Migration of antigen-specific T cells away from CXCR4-binding human immunodeficiency virus type 1 gp120

Cell-mediated immunity depends in part on appropriate migration and localization of cytotoxic T lymphocytes (CTL), a process regulated by chemokines and adhesion molecules. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode chemotactically active proteins, suggesting that dysregulation of immune cell trafficking may be a strategy for immune evasion. HIV-1 gp120, a retroviral envelope protein, has been shown to act as a T-cell chemoattractant via binding to the chemokine receptor and HIV-1 coreceptor CXCR4. We have previously shown that T cells move away from the chemokine stromal cell-derived factor 1 (SDF-1) in a concentration-dependent and CXCR4 receptor-mediated manner. Here, we demonstrate that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein. This migratory response is CD4 independent and inhibited by anti-CXCR4 antibodies and pertussis toxin. Additionally, the expression of X4 gp120 by target cells reduces CTL efficacy in an in vitro system designed to account for the effect of cell migration on the ability of CTL to kill their target cells. Recombinant X4 gp120 also significantly reduced antigen-specific T-cell infiltration at a site of antigen challenge in vivo. The repellant activity of HIV-1 gp120 on immune cells in vitro and in vivo was shown to be dependent on the V2 and V3 loops of HIV-1 gp120. These data suggest that the active movement of T cells away from CXCR4-binding HIV-1 gp120, which we previously termed fugetaxis, may provide a novel mechanism by which HIV-1 evades challenge by immune effector cells in vivo.     

Urban and rural differences in mortality and causes of death in historical Poland

The purpose of this paper is to document and interpret urban-rural differences in mortality in the past. To this end, we used data on mortality in Wielkopolska, Poland, in the 19th century and at the beginning of the 20th century. The data on mortality in rural areas (N = 1,173,910 deceased), small towns (N = 573,903 deceased), and Poznań, the capital of the Wielkopolska region (N = 86,352 deceased), were gathered from original Prussian statistical yearbooks (Preussische Statistik). Causes of death were also analyzed (rural areas, N = 449,576 deceased; small towns, N = 238,365 deceased; Poznań, N = 61,512 deceased). Mortality measures such as crude death rate (CDR), infant death rate (IDR), and neonatal and postneonatal death rates were calculated. Life tables were constructed for both stationary and stable population models and measures of the opportunity for natural selection calculated (Crow's index I(m), potential gross reproduction rate R(pot), and biological state index I(bs)). Relative frequencies of leading causes of death were computed. Stratification depending on the place of residence was evident in all mortality measures as well as in the values of the life tables and the measures of the opportunity for natural selection, but it was reverse of what is observed today in developed countries. In Poznań (a large industrial city), the mortality situation was the least favorable. It was caused by large population density, lack of water supply and sewage systems (up to 1896), and bad working conditions. The values of CDR ranged between 26.89-31.46, and IDR between 190.6-280.5. Newborn life expectancy (for a stable population model) was 31.6 years, I(m) = 0.79, R(pot) = 0.85, and I(bs) = 0.47. The most common causes of death were tuberculosis, other diseases of the respiratory and circulatory systems, dysentery and diarrhea, and cancer. These diseases were less common in rural areas, so they had the most favorable values of mortality measures (CDR between 22.87-27.32, IDR between 181.8-219.4, life expectancy of newborn e(0) = 42.12, I(m) = 0.55, R(pot) = 0.93, I(bs) = 0.60). Infectious diseases (other than tuberculosis), frailty at birth, and frailty in old age were the most frequent causes of death in rural areas. Small towns (population <20,000) had a mortality intermediate between city and rural areas.     

Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes

BACKGROUND: Skin injury leads to the release of heme, a potent prooxidant which is degraded by heme oxygenase-1 (HO-1) to carbon monoxide, iron, and biliverdin, subsequently reduced to bilirubin. Recently the involvement of HO-1 in angiogenesis has been shown; however, the role of heme and HO-1 in wound healing angiogenesis has not been yet investigated. RESULTS: Treatment of HaCaT keratinocytes with hemin (heme chloride) induced HO-1 expression and activity. The effect of heme on vascular endothelial growth factor (VEGF) synthesis is variable: induction is significant after a short, 6 h treatment with heme, while longer stimulation may attenuate its production. The involvement of HO-1 in VEGF synthesis was confirmed by inhibition of VEGF expression by SnPPIX, a blocker of HO activity and by attenuation of HO-1 mRNA expression with specific siRNA. Importantly, induction of HO-1 by hemin was able to overcome the inhibitory effect of high glucose on VEGF synthesis. Moreover, HO-1 expression was also induced in keratinocytes cultured in hypoxia, with concomitant augmentation of VEGF production, which was further potentiated by hemin stimulation. Accordingly, conditioned media from keratinocytes overexpressing HO-1 enhanced endothelial cell proliferation and augmented formation of capillaries in angiogenic assay in vitro. CONCLUSIONS: HO-1 is involved in hemin-induced VEGF expression in HaCaT and may play a role in hypoxic regulation of this protein. HO-1 overexpression may be beneficial in restoring the proper synthesis of VEGF disturbed in diabetic conditions.     

Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis

Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139-151 (PLP139-151) immunization. In contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other inflamed tissue did not modulate the expression of EAE. In animals in which EAE had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in response to PLP139-151 that correlated with elevated IFN-gamma and NO production. Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from untreated EAE mice, in addition to depletion experiments, showed that NK cells reduced reactivity to PLP139-151. Transfer of NK cells from Hsp70-pc-immunized mice to recipients sensitized for EAE abolished disease development. Thus, we propose that Hsp70 demonstrate the ability to bind to peptides generated during brain inflammation and to induce a regulatory NK cell population that is capable of preventing subsequent autoimmunization for EAE.     

Gene mapping of 28S and 5S rDNA sites in the spined loach Cobitis taenia (Pisces, Cobitidae) from a diploid population and a diploid–tetraploid population

We compare the chromosomal 28S and 5S rDNA patterns of the spined loach C. taenia (2n = 48) from an exclusively diploid population and from a diploid–polyploid population using 28S and 5S rDNA probe preparation and labelling, and fluorescence in situ hybridization (FISH). The 5S rDNA was located in two to three chromosome pairs, and separated from the 28S loci for the males and one female (F1) from the diploid population. Loaches from a diploid–polyploid population, and one female (F2) from the diploid population were characterized by at least one chromosome pair with 5S and 28S overlapping signals. The fishes differed mainly in their number of 28S rDNA loci, located on 3–6 chromosomes. All individuals from both populations were characterized by one acrocentric chromosome bearing a 28S rDNA signal on the telomeres of its long arm. The number of major ribosomal DNA in the karyotype of C. taenia by FISH was always higher than the number of Ag-NORs. Our data confirm the extensive polymorphism of NORs in both populations, as already has been observed in closely related Cobitis species, and less polymorphic 5S rDNA pattern. However, this preliminary result highlights the need for a wider scale study.     

Fluoxetine results in misleading conclusions on fish behavior

Fluoxetine is an antidepressant medicine causing relaxation and mood improvement in people, with silencing certain personality traits in some cases. The question arise if such phenomena can be observed in nontarget organisms such as fish. Fluoxetine affects fishes behavior; however, it is not known if the medicine affects its “personality.” This study aimed to evaluate the reaction of the invasive Neogobius fluviatilis and native Gobio gobio individuals to fluoxetine at environmental concentration of 360 ng/L. We prepared three variants of the experiments: (a) behavioral trials with unexposed fishes, (b) behavioral trials with the same fishes after 21 days of fluoxetine exposure, and (c) behavioral trials with the same fishes after 21‐day depuration period, that is, without fluoxetine. The fishes reaction time (RT), that is, difference in time spent on reaching food with and without the necessity of overcoming the obstacle, was analyzed. Additionally, the personality, bold or shy, traits of each fish individual, was assigned. The results indicated that environmental concentrations of the antidepressant influenced RT. The average RT of the fishes cultured with fluoxetine was by 7‐min shorter in comparison with the nonexposed control. Share of individuals exposed to fluoxetine assigned as bold raised to 71.4% in comparison with 46.4% in nonexposed control. This sheds new light on wild fishes behavior caught from freshwater. Environmental concentrations of the antidepressant influenced the time of fishes reaction and share individuals assigned as bold. Moreover, 21‐day recovery lasting might be not enough to get fluoxetine effect on fishes.     

Macrozoobenthos of two Antarctic glacial coves: a comparison with non-disturbed bottom areas

There are only few studies on shallow Antarctic benthic communities associated with habitats affected by intense mineral sedimentation inflow. The analysis of macrofaunal communities associated with two shallow, isolated glacial coves was performed in Admiralty Bay (King George Island) and compared with non-disturbed sites. Multivariate analyses (hierarchical classification, nMDS) clearly separated glacial cove communities (two assemblages) from the sites situated outside both basins (two assemblages). The community influenced by the streamflow of glacial discharge of meltwater situated in the area with sandy–clay–silt sediments had a very low species richness, diversity and abundance. It was dominated by eurytopic, motile deposit feeding polychaetes such as Mesospio moorei, Tharyx cincinnatus and Leitoscoloplos kerguelensis as well as the bivalve Yoldia eightsi. The second glacial community of the area located at a grater distance from the outlet of the stream was characterized by sandy–clay–silt and clay–silt deposits and showed also a low diversity and species richness. The most abundant here were peracarid crustaceans, with the dominant opportunistic feeder Cheirimedon femoratus. Community from the non-disturbed area with silty–clay–sand, and silty–sand sediments had higher species richness and diversity. The assemblage of fauna from the sandy bottom has values of those two indexes similar to those found in the disturbed areas.     

Analysis of mercury levels in historical bone material from syphilitic subjects--pilot studies (short report)

The aim of the present work is to study the remains of seven individuals with typical symptoms of tertiary syphilis in terms of mercury content in bones, thereby verifying whether they were subjected to treatment and, if they were, how long their organisms were exposed to toxic mercury fumes. Mercury was used, mainly in the Middle Ages and in the early modern period, as a preventive measure in case of individuals suffering from syphilis, a venereal disease, and also leprosy. Syphilitic patients treated this way should demonstrate increased concentration of mercury in their bones. The skeletons studied in the present work originate from various archaeological sites in southern and north-central Poland. The analyses concerned individuals with diagnosed syphilis as well as healthy individuals who constituted the control group. The analyses were performed by the LA-ICP-MS technique, with the use of laser Nd: YAG, Macro, 266 nm, New Wave, USA, coupled with Spectrometer Elan DRC-e Perkin Elmer, USA. The content analysis of the studied bone material revealed with high probability that the contact method of mercurial treatment was used only in the case of two women from north-central Poland, deceased at the turn of the 15th century at the earliest.