hispanic whites. Cigarette price and tax changes were likely to have a smaller effect on individuals with annual income under $25,000 relative to individuals with higher income levels. CONCLUSIONS: Increases in cigarette prices and taxes are significantly associated with a reduction in smoking prevalence and an increased likelihood of quitting smoking among adults across different demographic and socioeconomic groups. However, as cigarette price and tax changes disproportionately affect low-income individuals, raising cigarette prices and taxes may deepen income disparities.

An unequal endotoxin distribution in typical house types of Ho Chi Minh city.

BACKGROUND: Endotoxin exposure may cause asthma exacerbations and contribute to non-atopic respiratory diseases. Viet Nam, a country with multiple house types, is lacking data on indoor contamination by endotoxin in regard with house types. OBJECTIVE: The comparison of measured settled dust endotoxin levels among house types in Ho Chi Minh city will allow to classify the house types regarding health risks. METHODS: This study is a cross-sectional study. Five identified house types were selected: apartment (APA), rental (REN), rural (RUR), slum (SLU) and tube house (TUB). One hundred house's endotoxin contamination was evaluated by questionnaire and dust sampling. Endotoxin concentration was measured by kinetic chromogenic Limulus assay. RESULTS: dotoxin concentration (geometric mean 126.0 EU/mg, 95%CI 118.3-133.7) is particularly high in settled house dust compared to western countries and is significantly associated with the house type. The highest level was found in RUR in each room (p = 0.002 for living room; p < 0.0001 for bedrooms and for kitchens). Concerning levels in the different rooms, APA and TUB form a low group while REN and SLU (p < 0.001) form a median group and RUR the highest (p < 0.001). Differences in endotoxin levels were associated to the presence of dog, chicken and farm animals, wood cooking, air-conditioning usage. CONCLUSIONS: Further understanding of the relevant factors to endotoxin levels would contribute to prevent asthma exacerbations and chronic respiratory diseases. Public health interventions to reduce exposure to endotoxin include improving housing conditions, eliminating risk factors and a priority to high-risk house types.

Is mammography screening beneficial: An individual-based stochastic model for breast cancer incidence and mortality.

The benefits of mammography screening have been controversial, with conflicting findings from various studies. We hypothesize that unmeasured heterogeneity in tumor aggressiveness underlies these conflicting results. Based on published data from the Canadian National Breast Screening Study (CNBSS), we develop and parameterize an individual-based mechanistic model for breast cancer incidence and mortality that tracks five stages of breast cancer progression and incorporates the effects of age on breast cancer incidence and all-cause mortality. The model accurately reproduces the reported outcomes of the CNBSS. By varying parameters, we predict that the benefits of mammography depend on the effectiveness of cancer treatment and tumor aggressiveness. In particular, patients with the most rapidly growing or potentially largest tumors have the highest benefit and least harm from the screening, with only a relatively small effect of age. However, the model predicts that confining mammography to populations with a high risk of acquiring breast cancer increases the screening benefit only slightly compared with the full population.

Consequences of a match made in hell: the harm caused by menthol smoking to the African American population over 1980-2018.

BACKGROUND: For many years, national surveys have shown a consistently disproportionately high prevalence of menthol smokers among African Americans compared with the general population. However, to our knowledge, no prior study has quantified the harm that menthol smoking has caused on that population. In this work, we estimate the public health harm that menthol cigarettes have caused to the African American community over the last four decades. METHODS: Using National Health Interview Survey data, we employed a well-established simulation model to reproduce the observed smoking trajectory over 1980-2018 in the African American population. Then, we repeat the experiment, removing the effects of menthol on the smoking initiation and cessation rates over that period, obtaining a new hypothetical smoking trajectory. Finally, we compared both scenarios to calculate the public health harm attributable to menthol cigarettes over 1980-2018. RESULTS: Our results show that menthol cigarettes were responsible for 1.5 million new smokers, 157 000 smoking-related premature deaths and 1.5 million life-years lost among African Americans over 1980-2018. While African Americans constitute 12% of the total US population, these figures represent, respectively, a staggering 15%, 41% and 50% of the total menthol-related harm. DISCUSSION: Our results show that menthol cigarettes disproportionally harmed African Americans significantly over the last 38 years and are responsible for exacerbating health disparities among that population. Removing menthol cigarettes from the market would benefit the overall US population but, particularly, the African American community.

Short communication: Implementation of a breeding value for heat tolerance in Australian dairy cattle.

Excessive ambient temperature and humidity can impair milk production and fertility of dairy cows. Selection for heat-tolerant animals is one possible option to mitigate the effects of heat stress. To enable selection for this trait, we describe the development of a heat tolerance breeding value for Australian dairy cattle. We estimated the direct genomic values of decline in milk, fat, and protein yield per unit increase of temperature-humidity index (THI) using 46,726 single nucleotide polymorphisms and a reference population of 2,236 sires and 11,853 cows for Holsteins and 506 sires and 4,268 cows for Jerseys. This new direct genomic value is the Australian genomic breeding value for heat tolerance (HT ABVg). The components of the HT ABVg are the decline in milk, fat, and protein per unit increase in THI when THI increases above the threshold of 60. These components are weighted by their respective economic values, assumed to be equivalent to the weights applied to milk, fat, and protein yield in the Australian selection indices. Within each breed, the HT ABVg is then standardized to have a mean of 100 and standard deviation (SD) of 5, which is consistent with the presentation of breeding values for many other traits in Australia. The HT ABVg ranged from -4 to +3 SD in Holsteins and -3 to +4 SD in Jerseys. The mean reliabilities of HT ABVg among validation sires, calculated from the prediction error variance and additive genetic variance, were 38% in both breeds. The range in ABVg and their reliability suggests that HT can be improved using genomic selection. There has been a deterioration in the genetic trend of HT, and to moderate the decline it is suggested that the HT ABVg should be included in a multitrait economic index with other traits that contribute to farm profit.

Genomic selection for tolerance to heat stress in Australian dairy cattle.

Temperature and humidity levels above a certain threshold decrease milk production in dairy cattle, and genetic variation is associated with the amount of lost production. To enable selection for improved heat tolerance, the aim of this study was to develop genomic estimated breeding values (GEBV) for heat tolerance in dairy cattle. Heat tolerance was defined as the rate of decline in production under heat stress. We combined herd test-day recording data from 366,835 Holstein and 76,852 Jersey cows with daily temperature and humidity measurements from weather stations closest to the tested herds for test days between 2003 and 2013. We used daily mean values of temperature-humidity index averaged for the day of test and the 4 previous days as the measure of heat stress. Tolerance to heat stress was estimated for each cow using a random regression model with a common threshold of temperature-humidity index=60 for all cows. The slope solutions for cows from this model were used to define the daughter trait deviations of their sires. Genomic best linear unbiased prediction was used to calculate GEBV for heat tolerance for milk, fat, and protein yield. Two reference populations were used, the first consisted of genotyped sires only (2,300 Holstein and 575 Jersey sires), and the other included genotyped sires and cows (2,189 Holstein and 1,188 Jersey cows). The remainder of the genotyped sires were used as a validation set. All animals had genotypes for 632,003 single nucleotide polymorphisms. When using only genotyped sires in the reference set and only the first parity data, the accuracy of GEBV for heat tolerance in relation to changes in milk, fat, and protein yield were 0.48, 0.50, and 0.49 in the Holstein validation sires and 0.44, 0.61, and 0.53 in the Jersey validation sires, respectively. Some slight improvement in the accuracy of prediction was achieved when cows were included in the reference population for Holsteins. No clear improvements in the accuracy of genomic prediction were observed when data from the second and third parities were included. Correlations of GEBV for heat tolerance with Australian Breeding Values for other traits suggested heat tolerance had a favorable genetic correlation with fertility (0.29-0.39 in Holsteins and 0.15-0.27 in Jerseys), but unfavorable correlations for some production traits. Options to improve heat tolerance with genomic selection in Australian dairy cattle are discussed.

Extensive variation between tissues in allele specific expression in an outbred mammal.

BACKGROUND: Allele specific gene expression (ASE), with the paternal allele more expressed than the maternal allele or vice versa, appears to be a common phenomenon in humans and mice. In other species the extent of ASE is unknown, and even in humans and mice there are several outstanding questions. These include; to what extent is ASE tissue specific? how often does the direction of allele expression imbalance reverse between tissues? how often is only one of the two alleles expressed? is there a genome wide bias towards expression of the paternal or maternal allele; and finally do genes that are nearby on a chromosome share the same direction of ASE? Here we use gene expression data (RNASeq) from 18 tissues from a single cow to investigate each of these questions in turn, and then validate some of these findings in two tissues from 20 cows. RESULTS: Between 40 and 100 million sequence reads were generated per tissue across three replicate samples for each of the eighteen tissues from the single cow (the discovery dataset). A bovine gene expression atlas was created (the first from RNASeq data), and differentially expressed genes in each tissue were identified. To analyse ASE, we had access to unambiguously phased genotypes for all heterozygous variants in the cow's whole genome sequence, where these variants were homozygous in the whole genome sequence of her sire, and as a result we were able to map reads to parental genomes, to determine SNP and genes showing ASE in each tissue. In total 25,251 heterozygous SNP within 7985 genes were tested for ASE in at least one tissue. ASE was pervasive, 89 % of genes tested had significant ASE in at least one tissue. This large proportion of genes displaying ASE was confirmed in the two tissues in a validation dataset. For individual tissues the proportion of genes showing significant ASE varied from as low as 8-16 % of those tested in thymus to as high as 71-82 % of those tested in lung. There were a number of cases where the direction of allele expression imbalance reversed between tissues. For example the gene SPTY2D1 showed almost complete paternal allele expression in kidney and thymus, and almost complete maternal allele expression in the brain caudal lobe and brain cerebellum. Mono allelic expression (MAE) was common, with 1349 of 4856 genes (28 %) tested with more than one heterozygous SNP showing MAE. Across all tissues, 54.17 % of all genes with ASE favoured the paternal allele. Genes that are closely linked on the chromosome were more likely to show higher expression of the same allele (paternal or maternal) than expected by chance. We identified several long runs of neighbouring genes that showed either paternal or maternal ASE, one example was five adjacent genes (GIMAP8, GIMAP7 copy1, GIMAP4, GIMAP7 copy 2 and GIMAP5) that showed almost exclusive paternal expression in brain caudal lobe. CONCLUSIONS: Investigating the extent of ASE across 18 bovine tissues in one cow and two tissues in 20 cows demonstrated 1) ASE is pervasive in cattle, 2) the ASE is often MAE but ranges from MAE to slight overexpression of the major allele, 3) the ASE is most often tissue specific and that more than half the time displays divergent allele specific expression patterns across tissues, 4) across all genes there is a slight bias towards expression of the paternal allele and 5) genes expressing the same parental allele are clustered together more than expected by chance, and there are several runs of large numbers of genes expressing the same parental allele.

Antimicrobial activity of doubly-stapled alanine/lysine-based peptides.

In this study, we examined the potential of Verdine's double-stapling system for the de novo design of amphipathic helical antimicrobial peptides. We designed, synthesized, and tested a prototypical doubly-stapled helix of an alanine/lysine based model sequence, which showed reasonable antimicrobial activities and highly increased proteolytic stability. We then show that its hemolytic activity as well as antimicrobial activities can be further manipulated through the systematic modifications. Overall, the preliminary results obtained from this study imply that the doubly-stapled helices of short peptides can serve as a highly promising scaffold for the rational design of potent, selective, and metabolically stable antimicrobial peptides that can combat against the growing problems of antibiotic-resistance.

Photoelectrochemical hydrogen production on InP nanowire arrays with molybdenum sulfide electrocatalysts.

Semiconductor nanowire arrays are expected to be advantageous for photoelectrochemical energy conversion due to their reduced materials consumption. In addition, with the nanowire geometry the length scales for light absorption and carrier separation are decoupled, which should suppress bulk recombination. Here, we use vertically aligned p-type InP nanowire arrays, coated with noble-metal-free MoS3 nanoparticles, as the cathode for photoelectrochemical hydrogen production from water. We demonstrate a photocathode efficiency of 6.4% under Air Mass 1.5G illumination with only 3% of the surface area covered by nanowires.

Efficiency enhancement of InP nanowire solar cells by surface cleaning.

We demonstrate an efficiency enhancement of an InP nanowire (NW) axial p-n junction solar cell by cleaning the NW surface. NW arrays were grown with in situ HCl etching on an InP substrate patterned by nanoimprint lithography, and the NWs surfaces were cleaned after growth by piranha etching. We find that the postgrowth piranha etching is critical for obtaining a good solar cell performance. With this procedure, a high diode rectification factor of 10(7) is obtained at ±1 V. The resulting NW solar cell exhibits an open-circuit voltage (Voc) of 0.73 V, a short-circuit current density (Jsc) of 21 mA/cm(2), and a fill factor (FF) of 0.73 at 1 sun. This yields a power conversion efficiency of up to 11.1% at 1 sun and 10.3% at 12 suns.

New Estimates of Smoking-Attributable Mortality in the U.S. From 2020 Through 2035.

INTRODUCTION: The often-cited Centers for Disease Control and Prevention (CDC) estimate of 480,000 annual U.S. smoking-attributable deaths (SADs), including 439,000 first-hand smoke deaths, derives from 2005 to 2009 data. Since then, adult smoking prevalence has decreased by 40%, while the population has grown and the smoking population aged. An updated estimate is presented to determine whether the CDC figure remains accurate or has changed substantially. In addition, the likely annual smoking-related mortality toll is projected through 2035. METHODS: A well-established model of smoking prevalence and health effects is employed to estimate annual SADs among individuals exposed to first-hand smoke in the U.S. for two distinct periods: 2005-2009 and 2020-2035. The estimate for 2005-2009 serves as a benchmark to evaluate the reliability of the model's estimate in comparison to CDC's. The projections for 2020-2035 provide up-to-date figures for SADs, predicting how annual SADs are likely to change in the coming years. Data were collected between 2005 and 2020. The analysis was conducted in 2023. RESULTS: This study's estimate of 420,000 first-hand smoke deaths over 2005-2009 is 95.7% of CDC's estimate during the same period. The model projections indicate that SADs among individuals who currently smoke or formerly smoked have increased modestly since 2005-2009. Beginning in 2020, annual SADs will remain relatively stable at approximately 450,000 before starting to decline around 2030. CONCLUSIONS: These findings suggest that the CDC estimate of the annual mortality burden of smoking remains valid. Despite U.S. population growth and the aging of the smoking population, substantial reductions in smoking will finally produce a steady, if gradual, decline in SADs beginning around 2030.