Motor activity and trajectory control during escape jumping in the locust <Emphasis Type="Italic">Locusta migratoria</Emphasis>

We investigated the escape jumps that locusts produce in response to approaching objects. Hindleg muscular activity during an escape jump is similar to that during a defensive kick. Locusts can direct their escape jumps up to 50° either side of the direction of their long axis at the time of hindleg flexion, allowing them to consistently jump away from the side towards which an object is approaching. Variation in jump trajectory is achieved by rolling and yawing movements of the body that are controlled by the fore- and mesothoracic legs. During hindleg flexion, a locust flexes the foreleg ipsilateral to its eventual jump trajectory and then extends the contralateral foreleg. These foreleg movements continue throughout co-contraction of the hindleg tibial muscles, pivoting the locust’s long axis towards its eventual jump trajectory. However, there are no bilateral differences in the motor programs of the left and right hindlegs that correlate with jump trajectory. Foreleg movements enable a locust to control its jump trajectory independent of the hindleg motor program, allowing a decision on jump trajectory to be made after the hindlegs have been cocked in preparation for a jump.     

Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex

Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-alpha as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.     

2,3-Diaminopyridine as a platform for designing structurally unique nonpeptide bradykinin B1 receptor antagonists

A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described.     

Evidence for L-dopa incorporation into cell proteins in patients treated with levodopa

Levodopa (L-dopa) is the most widely used agent for the symptomatic relief of Parkinson's disease. There is concern that chronic L-dopa treatment may be detrimental, with some studies suggesting that L-dopa may be neurotoxic. A potentially important mechanism whereby L-dopa may exert neurotoxic effects has been overlooked: that of the incorporation of L-dopa into proteins by protein synthesis. L-Dopa competes with tyrosine as a substrate in protein synthesis in vitro. We provide evidence that L-dopa can also be incorporated into proteins in vivo. Blood from L-dopa-treated and -non-treated patients was separated into protein, erythrocyte and lymphocyte fractions and levels of protein-incorporated dopa quantified by HPLC. Levels of protein-incorporated dopa were significantly increased in lymphocyte cell proteins from L-dopa-treated patients. This has not arisen from oxidative pathways as there was no evidence of oxidative damage to proteins. In addition, there was no increase in protein-incorporated dopa in erythrocytes, which are not actively synthesizing proteins. We suggest that protein-incorporated dopa could also be generated in the CNS. The accumulation of protein-incorporated dopa in cells is associated with oxidative stress and impaired function and could contribute to some of the problems associated with long-term L-dopa treatment.     

Foraging success under uncertainty: search tradeoffs and optimal space use

Understanding the structural complexity and the main drivers of animal search behaviour is pivotal to foraging ecology. Yet, the role of uncertainty as a generative mechanism of movement patterns is poorly understood. Novel insights from search theory suggest that organisms should collect and assess new information from the environment by producing complex exploratory strategies. Based on an extension of the first passage time theory, and using simple equations and simulations, we unveil the elementary heuristics behind search behaviour. In particular, we show that normal diffusion is not enough for determining optimal exploratory behaviour but anomalous diffusion is required. Searching organisms go through two critical sequential phases (approach and detection) and experience fundamental search tradeoffs that may limit their encounter rates. Using experimental data, we show that biological search includes elements not fully considered in contemporary physical search theory. In particular, the need to consider search movement as a non‐stationary process that brings the organism from one informational state to another. For example, the transition from remaining in an area to departing from it may occur through an exploratory state where cognitive search is challenged. Therefore, a more comprehensive view of foraging ecology requires including current perspectives about movement under uncertainty.     

MANAGEMENT OF EARLY PROSTATIC CARCINOMA

It is important to make a diagnosis of prostatic carcinoma as early as possible, because early treatment gives the best results whether radical prostatectomy is done or endocrine therapy used. Open perineal biopsy is the most accurate method of making a diagnosis. Perineal needle biopsy or the newer approach of transrectal needle biopsy is probably about 75 per cent accurate in making a diagnosis.Ten-year survival with conservative therapy, as determined in a review of a series of cases, was 50 per cent—about the same as that following radical prostatectomy; but the patients with prostatectomy are clinically free of malignant disease whereas the former are not. Radical prostatectomy is indicated in a few selected cases.The results from endocrine therapy begun immediately after diagnosis are significantly better than those from delayed treatment. Orchiectomy and estrogens promise a little longer survival than estrogens alone.     

Developmental regulation of aldoxime formation in seedlings and mature plants of Chinese cabbage (Brassica campestris ssp. pekinensis) and oilseed rape (Brassica napus): Glucosinolate and IAA biosynthetic enzymes

The first steps in the biosynthesis of glucosinolates and indole-3-acetic acid (IAA) in oilseed rape (Brassica napus L.) and Chinese cabbage (Brassica campestris ssp. pekinensis) involve the formation of aldoximes. In rape the formation of aldoximes from chain-extended amino acids, for aromatic and aliphatic glucosinolate biosynthesis, is catalysed by microsomal flavin-containing monooxygenases. The formation of indole-3-aldoxime from l-tryptophan, the potential precursor of both indole-3-acetic acid and indolyl-glucosinolates, is catalysed by several microsomal peroxidases. The biosynthesis of glucosinolates and indole-3-acetic acid was shown to be under developmental control in oilseed rape and Chinese cabbage. No monooxygenase activities were detected in cotyledons or old leaves of either species. The highest monooxygenase activities were found in young expanding leaves; as the leaves reached full expansion and matured the activities decreased rapidly. The indole-aldoxime-forming activity was found in all of the tissues analysed, but there was also a clear decrease in foliar activity with maturity in leaves of rape and Chinese cabbage. Partial characterisation of the Chinese cabbage monooxygenases showed that they have essentially identical properties to the previously characterised rape enzymes; they are not cytochrome P450-type enzymes, but resemble flavin-containing monooxygenases. No monooxygenase inhibitors were detected in microsomes prepared from either cotyledons or old leaves.Abbreviations DHMet dihomomethionine - FMO flavin-containing monooxygenase - HPhe homophenylalanine - IAA indole-3-acetic acid - l-Phe l-phenylalanine - l-Trp l-tryptophan - MO monooxygenase - IAALD indole-3-acetaldehyde - IAOX indole-3-aldoxime - THMet trihomomethionine     

Response of compressed skinned skeletal muscle fibers to conditions that simulate fatigue

Myburgh, Kathryn H., and Roger Cooke. Response ofcompressed skinned skeletal muscle fibers to conditions that simulate fatigue. J. Appl. Physiol. 82(4):1297-1304, 1997.During fatigue, muscles become weaker, slower,and more economical at producing tension. Studies of skinned musclefibers can explain some but not all of these effects, and, inparticular, they are less economical in conditions that simulatefatigue. We investigated three factors that may contribute to thedifferent behavior of skinned fibers. 1) Skinned fibers have increasedmyofilament lattice spacing, which is reversible by osmoticcompression. 2) A myosin subunit becomes phosphorylated during fatigue.3) Inosine 5-monophosphate (IMP) accumulates during fatigue. We tested the response ofphosphorylated and unphosphorylated single skinned fibers (isometrictension, contraction velocity, and adenosinetriphosphatase activity) to changes in lattice spacing (0-5% dextran) and IMP (0-5 mM)in the presence of altered concentrations ofP_i (3-25 mM),H⁺ (pH 7-6.2), and ADP(0-5 mM). The response of maximally activated skinned fibers tothe direct metabolites of ATP hydrolysis is not altered by osmoticcompression, phosphorylating myosin subunits, or increasing IMPconcentration. These factors, therefore, do not explain the discrepancybetween intact and skinned fibers during fatigue.

     

Formation of collagen-glycosaminoglycan blended nanofibrous scaffolds and their biological properties

The development of blended collagen and glycosaminoglycan (GAG) scaffolds can potentially be used in many soft tissue engineering applications since the scaffolds mimic the structure and biological function of native extracellular matrix (ECM). In this study, we were able to obtain novel nanofibrous collagen-GAG scaffolds by electrospinning collagen blended with chondroitin sulfate (CS), a widely used GAG, in a mixed solvent of trifluoroethanol and water. The electrospun collagen-GAG scaffold with 4% CS (COLL-CS-04) exhibited a uniform fiber structure with nanoscale diameters. A second collagen-GAG scaffold with 10% CS consisted of smaller diameter fibers but exhibited a broader diameter distribution due to the different solution properties in comparison with COLL-CS-04. After cross-linking with glutaraldehyde vapor, the collagen-GAG scaffolds became more biostable and were resistant to collagenase degradation. This is evidently a more favorable environment allowing increased proliferation of rabbit conjunctiva fibroblast on the scaffolds. Incorporation of CS into collagen nanofibers without cross-linking did not increase the biostability but still promoted cell growth. The potential of applying the nanoscale collagen-GAG scaffold in tissue engineering is significant since the nanodimension fibers made of natural ECM mimic closely the native ECM found in the human body. The high surface area characteristic of this scaffold may maximize cell-ECM interaction and promote tissue regeneration faster than other conventional scaffolds.     

Genetic population structure of Natterer's bats explained by mating at swarming sites and philopatry

During autumn 'swarming', large numbers of temperate bats chase each other in and around underground sites. Swarming has been proposed to be a mating event, allowing interbreeding between bats from otherwise isolated summer colonies. We studied the population structure of the Natterer's bat (Myotis nattereri), a swarming species in northern England, by sampling bats at seven sites in two swarming areas and at 11 summer colonies. Analysis of molecular variance (amova) and genetic assignment analyses showed that the swarming areas (60 km apart) support significantly different populations. A negative correlation was found between the distance of a summer colony from a swarming area and the assignment of bats to that area. High gene diversity was found at all sites (HE = 0.79) suggesting high gene flow. This was supported by a low FST (0.017) among summer colonies and the absence of isolation by distance or substructure among colonies which visit one swarming area. The FST, although low, was significantly different from zero, which could be explained by a combination of female philopatry and male-mediated gene flow through mating at swarming sites with bats from other colonies. Modelling suggested that if effective size of the summer colonies (Ne) was low to moderate (10-30), all mating must occur at the swarming sites to account for the observed FST. If the Ne was higher (50), in addition to random mating during swarming, there may be nonrandom mating at swarming sites or some within-colony mating. Conservation of swarming sites that support potentially large populations is discussed.