The benefits of interpopulation hybridization diminish with increasing divergence of small populations

Interpopulation hybridization can increase the viability of small populations suffering from inbreeding and genetic drift, but it can also result in outbreeding depression. The outcome of hybridization can depend on various factors, including the level of genetic divergence between the populations, and the number of source populations. Furthermore, the effects of hybridization can change between generations following the hybridization. We studied the effects of population divergence (low vs. high level of divergence) and the number of source populations (two vs. four source populations) on the viability of hybrid populations using experimental Drosophila littoralis populations. Population viability was measured for seven generations after hybridization as proportion of populations facing extinction and as per capita offspring production. Hybrid populations established at the low level of population divergence were more viable than the inbred source populations and had higher offspring production than the large control population. The positive effects of hybridization lasted for the seven generations. In contrast, at the high level of divergence, the viability of the hybrid populations was not significantly different from the inbred source populations, and offspring production in the hybrid populations was lower than in the large control population. The number of source populations did not have a significant effect at either low or high level of population divergence. The study shows that the benefits of interpopulation hybridization may decrease with increasing divergence of the populations, even when the populations share identical environmental conditions. We discuss the possible genetic mechanisms explaining the results and address the implications for conservation of populations.     

Distribution of histamine in the rat kidney during pregnancy and development

Summary An antiserum against conjugated histamine and two oligonucleotide probes that detect the mRNA encoding L-histidine decarboxylase (HDC) involved in histamine synthesis were used to study the appearance of histamine and its location in the kidneys of fetal, newborn and young postnatal rats and in the kidneys of pregnant rats. On embryonic days 16 and 18 (E16 and E18), some HA-immunoreactive (HA-ir) cells were found within the largest S-shaped bodies. Histamine was found to appear rapidly between the 18th and 20th embryonic days in the convoluted tubules of the kidneys. On postnatal day 0 (P0), the distal convoluted tubules and collecting ducts exhibited bright fluorescence, the intensity of which decreased quickly so that it was faint on day P4 and absent at later stages. In kidneys of pregnant rats HA-ir was found in the epithelium of both the Bowman's capsule, collecting ducts and in a few cells within the tubules. Nonuniform HA-ir was also detected within glomeruli. No evidence for the presence of L-histidine decarboxylase mRNA in kidneys of fetuses or pregnant rats was seen. It is concluded that distinct structures in the developing rat kidney contain histamine during a period around birth from day E20 to day P4. In the pregnant rat, the epithelium that is in direct contact with the urine flow is immunoreactive for histamine from day 16 to 20 of pregnancy. The results suggest that histamine is not synthesized locally in the kidneys but rather originates from other tissues.     

Risk factors and 25 year risk of coronary heart disease in a male population with a high incidence of the disease: the Finnish cohorts of the seven countries study.

OBJECTIVE--To assess the efficacy of high serum cholesterol concentration, raised blood pressure, and smoking as predictors of coronary heart disease. DESIGN--Prospective cohort study of middle aged men conducted over 25 years. SETTING--Finish components of an ongoing international study (seven countries study). PARTICIPANTS--1520 Men who at age 40-59 in 1959 were free of clinically evident heart disease. INTERVENTIONS--At each follow up visit a detailed medical examination including resting electrocardiography was performed, blood pressure and serum total cholesterol concentration were measured, and smoking was assessed. MEASUREMENTS AND MAIN RESULTS--825 Deaths (54% of participants) occurred during follow up, of which 335 were due to coronary heart disease. The hazard ratio for death from coronary heart disease with respect to risk factors at entry were: for serum cholesterol concentrations above 8.4 mmol/l v below 5.2 mmol/l, 2.68 (95% confidence interval 1.62 to 4.42); for systolic blood pressure in the highest quintile v that in the lowest quintile, 2.46 (1.72 to 3.50); and for smoking 10 or more cigarettes daily v never smoking, 1.95 (1.36 to 2.79). The hazard ratios with respect to cholesterol concentrations and blood pressure remained constant during follow up but the ratio with respect to smoking diminished, mainly owing to men giving up the habit. The estimated conditional probability of a 50 year old man dying of coronary heart disease in the next 25 years ranged from 12% among those with the most favourable risk factor profile to 75% among those with the least favourable profile. CONCLUSIONS--High risk factor levels (as determined in this study) in middle aged men may greatly increase the absolute probability of death from coronary heart disease when the period of study is relevant to the human life span.     

Changes in coronary risk factors during comprehensive five-year community programme to control cardiovascular diseases (North Karelia project).

A comprehensive community programme to control cardiovascular diseases (CVD) in North Karelia, Finland, was carried out during 1972-7. The central intermediate objective of the programme was to reduce the prevalence of smoking, the serum cholesterol concentration, and raised blood-pressure values among the population of the area. The effect was evaluated by examining independent representative population samples in 1972 and 1977 in both the county of North Karelia and a matched control county. Over 10 000 subjects were studied each time, the participation rate being around 90%. The decrease that occurred in the risk factors, especially in men, was in general greater in North Karelia compared with the control county. When a multiple logistic function was used for the three risk factors an overall mean net reduction of 17% among men and 12% among women was observed in the estimated risk for coronary heart disease in North Karelia. This community programme effectively reduced the levels of the three main risk factors for CVD in the population, and thus mortality and morbidity from CVD should fall. This is assessed in further studies.     

Selective binding of collagen subtypes by integrin alpha 1I, alpha 2I, and alpha 10I domains

Four integrins, namely alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and alpha(11)beta(1), form a special subclass of cell adhesion receptors. They are all collagen receptors, and they recognize their ligands with an inserted domain (I domain) in their alpha subunit. We have produced the human integrin alpha(10)I domain as a recombinant protein to reveal its ligand binding specificity. In general, alpha(10)I did recognize collagen types I-VI and laminin-1 in a Mg(2+)-dependent manner, whereas its binding to tenascin was only slightly better than to albumin. When alpha(10)I was tested together with the alpha(1)I and alpha(2)I domains, all three I domains seemed to have their own collagen binding preferences. The integrin alpha(2)I domain bound much better to fibrillar collagens (I-III) than to basement membrane type IV collagen or to beaded filament-forming type VI collagen. Integrin alpha(1)I had the opposite binding pattern. The integrin alpha(10)I domain was similar to the alpha(1)I domain in that it bound very well to collagen types IV and VI. Based on the previously published atomic structures of the alpha(1)I and alpha(2)I domains, we modeled the structure of the alpha(10)I domain. The comparison of the three I domains revealed similarities and differences that could potentially explain their functional differences. Mutations were introduced into the alphaI domains, and their binding to types I, IV, and VI collagen was tested. In the alpha(2)I domain, Asp-219 is one of the amino acids previously suggested to interact directly with type I collagen. The corresponding amino acid in both the alpha(1)I and alpha(10)I domains is oppositely charged (Arg-218). The mutation D219R in the alpha(2)I domain changed the ligand binding pattern to resemble that of the alpha(1)I and alpha(10)I domains and, vice versa, the R218D mutation in the alpha(1)I and alpha(10)I domains created an alpha(2)I domain-like ligand binding pattern. Thus, all three collagen receptors appear to differ in their ability to recognize distinct collagen subtypes. The relatively small structural differences on their collagen binding surfaces may explain the functional specifics.     

Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis

Cathepsin C activates serine proteases expressed in hematopoietic cells by cleaving an N-terminal dipeptide from the proenzyme upon granule packaging. The lymphocytes of cathepsin C-null mice are therefore proposed to totally lack granzyme B activity and perforin-dependent cytotoxicity. Surprisingly, we show, using live cell microscopy and other methodologies, that cells targeted by allogenic CD8(+) cytotoxic T lymphocyte (CTL) raised in cathepsin C-null mice die through perforin-dependent apoptosis indistinguishable from that induced by wild-type CTL. The cathepsin C-null CTL expressed reduced but still appreciable granzyme B activity, but minimal granzyme A activity. Also, in contrast to mice with inactivation of both their granzyme A/B genes, cathepsin C deficiency did not confer susceptibility to ectromelia virus infection in vivo. Overall, our results indicate that although cathepsin C clearly generates the majority of granzyme B activity, some is still generated in its absence, pointing to alternative mechanisms for granzyme B processing and activation. Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A/B deficiency.     

Hierarchical status and colour preference in Nile tilapia (<Emphasis Type="Italic">Oreochromis niloticus</Emphasis>)

We studied the colour preference of isolated Nile tilapia (Oreochromis niloticus) and whether previous residence or body size can affect environmental colour choice. In the first phase, a cylindrical tank was divided into five differently coloured compartments (yellow, blue, green, white and red), a single fish was introduced into the tank and the frequency at which this fish visited each compartment was recorded over a 2-day study period. An increasingly larger fish (approx +2 cm in length each time) was then added into the tank on each of days 3, 5 and 7 (=four fish in the tank by day 7), and the frequency at which each fish visited the different compartments of the tank was observed twice a day to obtain visit frequency data on the differently sized fishes. This experiment was replicated six times. In the first phase, the solitary fish established residence inside the yellow compartment on the first and second days. Following the introduction of a larger fish, the smaller fish was displaced from the occupied compartment. Nile tilapia possibly shows this preference for yellow as a function of its visual spectral sensitivity and/or the spectral characteristics of its natural environment. Moreover, body size is an important factor in determining hierarchical dominance and territorial defence, and dominant fish chose the preferred environmental colour compartment as their territory.     

Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a

Oxidatively modified low-density lipoproteins (Ox-LDL) and complement anaphylatoxins C3a and C5a are colocalized in atherosclerotic lesions. Anaphylatoxin C3a also binds and breaks bacterial lipid membranes and phosphatidylcholine liposomes. The role of oxidized lipid adducts in C3a binding to Ox-LDL and apoptotic cells was investigated. Recombinant human C3a bound specifically to low-density lipoprotein and bovine serum albumin modified with malondialdehyde (MDA) and malondialdehyde acetaldehyde (MAA) in chemiluminescence immunoassays. No binding was observed to native proteins, LDL oxidized with copper ions (CuOx-LDL), or phosphocholine. C3a binding to MAA-LDL was inhibited by two monoclonal antibodies specific for MAA-LDL. On agarose gel electrophoresis, C3a comigrated with MDA-LDL and MAA-LDL, but not with native LDL or CuOx-LDL. C3a bound to apoptotic cells in flow cytometry. C3a opsonized MAA-LDL and was taken up by J774A.1 macrophages in immunofluorescence analysis. Complement-activated human serum samples (n=30) showed increased C3a binding to MAA-LDL (P<0.001) and MDA-LDL (P<0.001) compared to nonactivated samples. The amount of C3a bound to MAA-LDL was associated with total complement activity, C3a desArg concentration, and IgG antibody levels to MAA-LDL. Proteins containing MDA adducts or MAA adducts may bind C3a in vivo and contribute to inflammatory processes involving activation of the complement system in atherosclerosis.     

Gamma-irradiated influenza virus uniquely induces IFN-I mediated lymphocyte activation independent of the TLR7/MyD88 pathway

Background

We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression of CD69 and CD86, but not CD25. This partial lymphocytes activation is mediated by type-I interferons (IFN-I). Importantly, we have shown that γ-irradiated SFV does not induce IFN-I and the associated lymphocyte activation.

Principal Findings

Here we report that, in contrast to SFV, γ-irradiated influenza A virus elicits partial lymphocyte activation in vivo. Furthermore, we show that when using influenza viruses inactivated by a variety of methods (UV, ionising radiation and formalin treatment), as well as commercially available influenza vaccines, only γ-irradiated influenza virus is able to trigger IFN-I-dependent partial lymphocyte activation in the absence of the TLR7/MyD88 signalling pathways.

Conclusions

Our data suggest an important mechanism for the recognition of γ-irradiated influenza vaccine by cytosolic receptors, which correspond with the ability of γ-irradiated influenza virus to induce cross-reactive and cross-protective cytotoxic T cell responses.