Tickle with a feather

Support the hanging body and cut through the rope gently. Until the arrival of a medical man apply leeches to the temple and take blood with cupping glasses. These were the serious instructions given to the reader in 1870 by the well-known publisher Samuel Beeton (husband of Mrs Beeton of cookery fame) and may be found in his book of 365 pages, All About Everything, sold in those days for 2/- (two shillings), or 2/6d with cloth gilt. In our age of antibiotics you will find its advice on medicines, health and general topics curious, but some may still be successful ... Do you suffer from ague? Well, here's the cure - it's a favourite and considered most efficacious, and I bet granddad enjoyed it: beat up a new-laid egg in a glass of brandy and take on going to bed. Equally popular was 3 grams of snake root, 40 grams of wormwood, and '/2 oz of best powdered Jesuit bark - taken in a half pint of port wine.SAMJ Volume 85 No.6 June 199

A Crh-specific function in carbon catabolite repression in Bacillus subtilis

Carbon catabolite repression in Bacillus subtilis is mediated by phosphorylation of the phosphoenolpyruvate: carbohydrate phosphotransferase system intermediate HPr at a serine residue catalyzed by HPr kinase. The orthologous protein Crh functions in a similar way, but, unlike HPr, it is not functional in carbohydrate uptake. A specific function for Crh is not known. The role of HPr and Crh in repressing the citM gene encoding the Mg2+-citrate transporter was investigated during growth of B. subtilis on different carbon sources. In glucose minimal medium, full repression was supported by both HPr and Crh. Strains deficient in Crh or the regulatory function of HPr revealed the same repression as the wild-type strain. In contrast, in a medium containing succinate and glutamate, repression was specifically mediated via Crh. Repression was relieved in the Crh-deficient strain, but still present in the HPr mutant strain. The data are the first demonstration of a Crh-specific function in B. subtilis and suggest a role for Crh in regulation of expression during growth on substrates other than carbohydrates. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies

Fishing indirectly structures macroalgal assemblages by altering herbivore behavior.

Fishing has clear direct effects on harvested species, but its cascading, indirect effects are less well understood. Fishing disproportionately removes larger, predatory fishes from marine food webs. Most studies of the consequent indirect effects focus on density-mediated interactions where predator removal alternately drives increases and decreases in abundances of successively lower trophic-level species. While prey may increase in number with fewer predators, they may also alter their behavior. When such behavioral responses impact the food resources of prey species, behaviorally mediated trophic cascades can dramatically shape landscapes. It remains unclear whether this pathway of change is typically triggered by ocean fishing. By coupling a simple foraging model with empirical observations from coral reefs, we provide a mechanistic basis for understanding and predicting how predator harvest can alter the landscape of risk for herbivores and consequently drive dramatic changes in primary producer distributions. These results broaden trophic cascade predictions for fisheries to include behavioral changes. They also provide a framework for detecting the presence and magnitude of behaviorally mediated cascades. This knowledge will help to reconcile the disparity between expected and observed patterns of fishing-induced cascades in the sea

Metric mechanics with nontrivial topology: Actuating irises, cylinders, and evertors.

Liquid crystal elastomers contract along their director on heating and recover on cooling, offering great potential as actuators and artificial muscles. If a flat sheet is programed with a spatially varying director pattern, then it will actuate into a curved surface, allowing the material to act as a strong machine such as a grabber or lifter. Here we study the actuation of programed annular sheets which, owing to their central hole, can sidestep constraints on area and orientation. We systematically catalog the set of developable surfaces encodable via axisymmetric director patterns and uncover several qualitatively new modes of actuation, including cylinders, irises, and everted surfaces in which the inner boundary becomes the outer boundary after actuation. We confirm our designs with a combination of experiments and numerics. Many of our actuators can reattain their initial inner or outer radius upon completing actuation, making them particularly promising, as they can avoid potentially problematic stresses in their activated state even when fixed onto a frame or pipe

Shape programming lines of concentrated Gaussian curvature

Liquid crystal elastomers (LCEs) can undergo large reversible contractions along their nematic director upon heating or illumination. A spatially patterned director within a flat LCE sheet thus encodes a pattern of contraction on heating, which can morph the sheet into a curved shell, akin to how a pattern of growth sculpts a developing organism. Here we consider, theoretically, numerically and experimentally, patterns constructed from regions of radial and circular director, which, in isolation, would form cones and anticones. The resultant surfaces contain curved ridges with sharp V-shaped cross-sections, associated with the boundaries between regions in the patterns. Such ridges may be created in positively and negatively curved variants and, since they bear Gauss curvature (quantified here via the Gauss-Bonnet theorem), they cannot be flattened without energetically prohibitive stretch. Our experiments and numerics highlight that, although such ridges cannot be flattened isometrically, they can deform isometrically by trading the (singular) curvature of the V angle against the (finite) curvature of the ridge line. Furthermore, in finite thickness sheets, the sharp ridges are inevitably non-isometrically blunted to relieve bend, resulting in a modest smearing out of the encoded singular Gauss curvature. We close by discussing the use of such features as actuating linear features, such as probes, tongues and limbs, and highlighting the similarities between these patterns of shape change and those found during the morphogenesis of several biological systems.F.F. and M.W. were supported by the EPSRC [grant number EP/P034616/1]. M.W. is grateful for support from the ELBE Visiting Faculty Program, Dresden. D.D. was supported by the EPSRC Centre for Doctoral Training in Computational Methods for Materials Science [grant no. EP/L015552/1]. J.S.B. was supported by a UKRI “future leaders fellowship” [grant number MR/S017186/1]. This material is partially based upon work supported by the National Science Foundation under Grant DMR 2041671

Introduction to the Workshop

Public health administrators are forced to consider efficiency as a criterion in their choice of preventive programs because of the numerous programs to choose from, restricted budgets, and declining caries experience in children. Interest in cost effectiveness in dental prevention has risen considerably since the initial conference on this issue at the University of Michigan in 1978. This article introduces the goals of the workshop, the nature of the work groups, and the data they will use.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66042/1/j.1752-7325.1989.tb02083.x.pd

MOBP and HIP1 in multiple system atrophy: new α‐synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis

Aims: MSA is a fatal neurodegenerative disease. Similar to Parkinson’s disease (PD), MSA is an α‐synucleinopathy, and its pathological hallmark consists of glial cytoplasmic inclusions (GCIs) containing α‐synuclein in oligodendrocytes. We previously identified consistent changes in MOBP and HIP1 DNA methylation status in MSA. We hypothesized that if differential DNA methylation at these loci is mechanistically relevant for MSA, it should have downstream consequences on gene regulation. / Methods: We investigated the relationship between MOBP and HIP1 DNA methylation and mRNA levels in cerebellar white matter from MSA and healthy controls. Additionally, we analysed protein expression using western blotting, immunohistochemistry and proximity ligation assays. / Results: We found decreased MOBP mRNA levels significantly correlated with increased DNA methylation in MSA. For HIP1, we found a distinct relationship between DNA methylation and gene expression levels in MSA compared to healthy controls, suggesting this locus may be subjected to epigenetic remodelling in MSA. Although soluble protein levels for MOBP and HIP1 in cerebellar white matter were not significantly different between MSA cases and controls, we found striking differences between MSA and other neurodegenerative diseases, including PD and Huntington’s disease. We also found that MOBP and HIP1 are mislocalized into the GCIs in MSA, where they appear to interact with α‐synuclein. / Conclusions: This study supports a role for DNA methylation in downregulation of MOBP mRNA in MSA. Most importantly, the identification of MOBP and HIP1 as new constituents of GCIs emphasizes the relevance of these two loci to the pathogenesis of MSA

Homicide and geographic access to gun dealers in the United States

<p>Abstract</p> <p>Background</p> <p>Firearms are the most commonly used weapon to commit homicide in the U.S. Virtually all firearms enter the public marketplace through a federal firearms licensee (FFL): a store or individual licensed by the federal government to sell firearms. Whether FFLs contribute to gun-related homicide in areas where they are located, in which case FFLs may be a homicide risk factor that can be modified, is not known.</p> <p>Methods</p> <p>Annual county-level data (1993–1999) on gun homicide rates and rates of FFLs per capita were analyzed using negative binomial regression controlling for socio-demographic characteristics. Models were run to evaluate whether the relation between rates of FFLs and rates of gun homicide varied over the study period and across counties according to their level of urbanism (defined by four groupings, as below). Also, rates of FFLs were compared against FS/S – which is the proportion of suicides committed by firearm and is thought to be a good proxy for firearm availability in a region – to help evaluate how well the FFL variable is serving as a way to proxy firearm availability in each of the county types of interest.</p> <p>Results</p> <p>In major cities, gun homicide rates were higher where FFLs were more prevalent (rate ratio [RR] = 1.70, 95% CI 1.03–2.81). This association increased (p < 0.01) from 1993 (RR = 1.69) to 1999 (RR = 12.72), due likely to federal reforms that eliminated low-volume dealers, making FFL prevalence a more accurate exposure measure over time. No association was found in small towns. In other cities and in suburbs, gun homicide rates were significantly lower where FFLs were more prevalent, with associations that did not change over the years of the study period. FFL prevalence was correlated strongly (positively) with FS/S in major cities only, suggesting that the findings for how FFL prevalence relates to gun homicide may be valid for the findings pertaining to major cities but not to counties of other types.</p> <p>Conclusion</p> <p>Modification of FFLs through federal, state, and local regulation may be a feasible intervention to reduce gun homicide in major cities.</p

Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials