Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

Background  

Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.     

Reduced Global Genetic Differentiation of Exploited Marine Fish Species

Knowledge on genetic structure is key to understand species connectivity patterns and to define the spatiotemporal scales over which conservation management plans should be designed and implemented. The distribution of genetic diversity (within and among populations) greatly influences species ability to cope and adapt to environmental changes, ultimately determining their long-term resilience to ecological disturbances. Yet, the drivers shaping connectivity and structure in marine fish populations remain elusive, as are the effects of fishing activities on genetic subdivision. To investigate these questions, we conducted a meta-analysis and compiled genetic differentiation data (F_ST/Φ_ST estimates) for more than 170 fish species from over 200 published studies globally distributed. We modeled the effects of multiple life-history traits, distance metrics, and methodological factors on observed population differentiation indices and specifically tested whether any signal arising from different exposure to fishing exploitation could be detected. Although the myriad of variables shaping genetic structure makes it challenging to isolate the influence of single drivers, results showed a significant correlation between commercial importance and genetic structure, with widespread lower population differentiation in commercially exploited species. Moreover, models indicate that variables commonly used as proxy for connectivity, such as larval pelagic duration, might be insufficient, and suggest that deep-sea species may disperse further. Overall, these results contribute to the growing body of knowledge on marine genetic connectivity and suggest a potential effect of commercial fisheries on the homogenization of genetic diversity, highlighting the need for additional research focused on dispersal ecology to ensure long-term sustainability of exploited marine species.     

Interspecific Introgression in Cetaceans: DNA Markers Reveal Post-F1 Status of a Pilot Whale

Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus) are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region) and eight nuclear loci (microsatellites) as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain), one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals.     

Emerging Patterns of HIV Infection and Control in the Philippines

A total of 50 carriers of the human immunodeficiency virus (HIV), 46 of them female prostitutes, have been detected through seroprevalence surveys by the Department of Health, Manila. Infection rates are highest in two small cities near foreign military bases and in the tourist district of MetroManila. Nine patients with the acquired immunodeficiency syndrome (AIDS) who contracted the disease outside the country have been reported, with opportunistic infections being the major clinical feature. Public information measures heavily utilize the mass media, and there is anecdotal evidence that awareness of the disease among the urban population is increasing. The National AIDS Committee foresees that a large proportion of the cases seen in the Philippines over the next few years will be returning nationals who were infected abroad.     

Allosteric activation of rat liver microsomal [hydroxymethylglutaryl-CoA reductase (NADPH)]kinase by nucleoside phosphates

Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase kinase activity is enhanced about 5 fold by 2 mM of either AMP or ADP. Activation constants, Ka, for AMP and ADP are 17 microM and 430 microM respectively, showing that AMP is a more potent activator than ADP. This property is expressed by increasing not only the rate of reductase inactivation but also the rate of reductase phosphorylation from [gamma-32P]ATP. GTP can replace ATP as substrate of reductase kinase but GMP and GDP cannot replace AMP as activators. Kinetic studies show that ATP can only act as a substrate. Nucleoside mono or diphosphates and nucleoside triphosphates, thus, appear to bind to different sites on microsomal HMG-CoA reductase kinase. Nucleoside mono or diphosphates act as allosteric activators of reductase kinase. The adenosyl moiety and the unaltered phosphate ester at the 5' position are two essential features of the activator molecule. Phosphorylation of reductase either by microsomal or cytosolic AMP-activated reductase kinase produces an 80% inactivation, with a concomitant incorporation of 0.8 mol of 32P per mol of reductase (Mr 55,000). In both cases exhaustive tryptic digestion of 32P-labeled HMG-CoA reductase, which had been denatured in 2M urea, yields two major phosphopeptides, the phosphoryl group being bound to serine residues.     

Nitrogen fixation and nitrate reduction in the root nodules of legumes

Published data on, and hypotheses regarding the effect of NO⁻₃ on functioning of legume root nodules are reviewed. It is concluded that a short-term reversible effect of NO⁻₃ may act via an increased resistance to O₂ diffusion in nodules; this is coupled to decreased bacteroid respiration. For longer exposures to NO⁻₃ nodule activity is irreversibly lost, but how this relates to carbohydrate deprivation or NO-₂ accumulation is unclear. Complicating factors include denitrification reactions and the interaction of NO⁻₂ with leghaemoglobin.     

Affinity labeling of the catalytic and AMP allosteric sites of 3-hydroxy-3-methylglutaryl-coenzyme A reductase kinase by 5'-p-fluorosulfonylbenzoyladenosine

The nucleotide analogue 5'-p-fluorosulfonylbenzoyladenosine (FSBA) reacts irreversibly with rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is about 10 times higher (kappa 1 = 0.112 min-1) than the rate constant of inactivation (kappa 2 = 0.0106 min-1). There is a good correspondence between the time-dependent inactivation of reductase kinase and the time-dependent incorporation of 5'-p-sulfonylbenzoyl[14C]adenosine ([14C]SBA). An average of 1.65 mol of reagent/mol of enzyme subunit is bound when reductase kinase is completely inactivated. The time-dependent incorporation is consistent with the postulate that covalent reaction of 1 mol of SBA/mol of subunit causes complete loss of AMP activation, whereas reaction of another mole of SBA/mol of subunit would lead to total inactivation. Protection against inactivation by the reagent is provided by the addition of Mg2+, AMP, Mg-ATP, or Mg-AMP to the incubation mixtures. In contrast, addition of ATP, 2'-AMP, or 3'-AMP has no effect on the rate constants. Mg-ATP protects preferentially the catalytic site against inactivation, whereas Mg-AMP at low concentration protects preferentially the allosteric site. Mg-ADP affords less protection than Mg-AMP to the allosteric site when both nucleotides are present at a concentration of 50 microM with 7.5 mM Mg2+. Experiments done with [14C]FSBA in the presence of some protectants have shown that a close correlation exists between the pattern of protection observed and the binding of [14C]SBA. The postulate is that there exists a catalytic site and an allosteric site in the reductase kinase subunit and that Mg-AMP is the main allosteric activator of the enzyme.