Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses

Abstract: Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased T(H)2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T(H)2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Quality-Of-Life Assessment: Can We Keep it Simple?

Abstract: The importance of general statistical principles of study design and analysis to quality-of-life assessment in clinical trials is emphasized. Basic methods are reviewed briefly, with reference to three examples. Careful use of standard tools supplemented with context-specific scales is recommended. Problems of weighting and aggregation are discussed; the use of simple weighting schemes supplemented by sensitivity analysis is suggested. Some technical issues are explored, including factorial question structure, components of variance to distinguish mean treatment and patient-specific treatment effects and informative loss to follow-up

Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure

Abstract: To understand how nuclear processes involving DNA are regulated, knowledge of the determinants of chromatin condensation is required. From recent structural studies it has been concluded that the formation of the 30-nm chromatin fiber does not require the linker histone. Here, by comparing the linker histone-dependent compaction of long, reconstituted nucleosome arrays with different nucleosome repeat lengths (NRLs), 167 and 197 bp, we establish that the compaction behavior is both NRL- and linker histone-dependent. Only the 197-bp NRL array can form 30-nm higher-order chromatin structure. Importantly for understanding the regulation of compaction, this array shows a cooperative linker histone-dependent compaction. The 167-bp NRL array displays a limited linker histone-dependent compaction, resulting in a thinner and topologically different fiber. These observations provide an explanation for the distribution of NRLs found in nature.

Polyneuronal innervation of spiny stellate neurons in cat visual cortex

Abstract: Our hypothesis was that spiny stellate neurons in layer 4 of cat visual cortex receive polyneuronal innervation. We characterised the synapses of four likely sources of innervation by three simple criteria: the type of synapse, the target (spine, dendritic shaft), and the area of the presynaptic bouton. The layer 6 pyramids had the smallest boutons and formed asymmetric synapses mainly with the dendritic shaft. The thalamic afferents had the largest boutons and formed asymmetric synapses mainly with spines. The spiny stellates had medium-sized boutons and formed asymmetric synapses mainly with spines. We used these to make a "template" to match against the boutons forming synapses with the spiny stellate dendrite. Of the asymmetric synapses, 45% could have come from layer 6 pyramidal neurons, 28% from spiny stellate neurons, and 6% from thalamic afferents. The remaining 21% of asymmetric synapses could not be accounted for without assuming some additional selectivity of the presynaptic axons. Additional asymmetric synapses may come from a variety of sources, including other cortical neurons and subcortical nuclei such as the claustrum. Of the symmetric synapses, 84% could have been provided by clutch cells, which form large boutons. The remainder, formed by small boutons, probably come from other smooth neurons in layer 4, e.g., neurogliaform and bitufted neurons. Our analysis supports the hypothesis that the spiny stellate receives polyneuronal innervation, perhaps from all the sources of boutons in layer 4. Although layer 4 is the major recipient of thalamic afferents, our results show that they form only a few percent of the synapses of layer 4 spiny stellate neurons.