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The information provided will prove helpful to make reliable inferences based on the manual inspection of individual phosphosites.Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. see more However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still growing spectrum of biological functions and also promoted the substrate discovery of these proteases. In this review, we will summarise the current hypotheses how phenotypes of these mouse models are linked to the molecular function of the enzymes. At the cellular level, SPP/SPPL-mediated cleavage events rather provide specific regulatory switches than unspecific bulk proteolysis. By this means, a plethora of different cell biological pathways is influenced including signal transduction, membrane trafficking and protein glycosylation.Faithful chromosome segregation during mitosis in eukaryotes requires attachment of the kinetochore, a large protein complex assembled on the centromere of each chromosome, to the spindle microtubules. The kinetochore is a structural interface for the microtubule attachment and provides molecular surveillance mechanisms that monitor and ensure the precise microtubule attachment as well, including error correction and spindle assembly checkpoint. During mitotic progression, the kinetochore undergoes dynamic morphological changes that are observable through electron microscopy as well as through fluorescence microscopy. These structural changes might be associated with the kinetochore function. In this review, we summarize how the dynamics of kinetochore morphology are associated with its functions and discuss recent findings on the switching of protein interaction networks in the kinetochore during cell cycle progression.OBJECTIVES The Central African Republic (CAR), a site of recurrent disease emergence, developed a noteworthy epidemiological surveillance system from the colonial period, but its health measures have remained among the world's lowest. To understand this disparity between surveillance and public health, we examined selected moments in its history of surveillance and changing relations with public health structures. METHODS We conducted archival research in CAR and French archives and 18 semi-structured interviews with key researchers working in CAR. RESULTS We find long-term continuities in privileging surveillance over the health system and population health, making the CAR a "hotspot" for emerging diseases and a "blind spot" of primary health care. From the colonial period, the country attracted considerable support for surveillance, without concomitant investment in public health system. Political disputes and financial constraints have obscured real primary care needs on the ground. CONCLUSIONS As both a hotspot and a blind spot for global health, the CAR signals the need to reorient health interventions to address the long-term health of Central African people.OBJECTIVES To explore the longitudinal association between food groups and memory loss and comorbid heart disease and diabetes (both Type 1 and 2) for people living in New South Wales, Australia. METHODS We assessed 139,096 adults (aged 45 years and over) from the 45 and Up Study who completed both baseline (2006-2009) and follow-up (2012-2015) surveys. Mixed linear and generalized estimating equation models were used to examine the longitudinal associations. RESULTS High consumption of fruit, vegetable and protein-rich food associated with lower odds of memory loss. High consumption of fruit and vegetables also associated with lower odds of comorbid heart disease (p ≤ 0.001). People who aged ≥ 80 years with low consumption of cereals had the highest odds of memory loss and comorbid heart disease than people in other age groups (p less then 0.01). CONCLUSIONS The results highlighted the longitudinal association of fruit and vegetable in relation to memory loss and comorbid heart disease. Age effects on cereals consumption which have an influence on memory loss and comorbid heart disease.According to the manufacturer's instructions the application of a PHILOS plate is restricted to humeral fractures. An extension to other anatomical regions of the body is not provided; however, based on the anatomical design of the plate it was observed that the application of this plate also appears to be possible for the distal tibia. This article reports three different osteosyntheses by a reverse PHILOS plate on the medial malleolus and on the distal tibia posteriorly with a short and a long PHILOS plate design. In summary, the applications have so far resulted in primary wound healing with correct consolidation of the fractures.BACKGROUND Various patterns of colonic mucosal irregularity have been recorded on contrast enema, each with individually very low sensitivity, but high specificity. OBJECTIVE To assess the accuracy of the radiologic features of Hirschsprung disease utilising a unifying stratification of any form of colonic mucosal irregularity on contrast enema. MATERIALS AND METHODS We conducted a retrospective study of children with suspected Hirschsprung disease managed at a tertiary South African hospital from January 2009 through April 2015. Three observers independently reviewed abdominal radiographs and contrast enemas. The enema analysis included a unifying category of any form of colonic mucosal irregularity. Radiologic features were compared with rectal biopsy results. We used descriptive statistics and the Fisher exact test to compare the radiologic features of children with and without Hirschsprung disease. RESULTS Ninety-two children with median age of 37 days (range 3 days to 11 years) were included; 50 had biopsy-proven Hirschsprung disease.
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