Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families

BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility. In Poland standard BRCA gene test is usually limited to Polish founder BRCA1 mutations: 5382insC, C61G and 4153delA. To date, just a few single large genomic rearrangements (LGRs) of BRCA1 gene have been reported in Poland. Here we report the first comprehensive analysis of large mutations in BRCA1 and BRCA2 genes in this country. We screened LGRs in BRCA1 and BRCA2 genes by multiplex ligation-dependent probe amplification in 200 unrelated patients with strong family history of breast/ovarian cancers and negative for BRCA1 Polish founder mutations. We identified three different LGRs in BRCA1 gene: exons 13-19 deletion, exon 17 deletion and exon 22 deletion. No LGR was detected in BRCA2 genes. Overall, large rearrangements accounted for 3.7 % of all BRCA1 mutation positive families in our population and 1.5 % in high-risk families negative for Polish founder mutation.     

Association of common WRAP 53 variant with ovarian cancer risk in the Polish population

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogensis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53–TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53–WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.     

Pelagic fish and zooplankton species assemblages in relation to water mass characteristics in the northern Bering and southeast Chukchi seas

This research explores the distributions and community composition of pelagic species in the sub-Arctic and Arctic waters of the northern Bering and central and southern Chukchi seas during September 2007 by linking pelagic zooplankton and fish assemblages to water masses. Juvenile saffron cod (Eleginus gracilis), polar cod (Boreogadus saida), and shorthorn sculpin (Myoxocephalus scorpius) were most abundant in warm, low salinity Alaska Coastal Water (ACW) of the central Chukchi Sea, characterized by low chlorophyll, low nutrients, and small zooplankton taxa. Adult Pacific herring (Clupea pallasii) were more abundant in the less stratified Bering Strait waters and in the colder, saltier Bering Shelf Water of the northern Bering and southern Chukchi seas, characterized by high chlorophyll, high nutrients, and larger zooplankton taxa. Juvenile pink (Oncorhynchus gorbuscha) and chum (O. keta) salmon were most abundant in the less stratified ACW in the central Chukchi Sea and Bering Strait. Abundances of large zooplankton were dominated by copepods (Eucalanus bungii, Calanus glacialis/marshallae, Metridia pacifica) followed by euphausiids (juvenile Thysanoessa raschii and unidentified taxa), whereas small zooplankton were dominated by bivalve larvae and copepods (Centropages abdominalis, Oithona similis, Pseudocalanus sp.). Pelagic community composition was related to environmental factors, with highest correlations between bottom salinity and large zooplankton taxa, and latitude and fish species. These data were collected in a year with strong northward retreat of summer sea ice and therefore provide a baseline for assessing the effects of future climate warming on pelagic ecosystems in sub-Arctic and Arctic regions.     

Ultrastructural and Biogeochemical Features of Microbiotic Soil Crusts and their Implications in a Semi-Arid Habitat

This investigation was designed to explore the relationships between lichen symbionts (phycobiont and mycobiont) and the substrate on which they grow by examining the chemical and ultrastructural features of the lichen-soil interface. These lichens form an integral part of microbiotic soil crusts. Fragments of three different lichen biotypes growing over gypsum crystals and marls were fixed and embedded in resin. The lichen-substratum interface was then examined by scanning electron microscopy with backscattered electron imaging. In situ observation, microanalytical (EDS), and FT-Raman plus infrared spectroscopy of the lichen-substratum interface indicated that different ultrastructural features of the mycobiont were related to biogeochemical processes and Ca 2+ distribution in the soil crust. Phycobionts were observed to make direct contact with the substratum and to be surrounded by a nondifferentiated thallus structure. These observations suggest that they can grow outside the thallus in the early stages of lichen development in the semi-arid conditions of their habitat. The particular ultrastructural features of the lichen thallus and of the lichen-substratum interface appear to have marked effects on runoff phenomena and ponding generation of the surface.     

Divergent requirements for fibroblast growth factor signaling in zebrafish maxillary barbel and caudal fin regeneration

The zebrafish maxillary barbel is an integumentary organ containing skin, glands, pigment cells, taste buds, nerves, and endothelial vessels. The maxillary barbel can regenerate (LeClair & Topczewski 2010); however, little is known about its molecular regulation. We have studied fibroblast growth factor (FGF) pathway molecules during barbel regeneration, comparing this system to a well‐known regenerating appendage, the zebrafish caudal fin. Multiple FGF ligands (fgf20a, fgf24), receptors (fgfr1‐4) and downstream targets (pea3, il17d) are expressed in normal and regenerating barbel tissue, confirming FGF activation. To test if specific FGF pathways were required for barbel regeneration, we performed simultaneous barbel and caudal fin amputations in two temperature‐dependent zebrafish lines. Zebrafish homozygous for a point mutation in fgf20a, a factor essential for caudal fin blastema formation, regrew maxillary barbels normally, indicating that the requirement for this ligand is appendage‐specific. Global overexpression of a dominant negative FGF receptor, Tg(hsp70l:dn‐fgfr1:EGFP)^pd1 completely blocked fin outgrowth but only partially inhibited barbel outgrowth, suggesting reduced requirements for FGFs in barbel tissue. Maxillary barbels expressing dn‐fgfr1 regenerated peripheral nerves, dermal connective tissue, endothelial tubes, and a glandular epithelium; in contrast to a recent report in which dn‐fgfr1 overexpression blocks pharyngeal taste bud formation in zebrafish larvae (Kapsimali et al. 2011), we observed robust formation of calretinin‐positive tastebuds. These are the first experiments to explore the molecular mechanisms of maxillary barbel regeneration. Our results suggest heterogeneous requirements for FGF signaling in the regeneration of different zebrafish appendages (caudal fin versus maxillary barbel) and taste buds of different embryonic origin (pharyngeal endoderm versus barbel ectoderm).     

Climate change impact on development rates of the codling moth (Cydia pomonella L.) in the Wielkopolska region, Poland

The main goal of this paper is to estimate how the observed and predicted climate changes may affect the development rates and emergence of the codling moth in the southern part of the Wielkopolska region in Poland. In order to simulate the future climate conditions one of the most frequently used A1B SRES scenarios and two different IPCC climate models (HadCM3 and GISS modelE) are considered. A daily weather generator (WGENK) was used to generate temperature values for present and future climate conditions (time horizons 2020–2040 and 2040–2060). Based on the generated data set, the degree-days values were then calculated and the emergence dates of the codling moth at key stages were estimated basing on the defined thresholds. Our analyses showed that the average air surface temperature in the Wielkopolska region may increase from 2.8°C (according to GISS modelE) even up to 3.3°C (HadCM3) in the period of 2040–2060. With the warming climate conditions the cumulated degree-days values may increase at a rate of about 142 DD per decade when the low temperature threshold (T _low ) of 0°C is considered and 91 DD per decade when T _low ?=?10°C. The key developmental stages of the codling moth may occur much earlier in the future climate conditions than currently, at a rate of about 3.8–6.8 days per decade, depending on the considered GCM model and the pest developmental stage. The fastest changes may be observed in the emergence dates of 95% of larvae of the second codling moth generation. This could increase the emergence probability of the pest third generation that has not currently occurred in Poland.     

One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic—Lasalocid acid

Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a–2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a–2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC₅₀: 3.2–7.3 μM), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell.     

PEG conjugates of potent α4 integrin inhibitors,maintaining sustained levels and bioactivity in vivo,following subcutaneous administration

Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO₂H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats.