A Switch in the Control of Growth of the Wing Imaginal Disks of Manduca sexta

Background: Insulin and ecdysone are the key extrinsic regulators of growth for the wing imaginal disks of insects. In vitro tissue culture studies have shown that these two growth regulators act synergistically: either factor alone stimulates only limited growth, but together they stimulate disks to grow at a rate identical to that observed in situ. It is generally thought that insulin signaling links growth to nutrition, and that starvation stops growth because it inhibits insulin secretion. At the end of larval life feeding stops but the disks continue to grow, so at that time disk growth has become uncoupled from nutrition. We sought to determine at exactly what point in development this uncoupling occurs. Methodology: Growth and cell proliferation in the wing imaginal disks and hemolymph carbohydrate concentrations were measured at various stages in the last larval instar under experimental conditions of starvation, ligation, rescue, and hormone treatment. Principal Findings: Here we show that in the last larval instar of M. sexta, the uncoupling of nutrition and growth occurs as the larva passes the critical weight. Before this time, starvation causes a decline in hemolymph glucose and trehalose and a cessation of wing imaginal disks growth, which can be rescued by injections of trehalose. After the critical weight the trehalose response to starvation disappears, and the expression of insulin becomes decoupled from nutrition. After the critical weight the wing disks loose their sensitivity to repression by juvenile hormone, and factors from the abdomen, bu

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

Apicotomy: a root apical fracture for surgical treatment of impacted upper canines

Impacted canines, due to systemic or local factors, represent a frequent problem in most populations. Surgical intervention usually involves exposure for spontaneous eruption, exposure for orthodontic traction or extraction. The author presents the apicotomy technique, which has been successfully used during the past twenty years for conservative intervention in cases of impacted upper canines with dilaceration or apical root-ankylosis. This original method involves surgical fracture of the root apex, followed by orthodontic traction of the corono-radicular region

Saccharomyces cerevisiae chitin biosynthesis activation by N-acetylchitooses depends on size and structure of chito-oligosaccharides

<p>Abstract</p> <p>Background</p> <p>To explore chitin synthesis initiation, the effect of addition of exogenous oligosaccharides on <it>in vitro </it>chitin synthesis was studied. Oligosaccharides of various natures and lengths were added to a chitin synthase assay performed on a <it>Saccharomyces cerevisiae </it>membrane fraction.</p> <p>Findings</p> <p><it>N</it>-acetylchito-tetra, -penta and -octaoses resulted in 11 to 25% [¹⁴C]-GlcNAc incorporation into [¹⁴C]-chitin, corresponding to an increase in the initial velocity. The activation appeared specific to <it>N</it>-acetylchitooses as it was not observed with oligosaccharides in other series, such as beta-(1,4), beta-(1,3) or alpha-(1,6) glucooligosaccharides.</p> <p>Conclusions</p> <p>The effect induced by the <it>N</it>-acetylchitooses was a saturable phenomenon and did not interfere with free GlcNAc and trypsin which are two known activators of yeast chitin synthase activity <it>in vitro</it>. The magnitude of the activation was dependent on both oligosaccharide concentration and oligosaccharide size.</p

Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP

Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE2 in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = −0.9; −0.1), and in duodenal lesions (P = 0.04, 95 CI % = −0.9; −0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE2 levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP

A lightweight sensing platform for monitoring sleep quality and posture: a simulated validation study

Background The prevalence of self-reported shoulder pain in the UK has been estimated at 16%. This has been linked with significant sleep disturbance. It is possible that this relationship is bidirectional, with both symptoms capable of causing the other. Within the field of sleep monitoring, there is a requirement for a mobile and unobtrusive device capable of monitoring sleep posture and quality. This study investigates the feasibility of a wearable sleep system (WSS) in accurately detecting sleeping posture and physical activity. Methods Sixteen healthy subjects were recruited and fitted with three wearable inertial sensors on the trunk and forearms. Ten participants were entered into a ‘Posture’ protocol; assuming a series of common sleeping postures in a simulated bedroom. Five participants completed an ‘Activity’ protocol, in which a triphasic simulated sleep was performed including awake, sleep and REM phases. A combined sleep posture and activity protocol was then conducted as a ‘Proof of Concept’ model. Data were used to train a posture detection algorithm, and added to activity to predict sleep phase. Classification accuracy of the WSS was measured during the simulations. Results The WSS was found to have an overall accuracy of 99.5% in detection of four major postures, and 92.5% in the detection of eight minor postures. Prediction of sleep phase using activity measurements was accurate in 97.3% of the simulations. The ability of the system to accurately detect both posture and activity enabled the design of a conceptual layout for a user-friendly tablet application. Conclusions The study presents a pervasive wearable sensor platform, which can accurately detect both sleeping posture and activity in non-specialised environments. The extent and accuracy of sleep metrics available advances the current state-of-the-art technology. This has potential diagnostic implications in musculoskeletal pathology and with the addition of alerts may provide therapeutic value in a range of areas including the prevention of pressure sores

Population Structure of Staphylococcus aureus from Remote African Babongo Pygmies

Staphylococcus aureus is a bacterium that colonizes humans worldwide. The anterior nares are its main ecological niche. Carriers of S. aureus are at a higher risk of developing invasive infections. Few reports indicated a different clonal structure and profile of virulence factors in S. aureus isolates from Sub-Saharan Africa. As there are no data about isolates from remote indigenous African populations, we conducted a cross-sectional survey of S. aureus nasal carriage in Gabonese Babongo Pygmies. The isolates were characterized regarding their susceptibility to antibiotic agents, possession of virulence factors and clonal lineage. While similar carriage rates were found in populations of industrialized countries, isolates that encode the genes for the Panton-Valentine leukocidin (PVL) were clearly more prevalent than in European countries. Of interest, many methicillin-susceptible S. aureus isolates from Babongo Pygmies showed the same genetic background as pandemic methicillin-resistant S. aureus (MRSA) clones. We advocate a surveillance of S. aureus in neglected African populations to control the development of resistance to antibiotic drugs with particular respect to MRSA and to assess the impact of the high prevalence of PVL-positive isolates

The Importance of Tree Size and Fecundity for Wind Dispersal of Big-Leaf Mahogany

Seed dispersal by wind is a critical yet poorly understood process in tropical forest trees. How tree size and fecundity affect this process at the population level remains largely unknown because of insufficient replication across adults. We measured seed dispersal by the endangered neotropical timber species big-leaf mahogany (Swietenia macrophylla King, Meliaceae) in the Brazilian Amazon at 25 relatively isolated trees using multiple 1-m wide belt transects extended 100 m downwind. Tree diameter and fecundity correlated positively with increased seed shadow extent; but in combination large, high fecundity trees contributed disproportionately to longer-distance dispersal events (>60 m). Among three empirical models fitted to seed density vs. distance in one dimension, the Student-t (2Dt) generally fit best (compared to the negative exponential and inverse power). When seedfall downwind was modelled in two dimensions using a normalised sample, it peaked furthest downwind (c. 25 m) for large, high-fecundity trees; with the inverse Gaussian and Weibull functions providing comparable fits that were slightly better than the lognormal. Although most seeds fell within 30 m of parent trees, relatively few juveniles were found within this distance, resulting in juvenile-to-seed ratios peaking at c. 35–45 m. Using the 2Dt model fits to predict seed densities downwind, coupled with known fecundity data for 2000–2009, we evaluated potential Swietenia regeneration near adults (≤30 m dispersal) and beyond 30 m. Mean seed arrival into canopy gaps >30 m downwind was more than 3× greater for large, high fecundity trees than small, high-fecundity trees. Tree seed production did not necessarily scale up proportionately with diameter, and was not consistent across years, and this resulting intraspecific variation can have important consequences for local patterns of dispersal in forests. Our results have important implications for management and conservation of big-leaf mahogany populations, and may apply to other threatened wind-dispersed Meliaceae trees

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex