The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Interpreting household survey data intended to measure insecticide-treated bednet coverage: results from two surveys in Eritrea

BACKGROUND: As efforts are currently underway to roll-out insecticide-treated bednets (ITNs) to populations within malarious areas in Africa, there is an unprecedented need for data to measure the effectiveness of such programmes in terms of population coverage. This paper examines methodological issues to using household surveys to measure core Roll Back Malaria coverage indicators of ITN possession and use. METHODS: ITN coverage estimates within Anseba and Gash Barka Provinces from the 2002 Eritrean Demographic and Health Survey, implemented just prior to a large-scale ITN distribution programme, are compared to estimates from the same area from a sub-national Bednet Survey implemented 18 months later in 2003 after the roll-out of the ITN programme. RESULTS: Measures of bednet possession were dramatically higher in 2003 compared to 2002. In 2003, 82.2% (95% confidence interval (CI) 77.4–87.0) of households in Anseba and Gash Barka possessed at least one ITN. RBM coverage indicators for ITN use were also dramatically higher in 2003 as compared to 2002, with 76.1% (95% CI 69.9–82.2) of children under five years old and 52.4% (95% CI 38.2–66.6) of pregnant women sleeping under ITNs. The ITN distribution programme resulted in a gross increase in ITN use among children and pregnant women of 68.3% and 48% respectively. CONCLUSION: Eritrea has exceeded the Abuja targets of 60% coverage for ITN household possession and use among children under five years old within two malarious provinces. Results point to several important potential sources of bias that must be considered when interpreting data for ITN coverage over time, including: disparate survey universes and target populations that may include non-malarious areas; poor date recall of bednet procurement and treatment; and differences in timing of surveys with respect to malaria season

Synthetic asters as elastic and radial skeletons

The radial geometry with rays radiated from a common core occurs ubiquitously in nature for its symmetry and functions. Herein, we report a class of synthetic asters with well-defined core-ray geometry that can function as elastic and radial skeletons to harbor nano- and microparticles. We fabricate the asters in a single, facile, and high-yield step that can be readily scaled up; specifically, amphiphilic gemini molecules self-assemble in water into asters with an amorphous core and divergently growing, twisted crystalline ribbons. The asters can spontaneously position microparticles in the cores, along the radial ribbons, or by the outer rims depending on particle sizes and surface chemistry. Their mechanical properties are determined on single- and multiple-aster levels. We further maneuver the synthetic asters as building blocks to form higher-order structures in virtue of aster-aster adhesion induced by ribbon intertwining. We envision the astral structures to act as rudimentary spatial organizers in nanoscience for coordinated multicomponent systems, possibly leading to emergent, synergistic functions

The Burden of Trachoma in Ayod County of Southern Sudan

Trachoma, a neglected tropical disease, is the leading cause of infectious blindness and is targeted for global elimination by the year 2020. We conducted a survey in Ayod County of Jonglei State, Southern Sudan, to determine whether blinding trachoma was a public health problem and to plan interventions to control this disease. We found the burden of trachoma in Ayod to be one of the most severe ever documented. Not only were adults affected by the advanced manifestations of the disease as is typical for older age groups, but young children were also affected. At least one person with clinical signs of trachoma was found in nearly every household, and 1 in 3 households had a person with severe blinding trachoma. Characteristics previously identified as risk factors were ubiquitous among surveyed households, but we were unable to identify why trachoma is so severe in this location. Surgical interventions are needed urgently to improve vision and prevent irreversible blindness in children and adults. Mass antibiotic distribution may alleviate current infections and transmission of trachoma may be reduced if communities adopt the behavior of face washing and safe disposal of human waste. Increasing access to improved water sources may not only improve hygiene but also reduce the spread of guinea worm and other water-borne diseases

Madagascar corals track sea surface temperature variability in the Agulhas Current core region over the past 334 years

The Agulhas Current (AC) is the strongest western boundary current in the Southern Hemisphere and is key for weather and climate patterns, both regionally and globally. Its heat transfer into both the midlatitude South Indian Ocean and South Atlantic is of global significance. A new composite coral record (Ifaty and Tulear massive Porites corals), is linked to historical AC sea surface temperature (SST) instrumental data, showing robust correlations. The composite coral SST data start in 1660 and comprise 200 years more than the AC instrumental record. Numerical modelling exhibits that this new coral derived SST record is representative for the wider core region of the AC. AC SSTs variabilities show distinct cooling through the Little Ice Age and warming during the late 18th, 19th and 20th century, with significant decadal variability superimposed. Furthermore, the AC SSTs are teleconnected with the broad southern Indian and Atlantic Oceans, showing that the AC system is pivotal for inter-ocean heat exchange south of Africa

Intrapericardial Delivery of Gelfoam Enables the Targeted Delivery of Periostin Peptide after Myocardial Infarction by Inducing Fibrin Clot Formation

Background: Administration of a recombinant peptide of Periostin (rPN) has recently been shown to stimulate cardiomyocyte proliferation and angiogensis after myocardial infarction (MI). However, strategies for targeting the delivery of rPN to the heart are lacking. Intrapericardial administration of drug-eluting hydrogels may provide a clinically viable strategy for increasing myocardial retention, therapeutic efficacy, and bioactivity of rPN and to decrease systemic re-circulation. Methods and Results: We investigated the ability of intrapericardial injections of drug-eluting hydrogels to deliver and prolong the release of rPN to the myocardium in a large animal model of myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly used in surgery, and is known to stimulate fibrin clot formation. We show that Gelfoam disks loaded with rPN, when implanted within the pericardium or peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into the pericardial cavity of pigs, following a complete occlusion of the left anterior descending artery, leads to greater induction of cardiomyocyte mitosis, increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared to direct injection of rPN alone. Conclusions: The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium

Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman

<p>Abstract</p> <p>Background</p> <p>Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology.</p> <p>Methods</p> <p>We analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17β-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17β-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene.</p> <p>Results</p> <p>A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation.</p> <p>Conclusion</p> <p>At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.</p

Where Do We Go from Here? Prevalence of Trachoma Three Years after Stopping Mass Distribution of Antibiotics in the Regions of Kayes and Koulikoro, Mali

Trachoma, a blinding bacterial disease, is targeted for elimination by 2020. To achieve the elimination target, the World Health Organization (WHO) recommends member states implement the SAFE strategy; surgery, mass administration of antibiotics, promotion of hygiene and facial cleanliness and water and sanitation as environmental improvements. We present results from evaluation surveys conducted in 2006 and 2009 from the regions of Kayes and Koulikoro, Mali. Prevalence of active trachoma in 2006 was below baseline intervention thresholds in all surveyed districts and the national program stopped antibiotic distribution. The prevalence of trachoma in 2009 remained well below levels in 1998. However, in 8 of 13 districts compared, the prevalence of active trachoma was higher in 2009 than 2006. Three years of antibiotic intervention did not equate in all districts to a sustained reduction of active trachoma. No surveillance activities were implemented after stopping interventions. Surgical interventions may have reduced the burden of blinding trachoma but there is an ongoing need for surgeries specifically targeting affected women. Four districts meet the WHO criteria for resuming district-wide mass antibiotic distribution. A community-by-community approach to elimination may be needed in other districts. The promotion of facial cleanliness and good hygiene behavior should be reintroduced

Bias and Evolution of the Mutationally Accessible Phenotypic Space in a Developmental System

Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype-dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change