Common input to different regions of biceps brachii long head

The purpose of the experiment was to compare the level of synchronization exhibited by pairs of motor units located within and between functionally distinct regions of the biceps brachii muscle. Pairs of single motor units were recorded from seven subjects using separate electrodes located in the lateral and medial aspects of the long head of biceps brachii. Participants were required to exert a combination of flexion and supination torques so that both motor units discharged at approximately 10 pps for a parts per thousand yen200 s and the level of motor unit synchronization could be quantified. When motor unit recordings were sufficiently stable at the completion of this synchrony task, a series of ramp contractions with multiple combinations of flexion and supination torques were performed to characterize the recruitment thresholds of the motor units. Common input strength (CIS) was significantly greater (P <0.01) for the within-region pairs of motor units (0.28 extra sync. imps/s, n = 26) than for the between-region pairs (0.13 extra sync. imps/s, n = 18), but did not differ significantly for the 12 within-region pairs from the lateral head and 14 from the medial head (0.27 vs. 0.29 extra sync. imps/s; P = 0.83). Recruitment thresholds were measured for 33 motor units, but there was only a weak association between CIS and the respective recruitment patterns for motor unit pairs (n = 9). The present investigation provides evidence of a differential distribution of synaptic input across the biceps brachii motor neuron pool, but this appears to have minimal association with the recruitment patterns for individual motor units.

Long-lived near-infrared luminescent lanthanide complexes of imidodiphosphinate

Near-infrared emitting complexes of Nd(III), Er(III), and Yb(III) based on hexacoordinate lanthanide ions with an aryl functionalized imidodiphosphinate ligand, tpip, have been synthesized and fully characterized. Three tpip ligands form a shell around the lanthanide with the ligand coordinating via the two oxygens leading to neutral complexes, Ln(tpip)(3). In the X-ray crystal structures of Er(III) and Nd(III) complexes there is evidence of CH-pi interactions between the phenyl groups. Photophysical investigations of solution samples of the complexes demonstrate that all complexes exhibit relatively long luminescence lifetimes in nondeuteurated solvents. Luminescence studies of powder samples have also been recorded for examination of the properties of NIR complexes in the solid state for potential material applications. The results underline the effective shielding of the lanthanide by the twelve phenyl groups of the tpip ligands and the reduction of high-energy vibrations in close proximity to the lanthanide, both features important in the design of NIR emitting lanthanide complexes.

Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes

There has been a long history of defining T cell epitopes to track viral immunity and to design rational vaccines, yet few data of this type exist for bacterial infections. Bacillus anthracis, the causative agent of anthrax, is both an endemic pathogen in many regions and a potential biological warfare threat. T cell immunity in naturally infected anthrax patients has not previously been characterized, which is surprising given concern about the ability of anthrax toxins to subvert or ablate adaptive immunity. We investigated CD4 T cell responses in patients from the Kayseri region of Turkey who were previously infected with cutaneous anthrax. Responses to B. anthracis protective Ag and lethal factor (LF) were investigated at the protein, domain, and epitope level. Several years after antibiotic-treated anthrax infection, strong T cell memory was detectable, with no evidence of the expected impairment in specific immunity. Although serological responses to existing anthrax vaccines focus primarily on protective Ag, the major target of T cell immunity in infected individuals and anthrax-vaccinated donors was LF, notably domain IV. Some of these anthrax epitopes showed broad binding to several HLA class alleles, but others were more constrained in their HLA binding patterns. Of specific CD4 T cell epitopes targeted within LF domain IV, one is preferentially seen in the context of bacterial infection, as opposed to vaccination, suggesting that studies of this type will be important in understanding how the human immune system confronts serious bacterial infection.

A long-term study (1949-2005) of experimental introductions to an island; freshwater amphipods (Crustacea) in the Isle of Man (British Isles)

Using data from field introduction experiments with Gammarus spp. conducted in the rivers of a small island, commencing in 1949, with resampling in the 60s, 70s, 80s, 90s and finally in 2005, we aimed to examine the long-term interaction of the native freshwater amphipod Gammarus duebeni celticus with the introduced G. pulex. Using physico-chemical data from a 2005 island-wide survey, we also aimed to find what environmental factors could influence the distribution of the two species.

High dispersal potential has maintained long-term population stability in the North Atlantic copepod Calanus finmarchicus

The cool-water copepod Calanus finmarchicus is a key species in North Atlantic marine ecosystems since it represents an important food resource for the developmental stages of several fish of major economic value. Over the last 40 years, however, data from the Continuous Plankton Recorder survey have highlighted a 70 per cent reduction in C. finmarchicus biomass, coupled with a gradual northward shift in the species's distribution, which have both been linked with climate change. To determine the potential for C. finmarchicus to track changes in habitat availability and maintain stable effective population sizes, we have assessed levels of gene flow and dispersal in current populations, as well as using a coalescent approach together with palaeodistribution modelling to elucidate the historical population demography of the species over previous changes in Earth's climate. Our findings indicate high levels of dispersal and a constant effective population size over the period 359 000-566 000 BP and suggest that C. finmarchicus possesses the capacity to track changes in available habitat, a feature that may be of crucial importance to the species's ability to cope with the current period of global climate change.

Identification of residues important for agonist recognition and activation in GPR40

GPR40 was formerly an orphan G protein-coupled receptor whose endogenous ligands have recently been identified as free fatty acids (FFAs). The receptor, now named FFA receptor 1, has been implicated in the pathophysiology of type 2 diabetes and is a drug target because of its role in FFA-mediated enhancement of glucose-stimulated insulin release. Guided by molecular modeling, we investigated the molecular determinants contributing to binding of linoleic acid, a C18 polyunsaturated FFA, and GW9508, a synthetic small molecule agonist. Twelve residues within the putative GPR40-binding pocket including hydrophilic/positively charged, aromatic, and hydrophobic residues were identified and were subjected to site-directed mutagenesis. Our results suggest that linoleic acid and GW9508 are anchored on their carboxylate groups by Arg183, Asn244, and Arg258. Moreover, His86, Tyr91, and His137 may contribute to aromatic and/or hydrophobic interactions with GW9508 that are not present, or relatively weak, with linoleic acid. The anchor residues, as well as the residues Tyr12, Tyr91, His137, and Leu186, appear to be important for receptor activation also. Interestingly, His137 and particularly His86 may interact with GW9508 in a manner dependent on its protonation status. The greater number of putative interactions between GPR40 and GW9508 compared with linoleic acid may explain the higher potency of GW9508.

Evidence That Interspecies Polymorphism in the Human and Rat Cholecystokinin Receptor-2 Affects Structure of the Binding Site for the Endogenous Agonist Cholecystokinin

The cholecystokinin (CCK) receptor-2 exerts very important central and peripheral functions by binding the neuropeptides cholecystokinin or gastrin. Because this receptor is a potential therapeutic target, great interest has been devoted to the identification of efficient antagonists. However, interspecies genetic polymorphism that does not alter cholecystokinin-induced signaling was shown to markedly affect activity of synthetic ligands. In this context, precise structural study of the agonist binding site on the human cholecystokinin receptor-2 is a prerequisite to elucidating the molecular basis for its activation and to optimizing properties of synthetic ligands. In this study, using site-directed mutagenesis and molecular modeling, we delineated the binding site for CCK on the human cholecystokinin receptor-2 by mutating amino acids corresponding to that of the rat homolog. By doing so, we demonstrated that, although resembling that of rat homolog, the human cholecystokinin receptor-2 binding site also displays important distinct structural features that were demonstrated by susceptibility to several point mutations (F120A, Y189A, H207A). Furthermore, docking of CCK in the human and rat cholecystokinin receptor-2, followed by dynamic simulations, allowed us to propose a plausible structural explanation of the experimentally observed difference between rat and human cholecystokinin-2 receptors.

SuperWASP observations of long timescale photometric variations in cataclysmic variables

Aims: We investigated whether the predictions and results of Stanishev et al. (2002, A&A, 394, 625) concerning a possible relationship between eclipse depths in PX And and its retrograde disc precession phase, could be confirmed in long term observations made by SuperWASP. In addition, two further CVs (DQ Her and V795 Her) in the same SuperWASP data set were investigated to see whether evidence of superhump periods and disc precession periods were present and what other, if any, long term periods could be detected. Methods: Long term photometry of PX And, V795 Her and DQ Her was carried out and Lomb-Scargle periodogram analysis undertaken on the resulting light curves. For the two eclipsing CVs, PX And and DQ Her, we analysed the potential variations in the depth of the eclipse with cycle number. Results: The results of our period and eclipse analysis on PX And confirm that the negative superhump period is 0.1417 ± 0.0001d. We find no evidence of positive superhumps in our data suggesting that PX And may have been in a low state during our observations. We improve on existing estimates of the disc precession period and find it to be 4.43 ± 0.05d. Our results confirm the predictions of Stanishev et al. (2002). We find that DQ Her does not appear to show a similar variation for we find no evidence of negative superhumps or of a retrograde disc precession. We also find no evidence of positive superhumps or of a prograde disc precession and we attribute the lack of positive superhumps in DQ Her to be due to the high mass ratio of this CV. We do however find evidence for a modulation of the eclipse depth over a period of 100 days which may be linked with solar-type magnetic cycles which give rise to long term photometric variations. The periodogram analysis for V795 Her detected the likely positive superhump period 0.1165d, however, neither the 0.10826d orbital period nor the prograde 1.53d disc precession period were seen. Here though we have found a variation in the periodogram power function at the positive superhump period, over a period of at least 120 days.

Professional perspectives on decision making about the long-term care of older people

With the increasing pressure on social and health care resources, professionals have to be more explicit in their decision making regarding the long-term care of older people. This grounded theory study used 19 focus groups and nine semi-structured interviews (99 staff in total) to explore professional perspectives on this decision making. Focus group participants and interviewees comprised care managers, social workers, consultant geriatricians, general medical practitioners, community nurses, home care managers, occupational therapists and hospital discharge support staff. The emerging themes spanned context, clients, families and services. Decisions were often prompted by a crisis, hindering professionals seeking to make a measured assessment. Fear of burglary and assault, and the willingness and availability of family to help were major factors in decisions about living at home. Service availability in terms of public funding for community care, the availability of home care workers and workload pressures on primary care services influenced decision 'thresholds' regarding admission to institutional care. Assessment tools designed to assist decision making about the long-term care of older people need to take into account the critical aspects of individual fears and motivation, family support and the availability of publicly funded services as well as functional and medical needs.

Micro-environmental change as a trigger for granite decay in offshore Irish lighthouses: implications for the long-term preservation of operational historic buildings.

Following automation of lighthouses around the coastline of Ireland, reports of accelerated deterioration of interior granite stonework have increased significantly with an associated deterioration in the historic structure and rise in related maintenance costs. Decay of granite stone- work primarily occurs through granular disintegration with the effective grusification of granite surfaces. A decay gradient exists within the towers whereby the condition of granite in the lower levels is much worse than elsewhere. The lower tower levels are also regions with highest rela- tive humidity values and greatest salt concentrations. Data indicate that post-automation decay may have been trig- gered by a change in micro-environmental conditions within the towers associated with increased episodes of condensation on stone surfaces. This in turn appears to have facilitated deposition and accumulation of hygro- scopic salts (e.g. NaCl) giving rise to widespread evidence of deliquescence in the lower tower levels. Evidence indicates that the main factors contributing to accelerated deterioration of interior granite stonework are changes in micro-environmental conditions, salt weathering, chemical weathering through the corrosive effect of strongly alkaline conditions on alumino-silicate minerals within the granite and finally, the mica-rich characteristics of the granite itself which increases its structural and chemical susceptibility to subaerial weathering processes by creating points of weakness within the granite. This case study demonstrates how seemingly minor changes in micro-environmental conditions can unintentionally trigger the rapid and extensive deterioration of a previously stable rock type and threaten the long-term future of nationally iconic opera- tional historic structures.