The effect of food consumption on sodium and water balance in the predaceous diving beetle,Dytiscus verticalis

Summary Sodium and water balance ofDytiscus verticalis in fresh water were investigated under three feeding regimes: unfed, and fed a diet either low or high in sodium chloride. Unfed sodium influx was 0.13 and sodium efflux was 0.74 moles/100 gwm·h. These values are low in comparison with most freshwater animals. The electrical potential difference across the integument in artificial soft water (ASW) was about 150 mV smaller than the potential necessary to maintain sodium balance in the absence of active transport. However, sodium influx did not show saturation kinetics over an external concentration range of 91 to 1725 M. Unfed beetles failed to arrest net sodium loss to baths that were initially distilled water or ASW, even when bath sodium concentrations reached 75–298 M. The long-term rate of net sodium loss ranged from 0.61 to 4.4 moles/100 gwm·h for four sets of animals. Beetles decreased sodium efflux during a period of fasting. During subsequent feeding, beetles fed a high sodium diet (HSD) increased sodium efflux while beetles fed a low sodium diet (LSD) maintained low rates of sodium efflux. HSD fed beetles increased body sodium and hemolymph sodium concentration, and expanded extracellular fluid, relative to LSD fed beetles. Thus beetles cannot achieve sodium balance in fresh water without dietary sodium input, although they are able to regulate sodium loss.Abbreviations gwm grams wet mass - ASW artificial soft water - DW distilled water - HSD high sodium diet - LSD low sodium diet - ECF extracellular fluid volume     

A Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy

The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls. Expression of either variant resulted in significantly reduced TLR3-mediated signaling after stimulation with synthetic double-stranded RNA. Furthermore, Coxsackievirus B3 infection of cell lines expressing mutated TLR3 abrogated activation of the type I interferon pathway, leading to increased viral replication. TLR3-mediated type I interferon signaling required cellular autophagy and was suppressed by 3-methyladenine and bafilomycin A1, by inhibitors of lysosomal proteolysis, and by reduced expression of Beclin 1, Atg5, or microtubule-associated protein 1 light chain 3β (MAP1LC3β). However, TLR3-mediated signaling was restored upon exogenous expression of Beclin 1 or a variant MAP1LC3β fusion protein refractory to RNA interference. These data suggest that individuals harboring these variants may have a blunted innate immune response to enteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology.     

Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths

Background

Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie?

Results

We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered.

Conclusion

The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.

     

Stable complexes of axoplasmic vesicles and microtubules: protein composition and ATPase activity

Fast transport of axonal vesicles and organelles is a microtubule-associated movement (Griffin, J. W., K. E. Fahnestock, L. Price, and P. N. Hoffman, 1983, J. Neuroscience, 3:557-566; Schnapp, B. J., R. D. Vale, M. P. Sheetz, and T. S. Reese, 1984, Cell, 40:455-462; Allen, R. D., D. G. Weiss, J. H. Hayden, D. T. Brown, H. Fujiwake, and M. Simpson, 1985, J. Cell Biol., 100:1736-1752). Proteins that mediate the interactions of axoplasmic vesicles and microtubules were studied using stable complexes of microtubules and vesicles (MtVC). These complexes formed spontaneously in vitro when taxol-stabilized microtubules were mixed with sonically disrupted axoplasm from the giant axon of the squid Loligo pealei. The isolated MtVCs contain a distinct subset of axoplasmic proteins, and are composed primarily of microtubules and attached membranous vesicles. The MtVC also contains nonmitochondrial ATPase activity. The binding of one high molecular mass polypeptide to the complex is significantly enhanced by ATP or adenyl imidodiphosphate. All of the axoplasmic proteins and ATPase activity that bind to microtubules are found in macromolecular complexes and appear to be vesicle-associated. These data allow the identification of several vesicle-associated proteins of the squid giant axon and suggest that one or more of these polypeptides mediates vesicle binding to microtubules.     

An X-autosome fusion chromosome of Caenorhabditis elegans

Summary The translocation mnT12(IV;X) is a fusion of holocentric chromosomes IV and X, the breakpoints occurring near the left end of IV and the right end of X. Animals homozygous for mnT12 are viable and fertile; they contain five pairs of chromosomes rather than the normal set of six pairs. The mnT12 chromosome is larger than all wild-type chromosomes and thus identifies linkage groups IV and X cytologically. Hermaphrodites heterozygous for mnT12 show high frequency meiotic nondisjunction both between mnT12 and the X chromosome, which results in a high incidence of male self progeny (27% compared to the wild-type incidence of 0.2%), and between mnT12 and chromosome IV, which results in a high incidence of self progeny essentially trisomic for chromosome IV (karyotype IV/mnT12/mnT12). The viability of chromosome IV trisomics has been confirmed by constructing animals trisomic for only normal copies of chromosome IV; these animals are morphologically wild type. Meiotic chromosome disjunction in mnT12 homozygotes appears to be normal, although the frequency of recombination between markers that are normally X-linked is significantly reduced. Males of genotype IV/mnT12/0 are fertile. They can be thought of as having a neo-X(mnT12) neo-Y(normal IV) karyotype since it is possible to maintain a male-hermaphrodite stock of C. elegans consisting of such males and hermaphrodites carrying two neo-X chromosomes and no neo-Y; the organism is thus converted from an XO:XX type of sex determination to an XX:XX system.     

Relationship between probable dominant phosphate compound in soil and phosphorus availability to plants

Summary Surface soil materials from the 0- to 15 cm depth of 12 sites that were suspected to contain high levels of P, as a result of years of repeated applications of either inorganic or organic P fertilizers, were cropped with wheat and alfalfa in the greenhouse for about one year. The total P removed in plant materials provided an estimate of the plant available P in the soils. The probable dominant phosphate compound controlling the release of P in the soil solution during cropping was determined using the GEOCHEM program and an activity diagram. The data show that P availability is partly dependent on the stability of the phosphate compound present, although the relative positions of the points on the activity diagram show no quantitative relationship with either the total plant P uptake or the phosphate buffering capacity of the soils. The positions of the points, however, indicate that with time the formation of more stable P compounds during cropping could be attributed to reactions in the soil as well as to crop removal. The more soluble compounds could have recrystallized or were transformed into compounds of lower solubility. There is also the possibility that the more soluble P compounds were exhausted by crop removal leaving behind the less soluble compounds.     

Direct evidence for the existence of nominal antigen binding sites on T cell surface Ti alpha-beta heterodimers of MHC-restricted T cell clones

The binding of nominal antigen to Ti alpha-beta heterodimers on MHC-restricted human T cell clones specific for fluorescein-5-isothiocyanate (FL) was detected by flow cytometry and affinity chromatography. The FL-Ti interaction is of physiologic significance, since T cell activation is induced by cross-linked arrays of FL in the absence of the specific MHC recognition. High antigen valence is required to achieve stable binding to cells and subsequent activation, which is consistent with estimated Ti-FL association constants of less than 3 X 10(5) l/mol. In addition to providing direct evidence that the Ti alpha-beta heterodimer is the receptor for antigen, these data suggest that nominal antigen binding sites exist on the Ti molecules of at least some MHC-restricted clones.