Review of Native Fragile Sites in Saccharomyces Cerevisiae: A Comparison to Human Fragile Sites

Saccharomyces cerevisiae (S. cerevisiae) was the first eukaryote to have its full genome sequenced, which makes it one of the longest studied genomes. The scientific community has established that S. cerevisiae is a useful model in the study of human diseases due to the homology that exists in numerous human and yeast genes. Yeast artificial chromosomes (YACs) have been developed that contain inserts of human DNA. These YACs can be used to study the mechanisms that cause DNA fragility in humans by placing a known human fragile site within a YAC. Though it is useful to study human DNA inserted into yeast to monitor the inherent fragility of the sequence, studying the nature of native yeast fragile sites may have benefits as well. The types of native fragile sites in Saccharomyces cerevisiae include Mec1 mutant, hydroxyurea, palindromic, ty-element, and Pol1 mutant induced fragile sites. Many of the mechanisms of yeast DNA fragility are similar to those of human DNA. The purpose of this review is to compare and contrast the mechanisms of fragility in S. cerevisiae and human DNA. Though human and yeast fragile sites are not always caused by similar means, with further study of the native fragile sites in S. cerevisiae, more similarities may be found that can give further insight into the human fragile sites and diseases caused by them

The ability of Phyllospadix spp., a pair of intertidal foundation species, to maintain biodiversity and ameliorate CO2 stress in rocky shore tidepools

Ocean acidification (OA) is often demonstrated to have negative effects on marine organisms, but less is known about whether marine organisms can mediate OA effects. I examined relationships between surfgrass (Phyllospadix spp.), a foundation species and tidepool biodiversity, and its ability to mediate fluctuations in pH and dissolved oxygen (OA; DO) which are stressors in tidepools. I surveyed tidepools in northern California, where I quantified biodiversity, pH, and DO, and related those variables to surfgrass abundance. Laboratory and field experiments manipulating CO2 and surfgrass presence were done to examine surfgrass effects on day/night pH and DO fluctuations in simulated and natural tidepools. Intermediate surfgrass abundance was associated with the greatest tidepool biodiversity in the field, suggesting amelioration of abiotic conditions up to intermediate abundances, but exacerbated OA and DO stress at higher abundances. In the lab, diel pH and DO fluctuations were highest in simulated tidepools that contained surfgrass compared to pools without surfgrass, indicating the role of surfgrass photosynthesis and respiration in modulating seawater chemistry. In the field, tidepool pH and DO were higher in the day and lower at night, consistent with results from the laboratory experiment. Interestingly, day/night fluctuations in pH were highest in tidepools with intermediate rather than high surfgrass abundance, suggesting the intriguing possibility that surfgrass modulates tidepool pH both directly via metabolic activity but also indirectly by facilitating macrophyte diversity at intermediate abundances. Taken together, these results suggest that surfgrass may act as a foundation species in tidepools, by mediating tidepool pH and influencing species diversity, which has important implications for the fate of these communities in the face of rapidly-changing global climates

Measuring antibiotic availability and use in 20 low- and middle-income countries

Objective To assess antibiotic availability and use in health facilities in low- and middle-income countries, using the service provision assessment and service availability and readiness assessment surveys. Methods We obtained data on antibiotic availability at 13 561 health facilities in 13 service provision assessment and 8 service availability and readiness assessment surveys. In 10 service provision assessment surveys, child consultations with health-care providers were observed, giving data on antibiotic use in 22 699 children. Antibiotics were classified as access, watch or reserve, according to the World Health Organization’s AWaRe categories. The percentage of health-care facilities across countries with specific antibiotics available and the proportion of children receiving antibiotics for key clinical syndromes were estimated. Findings The surveys assessed the availability of 27 antibiotics (19 access, 7 watch, 1 unclassified). Co-trimoxazole and metronidazole were most widely available, being in stock at 89.5% (interquartile range, IQR: 11.6%) and 87.1% (IQR: 15.9%) of health facilities, respectively. In contrast, 17 other access and watch antibiotics were stocked, by fewer than a median of 50% of facilities. Of the 22 699 children observed, 60.1% (13 638) were prescribed antibiotics (mostly co-trimoxazole or amoxicillin). Children with respiratory conditions were most often prescribed antibiotics (76.1%; 8972/11 796) followed by undifferentiated fever (50.1%; 760/1518), diarrhoea (45.7%; 1293/2832) and malaria (30.3%; 352/1160). Conclusion Routine health facility surveys provided a valuable data source on the availability and use of antibiotics in low- and middle-income countries. Many access antibiotics were unavailable in a majority of most health-care facilities

Dissipative Taylor-Couette flows under the influence of helical magnetic fields

The linear stability of MHD Taylor-Couette flows in axially unbounded cylinders is considered, for magnetic Prandtl number unity. Magnetic fields varying from purely axial to purely azimuthal are imposed, with a general helical field parameterized by \beta=B_\phi/B_z. We map out the transition from the standard MRI for \beta=0 to the nonaxisymmetric Azimuthal MagnetoRotational Instability (AMRI) for \beta\to \infty. For finite \beta, positive and negative wave numbers m, corresponding to right and left spirals, are no longer identical. The transition from \beta=0 to \beta\to\infty includes all the possible forms of MRI with axisymmetric and nonaxisymmetric modes. For the nonaxisymmetric modes, the most unstable mode spirals in the opposite direction to the background field. The standard (\beta=0) MRI is axisymmetric for weak fields (including the instability with the lowest Reynolds number) but is nonaxisymmetric for stronger fields. If the azimuthal field is due in part to an axial current flowing through the fluid itself (and not just along the central axis), then it is also unstable to the nonaxisymmetric Tayler instability, which is most effective without rotation. For large \beta this instability has wavenumber m=1, whereas for \beta\simeq 1 m=2 is most unstable. The most unstable mode spirals in the same direction as the background field.Comment: 9 pages, 11 figure

Global axisymmetric Magnetorotational Instability with density gradients

We examine global incompressible axisymmetric perturbations of a differentially rotating MHD plasma with radial density gradients. It is shown that the standard magnetorotational instability, (MRI) criterion drawn from the local dispersion relation is often misleading. If the equilibrium magnetic field is either purely axial or purely toroidal, the problem reduces to finding the global radial eigenvalues of an effective potential. The standard Keplerian profile including the origin is mathematically ill-posed, and thus any solution will depend strongly on the inner boundary. We find a class of unstable modes localized by the form of the rotation and density profiles, with reduced dependence on boundary conditions.Comment: 22 pages, 5 figure

Direct enhancement of nuclear singlet order by dynamic nuclear polarization

Hyperpolarized singlet order is available immediately after dissolution DNP, avoiding need for additional preparation steps. We demonstrate this procedure on a sample of [1,2–13C2]pyruvic aci

The Origin of Solar Activity in the Tachocline

Solar active regions, produced by the emergence of tubes of strong magnetic field in the photosphere, are restricted to within 35 degrees of the solar equator. The nature of the dynamo processes that create and renew these fields, and are therefore responsible for solar magnetic phenomena, are not well understood. We analyze the magneto-rotational stability of the solar tachocline for general field geometry. This thin region of strong radial and latitudinal differential rotation, between the radiative and convective zones, is unstable at latitudes above 37 degrees, yet is stable closer to the equator. We propose that small-scale magneto-rotational turbulence prevents coherent magnetic dynamo action in the tachocline except in the vicinity of the equator, thus explaining the latitudinal restriction of active regions. Tying the magnetic dynamo to the tachocline elucidates the physical conditions and processes relevant to solar magnetism.Comment: 10 pages, 1 figure, accepted for publication in ApJ

Synaptic protein levels altered in vascular dementia

Synaptic protein levels altered in vascular dementi

Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment

Helicity and alpha-effect by current-driven instabilities of helical magnetic fields

Helical magnetic background fields with adjustable pitch angle are imposed on a conducting fluid in a differentially rotating cylindrical container. The small-scale kinetic and current helicities are calculated for various field geometries, and shown to have the opposite sign as the helicity of the large-scale field. These helicities and also the corresponding $\alpha$-effect scale with the current helicity of the background field. The $\alpha$-tensor is highly anisotropic as the components $\alpha_{\phi\phi}$ and $\alpha_{zz}$ have opposite signs. The amplitudes of the azimuthal $\alpha$-effect computed with the cylindrical 3D MHD code are so small that the operation of an $\alpha\Omega$ dynamo on the basis of the current-driven, kink-type instabilities of toroidal fields is highly questionable. In any case the low value of the $\alpha$-effect would lead to very long growth times of a dynamo in the radiation zone of the Sun and early-type stars of the order of mega-years.Comment: 6 pages, 7 figures, submitted to MNRA