A comparative study of Multiple versus Single infection doses of Schistosoma haematobium in Golden hamsters ( Mesocricetus auratus )

Schistosoma haematobium is widely distributed in Africa. In Kenya, endemic areas include the upper and the lower regions of the Coast Province, Lake Victoria and the Kano plains. Low infection rates over prolonged periods of time characterize schistosome infections of people living in endemic areas. However, the common laboratory practice is to expose the definitive host to a single high dose. In order to utilize the laboratory results appropriately, it is important to know whether or not a large single infection has similar results to multiple small doses. In this study, immune responses, worm burden, gross and histopathological patterns of multiple infection of S. haematobiumium in the Golden hamster ( Mesocricetus auratus ) were compared with those of single exposure. Multiple infections with low doses of the parasite did not seem to be protective, as suggested by; more worms, worse gross and histopathology in multiple low dose group compared to single high dose group. Most probably there is an antigenic threshold, which needs to be attained before protective mechanisms come into play. Although necessary for protection, there was no direct correlation between IgG levels and degree of protection

Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034

Crystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials

A comparative study of Multiple versus Single infection doses of Schistosoma haematobium in Golden hamsters ( Mesocricetus auratus )

Schistosoma haematobium is widely distributed in Africa. In Kenya, endemic areas include the upper and the lower regions of the Coast Province, Lake Victoria and the Kano plains. Low infection rates over prolonged periods of time characterize schistosome infections of people living in endemic areas. However, the common laboratory practice is to expose the definitive host to a single high dose. In order to utilize the laboratory results appropriately, it is important to know whether or not a large single infection has similar results to multiple small doses. In this study, immune responses, worm burden, gross and histopathological patterns of multiple infection of S. haematobiumium in the Golden hamster ( Mesocricetus auratus ) were compared with those of single exposure. Multiple infections with low doses of the parasite did not seem to be protective, as suggested by; more worms, worse gross and histopathology in multiple low dose group compared to single high dose group. Most probably there is an antigenic threshold, which needs to be attained before protective mechanisms come into play. Although necessary for protection, there was no direct correlation between IgG levels and degree of protection

The status of flora and fauna in the Nzoia River drainage basin in western Kenya

The species richness of flora and fauna in the Nzoia River drainage basin is documented through a study of museum specimens,  catalogues and databases. The catchment area and basin covers 2.2% (12900/580367 km2) of Kenya’s total land area with an altitudinal range of 1140 to 4300 m and varied ecosystem and land uses. We recorded approximately 9.3% (3239/34677) of Kenya’s current known species of vascular plants, invertebrates (insects and spiders), fish, amphibians, reptiles, birds and mammals. Bird species made up the highest proportion 58.3% (650/1114) of the national total followed by amphibians 37.3% (41/110), reptiles 45.0% (86/191), mammals 31.3% (122/390), vascular plants 17.9% (1251/7000), fish 6.7% (58/872) (32.2% (58/180) for freshwater fish only) and invertebrates (insects and spiders) 4.1% (1031/25000). Ninety-five species recorded in this area are endemic to Kenya and 42 globally threatened. The species recorded contribute to several ecosystem services including pest control, pollination, bio-indicators, medicine and cosmetics, building materials, ecotourism, research and education. Data available differed substantially across counties and taxon groups with gaps apparent in five counties (Bungoma, Busia, Elgeyo Marakwet, Siaya and Usain Gishu) and four taxa plants, invertebrates, fungi and bacteria where a dearth of information exists. To fill these gaps we recommend prioritisng future survey effort on taxa and counties with fewer than 10% of the total numbers of records

Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis

Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. The outer layer of kinetochores transiently expands in early mitosis to form a fibrous corona, and compacts following microtubule capture. Here we show that the dynein adaptor Spindly and the RZZ (ROD-Zwilch-ZW10) complex drive kinetochore expansion in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ-Spindly complexes into a filamentous meshwork in cells and in vitro. Concurrent with kinetochore expansion, Spindly potentiates kinetochore compaction by recruiting dynein via three conserved short linear motifs. Expanded kinetochores unable to compact engage in extensive, long-lived lateral microtubule interactions that persist to metaphase, and result in merotelic attachments and chromosome segregation errors in anaphase. Thus, dynamic kinetochore size regulation in mitosis is coordinated by a single, Spindly-based mechanism that promotes initial microtubule capture and subsequent correct maturation of attachments

Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort studyResearch in Context

Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences