Age-dependent female responses to a male ejaculate signal alter demographic opportunities for selection

A central tenet of evolutionary explanations for ageing is that the strength of selection wanes with age. However, data on age-specific expression and benefits of sexually selected traits are lacking—particularly for traits subject to sexual conflict. We addressed this by using as a model the responses of Drosophila melanogaster females of different ages to receipt of sex peptide (SP), a seminal fluid protein transferred with sperm during mating. SP can mediate sexual conflict, benefitting males while causing fitness costs in females. Virgin and mated females of all ages showed significantly reduced receptivity in response to SP. However, only young virgin females also showed increased egg laying; hence, there was a narrow demographic window of maximal responses to SP. Males gained significant ‘per mating’ fitness benefits only when mating with young females. The pattern completely reversed in matings with older females, where SP transfer was costly. The overall benefits of SP transfer (hence opportunity for selection) therefore reversed with female age. The data reveal a new example of demographic variation in the strength of selection, with convergence and conflicts of interest between males and ageing females occurring over different facets of responses to a sexually antagonistic trait

MicroRNAs influence reproductive responses by females to male sex peptide in Drosophila melanogaster

Across taxa, female behavior and physiology changes significantly following the receipt of ejaculate molecules during mating. For example, receipt of sex peptide (SP) in female Drosophila melanogaster significantly alters female receptivity, egg production, lifespan, hormone levels, immunity, sleep and feeding patterns. These changes are underpinned by distinct tissue- and time-specific changes in diverse sets of mRNAs. However, little is yet known about the regulation of these gene expression changes, and hence the potential role of microRNAs (miRNAs), in female post-mating responses. A preliminary screen of genomic responses in females to receipt of SP suggested that there were changes in the expression of several miRNAs. Here we tested directly whether females lacking four of the candidate miRNAs highlighted (miR-279, miR-317, miR-278 and miR-184) showed altered fecundity, receptivity and lifespan responses to receipt of SP, when mated once or continually to SP null or control males. The results showed that miRNA-lacking females mated to SP null males exhibited altered receptivity, but not reproductive output, in comparison to controls. However, these effects interacted significantly with the genetic background of the miRNA-lacking females. No significant survival effects were observed in miRNA-lacking females housed continually with SP null or control males. However, continual exposure to control males that transferred SP resulted in significantly higher variation in miRNA-lacking female lifespan than did continual exposure to SP null males. The results provide the first insight into the effects and importance of miRNAs in regulating post-mating responses in females

Paget's disease of bone-associated osteosarcoma: molecular basis, signs and symptoms, treatment and research

Darrell Green is a Big C-funded molecular biologist at the University of East Anglia, performing research towards a PhD. He works with Professor Tamas Dalmay, Head of Biological Sciences and Chair of RNA Biology at the University of East Anglia and Professor Bill Fraser who is a Trustee of The Paget’s Association, Director of The Norfolk Bone and Joint Centre, the Bioanalytical Facility and Head of Department of Medicine at Norwich Medical School and Consultant Metabolic Physician at the Norfolk and Norwich University Hospital. Here they discuss the molecular basis of Paget’s associated osteosarcoma, identifi cation of patients at risk, signs and symptoms, treatment and current research

The role of small RNAs in Paget's associated osteosarcoma

Small RNAs (sRNAs) are a class of non-coding RNA molecules that arekey regulators of gene expression. SRNAs are also specific biomarkersdue to their dysregulation in disease. Next generation sequencing is thegold standard for sRNA discovery, profiling and expression analysis.Bias has been found in different platforms of sequencing due to RNAligase preference for sequence complementarity between sRNA andadapters. We developed high definition (HD) adapters to overcome thebias. We applied the use of HD adapters and sequencing to our studiesof bone cancer. One of these studies investigated sRNA expression inPaget’s associated osteosarcoma, a rare complication of Paget’s diseaseof bone that carries a poor prognosis. We found that expression of amicroRNA, miR-16, was highly expressed in Paget’s associated osteo-sarcoma tissue when compared to controls and Paget’s disease of bone.Bioinformatics analysis revealed miR-16 directly targets the sequesto-some 1 (SQSTM1) messenger RNA. SQSTM1 protein has long been as-sociated with Paget’s disease of bone development. SQSTM1 was hy-pothesised to be involved with transformation to osteosarcoma asSQSTM1 variants are positively associated with disease severity. Wespeculated that negative regulation of SQSTM1 by miR-16 incapacitatesSQSTM1’s role in the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-like 2 (NFE2L2) pathway, a major cellulardefence mechanism against oxidative stress and cancer development.Molecular testing may help provide a robust diagnosis and is particu-larly useful in rare cancers such as Paget’s associated osteosarcomawhere transformation is often missed until late stage. We are now in-vestigating this biological data further, using single cell simultaneousgenome and transcriptome sequencing

The role of small RNAs in Paget's associated osteosarcoma

Small RNAs (sRNAs) are a class of non-coding RNA molecules that arekey regulators of gene expression. SRNAs are also specific biomarkersdue to their dysregulation in disease. Next generation sequencing is thegold standard for sRNA discovery, profiling and expression analysis.Bias has been found in different platforms of sequencing due to RNAligase preference for sequence complementarity between sRNA andadapters. We developed high definition (HD) adapters to overcome thebias. We applied the use of HD adapters and sequencing to our studiesof bone cancer. One of these studies investigated sRNA expression inPaget’s associated osteosarcoma, a rare complication of Paget’s diseaseof bone that carries a poor prognosis. We found that expression of amicroRNA, miR-16, was highly expressed in Paget’s associated osteo-sarcoma tissue when compared to controls and Paget’s disease of bone.Bioinformatics analysis revealed miR-16 directly targets the sequesto-some 1 (SQSTM1) messenger RNA. SQSTM1 protein has long been as-sociated with Paget’s disease of bone development. SQSTM1 was hy-pothesised to be involved with transformation to osteosarcoma asSQSTM1 variants are positively associated with disease severity. Wespeculated that negative regulation of SQSTM1 by miR-16 incapacitatesSQSTM1’s role in the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-like 2 (NFE2L2) pathway, a major cellulardefence mechanism against oxidative stress and cancer development.Molecular testing may help provide a robust diagnosis and is particu-larly useful in rare cancers such as Paget’s associated osteosarcomawhere transformation is often missed until late stage. We are now in-vestigating this biological data further, using single cell simultaneousgenome and transcriptome sequencing

Completion Characteristics of Non-Hispanic Blacks with Tuberculosis and HIV

Tuberculosis (TB) and human immunodeficiency virus (HIV) are difficult conditions to manage, in tandem they pose even more challenges to public health programs in identifying coinfection to ensure that all TB cases are treated to completion of therapy (COT). The purpose of this study was to test variables that predicted COT among the HIV/TB coinfected population of non-Hispanic, U.S.-born Blacks alive at the time of diagnosis. Social determinants of health were the theoretical foundation used to guide the study based on data from the Report of Verified Cases of TB (RVCT) between 2009 and 2014. Relationships were tested between ethnic/racial group membership and the likelihood of COT, and whether any association to COT was moderated by COT eligibility; a Centers for Disease Control and Prevention calculated algorithm considering disease severity, site, age, and disease complexity. The research design was a longitudinal quantitative approach using binary logistic regression to identify correlated variables associated with COT in the final model. The results showed no statistically significant differences among racial/ethnic groups, age, and gender for COT. COT was moderated by COT eligibility; odds ratio (5.4 - 11.6) times more likely to complete therapy. This study supports positive social change for programs by providing data driven outcomes to providers that support outreach, patient education, and disease prevention. In addition, this research describes an evaluation metric based on performance to set a foundation for collaboration among partners who manage other comorbidities in the United States

Air quality and bird health status in three types of commercial egg layer houses

In this field observational study, 3 types of laying-hen houses, namely, high-rise (HR), manure-belt (MB), and cage-free floor-raised (FR), were monitored for air temperature, RH, CO2 , and atmospheric NH3 under winter and summer conditions in Iowa. Under winter conditions, the HR and MB houses had more comfortable temperature and NH3 levels (mean 24.6 and 20.6°C, and maximum 9 to 24 ppm of NH3 , respectively) than the FR houses (mean 15.5°C and maximum 85 to 89 ppm of NH3 , respectively), and house temperature varied more with outside conditions. Under summer conditions, house temperature showed the least increase above ambient in the FR houses (mean 0.3°C vs. 4.7 and 1.2°C for the MB and HR houses, respectively), and NH3 levels were similar for all housing types (mean 3 to 9 ppm). Examination of the hen health status revealed differences in pathogen prevalence between housing systems for winter and summer, but not conclusively in favor of one system over another. Results of this study indicate that the benefits of each system were season dependent. Further monitoring of the environment, bird health, and production performance over an extended period (e.g., 1 yr) to quantify the benefits and limitations of each system is warranted. Information of this nature will aid in optimizing hen housing systems for enhanced bird welfare and sustained production efficiency for the egg industr

Air Quality and Hen Health Status in Three Types of Commercial Laying Hen Houses

Environmental conditions and bird health are important elements in assessment of animal welfare for laying hen housing systems, but limited information is available comparing different types of systems. Three types of laying hen houses - caged high-rise, caged manure-belt, and cage-free floor-raised - were monitored for temperature, relative humidity, carbon dioxide, and atmospheric ammonia during winter and summer conditions in Iowa. During winter conditions, temperature and ammonia concentrations were maintained at a more comfortable level for the caged facilities. During summer conditions, temperature showed the least rise above ambient for the cage-free facilities, and ammonia was maintained at similar levels for all housing types. Assessment of hen health status revealed differences in pathogen frequency between housing systems for winter and summer, but not conclusively in favor of one system over another. The results of this observational study indicate that each system may offer benefits during specific weather conditions. Further monitoring to quantify the benefits of each system should be completed

Methods of treatment and diagnosis of tumours

The invention relates to a method of treating a cartilage matrix-forming bone tumour and/or a metastatic cancer originating from a cartilage matrix-forming bone tumour, for example chondrosarcoma, in which one or more of an inhibitor of RUNX2 activity, an inhibitor of RUNX2 expression, an inhibitor of YBX1 activity and an inhibitor of YBX1 expression, is administered to a subject in need thereof. The invention also relates to an in vitro method for detecting the presence of a cartilage matrix-forming bone tumour in a subject or the risk of a subject developing a cartilage matrix-forming bone tumour, for example chondrosarcoma, in which the following steps are performed: (i) measuring the expression level of at least one of RUNX2 and YBX1 in a biological sample obtained from a subject , and (ii) com paring the expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject with the respective expression level of RUNX2 and/or YBX1 in normal cartilage or other biological material. A higher expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject compared to the respective expression level of RUNX2 and/or YBX1 in the normal cartilage or other biological material indicates the presence of or an increased risk of developing a cartilage matrix-forming bone tumour