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61.
Yuko Haida Shigaku Ikeda Atsushi Takagi Etsuko Komiyama Tomotaka Mabuchi Akira Ozawa Jerzy K. Kulski Hidetoshi Inoko Akira Oka 《Immunogenetics》2013,65(7):553-557
Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease involving hair loss, but its pathogenesis remains poorly understood. Many autoimmune diseases are genetically associated with alleles of the human leukocyte antigen (HLA) genes within the major histocompatibility complex. Associations between AA and HLA genes were previously observed in some different ethnic groups. However, the results were inconsistent, and a primary susceptibility HLA gene and/or region has not yet been assigned for AA. The aim of this study was to evaluate whether an allele of the HLA-C locus, HLA-C*07:04, which was strongly associated with AA in Chinese Hans, could be replicated in the Japanese population. The HLA-C locus was genotyped by the SSO method using 156 AA patients and 560 healthy controls. As a consequence, among the 17 alleles detected, only two alleles, C*04:01 (OR?=?2.25, CI 95 %?=?1.35–3.75, P?=?1.84E-03) and C*15:02 (OR?=?2.52, CI 95 %?=?1.37–4.64, P?=?2.90E-03), were significantly associated with AA after Bonferroni correction. Further, the stratification analysis suggested that C*04:01, C*07:02, and C*15:02 represented different AA genetic risk factors in each sub-phenotype. 相似文献
62.
Sławomir Wąsik Michał Arabski Zuzanna Drulis-Kawa Jerzy Gubernator 《European biophysics journal : EBJ》2013,42(7):549-558
The paper presents experimental investigations of diffusion of antibiotics (ciprofloxacin or ampicillin) into the water phase from mixtures of neutral or negatively charged liposomes, and antibiotic–liposome interactions. Using the laser interferometry technique, the amounts and fluxes of released antibiotics, concentration field evolution, and the velocity of the concentration boundary layer’s “growth” were determined. To avoid the limitations of membranes, a measurement system without the artificial boundary of phases with a free water–solution interface has been proposed. It was found that the diffusion of anionic and neutral liposomes into the water phase was insignificant and mainly the diffusion of antibiotics was measured. Differences in the diffusion kinetics of ciprofloxacin and ampicillin from liposomal solutions to the water phase were observed. Ampicillin diffused more efficiently than ciprofloxacin regardless of the liposomal solution type. Moreover, the amount of ampicillin and ciprofloxacin released from the anionic liposomal phase was higher than that from the neutral one. Our results confirm that ciprofloxacin at neutral pH shows little tendency to bind neutral liposomes. Additionally, it was also observed that ciprofloxacin disrupts negatively charged liposomes as a final effect of antibiotic–lipid interactions. 相似文献
63.
Ewa Kosior-Jarecka Urszula ?ukasik Dominika Wróbel-Dudzińska Janusz Kocki Joanna Bartosińska Agnieszka Witczak Gra?yna Chodorowska Jerzy Mosiewicz Tomasz ?arnowski 《PloS one》2016,11(1)
Aim
The purpose of this study was to evaluate the influence of polymorphisms of the eNOS gene on the clinical status of patients with normal and high tension glaucoma.Methods
266 Polish Caucasian patients with primary open angle glaucoma were studied. Of the 266, 156 had normal tension glaucoma (NTG) and 110 high tension glaucoma (HTG). DNA material was isolated from peripheral venous blood using commercial kits. Real-time PCR reaction was used to amplify the promoter site of the endothelial nitric oxide synthase (eNOS) gene, including the single nucleotide polymorphism (SNP) site T-786C and part of the 7th exon of eNOS, including G894T SNP. Genotypes were determined with TaqMan SNP Genotyping Assays.Results
There were no significant differences in frequencies of the allelic variants of both polymorphisms. In G894T SNP, however, the wild GG form was more common in the HTG group. The SNP of the eNOS gene did not significantly influence the progression rate in either of the groups studied. There were no differences in variants of the eNOS gene regarding the necessity for and success of surgery and the progression of the disease. In the NTG group, no statistical correlation was observed between G894T, T786C polymorphism variants, and risk factors such as optic disc haemorrhages, optic disc notches, and peripapillary atrophy. Mean diastolic and systolic pressure during the day and night were lowest in NTG patients with the CC variant of the T786C polymorphism. No statistical correlation was observed between the G894T and T786C polymorphisms and capillaroscopic examination results.Conclusions
Genotype frequencies are similar for both the eNOS G894T and T-786C polymorphisms in NTG and HTG patients. These polymorphisms do not correlate with risk factors and do not influence the state of the capillary system in NTG patients. Systolic blood pressure is lower in NTG patients with mutated alleles of both polymorphisms. 相似文献64.
Jan Jankowski Magdalena Kubińska Jerzy Juśkiewicz Anna Czech 《Archives of animal nutrition》2016,70(2):127-140
A total of 490 eight-week-old female Hybrid Converter turkeys (body weight 4.11 ± 0.03 kg) were divided into 5 groups with 7 replicates of 14 birds each. For 8 weeks, basal diets were supplemented with methionine (Met) at following levels (weeks 9–12/weeks 13–16 of age): Group 1 – 0.34/0.29%, Group 2 – 0.39/0.34%, Groups 3 and 4 – 0.45/0.38% and 0.51/0.41%, respectively, Group 5 – 0.58/0.47%. Only in the first feeding phase the body weight gain (BWG) was affected by Met levels with the significantly highest BWG in Group 3. No treatment effects were found for feed conversion ratio, carcass yield, carcass composition and meat colour. The blood superoxide dismutase activity was significantly highest in Groups 2 and 3. The concentrations of reduced glutathione in the liver were linearly increased (p = 0.018), whereas the ratio of reduced glutathione to oxidised glutathione was highest in Group 3 (quadratic contrast, p = 0.004). It can be concluded that turkeys from Group 3 (Met levels age depending 15% and 10% above recommendations by NRC) were characterised by a well-balanced physiological response. Attention should be paid to the immune response of birds to higher dietary Met levels: plasma IgA concentrations decreased, whereas IL-6 and TNF-α levels increased in turkeys fed diets with the highest Met content. 相似文献
65.
Diverse mechanisms of metaeffector activity in an intracellular bacterial pathogen,Legionella pneumophila
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Peter J Stogios Mariya Morar Chitong Rao Rosa Di Leo Elena Evdokimova Mandy Lam Christina Oatway Marianne E Cuff Jerzy Osipiuk Karolina Michalska Boguslaw P Nocek Mikko Taipale Alexei Savchenko Alexander W Ensminger 《Molecular systems biology》2016,12(12)
Pathogens deliver complex arsenals of translocated effector proteins to host cells during infection, but the extent to which these proteins are regulated once inside the eukaryotic cell remains poorly defined. Among all bacterial pathogens, Legionella pneumophila maintains the largest known set of translocated substrates, delivering over 300 proteins to the host cell via its Type IVB, Icm/Dot translocation system. Backed by a few notable examples of effector–effector regulation in L. pneumophila, we sought to define the extent of this phenomenon through a systematic analysis of effector–effector functional interaction. We used Saccharomyces cerevisiae, an established proxy for the eukaryotic host, to query > 108,000 pairwise genetic interactions between two compatible expression libraries of ~330 L. pneumophila‐translocated substrates. While capturing all known examples of effector–effector suppression, we identify fourteen novel translocated substrates that suppress the activity of other bacterial effectors and one pair with synergistic activities. In at least nine instances, this regulation is direct—a hallmark of an emerging class of proteins called metaeffectors, or “effectors of effectors”. Through detailed structural and functional analysis, we show that metaeffector activity derives from a diverse range of mechanisms, shapes evolution, and can be used to reveal important aspects of each cognate effector's function. Metaeffectors, along with other, indirect, forms of effector–effector modulation, may be a common feature of many intracellular pathogens—with unrealized potential to inform our understanding of how pathogens regulate their interactions with the host cell. 相似文献
66.
67.
Annette Masuch Kathrin Budde Gabi Kastenmüller Anna Artati Jerzy Adamski Henry Vlzke Matthias Nauck Maik Pietzner 《Journal of cellular and molecular medicine》2019,23(8):5144-5153
Metabolomics studies now approach large sample sizes and the health characterization of the study population often include complete blood count (CBC) results. Upon careful interpretation the CBC aids diagnosis and provides insight into the health status of the patient within a clinical setting. Uncovering metabolic signatures associated with parameters of the CBC in apparently healthy individuals may facilitate interpretation of metabolomics studies in general and related to diseases. For this purpose 879 subjects from the population‐based Study of Health in Pomerania (SHIP)‐TREND were included. Using metabolomics data resulting from mass‐spectrometry based measurements in plasma samples associations of specific CBC parameters with metabolites were determined by linear regression models. In total, 118 metabolites significantly associated with at least one of the CBC parameters. Strongest associations were observed with metabolites of heme degradation and energy production/consumption. Inverse association seen with mean corpuscular volume and mean corpuscular haemoglobin comprised metabolites potentially related to kidney function. The presently identified metabolic signatures are likely derived from the general function and formation/elimination of blood cells. The wealth of associated metabolites strongly argues to consider CBC in the interpretation of metabolomics studies, in particular if mutual effects on those parameters by the disease of interest are known. 相似文献
68.
It is well proved that the probability that a protein interacts with itself is higher than that it interacts with another protein. It has been recently shown that the probability of interaction is also higher for proteins with significant sequence similarity. In this paper we show that proteins sharing identical PFAM domains interact more often than expected by chance in Saccharomyces cerevisiae and Escherichia coli. We also analyze the variety of domain interfaces used by homologous proteins to interact and show that the overrepresentation of interactions between homological proteins is not caused by small number of pairs of identical "sticky domains" shared between interacting proteins. 相似文献
69.
Dyguda-Kazimierowicz E Sokalski WA Leszczyński J 《Journal of molecular modeling》2007,13(6-7):839-849
The subject of this study was an analysis of the role of active site residues in the phosphoryl transfer reaction catalyzed
by 4-methyl-5-β-hydroxyethylthiazole kinase (ThiK). The ThiK-catalyzed reaction is of special interest due to the lack of
a highly conserved aspartate residue serving as a catalytic base. ONIOM(B3LYP:PM3) models of stationary points along the reaction
pathway consisted of reactants, two magnesium ions and several highly conserved ThiK active site residues. The results indicate
that an SN2-like mechanism of ThiK, with γ-phosphate acting as an alcohol-activating base is reasonable. Geometries of substrates, transition
state and products were utilized in the non-empirical analysis of the physical nature of catalytic interactions taking place
in the ThiK active site. The role of particular residues was investigated in terms of their ability to preferentially stabilize
the transition state relative to substrates (differential transition state stabilization, DTSS) or products (differential
product stabilization, DPS). It seems that Mg2, Glu126 and Cys198 play a major catalytic role, whereas Mg1 and the same Cys198
are responsible for product release. It is remarkable that no dominant role of an electrostatic term in the interactions involved
in catalytic activity is observed for product release. Determination of catalytic fields expressing differential electrostatic
potential of the transition state with respect to substrates revealed the optimal electrostatic features of an ideal catalyst
for the studied reaction. The predicted catalytic environment is in agreement with experimental data showing increased catalytic
activity of ThiK upon mutation of Cys198 to aspartate.
Figure Catalytic fields for ThiK-catalyzed reaction juxtaposed with the positions of active site residues of a model system. Magnesium
ions are considered part of the transition state/reactants. The surface of constant electronic density is colored according
to differential electrostatic potential of transition state with respect to reactants. The sign of the differential potential
reflects the electrostatic properties of a complementary molecular environment. Red (green) color denotes regions where a negative (positive) charge would be optimal for catalytic activity 相似文献
70.
Hao Jie Wong Nuradilla Mohamad-Fauzi Mohammed Rizman-Idid Peter Convey Jerzy Smykla Siti Aisyah Alias 《Environmental microbiology》2022,24(7):3164-3180
Solar radiation regulates most biological activities on Earth. Prolonged exposure to solar UV radiation can cause deleterious effects by inducing two major types of DNA damage, namely, cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts. These lesions may be repaired by the photoreactivation (Phr) and nucleotide excision repair (NER) pathways; however, the principal UV-induced DNA repair pathway is not known in the fungal genus Pseudogymnoascus. In this study, we demonstrated that an unweighted UV-B dosage of 1.6 kJ m−2 d−1 significantly reduced fungal growth rates (by between 22% and 35%) and inhibited conidia production in a 10 d exposure. The comparison of two DNA repair conditions, light or dark, which respectively induced photoreactivation (Phr) and NER, showed that the UV-B-induced CPDs were repaired significantly more rapidly in light than in dark conditions. The expression levels of two DNA repair genes, RAD2 and PHR1 (encoding a protein in NER and Phr respectively), demonstrated that NER rather than Phr was primarily activated for repairing UV-B-induced DNA damage in these Pseudogymnoascus strains. In contrast, Phr was inhibited after exposure to UV-B radiation, suggesting that PHR1 may have other functional roles. We present the first study to examine the capability of the Arctic and Antarctic Pseudogymnoascus sp. to perform photoreactivation and/or NER via RT-qPCR approaches, and also clarify the effects of light on UV-B-induced DNA damage repair in vivo by quantifying cyclobutene pyrimidine dimers and pyrimidine 6-4 pyrimidone photoproducts. Physiological response data, including relative growth rate, pigmentation and conidia production in these Pseudogymnoascus isolates exposed to UV-B radiation are also presented. 相似文献