Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference

Host base excision repair (BER) proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1) and mutY homolog (MYH) as well as DNA polymerase beta (Polβ). While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 59dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggeted Polβ DNA synthesis activity is not necessary while 59dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level. © 2014 Bennett et al

Surviving streptococcal toxic shock syndrome: a case report

Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans) streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored

Basin-Scale Control on the Phytoplankton Biomass in Lake Victoria, Africa

The relative bio-optical variability within Lake Victoria was analyzed through the spatio-temporal decomposition of a 1997–2004 dataset of remotely-sensed reflectance ratios in the visible spectral range. Results show a regular seasonal pattern with a phase shift (around 2 months) between the south and north parts of the lake. Interannual trends suggested a teleconnection between the lake dynamics and El-Niño phenomena. Both seasonal and interannual patterns were associated to conditions of light limitation for phytoplankton growth and basin-scale hydrodynamics on phytoplankton access to light. Phytoplankton blooms developed during the periods of lake surface warming and water column stability. The temporal shift apparent in the bio-optical seasonal cycles was related to the differential cooling of the lake surface by southeastern monsoon winds. North-south differences in the exposure to trade winds are supported by the orography of the Eastern Great Rift Valley. The result is that surface layer warming begins in the northern part of the lake while the formation of cool and dense water continues in the southern part. The resulting buoyancy field is sufficient to induce a lake-wide convective circulation and the tilting of the isotherms along the north-south axis. Once surface warming spreads over the whole lake, the phytoplankton bloom dynamics are subjected to the internal seiche derived from the relaxation of thermocline tilting. In 1997–98, El-Niño phenomenon weakened the monsoon wind flow which led to an increase in water column stability and a higher phytoplankton optical signal throughout the lake. This suggests that phytoplankton response to expected climate scenarios will be opposite to that proposed for nutrient-limited great lakes. The present analysis of remotely-sensed bio-optical properties in combination with environmental data provides a novel basin-scale framework for research and management strategies in Lake Victoria

MER41 Repeat Sequences Contain Inducible STAT1 Binding Sites

Chromatin immunoprecipitation combined with massively parallel sequencing methods (ChIP-seq) is becoming the standard approach to study interactions of transcription factors (TF) with genomic sequences. At the example of public STAT1 ChIP-seq data sets, we present novel approaches for the interpretation of ChIP-seq data

Wing pathology of white-nose syndrome in bats suggests life-threatening disruption of physiology

White-nose syndrome (WNS) is causing unprecedented declines in several species of North American bats. The characteristic lesions of WNS are caused by the fungus Geomyces destructans, which erodes and replaces the living skin of bats while they hibernate. It is unknown how this infection kills the bats. We review here the unique physiological importance of wings to hibernating bats in relation to the damage caused by G. destructans and propose that mortality is caused by catastrophic disruption of wing-dependent physiological functions. Mechanisms of disease associated with G. destructans seem specific to hibernating bats and are most analogous to disease caused by chytrid fungus in amphibians

Glomerulocystic kidney disease

Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease

Combination therapy in hypertension: An update

Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females

Evidence for Widespread Genomic Methylation in the Migratory Locust, Locusta migratoria (Orthoptera: Acrididae)

The importance of DNA methylation in mammalian and plant systems is well established. In recent years there has been renewed interest in DNA methylation in insects. Accumulating evidence, both from mammals and insects, points towards an emerging role for DNA methylation in the regulation of phenotypic plasticity. The migratory locust (Locusta migratoria) is a model organism for the study of phenotypic plasticity. Despite this, there is little information available about the degree to which the genome is methylated in this species and genes encoding methylation machinery have not been previously identified. We therefore undertook an initial investigation to establish the presence of a functional DNA methylation system in L. migratoria. We found that the migratory locust possesses genes that putatively encode methylation machinery (DNA methyltransferases and a methyl-binding domain protein) and exhibits genomic methylation, some of which appears to be localised to repetitive regions of the genome. We have also identified a distinct group of genes within the L. migratoria genome that appear to have been historically methylated and show some possible functional differentiation. These results will facilitate more detailed research into the functional significance of DNA methylation in locusts

Small-scale coexistence of two mouse lemur species (Microcebus berthae and M. murinus) within a homogeneous competitive environment

Understanding the co-occurrence of ecologically similar species remains a puzzling issue in community ecology. The species-rich mouse lemurs (Microcebus spec.) are distributed over nearly all remaining forest areas of Madagascar with a high variability in species distribution patterns. Locally, many congeneric species pairs seem to co-occur, but only little detailed information on spatial patterns is available. Here, we present the results of an intensive capture–mark–recapture study of sympatric Microcebus berthae and M. murinus populations that revealed small-scale mutual spatial exclusion. Nearest neighbour analysis indicated a spatial aggregation in Microcebus murinus but not in M. berthae. Although the diet of both species differed in proportions of food categories, they used the same food sources and had high feeding niche overlap. Also, forest structure related to the spatial distribution of main food sources did not explain spatial segregation because parts used by each species exclusively did not differ in density of trees, dead wood and lianas. We propose that life history trade-offs that result in species aggregation and a relative increase in the strength of intra-specific over inter-specific competition best explain the observed pattern of co-occurrence of ecologically similar congeneric Microcebus species

A general method for controlling and resolving rotational orientation of molecules in molecule-surface collisions

Theoretical Chemistr