Molecular genetics of Alzheimer's disease: presenilin 1 gene analysis in a cohort of patients from the Poznań region

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and personality changes. Pathological hallmarks of AD are: deposition of amyloid plaques and neurofibrillary tangles in the brain, accompanied by neuronal and synaptic loss. The genetic background of AD is heterogeneous and strongly depends on the form of the disease. In most of the families with early-onset AD (EOAD) (10% of the total population of patients), the disease segregates as an autosomal dominant fully penetrant trait. To date, some missense mutations in three genes encoding the amyloid precursor protein, presenilin 1 (PS1) and 2 (PS2) have been found to cause familial EOAD. We screened for mutations in the presenilin genes in a sample of 55 patients with familial or sporadic form of EOAD from the Poznan region. We found 4 missense mutations in the PS1 gene: A246E in exon 7, P267L in exon 8, E318G in exon 9, and L424R in exon 12 among 5 unrelated patients. The frequency of PS1 mutations was 11% (5 of 55) in the whole sample of the patients with EOAD or 50% (3 of 6) if the analysis was restricted to familial cases with a positive history of dementia in the patient's family.     

Trends in atmospheric concentrations of weed pollen in the context of recent climate warming in Poznań (Western Poland)

A significant increase in summer temperatures has been observed for the period 1996–2011 in Poznań, Poland. The phenological response of four weed taxa, widely represented by anemophilous species (Artemisia spp., Rumex spp. and Poaceae and Urticaceae species) to this recent climate warming has been analysed in Poznań by examining the variations in the course of airborne pollen seasons. Pollen data were collected by 7-day Hirst-type volumetric trap. Trends in pollen seasons were determined using Mann–Kendall test and Sen’s slope estimator, whereas the relationships between meteorological and aerobiological data were established by Spearman’s rank correlation coefficient. Significant trends in pollen data were detected. The duration of pollen seasons of all analysed taxa increased (from +2.0 days/year for Urticaceae to +3.8 days/year for Rumex), which can be attributed to a delay in pollen season end dates rather than earlier start dates. In addition, the intensity of Artemisia pollen seasons significantly decreased and correlates with mean July–September daily minimum temperatures (r?=??0.644, p?Rumex pollen seasons. The results of this study show that observed shifts in weed pollen seasons in Poznań, i.e. longer duration and later end dates, might be caused by the recorded increase in summer temperature. This influence was the strongest in relation to Artemisia, which is the taxon that flowers latest in the year. The general lack of significant correlations between Rumex and Urticaceae pollen seasons and spring and/or summer temperature suggests that other factors, e.g. land use practices, could also be partially responsible for the observed shifts in pollen seasons.     

Variability of Mercury Concentrations in Soil and Leaves of Acer plantanoides and Tilia platyphyllos in Poznań City,Poland

The paper presents the results of research on mercury in the soil and leaves of maple (Acer plantanoides) and linden (Tilia platyphyllos) collected in the four districts of the city of Poznań (Poland), which differ in terms of anthropogenic pressure. The average concentration of mercury in soil was 132 μg kg^?1. The highest concentration of mercury was determined in Tilia platyphyllos (233 μg kg^?1), whereas in Acer plantanoides it amounted to 207 μg kg^?1. Based on the study, it was found that the highest concentration of mercury in the investigated leaf species was observed in the samples collected in the districts of Grunwald, Je?yce, and Old Town. The lowest concentration was observed in the samples collected in the district of New Town. The comparison of the obtained results of mercury concentration in soil and leaf samples was made in terms of anthropogenic pressure in the investigated areas and depending on the studied leaf species. Based on the statistical analysis, it was found that there is no statistically significant relationship between mercury concentration in both studied species of trees. There was, however, a relationship between the mercury concentration in leaves and soil.     

Variation in pollen concentration of the mostallergenic taxa in Poznań (Poland), 1995–1996

The airborne pollen concentration of the four mostfrequent and most allergenic taxa in Poland; Alnus, Betula, Poaceae, and Artemisia atPozna in the years 1995–1996 has been analyzed,using a Hirst-type volumetric spore trap. Theappearance of the earliest pollen producing taxa wasobserved as early as January and February, which isrelevant information for people subject to allergiesin the Pozna region, where Spring usually beginsin March. The periods of high and very high pollenconcentration of individual taxa have been comparedfor the two years.     

Urban rotifers: structure and densities of rotifer communities in water bodies of the Poznań agglomeration area (western Poland)

The rotifer fauna of 19 mostly small water bodies (natural and artificial ponds, clay-pits and pools) in Pozna was studied on four occasions during 1996–98 to determine the suitability of urban areas for rotifer habitats. Rotifers were present in all the water bodies studied, with 114 species in 39 genera found, representing ca. 25% of all rotifers recorded from Poland. Mean diversity was 10 spp (range 1–36). Most common were: Brachionus angularis and Keratella cochlearis (spring), Colurella uncinata, Lecane closterocercaand Lepadella patella (summer) and L. closterocerca and K. cochlearis (autumn). Rotifer densities (1-1503 ind l^–1), Shannon's diversity (H 0.00-3.71) and dominant species differed in different water-bodies. The index of percentage similarity of community showed strong differences in qualitative structure of rotifer assemblages. The different types of water habitats, both the existing or the newly created in towns, may explain the relatively high diversity of rotifer communities observed in the urban areas studied.     

Extensive sequence variation in the 3′ untranslated region of the KRAS gene in lung and ovarian cancer cases

While cancer is a serious health issue, there are very few genetic biomarkers that predict predisposition, prognosis, diagnosis, and treatment response. Recently, sequence variations that disrupt microRNA (miRNA)-mediated regulation of genes have been shown to be associated with many human diseases, including cancer. In an early example, a variant at one particular single nucleotide polymorphism (SNP) in a let-7 miRNA complementary site in the 3′ untranslated region (3′ UTR) of the KRAS gene was associated with risk and outcome of various cancers. The KRAS oncogene is an important regulator of cellular proliferation, and is frequently mutated in cancers. To discover additional sequence variants in the 3′ UTR of KRAS with the potential as genetic biomarkers, we resequenced the complete region of the 3′ UTR of KRAS in multiple non-small cell lung cancer and epithelial ovarian cancer cases either by Sanger sequencing or capture enrichment followed by high-throughput sequencing. Here we report a comprehensive list of sequence variations identified in cases, with some potentially dysregulating expression of KRAS by altering putative miRNA complementary sites. Notably, rs712, rs9266, and one novel variant may have a functional role in regulation of KRAS by disrupting complementary sites of various miRNAs, including let-7 and miR-181.     

Variations and trends of birch pollen seasons during 15 years (1996–2010) in relation to weather conditions in Poznań (western Poland)

Birch (Betula) pollen seasons were examined in relation to meteorological conditions in Poznań (1996–2010). Birch pollen grains were collected using a volumetric spore trap. An alternate biennial cycle of birch pollen season intensity was noticed in Poznań. The main factors influencing birch pollen season intensity were average daily minimum temperatures during the second fortnight of May and the month of June one year before pollination as well as the intensity of the pollen season of the previous year. Most of the pollen grains are recorded during the first week of the season; the number of pollen grains recorded at this time is positively correlated with mean maximum temperature and negatively correlated with daily rainfall. The significant effect of rainfall in reducing the season pollen index was noticed only during weak pollen seasons (season pollen index <?mean). In addition, mean daily maximum temperature during the first two weeks of the birch pollen season markedly influences its duration. No significant trends in duration and intensity of the pollen season were recorded, however, a slight tendency towards early pollination was observed (?0.4 days/year, p?=?0.310).     

Flowering phenology and potential pollen emission of three <Emphasis Type="Italic">Artemisia</Emphasis> species in relation to airborne pollen data in Poznań (Western Poland)

Artemisia pollen is an important allergen in Europe. In Poznań (Western Poland), three Artemisia species, A. vulgaris, A. campestris and A. absinthium, are widely distributed. However, the contributions of these species to the total airborne pollen are unknown. The aim of the study was to determine the flowering phenology and pollen production of the three abovementioned species and to construct a model of potential Artemisia pollen emission in the study area. Phenological observations were conducted in 2012 at six sites in Poznań using a BBCH phenological scale. Pollen production was estimated by counting the pollen grains per flower and recalculating the totals per inflorescence, plant and population in the study area. Airborne pollen concentrations were obtained using a Hirst-type volumetric trap located in the study area. Artemisia vulgaris began to flower the earliest, followed by A. absinthium and then A. campestris. The flowering of A. vulgaris corresponded to the first peak in the airborne pollen level, and the flowering of A. campestris coincided with the second pollen peak. The highest amounts of pollen per single plant were produced by A. vulgaris and A. absinthium. A. campestris produced considerably less pollen, however, due to its common occurrence, it contributed markedly (30 %) to the summation of total of recorded pollen. A. vulgaris is the most important pollen source in Poznań, but the roles of two other Artemisia species cannot be ignored. In particular, A. campestris should be considered as an important pollen contributor and likely might be one of the main causes of allergic reactions during late summer.     

Strand symmetry of mutation rates in theβ-globin region

Summary It has been suggested that there may be inequalities in the types of substitution on the two DNA strands (in particular, in the frequencies of transversions from R to Y and from Y to R) due to a higher error rate on the lagging than the leading strand during replication. Reexamination of 11 kb of the -globin region sequenced in six primates fails to confirm this suggestion. Examination of the 73-kb -globin region sequenced in humans shows that the frequency of pyrimidines in different parts of this region is more variable than expected in a random sequence, but the pattern is more consistent with nonrandomness generated by DNA turnover mechanisms than with strand asymmetry due to a higher error rate on the lagging strand.     

Automated region of interest analysis of dynamic Ca²⁺ signals in image sequences

Ca(2+) signals are commonly measured using fluorescent Ca(2+) indicators and microscopy techniques, but manual analysis of Ca(2+) measurements is time consuming and subject to bias. Automated region of interest (ROI) detection algorithms have been employed for identification of Ca(2+) signals in one-dimensional line scan images, but currently there is no process to integrate acquisition and analysis of ROIs within two-dimensional time lapse image sequences. Therefore we devised a novel algorithm for rapid ROI identification and measurement based on the analysis of best-fit ellipses assigned to signals within noise-filtered image sequences. This algorithm was implemented as a plugin for ImageJ software (National Institutes of Health, Bethesda, MD). We evaluated the ability of our algorithm to detect synthetic Gaussian signal pulses embedded in background noise. The algorithm placed ROIs very near to the center of a range of signal pulses, resulting in mean signal amplitude measurements of 99.06 ± 4.11% of true amplitude values. As a practical application, we evaluated both agonist-induced Ca(2+) responses in cultured endothelial cell monolayers, and subtle basal endothelial Ca(2+) dynamics in opened artery preparations. Our algorithm enabled comprehensive measurement of individual and localized cellular responses within cultured cell monolayers. It also accurately identified characteristic Ca(2+) transients, or Ca(2+) pulsars, within the endothelium of intact mouse mesenteric arteries and revealed the distribution of this basal Ca(2+) signal modality to be non-Gaussian with respect to amplitude, duration, and spatial spread. We propose that large-scale statistical evaluations made possible by our algorithm will lead to a more efficient and complete characterization of physiologic Ca(2+)-dependent signaling.     

Six authors in search of a citation: villains or victims of the Vancouver convention?

OBJECTIVES--To analyse trends in the number of authors per article over the past 10 years. DESIGN--Analysis of articles from random volumes of eight biomedical journals. SUBJECTS--Cell, Nature, Proceedings of the National Academy of Sciences USA (PNAS), Journal of Clinical Investigation (JCI), Biochemical and Biophysical Research Communications (BBRC), Journal of Clinical Oncology (JCO), New England Journal of Medicine (NEJM), Lancet. MAIN OUTCOME MEASURES--Median and modal numbers of authors. RESULTS--All journals except Cell and Nature showed a trend towards increasing authorship numbers over the study period. The trend was most noticeable in journals such as JCO which feature clinical research. General medical journals (Lancet, NEJM) with a median of six to seven authors per article published far fewer seven author than six author studies, which suggests that author number may be influenced by the Vancouver convention which precludes citation of more than six authors. CONCLUSIONS--The phenomenon of expanding authorship in biomedical journal articles is not explained by the hypothesis that newer research technologies have necessitated more extensive collaboration. Rather, the data suggest that conferral of authorship may sometimes have a volitional component which contributes to rising author numbers. It is proposed that replacement of the Vancouver convention with a "first author, last author" citation system may help stem this rise in author numbers.     

Sequence Variation in the Gpl20 region of SHIV-CN97001 during in vivo Passage

SHIV-CN97001 played an important role in assessing the immune effect and strategy of the AIDS vaccine which included genes of the predominant prevalent HIV-1 strain in China. In this study, SHIV-CN97001 was in vivo passaged serially to construct pathogenic SHIV-CN97001/rhesus macaques model. To identify variation in the gp120 region of SHIV-CN97001 during passage, the fragments of gp120 gene were amplified by RT-PCR from the plasma of SHIV-CN97001 infected animals at the peak viral load time point and the gene distances （divergence, diversity） were calculated using DISTANCE. The analysis revealed that the genetic distances of SHIV-CN97001 in the third passage animals were the highest during in vivo passage. It had a relationship between viral divergence from the founder strain and viral replication ability. The nucleic acid sequence of the V3 region was highly conservative. All of the SHIV-CN97001 strains had V3 loop central motif （GPGQ） and were predicted to be using CCR5 co-receptor on the basis of the critical amino acids within V3 loop. These results show that there was no significant increase in the genetic distance during serial passage, and SHIV-CN97001 gp120 gene evolved toward ancestral states upon transmission to a new host. This could partly explain why there was no pathogenic viral strain obtained during in vivo passage.     

Frequent loss of heterozygosity in the β2-microglobulin region of chromosome 15 in primary human tumors

Downregulation or total loss of HLA class I expression on tumor cells is known as a mechanism of cancer immune escape. Alterations of the HLA phenotype are frequently due to mutations affecting genes encoding the HLA class I heavy chains located on chromosome 6p21 or the β2-microglobulin (β2m) gene encoding the light chain of the HLA complex located on chromosome 15q21. Frequently irreversible total loss of HLA class I molecules is due to the coincidence of two molecular events, the mutation of one β2m gene and the loss of the second copy. The latter is detectable as loss of heterozygosity (LOH) of microsatellite markers in the β2m region on chromosome 15q21 (LOH-15q21). Thus, LOH-15q21 might be an important event in the processes of HLA class I downregulation and total loss. Here we studied the frequency of LOH-15q21 in tumor tissues of different entities. By determining the status of heterozygosity of two microsatellite markers we detected LOH-15q21 in 44% of bladder carcinomas (n = 69), in 35% of colon carcinomas (n = 95), in 16% of melanomas (n = 70) but only in 7% of renal cancers (n = 45). Moreover, we observed a frequent coincidence of LOH-15q21 and LOH-6p21 in colorectal carcinoma, bladder carcinoma and melanoma, but not for renal carcinoma. We believe that the high incidence of LOH-15q21 in some malignancies and especially the coincidence of LOH-15q21 and LOH-6p21 might have a strong impact on tumor immunogenicity and on the efficiency of cancer immunotherapy.     

Absorption of DNA in the region of vacuum-uv (3–25 eV)

By means of a device that might be considered a modern version of "Ulbricht's sphere" the absorption spectrum and the photoelectric emission of calf thymus DNA was measured in the region of 3 to 25 eV (400 to 50 nm). A tentative explanation of the general shape of the absorption spectrum and of its 6 maxima is given. The results permit a much better insight into some biologic effects of vacuum-uv to be gained than hitherto possible.