Transition from Environmental to Partial Genetic Sex Determination in Daphnia through the Evolution of a Female-Determining Incipient W Chromosome.

Sex chromosomes can evolve during the evolution of genetic sex determination (GSD) from environmental sex determination (ESD). Despite theoretical attention, early mechanisms involved in the transition from ESD to GSD have yet to be studied in nature. No mixed ESD-GSD animal species have been reported, except for some species of Daphnia, small freshwater crustaceans in which sex is usually determined solely by the environment, but in which a dominant female sex-determining locus is present in some populations. This locus follows Mendelian single-locus inheritance, but has otherwise not been characterized genetically. We now show that the sex-determining genomic region maps to the same low-recombining peri-centromeric region of linkage group 3 (LG3) in three highly divergent populations of D. magna, and spans 3.6 Mb. Despite low levels of recombination, the associated region contains signs of historical recombination, suggesting a role for selection acting on several genes thereby maintaining linkage disequilibrium among the 36 associated SNPs. The region carries numerous genes involved in sex differentiation in other taxa, including transformer2 and sox9. Taken together, the region determining the genetic females shows characteristics of a sex-related supergene, suggesting that LG3 is potentially an incipient W chromosome despite the lack of significant additional restriction of recombination between Z and W. The occurrence of the female-determining locus in a pre-existing low recombining region illustrates one possible form of recombination suppression in sex chromosomes. D. magna is a promising model for studying the evolutionary transitions from ESD to GSD and early sex chromosome evolution.

Successful Treatment of a Pacemaker Infection with Intraperitoneal Daptomycin.

We investigated the pharmacokinetics of intraperitoneal administration of daptomcyin in a peritoneal dialysis (PD) patient treated for a pacemaker infection with Staphylococcus epidermidis. After initial start of intravenous daptomycin at 9 mg/kg body weight every 48 hours, the therapy was switched to intraperitoneal administration of 5.3 mg/kg body weight in 1 L icodextrin 7.5% with a dwell time of 12 hours overnight every 48 hours. Therapeutic drug monitoring (TDM) was performed at 4 hours and 24 hours after dose administration. Due to high peak concentration above target peak concentration, the dose was reduced to a final maintenance dose of 3.2 mg/kg body weight. Data from this single case suggest that serum drug concentration above the minimal inhibitory concentration (MIC) can be easily achieved with intraperitoneal administration of daptomycin every 48 hours even with a lower dose, as recommended for the intravenous administration, but measurement of serum concentration and dose adjustments are mandatory in such cases.

Uncovering Cryptic Asexuality in Daphnia magna by RAD Sequencing.

The breeding systems of many organisms are cryptic and difficult to investigate with observational data, yet they have profound effects on a species' ecology, evolution, and genome organization. Genomic approaches offer a novel, indirect way to investigate breeding systems, specifically by studying the transmission of genetic information from parents to offspring. Here we exemplify this method through an assessment of self-fertilization vs. automictic parthenogenesis in Daphnia magna. Self-fertilization reduces heterozygosity by 50% compared to the parents, but under automixis, whereby two haploid products from a single meiosis fuse, the expected heterozygosity reduction depends on whether the two meiotic products are separated during meiosis I or II (i.e., central vs. terminal fusion). Reviewing the existing literature and incorporating recombination interference, we derive an interchromosomal and an intrachromosomal prediction of how to distinguish various forms of automixis from self-fertilization using offspring heterozygosity data. We then test these predictions using RAD-sequencing data on presumed automictic diapause offspring of so-called nonmale producing strains and compare them with "self-fertilized" offspring produced by within-clone mating. The results unequivocally show that these offspring were produced by automixis, mostly, but not exclusively, through terminal fusion. However, the results also show that this conclusion was only possible owing to genome-wide heterozygosity data, with phenotypic data as well as data from microsatellite markers yielding inconclusive or even misleading results. Our study thus demonstrates how to use the power of genomic approaches for elucidating breeding systems, and it provides the first demonstration of automictic parthenogenesis in Daphnia.

Increased mortality after a first myocardial infarction in human immunodeficiency virus-infected patients; a nested cohort study.

AIMS: HIV infection may be associated with an increased recurrence rate of myocardial infarction. Our aim was to determine whether HIV infection is a risk factor for worse outcomes in patients with coronaray artery disease. METHODS: We compared data aggregated from two ongoing cohorts: (i) the Acute Myocardial Infarction in Switzerland (AMIS) registry, which includes patients with acute myocardial infarction (AMI), and (ii) the Swiss HIV Cohort Study (SHCS), a prospective registry of HIV-positive (HIV+) patients. We included all patients who survived an incident AMI occurring on or after 1st January 2005. Our primary outcome measure was all-cause mortality at one year; secondary outcomes included AMI recurrence and cardiovascular-related hospitalisations. Comparisons used Cox and logistic regression analyses, respectively. RESULTS: There were 133 HIV+, (SHCS) and 5,328 HIV-negative [HIV-] (AMIS) individuals with incident AMI. In the SHCS and AMIS registries, patients were predominantly male (72% and 85% male, respectively), with a median age of 51 years (interquartile range [IQR] 46-57) and 64 years (IQR 55-74), respectively. Nearly all (90%) of HIV+ individuals were on successful antiretroviral therapy. During the first year of follow-up, 5 (3.6%) HIV+ and 135 (2.5%) HIV- individuals died. At one year, HIV+ status after adjustment for age, sex, calendar year of AMI, smoking status, hypertension and diabetes was associated with a higher risk of death (HR 4.42, 95% CI 1.73-11.27). There were no significant differences in recurrent AMIs (4 [3.0%] HIV+ and 146 [3.0%] HIV- individuals, OR 1.16, 95% CI 0.41-3.27) or in hospitalization rates (OR 0.68 [95% CI 0.42-1.11]). CONCLUSIONS: HIV infection was associated with a significantly increased risk of all-cause mortality one year after incident AMI.

Hemolytic uremic syndrome in a 65-Year-old male linked to a very unusual type of stx2e- and eae-harboring O51:H49 shiga toxin-producing Escherichia coli.

We report on a 65-year-old male patient with a Shiga toxin-producing Escherichia coli O51:H49 gastrointestinal infection and sepsis associated with hemolytic uremic syndrome (HUS) with a fatal outcome. The strains isolated harbored stx2e and eae, a very unusual and new virulence profile for an HUS-associated enterohemorrhagic E. coli.

A short tool to screen HIV-infected patients for mild neurocognitive disorders - a pilot study.

BACKGROUND: We aimed to evaluate the accuracy and acceptability of a short screening test battery for mild neurocognitive deficits. METHODS: HIV-infected individuals with a suppressed viral load were examined at the University Hospital Basel with a screening test consisting of a questionnaire and selected cognitive tests, administered by trained nurses, followed by an in-depth neuropsychological examination. Test acceptance was evaluated with a questionnaire. RESULTS: 30 patients were included in this study (median age of 52.5 years (interquartile range (IQR) 47-64), prior AIDS-defining condition in 37%, median CD4 cell count 658 (IQR 497-814) cells/µl). Overall, 25 (83%) patients were diagnosed with HIV-associated neurocognitive disorders (HAND) on in-depth neuropsychological assessment (16 patients had asymptomatic neurocognitive impairment (ANI), 8 a mild neurocognitive disorder (MND) and 1 patient HIV-associated dementia (HAD). Among 25 patients with HAND, only 9 patients (36%) were complaining of memory loss. The screening battery revealed neurocognitive deficits in 17 (57%) patients (sensitivity 64%, specificity 80%, positive predictive value 94% and negative predictive value 31%). Most patients (83%) estimated the screening test as valuable and not worrisome. CONCLUSIONS: A questionnaire combined with selected neuropsychological tests is a short, easy-to-perform very well accepted screening tool for mild neurocognitive disorders in asymptomatic HIV-infected individuals.

Increased seed survival and seedling emergence in a polyploid plant invader.

PREMISE OF THE STUDY: Because seeds have essential functions in the life cycle of plants, even subtle changes in their characteristics may have important demographic consequences. In this study, we examined whether potential changes in seed characteristics as a result of polyploidy or postintroduction evolution may have contributed to the invasion of Centaurea stoebe (Asteraceae). This plant occurs as diploid and tetraploid cytotypes in its native range in Europe, whereas only tetraploids have been found and become invasive in North America. Specific comparisons among these three "geo-cytotypes" allow us to explore hypotheses of preadaptation resulting from polyploidy (European diploids vs. European tetraploids) and postintroduction evolution (European tetraploids vs. North American tetraploids). METHODS: Using seeds collected from plants of each geo-cytotype grown in a common maternal environment, we compared seed mass, morphology (achene and pappus size), dispersal potential (falling velocity, seed roughness), survival, germination, and seedling emergence in a combination of laboratory, greenhouse and field experiments. KEY RESULTS: We found increased seed mass in North American tetraploids compared with European tetraploids. Seed morphology and dispersal potential were largely similar in all geo-cytotypes. Seed survival under field conditions was higher in native and invasive tetraploids compared with diploids. Germination in the laboratory was similar among all geo-cytotypes, but seedling emergence under field conditions was higher in invasive tetraploids than in the other geo-cytotypes. CONCLUSIONS: Our findings suggest that a combination of preadaptation due to polyploidy (increased seed survival) and further postintroduction evolution in North American tetraploids (increased seed mass and seedling emergence) may have contributed to their invasion.