Reproductive biology of Dikerogammarus haemobaphes: an invasive gammarid (Crustacea: Amphipoda) colonizing running waters in Central Europe

Dikerogammarus haemobaphes is a Ponto-Caspian gammarid that has invaded vast areas in Central and Western Europe. Our paper is a first presentation of its life history features in an invaded region. The study was conducted in the Vistula River in Poland from autumn 2003 to autumn 2005 in two sites differing in hydrological conditions with one being water reservoir. The results showed that the reproductive period lasted 8 months from April till October in both sites. Three generations per 1 year were observed: autumn (overwintering), spring and summer. Ten cohorts per year were distinguished. The individuals from the reservoir were much bigger than those from the other site. The fecundity of those specimens was also higher and they laid 52 eggs per clutch in average in comparison with 37 eggs in the river itself. The strong relationship between the number of embryos (in developmental stage 2) per clutch and the length of females was noticed. The overall mean egg size of stage 2 of D. haemobaphes was 0.430 ± 0.029 mm which is smaller than noted for native species such as Gammarus fossarum. A potentially high reproductive capacity, comparatively small eggs, short time of eggs’ development, fast reaching sexual maturation, short life span, tolerance to a wide range of environmental conditions, all promote the invasion of this Ponto-Caspian gammarid in freshwater ecosystems of the temperate climate zone.     

Genetic Differences between the Determinants of Lipid Profile Phenotypes in African and European Americans: The Jackson Heart Study

Genome-wide association analysis in populations of European descent has recently found more than a hundred genetic variants affecting risk for common disease. An open question, however, is how relevant the variants discovered in Europeans are to other populations. To address this problem for cardiovascular phenotypes, we studied a cohort of 4,464 African Americans from the Jackson Heart Study (JHS), in whom we genotyped both a panel of 12 recently discovered genetic variants known to predict lipid profile levels in Europeans and a panel of up to 1,447 ancestry informative markers allowing us to determine the African ancestry proportion of each individual at each position in the genome. Focusing on lipid profiles—HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG)—we identified the lipoprotein lipase (LPL) locus as harboring variants that account for interethnic variation in HDL-C and TG. In particular, we identified a novel common variant within LPL that is strongly associated with TG (p=2.7×10⁻⁶) and explains nearly 1% of the variability in this phenotype, the most of any variant in African Americans to date. Strikingly, the extensively studied “gain-of-function” S447X mutation at LPL, which has been hypothesized to be the major determinant of the LPL-TG genetic association and is in trials for human gene therapy, has a significantly diminished strength of biological effect when it is found on a background of African rather than European ancestry. These results suggest that there are other, yet undiscovered variants at the locus that are truly causal (and are in linkage disequilibrium with S447X) or that work synergistically with S447X to modulate TG levels. Finally, we find systematically lower effect sizes for the 12 risk variants discovered in European populations on the African local ancestry background in JHS, highlighting the need for caution in the use of genetic variants for risk assessment across different populations.     

Changes in the Growth, Chemical Composition, and Antioxidant Activity in the Aquatic Plant Wolffia arrhiza (L.) Wimm. (Lemnaceae) Exposed to Jasmonic Acid

The present study was undertaken to test the influence of exogenously applied jasmonic acid (JA) at concentrations of 0.01–100 μM upon the growth and metabolism of the aquatic plant Wolffia arrhiza (Lemnaceae). JA acted in a concentration-dependent manner. JA at 0.1 μM stimulated plant growth and accumulation of cellular components (proteins, monosaccharides, chlorophylls, phaeophytins, and carotenoids). Treatment with JA at 0.1 μM enhanced W. arrhiza viability by the induction of biomass production and increased the level of photosynthetic pigments, monosaccharides, and soluble proteins. Moreover, JA at 0.1 μM activated the enzymatic (catalase, ascorbate peroxidase, NADH peroxidase) and nonenzymatic antioxidant (ascorbate, glutathione) system in W. arrhiza and, therefore, suppressed lipid peroxidation. In contrast, decreases in fresh weight, major photosynthetic pigments, monosaccharides, and soluble protein content were observed in W. arrhiza exposed to 100 μM JA. JA applied at 100 μM also stimulated the formation of lipid peroxides which are responsible for membrane damage. In the presence of 100 μM JA, antioxidant enzyme (catalase, ascorbate peroxidase, NADH peroxidase) activity and ascorbate as well as glutathione content were inhibited. The data support the hypothesis that JA plays an important role in W. arrhiza growth and metabolism, regulating oxidative status by direct influence on the enzymatic as well as nonenzymatic antioxidant machinery.     

Impaired Replication Capacity of Acute/Early Viruses in Persons Who Become HIV Controllers

Human immunodeficiency virus type 1 (HIV-1) controllers maintain viremia at <2,000 RNA copies/ml without antiretroviral therapy. Viruses from controllers with chronic infection were shown to exhibit impaired replication capacities, in part associated with escape mutations from cytotoxic-T-lymphocyte (CTL) responses. In contrast, little is known about viruses during acute/early infection in individuals who subsequently become HIV controllers. Here, we examine the viral replication capacities, HLA types, and virus sequences from 18 HIV-1 controllers identified during primary infection. gag-protease chimeric viruses constructed using the earliest postinfection samples displayed significantly lower replication capacities than isolates from persons who failed to control viremia (P = 0.0003). Protective HLA class I alleles were not enriched in these early HIV controllers, but viral sequencing revealed a significantly higher prevalence of drug resistance mutations associated with impaired viral fitness in controllers than in noncontrollers (6/15 [40.0%] versus 10/80 [12.5%], P = 0.018). Moreover, of two HLA-B57-positive (B57⁺) controllers identified, both harbored, at the earliest time point tested, signature escape mutations within Gag that likewise impair viral replication capacity. Only five controllers did not express “protective” alleles or harbor viruses with drug resistance mutations; intriguingly, two of them displayed typical B57 signature mutations (T242N), suggesting the acquisition of attenuated viruses from B57⁺ donors. These data indicate that acute/early stage viruses from persons who become controllers have evidence of reduced replication capacity during the initial stages of infection which is likely associated with transmitted or acquired CTL escape mutations or transmitted drug resistance mutations. These data suggest that viral dynamics during acute infection have a major impact on HIV disease outcome.Human immunodeficiency virus type I (HIV-1)-infected individuals who control viremia spontaneously without antiviral therapy have been termed HIV controllers (3, 18, 21, 48, 52). Unraveling the mechanisms associated with this phenotype should provide important insights regarding HIV pathogenesis and could contribute to vaccine development.Host and viral genetics, as well as host innate and adaptive immune responses, influence the rate of disease progression in HIV-1 infection (reviewed in reference 18). Several studies have reported the correlation between in vitro HIV replication capacity and level of plasma virus loads or disease progression in individuals with chronic infection (6, 13, 35, 45, 50, 55). Studies of HIV-1 elite controllers (EC), who control viremia to below the limit of detection in commercial assays, have revealed the presence of replication-competent viruses in these individuals (7), although these viruses appear to be less fit based on studies of envelope (35) and Gag-protease (45). This fitness defect in the chronic phase of infection is due at least in part to fitness-impairing mutations induced by cytotoxic-T-lymphocyte (CTL) responses restricted by “protective” HLA class I alleles (46).In contrast, little is known about viruses obtained from the acute/early phase of infection in persons who subsequently become HIV-1 controllers, largely due to the difficulty in enrolling such people during the acute/early phase of infection. The characterization of acute/early-phase viruses in individuals who subsequently achieve low set-point virus loads is of paramount importance to our understanding of the mechanisms of HIV-1 control.In the present study, we analyzed acute/early-phase plasma HIV RNA sequences from 18 untreated individuals who were diagnosed during the acute/early phase and subsequently became controllers (<2,000 RNA copies/ml). We compared these to sequences from a group of HIV-1 noncontrollers enrolled similarly during acute/early infection. We also generated chimeric viruses carrying patient-derived gag-protease sequences from acute/early-phase infection and compared the viral replication capacities of the chimeric viruses from controllers and from noncontrollers.We observed that the chimeric viruses derived from controllers have significantly reduced replicative capacities compared to those from noncontrollers. Moreover, we observed that at least 80% of these individuals who go on to become controllers featured transmission of attenuated drug-resistant viruses, transmission of HLA-B57-restricted CTL escape variants to HLA-mismatched recipients, selection of attenuated CTL escape variants in HLA-B57-positive (B57⁺) recipients, or combinations of these factors. Taken together, these results indicate that the initial viral dynamics have a major influence on the subsequent course of disease.     

Age, reproduction and fecundity of the spined loach Cobitis taenia L. (Pisces, Cobitidae) from Lake Klawój (Poland)

This is the first study concerning the features of the reproduction process of the karyologically identified spined loach C. taenia (2n=48). The histology of 71 ovaries, and gonadosomatic index (GSI) of karyologically identified spined loach Cobitis taenia L. from Lake Klawój (Northern Poland) were examined. The absolute and relative fecundity of 25 females was estimated by gravimetric method. The age of fish was determined according to the annual increments of otholits. The spawning of C. taenia from Lake Klawój took place from May to July, at a water temperature exceeding 18.5 degrees C. The GSI values at the beginning of the reproduction period ranged from 7 to 19%. The average absolute fecundity of females was 2078 eggs, with the number ranging from 869 to 3371 eggs. High individual variability in the gonad histology and the GSI values during the reproductive period was observed. Such variability could be the result of beginning the reproduction process in the fish at various times and, probably, due to the various numbers of batches laid and various numbers of eggs per batch.     

New strategies for cardiovascular gene therapy

Cardiovascular diseases are among the major targets for gene therapy. Initially, clinical experiments of gene transfer of vascular endothelial growth factor (VEGF) improved vascularization and prevented the amputation in patients with critical leg ischemia. However, the majority of trials did not provide conclusive results and therefore further preclinical studies are required. Importantly, data indicate the necessity of regulated expression of angiogenic factors, particularly VEGF, to obtain the therapeutic effect. It is also suggested that the combined delivery of two or more genes may improve the formation of mature vasculature and therefore may be more effective in the amelioration of ischemia. Moreover, experimental approaches in animal models displayed the promise of gene transfer modulating the inflammatory processes and oxidant status of the cells. Particularly, the concept of preemptive gene therapy has been tested, and recent studies have demonstrated that overexpression of heme oxygenase-1 or extracellular superoxide dismutase can prevent heart injury by myocardial infarction induced several weeks after gene instillation. The combination of a preemptive strategy with regulated gene expression, using the vectors in which the therapeutic transgene is driven by exogenously or endogenously controllable promoter, offers another modality. However, we hypothesize that regulatable gene therapy, dependent on the activity of endogenous factors, might be prone to limitations owing to the potential disturbance in the expression of endogenous genes. Here, we demonstrated some indications of these drawbacks. Therefore, the final acceptance of these promising strategies for clinical trials requires careful validation in animal experiments.     

Subcellular distribution of metallothionein and cadmium in the liver and kidneys of bank voles (Clethrionomys glareolus) exposed to dietary cadmium

Metallothionein (MT) and cadmium (Cd) contents were determined in the subcellular fractions of the liver and kidneys of bank voles exposed for 6 weeks to elevated levels of dietary Cd-40 and 80 g g^-1 dry weight. Hepatic and renal MT was detected exclusively in the cytosol, while Cd was found in the cytosol (73–79% of the total content), nuclei (14–18%) and particulates (4–9%). The concentration of MT in the cytosol as well as Cd content in the particular subcellular fractions appeared to be a dose-dependent. The absence of MT in the nuclear and particulate fractions implied that Cd present in these compartments was not bound to the protein that is considered to provide protection against the toxic metal. Therefore, it is assumed that this component of intracellular Cd could be responsible for the histopathological changes that occurred in the liver (granuloma and focal hepatocyte swelling) and kidneys (focal degeneration of proximal tubules) of bank voles exposed to the higher level of dietary Cd.     

On the peptide-antipeptide interactions in interleukin-1 receptor system

Interleukin-1 receptor antagonist (IL-1Ra) and vaccinia virus protein C10L share a VTXFYF motif, with X being Lys or Arg residue, respectively. Peptides of such sequence compete successfully with IL-1 for the cellular receptor. A pair of complementary peptides, based on the Siemion's hypothesis on the periodicity of the genetic code (QWLNIN and QWANIN), and another pair, in which, following the Root- Bernstein theory, Lys was used as complementary amino acid to Phe (QWLKIK and QWAKIK), were investigated for the peptide-antipeptide interactions using mass spectrometry (ESI-MS) and circular dichroism (CD) methods. The CD measurements indicated some conformational changes, more pronounced in the Siemion's pairs, however, no heterodimer formation was found by MS. In the region of IL-1 receptor situated close to the position of IL-1Ra in the IL-1Ra-receptor complex, a KQKL motif is present, suggesting a possibility of complementary recognition of the Root-Bernstein type in the IL-1 receptor. The biological activity of the complementary peptides is similar to that of the original ones. They efficiently compete with IL-1 and show moderate immunosuppressory activity in humoral and cellular immune response. The inhibition of the IL-1-IL-1 receptor interaction may result from the complementary peptides acting as mini-receptors with affinity for IL-1.     

A high-density admixture map for disease gene discovery in african americans

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.