Isolation of the MurineNbr1Gene Adjacent to the MurineBrca1Gene

The humanNBR1cDNA has previously been identified using polyclonal sera to CA125, an ovarian tumor antigen used in monitoring ovarian cancer. The gene was mapped to theBRCA1region on chromosome 17q21 and subsequently found to lie in close proximity to the recently identifiedBRCA1gene. The NBR1 protein has a B-box motif but the function of the protein is as yet unknown. To investigate the function and importance of this gene, we have studied the conservation of this gene in other species and in particular in the mouse. We have isolated murineNbr1cDNA and genomic clones. Translation of the cDNA sequence indicates that the protein is highly conserved, being 89% similar and 84% identical to the human. Analysis of the murineNbr1genomic clones indicates that it maps less than 1 kb from theBrca1gene and that, unlike that in human, this region is not duplicated.     

Measuring readmission rates.

OBJECTIVE--To assess the feasibility of extracting data on readmissions and readmission rates from Körner data for use as health service indicators. DESIGN--Retrospective analysis of inpatient Körner data for January 1988 to April 1989. SETTING--Three districts in North East Thames region. MAIN OUTCOME MEASURES--Number of readmissions after index discharge for all acute specialties combined and by specialty (general medicine, general surgery, gynaecology, trauma and orthopaedics, and geriatrics); readmission rates at 28 days after index discharge; and rates standardised for age group and sex by specialty and by consultant. RESULTS--All specialties showed an early peak in number of admissions, which levelled off by 28 days. Readmission rates at 28 days were appreciably lower in surgical specialties than in medical specialties (for example, general surgery 4.1% v geriatric medicine 15.1%). They were related to age and sex of the patient. Rates standardised for these variables did not significantly differ by district. Likewise, significant differences in standardised rates were not obtained for consultants within a specialty in one district. CONCLUSIONS--Readmission rates may be measured with Körner data. The pattern of readmissions with time means that readmission rates should be measured at not more than 28 days after the index discharge; the rates require standardisation for age and sex. Annual comparisons of standardised rates may be made among districts for combinations of specialties; those among individual consultants or specialties are unlikely to be statistically valid.     

Phosphorylation influences the binding of the yeast RAP1 protein to the upstream activating sequence of the PGK gene.

Yeast repressor activator protein 1 (RAP1) binds in vitro to specific DNA sequences that are found in diverse genetic elements. Expression of the yeast phosphoglycerate kinase gene (PGK) requires the binding of RAP1 to the activator core sequence within the upstream activating sequence (UAS) of PGK. A DNA fragment Z+ which contains the activator core sequence of the PGK(UAS) has been shown to bind RAP1. Here we report that phosphatase treatment of RAP1 affected its binding to the PGK(UAS) but that this depended on the nature of the sequence flanking the 5' end of the activator core sequence. When the sequence flanking the 5' end of the activator core sequence was different from the PGK RAP1-binding site, phosphatase treatment of RAP1 decreased its binding to the DNA. When the 5' end of the binding site was a match to the PGK RAP1-binding site dephosphorylation of RAP1 increased RAP1 binding to the DNA. These observations were reproduced when the minimal functional DNA-binding domain of the RAP1 protein was used, implicating a phosphorylation-dependent binding of RAP1. This is the first evidence for phosphorylation-dependent binding of RAP1.     

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure – replication timing, lamina association and Hi-C inter-locus interactions — and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution.     

Climate change affects the early-life history of a freshwater turtle in a severely drying region

Freshwater turtles are one of the most threatened vertebrate groups. Climate change is a major threat to these species, with impacts affecting all life-history stages. There is currently a limited understanding of how changes in climate may alter the environmental triggers for hatching and emergence from the nests of freshwater turtle hatchlings. This precludes making predictions about how climate change may impact freshwater turtle recruitment success. The southwestern snake-necked turtle (Chelodina oblonga) is endemic to south-western Australia, a global biodiversity hotspot that has undergone severe climatic drying. Recruitment failure is thought to be occurring in many populations of the species. However, there is little understanding as to how environmental change may be influencing recruitment. This study aimed to: (1) determine the incubation duration and hatching and hatchling emergence success of C. oblonga, (2) determine if the species exhibits hatching or emergence synchrony and/or delayed emergence and (3) quantify the effects of temperature and rainfall on hatchling emergence. Using this information, the study assesses how climatic drying and warming may be impacting C. oblonga's early life-history. Between 2018 and 2020 nest sites were monitored around a large urban wetland with weekly assessments of egg and hatchling status. Incubation duration and hatching and hatchling emergence success were calculated, and generalized linear models were built to determine how temperature and/or rainfall predicted emergence. Hatchlings either emerged shortly after hatching or overwintered in the nest, and both hatching and emergence were asynchronous. Both emergence periods were positively associated with temperature and rainfall. This study reveals that incubation duration, hatching success, hatchling emergence and survival are all likely to be impacted by recent and projected climate change, and especially drying. Warming and drying are predicted for many temperate regions globally, and it is therefore important that their impacts on the early life history of freshwater turtles be better understood.     

Effects of resource availability and propagule supply on native species recruitment in sagebrush ecosystems invaded by Bromus tectorum

Resource availability and propagule supply are major factors influencing establishment and persistence of both native and invasive species. Increased soil nitrogen (N) availability and high propagule inputs contribute to the ability of annual invasive grasses to dominate disturbed ecosystems. Nitrogen reduction through carbon (C) additions can potentially immobilize soil N and reduce the competitiveness of annual invasive grasses. Native perennial species are more tolerant of resource limiting conditions and may benefit if N reduction decreases the competitive advantage of annual invaders and if sufficient propagules are available for their establishment. Bromus tectorum, an exotic annual grass in the sagebrush steppe of western North America, is rapidly displacing native plant species and causing widespread changes in ecosystem processes. We tested whether nitrogen reduction would negatively affect B. tectorum while creating an opportunity for establishment of native perennial species. A C source, sucrose, was added to the soil, and then plots were seeded with different densities of both B. tectorum (0, 150, 300, 600, and 1,200 viable seeds m⁻²) and native species (0, 150, 300, and 600 viable seeds m⁻²). Adding sucrose had short-term (1 year) negative effects on available nitrogen and B. tectorum density, biomass and seed numbers, but did not increase establishment of native species. Increasing propagule availability increased both B. tectorum and native species establishment. Effects of B. tectorum on native species were density dependent and native establishment increased as B. tectorum propagule availability decreased. Survival of native seedlings was low indicating that recruitment is governed by the seedling stage.     

Aging and primate male sexual behavior

Old male rhesus macaques display less sexual behavior than young and middle-aged males. The decrease in sexual activity occurs without a statistically significant decline in gonadal hormones or change in diurnal patterns of serum T, DHT, or LH. Levels of sexual activity are not increased by administering T to old intact males. However, the hormone is effective in increasing sexual behavior in old long-term-castrated males. Performance can be increased to levels observed in equally old untreated intact males. Readily detectable physical disabilities of old age have been observed to impair sexual performance, but the observed general decline in sexual activity cannot be accounted for by known physical disabilities. Novelty, as represented by a change in female partner or by a change in environment, has not increased sexual performance in old rhesus males. Only when old males were paired with empirically selected preferred females is their sexual behavior increased to levels displayed by young males. Drugs reported to increase levels of sexual behavior in rats have thus far been less effective in old rhesus males than powdered rhinoceros horn has been in man. The probable absence of a placebo effect in rhesus males should increase their usefulness as an animal model for the study of sexual behavior in aging men.