Regional distribution of type II Ca^(2+)/calmodulin-dependent protein kinase in rat brain

The distribution of type II Ca^(2+)/calmodulin-dependent protein kinase has been mapped in rat brain by immunochemical and immunohistochemical methods using an antibody against its alpha-subunit. The concentration of the kinase, measured by radioimmunoassay, varies markedly in different brain regions. It is most highly concentrated in the telencephalon where it comprises approximately 2% of the total hippocampal protein, 1.3% of cortical protein, and 0.7% of striatal protein. It is less concentrated in lower brain structures, ranging from about 0.3% of hypothalamic protein to 0.1% of protein in the pons/medulla. The gradient of staining intensity observed in brain sections by immunohistochemistry corroborates this distribution. Neurons and neuropil of the hippocampus are densely stained, whereas little staining is observed in lower brain regions such as the superior colliculus. Within the diencephalon and midbrain, dense staining is observed only in thalamic nuclei and the substantia nigra. The skewed distribution of alpha-subunit appears to be due in part to the occurrence in the cerebellum and pons/medulla of forms of the kinase with a high ratio of beta- to alpha-subunits. However, most of the variation is due to the extremely high concentration of the kinase in particular neurons, especially those of the hippocampus, cortex and striatum. The unusually high expression of the kinase in these neurons is likely to confer upon them specialized responses to calcium ion that are different from those of neurons in lower brain regions

Purification and characterization of a calmodulin-dependent protein kinase that is highly concentrated in brain

A calcium and calmodulin-dependent protein kinase has been purified from rat brain. It was monitored during the purification by its ability to phosphorylate the synaptic vesicle-associated protein, synapsin I. A 300-fold purification was sufficient to produce kinase that is 90-95% pure as determined by scans of stained sodium dodecyl sulfate-polyacrylamide gels and has a specific activity of 2.9 mumol of 32P transferred per min/mg of protein. Thus, the kinase is a relatively abundant brain enzyme, perhaps comprising as much as 0.3% of the total brain protein. The Stokes radius (95 A) and sedimentation coefficient (16.4 S) of the kinase indicate a holoenzyme molecular weight of approximately 650,000. The holoenzyme is composed of three subunits as judged by their co-migration with kinase activity during the purification steps and co-precipitation with kinase activity by a specific anti-kinase monoclonal antibody. The three subunits have molecular weights of 50,000, 58,000, and 60,000, and have been termed alpha, beta', and beta, respectively. The alpha- and beta-subunits are distinct peptides, however, beta' may have been generated from beta by proteolysis. All three of these subunits bind calmodulin in the presence of calcium and are autophosphorylated under conditions in which the kinase is active. The subunits are present in a ratio of about 3 alpha-subunits to 1 beta/beta'-subunit. We therefore postulate that the 650,000-Da holoenzyme consists of approximately 9 alpha-subunits and 3 beta/beta'-subunits. The abundance of this calmodulin-dependent protein kinase indicates that its activation is likely to be an important biochemical response to increases in calcium ion concentration in neuronal tissue

A scorecard of progress towards measles elimination in 15 west African countries, 2001-19: a retrospective, multicountry analysis of national immunisation coverage and surveillance data.

BACKGROUND: The WHO Regional Office for the Africa Regional Immunization Technical Advisory Group, in 2011, adopted the measles control and elimination goals for all countries of the African region to achieve in 2015 and 2020 respectively. Our aim was to track the current status of progress towards measles control and elimination milestones across 15 west African countries between 2001 and 2019. METHODS: We did a retrospective multicountry series analysis of national immunisation coverage and case surveillance data from Jan 1, 2001, to Dec 31, 2019. Our analysis focused on the 15 west African countries that constitute the Economic Community of West African States. We tracked progress in the coverage of measles-containing vaccines (MCVs), measles supplementary immunisation activities, and measles incidence rates. We developed a country-level measles summary scorecard using eight indicators to track progress towards measles elimination as of the end of 2019. The summary indicators were tracked against measles control and elimination milestones. FINDINGS: The weighted average regional first-dose MCV coverage in 2019 was 66% compared with 45% in 2001. 73% (11 of 15) of the west African countries had introduced second-dose MCV as of December, 2019. An estimated 4 588 040 children (aged 12-23 months) did not receive first-dose MCV in 2019, the majority (71%) of whom lived in Nigeria. Based on the scorecard, 12 (80%) countries are off-track to achieving measles elimination milestones; however, Cape Verde, The Gambia, and Ghana have made substantial progress. INTERPRETATION: Measles will continue to be endemic in west Africa after 2020. The regional measles incidence rate in 2019 was 33 times the 2020 elimination target of less than 1 case per million population. However, some hope exists as countries can look at the efforts made by Cape Verde, The Gambia, and Ghana and learn from them. FUNDING: None

Developing a Tool to Cost Gaps in Implementation of IHR (2005) Core Capacities

In May 2013, over 100 WHO Member States (MS) reported not having met their national International Health Regulations (2005) core capacity requirements. Many MS need support in identifying activities and associated costs to support building capacity. WHO developed a costing tool organized by the IHR (2005) Core Capacities and public health core functions. The tool will provide users with estimated annualized costs for developing and sustaining public health activities relevant to IHR (2005) implementation. Providing National Focal Points with costs estimates and generalized plans of action facilitates allocation of funds and development of IHR capacities and public health functions