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31.
Natalie Saini Yu Zhang Yuri Nishida Ziwei Sheng Shilpa Choudhury Piotr Mieczkowski Kirill S. Lobachev 《PLoS genetics》2013,9(6)
DNA sequences capable of adopting non-canonical secondary structures have been associated with gross-chromosomal rearrangements in humans and model organisms. Previously, we have shown that long inverted repeats that form hairpin and cruciform structures and triplex-forming GAA/TTC repeats induce the formation of double-strand breaks which trigger genome instability in yeast. In this study, we demonstrate that breakage at both inverted repeats and GAA/TTC repeats is augmented by defects in DNA replication. Increased fragility is associated with increased mutation levels in the reporter genes located as far as 8 kb from both sides of the repeats. The increase in mutations was dependent on the presence of inverted or GAA/TTC repeats and activity of the translesion polymerase Polζ. Mutagenesis induced by inverted repeats also required Sae2 which opens hairpin-capped breaks and initiates end resection. The amount of breakage at the repeats is an important determinant of mutations as a perfect palindromic sequence with inherently increased fragility was also found to elevate mutation rates even in replication-proficient strains. We hypothesize that the underlying mechanism for mutagenesis induced by fragile motifs involves the formation of long single-stranded regions in the broken chromosome, invasion of the undamaged sister chromatid for repair, and faulty DNA synthesis employing Polζ. These data demonstrate that repeat-mediated breaks pose a dual threat to eukaryotic genome integrity by inducing chromosomal aberrations as well as mutations in flanking genes. 相似文献
32.
Piotr Sorokowski Agnieszka Sorokowska Dariusz P. Danel 《Economics & Human Biology》2013,11(3):382-390
Many studies have investigated how different variables influence the reproductive success (RS) in the populations of natural birth control. Here, we tested hypotheses about positive relationship between wealth, height and several measures of RS in an indigenous, traditional society from West Papua. The study was conducted among the Yali tribe in a few small, isolated mountain villages. In this tribe, a man's wealth is measured by the number of pigs he possesses. We found that wealth was related to fertility and number of living children, but not to child mortality in both men and women. Additionally, child mortality increased with the number of children in a family. Finally, we did not observe any relationship between height and reproductive success measures or wealth. We provide several possible explanations of our results and also put forward hypothetical background for further studies of indigenous populations. 相似文献
33.
Andrzej Matyja Krzysztof Gil Artur Pasternak Krystyna Sztefko Mariusz Gajda Krzysztof A. Tomaszewski Maciej Matyja Jerzy A. Walocha Jan Kulig Piotr Thor 《Journal of cellular and molecular medicine》2013,17(6):734-742
The major mechanisms of gallstone formation include biliary cholesterol hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a key event that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. Telocytes, a new type of interstitial cells, have been recently identified in many organs, including gallbladder. Considering telocyte functions, it is presumed that these cells might be involved in the signalling processes. The purpose of this study was to correlate the quantity of telocytes in the gallbladder with the lithogenicity of bile. Gallbladder specimens were collected from 24 patients who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control group consisted of 25 consecutive patients who received elective treatment for pancreatic head tumours. Telocytes were visualized in paraffin sections of gallbladders with double immunofluorescence using primary antibodies against c‐Kit (anti‐CD117) and anti‐mast cell tryptase. Cholesterol, phospholipid and bile acid levels were measured in gallbladder bile. The number of telocytes in the gallbladder wall was significantly lower in the study group than that in the control group (3.03 ± 1.43 versus 6.34 ± 1.66 cell/field of view in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. The results suggest that bile composition may play an important role in the reduction in telocytes density in the gallbladder. 相似文献
34.
Piotr Wysoczanski Robert J. Mart E. Joel Loveridge Christopher Williams Sara B.-M. Whittaker Matthew P. Crump Rudolf K. Allemann 《Biomolecular NMR assignments》2013,7(2):187-191
Here we report the 1H, 13C and 15N resonance assignments of free Bcl-xL and of Bcl-xL in complex with an azobenzene-modified peptide derived from the BH3 domain of the pro-apoptotic Bak. The spectra suggest predominantly folded proteins; chemical shift difference analysis provides a detailed view of the reorganization occurring on peptide binding. 相似文献
35.
Izabela Chojnicka Krzysztof Gajos Katarzyna Strawa Gra?yna Broda Sylwia Fudalej Marcin Fudalej Piotr Stawiński Aleksandra Pawlak Pawe? Krajewski Marcin Wojnar Rafa? P?oski 《PloS one》2013,8(2)
Background
rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.Methods
We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.Results
We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR = 1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).Conclusions
In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol. 相似文献36.
Piotr Bursztyka Dominique Saffray Céline Lafont-Lecuelle Antoine Brin Patrick Pageat 《PloS one》2013,8(11)
Evidence that terrestrial gastropods are able to detect chemical cues from their predators is obvious yet scarce, despite the scientific relevance of the topic to enhancing our knowledge in this area. This study examines the influence of cuticular extracts from predacious ground beetles (Carabus auratus, Carabus hispanus, Carabus nemoralis and Carabus coriaceus), and a neutral insect species (Musca domestica) on the shelter-seeking behavior of naive slugs (Deroceras reticulatum). Slugs, known to have a negative phototactic response, were exposed to light, prompting them to make a choice between either a shelter treated with a cuticular extract or a control shelter treated with pure ethyl alcohol. Their behavioral responses were recorded for one hour in order to determine their first shelter choice, their final position, and to compare the percentage of time spent in the control shelters with the time spent in the treated shelters.The test proved to be very effective: slugs spent most of the experiment in a shelter. They spent significantly more time in the control shelter than in the shelter treated with either C. nemoralis (Z = 2.43; p = 0.0151; Wilcoxon matched-pairs signed-ranks test) or C. coriaceus cuticular extracts (Z = 3.31; p<0.01; Wilcoxon matched-pairs signed-ranks test), with a seemingly stronger avoidance effect when presented with C. coriaceus extracts. The other cuticular extracts had no significant effect on any of the behavioral items measured. Although it cannot be entirely excluded that the differences observed, are partly due to the intrinsic properties of the vehicle employed to build the cuticular extracts, the results suggest that slugs can innately discriminate amongst different potential predators and adjust their behavioral response according to the relevance of the threat conveyed by their predator’s chemical cues. 相似文献
37.
Dorota Dziadkowiec Karol Kramarz Karolina Kanik Piotr Wi?niewski Antony M. Carr 《Nucleic acids research》2013,41(17):8196-8209
Previously we identified Rrp1 and Rrp2 as two proteins required for the Sfr1/Swi5-dependent branch of homologous recombination (HR) in Schizosaccharomyces pombe. Here we use a yeast two-hybrid approach to demonstrate that Rrp1 and Rrp2 can interact with each other and with Swi5, an HR mediator protein. Rrp1 and Rrp2 form co-localizing methyl methanesulphonate–induced foci in nuclei, further suggesting they function as a complex. To place the Rrp1/2 proteins more accurately within HR sub-pathways, we carried out extensive epistasis analysis between mutants defining Rrp1/2, Rad51 (recombinase), Swi5 and Rad57 (HR-mediators) plus the anti-recombinogenic helicases Srs2 and Rqh1. We confirm that Rrp1 and Rrp2 act together with Srs2 and Swi5 and independently of Rad57 and show that Rqh1 also acts independently of Rrp1/2. Mutants devoid of Srs2 are characterized by elevated recombination frequency with a concomitant increase in the percentage of conversion-type recombinants. Strains devoid of Rrp1 or Rrp2 did not show a change in HR frequency, but the number of conversion-type recombinants was increased, suggesting a possible function for Rrp1/2 with Srs2 in counteracting Rad51 activity. Our data allow us to propose a model placing Rrp1 and Rrp2 functioning together with Swi5 and Srs2 in a synthesis-dependent strand annealing HR repair pathway. 相似文献
38.
Attachment of Brachyspira hyodysenteriae to intestinal epithelial cell lines and its possible mediation by outer membrane proteins (OMPs) of the spirochete were examined. Different B. hyodysenteriae serotypes were shown to adhere to rat and swine intestinal epithelial cells (IEC-18 and IPEC-J2) in vitro but not to the human rectal tumor cell line (HRT-18). Adherence of strain B204 to IPEC-J2 cells was reduced by rOMP-specific antisera in amounts of 29 % (anti-rBhlp29.7), 59 % (anti-rBhlp16), 70 % (anti-rBhmp39h), and 74 % (anti-rBhmp39h), respectively. By use of pooled antisera against Bhlp16 and Bhmp39f inhibition rates of the other serotypes ranged from 53 to 91 %. In a western blot assay OMPs of all serotypes but one were detected by the respective rOMP antisera. Altogether the results indicated that OMPs of B. hyodysenteriae displayed a serotype overlapping antigenicity and mediated adherence of the spirochetes to animal cell cultures. 相似文献
39.
Ole J Hamming Ewa Terczyńska‐Dyla Gabrielle Vieyres Ronald Dijkman Sanne E Jørgensen Hashaam Akhtar Piotr Siupka Thomas Pietschmann Volker Thiel Rune Hartmann 《The EMBO journal》2013,32(23):3055-3065
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL‐10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N‐linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection. 相似文献
40.
Magdalena K?dzierska Rafa? G?owacki Urszula Czernek Katarzyna Szyd?owska-Pazera Piotr Potemski Janusz Piekarski Arkadiusz Jeziorski Beata Olas 《Molecular and cellular biochemistry》2013,372(1-2):47-55
Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox?) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment. 相似文献