Rola leptyny w regulacji metabolizmu lipidów i węglowodanów

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Patrycja Gogga*

2011-01-01

Full Text Available Leptyna jest białkiem wydzielanym głównie przez tkankę tłuszczową, a jej stężenie we krwi jest ściśle związane z ilością zapasów energetycznych zgromadzonych w adipocytach. Jako hormon leptyna ma niezwykle szeroki zakres działania. Białko to bezpośrednio lub za pośrednictwem układu współczulnego bierze udział w regulacji metabolizmu energetycznego. Leptyna hamuje biosyntezę triacylogliceroli w wątrobie i tkance tłuszczowej, a także w mięśniach szkieletowych, obniżając tym samym ilość odkładanych w nich lipidów. W adipocytach leptyna zmniejsza ekspresję genów kodujących syntazę kwasów tłuszczowych (FAS i karboksylazę acetylo-CoA (ACC – główne enzymy szlaku biosyntezy kwasów tłuszczowych. Zwiększa z kolei ekspresję genu kodującego lipazę zależną od hormonów (HSL, co stymuluje hydrolizę triacylogliceroli w tkance tłuszczowej. Ponadto leptyna wzmaga utlenianie kwasów tłuszczowych w adipocytach, mięśniach szkieletowych oraz w mięśniu sercowym, wywołując wzrost ekspresji genów kodujących podstawowe dla tego procesu enzymy, palmitoilotransferazę karnitynową 1 (CPT1 i dehydrogenazę acylo-CoA o średniej długości łańcucha (MCAD. Wykazano również, że hormon ten zwiększa wrażliwość tkanek na insulinę i poprawia tolerancję glukozy – pod wpływem leptyny wzrasta transport glukozy do komórek oraz intensywność glikolizy.Wiadomo, że leptyna bierze udział w długoterminowej regulacji pobierania pokarmu, jednak coraz więcej badań wskazuje, że ma ona również wpływ na przemiany substratów energetycznych w tkankach obwodowych. Leptyna może zatem kontrolować homeostaz�� energetyczną organizmu wywołując zmiany metabolizmu lipidów i węglowodanów, przede wszystkim w tkance tłuszczowej i w mięśniach.

Ocular phenotypes associated with two mutations (R121W, C126X) in the Norrie disease gene.

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Kellner, U; Fuchs, S; Bornfeld, N; Foerster, M H; Gal, A

1996-06-01

To describe the ocular phenotypes associated with 2 mutations in the Norrie disease gene including a manifesting carrier. Ophthalmological examinations were performed in 2 affected males and one manifesting carrier. Genomic DNA was analyzed by direct sequencing of the Norrie disease gene. Family I: A 29-year-old male had the right eye enucleated at the age of 3 years. His left eye showed severe temporal dragging of the retina and central scars. Visual acuity was 20/300. DNA analysis revealed a C-to-T transition of the first nucleotide in codon 121 predicting the replacement of arginine-121 by tryptophan (R121W). Both the mother and maternal grandmother carry the same mutation in heterozygous form. Family 2: A 3-month-old boy presented with severe temporal dragging of the retina on both eyes and subsequently developed retinal detachment. Visual acuity was limited to light perception. His mother's left eye was amaurotic and phthitic. Her right eye showed severe retinal dragging, visual acuity was reduced to 20/60. DNA analysis revealed a T-to-A transversion of the third nucleotide in codon 126 creating a stop codon (C126X). The mother and maternal grandmother were carriers. Mutations in the Norrie disease gene can lead to retinal malformations of variable severity both in hemizygous males and manifesting carriers.

Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

Science.gov (United States)

Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

2018-03-01

Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

At R407/R408

CERN Multimedia

1974-01-01

R407/R408 were experiments designed by the CERN-Collège de France-Heidelberg-Karlsruhe Collaboration to study two-particle correlations in the fragmentation region requiring a large transverse momentum particle in the forward direction. Atmospheric pressure Cerenkov counters were part of the additional equipment set up during 1974 at the SFM facility. Here Paul Hanke multi-reflected on Cerenkov mirrors.

Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

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Crinò Antonino

2009-03-01

Full Text Available Abstract Background Melanocortin-4-receptor (MC4R mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype. Methods To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index ≥ 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese, obesity onset before the 10 years old, height ≥ 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 ± 3.1, mean BMI 30.8 ± 5.4 and in 200 controls (mean age 8.1 ± 2.8; mean BMI 14.2 ± 2.5. Results Three mutations have been found in five obese children. The S127L (C380T, found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T and the Y332H (T994C mutations were found in two patients. Functional studies showed that only Q307X impaired protein function. Conclusion The low prevalence of MC4R mutations (1.6% in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.

MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

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Timur Selçuk Akpınar

2013-03-01

Full Text Available OBJECTIVE: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K were described in patients with essential thrombocythemia (ET and primary (idiopathic myelofibrosis (PMF. The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. METHODS: A total of 77 patients (66 were diagnosed with ET and 11 with PMF and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66 and 6 had PMF (54.5%, 6/11. In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively, had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. CONCLUSION: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation.

Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.

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Kim, Juwon; Jung, Jinsei; Lee, Min Goo; Choi, Jae Young; Lee, Kyung-A

2015-06-19

GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- and Cx26-V37I-transfected cells, with greater extent in Cx26-R75Q and Cx26-R75Q+V37I cells. Interestingly, our patient and his father with the mutations had more residual hearing compared with patients with the dominant mutation alone. Although the difference in hemichannel activity between R75Q alone and R75Q in combination with V37I failed to reach significance, it is of note that there is a possibility that V37I located upstream of R75Q might have the ability to ameliorate R75Q expression. Our study emphasizes the importance of cis mutations with R75Q, as the gene effect of R75Q can be modulated depending on the type of additional mutation.

Średniowieczne rękopisy ze zbiorów toruńskich bibliotek i archiwów

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Janusz Tandecki

2012-12-01

Full Text Available Największa liczba typowych bibliotecznych rękopisów średniowiecznych przechowywana jest w zbiorach Biblioteki Uniwersyteckiej w Toruniu. Wszystkie one trafiły tu po zakończeniu II wojny światowej, przede wszystkim w latach 1945-1947, gdzie w bibliotece umieszczono je wśród tzw. „zbiorów zabezpieczonych”. Obecnie w skład tego zbioru wchodzi 770 jednostek inwentarzowych oraz 6 metrów bieżących materiałów nie zinwentaryzowanych. Dzisiejszą kolekcję 71 średniowiecznych rękopisów Biblioteki UMK tworzą przede wszystkim dawne zbiory Państwowej i Uniwersyteckiej Biblioteki w Królewcu. Obejmują one dzieła religijne, prawnicze, teksty historyczne, medyczne i astronomiczne.Kolejną biblioteką toruńską, w której przechowywane są rękopisy średniowieczne jest Wojewódzka Biblioteka Publiczna-Książnica Kopernikańska w Toruniu. W jej zbiorach zachowało się w sumie 19 rękopisów (m.in. kalendarze, modlitewniki, żywoty świętych z tego okresu (do 1500 r., zapisanych po łacinie, niemiecku i w języku greckim.Spora liczba średniowiecznych ksiąg urzędowych wytworzonych w kancelarii Starego i Nowego Miasta Torunia przechowywana jest również w zasobie Archiwum Państwowego w Toruniu. Wśród nich są także rękopisy o charakterze zbliżonym do bibliotecznych.

Gain-of-function R225W mutation in human AMPKgamma(3 causing increased glycogen and decreased triglyceride in skeletal muscle.

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Sheila R Costford

Full Text Available BACKGROUND: AMP-activated protein kinase (AMPK is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory gamma(3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations. Here we report the first gain-of-function mutation in the muscle-specific regulatory gamma(3 subunit in humans. METHODS AND FINDINGS: We sequenced the exons and splice junctions of the AMPK gamma(3 gene (PRKAG3 in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The gamma(3 R225W mutation is homologous in location to the gamma(2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the gamma(3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN- pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a approximately 90% increase of skeletal muscle glycogen content and a approximately 30% decrease in intramuscular triglyceride (IMTG. CONCLUSIONS: We have identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3 subunit of AMPK in humans. The gamma(3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP

The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability.

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Smelter, Dan F; de Lange, Willem J; Cai, Wenxuan; Ge, Ying; Ralphe, J Carter

2018-06-01

Cardiac myosin-binding protein C (cMyBP-C) is a functional sarcomeric protein that regulates contractility in response to contractile demand, and many mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight into the effects of disease-causing cMyBP-C missense mutations on contractile function, we expressed the pathogenic W792R mutation (substitution of a highly conserved tryptophan residue by an arginine residue at position 792) in mouse cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects using three-dimensional engineered cardiac tissue constructs (mECTs). Based on complete conservation of tryptophan at this location in fibronectin type II (FnIII) domains, we hypothesized that the W792R mutation affects folding of the C6 FnIII domain, destabilizing the mutant protein. Adenoviral transduction of wild-type (WT) and W792R cDNA achieved equivalent mRNA transcript abundance, but not equivalent protein levels, with W792R compared with WT controls. mECTs expressing W792R demonstrated abnormal contractile kinetics compared with WT mECTs that were nearly identical to cMyBP-C-deficient mECTs. We studied whether common pathways of protein degradation were responsible for the rapid degradation of W792R cMyBP-C. Inhibition of both ubiquitin-proteasome and lysosomal degradation pathways failed to increase full-length mutant protein abundance to WT equivalence, suggesting rapid cytosolic degradation. Bacterial expression of WT and W792R protein fragments demonstrated decreased mutant stability with altered thermal denaturation and increased susceptibility to trypsin digestion. These data suggest that the W792R mutation destabilizes the C6 FnIII domain of cMyBP-C, resulting in decreased full-length protein expression. This study highlights the vulnerability of FnIII-like domains to mutations that alter domain stability and further indicates that missense mutations in cMyBP-C can cause disease through a mechanism of

Jak różnicować wymioty u noworodków i niemowląt? Część II. Gastroenterologiczne i alergologiczne przyczyny wymiotów

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Anna Stańczyk-Przyłuska

2014-03-01

Full Text Available Najczęstszą przyczyną wymiotów w wieku niemowlęcym są błędy w karmieniu. Ich rozpoznanie wymaga wnikliwej analizy sposobu żywienia oraz przygotowywania posiłków. Optymalne warunki dla takiej oceny stwarza kilkudniowa obserwacja dziecka. Również zaburzenia więzi matki z dzieckiem mogą się istotnie przyczyniać do większej częstości zwracania pokarmu. Znaczna część incydentów wymiotów niemowlęcych nie wynika z zaburzeń chorobowych, a jedynie z fizjologicznej niedojrzałości górnego odcinka przewodu pokarmowego. Refluks żołądkowo-przełykowy uważany jest za zjawisko normalne, o przejściowym charakterze, będące konsekwencją anatomicznej i czynnościowej niedojrzałości przewodu pokarmowego młodszych niemowląt. Leczenia wymagają jedynie te dzieci, u których refluks żołądkowo-przełykowy wywołuje takie objawy kliniczne, jak: zaburzenia rozwoju fizycznego, niepokój, zaburzenia połykania, wheezing, kaszel lub bezdechy, albo prowadzi do rozwoju powikłań, np. zapalenia przełyku, jego zwężenia czy przełyku Barretta. Kolejną najczęściej rozpoznawaną przyczyną wymiotów w wieku niemowlęcym są różne manifestacje kliniczne alergii na pokarmy. Immunologiczna reakcja na białka pokarmowe może wywoływać mniej niż 1% przypadków wymiotów, a ich rozpoznanie powinno zostać potwierdzone w teście eliminacji i prowokacji. Wiele innych chorób przewodu pokarmowego również może prowadzić do wymiotów, m.in. infekcyjne zapalenie żołądka i jelit, nieswoiste zapalenie jelit, nietolerancje pokarmowe, a także cholestaza zewnątrzwątrobowa oraz zapalenie trzustki.

Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population.

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Kucinskas, Laimutis; Juzenas, Simonas; Sventoraityte, Jurgita; Cedaviciute, Ruta; Vitkauskiene, Astra; Kalibatas, Vytenis; Kondrackiene, Jurate; Kupcinskas, Limas

2012-04-01

HFE-hemochromatosis is a common autosomal recessive disease caused by HFE gene mutations and characterized as iron overload and failure of different organs. The aim of this study was to determine the prevalence of C282Y (c.845 G>A), H63D (c.187 C>G), and S65C (c.193A>T) alleles of HFE gene in the Lithuanian population. One thousand and eleven healthy blood donors of Lithuanian nationality were examined in four different ethnic Lithuanian regions to determine HFE gene alleles and genotype frequencies. The samples of DNA were analyzed for the presence of restriction fragment length polymorphism and validated by DNA sequencing. Among 1,011 blood donors tested, the frequency of C282Y, H63D, and S65C alleles were 2.6%, 15.9%, and 1.9%, respectively. One third of the tested subjects (n = 336) had at least one of the C282Y or H63D HFE gene mutations. The screening of Lithuanian blood donors has detected 13 (1.3%) subjects with a genotype C282Y/C282Y or C282Y/H63D responsible for the development of HFE-hemochromatosis. The prevalence of C282Y mutation was significantly higher among the inhabitants of Zemaitija (Somogitia) at the Baltic Sea area (5.9%) in comparison to the regions of continental part of Lithuania (2.4% in Dzukija, 2.3% in Aukstaitija, and 2% in Suvalkija, p HFE gene mutations in ethnic Lithuanians showed that the frequencies of H63D, C282Y, and S65C of HFE gene alleles are similar to the other North-Eastern Europeans, especially in the Baltic region (Estonia, Latvia), Poland, and part of Russia (Moscow region).

An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

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Hanker, Ariella B; Brewer, Monica Red; Sheehan, Jonathan H; Koch, James P; Sliwoski, Gregory R; Nagy, Rebecca; Lanman, Richard; Berger, Michael F; Hyman, David M; Solit, David B; He, Jie; Miller, Vincent; Cutler, Richard E; Lalani, Alshad S; Cross, Darren; Lovly, Christine M; Meiler, Jens; Arteaga, Carlos L

2017-06-01

We report a HER2 T798I gatekeeper mutation in a patient with HER2 L869R -mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2 L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3 E928G , also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2 T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2 T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2 L869R but not HER2 L869R/T798I In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2 L869R/T798I -induced signaling and cell growth. Acquisition of HER2 T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2 L869R is a driver mutation. HER2 T798I -mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. Significance: We found an acquired HER2 gatekeeper mutation in a patient with HER2 -mutant breast cancer upon clinical progression on neratinib. We speculate that HER2 T798I may arise as a secondary mutation following response to effective HER2 tyrosine kinase inhibitors (TKI) in other cancers with HER2 -activating mutations. This resistance may be overcome by other irreversible HER2 TKIs, such as afatinib. Cancer Discov; 7(6); 575-85. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

2015-07-15

To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

Energy Technology Data Exchange (ETDEWEB)

Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

~ i t i d e r m a t o ~ h ~ t i c Activities of Nine (9) Essential Oils J.R. ...

African Journals Online (AJOL)

i t i d e r m a t o ~ h ~ t i c Activities of Nine (9) Essential Oils. J.R. KUIATE", S.P. KUATE'.~, N.E. KEMADJOU~, S. DJOKOUA~, F. ZIFACK~ AND J. ~. 0. ~. 0. ~. I Department of Biochemistry, FS, University of Dschang, P.O. Box 67 Dschang, Cameroon. 2~epartment of Biochemistry, FS, University of Yaoundt!, P.O. Box 812 ...

Spectrum of CFTR gene mutations in Ecuadorian cystic fibrosis patients: the second report of the p.H609R mutation.

Science.gov (United States)

Ortiz, Sofía C; Aguirre, Santiago J; Flores, Sofía; Maldonado, Claudio; Mejía, Juan; Salinas, Lilian

2017-11-01

High heterogeneity in the CFTR gene mutations disturbs the molecular diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our country, the present study aims to define a panel of common CFTR gene mutations by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients. Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis were included. Twenty-seven exons of CFTR gene were sequenced to find sequence variations. Prevalence of pathogenic variations were determined and compared with other countries' data. We found 70 sequence variations. Eight of these are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian population. Mutation prevalence differences between Ecuadorian population and other Latin America countries were found. The panel of mutations suggested as an initial screening for the Ecuadorian population with cystic fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. © 2017 NETLAB Laboratorios Especializados. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Deskrypcja różnic powierzchni plantokonturogramu między lewą a prawą stopą populacji dziewcząt w wieku od 4 do 18 lat, w ujęciu odsetkowym i w świetle mory projekcyjnej

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Mirosław Mrozkowiak

2015-11-01

    Mirosław Mrozkowiak Uniwersytet Kazimierza Wielkiego Bydgoszcz e-mail: magmar54@interia.pl strona: http://wadypostawy.republika.pl     Słowa kluczowe: powierzchnia podeszwowa stopy, obciążenie masą ciała.   Streszczenie   Wstęp. Stopa spełnia węzłową rolę w lokomocji i motoryczności człowieka. Jej konstrukcja w postaci uformowanego sklepienia podłużnego i poprzecznego zapewnia odpowiednie amortyzowanie wszelkich obciążeń, nacisków i wstrząsów, utrzymuje ciało w pozycji spionizowanej, umożliwia poruszanie się, skakanie i bieganie. Cel. Określenie różnic powierzchni plantokonturogramów stóp w warunkach obciążenia masą własną, populacji żeńskiej w wieku od 4 do 18 lat w ujęciu odsetkowym. Materiał i metodyka. Badaniami objęto populację 9804 kobiet w wieku od 4 do 18 lat, z wybranych losowo przedszkoli i szkół regionu Warmińsko – Mazurskiego. Metodyka badań obejmowała pomiar powierzchni plantokonturogramu stóp (Gamma. Do oceny wykorzystano stanowisko do komputerowej oceny postawy ciała, techniką mory projekcyjnej – Posturometr M. Wyniki. Wyniki badań opracowano graficznie, przedstawiając przebieg zmian odsetka różnic powierzchni plantokonturogramu lewej i prawej stopy dla płci żeńskiej i obojga płci. Wnioski.    1. U dziewcząt o większej powierzchni plantokonturogramu lewej stopy odsetki różnic są        większe niż u dziewcząt o większej powierzchni plantokonturogramu prawej stopy.    2. Wielkość odsetka różnic powierzchni stóp dziewcząt jest zbliżony do wielkości        uzyskanych przez osobników obojga płci do 17 r.ż., dalej następuje gwałtowny wzrost        wielkości różnic u osobników obojga płaci, posiadających większą powierzchnię        plantokonturogramu lewej stopy.   Keywords: plantar surface of the foot, the load weight.   Abstract   Admission. The rate meets the nodal role in human locomotion and motor skills. Its structure

Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America

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Suffys Philip N

2009-02-01

Full Text Available Abstract Background Mutations associated with resistance to rifampin or streptomycin have been reported for W/Beijing and Latin American Mediterranean (LAM strain families of Mycobacterium tuberculosis. A few studies with limited sample sizes have separately evaluated mutations in katG, ahpC and inhA genes that are associated with isoniazid (INH resistance. Increasing prevalence of INH resistance, especially in high tuberculosis (TB prevalent countries is worsening the burden of TB control programs, since similar transmission rates are noted for INH susceptible and resistant M. tuberculosis strains. Results We, therefore, conducted a comprehensive evaluation of INH resistant M. tuberculosis strains (n = 224 from three South American countries with high burden of drug resistant TB to characterize mutations in katG, ahpC and inhA gene loci and correlate with minimal inhibitory concentrations (MIC levels and spoligotype strain family. Mutations in katG were observed in 181 (80.8% of the isolates of which 178 (98.3% was contributed by the katG S315T mutation. Additional mutations seen included oxyR-ahpC; inhA regulatory region and inhA structural gene. The S315T katG mutation was significantly more likely to be associated with MIC for INH ≥2 μg/mL. The S315T katG mutation was also more frequent in Haarlem family strains than LAM (n = 81 and T strain families. Conclusion Our data suggests that genetic screening for the S315T katG mutation may provide rapid information for anti-TB regimen selection, epidemiological monitoring of INH resistance and, possibly, to track transmission of INH resistant strains.

Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

DEFF Research Database (Denmark)

Lindquist, S.G.; Holm, I.E.; Schwartz, M.

2008-01-01

We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic an......We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre...

Ocena występowania wad stóp u dzieci w wieku 9-10 lat w środowisku miejskim i wiejskim = Estimate the prevalence the feet defects in children aged 9-10 years in the urban and rural environment

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Anna Plaskiewicz

2015-04-01

3 Wydział Kultury Fizycznej, Zdrowia i Turystyki, Uniwersytet Kazimierza Wielkiego w Bydgoszczy   Streszczenie   Wstęp. Wady stóp u dzieci są powszechnym problemem medyczno–społecznym w Polsce i na Świecie. Styl i szybkie tempo życia współczesnego człowieka wpływają niekorzystnie na postawę ciała, a stopy są szczególnie narażone na niekorzystny wpływ działania czynników środowiska zewnętrznego. Cel pracy. Celem pracy jest ocena występowania wad stóp u dzieci w wieku 9-10 lat w środowisku miejskim i wiejskim. Materiał i metody. Badaniami objęto grupę 40 dzieci w wieku 9-10 lat. Ze względu na miejsce zamieszkania dzieci podzielono na dwie grupy. Analizę stóp wykonano metodą platurograficzną polegającą na sporządzeniu odcisków podporowej powierzchni stopy. Oceniano wskaźniki opisujące wady stóp tj: wskaźnik „Ky” Sztritera-Godunowa, wskaźnik kątowy Clarke’a (CI, wskaźnik Wejsfloga, kąt piętowy oraz kąt koślawości palucha. Wyniki. Wśród przebadanych dzieci najczęstszą wadą stóp było płaskostopie. Zaobserwowano minimalnie mniej wad stóp u dzieci ze wsi w porównaniu z dziećmi mieszkającymi w mieście, jednak różnice nie są istotne statystycznie. Nie zaobserwowano różnic związanych z występowaniem wad stóp pomiędzy dziećmi ze wsi i z miasta. Wnioski. 1. Większość dzieci zarówno z miasta (65% jak i ze wsi (75% ma prawidłowo ukształtowane stopy. 2. Najczęstszą wadą stóp występującą wśród przebadanych dzieci jest płaskostopie. 3. Nie zaobserwowano istotnych różnic statystycznych w ocenie stóp pomiędzy dziećmi mieszkającymi w środowisku miejskim i wiejskim.   Abstract   Introduction. Feet defects in children is a common socio-medical problem in Poland and the world. Lifestyle of modern man adversely affect posture. The feet are particularly vulnerable to the adverse effects factors the external environment. Aim of the study. The aim of the study is to estimate the

Generation of an isogenic, gene-corrected iPSC line from a pre-symptomatic 28-year-old woman with an R406W mutation in the microtubule associated protein tau (MAPT) gene

DEFF Research Database (Denmark)

Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a pre-symptomatic carrier of the R406W mutation in the MAPT-gene....

Identification of a novel p.R1443W mutation in RP1 gene associated with retinitis pigmentosa sine pigmento

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Li Ma

2013-08-01

Full Text Available AIM: To screen mutations in the retinitis pigmentosa 1 (RP1 gene and the rhodopsin (RHO gene in Chinese patients with retinitis pigmentosa sine pigmento (RPSP and describe the genotype-phenotype relationship of the mutations.METHODS:Twenty affected, unrelated Chinese individuals with RPSP (4 autosomal dominant RPSP, 12 autosomal recessive RPSP and 4 unknown inheritance pattern were recruited between 2009 and 2012. The clinical features were determined by complete ophthalmologic examinations. Polymerase chain reaction (PCR and direct DNA sequencing were used to screen the entire coding region and splice junctions of the RP1 gene and the RHO gene. The cosegregation analysis and population frequency studies were performed for patients with identified mutations.RESULTS: Five variants in the RP1 gene and one in the RHO gene were detected in 20 probands. Four missense changes (rs444772, rs446227, rs414352, rs441800 and one non-coding variant (rs56340615 were common SNPs and none of them showed a significant relationship with RPSP. A missense mutation p.R1443W was identified in the RP1 gene in three affected individuals from a family with autosomal dominant RPSP and was found to cosegregate with the phenotype in this family, suggestive of pathogenic. In addition, population frequency analysis showed the p.R1443W mutation was absent in 300 healthy controls.CONCLUSION: The identification of p.R1443W mutation cosegregating in a family with autosomal dominant RPSP highlights an atypical phenotype of the RP1 gene mutation, while RHO gene is not associated with the pathogenesis of RPSP in this study. To our knowledge, this is the fist mutation identified to associate with RPSP.

Identification of a novel p.R1443W mutation in RP1 gene associated with retinitis pigmentosa sine pigmento.

Science.gov (United States)

Ma, Li; Sheng, Xun-Lun; Li, Hui-Ping; Zhang, Fang-Xia; Liu, Ya-Ni; Rong, Wei-Ning; Zhang, Jian-Ling

2013-01-01

To screen mutations in the retinitis pigmentosa 1 (RP1) gene and the rhodopsin (RHO) gene in Chinese patients with retinitis pigmentosa sine pigmento (RPSP) and describe the genotype-phenotype relationship of the mutations. Twenty affected, unrelated Chinese individuals with RPSP (4 autosomal dominant RPSP, 12 autosomal recessive RPSP and 4 unknown inheritance pattern) were recruited between 2009 and 2012. The clinical features were determined by complete ophthalmologic examinations. Polymerase chain reaction (PCR) and direct DNA sequencing were used to screen the entire coding region and splice junctions of the RP1 gene and the RHO gene. The cosegregation analysis and population frequency studies were performed for patients with identified mutations. Five variants in the RP1 gene and one in the RHO gene were detected in 20 probands. Four missense changes (rs444772, rs446227, rs414352, rs441800) and one non-coding variant (rs56340615) were common SNPs and none of them showed a significant relationship with RPSP. A missense mutation p.R1443W was identified in the RP1 gene in three affected individuals from a family with autosomal dominant RPSP and was found to cosegregate with the phenotype in this family, suggestive of pathogenic. In addition, population frequency analysis showed the p.R1443W mutation was absent in 300 healthy controls. The identification of p.R1443W mutation cosegregating in a family with autosomal dominant RPSP highlights an atypical phenotype of the RP1 gene mutation, while RHO gene is not associated with the pathogenesis of RPSP in this study. To our knowledge, this is the fist mutation identified to associate with RPSP.

The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T).

Science.gov (United States)

Gumus, Evren

2018-05-07

Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV) gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January⁻December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T) mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP), do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS) analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

Ból w klatce piersiowej – podobne objawy, a różne rozpoznania i przebieg kliniczny – opisy przypadków

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Anna Kaźmierczak-Dziuk

2011-12-01

Full Text Available Ból w klatce piersiowej jest najczęstszym objawem chorób układu krążenia, może być jednak spowodowany zaburzeniami ze strony innych układów i narządów. Ustalenie przyczyny bólu nie jest łatwe, niemniej jednak kluczowe w procesie diagnostycznym. W różnicowaniu należy wziąć pod uwagę przede wszystkim choroby najczęściej występujące oraz te, które zagrażają bezpośrednio życiu i zdrowiu pacjenta. Są to stany związane z niedokrwieniem mięśnia serca: niestabilna dławica piersiowa, zawał mięśnia serca. Podczas oceny chorego konieczne jest uwzględnienie przyczyn bólu w klatce piersiowej pochodzących z wnętrza klatki piersiowej (aorta, tętnica płucna, śródpiersie, przełyk, tchawica, oskrzela, opłucna, ze ściany klatki piersiowej (nerwy czuciowe, połączenia chrzęstno-kostne, kręgosłup, skóra, ze strony jamy brzusznej (żołądek, dwunastnica, trzustka, pęcherzyk żółciowy, a także dolegliwości o podłożu psychogennym. W procesie diagnostycznym należy brać pod uwagę charakter bólu, jego czas trwania, sytuacje prowokujące i zmniejszające ból, a także objawy towarzyszące. Do czasu zakończenia postępowania diagnostycznego chory z bólem w klatce piersiowej powinien być traktowany jak pacjent o istotnie podwyższonym ryzyku sercowo-naczyniowym. Dokładnie przeprowadzona diagnostyka różnicowa pozwala na ustalenie prawidłowego rozpoznania i włączenie odpowiedniego leczenia. W pracy przedstawiono opisy pięciu przypadków klinicznych chorych z bólem w klatce piersiowej. Pomimo podobnych objawów u każdego z prezentowanych pacjentów ustalono inne rozpoznanie, a przebieg kliniczny był w każdym przypadku zupełnie odmienny.

Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene.

OpenAIRE

Jennings, J. E.; Georgitsi, M.; Holdaway, I.; Daly, Adrian; Tichomirowa, M.; Beckers, Albert; Aaltonen, Lauri A; Karhu, A.; Cameron, F. J.

2009-01-01

OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors. DESIGN AND METHODS: Case series with germline screening of AIP and haplotype analyses among R271W families. RESULTS: This previously unreported kind...

Phenylketonuria mutation analysis in Northern Ireland: A rapid stepwise approach

Energy Technology Data Exchange (ETDEWEB)

Zschocke, J.; Graham, C.A.; Nevin, N.C. [Queen`s Univ., Belfast (Australia)] [and others

1995-12-01

We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, 165T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting. 19 refs., 5 tabs.

Zasady żywienia dzieci w drugim i trzecim roku życia

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Adam J. Sybilski

2010-11-01

Full Text Available W artykule przedstawiono aktualny stan wiedzy na temat zasad żywienia dzieci w 2. i 3. roku życia. W okresie poniemowlęcym zapotrzebowanie energetyczne dziecka zmniejsza się do ok. 90 kcal/kg mc./dobę. Zmianie ulega również tempo jego wzrostu. Połowa energii wydatkowana jest na potrzeby aktywności fizycznej, więc potrzeby żywieniowe dziecka są od nich uzależnione. Rozkład podaży energii pozabiałkowej powinien wynosić 60-65% z węglowodanów i 35-40% z tłuszczu. Należy zadbać o stopniowe wzbogacanie diety o kwasy tłuszczowe (NNKT, zawarte w olejach roślinnych, tłustych rybach morskich, orzechach oraz zielonych warzywach. Do 2. roku życia zalecana jest dieta bogata w tłuszcze, głównie pochodzące z masła, następnie należy stopniowo ograniczać tłuszcze zwierzęce, aby uniknąć otyłości. Dziecku nie należy podawać tłustych mięs oraz surowych jaj, gdyż zawierają one awidynę. Do 3. roku życia korzystniejsze jest podawanie mieszanek mlecznych typu „junior” niż pełnego mleka krowiego. Rekomendowane produkty zbożowe zawierające węglowodany to przede wszystkim pieczywo razowe oraz grube kasze. Zapotrzebowanie na płyny u małego dziecka wynosi ok. 950 ml/dobę. Najlepsze do picia są woda, niesłodzone herbatki ziołowe i naturalne soki owocowe. Ważna jest też forma, czyli w jaki sposób przyjmowane są pokarmy. Należy kształtować w dziecku dobre nawyki i przyzwyczajenia związane z jedzeniem, kierując się zasadą 4U: urozmaicenie, umiar, unikanie i uregulowanie. Obecnie można zauważyć poprawę w stanie odżywienia polskich dzieci, choć nadal sposób ich żywienia bywa niezadowalający. Do najczęstszych błędów zalicza się nadmierne używanie soli, mało urozmaiconą dietę, brak czasu i zniecierpliwienie w czasie posiłków, nerwową atmosferę w czasie posiłków oraz nadmierne rozdrabnianie produktów.

Generation of an isogenic, gene-corrected iPSC line from a symptomatic 59-year-old female patient with frontotemporal dementia caused by an R406W mutation in the microtubule associated protein tau (MAPT) gene

DEFF Research Database (Denmark)

Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene....

The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T

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Evren Gumus

2018-05-01

Full Text Available Background: Familial Mediterranean Fever (FMF is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. Methods: In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January–December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Results: Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. Conclusions: One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP, do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

Mucopolysaccharidosis type I: molecular characteristics of two novel alpha-L-iduronidase mutations in Tunisian patients

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Chahed Henda

2011-06-01

the enzyme defect and resulting in MPS I clinical phenotype. More than 100 mutations have been reported in patients with the MPS I subtypes (Human Gene Mutation Database; http://www.hgmd.org. High prevalence of the common mutations p.W402X and p.Q70X has been described; both of them in the severe clinical forms 45. A high prevalence of common mutation p.P533R has also been described in MPS I patients with various phenotypes 56. In addition, rare mutations including single base substitution, deletion, insertion and splicing site mutation have been identified 7, indicating a high degree of allelic heterogeneity in IDUA gene. Here, we described two novel IDUA mutations in MPS I Tunisian patients. These lesions were homoallelic in all the patients of the six families investigated as consanguineous marriages are still frequent in Tunisia 8.

Wpływ leptyny i adiponektyny na procesy chondrogenezy i osteoblastogenezy – znaczenie w patogenezie reumatoidalnego zapalenia stawów

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Urszula Skalska

2011-04-01

Full Text Available Leptyna i adiponektyna to klasyczne adipokiny produkowane przezbiałą tkankę tłuszczową. Mają one działanie plejotropowe; ich rolębada się w takich chorobach, jak reumatoidalne zapalenie stawówczy choroba zwyrodnieniowa stawów. Dotąd nie wiadomo, jakidokładnie wpływ wywierają one na procesy chondrogenezyi osteoblastogenezy. Te dwa procesy są bardzo istotne z punktuwidzenia reumatoidalnego zapalenia stawów, gdyż w chorobie tejdochodzi do destrukcji chrząstki i kości stawowej. Istotne jestokreślenie, jaką rolę odgrywają adipokiny w reumatoidalnymzapaleniu stawów oraz w jaki sposób wpływają na różnicowaniekomórek mezenchymalnych. W niniejszej pracy przedstawionoobecną wiedzę na temat roli adiponektyny i leptyny w procesachosteogenezy i chondrogenezy (tab. I i II.

Prevalence of melanocortin receptor 4 (MC4R) V103I gene variant and its association with obesity among the Kampar Health Clinic cohort, Perak, Malaysia.

Science.gov (United States)

Chua, H N; Fan, S H; Say, Y H

2012-04-01

This study investigated the prevalence of the Melanocortin receptor 4 (MC4R) V1031 gene variant and its association with obesity among a cohort of 254 patients (101 males; 118 obese) attending the Kampar Health Clinic. Genotyping revealed the mutated I allele frequency of 0.02, no homozygous mutated (II), and similar distribution of V and I alleles across BMI groups, genders and ethnic groups. No significant difference was found for the means of anthropometric measurements between alleles. Prevalence of this gene variant among the Malaysian cohort was similar with previous populations (2-4% of mutated allele carrier), but was not associated with obesity.

Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation

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Shishi Li

2018-03-01

Full Text Available Summary: Hypertrophic cardiomyopathy (HCM is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2. The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM. : In this article, Yan Q, Liu Z, Huang W, and colleagues show that patient-specific iPSCs as well as their derived cardiomyocytes carrying the m.2336T>C mutation in MT-RNR2 were generated to understand the pathogenic mechanism of maternally inherited HCM. MT-RNR2 mutation resulted in mitochondrial dysfunctions and ultrastructure defects, which induced abnormal Ca2+ homeostasis, then HCM-specific cellular and electrophysiological characteristics in iPSC-CMs. Keywords: mitochondrion, hypertrophic cardiomyopathy, induced pluripotent stem cells, MT-RNR2, maternal inheritance

Skład kwasów tłuszczowych i twardość czekolad gorzkich o różnej zawartości miazgi kakaowej = Fatty acid composition and hardness of dark chocolates with different content of cacao mass

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Renata Taradejna

2015-09-01

Wydział Nauki o Żywności, Uniwersytet Warmińsko-Mazurski w Olsztynie     Uniwersytet Warmińsko-Mazurski w Olsztynie Katedra Przetwórstwa i Chemii Surowców Roślinnych Pl. Cieszyński 1, 10-726 Olsztyn e-mail: beata.wronowska@uwm.edu.pl     Abstrakt W pracy analizowano zróżnicowanie dostępnych na rynku czekolad gorzkich pod względem składu kwasów tłuszczowych oraz twardości. Materiałem badawczym było 14 czekolad gorzkich pochodzących od różnych firm o zawartości miazgi kakaowej od 45% do 90%. Skład kwasów tłuszczowych oznaczono chromatograficznie, a twardość zmierzono w teście łamania za pomocą uniwersalnej maszyny testującej. Wykazano, że 6 czekolad zawierało w swoim składzie poniżej 65% miazgi kakaowej, nie spełniając wymagań określonych w polskiej normie dla czekolady gorzkiej. Pomimo tego, prawie wszystkie czekolady miały skład kwasów tłuszczowych typowy dla tłuszczu kakaowego; udziały kwasów oleinowego, stearynowego i palmitynowego wynosiły odpowiednio: 31,2-33,1%, 34,1-36,8% i 25,5-29,0%. Tylko w przypadku jednej czekolady stwierdzono wyższy udział kwasu palmitynowego (33,8%, natomiast niższy kwasów oleinowego i stearynowego (odpowiednio 29,4% i 32,9%. Badane czekolady gorzkie cechowały się zróżnicowaną twardością, na co wskazywały wartości siły kształtujące się w szerokim zakresie (24,2-85,6 N. Nie zaobserwowano zależności pomiędzy składem kwasów tłuszczowych a wartością siły potrzebnej do złamania kostki czekolady.   Słowa kluczowe: czekolada gorzka, miazga kakaowa, kwasy tłuszczowe, twardość.       Abstract The study analysed the diversity of commercially available dark chocolate in terms of fatty acid composition and hardness. The research material was 14 bitter chocolate from different companies about the content of cocoa mass from 45% to 90%. The fatty acid composition was determined by chromatography, and the hardness measured by the breaking test with the universal

Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH).

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Koika, Vasiliki; Varnavas, Petros; Valavani, Helen; Sidis, Yisrael; Plummer, Lacey; Dwyer, Andrew; Quinton, Richard; Kanaka-Gantenbein, Christine; Pitteloud, Nelly; Sertedaki, Amalia; Dacou-Voutetakis, Catherine; Georgopoulos, Neoklis A

2013-03-01

FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino acid substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes. Two unrelated GnRH deficient probands were found to harbor mutations in FGFR1 (R254W and R254Q). Mutant signaling activity and expression levels were evaluated in vitro and compared to a wild type (WT) receptor. Signaling activity was determined by a FGF2/FGFR1 dependent transcription reporter assay. Receptor total expression levels were assessed by Western blot and cell surface expression was measured by a radiolabeled antibody binding assay. The R254W maximal receptor signaling capacity was reduced by 45% (p<0.01) while R254Q activity was not different from WT. However, both mutants displayed diminished total protein expression levels (40 and 30% reduction relative to WT, respectively), while protein maturation was unaffected. Accordingly, cell surface expression levels of the mutant receptors were also significantly reduced (35% p<0.01 and 15% p<0.05, respectively). The p.R254W and p.R254Q are both loss-of-function mutations as demonstrated by their reduced overall and cell surface expression levels suggesting a deleterious effect on receptor folding and stability. It appears that a tryptophan substitution at R254 is more disruptive to receptor structure than the more conserved glutamine substitution. No clear correlation between the severity of in vitro loss-of-function and phenotypic presentation could be assigned. Copyright © 2012 Elsevier B.V. All rights reserved.

Replication-dependent 65R→K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V

International Nuclear Information System (INIS)

Sharma, Prem L.; Nurpeisov, Viktoria; Lee, Kimberly; Skaggs, Sara; Di San Filippo, Christina Amat; Schinazi, Raymond F.

2004-01-01

Understanding of the mechanisms of interaction among nucleoside reverse transcriptase inhibitor (NRTI)-selected mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) coding sequence is essential for the design of newer drugs and for enhancing our vision of the structure function relationship among amino acids of the polymerase domain of HIV-1. Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics. A novel NRTI (-)-β-D-dioxolane-guanosine (DXG) is known to select in vitro either the 65R or 74V mutant virus (Antimicrob. Agents Chemother. 44 (2000) 1783). These mutations were not selected together during repeated passaging of the HIV-1 in the presence of this drug. To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background. Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R→K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication kinetic assays in MT-2 cells demonstrated that double mutant 65R + 74V is highly attenuated for replication and the initiation of reversion is related to the increase in RT activity. Additionally, the suppression of viral replication in the presence of DXG or under suboptimal human recombinant interleukin-2 leads to minimal or no 65R→K reversion. These observations provide evidence that 65R→K reversion in the double mutant 65R + 74V is dependent on a specific rate of viral replication in a pNL4-3 background. A similar phenomenon may occur in vivo, which may have implications for treatment management strategies

Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.

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Gregorio-Teruel, Lucia; Valente, Pierluigi; González-Ros, José Manuel; Fernández-Ballester, Gregorio; Ferrer-Montiel, Antonio

2014-03-01

The transient receptor potential vanilloid receptor subtype I (TRPV1) channel acts as a polymodal sensory receptor gated by chemical and physical stimuli. Like other TRP channels, TRPV1 contains in its C terminus a short, conserved domain called the TRP box, which is necessary for channel gating. Substitution of two TRP box residues-I696 and W697-with Ala markedly affects TRPV1's response to all activating stimuli, which indicates that these two residues play a crucial role in channel gating. We systematically replaced I696 and W697 with 18 native l-amino acids (excluding cysteine) and evaluated the effect on voltage- and capsaicin-dependent gating. Mutation of I696 decreased channel activation by either voltage or capsaicin; furthermore, gating was only observed with substitution of hydrophobic amino acids. Substitution of W697 with any of the 18 amino acids abolished gating in response to depolarization alone, shifting the threshold to unreachable voltages, but not capsaicin-mediated gating. Moreover, vanilloid-activated responses of W697X mutants showed voltage-dependent gating along with a strong voltage-independent component. Analysis of the data using an allosteric model of activation indicates that mutation of I696 and W697 primarily affects the allosteric coupling constants of the ligand and voltage sensors to the channel pore. Together, our findings substantiate the notion that inter- and/or intrasubunit interactions at the level of the TRP box are critical for efficient coupling of stimulus sensing and gate opening. Perturbation of these interactions markedly reduces the efficacy and potency of the activating stimuli. Furthermore, our results identify these interactions as potential sites for pharmacological intervention.

Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

DEFF Research Database (Denmark)

Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

2011-01-01

T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

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2010-01-01

Background Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

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Pedersen Niels C

2007-04-01

Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

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Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

2015-01-01

T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

Prevalence of drug-resistant mutation among drug-treated HIV/AIDS inpatient in Airlangga University teaching hospital, Surabaya, Indonesia

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Rachman, B. E.; Khairunisa, S. Q.; Witaningrum, A. M.; Yunifiar, M. Q.; Widiyanti, P.; Nasronudin

2018-03-01

Increased use of antiretroviral therapy did not completely reduce the incidence of HIV/AIDShospitalization. Various factors can be involved. The aim of this study is to examine HIV-1 drug resistance mutations profile in drug-treated HIV/AIDS patients who underwent hospitalization. HIV/AIDS patients who are admitted to hospital who had received ART are included in the study and then examined for the presence of drug resistance-associated mutations. A total of 17 samples were included in the study, but only 11 samples that could be sequence analyzed. On the mutation examination of drug resistance in reverse transcriptase gene, it werefound a major mutation in K103N (9%) and G190A (9%). Most minor mutations were found in A98S (18.1%), followed by M41L, M184V, L210W, T215Y, V108l, Y181C and H221Y at 9% each. Whereas, on examination of drug resistance mutations in protease genes, there is a major mutation in I84V of 9%. Most minor mutations on M36I (45.4%), followed by L10I (36.3%), H69K (36.3%), I93L (27.2%), G16E, L89M, K20R 18.1%, L64V and V771I 9% respectively.A large number of mutated samples pose a challenge in long-term antiretroviral treatment, so a breakthrough policy is needed to minimize the impact.

Mutations causative of familial hypercholesterolaemia

DEFF Research Database (Denmark)

Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

2016-01-01

causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLR[W23X;W66G;W556S] and APOB[R3500Q] accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information......-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH...

Mutational analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in Tunisian patients with nonsyndromic hearing loss

International Nuclear Information System (INIS)

Mkaouar-Rebai, Emna; Tlili, Abdelaziz; Masmoudi, Saber; Louhichi, Nacim; Charfeddine, Ilhem; Amor, Mohamed Ben; Lahmar, Imed; Driss, Nabil; Drira, Mohamed; Ayadi, Hammadi; Fakhfakh, Faiza

2006-01-01

We explored the mitochondrial 12S rRNA and the tRNA Ser(UCN) genes in 100 Tunisian families affected with NSHL and in 100 control individuals. We identified the mitochondrial A1555G mutation in one out of these 100 families and not in the 100 control individuals. Members of this family harbouring the A1555G mutation showed phenotypic heterogeneity which could be explained by an eventual nuclear-mitochondrial interaction. So, we have screened three nuclear genes: GJB2, GJB3, and GJB6 but we have not found correlation between the phenotypic heterogeneity and variants detected in these genes. We explored also the entire mitochondrial 12S rRNA and the tRNA Ser(UCN) genes. We detected five novel polymorphisms: T742C, T794A, A813G, C868T, and C954T, and 12 known polymorphisms in the mitochondrial 12S rRNA gene. None of the 100 families or the 100 controls were found to carry mutations in the tRNA Ser(UCN) gene. We report here First mutational screening of the mitochondrial 12S rRNA and the tRNA Ser(UCN) genes in the Tunisian population which describes the second family harbouring the A1555G mutation in Africa and reveals novel polymorphisms in the mitochondrial 12S rRNA gene

Mutations affecting RNA polymerase I-stimulated exchange and rDNA recombination in yeast

International Nuclear Information System (INIS)

Lin, Y.H.; Keil, R.L.

1991-01-01

HOT1 is a cis-acting recombination-stimulatory sequence isolated from the rDNA repeat unit of yeast. The ability of HOT1 to stimulate mitotic exchange appears to depend on its ability to promote high levels of RNA polymerase I transcription. A qualitative colony color sectoring assay was developed to screen for trans-acting mutations that alter the activity of HOT1. Both hypo-recombination and hyper-recombination mutants were isolated. Genetic analysis of seven HOT1 recombination mutants (hrm) that decrease HOT1 activity shows that they behave as recessive nuclear mutations and belong to five linkage groups. Three of these mutations, hrm1, hrm2, and hrm3, also decrease rDNA exchange but do not alter recombination in the absence of HOT1. Another mutation, hrm4, decreases HOT1-stimulated recombination but does not affect rDNA recombination or exchange in the absence of HOT1. Two new alleles of RAD52 were also isolated using this screen. With regard to HOT1 activity, rad52 is epistatic to all four hrm mutations indicating that the products of the HRM genes and of RAD52 mediate steps in the same recombination pathway. Finding mutations that decrease both the activity of HOT1 and exchange in the rDNA supports the hypothesis that HOT1 plays a role in rDNA recombination

ZUŻYCIE NOŚNIKÓW ENERGII W BUDYNKU JEDNORODZINNYM NA CELE OGRZEWANIA CIEPŁEJ WODY UŻYTKOWEJ I POTRZEB BYTOWYCH

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Aleksander STARAKIEWICZ

Full Text Available W artykule, przedstawiono faktyczne zużycie energii w istniejącym budynku jednorodzinnym w latach 2009 – 2015. Podstawą analizy są dane rzeczywistego zużycia nośników energii elektrycznej, węgla kamiennego, drewna przez instalację c.w.u. i c.o., ciepłej wody użytkowej, energii z kolektorów słonecznych oraz czasu pracy instalacji słonecznej. Przedstawiono również miesięczne zużycie rodzajów energii w systemie ogrzewania i ciepłej wody użytkowej w 2010 r. Omówiono wyposażenie budynku w instalacje wewnętrzne i sprzęt AGD oraz ich wpływ na ilość zużywanych nośników energii.

Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): new biomarkers in ankylosing spondylitis.

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Bodnár, Nóra; Szekanecz, Zoltán; Prohászka, Zoltán; Kemény-Beke, Adám; Némethné-Gyurcsik, Zsuzsanna; Gulyás, Katalin; Lakos, Gabriella; Sipka, Sándor; Szántó, Sándor

2012-01-01

Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS. Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices. Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3-31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4-13.3 U/mL) (p20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2-1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5-88.5 AU/mL) (p<0.001). Correlation analysis revealed that both anti-MCV positivity (r=0.613; p=0.012) and absolute serum anti-MCV levels (r=0.553; p=0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR (r=0.437; p=0.03). Anti-MCV and anti-hsp65 may be novel biomarkers in AS. Copyright © 2011. Published by Elsevier SAS.

Hereditary sensory and autonomic neuropathy type I in a Chinese family: British C133W mutation exists in the Chinese.

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Bi, Hongyan; Gao, Yunying; Yao, Sheng; Dong, Mingrui; Headley, Alexander Peter; Yuan, Yun

2007-10-01

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disorder of the peripheral nervous system characterized by marked progressive sensory loss, with variable autonomic and motor involvement. The HSAN I locus maps to chromosome 9q22.1-22.3 and is caused by mutations in the gene coding for serine palmitoyltransferase long chain base subunit 1 (SPTLC1). Sequencing in HSAN I families have previously identified mutations in exons 5, 6 and 13 of this gene. Here we report the clinical, electrophysiological and pathological findings of a proband in a Chinese family with HSAN I. The affected members showed almost typical clinical features. Electrophysiological findings showed an axonal, predominantly sensory, neuropathy with motor and autonomic involvement. Sural nerve biopsy showed loss of myelinated and unmyelinated fibers. SPTLC1 mutational analysis revealed the C133W mutation, a mutation common in British HSAN I families.

Rola wielonienasyconych kwasów tłuszczowych omega-3 w etiopatogenezie i leczeniu zaburzeń psychicznych

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Tomasz Pawełczyk

2010-12-01

Full Text Available Wielonienasycone kwasy tłuszczowe (WKT omega-3 są niezbędne do prawidłowego rozwoju i funkcji ośrodkowego układu nerwowego. Stanowią istotny element strukturalny neuronalnych błon komórkowych oraz są źródłem aktywnych biologicznie substancji, które pełnią złożone funkcje sygnałowe oraz uczestniczą w przekazywaniu informacji wewnątrz komórek. Zaburzenia metabolizmu lipidów i WKT obserwuje się w przebiegu wielu zaburzeń i chorób psychicznych: schizofrenii, zaburzeń afektywnych, zespołu nadpobudliwości psychoruchowej z deficytem uwagi, autyzmu i innych. Dysfunkcje te mają podłoże genetyczne i wraz z innymi nieprawidłowościami przyczyniają się do zwiększenia podatności na wystąpienie objawów psychopatologicznych danego zaburzenia. Ponadto dieta mieszkańców większości krajów europejskich nie zapewnia wystarczającej ilości WKT omega-3, które należą do substancji egzogennych, tj. niesyntetyzowanych w wystarczającej ilości w organizmie ludzkim. Co więcej, w przebiegu wielu zaburzeń psychicznych dochodzi do nadmiernej utraty długołańcuchowych WKT za pośrednictwem procesów ekscytotoksyczności i stresu oksydacyjnego, co dalej przyczynia się do uszczuplenia dostępnej puli WKT. W przypadku schizofrenii liczne badania eksperymentalne i kliniczne doprowadziły badaczy do sformułowania hipotezy wyjaśniającej rozwój tej choroby w oparciu o występowanie dysfunkcji metabolizmu lipidów. W pracy przedstawiono przegląd aktualnego piśmiennictwa oraz wyniki oryginalnych badań przeprowadzonych przez autorów zajmujących się problematyką zaburzeń metabolizmu WKT u chorych z wymienionymi wyżej zaburzeniami psychicznymi.

Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death

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Crotti, Lia; Tester, David J.; White, Wendy M.; Bartos, Daniel C.; Insolia, Roberto; Besana, Alessandra; Kunic, Jennifer D.; Will, Melissa L.; Velasco, Ellyn J.; Bair, Jennifer J.; Ghidoni, Alice; Cetin, Irene; Van Dyke, Daniel L.; Wick, Myra J.; Brost, Brian; Delisle, Brian P.; Facchinetti, Fabio; George, Alfred L.; Schwartz, Peter J.; Ackerman, Michael J.

2013-01-01

Importance Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. Objective To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. Design, Setting, and Patients In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Main Outcomes and Measures Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. Results The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation

WYSTĘPOWANIE ROŚLIN INWAZYJNYCH W OBRĘBIE BUDOWLI I POWIERZCHNI UTWARDZONYCH W DOLINACH RZECZNYCH KARPAT I KOTLINY SANDOMIERSKIEJ

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Dominik WRÓBEL

Full Text Available Badania terenowe, prowadzone w latach 2010-2016, w dolinach rzecznych polskiej części Karpat oraz w Kotlinie Sandomierskiej i w przylegającym do niej odcinku doliny Wisły, miały za zadanie uzupełnić, wiedzę o występowaniu inwazyjnych gatunków roślin (inwaderów w najsilniej przekształconych dolinach rzecznych, a w szczególności określić typy zabudowy dolin rzecznych, sprzyjające rozprzestrzenianiu się tych gatunków. Przeanalizowano 118 transektów zlokalizowanych zarówno w regionach górskich, podgórskich i nizinnych, w odcinkach uregulowanych jak i nieuregulowanych dolin rzecznych, cieków o różnej wielkości. Wyodrębniono główne typy/kategorie zabudowy, łączące w sobie: obiekty hydrotechniczne i przeciwpowodziowe, w tym obwałowania, umocnienia brzegowe i ostrogi korytowe (I, mieszkalną i usługową zabudowę śródmiejską (II, drogowe i kolejowe linie komunikacyjne, w tym mosty (III, wyrobiska górnicze, zabudowę produkcyjną, wydobywczą, magazynową i towarzyszącą (IV, zabudowę rozproszoną, ogródki działkowe (V oraz odrębne place, parkingi i składowiska (VI. Na częściach transektów, obejmujących różne formy zabudowy, najczęściej zanotowano występowanie Solidago gigantea / S. canadensis (46, Impatiens glandulifera (30, Echinocystis lobata (22, Robinia pseudoacacia (17, Helianthus tuberosus (15 i Impatiens parviflora (15. Największa liczba stanowisk gatunków inwazyjnych w relacji do wszystkich ich stwierdzeń została zanotowana na różnego rodzaju budowlach hydrotechnicznych, w tym na umocnieniach brzegowych różnego typu. Obserwacje prowadzone w zakresie wpływu inwestycji regulacyjnych na szatę roślinną wskazują, że nie ma istotnych różnic co do zastosowanych sposobów zabudowy umocnieniowej brzegów, które można byłoby uznać za bardziej przyjazne środowisku. W każdym przypadku następuje pozostawianie odkrytego podłoża i promowanie wkraczania inwaderów.

Fundus albipunctatus associated with compound heterozygous mutations in RPE65

DEFF Research Database (Denmark)

Schatz, Patrik; Preising, Markus; Lorenz, Birgit

2011-01-01

To describe a family with an 18-year-old woman with fundus albipunctatus and compound heterozygous mutations in RPE65 whose unaffected parents and 1 female sibling harbored single heterozygous RPE65 mutations.......To describe a family with an 18-year-old woman with fundus albipunctatus and compound heterozygous mutations in RPE65 whose unaffected parents and 1 female sibling harbored single heterozygous RPE65 mutations....

Czynniki ryzyka upadków i złamań kości u pacjentów chorych na reumatoidalne zapalenie stawów

Directory of Open Access Journals (Sweden)

Krzysztof Tomaszewski

2010-04-01

Full Text Available Cel pracy: Ocena czynników ryzyka i częstości występowaniaupadków i złamań kości u chorych na reumatoidalne zapaleniestawów (RZS. Materiał i metody: Do badania kwalifikowano pacjentów chorychna RZS (spełniających kryteria ACR z 1984 r.. Dane na temat stanuzdrowia zebrano na podstawie ankiety zawierającej Kwestio -nariusz Oceny Stanu Zdrowia (HAQ, pytań dotyczących chorób,przyjmowanych leków, upadków i złamań kości w okresie ostatnich12 miesięcy. Wyniki: Przebadano 167 kobiet (89,8% i 19 mężczyzn (średni wiek± SD 58,5 ±13,8 roku. Średni czas trwania choroby wynosił14,4 ±10,7 roku. Średnia wartość HAQ 1,36 ±0,76. Z grupy 186 osóbupadek przydarzył się 80 badanym (43%. U 28 chorych (35%upadek zakończył się złamaniem bądź złamaniami obwodowymi.Liczba upadków dodatnio korelowała z wynikiem HAQ (r = 0,32;p < 0,05 oraz czasem trwania choroby (r = 0,31; p < 0,05.Głównymi czynnikami ryzyka upadków w badanej grupie byłyzawroty głowy [iloraz szans (OR = 2,68], stosowanie lekówhipotensyjnych (OR = 2,27 i przeciwdepresyjnych (OR = 2,56,deformacje stóp (OR = 3,14 oraz wysoki wskaźnik HAQ(OR = 2,08. Czas trwania RZS (OR = 1,05 i wiek (OR = 1,04 praktycznienie wpływały na ryzyko upadków. Głównymi czynnikamiryzyka złamań kości w badanej grupie były osteoporoza (t-score< –2,5 (OR = 4,70, stosowanie leków hipotensyjnych (OR = 4,98,deformacje stóp (OR = 4,82, zawroty głowy (OR = 3,30 orazwysoki wskaźnik HAQ (OR = 3,12. Wnioski: Upadki są poważnym problemem w przebiegu RZS.Głównymi czynnikami sprzyjającymi upadkom i złamaniomu chorych na RZS są deformacje stóp, zawroty głowy, zażywanieleków obniżających ciśnienie tętnicze oraz wysoka wartość HAQ.

Metformina – mechanizmy działania i zastosowanie w terapii cukrzycy typu 2[i][/i

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Marzena Grzybowska

2011-01-01

Full Text Available Metformina jest obecnie najczęściej zalecanym lekiem w terapii cukrzycy typu 2. Mimo iż ta pochodna biguanidu jest stosowana od ponad 50 lat, mechanizm jej działania nie został dokładnie poznany. W pracy przedstawiono najnowsze doniesienia o mechanizmach antyhiperglikemicznego działania metforminy. Obejmują one: zmniejszenie wchłaniania glukozy w jelicie cienkim, zwiększony transport glukozy do komórek, obniżenie osoczowego stężenia wolnych kwasów tłuszczowych oraz hamowanie glukoneogenezy. Szczególną rolę w tych procesach odgrywa aktywacja kinazy białkowej aktywowanej przez AMP. Najnowsze odkrycia umożliwiły poznanie mechanizmów działania przeciwmiażdżycowego, hipotensyjnego i przeciwnowotworowego metforminy oraz jej wpływu na czynność śródbłonka naczyń. Plejotropowe działanie metforminy obejmuje wpływ na profil lipidowy osocza, zmniejszenie stresu oksydacyjnego, a także zwiększenie aktywności fibrynolitycznej osocza. Mimo że metformina nie jest metabolizowana, najnowsze badania wykazały, że jest aktywnie transportowana do hepatocytów, a także do komórek nabłonka kanalików nerkowych, odpowiednio przez OCT1 (organic cation transporter 1, kodowany przez gen SLC22A1 oraz OCT2 (kodowany przez [i]SLC22A2[/i]. Z kolei transporter MATE1 (multidrug and toxin extrusion 1 protein, kodowany przez gen [i]SLC47A1[/i] umożliwia wydzielanie metforminy z tych komórek do żółci lub moczu. Polimorfizm genów transporterów metforminy może się przyczynić do istotnych różnic w reakcji na lek.

R248Q mutation--Beyond p53-DNA binding.

Science.gov (United States)

Ng, Jeremy W K; Lama, Dilraj; Lukman, Suryani; Lane, David P; Verma, Chandra S; Sim, Adelene Y L

2015-12-01

R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor groove of DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that the R248Q mutation resulted in conformation changes in parts of DBD far from the mutation site. However, how information propagates from the mutation site to the rest of the DBD is still not well understood. We performed a series of all-atom molecular dynamics (MD) simulations to dissect sterics and charge effects of R248 on p53-DBD conformation: (i) wild-type p53 DBD; (ii) p53 DBD with an electrically neutral arginine side-chain; (iii) p53 DBD with R248A; (iv) p53 DBD with R248W; and (v) p53 DBD with R248Q. Our results agree well with experimental observations of global conformational changes induced by the R248Q mutation. Our simulations suggest that both charge- and sterics are important in the dynamics of the loop (L3) where the mutation resides. We show that helix 2 (H2) dynamics is altered as a result of a change in the hydrogen bonding partner of D281. In turn, neighboring L1 dynamics is altered: in mutants, L1 predominantly adopts the recessed conformation and is unable to interact with the major groove of DNA. We focused our attention the R248Q mutant that is commonly found in a wide range of cancer and observed changes at the zinc-binding pocket that might account for the dominant negative effects of R248Q. Furthermore, in our simulations, the S6/S7 turn was more frequently solvent exposed in R248Q, suggesting that there is a greater tendency of R248Q to partially unfold and possibly lead to an increased aggregation propensity. Finally, based on the observations made in our simulations, we propose strategies for the rescue of R248Q mutants. © 2015 Wiley Periodicals, Inc.

Resistance to linezolid in Staphylococcus spp. clinical isolates associated with ribosomal binding site modifications: novel mutation in domain V of 23S rRNA.

Science.gov (United States)

Musumeci, Rosario; Calaresu, Enrico; Gerosa, Jolanda; Oggioni, Davide; Bramati, Simone; Morelli, Patrizia; Mura, Ida; Piana, Andrea; Are, Bianca Maria; Cocuzza, Clementina Elvezia

2016-10-01

Linezolid is the main representative of the oxazolidinones, introduced in 2000 in clinical practice to treat severe Gram-positive infections. This compound inhibits protein synthesis by binding to the peptidyl transferase centre of the 50S bacterial ribosomal subunit. The aim of this study was to characterize 12 clinical strains of linezolid-resistant Staphylococcus spp. isolated in Northern Italy. All isolates of Staphylococcus spp. studied showed a multi-antibiotic resistance phenotype. In particular, all isolates showed the presence of the mecA gene associated with SSCmec types IVa, V or I. Mutations in domain V of 23S rRNA were shown to be the most prevalent mechanism of linezolid resistance: among these a new C2551T mutation was found in S. aureus, whilst the G2576T mutation was shown to be the most prevalent overall. Moreover, three S. epidermidis isolates were shown to have linezolid resistance associated only with alterations in both L3 and L4 ribosomal proteins. No strain was shown to harbor the previously described cfr gene. These results have shown how the clinical use of linezolid in Northern Italy has resulted in the selection of multiple antibiotic-resistant clinical isolates of Staphylococcus spp., with linezolid resistance in these strains being associated with mutations in 23S rRNA or ribosomal proteins L3 and L4.

Normal IncA Expression and Fusogenicity of Inclusions in Chlamydia trachomatis Isolates with the incA I47T Mutation

OpenAIRE

Pannekoek, Yvonne; van der Ende, Arie; Eijk, Paul P.; van Marle, Jan; de Witte, Moniek A.; Ossewaarde, Jacobus M.; van den Brule, Adriaan J. C.; Morré, Servaas A.; Dankert, Jacob

2001-01-01

To investigate the correlation between the incA I47T mutation in Chlamydia trachomatis and the nonfusogenic phenotype, the incA genes of 25 isolates were sequenced. Four major sequence types were identified. Seven isolates (28%) had the I47T mutation. Isolates representing the four sequence types expressed IncA in the membrane of one large single inclusion. In conclusion, the incA I47T mutation is not associated with the nonfusogenic phenotype.

Spuścizny konserwatorów zbiorów, kierowników i dyrektorów Biblioteki Poznańskiego Towarzystwa Przyjaciół Nauk

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Michał Boksa

2011-01-01

Full Text Available Artykuł prezentuje sylwetki konserwatorów zbiorów, kierowników i dyrektorów Biblioteki Poznańskiego Towarzystwa Przyjaciół Nauk (PTPN oraz to, co po nich pozostało w postaci archiwaliów. Od momentu powstania Biblioteka PTPN gromadziła rękopisy lub całe spuścizny wybitnych osób, w tym kierujących tą placówką. Również inne biblioteki i archiwa zakładowe instytucji, z którymi byli oni związani, włączały do swych zbiorów ich materiały archiwalne. Spuścizny Ludwiki Dobrzyńskiej-Rybickiej i Ryszarda Marciniaka znajdują się zarówno w Bibliotece PTPN, jak i w Polskiej Akademii Nauk Archiwum w Warszawie Oddział w Poznaniu. Znaczna część materiałów archiwalnych Bolesława Erzepkiego trafiła natomiast do Działu Zbiorów Specjalnych Biblioteki Raczyńskich w Poznaniu. Szczątkowe materiały archiwalne można też znaleźć w Archiwum Uniwersytetu im. Adama Mickiewicza w Poznaniu (Ludwika Dobrzyńska-Rybicka oraz w Archiwum Biblioteki Uniwersyteckiej w Poznaniu (Ludwika Dobrzyńska-Rybicka, Jan Baumgart, Aniela Koehlerówna.

Hypophosphatemic osteomalacia and bone sclerosis caused by a novel homozygous mutation of the FAM20C gene in an elderly man with a mild variant of Raine syndrome.

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Takeyari, Shinji; Yamamoto, Takehisa; Kinoshita, Yuka; Fukumoto, Seiji; Glorieux, Francis H; Michigami, Toshimi; Hasegawa, Kosei; Kitaoka, Taichi; Kubota, Takuo; Imanishi, Yasuo; Shimotsuji, Tsunesuke; Ozono, Keiichi

2014-10-01

Hypophosphatemia and increased serum fibroblast growth factor 23 (FGF23) levels have been reported in young brothers with compound heterozygous mutations for the FAM20C gene; however, rickets was not observed in these cases. We report an adult case of Raine syndrome accompanying hypophosphatemic osteomalacia with a homozygous FAM20C mutation (R408W) associated with increased periosteal bone formation in the long bones and an increase in bone mineral density in the femoral neck. The patient, a 61-year-old man, was born from a cousin-to-cousin marriage. A short stature and severe dental demineralization were reported at an elementary school age. Hypophosphatemia was noted inadvertently at 27years old, at which time he started to take an active vitamin D metabolite (alphacalcidol) and phosphate. He also manifested ossification of the posterior longitudinal ligament. On bone biopsy performed at the age of 41years, we found severe osteomalacia surrounding osteocytes, which appeared to be an advanced form of periosteocytic hypomineralized lesions compared to those reported in patients with X-linked hypophosphatemic rickets. Laboratory data at 61years of age revealed markedly increased serum intact-FGF23 levels, which were likely to be the cause of hypophosphatemia and the decreased level of 1,25(OH)2D. We recently identified a homozygous FAM20C mutation, which was R408W, in this patient. When expressed in HEK293 cells, the R408W mutant protein exhibited impaired kinase activity and secretion. Our findings suggest that certain homozygous FAM20C mutations can cause FGF23-related hypophosphatemic osteomalacia and indicate the multiple roles of FAM20C in bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Modification of UV-induced mutation frequency and cell survival of Escherichia coli B/r WP2 trpE65 by treatment before irradiation

International Nuclear Information System (INIS)

Doudney, C.O.; Rinaldi, C.N.

1984-01-01

The UV radiation survival curve of exponentially growing cultures of Escherichia coli B/r WP2 trpE65 was modified by pretreatment for short incubation periods (up to 20 min) with chloramphenicol such that an extended exponential section of intermediate slope appeared between the shoulder and the final exponential slope. Surges of mutation to tryptophan independence occurred with each increase in slope of the survival curve. These surges were separated by extended sections of little mutation. Nalidixic acid prevented both the changes in survival and mutation. Mutation curves obtained with overnight cultures had three extended sections of little mutation alternating with section of high mutation. Reincubation for 60 min in fresh medium reduced or eliminated the low-response sections. These reappeared after 80 to 90 min, when DNA had doubled in the culture and before the initial synchronous cell divisions had occurred. Nalidixic acid prevented this reappearance

Czy koarktacja aorty nadal jest przyczyną nadciśnienia tętniczego u nastolatków?

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Anna Półtorak-Krawczyk

2010-11-01

Full Text Available Koarktacja aorty stanowi około 5% wszystkich wrodzonych wad serca. W diagnostyce różnicowej nadciśnienia tętniczego (NT u nastoletnich pacjentów częstość występowania zwężenia cieśni aorty jako przyczyny NT szacuje się na około 3%. W naszym ośrodku na przełomie roku 2008/2009 (6 miesięcy wśród nastolatków diagnozowanych z powodu nadciśnienia tętniczego wykryto trzy przypadki koarktacji aorty (5,2%. Piętnastoletni chłopiec, B.J., został przyjęty do szpitala z powodu kłucia w okolicy serca i podwyższonych wartości ciśnienia tętniczego (maks. 170/90 mm Hg. Tętno na tętnicach udowych było wyczuwalne, ale słabiej niż na kończynach górnych. W badaniach dodatkowych – ciśnienie tętnicze (RR na kończynach dolnych: lewa (L – 112/51, prawa (P – 105/50 mm Hg; RR na kończynach górnych: L – 148/71, P – 144/65 mm Hg. Jedenastoletni chłopiec, R.C., został przyjęty do szpitala z powodu nieprawidłowych wartości ciśnienia tętniczego, którym towarzyszyły bóle głowy. Tętno na tętnicach udowych było słabo wyczuwalne. W badaniach dodatkowych – RR na kończynach dolnych: L – 84/44, P – 97/64 mm Hg; RR na kończynach górnych: L – 129/60, P – 139/61 mm Hg. Dwunastoletnią pacjentkę, P.D., przekazano ze szpitala powiatowego w trybie pilnym z powodu wysokiego ciśnienia tętniczego (190/105 mm Hg. Tętno na tętnicach udowych było bardzo słabo wyczuwalne. W badaniach dodatkowych – RR na kończynach dolnych: L – 93/55, P – 85/54 mm Hg; RR na kończynach górnych: L – 159/84, P – 162/86 mm Hg. Prezentowane przypadki mogły zostać zdiagnozowane znacznie wcześniej w oparciu o dokładne (np. bilansowe badanie fizykalne, które uwzględniałoby badanie tętna udowego w porównaniu z tętnem na kończynach górnych, a w przypadkach wątpliwych pomiar ciśnienia tętniczego na czterech kończynach. Chociaż koarktacja aorty jest rzadką przyczyną nadciśnienia tętniczego krwi w wieku m

Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation.

Science.gov (United States)

Lotinun, Sutada; Suwanwela, Jaijam; Poolthong, Suchit; Baron, Roland

2018-01-01

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W v and W sh /W sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast, W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

Prevalence of Dihydrofolate reductase gene mutations in Plasmodium falciparum isolate from pregnant women in Nigeria

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Olusola Ojurongbe

2011-12-01

Full Text Available We assessed the prevalence of Plasmodium falciparum and the frequency of the dhfr triple mutation that is associated with antifolate drug resistance among P. falciparumisolates obtained from pregnant women in Ilorin, Nigeria. The study included 179 women in the second and third trimester of pregnancy who have been exposed to intermittent preventive treatment in pregnancy (IPTp with sulfadoxinepyrimethamine. Thick and thin blood films and PCR were used for malaria parasite detection. Blood group and hemoglobin concentration were also determined. Mutations in P. falciparum dhfr were analyzed by sequencing DNA obtained from blood spots on filter paper. Prevalence of P. falciparum in the population (PCR corrected was 44.1% (79/179 with 66.7% and 33.3% in the second and third trimester, respectively. Primigravide (51.3% were more infected than multigravide (48.7% but the difference was not statistically significant. Women in blood group A had the highest P. falciparum malaria infection (30.8%. The mean hemoglobin concentration was lower among those infected with malaria parasite. Also, more women with the malaria parasite (38.4% had anemia compare to those without (21.4%. The prevalence of the P. falciparum dhfr mutant alleles was 64.1%, 61.5%, 38.5%, and 12.8% for I51, R59, N108 and T108, respectively. None of the samples had the L164 mutation. The combined triple dhfr mutation (51 + 59 + 108 in the population was 17.9% (7 of 39. Also, the prevalence of the triple mutant alleles was not significantly associated to the number of doses of SP taken by the women. These findings highlight the need for a regular assessment of IPTp/SP efficacy, and evaluation of possible alternative drugs.

Rewolucja i przewrót w historiografii. Bolszewizm w nowej perspektywie

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Damian Winczewski

2016-06-01

Full Text Available Celem artykułu jest omówienie serii esejów Johna Marota zebranych w książce The October Revolution in Prospect and Retrospect oraz zaprezentowanie tych tez autora, które zdają się wyróżniać na tle dotychczasowej historiografii dotyczącej Rewolucji Październikowej i polityki partii bolszewickiej. W ramach tego omówienia próbujemy zestawić poglądy autora z dotychczasowymi interpretacjami wydarzeń, do których treści zawarte w jego pracy się odnoszą i podjąć się oceny tego, na ile, po pierwsze, argumenty Marota wydają się być trafne, a po drugie, na ile są one rzeczywiście nowatorskie.

EGFR T790M mutation after chemotherapy for small cell lung cancer transformation of EGFR-positive non-small cell lung cancer

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Tomoaki Sonoda

Full Text Available In non-small cell lung cancer (NSCLC with an epidermal growth factor receptor (EGFR mutation, 50%–65% of cases acquire resistance after treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs because of an EGFR T790M point mutation and 3%–14% of these cases transformed to small cell lung cancer (SCLC. Generally, the EGFR T790M secondary mutation develops with ongoing ATP competitive inhibition. We present a case of a 76-year-old woman with lung adenocarcinoma harboring an EGFR-L858R mutation who received first-line gefitinib and developed SCLC transformation. She was administered several chemotherapy agents, including a platinum doublet. The primary lesion that showed SCLC transformation had reconverted to adenocarcinoma with EGFR L858R and T790M mutations at the time of a second re-biopsy. Therefore, she was administered osimertinib, which resulted in clinical remission. This case suggested that serial biopsies are necessary even after SCLC transformation. Keywords: NSCLC, EGFR mutation, SCLC transformation, T790M, Osimertinib

Detection of GAD65 Autoreactive T-Cells by HLA Class I Tetramers in Type 1 Diabetic Patients

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Laura Giuliani

2009-01-01

Full Text Available Type 1 diabetes (T1D is an autoimmune disease, in which pancreatic β cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of β cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65 ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.

SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.

Science.gov (United States)

Hanchate, Naresh Kumar; Giacobini, Paolo; Lhuillier, Pierre; Parkash, Jyoti; Espy, Cécile; Fouveaut, Corinne; Leroy, Chrystel; Baron, Stéphanie; Campagne, Céline; Vanacker, Charlotte; Collier, Francis; Cruaud, Corinne; Meyer, Vincent; García-Piñero, Alfons; Dewailly, Didier; Cortet-Rudelli, Christine; Gersak, Ksenija; Metz, Chantal; Chabrier, Gérard; Pugeat, Michel; Young, Jacques; Hardelin, Jean-Pierre; Prevot, Vincent; Dodé, Catherine

2012-08-01

Kallmann syndrome (KS) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance. Here, we report that Nrp1(sema/sema) mutant mice that lack a functional semaphorin-binding domain in neuropilin-1, an obligatory coreceptor of semaphorin-3A, have a KS-like phenotype. Pathohistological analysis of these mice indeed showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in increased mortality of newborn mice and reduced fertility in adults. We thus screened 386 KS patients for the presence of mutations in SEMA3A (by Sanger sequencing of all 17 coding exons and flanking splice sites) and identified nonsynonymous mutations in 24 patients, specifically, a frameshifting small deletion (D538fsX31) and seven different missense mutations (R66W, N153S, I400V, V435I, T688A, R730Q, R733H). All the mutations were found in heterozygous state. Seven mutations resulted in impaired secretion of semaphorin-3A by transfected COS-7 cells (D538fsX31, R66W, V435I) or reduced signaling activity of the secreted protein in the GN11 cell line derived from embryonic GnRH cells (N153S, I400V, T688A, R733H), which strongly suggests that these mutations have a pathogenic effect. Notably, mutations in other KS genes had already been identified, in heterozygous state, in five of these patients. Our findings indicate that semaphorin-3A signaling insufficiency contributes to the pathogenesis of KS and further substantiate the oligogenic pattern of inheritance in this developmental disorder.

SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.

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Naresh Kumar Hanchate

2012-08-01

Full Text Available Kallmann syndrome (KS associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance. Here, we report that Nrp1(sema/sema mutant mice that lack a functional semaphorin-binding domain in neuropilin-1, an obligatory coreceptor of semaphorin-3A, have a KS-like phenotype. Pathohistological analysis of these mice indeed showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in increased mortality of newborn mice and reduced fertility in adults. We thus screened 386 KS patients for the presence of mutations in SEMA3A (by Sanger sequencing of all 17 coding exons and flanking splice sites and identified nonsynonymous mutations in 24 patients, specifically, a frameshifting small deletion (D538fsX31 and seven different missense mutations (R66W, N153S, I400V, V435I, T688A, R730Q, R733H. All the mutations were found in heterozygous state. Seven mutations resulted in impaired secretion of semaphorin-3A by transfected COS-7 cells (D538fsX31, R66W, V435I or reduced signaling activity of the secreted protein in the GN11 cell line derived from embryonic GnRH cells (N153S, I400V, T688A, R733H, which strongly suggests that these mutations have a pathogenic effect. Notably, mutations in other KS genes had already been identified, in heterozygous state, in five of these patients. Our findings indicate that semaphorin-3A signaling insufficiency contributes to the pathogenesis of KS and further substantiate the oligogenic pattern of inheritance in this developmental disorder.

Charakterystyka etiologiczna udarów mózgu leczonych w Klinice Neurologii UM w Białymstoku z analizą czynników ryzyka

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Anna Syta-Krzyżanowska

2010-03-01

Full Text Available Wstęp: W przeprowadzonych w Polsce badaniach epidemiologicznych stwierdzono utrzymujący się od kilkunastu lat wysoki współczynnik zapadalności na pierwszy w życiu udar mózgu, wzrastający wykładniczo z wiekiem oraz połączony z wciąż dużą śmiertelnością. Poznanie czynników ryzyka oraz wprowadzenie profilaktyki może istotnie zmniejszyć powyższe wskaźniki. Celem pracy było przeprowadzenie analizy epidemiologicznej pacjentów z udarem mózgu hospitalizowanych na Pododdziale Udarowym Kliniki Neurologii USK w Białymstoku. Uwzględniono w szczególności etiologię z czynnikami ryzyka oraz śmiertelnością w zależności od wieku i płci chorych. Materiał i metody: Rozpatrzono wszystkie przypadki pacjentów hospitalizowanych w Klinice Neurologii USK w Białymstoku z powodu udaru mózgu w ciągu pełnego roku kalendarzowego. Posłużono się ankietami prowadzonymi w ramach Narodowego Programu Profilaktyki i Leczenia Chorób Sercowo-Naczyniowych (POLKARD. Obliczenia statystyczne wykonywano przy użyciu programu Statistica w wersji 8.0. Wyniki: Przeanalizowano wyniki 408 pacjentów, w tym 185 (45,3% kobiet oraz 223 (54,7% mężczyzn z rozpoznanym: krwotokiem podpajęczynówkowym – 6,9%, krwotokiem śródmózgowym – 12,5% oraz udarem niedokrwiennym – 80,6%. Etiologię zatorową pochodzenia sercowego zdiagnozowano u 39,4%, zakrzep dużych naczyń u 35%, natomiast udar zatokowy u 11,6% pacjentów. Najczęstszym czynnikiem ryzyka udaru niedokrwiennego mózgu było nadciśnienie tętnicze (81,2%, następnie migotanie przedsionków i choroba niedokrwienna serca (38%. Zmarło 11,6% chorych z udarem niedokrwiennym mózgu oraz 21,5% z udarem krwotocznym. Średnia śmiertelność wyniosła 13,5%. Wnioski: Najczęstszym czynnikiem ryzyka udaru mózgu było nadciśnienie tętnicze, które szczególnie często współwystępowało z dodatkowym czynnikiem ryzyka udaru niedokrwiennego mózgu. Prowadzenie leczenia udaru mózgu w pododdzia

Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.

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John W Yarham

2014-06-01

Full Text Available Identifying the genetic basis for mitochondrial diseases is technically challenging given the size of the mitochondrial proteome and the heterogeneity of disease presentations. Using next-generation exome sequencing, we identified in a patient with severe combined mitochondrial respiratory chain defects and corresponding perturbation in mitochondrial protein synthesis, a homozygous p.Arg323Gln mutation in TRIT1. This gene encodes human tRNA isopentenyltransferase, which is responsible for i6A37 modification of the anticodon loops of a small subset of cytosolic and mitochondrial tRNAs. Deficiency of i6A37 was previously shown in yeast to decrease translational efficiency and fidelity in a codon-specific manner. Modelling of the p.Arg323Gln mutation on the co-crystal structure of the homologous yeast isopentenyltransferase bound to a substrate tRNA, indicates that it is one of a series of adjacent basic side chains that interact with the tRNA backbone of the anticodon stem, somewhat removed from the catalytic center. We show that patient cells bearing the p.Arg323Gln TRIT1 mutation are severely deficient in i6A37 in both cytosolic and mitochondrial tRNAs. Complete complementation of the i6A37 deficiency of both cytosolic and mitochondrial tRNAs was achieved by transduction of patient fibroblasts with wild-type TRIT1. Moreover, we show that a previously-reported pathogenic m.7480A>G mt-tRNASer(UCN mutation in the anticodon loop sequence A36A37A38 recognised by TRIT1 causes a loss of i6A37 modification. These data demonstrate that deficiencies of i6A37 tRNA modification should be considered a potential mechanism of human disease caused by both nuclear gene and mitochondrial DNA mutations while providing insight into the structure and function of TRIT1 in the modification of cytosolic and mitochondrial tRNAs.

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal).

Science.gov (United States)

Spínola, Carla; Brehm, António; Spínola, Hélder

2011-01-01

Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that results from mutations in the HFE gene. Almost all patients with hereditary hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to hereditary hemochromatosis. One hundred and fifty-four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y, and S65C, by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33%, and 1% for H63D, C282Y, and S65C, respectively. Accordingly to our estimates, both genotypes associated to hereditary hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.

THE NOVEL OF THE JOURNALIST: ESRÂR-I CİNÂYÂT BİR GAZETECİNİN ROMANI: ESRÂR-I CİNÂYÂT

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Ferhat KORKMAZ

2011-09-01

Full Text Available Modernism in Turkish literature begins by the mediation of journal. Most of new literary types attained to our literature owe their existances and developments to journal. Yusuf Kâmil Paşa brings in first translation novel to Turkish by means of consecutive narrative for a newspaper. After that novels are published by means of consecutive narrative in Tanzimat era. Ahmet Mithat Efendi is both journalist and novelist. Ahmet Mithat Efendi who seeks compromise between journal and novel handles the contribution of both type to each other in Esrâr-ı Cinâyât novel. In the novel, he discusses the cooperation of a civil servant who encounters pressure and a true journalist for the criminals to be catched and handed over to the justice and for the relief of the conscience of public. The novelist that makes journal and journalist the most important component for the solution of events gives a lot of information about the journalism in Tanzimat era, as well. On this occasion, the affairs like journalism, typography, Newsprinting Regulation (Matbuat Nizamnamesi, freedom of notion newspaper- government relation and censorship become the most important matters that emphasize on in the novel. Türk edebiyatında modernleşme gazete aracılığıyla başlar. Edebiyatımıza yeni kazandırılan pek çok tür varlığını ve gelişimini gazeteye borçludur. Yusuf Kâmil Paşa, gazetede tefrika ettirmek suretiyle ilk çeviri romanı Türkçeye kazandırır. Bundan sonra Tanzimat döneminde roman, gazetelerde tefrika yoluyla yayımlanır. Ahmet Mithat Efendi hem gazeteci hem de romancıdır. Gazete ve roman arasında uzlaşma arayan Ahmet Mithat Efendi, Esrâr-ı Cinâyât romanında bu iki türün birbirine olan katkısını ele alır. Romanda doğruların yanında yer alan bir gazeteci ve baskıyla karşı karşıya kalan bir devlet memurunun suçluların yakalanıp adalete teslim edilmesi ve kamuoyunun vicdanının rahatlatılması için yaptıkları işbirliği

Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

Science.gov (United States)

Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

2018-01-01

Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa.

Science.gov (United States)

Brownstein, Zippora; Ben-Yosef, Tamar; Dagan, Orit; Frydman, Moshe; Abeliovich, Dvorah; Sagi, Michal; Abraham, Fabian A; Taitelbaum-Swead, Riki; Shohat, Mordechai; Hildesheimer, Minka; Friedman, Thomas B; Avraham, Karen B

2004-06-01

Usher syndrome is a frequent cause of the combination of deafness and blindness due to retinitis pigmentosa (RP). Five genes are known to underlie different forms of Usher syndrome type I (USH1). In the Ashkenazi Jewish population, the R245X mutation of the PCDH15 gene may be the most common cause of USH1 (Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RK, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB N Engl J Med 348: 1664-1670, 2003). To estimate what percentage of Ashkenazi Jewish children born with profound hearing loss will develop RP due to R245X, we examined the prevalence of the R245X PCDH15 mutation and its carrier rate among Ashkenazi Jews in Israel. Among probands diagnosed with nonsyndromic hearing loss not due to mutations of connexin 26 (GJB2) and/or connexin 30 (GJB6), and below the age of 10, 2 of 20 (10%) were homozygous for the R245X mutation. Among older nonsyndromic deaf individuals, no homozygotes were detected, although one individual was heterozygous for R245X. The carrier rate of the R245X mutation among the normal hearing Ashkenazi population in Israel was estimated at 1%. Ashkenazi Jewish children with profound prelingual hearing loss should be evaluated for the R245X PCDH15 mutation and undergo ophthalmologic evaluation to determine whether they will develop RP. Rehabilitation can then begin before loss of vision. Early use of cochlear implants in such cases may rescue these individuals from a dual neurosensory deficit.

WIEDZA I DEKLAROWANE POSTAWY RODZICÓW WOBEC SZCZEPIEŃ OCHRONNYCH DLA DZIECI W WARSZAWIE I TALLINIE

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Małgorzata Klotško

2015-12-01

Tel: 22 599 21 80 Fax: 22 599 21 81     Słowa kluczowe: szczepienia ochronne, zachowania zdrowotne, Polska, Estonia. Keywords: vaccination, health behaviors, Poland, Estonia.     Streszczenie   Wprowadzenie Szczepienia, jako jedno ze szczytowych osiągnięć w medycynie stanowią istotny element realizowania polityki zdrowotnej na szczeblu krajowym I globalnym. Regularne uodparnianie dzieci oraz ludzi dorosłych poprawiło jakość i przedłużyło długość życia. Ponadto szczepienia wyeliminowały ospę prawdziwą oraz przyczyniły się do ograniczenia występowania niektórych chorób takich jak polio, świnki czy tężca. Szczepienia zaliczane są do profilaktyki swoistej pierwszego rzędu, która ma za zadanie wpływać na jeden z trzech elementów łańcucha epidemicznego - na wrażliwą populację. Materiał i metody Materiał stanowiło 231 osób rodziców dzieci objętych obowiązkowymi szczepieniami ochronnymi w Warszawie i Tallinie. Wśród ankietowanych znalazły się 173 oraz 58 mężczyzn.. Badanie było przeprowadzone przy użyciu komputera CAWI (ang. Computer-Assisted Web Interview oraz  metodą papierową PAPI (ang. Paper nad Pencil Interview. Do obliczeń korelacji zastosowano test Chi, zaś za poziom istotności przyjęto wartość 0,05. Wyniki Po zastosowaniu metody top2boxes wynika, że w Estonii 30% wierzy w bezpieczeństwo szczepionek, natomiast 70% nie. W Polsce wynik ten kształtuje się odpowiednio na poziomie 38% i 62%. Po zastosowaniu metody top2boxes wynika, że w Estonii 48% badanych widzi w pormowaniu szczepień interes producentów, natomiast 52% nie zgadza się z tym.  Natomiast w Polsce na korzyści koncernów wskazuje 59% i 41 % zaprzecza tej teorii. Po zastosowaniu metody top2boxes okazuje się, że w Estonii 84% badanych popiera dobrowolność szczepień, natomiast 15% jest przeciwnych.  Natomiast w Polsce jest 65% zwolenników dobrowolności szczepień i 35 % jej przeciwników. Wnioski Rodzice w Estonii i Polsce s

Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay

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Rupreht Ruth

2007-11-01

Full Text Available Abstract Background Hereditary hemochromatosis (HH is a common genetic disease characterized by excessive iron overload that leads to multi-organ failure. Although the most prevalent genotype in HH is homozygosity for C282Y mutation of the HFE gene, two additional mutations, H63D and S65C, appear to be associated with a milder form of HH. The aim of this study was to develop a high-throughput assay for HFE mutations screening based on TaqMan technology and to determine the frequencies of HFE mutations in the Slovenian population. Methods Altogether, 1282 randomly selected blood donors from different Slovenian regions and 21 HH patients were analyzed for the presence of HFE mutations by an in-house developed real-time PCR assay based on TaqMan technology using shorter non-interfering fluorescent single nucleotide polymorphism (SNP-specific MGB probes. The assay was validated by RFLP analysis and DNA sequencing. Results The genotyping assay of the H63D, S65C and C282Y mutations in the HFE gene, based on TaqMan technology proved to be fast, reliable, with a high-throughput capability and 100% concordant with genotypes obtained by RFLP and DNA sequencing. The observed frequency of C282Y homozygotes in the group of HH patients was only 48%, others were of the heterogeneous HFE genotype. Among 1282 blood donors tested, the observed H63D, S65C and C282Y allele frequency were 12.8% (95% confidence interval (CI 11.5 – 14.2%, 1.8% (95% CI 1.4 – 2.5% and 3.6% (95% CI 3.0 – 4.5%, respectively. Approximately 33% of the tested subjects had at least one of the three HH mutations, and 1% of them were C282Y homozygotes or compound heterozygotes C282Y/H63D or C282Y/S65C, presenting an increased risk for iron overload disease. A significant variation in H63D allele frequency was observed for one of the Slovenian regions. Conclusion The improved real-time PCR assay for H63D, S65C and C282Y mutations detection is accurate, fast, cost-efficient and ready for

Normal IncA expression and fusogenicity of inclusions in Chlamydia trachomatis isolates with the incA I47T mutation

NARCIS (Netherlands)

Pannekoek, Y.; van der Ende, A.; Eijk, P. P.; van Marle, J.; de Witte, M. A.; Ossewaarde, J. M.; van den Brule, A. J.; Morré, S. A.; Dankert, J.

2001-01-01

To investigate the correlation between the incA I47T mutation in Chlamydia trachomatis and the nonfusogenic phenotype, the incA genes of 25 isolates were sequenced. Four major sequence types were identified. Seven isolates (28%) had the I47T mutation. Isolates representing the four sequence types

Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

DEFF Research Database (Denmark)

Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

2009-01-01

The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim.

Science.gov (United States)

Fiete, Dorothy; Mi, Yiling; Beranek, Mary; Baenziger, Nancy L; Baenziger, Jacques U

2017-05-01

Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. A recent whole-exome sequencing study identifies (c.229 C > T) in the GalNAc-4-ST1 glycosyltransferase (CHST8) as a disease-causing missense R77W mutation yielding the genodermatosis peeling skin syndrome (PSS) when homozygous. Cabral et al. (Genomics. 2012;99:202-208) cite this sequence change as reducing keratinocyte GalNAc-4-ST1 activity, thus decreasing glycosaminoglycan sulfation, as the mechanism for this blistering disorder. Such an identification could point toward potential clinical and/or prenatal diagnosis of a harmful medical condition. However, GalNAc-4-ST1 has minimal activity toward glycosaminoglycans, instead modifying terminal β1,4-linked GalNAc on N- and O-linked oligosaccharides on specific glycoproteins. We find expression, processing and catalytic activity of GalNAc-4-ST1 completely equivalent between wild type and (R77W) sulfotransferases. Moreover, keratinocytes have little or no GalNAc-4-ST1 mRNA, indicating that they do not express GalNAc-4-ST1. In addition, loss-of-function of GalNAc-4-ST1 primarily presents as reproductive system aberrations rather than skin effects. These findings, an allele frequency of 0.004357, and a 10-fold difference in prevalence of CHST8 (c.299 C > T, R77W) across different ethnic groups, suggest that this sequence represents a "passenger" distributed polymorphism, a simple sequence variant form of the enzyme having normal activity, rather than a "driver" disease-causing mutation that accounts for PSS. This study presents an example for guiding biomedical research initiatives, as well as medical and personal/family perspectives, regarding newly-identified genomic sequence

Emergence of methicillin-resistant coagulase-negative staphylococci resistant to linezolid with rRNA gene C2190T and G2603T mutations.

Science.gov (United States)

Cidral, Thiago André; Carvalho, Maria Cícera; Figueiredo, Agnes Marie Sá; de Melo, Maria Celeste Nunes

2015-10-01

The aim of this article were to determinate the mechanism of linezolid resistance in coagulase-negative methicillin-resistant staphylococci from hospitals in the northeast of Brazil. We identified the isolates using VITEK(®) 2 and MALDI-TOF. Susceptibility to antibiotics was measured by the disk-diffusion method and by Etest(®) . Extraction of the whole genome DNA was performed, followed by screening of all the strains for the presence of mecA and cfr genes. The domain V region of 23S rRNA gene was sequenced and then aligned with a linezolid-susceptible reference strain. Pulsed-field gel electrophoresis (PFGE) macro-restriction analysis was performed. Three linezolid-resistant Staphylococcus hominis and two linezolid-resistant Staphylococcus epidermidis strains were analyzed. The isolates showed two point mutations in the V region of the 23S rRNA gene (C2190T and G2603T). We did not detect the cfr gene in any isolate by PCR. The S. hominis showed the same pulsotype, while the S. epidermidis did not present any genetic relation to each other. In conclusion, this study revealed three S. hominis and two S. epidermidis strains with resistance to linezolid due to a double mutation (C2190T and G2603T) in the domain V of the 23S rRNA gene. For the first time, the mutation of C2190T in S. epidermidis is described. This study also revealed the clonal spread of a S. hominis pulsotype between three public hospitals in the city of Natal, Brazil. These findings highlight the importance of continued vigilance of linezolid resistance in staphylococci. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNASer(UCN) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss

International Nuclear Information System (INIS)

Yuan Huijun; Chen Jing; Liu Xin; Cheng Jing; Wang Xinjian; Yang Li; Yang Shuzhi; Cao Juyang; Kang Dongyang; Dai Pu; Zha, Suoqiang; Han Dongyi; Young Wieyen; Guan Minxin

2007-01-01

Mutations in mitochondrial DNA are one of the important causes of hearing loss. We report here the clinical, genetic, and molecular characterization of two Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset, and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 20% and 18%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 10% and 15%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T and CO1/tRNA Ser(UCN) G7444A mutations. Their distinct sets of mtDNA polymorphism belonged to Eastern Asian haplogroup C4a1, while other previously identified six Chinese mitochondrial genomes harboring the C1494T mutation belong to haplogroups D5a2, D, R, and F1, respectively. This suggested that the C1494T or G7444A mutation occurred sporadically and multiplied through evolution of the mitochondrial DNA (mtDNA). The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the 12S rRNA C1494T and CO1/tRNA Ser(UCN) G7444A mutations in those Chinese families. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families

Melancholia, tęsknota i saudade – czyli tożsamość narodowa Portugalczyków

OpenAIRE

Jurga, Marcin

2017-01-01

Artykuł unaocznia kluczowe znaczenie historii w procesie kształtowania tożsamości narodowej Portugalczyków. Artykuł analizuje m.in. portugalską tożsamość imperialną, mit sebastianizmu oraz fenomen saudade, a także podobieństwa i różnice w postrzeganiu historii w Portugalii i w Polsce. The article demonstrates the significance of history in the process of creating Portuguese national identity. It analyzes e.g. Portuguese imperial identity, the myth of King Sebastian (Sebastianism), the spec...

Le projet français P.I.V.E.R.T.

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Rous Jean-François

2012-11-01

Full Text Available P.I.V.E.R.T. is an ambitious project of development of the 3rd generation biorefinery by 2020. Conceived around a technological complex with strict environmental criteria (aiming at obtaining a label HQE, P.I.V.E.R.T. federates all the national and main roads lifeblood, of the sector (some international partnerships are also under development. The major objectives of the P.I.V.E.R.T. project are: a valorization of oilseeds, proteins and lignocellulosic plant in its entirety (approach ‘‘entire plants’’ ; an operation in closed circuit on the level of water and energy exchanges, the platform providing for its own needs, in a logic of industrial ecology ; collection and valorization of a significant part of the CO2 produced by the activities of the refinery. Two strategies will be developed jointly: on one hand the development of ‘‘platform’’ molecules entering the traditional circuits of chemistry, on the current markets with the renewable character, in addition, the development of new molecules having new properties, thus giving access to new markets. Thanks to the research and development realized by researchers dedicated to P.I.V.E.R.T., the industrial partners will have access to a capable structure to develop, and to test demonstrators preceding future industrial production units. Certain technological bricks could be tested in a large scale industrial platform dedicated to operational integration of innovations. The development of programming technologies of refineries will give to P.I.V.E.R.T. the means to develop new innovative processes and will give to the industrials the possibility of modeling their future production units.

Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation.

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Matsumoto, Takeshi; Fan, Xinping; Ishikawa, Eiji; Ito, Masaaki; Amano, Keishirou; Toyoda, Hidemi; Komada, Yoshihiro; Ohishi, Kohshi; Katayama, Naoyuki; Yoshida, Yoko; Matsumoto, Masanori; Fujimura, Yoshihiro; Ikejiri, Makoto; Wada, Hideo; Miyata, Toshiyuki

2014-11-01

Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of ≥20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan.

Instability of buried hydration sites increases protein subdomains fluctuations in the human prion protein by the pathogenic mutation T188R

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Katsufumi Tomobe

2016-05-01

Full Text Available The conformational change from the cellular prion protein (PrPc to scrapie prion protein (PrPsc is a key process in prion diseases. The prion protein has buried water molecules which significantly contribute to the stability of the protein; however, there has been no report investigating the influence on the buried hydration sites by a pathogenic mutation not adjacent to the buried hydration sites. Here, we perform molecular dynamics simulations of wild type (WT PrPc and pathogenic point mutant T188R to investigate conformational changes and the buried hydration sites. In WT-PrPc, four buried hydration sites are identified by residence time and rotational relaxation analysis. However, there are no stable buried hydration sites in one of T188R simulations, which indicates that T188R sometimes makes the buried hydration sites fragile. We also find that fluctuations of subdomains S1-H1-S2 and H1-H2 increase in T188R when the buried hydration sites become unstable. Since the side chain of arginine which is replaced from threonine in T188R is larger than of threonine, the side chain cannot be embedded in the protein, which is one of the causes of the instability of subdomains. These results show correlations between the buried hydration sites and the mutation which is far from them, and provide a possible explanation for the instability by mutation.

Instability of buried hydration sites increases protein subdomains fluctuations in the human prion protein by the pathogenic mutation T188R

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Tomobe, Katsufumi; Yamamoto, Eiji; Akimoto, Takuma; Yasui, Masato; Yasuoka, Kenji

2016-05-01

The conformational change from the cellular prion protein (PrPc) to scrapie prion protein (PrPsc) is a key process in prion diseases. The prion protein has buried water molecules which significantly contribute to the stability of the protein; however, there has been no report investigating the influence on the buried hydration sites by a pathogenic mutation not adjacent to the buried hydration sites. Here, we perform molecular dynamics simulations of wild type (WT) PrPc and pathogenic point mutant T188R to investigate conformational changes and the buried hydration sites. In WT-PrPc, four buried hydration sites are identified by residence time and rotational relaxation analysis. However, there are no stable buried hydration sites in one of T188R simulations, which indicates that T188R sometimes makes the buried hydration sites fragile. We also find that fluctuations of subdomains S1-H1-S2 and H1-H2 increase in T188R when the buried hydration sites become unstable. Since the side chain of arginine which is replaced from threonine in T188R is larger than of threonine, the side chain cannot be embedded in the protein, which is one of the causes of the instability of subdomains. These results show correlations between the buried hydration sites and the mutation which is far from them, and provide a possible explanation for the instability by mutation.

High frequency of Plasmodium falciparum chloroquine resistance marker (pfcrt T76 mutation) in Yemen: an urgent need to re-examine malaria drug policy.

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Al-Mekhlafi, Abdulsalam M; Mahdy, Mohammed A K; Al-Mekhlafi, Hesham M; Azazy, Ahmed A; Fong, Mun Yik

2011-05-27

Malaria remains a significant health problem in Yemen with Plasmodium falciparum being the predominant species which is responsible for 90% of the malaria cases. Despite serious concerns regarding increasing drug resistance, chloroquine is still used for the prevention and treatment of malaria in Yemen. This study was carried out to determine the prevalence of choloroquine resistance (CQR) of P. falciparum isolated from Yemen based on the pfcrt T76 mutation. A cross-sectional study was carried out among 511 participants from four governorates in Yemen. Blood samples were screened using microscopic and species-specific nested PCR based on the 18S rRNA gene to detect and identify Plasmodium species. Blood samples positive for P. falciparum were used for detecting the pfcrt T76 mutation using nested-PCR. The prevalence of pfcrt T76 mutation was 81.5% (66 of 81 isolates). Coastal areas/foothills had higher prevalence of pfcrt T76 mutation compared to highland areas (90.5% vs 71.8%) (p = 0.031). The pfcrt T76 mutation had a significant association with parasitaemia (p = 0.045). Univariate analysis shows a significant association of pfcrt T76 mutation with people aged > 10 years (OR = 9, 95% CI = 2.3 - 36.2, p = 0.001), low household income (OR = 5, 95% CI = 1.3 - 19.5, p = 0.027), no insecticide spray (OR = 3.7, 95% CI = 1.16 - 11.86, p = 0.025) and not sleeping under insecticide treated nets (ITNs) (OR = 4.8, 95% CI = 1.38 - 16.78, p = 0.01). Logistic regression model confirmed age > 10 years and low household income as predictors of pfcrt T76 mutation in Yemen P. falciparum isolates. The high prevalence of pfcrt T76 mutation in Yemen could be a predictive marker for the prevalence of P. falciparum CQR. This finding shows the necessity for an in-vivo therapeutic efficacy test for CQ. P. falciparum CQR should be addressed in the national strategy to control malaria.

Uzależnienie od Internetu (siecioholizm wśród młodzieży licealnej – konsekwencje zdrowotne i psychospołeczne

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Irena Białokoz-Kalinowska

2011-12-01

Full Text Available Wstęp: Dynamika rozwoju sfery informatycznej i medialnej we współczesnym świecie zmienia dotychczasowe formy funkcjonowania w życiu codziennym. Przykładem tego zjawiska jest Internet, który – powszechnie dostępny szerokiemu gronu odbiorców od zaledwie 20 lat – wyraźnie już wpłynął na styl życia całego społeczeństwa. Dzieci i młodzież stanowią szczególnie podatną grupę na oddziaływanie Internetu, a nieracjonalne korzystanie z niego może powodować niekorzystne skutki zdrowotne, z uzależnieniem włącznie. Cel pracy: Ocena ryzyka uzależnienia od Internetu wśród młodzieży licealnej. Materiał i metody: Badanie objęło 102 uczniów (43% badanej grupy stanowiły dziewczęta, 57% – chłopcy w wieku 17-19 lat (średnia wieku 18,3. W badaniu wykorzystano test Kimberly Young oraz kwestionariusz w opracowaniu własnym. Wyniki: Do grupy ryzyka uzależnienia od Internetu zakwalifikowano 20% badanych. Ponad 20 godzin tygodniowej aktywności w sieci deklarowało 22% respondentów, przy czym w grupie tej przeważali chłopcy – 78% vs 22% w grupie dziewcząt. Stwierdzono tendencję do zbyt długiego przebywania w sieci kosztem aktywnych form spędzania wolnego czasu i relacji bezpośrednich z rówieśnikami. Analiza form aktywności w Internecie wykazała preferencje zależne od płci. Chłopcy wybierali gry komputerowe 59% i strony o tematyce erotycznej 10%, zaś dziewczęta strony z muzyką 70%, wyszukiwarki internetowe 55%, portale aukcyjne 50% i społecznościowe 50%. U ponad 30% badanych występowały dolegliwości somatyczne związane z pracą przy komputerze. Wnioski: Nieracjonalne korzystanie z Internetu powoduje negatywne skutki w zakresie zdrowia somatycznego i psychospołecznego. Niezbędna jest zatem powszechna edukacja medialna zapobiegająca negatywnym zjawiskom związanym z korzystaniem z Internetu.

Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub-Saharan Africa: implications for the susceptibility to meningococcal disease.

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Franco-Jarava, C; Comas, D; Orren, A; Hernández-González, M; Colobran, R

2017-08-01

Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 families, and most C5 mutations (13 of 17) have been found in single families. However, the recently described C5 p.A252T mutation is reported to be associated with approximately 7% of meningococcal disease cases in South Africa. This finding raises the question of whether the mutation may be prevalent in other parts of Africa or other continental regions. The aim of this study was to investigate the prevalence of C5 p.A252T in Africa and other regions and discuss the implications for prophylaxis against meningococcal disease. In total, 2710 samples from healthy donors within various populations worldwide were analysed by quantitative polymerase chain reaction (qPCR) assay to detect the C5 p.A252T mutation. Eleven samples were found to be heterozygous for p.A252T, and nine of these samples were from sub-Saharan African populations (allele frequency 0·94%). Interestingly, two other heterozygous samples were from individuals in populations outside Africa (Israel and Pakistan). These findings, together with data from genomic variation databases, indicate a 0·5-2% prevalence of the C5 p.A252T mutation in heterozygosity in sub-Saharan Africa. Therefore, this mutation may have a relevant role in meningococcal disease susceptibility in this geographical area. © 2017 British Society for Immunology.

Nietrzymanie moczu a czynniki ryzyka i jakość życia kobiet w Zakładzie Opiekuńczo-Leczniczym w Kielcach

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Sławomir Dutkiewicz

2011-12-01

Full Text Available Wstęp: Jednym z najpoważniejszych problemów zdrowotnych jest nietrzymanie moczu (NTM. Częściej dotyczyon kobiet i dotyka ok. 3 mln kobiet rocznie. Cel pracy: Celem pracy była ocena czynników ryzyka NTM i wpływu tej dolegliwości na jakość życia kobietw Zakładzie Opiekuńczo-Leczniczym w Kielcach. Materiał i metody: Badano 60 kobiet po 50. r.ż. z NTM [w większości (76,7% badanych 71.–90. r.ż.]. Wyniki: U badanych 60 (100% kobiet z NTM współwystępowały nadciśnienie tętnicze ze względną niewydolnościąukładu krążenia, oddechowego, również ruchowego, a u 46 (77% kobiet także choroby przewlekłe,jak: cukrzyca, stwardnienie rozsiane, choroba Alzheimera, udar mózgu, depresja. Stwierdzono, iż na NTM u tychkobiet nie wpłynęły czynniki: wykształcenie i rodzaj pracy. Występowanie NTM korelowało u badanych kobietz powtarzającymi się zakażeniami moczu, które istotnie zależały od wieku badanych (p = 0,05 oraz od przyjmowanychleków moczopędnych, antydepresyjnych, przeciw nadciśnieniu tętniczemu. Wykazano także zależnośćod miejsca zamieszkania. Stwierdzono też występowanie NTM u badanych kobiet, które w przeszłości miałyzabiegi operacyjne na narządach okolicy miednicy mniejszej, a także rodziły więcej niż cztery razy. Wnioski: 1. U badanych kobiet po 70. r.ż. stwierdzono częstsze w porównaniu z młodszymi występowaniedysurii, naglących parć na mocz i nawrotów zakażeń moczu. 2. Nietrzymanie moczu u badanych wiązało sięz wieloma czynnikami ryzyka predysponującymi, promującymi oraz urazowymi. 3. Nietrzymanie moczu znaczniepogorszyło jakość życia u wszystkich badanych kobiet.

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

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Besic Nikola

2008-09-01

Full Text Available Abstract Background Two high-risk genes have been implicated in the development of CM (cutaneous melanoma. Germline mutations of the CDKN2A gene are found in CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease. The aims of our study were: to determine the prevalence of germline CDKN2A mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible CDK4 mutations, and to determine the frequency of variations in the MC1R gene. Methods From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing. Results Seven families with CDKN2A mutations were discovered (7/25 or 28.0%. The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54. One p14ARF variant was discovered in the control group and no mutations of the CDK4 gene were found. Most frequently found variants of the MC1R gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant. Conclusion The present study has shown high prevalence of p16INK4A mutations in Slovenian population of

Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.

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Anandapadamanaban, Madhanagopal; Pilstål, Robert; Andresen, Cecilia; Trewhella, Jill; Moche, Martin; Wallner, Björn; Sunnerhagen, Maria

2016-08-02

MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members. Copyright © 2016 Elsevier Ltd. All rights reserved.

A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.

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Hornemann, Thorsten; Penno, Anke; Richard, Stephane; Nicholson, Garth; van Dijk, Fleur S; Rotthier, Annelies; Timmerman, Vincent; von Eckardstein, Arnold

2009-04-01

Hereditary sensory neuropathy type 1 (HSAN I) is an autosomal dominant inherited neurodegenerative disorder of the peripheral nervous system associated with mutations in the SPTLC1 subunit of the serine palmitoyltransferase (SPT). Four missense mutations (C133W, C133Y, V144D and G387A) in SPTLC1 were reported to cause HSAN I. SPT catalyses the condensation of Serine and Palmitoyl-CoA, which is the first and rate-limiting step in the de novo synthesis of ceramides. Earlier studies showed that C133W and C133Y mutants have a reduced activity, whereas the impact of the V144D and G387A mutations on the human enzyme was not tested yet. In this paper, we show that none of the HSAN I mutations interferes with SPT complex formation. We demonstrate that also V144D has a reduced SPT activity, however to a lower extent than C133W and C133Y. In contrast, the G387A mutation showed no influence on SPT activity. Furthermore, the growth phenotype of LY-B cells--a SPTLC1 deficient CHO cell line--could be reversed by expressing either the wild-type SPTLC1 or the G387A mutant, but not the C133W mutant. This indicates that the G387A mutation is most likely not directly associated with HSAN I. These findings were genetically confirmed by the identification of a nuclear HSAN family which showed segregation of the G387A variant as a non-synonymous SNP.

Wpływ wykształcenia oraz aktywności fizycznej rodziców na poziom rozwoju zdolności szybkościowych dziewcząt wiejskich w młodszym wieku szkolnym

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Jarosław Fugiel

2009-06-01

Full Text Available Wstęp: Proces rozwoju motorycznego kształtowany jest przez czynniki biogeograficzne, społeczno-ekonomiczne oraz tryb życia, wynika również ze stanu zaawansowania rozwoju somatycznego. Znaczącą rolę przypisuje się zwłaszcza aktywności fizycznej, której poziom różnicowany jest głównie przez takie czynniki jak płeć, wiek,miejsce zamieszkania czy wykształcenie. Poziom aktywności fizycznej znacznie różni się w środowisku miejskim i wiejskim. Sytuacja ta w dużym stopniu wynika z odmiennych warunków socjalno-bytowych, różnic w ilości i dostępności do bazy sportowej oraz niższej świadomości dotyczącej promocji zdrowia. Również wykształcenie rodziców, które wpływa na poziom świadomości dotyczącej kształtowania rozwoju fizycznego potomstwa, jest niższe na wsi w porównaniu do populacji miejskiej. Czynniki te mogą decydować o poziomie i charakterze aktywności fizycznej oraz mogą wpływać na sprawność motoryczną dzieci i młodzieży wiejskiej. Celem pracy była ocena wpływu wykształcenia oraz aktywności fizycznej rodziców na poziom sprawności motorycznej dziewcząt wiejskich z Legnicko-Głogowskiego Zagłębia Miedziowego. Materiał i metody: Materiał do pracy zgromadzono w 1998 r. na terenie Zagłębia Miedziowego. Zbadano 69 dziewcząt w wieku 9 lat z wiejskich szkół okolic Legnicy i Głogowa. Zmierzono wysokość i masę ciała oraz przeprowadzono testy sprawności fizycznej: skok w dal z miejsca, rzut 1 kg piłką lekarską, bieg wahadłowy 10x5m i stukanie w krążki. Informacje na temat wykształcenia rodziców oraz ich aktywności fizycznej w zakresie uprawiania sportu uzyskano za pomocą ankiety. W analizie wykorzystano podstawowe obliczenia statystyczne oraz obliczono test t-Studenta dla grup niezależnych. Wyniki i wnioski: 1. Wykształcenie średnie lub wyższe ojca i matki wpływa na uzyskanie wyższego poziomu rozwoju somatycznego córek. Dziewczęta z tych grup uzyskują r

A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency.

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Nguyen, Thi Phuong Mai; Nguyen, Thu Hien; Ngo, Diem Ngoc; Vu, Chi Dung; Nguyen, Thi Kim Lien; Nong, Van Hai; Nguyen, Huy Hoang

2015-07-10

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5 years old at 2 years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription. Copyright © 2015 Elsevier B.V. All rights reserved.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

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Xia, Jun; Lu, Mi-Ze; Jiang, Yuan-Qiang; Yang, Guo-Hua; Zhuang, Yun; Sun, Hong-Li; Shen, Yun-Feng

2012-03-01

JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism

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Khateb, Mamduh; Ruimi, Nili; Khamisie, Hazem; Najajreh, Yousef; Mian, Afsar; Metodieva, Anna; Ruthardt, Martin; Mahajna, Jamal

2012-01-01

Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias. Despite high rates of clinical response, Ph (+) patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein. Of special interest is the ‘gatekeeper’ T315I mutation, which confers complete resistance to Abl kinase inhibitors. Recently, GNF-2, Abl allosteric kinase inhibitor, was demonstrated to possess cellular activity against Bcr-Abl transformed cells. Similarly to Abl kinase inhibitors (AKIs), GNF-2 failed to inhibit activity of mutated Bcr-Abl carrying the T315I mutation. Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs. In this study, we report a cooperation between AKIs and GNF-2 in inhibiting proliferation and clonigenicity of Ba/F3 cells carrying T315I mutated Bcr-Abl. Interestingly, cooperation was most evident between Dasatinib and GNF-2. Furthermore, we showed that GNF-2 was moderately active in inhibiting the activity of JAK2 kinase, and presence of AKIs augmented GNF-2 activity. Our data illustrated the ability of allosteric inhibitors such as GNF-2 to cooperate with AKIs to overcome T315I mutation by Bcr-Abl-independent mechanisms, providing a possibility of enhancing AKIs efficacy and overcoming resistance in Ph+ leukemia cells

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

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Ying Yang

2016-01-01

Full Text Available Maturity-onset diabetes of the young (MODY is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I and two HNF1A polymorphisms (p.I27L and p.S487N were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

Gradual Loss of ACTH Due to a Novel Mutation in LHX4: Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism

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Takagi, Masaki; Ishii, Tomohiro; Inokuchi, Mikako; Amano, Naoko; Narumi, Satoshi; Asakura, Yumi; Muroya, Koji; Hasegawa, Yukihiro; Adachi, Masanori; Hasegawa, Tomonobu

2012-01-01

Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations. This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic–pituitary -adrenal function is recommended for CH patients with LHX4 mutations. PMID:23029363

Rekomendacje Polskiego Towarzystwa Dermatologicznego dotyczące stosowania leków biologicznych w łuszczycy zwyczajnej i stawowej (łuszczycowym zapaleniu stawów

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Jacek Szepietowski

2010-02-01

Full Text Available Łuszczyca jest przewlekłą zapalną chorobą skóry dotyczącą około1–3% populacji rasy kaukaskiej. Wprowadzenie do leczenia tego schorzenialeków biologicznych, które cechują się dobrą skutecznościąi wysokim profilem bezpieczeństwa, spowodowało, że obecnie wieluchorych na łuszczycę może prowadzić normalny tryb życia. Z tegopowodu niezbędne jest, aby leki biologiczne były dostępne również dlapolskiej populacji pacjentów, zwłaszcza tych, u których inne metodyterapii okazały się nieskuteczne lub też nie mogą być stosowane. Obecnewytyczne opracowano w celu ułatwienia polskim dermatologomkwalifikowania pacjentów z łuszczycą do leczenia biologicznego i ichdalsze prowadzenie. Mamy nadzieję, że przedstawione wskazówkibędą cenną pomocą dla lekarzy, którzy dopiero rozpoczynają doświadczeniaz tą grupą leków.W polskich realiach ekonomicznych do leczenia biologicznego powinnibyć kwalifikowani pacjenci z łuszczycą zwyczajną o średnim lubdużym nasileniu, u których nie uzyskano poprawy po leczeniu z zastosowaniemprzynajmniej dwóch różnych metod tradycyjnej terapiiogólnej lub którzy mają przeciwwskazania do stosowania innychmetod terapii ogólnej. W przypadku łuszczycowego zapalenia stawówterapię lekami biologicznymi można rozważyć u pacjentów z jegoaktywną postacią, u których nie uzyskano wystarczającej poprawy pozastosowaniu przynajmniej dwóch przeciwreumatycznych leków modyfikujących przebieg choroby, podawanych w monoterapii lubpoliterapii. Autorzy nie rekomendują żadnego leku biologicznego jakopierwszego leku z wyboru. Decyzję tę lekarz podejmuje sam, w zależnościod indywidualnego przypadku i na podstawie bieżących danychpiśmiennictwa na temat ich skuteczności i bezpieczeństwa.

Stan wiedzy na temat czynników ryzyka i profilaktyki chorób cywilizacyjnych a zachowania zdrowotne pracowników medycznych i niemedycznych

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Grzegorz Józef Nowicki

2017-03-01

Full Text Available Cel pracy. Określenie stanu wiedzy na temat czynników ryzyka i profilaktyki wybranych chorób cywilizacyjnych i określenie związku z poziomem deklarowanych zachowań zdrowotnych wśród pracowników medycznych i niemedycznych. Materiał i metody. Badania przeprowadzono wśród 598 dorosłych osób pracujących, wykonujących zawody medyczne (grupa M i pozamedyczne (grupa P. Metodą badawczą był sondaż diagnostyczny przy użyciu Testu wiedzy na temat czynników ryzyka i profilaktyki chorób cywilizacyjnych (własnego autorstwa oraz Inwentarza Zachowań Zdrowotnych (IZZ. Wyniki. Analizując materiał badawczy na temat stanu wiedzy o czynnikach ryzyka i profilaktyce chorób cywilizacyjnych uzyskany od osób z grupy M, stwierdzono że: niski poziom wiedzy charakteryzował 1,97% (n=6 badanych, przeciętny 29,18% (n=89 a wysoki aż 68,85% (n=210. Natomiast w grupa P niski poziomem wiedzy charakteryzował 16,04% (n=47 respondentów, 55,29% (n=162 przeciętny, a 28,67% (n=84 – wysoki. Stwierdzono, że wśród badanych z grupy P wraz ze wzrostem poziomu wiedzy na temat czynników ryzyka i profilaktyki chorób cywilizacyjnych rośnie ocena ogólnego wskaźnika zachowań zdrowotnych oraz jego czterech kategorii (p<0,05. Wnioski. Stan wiedzy na temat czynników ryzyka i profilaktyki chorób cywilizacyjnych stanowi ważny czynnik determinujący poziom zachowań zdrowotnych głównie wśród osób wykonujących zawody pozamedyczne.

Interleukin-7 receptor-α gene mutations are not detected in adult T-cell acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Rozovski, Uri; Li, Ping; Harris, David; Ohanian, Maro; Kantarjian, Hagop; Estrov, Zeev

2014-01-01

Somatic mutations in cancer cell genes are classified according to their functional significance. Those that provide the malignant cells with significant advantage are collectively referred to as driver mutations and those that do not, are the passenger mutations. Accordingly, analytical criteria to distinguish driver mutations from passenger mutations have been recently suggested. Recent studies revealed mutations in interleukin-7 receptor-α (IL7R) gene in 10% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients and in only a few cases of pediatric B-ALL. IL7R mutations are also frequently found in patients with lung cancer, but whereas in pediatric T-ALL IL7R mutations are “drivers” (consisting of gain-of-function mutations within a narrow 50-base pair interval at exon 6 that confer cytokine-independent cell growth and promote tumor transformation), in lung cancer, mutations are substitution mutations randomly distributed across the gene and are probably only “passenger” events. Because the treatment response of adult T-ALL is significantly poorer than that of childhood T-ALL and because exon 6 IL7R mutations play a role in the pathogenesis of childhood T-ALL, we sought to determine how the pattern of IL7R mutations varies between adult and childhood T-ALL. To that end, we sequenced the 50-base pair interval in exon 6 of the IL7R of DNA obtained from bone marrow samples of 35 randomly selected adult patients with T-ALL. Our analysis revealed that none of these 35 samples carried an IL7R mutation in exon 6. Whether differences in the genetic makeup of adult and childhood T-ALL explain the differential response to therapy remains to be determined

High prevalence of Plasmodium falciparum pfcrt K76T mutation in ...

African Journals Online (AJOL)

This study investigated the prevalence of malaria in SCD patients and mutations associated with CQ resistance. Children diagnosed with sickle cell disease attending both outpatient clinic and those admitted at Bugando Medical Centre in north-western Tanzania were screened for malaria using thick blood smear. A dried ...

Repair of damage induced by ultraviolet radiation in mutator T-1 Escherichia coli transductants

International Nuclear Information System (INIS)

Sideropoulos, A.S.; Greenberg, J.; Warren, G.

1975-01-01

To ascertain whether a relationship commonly exists between azide resistance, ultraviolet (uv) resistance, and the mutator property (mut T-1), we performed uv survival and mutation frequency determinations with and without caffeine (2.571 mM) in nonmutator azide resistant (azi/sup r/) and phage mediated mut T-1 transductants of Escherichia coli K-12, B/r, B/r T-, Bs-1, and Bs-8. The strains constructed were assumed to be ''co-isogenic'' except for the mutator factor. The frequency of mutation to streptomycin resistance (str/sup r/) was relatively constant and approximated 2 x 10- 7 . Transductants carrying the azide marker with or without the mut T-1 gene had the same level of uv survival as the parent with the same mutator phenotype. Dark repair of the prelethal uv lesion is equally caffeine sensitive in the nonmutator and mutator HCR+ strains. Our results indicated that the mut T-1 strains possess an efficient dark repair system for uv damage and that the mechanism of mut T-1 action is independent of uv dark repair processes. (auth)

Krótkoterminowe zmiany maksymalnej temperatury powietrza w półroczu chłodnym w Polsce

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Dominika Ciaranek

2016-03-01

Full Text Available W opracowaniu przedstawiono analizę zmian temperatury powietrza z dnia na dzień (T2–T1 oraz w ciągu kolejnych trzech (T3–T1 i czterech dni (T4–T1. Zostały one wyliczone na podstawie dobowych wartości temperatury maksymalnej powietrza w półroczu chłodnym (X–III z pięciu stacji w Polsce (Łeba, Warszawa, Kraków, Poznań, Włodawa, z lat 1961–2010. Średnie wieloletnie różnice krótkoterminowych zmian temperatury maksymalnej w badanym półroczu wahały się w przedziale 1,7–2,4°C na różnych stacjach, natomiast w ekstremalnych przypadkach zmiany z dnia na dzień (głównie spadki osiągały wartość 20,3°C, a w ciągu kolejnych 3 lub 4 dni odpowiednio 24,0°C i 25,6°C. Stacje położone w środkowej Polsce charakteryzowały się podobnymi tendencjami zmian wartości temperatury. Największe różnice stwierdzono na stacjach w Łebie i Krakowie. W pracy szczególną uwagę zwrócono na liczbę dni z gwałtowną zmianą temperatury, za którą uznano różnicę większą bądź równą 10,0°C. Częstość takich dni w badanym wieloleciu stanowiła 9% przypadków, z niewielką przewagą spadków temperatury nad wzrostami. W wieloletnim przebiegu stwierdzono niewielką przewagę liczby przypadków gwałtownych zmian w pierwszym 25-leciu omawianego okresu (1961–1985 nad drugim (1986–2010.

Deskrypcja długości i szerokości stóp kobiet i mężczyzn w obciążeniu masą własną, w wieku od 4 do 18 lat w świetle mory projekcyjnej

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Mirosław Mrozkowiak

2015-09-01

Mirosław Mrozkowiak   Uniwersytet Kazimierza Wielkiego, Instytut Kultury Fizycznej, Bydgoszcz e-mail: magmar54@interia.pl, strona: http://wadypostawy.republika.pl   Słowa kluczowe: długość i szerokość stopy.   Streszczenie   Wstęp. Długość i szerokość stopy to cechy, których przyśpieszony wzrost w okresie pokwitania pojawia się najwcześniej. U chłopców przypada na okres między 12,5 a13 r.ż., wg innych doniesień długość i szerokość stopy u chłopców wzrasta do 18 r.ż. Z wiekiem stopa zmienia się z szerokiej i krótkiej u noworodków, do pośredniej u dzieci starszych. Cel. Określenie przebiegu zmian średnich wartości długości i szerokości stóp, okresów gwałtownego wzrostu i spowolnienia przyrostu badanych parametrów w grupie dziewcząt i chłopców w wieku od 4 do 18 lat. Materiał i metodyka. Pomiarami długości i szerokości stóp objęto populację 9804 dziewcząt i 8699 chłopców w wieku od 4 do 18 lat, z losowo wybranych przedszkoli i szkół regionu warmińsko–mazurskiego. Do oceny wykorzystano stanowisko do komputerowej oceny postawy ciała, techniką mory projekcyjnej. Wyniki. Krzywa średnich wartości długości stóp obojga płci ma bardzo zbliżony przebieg  do wykresu właściwej płci. Krzywa rozpoczyna się wartością P: 168,2, L:168,22 mm, kończy P: 238,0, L:233,3 mm. W 14 r.ż. występuje obniżenie wartości do P: 214,68, L:209,91 mm. Szerokość posiada wartość początkową P: 62,99, L:64,92 mm, końcową P: 90,8, L:90,18 mm. W 14 r.ż. występuje załamanie do wartości P: 81,82, L:82,39 mm. Wnioski     1. Przyrost długości i szerokości stóp populacji żeńskiej i męskiej od 4 do 18 r.ż. jest równomiernie intensywny, przy czym w 14 r.ż. następuje spowolnienie przyrostu wielkości badanych cech.     2. Przebieg zmian średnich wielkości długości i szerokości stopy w wieku od 4 do 18 lat regionu warmińsko – mazurskiego nie znajduje w pełni potwierdzenia w badaniach metod

1980 Directory of Experts on Organization and Management of Construction/CIB W-65 Commission.

Science.gov (United States)

1981-02-02

Juie I )7t) J,; o iri t An iiKoc h, The Rullr i Tenirn ogv i r.t 1hI r ir t ’’i tt - on tr hre ru It en 0 tt ts P h DOi 1fit I-s epr 1 𔃻 , i nrd Ma rin...Charge of Projects - Construction Company 1935 - 1939 Projects Design Engineer - Consultants Office PUBLICATIONS Pszenicid, M., Efficiency of System

POChP a astma oskrzelowa - podobieństwa i różnice w diagnostyce i leczeniu w pracy Ratownika Medycznego

OpenAIRE

Nowak, Jakub

2015-01-01

Nierecenzowany artykuł poglądowy Przewlekła obturacyjna choroba płuc i astma oskrzelowa to choroby rozpowszechnione we współczesnym świecie, szczególnie w krajach o wysokim stopniu cywilizacji. Stopień cywilizacji, który niesie ze sobą zanieczyszczenie środowiska naturalnego, gwałtowny wzrost tempa życia nasila występowanie chorób dających objawy duszności. Duszność spowodowana zaistniałą sytuacją stresową, schorzeniami kardiologicznymi, jak również chorobami dróg oddechowych. POChP, a...

Fluktuacja dynamiki i dymorfizm płciowy cech somatycznych, typu budowy i otłuszczenia ciała dzieci i młodzieży w wieku od 4 do 18 lat środowiska wiejskiego regionu warmińsko-mazurskiego

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Mirosław Mrozkowiak

2015-07-01

Mirosław Mrozkowiak   Mirosław Mrozkowiak Bioergonsport, Nowa Biała. Polska e-mail: magmar54@interia.pl strona: http://wadypostawy.republika.pl   Słowa kluczowe: wysokość i masa ciała, wskaźnik BMI, IR.   Streszczenie Wstęp. Mimo sekularnego zwiększenia wysokości ciała we wszystkich grupach i płciach, dystanse międzyśrodowiskowe nie wykazywały tendencji malejących, jednak wszystkie populacje dążą do pewnej stabilizacji. Powszechnie stosowany wskaźnik wagowo-wzrostowym BMI umożliwił diagnostykę otyłości i nadwagi, a wskaźnik IR określenie typu budowy ciała. Celem badań jest określenie dynamiki zmian i dymorfizmu płciowego cech somatycznych, typu budowy i otłuszczenia ciała dzieci i młodzieży w wieku od 4 do 18 lat środowiska wiejskiego, regionu warmińsko-mazurskiego Polski. Metoda i materiał. Z badań uzyskano 8270 obserwacji w tym 3384 wśród dziewcząt i 3786 chłopców. Pomiarów dokonano na wadze lekarskiej z dokładnością do 0,5 cm i 100 g. Wyniki. Statystykę opisową wskaźnika BMI przedstawiono w tab. 2 oraz ryc. 1. Dynamikę zmian i istotność różnic między płciami w kategoriach wiekowych w tab. 3 i 4 oraz ryc. 2. Statystykę opisową wskaźnika IR przedstawiono w tab. 5 i ryc. 3. Dynamikę zmian i istotność różnic między płciami w kategoriach wiekowych w tab. 6 i 7 oraz ryc. 4. W tab. 8 przedstawiono przyjętą interpretację wskaźnika IR, w 9 wskaźnika BMI, w tab. 10, 11 i 12 oraz ryc. od 5 do 9 przedstawiony jest odsetek typów budowy i otłuszczenia występujący w badanej kohorcie. Wnioski. 1. Średnia wysokość i masa ciała chłopców w wieku od 4 do 18 r.ż. jest większa niż dziewcząt w tym samym wieku. 2. Wśród dziewcząt i chłopców dominuje smukły typ budowy ciała. Wśród chłopców w wieku 17 lat występuje tylko typ smukły, a w 18 r.ż. średni. 3. Odsetek z niedowagą utrzymuje się na wysokim poziomie wśród dziewcząt i chłopców do 8 r.ż., później sukcesywnie obni

Potencjał olejków eterycznych w profilaktyce i terapii grzybic

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Monika Sienkiewicz

2008-10-01

Full Text Available Silne właściwości antyseptyczne olejków eterycznych znane są od wielu wieków. Są one produktami metabolizmu wtórnego roślin. Olejki eteryczne i ich składniki wykazują działanie hamujące wzrost wobec bakterii, grzybów, wirusów i pierwotniaków. Ich aktywność przeciwdrobnoustrojowa jest ściśle związana ze składem chemicznym. Do tej pory nie odnotowano doniesień o rosnącej oporności szczepów bakterii i grzybów na składniki olejków. Olejki eteryczne wykazują m.in. właściwości przeciwzapalne, przeciwbólowe i antyoksydacyjne. Do najbardziej skutecznych olejków o najsilniejszych właściwościach przeciwgrzybiczych należą olejki pozyskiwane z drzewa herbacianego, tymianku, oregano, cząbru, bazylii, szałwi, goździkowca i cynamonowca. Największą aktywnością charakteryzują się olejki zawierające fenole – tymol, karwakrol i eugenol. Olejki tymiankowy, oreganowy i cząbrowy zawierają tymol i karwakrol, natomiast pozyskiwane z goździkowca i z liści cynamonowca zawierają eugenol. Jeden z najbardziej efektywnych olejków jest pozyskiwany z drzewa herbacianego (Melaleuca alternifolia. Olejek ten wykazuje wysoką aktywność wobec Candida sp., Trichophyton sp. i Microsporum sp. Olejki tymiankowy, oreganowy i rozmarynowy ze względu na szerokie spektrum aktywności mogą być polecane w leczeniu zakażeń wywoływanych przez Candida albicans, Trichophyton sp., Epidermophyton floccosum i Microsporum canis. Olejek goździkowy i cynamonowy z liści wykazują znaczące działanie hamujące wobec Aspergillus flavus, Aspergillus parasiticus, Candida albicans i Cryptococcus neoformans. Olejki eteryczne oraz ich składniki mogą posiadać silne działanie immunostymulujące, zaliczamy do nich: olejek sosnowy, cytrynowy, geraniowy, a-pinen. Olejki eteryczne znalazły zastosowanie w leczeniu infekcji dermatologicznych pochodzenia grzybiczego. Dobre wyniki przynosi również stosowanie olejków w ginekologii i w terapii

An MPL W515L mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis: A case report.

Science.gov (United States)

Hao, Lin; Sen, Sandeep; Sugumar, Dhivya

2015-02-01

The current study presents the case of a 63-year-old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 μg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion-independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS-T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK-STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.

Bianchi type-I universe in f(R, T) modified gravity with quark matter and Λ

Science.gov (United States)

Ćaǧlar, Halife; Aygün, Sezgin

2017-02-01

In this study, we investigate homogeneous and anisotropic Bianchi type I universe in the presence of quark matter source in f(R, T) gravity (Harko et al. in Phys. Rev. D 84:024020, 2011) with cosmological constant Λ (where R is the Ricci scalar and T is the trace of the energy momentum tensor). For this aim we have used the anisotropy feature of Bianchi type I universe and equation of states (EoS) of quark matter. We explore the exact solution f(R,T)=R+2f(T) model for Bianchi type I universe model. When t→∞, we get very small cosmological constant value, this result agrees with recent observations.

Centralna Biblioteka Uniwersytecka Karola I w Bukareszcie

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Iuliana Grażyńska

2015-12-01

Full Text Available W artykule omówione zostały doświadczenia, jakie autorka zdobyła podczas stażu w ramach programu Erasmus w Centralnej Bibliotece Uniwersyteckiej Karola I w Bukareszcie, jednej z najbardziej dotkniętych przez los bibliotek. Autorka odnotowuje różnice i podobieństwa między rumuńskim i polskim systemem bibliotecznym, omawia metody opracowywania książek w Oddziale Zbiorów Specjalnych, pozostałe usługi biblioteczne oraz przypomina burzliwą historię biblioteki. Bukareszteńska Biblioteka Uniwersytecka pierwsza w Rumunii wprowadziła zintegrowany system informacji. Książki opracowuje się w programie komputerowym opisów bibliograficznych VUBIS, który używa formatu UN IMAR C. Współpraca biblioteki z partnerami zagranicznymi pozwala na dostęp do najnowszych wyników badań i kompleksowych usług badawczych.

Aloplastyka stawów śródręczno-paliczkowych ręki u chorych z reumatoidalnym zapaleniem stawów – wczoraj i dziś

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Iwona Słowińska

2011-10-01

Full Text Available W pracy przedstawiono historię leczenia operacyjnego stawówśródręczno-paliczkowych ręki z użyciem endoprotez u chorych nareumatoidalne zapalenie stawów w Klinice Reumoortopedii InstytutuReumatologii w Warszawie (ryc. 1–4.

[r,s,t]-colourings of paths

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Marta Salvador Villà

2007-01-01

Full Text Available The concept of \\([r,s,t]\\-colourings was recently introduced by Hackmann, Kemnitz and Marangio [A. Kemnitz, M. Marangio, \\([r,s,t]\\-Colorings of Graphs, Discrete Math., to appear] as follows: Given non-negative integers \\(r\\, \\(s\\ and \\(t\\, an \\([r,s,t]\\-colouring of a graph \\(G=(V(G,E(G\\ is a mapping \\(c\\ from \\(V(G \\cup E(G\\ to the colour set \\(\\{1,2,\\ldots ,k\\}\\ such that \\(|c(v_i-c(v_j| \\geq r\\ for every two adjacent vertices \\(v_i\\, \\(v_j\\, \\(|c(e_i-c(e_j| \\geq s\\ for every two adjacent edges \\(e_i\\, \\(e_j\\, and \\(|c(v_i-c(e_j| \\geq t\\ for all pairs of incident vertices and edges, respectively. The \\([r,s,t]\\-chromatic number \\(\\chi_{r,s,t}(G\\ of \\(G\\ is defined to be the minimum \\(k\\ such that \\(G\\ admits an \\([r,s,t]\\-colouring. In this paper, we determine the \\([r,s,t]\\-chromatic number for paths.

White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

Science.gov (United States)

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

White matter fiber-based analysis of T1w/T2w ratio map

Science.gov (United States)

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

Krioterapia ogólnoustrojowa zmniejsza aktywność fibrynolityczną krwi u chorych na reumatoidalne zapalenie stawów i osób z chorobą zwyrodnieniową stawów

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Julita Istrati

2010-06-01

Full Text Available W reumatoidalnym zapaleniu stawów (RZS istnieje podwyższoneryzyko występowania zawału serca i innych powikłań ze strony układukrążenia. W aktywnym RZS stwierdza się ponadto stan pobudzeniaukładu krzepnięcia i fibrynolizy, co w pewnym stopniu tłumaczyczęstsze incydenty sercowo-naczyniowe. Celem przeprowadzonychbadań było sprawdzenie, czy powszechnie uznana za bezpieczną,ogólnoustrojowa krioterapia stosowana w fizykoterapii RZS możezaburzać chwiejną równowagę układu hemostatycznego. Wykonanobadania wybranych parametrów układu krzepnięcia i fibrynolizyu 46 pacjentów z RZS oraz 20 pacjentów z chorobą zwyrodnieniowąstawów (OA, poddanych 10 cyklom leczenia w komorze kriogenicznej(w temperaturze –120°C przez 3 min. Stwierdzono, że taka terapianie powoduje hamowania odczynu ostrej fazy u chorych na RZS– stężenie białka C-reaktywnego (CRP we krwi nie uległo zmianie.Zaobserwowano natomiast zmiany w układzie fibrynolitycznymw postaci zmniejszenia stężenia tkankowego aktywatora plazminogenu(t-PA w osoczu i zwiększenia stężenia kompleksów plazminy––antyplazminy (PAP (p < 0,05 u chorych na RZS, a także zmniejszeniastężenia t-PA i zwiększenia stężenia inhibitora aktywatoraplazminogenu (PAI-1 (p < 0,05 u chorych na OA. Pomimo brakujakichkolwiek negatywnych objawów klinicznych związanych z tymizmianami autorzy uważają, że terapia chorych na RZS w komorzekriogenicznej może zaburzać równowagę w układzie hemostazy–fibrynolizy i u niektórych pacjentów może zwiększać ryzyko zakrzepicyi powikłań sercowo-naczyniowych.

Strong association between a splice mutation (IVS12+5G{r_arrow}A) and haplotype 6 in hereditary tyrosinemia type I

Energy Technology Data Exchange (ETDEWEB)

Tanguay, R.M.; St-Louis, M.; Gibson, K. [Universite Laval, Ste-Foy (Canada)] [and others

1994-09-01

Hereditary tyrosinemia type I (HT I; McKusick 276700) is a severe inborn error of tyrosine catabolism pathway caused by a deficiency of fumarylacetoacetate hydrolase (FAH). The highest frequency reported is the one in Saguenay-Lac St-Jean (Quebec, Canada) where 1:1,846 births are affected. The FAH gene has been cloned and several mutations have been described. Allele specific oligonucleotide (ASO) hybridization was used to examine the frequency of a splice (IVS12-5G{r_arrow}A) mutation recently reported and RFLP analysis was done to identify haplotypes related to HT I. The splice mutation was found on 45/50 alleles (90%) in patients from SLSJ and 12/66 (18%) alleles from patients world-wide. All 25 patients from the SLSJ region were positive with 20 being homozygous, indicating that this mutation is the major cause of HT I in French Canada. Of these 25 patients, 96% were positive for one haplotype called no 6 which is these 25 patients, 96% were positive for one haplotype called no 6 which is identified by TaqI, RsaI, BglII, MspI and KpnI digestions. These data show a really strong association between the mutation (IVS12+5G{r_arrow}A) and haplotype 6. Among our patients from around the world, {approximately}52% were positive for haplotype 6 indicating its strong relation with HT I. These results provide the rationale for DNA-based carrier testing for HT I in the F-C population at risk as well as in HT I patients in general.

Molecular analysis of congenital goitres with hypothyroidism caused by defective thyroglobulin synthesis. Identification of a novel c.7006C>T [p.R2317X] mutation and expression of minigenes containing nonsense mutations in exon 7.

Science.gov (United States)

Machiavelli, Gloria A; Caputo, Mariela; Rivolta, Carina M; Olcese, María C; Gruñeiro-Papendieck, Laura; Chiesa, Ana; González-Sarmiento, Rogelio; Targovnik, Héctor M

2010-01-01

Thyroglobulin (TG) deficiency is an autosomal-recessive disorder that results in thyroid dyshormonogenesis. A number of distinct mutations have been identified as causing human hypothyroid goitre. The purpose of this study was to identify and characterize new mutations in the TG gene in an attempt to increase the understanding of the genetic mechanism responsible for this disorder. A total of six patients from four nonconsanguineous families with marked impairment of TG synthesis were studied. Single-strand conformation polymorphism (SSCP) analysis, sequencing of DNA, genotyping, expression of chimeric minigenes and bioinformatic analysis were performed. Four different inactivating TG mutations were identified: one novel mutation (c.7006C>T [p.R2317X]) and three previously reported (c.886C>T [p.R277X], c.6701C>A [p.A2215D] and c.6725G>A [p.R2223H]). Consequently, one patient carried a compound heterozygous for p.R2223H/p.R2317X mutations; two brothers showed a homozygous p.A2215D substitution and the remaining three patients, from two families with typical phenotype, had a single p.R277X mutated allele. We also showed functional evidences that premature stop codons inserted at different positions in exon 7, which disrupt exonic splicing enhancer (ESE) sequences, do not interfere with exon definition and processing. In this study, we have identified a novel nonsense mutation p.R2317X in the acetylcholinesterase homology domain of TG. We have also observed that nonsense mutations do not interfere with the pre-mRNA splicing of exon 7. The results are in accordance with previous observations confirming the genetic heterogeneity of TG defects.

Two novel variants of human medium chain acyl-CoA dehydrogenase (MCAD). K364R, a folding mutation, and R256T, a catalytic-site mutation resulting in a well-folded but totally inactive protein

DEFF Research Database (Denmark)

O'Reilly, Linda P; Andresen, Brage S; Engel, Paul C

2005-01-01

was again totally inactive. Neither mutant showed marked depletion of FAD. The pure K364R protein was considerably less thermostable than wild-type MCAD. Western blots indicated that, although the R256T mutant protein is less thermostable than normal MCAD, it is much more stable than K364R. Though......Two novel rare mutations, MCAD approximately 842G-->C (R256T) and MCAD approximately 1166A-->G (K364R), have been investigated to assess how far the biochemical properties of the mutant proteins correlate with the clinical phenotype of medium chain acyl-CoA dehydrogenase (MCAD) deficiency. When...... the gene for K364R was overexpressed in Escherichia coli, the synthesized mutant protein only exhibited activity when the gene for chaperonin GroELS was co-overexpressed. Levels of activity correlated with the amounts of native MCAD protein visible in western blots. The R256T mutant, by contrast, displayed...

Michał Kalecki i problem racjonalnej alokacji zasobów w socjalizmie

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Damian Winczewski

2015-06-01

Full Text Available Celem artykułu jest rekonstrukcja poglądów Michała Kaleckiego i jego zwolenników na temat racjonalnej kalkulacji i alokacji zasobów w gospodarce socjalistycznej, a także próba zestawienia tych poglądów z poglądami zwolenników zarówno kapitalizmu, jak i alternatywnych modeli socjalizmu. Pod tym kątem przeanalizowano artykuły polskiego ekonomisty dotyczące schematu tworzenia się cen w kapitalizmie i socjalizmie, roli klasy robotniczej oraz systemu bodźców i sposobu zarządzania gospodarką. W artykule omówiono też poglądy autorów, którzy bazując na pracach Kaleckiego, podjęli się polemiki z obiegową narracją wyjaśniającą porażkę realnego socjalizmu. Zarówno realny kapitalizm, jak i realny socjalizm zmagają się z problemami niedoskonałej informacji i miękkich budżetów, nie istnieje również doskonały model zarządzania gospodarką, w związku z tym nie są to bezpośrednie przyczyny niepowodzenia projektu socjalistycznego. Oprócz problemu innowacji i optymalnych nakładów inwestycyjnych z perspektywy kaleckiańskiej zasadniczym problemem socjalizmu wydaje się ustanowienie właściwych stosunków produkcji w marksistowskim sensie, rozumianych jako zdemokratyzowanie relacji pomiędzy klasą robotniczą a warstwą zarządzającą produkcją.

Somatyczna determinacja płciowa w nadwadze i otyłości

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Michał Zych

2015-12-01

Full Text Available Wstęp: Somatyczne wielkości, takie jak masa (Mc i wysokość ciała (Wc, są używane do wyliczania wskaźników wagowo--wzrostowych i stanowią pomoc w diagnozowaniu nadwagi i otyłości. Cel pracy: Celem pracy jest ocena nadwagi i otyłości kobiet i mężczyzn w świetle prostych wskaźników somatycznych. Materiał i metody: W prezentowanej pracy porównano wskaźniki somatyczne 179 kobiet i 181 mężczyzn z nadwagą i otyłością. Do oceny somatycznej badanych użyto: Mc, Wc oraz wskaźników wagowo-wzrostowych: Queteleta, BMI, Rohrera i smukłości. Wyniki: W badanych grupach kobiety i mężczyźni byli w zbliżonym wieku, grupy te różniły się istotnie omawianymi wskaźnikami somatycznymi. Porównania podgrup kobiet i mężczyzn o podobnej wielkości BMI wykazały, że są oni w podobnym wieku i różnią się w zakresie Mc, Wc oraz wskaźników: Queteleta, Rohrera i smukłości. Natomiast między podgrupami kobiet, jak i między podgrupami mężczyzn, występowały istotne różnice wiekowe, Mc oraz wskaźników: BMI, Queteleta, Rohrera i smukłości. Wnioski: Powyższe dane wskazują, że pomimo braku różnic wieku między badanymi kobietami i mężczyznami z podobnym lub różnym BMI istnieje wyraźna somatyczna determinacja płciowa, natomiast w obrębie tej samej płci, różniącej się wskaźnikiem BMI, wiek badanych jest czynnikiem determinacji somatycznej. Wykazano też, że badane wskaźniki somatyczne mają różną moc predykcyjną w zakresie oceny nadwagi i stopnia otyłości badanych kobiet i mężczyzn.

VizieR Online Data Catalog: HD 163151: a new W UMa type system (Rodriguez+ 1998)

Science.gov (United States)

Rodríguez, E.; Claret, A.; García, J. M.; Zerbi, F. M.; Garrido, R.; Martín, S.; Akan, C.; Luedeke, K.; Keskin, V.; Ibanoglu, C.; Evren, S.; Tunca, Z.; Pekunlu, R.; Paparo, M.; Nuspl, J.; Krisciunas, K.; Jiang, S. Y.

1998-06-01

Table 2 contains 408 simultaneous measurements collected in each of the four uvby colours of the Stromgren photometric system for the W UMa system HD 163151. The data are magnitude differences (Du, Dv, Db, Dy, D(b-y), Dm1, Dc1) of the variable star minus comparison star in the standard system versus Heliocentric Julian Day. Tables 3, 4 and 5 are the same, but for Hβ (65 points), Johnson B data (212 points) and Johnson V data (355 points). The comparison star is HD 166095. The origin in time is the Julian Day 2449858. The observations were carried out (by E. Rodriguez, A. Claret, J.M. Garcia, F.M. Zerbi, R. Garrido, S. Martin, C. Akan, K. Luedeke, V. Keskin, C. Ibanoglu, S. Evren, Z. Tunca, R. Pekunlu, M. Paparo, J. Nuspl, K. Krisciunas and S.Y. Jiang) in 1995 during the course of a multisite campaign. The following telescopes were used: 90cm telescope of the Sierra Nevada Observatory, Spain (uvby-Hβ photometry); 50cm telescope at the Ege University Observatory, Turkey (BV-uvby); 50cm telescope at Piszkesteto mountain station, Konkoly Observatory, Hungary (BV); 50cm telescope at the Merate Observatory, Italy (V); 30cm telescope at Albuquerque, New Mexico, USA (V) and 15cm telescope at Mauna Kea, Hawaii, USA (V). (4 data files).

PROJEKTOWANIE NOWYCH I MODERNIZACJA ISTNIEJĄCYCH OBIEKTÓW MOSTOWYCH W ASPEKCIE OCHRONY PRZYRODY I KRAJOBRAZU NA PRZYKŁADZIE REALIZACJI W REGIONIE PODLASIA, WARMII I MAZUR

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Agnieszka JABŁOŃSKA-KRYSIEWICZ

Full Text Available W artykule przedstawiono, na wybranych przykładach zrealizowanych obiektów, podstawowe determinanty ochrony krajobrazu i przyrody, jakimi należy się kierować przy opracowaniu dokumentacji projektowej dla nowego, czy też dla remontowanego mostu na terenach krajobrazowo i przyrodniczo cennych. Kryterium uwarunkowań historyczno-krajobrazowych przy projektowaniu i modernizacji starych obiektów jest szczególnie ważne na terenach „Zielonych Płuc Polski” do jakich można zaliczyć obszar północno-wschodniej Polski. Szczególną uwagę zwrócono na zachowanie formy starych mostów łukowych ze sklepieniem ceglanym. Mosty te znajdują się często w złym stanie technicznym. Przedstawiono dwa rozwiązania konstrukcyjne stosowane przy przebudowie tego typu obiektów: zastosowanie wzmocnienia w postaci stalowych blach karbowanych opartych na żelbetowych przyczółkach oraz wykonanie żelbetowych łuków, oblicowanych cegłą klinkierową, opartych na istniejących podporach, wzmocnionych żelbetowym oczepem. Omówiono na przykładach wybranych obiektów podstawowe uwarunkowania środowiskowe brane pod uwagę przy projektowaniu mostów i przepustów na terenach wiejskich. Zwrócono uwagę na dostosowanie obiektu do otaczającego krajobrazu poprzez zastosowanie odpowiedniej roślinności, zarówno na zabezpieczeniu skarp jak i po obu stronach mostu. Przedstawiono możliwości wykonania przejść dla zwierząt w małych obiektach mostowych i przepustach. Zwrócono uwagę na zagadnienie estetycznego kształtowania konstrukcji mostowych jako dążenie do zachowania formy współgrającej z otoczeniem, szczególnie na obszarze miast, gdzie most jest ważnym punktem widokowym.

Historia i znaczenie zbiorów Biblioteki Katedry Filologii Germańskiej Uniwersytetu Mikołaja Kopernika w Toruniu – depozyt w Bibliotece Uniwersyteckiej w Toruniu

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Wiesław Sieradzan

2014-12-01

Full Text Available Jedną z bardziej interesujących części zbiorów Biblioteki Głównej UMK jest znajdujący się tam od niedawna depozyt Biblioteki Katedry Filologii Germańskiej. Jego geneza łączy się nierozerwalnie z dziejami Uniwersytetu oraz samej Katedry, kształcącej germanistów już od ponad 40 lat. Celem autora jest poznanie tego księgozbioru, zarówno pod względem jego proweniencji, jak i wartości dla germanistów i historyków. Ważną kwestia jest ustalenie głównych twórców biblioteki germanistycznej po II wojnie światowej, jak również po reaktywacji Katedry Filologii Germańskiej w 1969 r. Depozyt Katedry Filologii Germańskiej w BG UMK liczy 7627 tomów. Już sam fakt sposobu jego powstawania, szczególnie po II wojnie światowej, głównie drogą zabezpieczania zbiorów poniemieckich, a ponadto zakupów i darów, musiał wpłynąć na różnorodność gatunkową oraz proweniencję. W depozycie daje się zauważyć mnogość ośrodków, z których nastąpiło rozproszenie zbiorów bibliotecznych. W ujęciu geograficznym jest to obszar od Greifswaldu na zachodzie po Królewiec na wschodzie. Od Gdańska i Słupska na północy aż po Dzierżoniów (Reichenbach, Świdnicę (Schweidnitz oraz Wrocław na południu. W księgozbiorze tym można wyróżnić prozę i poezję niemiecką ze szczególnym uwzględnieniem twórców z XIX i pierwszej połowy XX w., następnie opracowania krytyczne literatury niemieckiej, słowniki języka niemieckiego w tym rozmaitych jego dialektów.Ustalenia niewątpliwie autora potwierdzają tezę, że charakteryzowany księgozbiór ma niewątpliwie nie tylko ciekawą proweniencję, często udokumentowaną znakami własnościowymi w postaci pięknych exlibrisów lub superexlibrisów, ale przede wszystkim znaczną wagę dla filologów germańskich. Może bowiem stanowić cenną pomoc naukową dla badań językoznawczych i historycznych (historia Niemiec i Skandynawii. Kryje on jeszcze, pomimo powyższych ustale

Zmiany sprawności funkcji poznawczych w trakcie suplementacji wielonienasyconymi kwasami tłuszczowymi omega-3 w grupie chorych na schizofrenię – przegląd systematyczny

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Marta Grancow-Grabka

2016-09-01

Full Text Available Deficyt w obszarze funkcjonowania poznawczego jest stałym fenomenem opisywanym w populacji osób z rozpoznaniem schizofrenii – w okresie przedchorobowym, w trakcie pogorszeń, jak również między kolejnymi epizodami. Zaburzenie funkcjonowania poznawczego stanowi niezależny czynnik rokowniczy w schizofrenii. Badania wskazują, że właśnie od tego wymiaru patologii zależą takie wykładniki funkcjonowania pacjentów, jak: wyniki leczenia i rehabilitacji, współpraca w leczeniu, funkcjonowanie zawodowe, rodzinne i społeczne, zdolność do samodzielnej egzystencji oraz jakość życia. Dotychczasowe metody leczenia schizofrenii nie zapewniają wystarczającej poprawy w zakresie tego wymiaru choroby. W okresie ostatnich 25 lat testowano użyteczność wielonienasyconych kwasów tłuszczowych omega-3 jako monoterapii oraz jako augmentacji leczenia przeciwpsychotycznego w schizofrenii. Uzyskane wyniki są niejednoznaczne, choć podkreśla się tzw. pozytywny trend uzyskiwanych wyników w zakresie poprawy objawowej. Stosunkowo rzadko oceniano wpływ suplementacji preparatami wielonienasyconych kwasów tłuszczowych omega-3 na funkcjonowanie poznawcze osób z rozpoznaniem schizofrenii. Korzystny wpływ suplementacji wielonienasyconymi kwasami tłuszczowymi na funkcjonowanie poznawcze ma uzasadnienie teoretyczne. Wśród znanych działań tych substancji mogących wpływać na usprawnienie funkcji poznawczych należy wymienić: działanie immunomodulacyjne w obrębie ośrodkowego układu nerwowego, poprawę parametrów stresu oksydacyjnego, zmiany w zakresie neurotransmisji oraz wpływ na procesy plastyczności neuronalnej. Celem niniejszej pracy jest przedstawienie systematycznego przeglądu wyników badań dotyczących zmian sprawności funkcjonowania poznawczego u osób z rozpoznaniem schizofrenii będących w trakcie suplementacji wielonienasyconymi kwasami tłuszczowymi omega-3.

Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene

Energy Technology Data Exchange (ETDEWEB)

Goltsov, A.A.; Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Konecki, D.S.; Lichter-Konecki, U.

1992-09-01

The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by the presence of an AT-rich (70%) minisatellite region. This region contains various multiples of 30-bp tandem repeats and is located 3 kb downstream of the final exon of the gene. PCR-mediated amplification of this region from haplotyped PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine copies of this repeat. These variations permit more detailed analysis of mutant haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria families demonstrates Mendelian segregation of these VNTR alleles, as well as associations between theses alleles and certain PAH mutations. The R261Q mutation, associated with haplotype 1, is associated almost exclusively with an allele containing eight repeats; the R408W mutation, when occurring on a haplotype 1 background, may also be associated with the eight-repeat VNTR allele. Other PAH mutations associated with haplotype 1, R252W and P281L, do not appear to segregate with specific VNTR alleles. The IVS-10 mutation, when associated with haplotype 6, is associated exclusively with an allele containing seven repeats. The combined use of this VNTR system and the existing RFLP haplotype system will increase the performance of prenatal diagnostic tests based on haplotype analysis. In addition, this VNTR may prove useful in studies concerning the origins and distributions of PAH mutations in different human populations. 32 refs., 3 figs., 3 tabs.

Hazır Gıda Ürünleri Satın Alma Davranışını Etkileyen Pazarlama Faktörlerinin İncelenmesi: Iğdır İlinde Bir Araştırma

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Faruk BAŞTÜRK

2014-04-01

Full Text Available Araştırmanın amacı, Iğdır’daki süper marketlerden hazır gıda satın alan tüketicilerin hazır gıda satın alımını etkileyen pazarlama karması faktörlerini analiz etmektir. Tüketicilerin hazır gıda satın alma davranışlarının yanı sıra bu satın almadan bekledikleri yararları işlevsel ve hazcı bazda incelemek araştırmanın diğer amacıdır. Araştırmanın yöntemi, tanımlayıcı nitelikte ve ampirik şekilde tasarlanmıştır. Araştırmada veri toplama yöntemi ankettir ve kolayda örnekleme yoluyla 408 gözleme ulaşılmıştır. Bulgulara göre, tüketicilerin satın alma davranışını etkileyen pazarlama karması faktörlerinin önem sırasının Ürün-Dağıtım, Fiyat, Ürün, Tutundurma-Dağıtım olduğu; tüketicilerin hazır gıda ürünlerini satın alırken İşlevselci davranışı Hazcılıktan daha fazla sergilediği ve İşlevselcilerin Hazcılara göre 4 pazarlama karması faktörüne daha fazla önem verdiği ortaya çıkmıştır. Sonuçta hazır gıda perakendecilerine özgü öneriler getirilmiştir.

Mutations in galactosemia

Energy Technology Data Exchange (ETDEWEB)

Reichardt, J.K.V. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

1995-10-01

This Letter raises four issues concerning two papers on galactosemia published in the March 1995 of the Journal. First, table 2 in the paper by Elsas et al. incorrectly attributes seven galactose-l-phosphate uridyl transferase (GALT) mutations (S135L, L195P, K285N, N314D, R333W, R333G, and K334R). The table also fails to mention that others have reported the same two findings attributed to {open_quotes}Leslie et al.; Elsas et al. and in press{close_quotes} and {open_quotes}Leslie et al.; Elsas et al.{close_quotes} The first finding on the prevalence of the Q188R galactosemia mutation in the G/G Caucasian population has also been described by Ng et al., and the second finding on the correlation of the N314D GALT mutation with the Duarte variant was reported by Lin et al. Second, Elsas et al. suggest that the E203K and N314D mutations may {open_quotes}produce intra-allelic complementation when in cis{close_quotes}. This speculation is supported by the activity data of individual III-2 but is inconsistent with the activities of three other individuals I-1, II-1, and III-1 of the same pedigree. The GALT activity measured in these three individuals suggests a dominant negative effect of E203K in E203K-N314D chromosomes, since they all have less than normal activity. Thus, the preponderance of the data in this paper is at odds with the authors speculation. It is worth recalling that Lin et al. also identified four N314D GALT mutations on 95 galactosemic chromosomes examined. A similar situation also appears to be the case in proband III-1 (with genotype E203K-N314D/IVSC) in the Elsas et al. paper. 9 refs.

Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark

DEFF Research Database (Denmark)

Jørgensen, Louise B; Christensen, Marianne B; Gerstoft, Jan

2003-01-01

The aim of this study was to monitor the prevalence of drug resistance mutations in newly diagnosed HIV-1 positive individuals in Denmark. In addition we assessed the prevalence of non-B subtypes based on phylogenetic analysis of the pol gene. Plasma samples from 104 newly diagnosed HIV-1 positive...... patients were obtained in the year 2000. The entire protease gene and 320 amino acids of the reverse transcriptase gene were genotyped. Sequences were obtained from 97 patients. No subjects displayed primary resistance mutations in the protease gene, whereas all carried 1 or more secondary mutations....... Resistance mutations in the RT-gene associated with NRTI-resistance were found in 1 patient, who was infected with zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S and L210S. The T215S mutation has been showed to be associated with reversion of zidovudine resistance. The T215...

Identification of novel splice site mutation IVS9 + 1(G > A) and novel complex allele G355R/R359X in Type 1 Gaucher patients heterozygous for mutation N370S.

Science.gov (United States)

Hoitsema, Kourtnee; Amato, Dominick; Khan, Aneal; Sirrs, Sandra; Choy, Francis Y M

2016-09-01

Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from deficient glucocerebrosidase activity. More than 350 mutations that cause Gaucher disease have been described to date. Novel mutations can potentially provide insight into the glucocerebrosidase structure-function relationship and biochemical basis of the disease. Here, we report the identification of two novel mutations in two unrelated patients with type I (non-neuronopathic) Gaucher disease: 1) a splice site mutation IVS9 + 1G > A; and (2) a complex allele (cis) G355R/R359X. Both patients have a common N370S mutation in the other allele. The splice site mutation results from an intronic base substitution (G to A, c.1328 + 1, g.5005) at the donor splice site of exon and intron 9. The complex allele results from two point mutations in exon 8 of glucocerebrosidase (G to C at c.1180, g.4396, and T to C at c. 1192, g.4408) substituting glycine by arginine (G355R) and arginine by a premature termination (R359X), respectively. In order to demonstrate that G355R/R359X are in cis arrangement, PCR-amplified glucocerebrosidase exon 8 genomic DNA from the patient was cloned into the vector pJET1.2 in Escherichia coli TOP10® strain. Out of the 15 clones that were sequence analyzed, 10 contained the normal allele sequence and 5 contained the complex allele G355R/R359X sequence showing both mutations in cis arrangement. Restriction fragment length polymorphism analysis using Hph1 restriction endonuclease digest was established for the IVS9 + 1G > A mutation for confirmation and efficient identification of this mutation in future patients. Past literature suggests that mutations affecting splicing patterns of the glucocerebrosidase transcript as well as mutations in Gaucher complex alleles are detrimental to enzyme activity. However, compound heterozygosity with N370S, a mild mutation, will lead to a mild phenotype. The cases reported here support these past findings.

Jeremias Hentschel Lesna Polonus (1662–1709 i jego księgozbiór. Fragment z dziejów biblioteki parafii luterańskiej w Lesznie.

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Kamila Szymańska

2015-12-01

Full Text Available Artykuł przedstawia postać diakona parafii luterańskiej w Lesznie Jeremiasa Hentschela (1662–1709, jego piśmienniczą aktywność oraz zbiór książek, które przekazał ufundowanej przez siebie bibliotece parafialnej. Przedmiotem daru była kwota 940 guldenów na budowę pomieszczenia biblioteki oraz 144 dzieła w 25 tomach, które nabył w latach 1682–1687. Woluminy te mają charakterystyczną proweniencję: wytłoczony na pergaminowych okładkach akronim JHLP – Jeremias Hentschel Lesna Polonus. Omawiany zbiór obejmuje liczne dysertacje akademickie wydane w czołowych ośrodkach ortodoksji luterańskiej, głównie w Jenie i Wittenberdze, teksty z zakresu filozofii, historii Kościoła, polemiki z innymi wyznaniami chrześcijańskimi. Teksty niereligijne stanowią margines.

Wielokryterialna ocena różnych wariantów lokalizacji ujęcia wód podziemnych dla oczyszczalni ścieków w Częstochowie

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Łukasz Kaczmarek

2015-03-01

Full Text Available Działalność przemysłowa wpływa bezpośrednio na środowisko. Przykładem tego jest wpływ ujęć wód podziemnych na warunki hydrogeologiczne. Kluczowym elementem tego zagadnienia jest wybór optymalnej lokalizacji projektowanego ujęcia. Przedstawiany artykuł opisuje wielokryterialną ocenę różnych wariantów lokalizacji ujęcia wód podziemnych. Woda z projektowanego ujęcia będzie dostarczana do oczysz­czalni ścieków w Częstochowie do celów technologicznych. W celu zaprojektowania odpowiedniej studni głębinowej spełniającej określone wymagania przeprowadzono ob­liczenia analityczne m.in. promienia leja depresji i głębokości depresji, izochromy 25 lat oraz ustalono wytyczne dla projektu studni. Wykonano również wykres zwierciadła wód podziemnych podczas interakcji z ujęciem. Rezultatem wyżej wymienionych obliczeń było określenie zasięgu leja depresji oraz wybór wariantu budowy dwóch studni w ra­mach jednego ujęcia wód podziemnych. Dzięki wykonanej analizie zweryfikowano moż­liwości wspomagania procesu podejmowania szybkich i racjonalnych decyzji dla dużych obszarów, gdzie występuje wiele czynników wpływu na wydajność studni głębinowej.

Stres i wypalenie zawodowe w pracy ratowników medycznych = Stress and a burn-out syndrome at work among paramedics

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Magdalena Żurowska-Wolak

2015-06-01

4.      Zakład Zdrowia Publicznego, Warszawski Uniwersytet Medyczny, Warszawa     Adres do korespondencji: Magdalena Żurowska-Wolak tel: 503 196 836;  e- mail: m_zurowska@vp.pl   Streszczenie: Zawód ratownika medycznego jest jednym zawodów, w których narażenie na stres jest wysokie oraz istnieje ryzyko wystąpienia zespołu wypalenia zawodowego. Celem badania było poznanie sposobów radzenia sobie ze stresem, stosowanych przez ratowników medycznych oraz występowania wśród nich objawów wypalenia zawodowego. Najczęstszym z nich było występowanie dużego zmęczenia po pracy. Większość badanych (64%  potwierdziła wykorzystywanie konstruktywnych sposobów radzenia sobie ze stresem, jak również niekonstruktywne stosowanie używek, w szczególności kofeiny i nikotyny, których spożycie wzrastało w sytuacjach trudnych. Na podstawie badań można wnioskować, że wśród ratowników medycznych, pracujących w Krakowie i okolicach, występuje niebezpiecznie dużo objawów wypalenia zawodowego. Świadczy to o potrzebie stworzenia i realizacji przez ich pracodawców działań, obniżających poziom stresu wśród pracowników oraz zapobiegających wystąpieniu wypalenia zawodowego – jak debriefing, trenieng technik radzenia sobie ze stresem czy wspierania aktywności fizycznej. Jest to o tyle istotne, iż skutki stresu oraz wypalenia odczuwają nie tylko sami ratownicy. Skutki te są dolegliwe także dla pracodawców, którzy zatrudniają gorzej funkcjonujących pracowników oraz pacjentów, otrzymujących usługi o niższej jakości.   Abstract: Paramedics are one of the professions where the risk of exposure to stress is high as well as the risk of occurrence of the burnout syndrome. The aim of the study was to analyze methods of stress reduction and symptoms of the burnout syndrome among 122 paramedics from Kraków and surrounding area. The most prevalent symptom was severe tiredness after working hours. The majority of respondents

Rodzicielskie zaangażowanie w naukę gimnazjalistów sprawnych i ze specjalnymi potrzebami edukacyjnymi

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Grzegorz Szumski

2015-12-01

Full Text Available Artykuł przedstawia wyniki badania sposobów angażowania się rodziców w naukę gimnazjalistów ze specjalnymi potrzebami edukacyjnymi (SEN i bez takich potrzeb oraz wpływ tego zaangażowania na osiągnięcia szkolne uczniów. Analizując wyniki uzyskane na próbie liczącej ponad 1500 gimnazjalistów, wśród których znalazło się ponad 300 uczniów z SEN, ustalono, że rodzice dzieci z obu grup sięgają z różnym nasileniem po poszczególne sposoby pomagania dzieciom. Rodzice dzieci z SEN zdecydowanie częściej bezpośrednio pomagali swoim dzieciom w odrabianiu zadań domowych, choć wykorzystywanie tej strategii jest ujemnie skorelowane z osiągnięciami szkolnymi uczniów w obu grupach. Uzyskane wyniki przeczą powszechnemu przekonaniu, że uczniowie z SEN wymagają innych sposobów rodzicielskiego wsparcia w nauce niż ich rówieśnicy o prawidłowym rozwoju. Wyniki te mogą mieć praktyczne znaczenie dla kształtowania przekonań rodziców i nauczycieli na temat skutecznych sposób wspierania osiągnięć szkolnych gimnazjalistów.

Probiotyki i prebiotyki w chorobach przewodu pokarmowego u dzieci

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Leokadia Bąk-Romaniszyn

2009-06-01

Full Text Available Probiotyki to żywe mikroorganizmy, które po spożyciu w odpowiedniej dawce wywierają korzystne działanie na organizm gospodarza. Najczęściej jako probiotyki stosowane są bakterie kwasu mlekowego Lactobacillus i Bifidobacterium oraz wybrane szczepy Streptococcus, Bacillus, jak również drożdże Saccharomyces boulardii. Zależnie od szczepu i dawki bakterie probiotyczne przywracają naturalny, właściwie funkcjonujący układ mikroflory jelitowej, hamują rozwój wielu mikroorganizmów chorobotwórczych, łagodzą przebieg oraz skracają czas trwania niektórych biegunek bakteryjnych i wirusowych, zapobiegają wystą- pieniu lub łagodzą przebieg biegunek poantybiotykowych, likwidują lub zmniejszają objawy nietolerancji laktozy, a także normalizują zaburzenia motoryki jelit. Prebiotyki to substancje zawarte w żywności (bądź do niej dodawane, które selektywnie pobudzają wzrost i/lub aktywność wybranych szczepów bakterii probiotycznych obecnych w przewodzie pokarmowym. Prebiotyki przez stymulację i tworzenie warunków dla wzrostu szczepów probiotycznych poprawiają skład biocenozy jelitowej, motorykę jelit, powodują ustąpienie klinicznych objawów chorób zapalnych jelit oraz wpływają korzystnie na odżywienie komórek nabłonka jelitowego. Probiotyki, prebiotyki, jak również ich połączenie – synbiotyki, w sposób naturalny, przez wielokierunkowe oddziaływanie lecznicze żywych kultur baterii, poprawiają stan naszego zdrowia, wspomagają terapie farmakologiczne i mają coraz większe znaczenie w nowoczesnej medycynie. W pracy omówiono udział probiotyków i prebiotyków w kształtowaniu się biocenozy przewodu pokarmowego oraz ich zastosowanie w profilaktyce i leczeniu wybranych chorób przewodu pokarmowego.

Punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori in Colombian populations.

Science.gov (United States)

Matta, Andrés Jenuer; Zambrano, Diana Carolina; Pazos, Alvaro Jairo

2018-04-14

To characterize punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori ( H. pylori ) and determine their association with therapeutic failure. PCR products of 23S rRNA gene V domain of 74 H. pylori isolates; 34 resistant to clarithromycin (29 from a low-risk gastric cancer (GC) population: Tumaco-Colombia, and 5 from a high-risk population: Tuquerres-Colombia) and 40 from a susceptible population (28 from Tumaco and 12 from Túquerres) were sequenced using capillary electrophoresis. The concordance between mutations of V domain 23S rRNA gene of H. pylori and therapeutic failure was determined using the Kappa coefficient and McNemar's test was performed to determine the relationship between H. pylori mutations and clarithromycin resistance. 23S rRNA gene from H. pylori was amplified in 56/74 isolates, of which 25 were resistant to clarithromycin (20 from Tumaco and 5 from Túquerres, respectively). In 17 resistant isolates (13 from Tumaco and 4 from Túquerres) the following mutations were found: A1593T1, A1653G2, C1770T, C1954T1, and G1827C in isolates from Tumaco, and A2144G from Túquerres. The mutations T2183C, A2144G and C2196T in H. pylori isolates resistant to clarithromycin from Colombia are reported for the first time. No association between the H. pylori mutations and in vitro clarithromycin resistance was found. However, therapeutic failure of eradication treatment was associated with mutations of 23S rRNA gene in clarithromycin-resistant H. pylori ( κ = 0.71). The therapeutic failure of eradication treatment in the two populations from Colombia was associated with mutations of the 23S rRNA gene in clarithromycin-resistant H. pylori .

First Detection of the Kdr Mutation T929I in Head Lice (Phthiraptera: Pediculidae) in Schoolchildren of the Metropolitan Area of Nuevo Leon and Yucatan, Mexico.

Science.gov (United States)

Ponce-Garcia, Gustavo; Villanueva-Segura, Karina; Trujillo-Rodriguez, Gerardo; Rodriguez-Sanchez, Iram P; Lopez-Monroy, Beatriz; Flores, Adriana E

2017-07-01

The head louse Pediculus humanus capitis (De Geer) is a hematophagous ectoparasite that inhabits the human scalp. Infestations by this insect are commonly known as pediculosis, which is more common in younger groups. These infestations are asymptomatic; however, skin irritation from scratching occasionally may cause secondary bacterial infections. In recent years, the prevalence of pediculosis has increased in children; this increase has been attributed to louse resistance to the insecticides used as a control measure for infestation. The aim of the present study was to determine the presence and frequency of the knockdown resistance mutation (kdr) T929I in 468 head lice collected from 32 elementary schools in the metropolitan area of Nuevo Leon (24) and Yucatan (8), Mexico. This is the first report of a knockdown resistance (kdr) mechanism in head lice from Mexico. The T929I mutation was present in all of the sampled schools, with variability observed in its allelic and genotypic frequencies. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

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Seung-Joo Hyun

2017-11-01

Full Text Available To define whether individual human leukocyte antigen (HLA class I allotypes are used preferentially in human cytomegalovirus (CMV-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

Pośrednictwo Jakuba Kazimierza Rubinkowskiego w konserwacji i zakupie książek dla Elżbiety Sieniawskiej w końcu pierwszej ćwierci XVIII w.

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Adam Kucharski

2015-12-01

Full Text Available Wielowymiarowa działalność toruńskiego rajcy i poczmistrza królewskiego Jakuba Kazimierza Rubinkowskiego zorientowana była głównie na prowadzenie agencji informacyjnej zajmującej się redagowaniem i kolportażem prasy rękopiśmiennej. Ważnym aspektem jego aktywności kulturalnej stało się również pośredniczenie w załatwianiu usług introligatorskich i kupnie książek dla hetmanowej wielkiej koronnej i kasztelanowej krakowskiej Elżbiety Sieniawskiej. Rubinkowski, szlachcic, a zarazem barokowy erudyta i zapalony bibliofil, był idealnym kandydatem do realizacji tych zadań. O jego przydatności decydowała silna pozycja Torunia na polskim rynku księgarskim gwarantująca możliwość nabywania poszukiwanych tomów ksiąg, zarówno krajowych, jak i zagranicznych autorów. Kwerenda księgarska obejmowała dzieła ojca Sieniawskiej, Stanisława Herakliusza Lubomirskiego, innych autorów polskich (również z obszaru Prus Królewskich, a także klasyków nowożytnej literatury europejskiej. Niemniej ważnym atutem Rubinkowskiego była również możliwość bezpośredniego kontaktu z toruńskim cechem mistrzów introligatorskich, co zapewniało Sieniawskiej sprawny proceder konserwacji i renowacji ksiąg, pochodzących głównie z jej biblioteki w Puławach. Rubinkowski, szczególnie w latach 1725–1726, wielokrotnie i skrupulatnie informował o zbliżających się aukcjach książek organizowanych w Toruniu, przyjmował księgi ekspediowane statkami z Puław oraz organizował transport powrotny z akupionych i odnowionych woluminów. W sumie w ciągu zaledwie dwóch lat przez jego ręce przewinęło się kilkaset książek, czyniąc go jednym z czołowych agentów księgarskich tego czasu w Rzeczypospolitej Obojga Narodów.

Evaluation of prevalence's of pfdhfr and pfdhps mutations in Angola

Science.gov (United States)

2011-01-01

Background Malaria is the major cause of morbidity and mortality in Angola. The most vulnerable groups to Plasmodium falciparum infection are pregnant women and children under five years of age. The use of an intermittent preventive treatment (IPT) with sulphadoxine/pyrimethamine (SP) in pregnant women was introduced in Angola in 2006 by the National Malaria Control Programme, and currently this strategy has been considered to be used for children malaria control. Considering the previous wide use of SP combination in Angola, together to the reported cases of SP treatment failure it is crucial the evaluation of the prevalence of five mutations in pfdhfr and pfdhps genes associated to P. falciparum resistance to SP before the introduction of S/P IPT in children. Methods The study was conducted in five provinces, with different transmission intensities: Huambo, Cabinda, Uíge, Kwanza Norte, and Malanje. The detection of the mutations in pfdhfr and pfdhps genes was carried out in 452 P. falciparum blood samples by PCR RFLP. Results For pfdhfr gene, 90,3% of the samples carried the mutation 51I, with 7.5% of mixed infections; 51% carried wild type allele 59C, with 29.2% mixed infections and; 99.1% of isolates harboured the mutant allele 108N. Concerning, pfdhps gene, 83,1% were mutant type 437G with 11% mixed infections , while 87% of the studied isolates were wild type for codon 540. Discussion This is the first representative epidemiological study of the whole Angola country on the prevalence of the genotypes associated with SP chemoresistance. A high frequency of individual mutations in both genes (51I and 108N in pfdhfr, and 437G in pfdhps) was found, besides a low prevalence of the quintuple mutation. Conclusion The data showed that the implementation IPT using SP in children needs to be reviewed. PMID:21288345

Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).

Science.gov (United States)

Albuisson, Juliette; Pêcheux, Chistophe; Carel, Jean-Claude; Lacombe, Didier; Leheup, Bruno; Lapuzina, Pablo; Bouchard, Philippe; Legius, Eric; Matthijs, Gert; Wasniewska, Malgorzata; Delpech, Marc; Young, Jacques; Hardelin, Jean-Pierre; Dodé, Catherine

2005-01-01

Kallmann syndrome (KAL) combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is due to Gonadotropin Releasing Hormone (GnRH) deficiency and anosmia is related to hypoplasia of the olfactory bulbs. Occasional symptoms include renal agenesis, bimanual synkinesia, cleft lip palate, dental agenesis. KAL is genetically heterogeneous and two genes have so far been identified, namely KAL1 (Xp22.3) and FGFR1/KAL2 (8p12), which underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. We studied a cohort of 98 unrelated Caucasian KAL patients. We identified KAL1 mutations in 14 patients, of which 7 (c.3G>A (p.M1?), g.IVS1+1G>T, c.570_571insA (p.R191fsX14), c.784G>C (p.R262P), c.958G>T (p.E320X), c.1651_1654delinsAGCT (p.P551_E552delinsSX), c.1711T>A (p.W571R)) have not been previously reported. In addition, we found FGFR1 mutations in 7 patients, namely c.303G>A (p.V102I), C.385A>C (p.D129A), c.810G>A (p.V273M), c.1093_1094delAG (p.R365fsX41), c.1561G>A (p.A520T), c.1836_1837insT (p.Y613fsX42), c.2190C>G (p.Y730X), all of which were novel mutations. In this study, unilateral renal agenesis and bimanual synkinesia were exclusively found associated with KAL1mutations, cleft palate and dental agenesia with FGFR1mutations. (c) 2004 Wiley-Liss, Inc.

Wybór najskuteczniejszej metody rekultywacji zbiorników wodnych z wykorzystaniem metody AHP

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Joanna Chmist

2016-06-01

Full Text Available Problem z jakością wód w zamkniętych zbiornikach jest znany od lat. Poprawa parametrów jakości wody w jeziorze zwiększa możliwości jego wykorzystania. Obecnie istnieje wiele metod rekultywacji zbiorników wodnych. Wybór odpowiedniej uwarunkowany jest zarówno oddziaływaniem różnorodnych czynników powodujących stopniową degradację jezior, jak i kosztami rekultywacji czy typem zbiornika. W artykule zaprezentowano praktyczne zastosowanie metody AHP w rozwiązaniu wielokryterialnych problemów rekultywacji zbiorników wodnych. Metoda ta umożliwia uwzględnienie wielu aspektów dotyczących danego problemu i znalezienie poszukiwanego rozwiązania zarówno na podstawie parametrów mierzalnych, jak i ocen ekspertów.

Transseksualizm – pytania i wątpliwości

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Magdalena Radko

2012-06-01

Full Text Available Wiek dojrzewania jest czasem określania własnej tożsamości, odkrywania pragnień, dążeń, również w sferze sek‑ sualności. Poszukiwanie siebie, własnej orientacji seksualnej, znajdowanie pierwszych obiektów pożądania jest dla adolescenta nowym, ważnym przeżyciem, wyzwalającym silne emocje. Czasami jednak młody człowiek staje wo‑ bec dużych trudności, bowiem to, co odkrywa w sobie, nie znajduje umocowania w społecznych normach, nie jest akceptowane przez rodzinę i otoczenie, a w związku z tym dla samego adolescenta staje się ciężarem trudnym do uniesienia. Konsekwencją nieradzenia sobie z własną seksualnością, jej odbiorem rodzinnym lub społecznym mogą być zaburzenia depresyjne, lękowe, zaburzenia odżywiania oraz różnorodne formy autoagresji. W obliczu wysokie‑ go ryzyka występowania zaburzeń psychicznych u osób w wieku rozwojowym, u których seksualność kształtuje się w sposób odmienny, należy rozważać szerokie spektrum czynników mogących determinować takie, a nie inne oblicze seksualności. Intencją autorów pracy było przedstawienie, w oparciu o przypadek kliniczny, historii człowieka odkry‑ wającego swoją tożsamość płciową, biorąc pod uwagę zarówno osobnicze uwarunkowania, przebyte zdarzenia trau‑ matyczne, jak i kontekst rodzinny pacjenta oraz konsekwencje procesu coming out. Autorzy starali się zwrócić uwagę na złożoność i wielostopniowość procesu ujawniania się, który stał się możliwy dopiero po zapewnieniu adolescen‑ towi zrozumienia, wsparcia i akceptacji. Tym samym ukazano kluczową rolę środowiska, które może sprzyjać pro‑ cesowi odkrywania się i umożliwić go lub przeciwnie – utrudnić czy też całkowicie go zablokować. Transseksualizm w różnych środowiskach budzi sporo kontrowersji, pytań i wątpliwości. Historia hospitalizowanego pacjenta obrazu‑ je złożoność problemów, z którymi zmagają się osoby z zaburzeniami to

Rola wybranych czynników ryzyka w etiopatogenezie i przebiegu choroby Alzheimera

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Robert Dudkowiak

2013-06-01

Full Text Available Choroba Alzheimera (Alzheimer’s disease, AD stanowi jedną z najczęstszych przyczyn otępienia w wieku starszym. Ma charakter postępujący i prowadzi do stopniowej degeneracji mózgu. Zapadalność na AD wzrasta wraz z wiekiem. Etiologia choroby jest wieloczynnikowa. Składają się na nią interakcje pomiędzy czynnikami genetycznymi a środowiskowymi, w tym m.in. stylem życia, dietą, aktywnością fizyczną i nałogami. Uważa się, że sposób odżywiania zbliżony w składzie do diety śródziemnomorskiej ma ochronne działanie i sprzyja długotrwałemu życiu w zdrowiu. Podwyższone stężenie homocysteiny oraz obniżone stężenie witaminy B12 może pośrednio wpływać na rozwój AD. Natomiast zwiększone spożycie kwasu foliowego, witaminy C i E może działać ochronnie. Niekorzystny wpływ na rozwój AD odnotowano zarówno w przypadku zbyt dużej masy ciała, jak i w przebiegu niedożywienia. Podkreśla się również związek pomiędzy naczyniopochodnym uszkodzeniem mózgu a rozwojem otępienia. Przemawia za tym fakt, że odpowiednia dieta, prawidłowy stan odżywienia, brak cukrzycy, unikanie palenia papierosów oraz zwrócenie uwagi na aktywność fizyczną odgrywają istotną rolę w zapobieganiu nie tylko chorobom układu sercowo-naczyniowego, ale także AD. Dane epidemiologiczne dowodzą, iż wraz ze starzeniem się społeczeństwa częstość występowania AD będzie wzrastać, tym samym zwiększy się liczba osób niezdolnych do samodzielnego funkcjonowania. Następstwem tego będzie wzrost obciążeń medycznych, kulturowych i ekonomicznych całego społeczeństwa. Dlatego znaczenie poszczególnych czynników ryzyka AD powinno być nadal zgłębiane, a skuteczna profilaktyka wprowadzana już we wczesnym okresie życia.

The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors.

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Ravi Kumar Verma

2018-01-01

Full Text Available The dopamine D2 and D3 receptors (D2R and D3R are important targets for antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand that simultaneously binds both the orthosteric binding site (OBS and a secondary binding pocket (SBP in both D2R and D3R, was found to be a negative allosteric modulator. Previous studies identified Glu2.65 in the SBP to be a key determinant of both the affinity of SB269652 and the magnitude of its cooperativity with orthosteric ligands, as the E2.65A mutation decreased both of these parameters. However, the proposed hydrogen bond (H-bond between Glu2.65 and the indole moiety of SB269652 is not a strong interaction, and a structure activity relationship study of SB269652 indicates that this H-bond may not be the only element that determines its allosteric properties. To understand the structural basis of the observed phenotype of E2.65A, we carried out molecular dynamics simulations with a cumulative length of ~77 μs of D2R and D3R wild-type and their E2.65A mutants bound to SB269652. In combination with Markov state model analysis and by characterizing the equilibria of ligand binding modes in different conditions, we found that in both D2R and D3R, whereas the tetrahydroisoquinoline moiety of SB269652 is stably bound in the OBS, the indole-2-carboxamide moiety is dynamic and only intermittently forms H-bonds with Glu2.65. Our results also indicate that the E2.65A mutation significantly affects the overall shape and size of the SBP, as well as the conformation of the N terminus. Thus, our findings suggest that the key role of Glu2.65 in mediating the allosteric properties of SB269652 extends beyond a direct interaction with SB269652, and provide structural insights for rational design of SB269652 derivatives that may retain its allosteric properties.

RHO Mutations (p.W126L and p.A346P in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

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Satoshi Katagiri

2014-01-01

Full Text Available Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP. Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L and c.1036G>C (p.A346P, one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

Probiotyki i prebiotyki w profilaktyce i leczeniu chorób u dzieci

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Leokadia Bąk-Romaniszyn

2010-11-01

Full Text Available Probiotyki to mikroorganizmy, które wywierają korzystne działanie na organizm gospodarza po spożyciu przez niego odpowiedniej dawki określonego szczepu. Najczęściej jako probiotyki stosowane są bakterie kwasu mlekowego Lactobacillus i Bifidobacterium oraz wybrane szczepy Streptococcus, Bacillus, a także drożdże Saccharomyces boulardii. Probiotyki wpływają korzystnie na skład środowiska ekologicznego przewodu pokarmowego, wykazując antagonizm w stosunku do drobnoustrojów chorobotwórczych kolonizujących błonę śluzową przewodu pokarmowego. Obecność w jelicie bakterii fermentacyjnych, głównie pałeczek kwasu mlekowego, a zwłaszcza typów adhezyjnych, chroni przed dyslokacją bakteryjną i enterotoksemią, normalizuje zaburzenia motoryki jelit i zmniejsza objawy nietolerancji laktozy. Prebiotyki to substancje naturalnie zawarte w żywności (bądź do niej dodawane, które selektywnie pobudzają wzrost i/lub aktywność wybranych szczepów bakterii probiotycznych obecnych w przewodzie pokarmowym. Probiotyki i prebiotyki, jak również ich połączenie – synbiotyki, występują w pożywieniu, mieszankach mlecznych, preparatach farmakologicznych, dodatkach do żywności, suplementach dietetycznych i w sposób naturalny poprawiają stan naszego zdrowia oraz mają coraz większe znaczenie w nowoczesnej medycynie. W pracy omówiono udział probiotyków i prebiotyków w kształtowaniu się biocenozy przewodu pokarmowego oraz w profilaktyce i leczeniu wybranych chorób u dzieci, jak: biegunki bakteryjne i wirusowe, dysbioza poantybiotykowa, martwica jelit noworodków, kolka jelitowa, nieswoiste zapalenia jelit, zaburzenia czynnościowe przewodu pokarmowego.

Identification of Missense Mutation (I12T in the BSND Gene and Bioinformatics Analysis

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Hina Iqbal

2011-01-01

Full Text Available Nonsyndromic hearing loss is a paradigm of genetic heterogeneity with 85 loci and 39 nuclear disease genes reported so far. Mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness and nonsyndromic nearing loss. We studied a Pakistani consanguineous family. Clinical examinations of affected individuals did not reveal the presence of any associated signs, which are hallmarks of the Bartter syndrome type IV. Linkage analysis identified an area of 18.36 Mb shared by all affected individuals between markers D1S2706 and D1S1596. A maximum two-point LOD score of 2.55 with markers D1S2700 and multipoint LOD score of 3.42 with marker D1S1661 were obtained. BSND mutation, that is, p.I12T, cosegregated in all extant members of our pedigree. BSND mutations can cause nonsyndromic hearing loss, and it is a second report for this mutation. The respected protein, that is, BSND, was first modeled, and then, the identified mutation was further analyzed by using different bioinformatics tools; finally, this protein and its mutant was docked with CLCNKB and REN, interactions of BSND, respectively.

Ocena rozpowszechnienia dolegliwości reumatycznych wśród osób w przedziale wiekowym 18-25 lat = Assessment of the prevalence of rheumatic ailments among people aged 18-25 years

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Kitowska, Wioleta

2016-01-01

Kitowska Wioleta. Ocena rozpowszechnienia dolegliwości reumatycznych wśród osób w przedziale wiekowym 18-25 lat = Assessment of the prevalence of rheumatic ailments among people aged 18-25 years. Journal of Education, Health and Sport. 2016;6(1):17-26. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.44536 http://ojs.ukw.edu.pl/index.php/johs/article/view/44536 http://pbn.nauka.gov.pl/works/689921 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011–...

Mediterranean glucose-6-phosphate dehydrogenase (G6PDC563T) mutation among jordanian females with acute hemolytic crisis

International Nuclear Information System (INIS)

Jabbar, A.A.; Kanakiri, N.; Kamil, M.; Rimawi, H.S.A.

2010-01-01

To evaluate the G6PDC563T Mediterranean mutation among Jordanian females who were admitted to Princess Rahma Teaching Hospital (PRTH) with/or previous history of favism. Study Design: A descriptive study. Place and Duration of Study: Jordanian University of Science and Technology and PRTH, from October 2003 to October 2004. Methodology: After obtaining approval from the Ethics Committee of Jordanian University of Science and Technology, a total of 32 females were included in this study. Samples from 15 healthy individual females were used as a negative control. Blood samples from these patients were collected and analyzed by allele-specific polymerase chain reaction (AS-PCR) to determine the G6PDC563T mutation. Results: Twenty one out of 32 patients were found to be G6PDC563T Mediterranean mutation (65.6%) positive. Three out of 21 patients were homozygous and remaining 18 were heterozygous for G6PDC563T Mediterranean mutation. Eleven (34.4%) out of 32 patients were found to be negative for G6PDC563T mutation indicating the presence of other G6PD mutations in the study sample. Conclusion: G6PDC563T Mediterranean mutation accounted for 65.6% of the study sample with favism in the North of Jordan. There is likely to be another G6PD deficiency variant implicated in acute hemolytic crisis (favism). (author)

Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

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Kana Tanahashi

Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

Mitochondrial tRNALeu(UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome.

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Ding, Yu; Xia, Bo-Hou; Zhang, Cai-Juan; Zhuo, Guang-Chao

2018-02-05

Polycystic ovary syndrome (PCOS) is a very prevalent endocrine disease affecting reproductive women. Clinically, patients with this disorder are more vulnerable to develop type 2 diabetes mellitus (T2DM), cardiovascular events, as well as metabolic syndrome (MetS). To date, the molecular mechanism underlying PCOS remains largely unknown. Previously, we showed that mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutation was an important cause for PCOS. In the current study, we described the clinical and biochemical features of a three-generation pedigree with maternally transmitted MetS, combined with PCOS. A total of three matrilineal relatives exhibited MetS including obesity, high triglyceride (TG) and Hemoglobin A1c (HbA1c) levels, and hypertension. Whereas one patient from the third generation manifestated PCOS. Mutational analysis of the whole mitochondrial genes from the affected individuals identified a set of genetic variations belonging to East Asia haplogroup B4b1c. Among these variants, the homoplasmic C3275T mutation disrupted a highly evolutionary conserved base-pairing (28A-46C) on the variable region of tRNA Leu(UUR) , whereas the T4363C mutation created a new base-pairing (31T-37A) in the anticodon stem of tRNA Gln , furthermore, the A8343G mutation occurred at the very conserved position of tRNA Lys and may result the failure in mitochondrial tRNAs (mt-tRNAs) metabolism. Biochemical analysis revealed the deficiency in mitochondrial functions including lower levels of mitochondrial membrane potential (MMP), ATP production and mtDNA copy number, while a significantly increased reactive oxygen species (ROS) generation was observed in polymononuclear leukocytes (PMNs) from the individuals carrying these mt-tRNA mutations, suggesting that these mutations may cause mitochondrial dysfunction that was responsible for the clinical phenotypes. Taken together, our data indicated that mt-tRNA mutations were associated with MetS and PCOS in this

Szpik kostny – funkcje fizjologiczne i udział w patogenezie reumatoidalnego zapalenia stawów

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Weronika Kurowska

2010-08-01

Full Text Available Wyniki badań prowadzonych w ostatnich latach wskazują, żeszpik kostny funkcjonuje nie tylko jako narząd krwiotwórczy, leczrównież jako wtórny narząd limfatyczny, w którym może być zainicjowanaodpowiedź immunologiczna. Dane eksperymentalnei obserwacje kliniczne wskazują, że szpik kostny uczestniczyw rozwoju reumatoidalnego zapalenia stawów, ponieważ jest miejscemakumulacji aktywowanych limfocytów i wytwarzania czynnikówprozapalnych. W artykule opisano w zarysie rolę szpiku kostnegow prawidłowej (fizjologicznej odpowiedzi immunologicznej.Przedstawiono również wyniki badań eksperymentalnych i klinicznych,które potwierdzają udział szpiku kostnego w patogeneziereumatoidalnego zapalenia stawów.

Generation of induced pluripotent stem cells (iPSCs from a Bernard–Soulier syndrome patient carrying a W71R mutation in the GPIX gene

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Lourdes Lopez-Onieva

2016-05-01

Full Text Available We generated an induced pluripotent stem cell (iPSC line from a Bernard–Soulier Syndrome (BSS patient carrying the mutation p.Trp71Arg in the GPIX locus (BSS1-PBMC-iPS4F4. Peripheral blood mononuclear cells (PBMCs were reprogrammed using heat sensitive non-integrative Sendai viruses containing the reprogramming factors Oct3/4, SOX2, KLF4 and c-MYC. Successful silencing of the exogenous reprogramming factors was checked by RT-PCR. Characterization of BSS1-PBMC-iPS4F4 included mutation analysis of GPIX locus, Short Tandem Repeats (STR profiling, alkaline phosphatase enzymatic activity, analysis of conventional pluripotency-associated factors at mRNA and protein level and in vivo differentiation studies. BSS1-PBMC-iPS4F4 will provide a powerful tool to study BSS.

SPECYFIKA REALIZACJI LINIOWYCH INWESTYCJI W PASIE DROGOWYM W AGLOMERACJI MIEJSKIEJ Z UWZGLĘDNIENIEM OBSZARÓW ZABYTKOWYCH

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Andrzej MARECKI

Full Text Available Treścią referatu jest problematyka budowlanego procesu inwestycyjnego w pasie drogowym na terenie miast. W aglomeracjach miejskich realizacja zadań związanych z budową, przebudową lub modernizacją ciągów drogowych lub sieci infrastruktury liniowej związana jest z pokonaniem szczególnych utrudnień. Wynika to nie tylko ze specyfiki technologicznej ale również z szeroko pojętej interakcji społecznych. Inwestorzy realizujący zadania w miastach muszą szukać nie tylko innowacyjnych rozwiązań technicznych ale również muszą spełniać, często - „wygórowane” oczekiwania społeczne. W referacie omówione zostaną typowe zagrożenia procesu inwestycyjnego na etapach koncepcji, projektowania, realizacji i eksploatacji - ze szczególnym uwzględnieniem aspektów dotyczących realizacji liniowych robót budowlanych na obszarach objętych warunkami ochrony, wynikającymi z zapisów ustawy o ochronie zabytków[1]. Należy podkreślić, że ochrona ta zgodnie z Art. 4 przedmiotowej Ustawy polega, na podejmowaniu przez organy administracji publicznej działań mających między innymi na celu: zapewnienie warunków prawnych, organizacyjnych i finansowych, umożliwiających trwałe zachowanie zabytków oraz ich zagospodarowanie i utrzymanie. Przekłada się to na obligatoryjny warunek prowadzenia prac konserwatorskich, restauratorskich i oczywiście robót budowlanych za pozwoleniem właściwego konserwatora zabytków i pod jego nadzorem. Realizacja liniowych zadań inwestycyjnych z natury rzeczy odbywa się nie tylko w obszarze wpływu zabytków nieruchomych ale także w bezpośrednim kontakcie z zabytkami archeologicznymi tj. – zabytkami nieruchomymi, będącymi powierzchniową, podziemną lub podwodną pozostałością egzystencji i działalności człowieka, złożoną z nawarstwień kulturowych i znajdujących się w nich wytworów bądź ich śladów. Warunkiem pogodzenia interesów stron tego skomplikowanego procesu

Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

International Nuclear Information System (INIS)

Assumpção, Juliana G; Zeferino, Luiz Carlos; Dufloth, Rozany M; Brandalise, Silvia Regina; Yunes, José Andres; Seidinger, Ana Luíza; Mastellaro, Maria José; Ribeiro, Raul C; Zambetti, Gerard P; Ganti, Ramapriya; Srivastava, Kumar; Shurtleff, Sheila; Pei, Deqing

2008-01-01

The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16) and MDM2 (SNP309) genes that may further diminish TP53 tumor suppressor activity. These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility

Zanik korowy tylny – obraz kliniczny, diagnostyka różnicowa i postępowanie

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Anna Barczak

2014-11-01

Full Text Available Zanik korowy tylny (posterior cortical atrophy, PCA to rzadki zespół otępienny z dominującymi zaburzeniami percepcji wzrokowej i deficytem funkcji wzrokowo-przestrzennych. Charakteryzuje się wczesnym początkiem – zwykle przed 65. rokiem życia. Schorzenie to jest najczęściej uznawane za atypową postać choroby Alzheimera, określaną jako jej wariant wzrokowy. U pacjentów obserwuje się trudności z czytaniem, rozpoznawaniem twarzy, obiektów i otoczenia, problemy konstrukcyjne, niemożność jednoczesnego spostrzegania kilku obiektów i sięgania po przedmioty znajdujące się w zasięgu ręki. Wymienione deficyty prowadzą do – wcześniejszej niż u osób z chorobą Alzheimera – utraty samodzielności. Zaburzenia procesów poznawczych wynikają z dysfunkcji jednego lub dwóch głównych szlaków przetwarzających informacje wzrokowe w mózgu (grzbietowego, pozwalającego na lokalizację bodźca, bądź brzusznego, odpowiedzialnego za rozpoznanie bodźca, a następnie z zaniku kory płatów ciemieniowych i/lub potylicznych. Schorzeniu może towarzyszyć bardziej złożona symptomatologia neurologiczna i psychiatryczna. W pracy przedstawiono obraz kliniczny i kryteria diagnostyczne zaniku korowego tylnego, neuropsychologiczne metody użyteczne w procesie diagnozowania, główne problemy związane z różnicowaniem oraz możliwości oddziaływania farmakologicznego i niefarmakologicznego.

Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes.

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Pardanani, Animesh; Lasho, Terra L; Finke, Christy; Mesa, Ruben A; Hogan, William J; Ketterling, Rhett P; Gilliland, Dwight Gary; Tefferi, Ayalew

2007-09-01

JAK2V617F and MPLW515L/K are myeloproliferative disorder (MPD)-associated mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+ cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L/K) to determine (a) the proportion of colonies harboring a particular mutation in the presence or absence of cytokines, (b) the lineage distribution of endogenous colonies for each mutation, and (c) the differences (if any) in the pattern of mutation among the various MPDs, as established by genotyping of individual colonies. Genotyping analysis revealed cohabitation of mutation-negative and mutation-positive endogenous colonies in polycythemia vera as well as other MPDs. Culture of progenitor cells harboring MPLW515L/K yielded virtually no endogenous erythroid colonies in contrast to JAK2V617F-harboring progenitor cells. The mutation pattern (i.e., relative distribution of homozygous, heterozygous, or wild-type colonies) was not a distinguishing feature among the MPDs, and MPLW515 mutations were detected in B and/or T lymphocytes in all three patients tested. These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell.

Süt ve Ürünlerinde CO2 Uygulamaları – II: Çiğ ve Pastörize Süt

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Enes Dertli

2015-02-01

Full Text Available Ürünlerin üretiminde hammaddeden kaynaklanan başlangıç bakteriyel yükün azaltılması, pastörizasyon sisteminin geliştirilmesi ve üretim işlemlerinden önceki kontaminasyonun önlenmesi gibi uygulamalar raf ömrünün uzatılmasında etkilidir. Karbon dioksit doğal olarak meydana gelen bir süt bileşenidir ve kesin mekanizması henüz anlaşılamamasına rağmen, ürünlerde bazı bozulma oluşturan mikroorganizmalara karşı inhibitör etkilidir. Uygulamada kullanılan yeni CO2 teknolojileri çiğ ve pastörize sütü içeren sütçülük ürünlerinde farklılığın artırılması, raf ömrünün ve kalitenin yükseltilmesi amacıyla sürekli geliştirilmektedir. Bu çalışmada CO2 kullanılarak çiğ ve pastörize sütün kalitesinin geliştirilmesi konusunda geçmişteki ve günümüzdeki araştırmalar detaylı olarak irdelenmiştir.

Wyznaczenie krzywej natężenia przepływu w przekroju cofki zbiorników wodnych w Zesławicach

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Bogusław Michalec

2016-03-01

Full Text Available W pracy przedstawiono wyniki pomiarów geodezyjnych i hydrometrycznych oraz obliczeń wykonanych w celu opracowania krzywej natężenia przepływu w przekroju Dłubni, zlokalizowanego w kilometrze 10+247. Pomiary geodezyjne przekroju poprzecznego i spadku podłużnego zwierciadła wody wykonano za pomocą niwelatora Topcon AT-G6, a osiem pomiarów hydrometrycznych wykonano za pomocą młynka indukcyjnego Nautilus C2000 OTT Hydrometrie. Natężenie przepływu obliczono metodą Harlachera na podstawie danych hydrometrycznych i za pomocą wzoru Chézy’ego. Stwierdzono, że przepływy niskie i średnie obliczone wzorem Chézy’ego są średnio pięciokrotnie wyższe od określonych metodą Harlachera. Przyczyną tak znacznych różnic uzyskanych wyników obliczeń natężania przepływu dla danego napełnienia jest układ dna koryta. Stwierdzono, że istotny wpływ na warunki przepływu wody przy przepływach niskich i średnich ma wzniesienie dna w świetle mostu, znajdującego się 203 m poniżej przekroju wodowskazowego. Stwierdzono również, że na kształt krzywej natężenia w tym przekroju ma również wpływ oddziaływanie spiętrzenia wody w zbiornikach w Zesławicach.

Finansowanie leczenia lekami biologicznymi chorych na reumatoidalne i młodzieńcze idiopatyczne zapalenia stawów w ramach programów zdrowotnych NFZ w latach 2004–2008

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Andrzej Śliwczyński

2010-02-01

Full Text Available Celem pracy była ocena realizacji obowiązujących w Polscew latach 2004–2008 programów leczenia lekami biologicznymichorych na reumatoidalne i młodzieńcze idiopatyczne zapaleniastawów. Leczenie jest prowadzone przez 81 ośrodków rozmieszczonychrównomiernie w całym kraju. W tym okresie leczonołącznie 8160 chorych. W 2008 r. leczonych było 2282 chorych, costanowi około 2% wszystkich chorych na reumatoidalne zapaleniestawów; 72% z nich stanowiły kobiety, najczęściej w wieku45–55 lat. Lekiem najczęściej stosowanym był etanercept, rzadziejinfliksymab, bardzo rzadko adalimumab i rituksymab. Pieniądzeprzeznaczane przez NFZ na ten rodzaj leczenia nie sąwykorzystywane w pełni, w 2008 r. nie wykorzystano 13,5%.W podsumowaniu podkreślono, że należy zwiększyć liczbę leczonychchorych poprzez poprawienie wykorzystania przeznaczanychnakładów, a następnie ich zwiększenie.

Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect

DEFF Research Database (Denmark)

Antonicka, Hana; Østergaard, Elsebet; Sasarman, Florin

2010-01-01

We investigated the genetic basis for a global and uniform decrease in mitochondrial translation in fibroblasts from patients in two unrelated pedigrees who developed Leigh syndrome, optic atrophy, and ophthalmoplegia. Analysis of the assembly of the oxidative phosphorylation complexes showed...... severe decreases of complexes I, IV, and V and a smaller decrease in complex III. The steady-state levels of mitochondrial mRNAs, tRNAs, and rRNAs were not reduced, nor were those of the mitochondrial translation elongation factors or the protein components of the mitochondrial ribosome. Using...... includes mtRF1a, mtRF1, and Ict1, all characterized by the presence of a GGQ motif at the active site. However, C12orf65 does not exhibit peptidyl-tRNA hydrolase activity in an in vitro assay with bacterial ribosomes. We suggest that it might play a role in recycling abortive peptidyl-tRNA species...

Three-dimensional structure of β-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W

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Weijers Rob NM

2010-06-01

Full Text Available Abstract Background We examined the effects of the R325W mutation on the three-dimensional (3D structure of the β-cell-specific Zn2+ (zinc transporter ZnT-8. Methods A model of the C-terminal domain of the human ZnT-8 protein was generated by homology modeling based on the known crystal structure of the Escherichia coli (E. coli zinc transporter YiiP at 3.8 Å resolution. Results The homodimer ZnT-8 protein structure exists as a Y-shaped architecture with Arg325 located at the ultimate bottom of this motif at approximately 13.5 Å from the transmembrane domain juncture. The C-terminal domain sequences of the human ZnT-8 protein and the E. coli zinc transporter YiiP share 12.3% identical and 39.5% homologous residues resulting in an overall homology of 51.8%. Validation statistics of the homology model showed a reasonable quality of the model. The C-terminal domain exhibited an αββαβ fold with Arg325 as the penultimate N-terminal residue of the α2-helix. The side chains of both Arg325 and Trp325 point away from the interface with the other monomer, whereas the ε-NH3+ group of Arg325 is predicted to form an ionic interaction with the β-COO- group of Asp326 as well as Asp295. An amino acid alignment of the β2-α2 C-terminal loop domain revealed a variety of neutral amino acids at position 325 of different ZnT-8 proteins. Conclusions Our validated homology models predict that both Arg325 and Trp325, amino acids with a helix-forming behavior, and penultimate N-terminal residues in the α2-helix of the C-terminal domain, are shielded by the planar surface of the three cytoplasmic β-strands and hence unable to affect the sensing capacity of the C-terminal domain. Moreover, the amino acid residue at position 325 is too far removed from the docking and transporter parts of ZnT-8 to affect their local protein conformations. These data indicate that the inherited R325W abnormality in SLC30A8 may be tolerated and results in adequate zinc transfer

29 CFR 408.5 - Annual financial report.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Annual financial report. 408.5 Section 408.5 Labor... STANDARDS LABOR ORGANIZATION TRUSTEESHIP REPORTS § 408.5 Annual financial report. During the continuance of... organization the annual financial report and any Form T-1 reports required by part 403 of this chapter, signed...

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.

Science.gov (United States)

Zucker-Franklin, D; Pancake, B A; Marmor, M; Legler, P M

1997-06-10

In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities.

Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

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Srivastava Kumar

2008-12-01

Full Text Available Abstract Background The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. Methods We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. Results The R337H mutation was found in three patients but in none of the controls (p = 0.0442. Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16 and MDM2 (SNP309 genes that may further diminish TP53 tumor suppressor activity. Conclusion These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.

Mutations in MC1R Gene Determine Black Coat Color Phenotype in Chinese Sheep

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Guang-Li Yang

2013-01-01

Full Text Available The melanocortin receptor 1 (MC1R plays a central role in regulation of animal coat color formation. In this study, we sequenced the complete coding region and parts of the 5′- and 3′-untranslated regions of the MC1R gene in Chinese sheep with completely white (Large-tailed Han sheep, black (Minxian Black-fur sheep, and brown coat colors (Kazakh Fat-Rumped sheep. The results showed five single nucleotide polymorphisms (SNPs: two non-synonymous mutations previously associated with coat color (c.218 T>A, p.73 Met>Lys. c.361 G>A, p.121 Asp>Asn and three synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu. c.735 C>T, p.245 Ile>Ile. Meanwhile, all mutations were detected in Minxian Black-fur sheep. However, the two nonsynonymous mutation sites were not in all studied breeds (Large-tailed Han, Small-tailed Han, Gansu Alpine Merino, and China Merino breeds, all of which are in white coat. A single haplotype AATGT (haplotype3 was uniquely associated with black coat color in Minxian Black-fur breed (P=9.72E-72, chi-square test. The first and second A alleles in this haplotype 3 represent location at 218 and 361 positions, respectively. Our results suggest that the mutations of MC1R gene are associated with black coat color phenotype in Chinese sheep.

New insights into thyroglobulin gene: molecular analysis of seven novel mutations associated with goiter and hypothyroidism.

Science.gov (United States)

Citterio, Cintia E; Machiavelli, Gloria A; Miras, Mirta B; Gruñeiro-Papendieck, Laura; Lachlan, Katherine; Sobrero, Gabriela; Chiesa, Ana; Walker, Joanna; Muñoz, Liliana; Testa, Graciela; Belforte, Fiorella S; González-Sarmiento, Rogelio; Rivolta, Carina M; Targovnik, Héctor M

2013-01-30

The thyroglobulin (TG) gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. Up to now, 62 inactivating mutations in the TG gene have been identified in patients with congenital goiter and endemic or non-endemic simple goiter. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report 13 patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and imaging evaluation. Single-strand conformation polymorphism (SSCP) analysis, endonuclease restriction analysis, sequencing of DNA, genotyping, population screening, and bioinformatics studies were performed. Molecular analyses revealed seven novel inactivating TG mutations: c.378C>A [p.Y107X], c.2359C>T [p.R768X], c.2736delG [p.R893fsX946], c.3842G>A [p.C1262Y], c.5466delA [p.K1803fsX1833], c.6000C>G [p.C1981W] and c.6605C>G [p.P2183R] and three previously reported mutations: c.886C>T [p.R277X], c.6701C>A [p.A2215D] and c.7006C>T [p.R2317X]. Six patients from two families were homozygous for p.R277X mutation, four were compound heterozygous mutations (p.Y107X/p.C1262Y, p.R893fsX946/p.A2215D, p.K1803fsX1832/p.R2317X), one carried three identified mutations (p.R277X/p.C1981W-p.P2183R) together with a hypothetical micro deletion and the remaining two siblings from another family with typical phenotype had a single p.R768X mutated allele. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of altered TG folding as a consequency of truncated TG proteins and missense mutations located in ACHE-like domain or that replace cysteine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Udział stresu w etiopatogenezie i przebiegu schizofrenii

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Adam Wysokiński

2016-09-01

Full Text Available Psychozy typu schizofrenii stanowią jeden z głównych problemów współczesnej psychiatrii. Wynika to z ich znacznego rozpowszechnienia w populacji ogólnej, ale również ze złożoności problemów psychiatryczno-psychologicznych, które składają się na obraz kliniczny schorzeń z tej grupy. Stan psychiczny osób chorych na schizofrenię jest wypadkową doświadczanych omamów, urojeń, objawów negatywnych, zaburzeń nastroju i zaburzeń funkcji poznawczych oraz działania rozmaitych stresorów. Wymienione objawy i zaburzenia wywierają przewlekły niekorzystny wpływ na funkcjonowanie zawodowe i rodzinne pacjentów, co nie tylko przekłada się na istotne pogorszenie jakości ich życia, lecz także eksponuje ich na rozmaite stresory psychospołeczne. Przewlekły nadmierny stres to zjawisko o potwierdzonej roli w wyzwalaniu pierwszego epizodu schizofrenii. Ponadto stres rzutuje na przebieg choroby –zwiększa ryzyko jej nawrotowości. Istotnym zadaniem lekarza psychiatry i psychologa jest zwrócenie uwagi na mechanizmy radzenia sobie ze stresem, jakimi dysponuje pacjent, gdyż dzięki nim będzie on w stanie skuteczniej radzić sobie w sytuacjach trudnych.

Gypsy Phenylketonuria: A point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia

Energy Technology Data Exchange (ETDEWEB)

Kalanin, J. [Institute for Clinical and Experical Medicine, Praha (Czechoslovakia); Takarada, Y. [Toyobo Research Center, Shiga (Japan); Kagawa, S.; Yamashita, K.; Ohtsuka, N.; Matsuoka, A. [Hyogo College of Medicine, Nishinomiya (Japan)

1994-01-15

A direct mutational analysis of the phenylalanine hydroxylase gene (PAH) in Gypsy families with phenylketonuria (PKU) has not yet been presented. However, they obviously represent a group at high risk for this inherited disease. The authors analyzed the PAH loci of 65 Gypsies originating from Eastern Slovakia by a combination of PCR amplification, direct sequencing and ASO hybridization. These studies uncovered 10 {open_quotes}classical PKU{close_quotes} patients to be homozygous for a R252W (CGG-TGG) transition, and 29 heterozygous carriers of this mutation. Fifteen control Caucasoid PKU patients from the Czech and Slovak Republics were selected. In this group they detected R252W mutation in two subjects (6.67% of all mutant alleles). Both were compound heterozygous for two different mutations. Previous haplotype studies of Welsh Gypsies with PKU were uninformative in the determination of heterozygosity. ASO hybridization served effectively for the consequent analyses in Gypsy PKU-related families and to identify the carriers among the unrelated subjects. 19 refs., 2 figs.

Ocena poziomu lęku i depresji u rodziców dzieci z zespołem nerczycowym – sposoby radzenia sobie z nimi i metody wsparcia

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Monika Pawlak-Bratkowska

2013-06-01

Full Text Available Wstęp i cele pracy: Idiopatyczny zespół nerczycowy w wieku rozwojowym przebiega nawrotowo i trwale zmie‑ nia życie dzieci oraz ich rodziców. Celem badania była ocena poziomu lęku i depresji u rodziców dzieci z zespo‑ łem nerczycowym. Materiał i metodyka: Badanie zaplanowano jako przekrojową próbę kliniczną wśród rodzi‑ ców dzieci chorujących na zespół nerczycowy w odniesieniu do rodziców dzieci zdrowych. Wszyscy badani (46 rodziców wypełniali: ankietę dotyczącą przebiegu choroby u dziecka, kwestionariusz STAI (Inwentarz stanu i cechy lęku, kwestionariusz Skali depresji Becka, kwestionariusz Skali kontroli emocji (CECS. Grupę kontrolną stanowiło 20 rodziców dzieci zdrowych. Wyniki: Rodzice dzieci z zespołem nerczycowym charakteryzowali się istotnie wyższym poziomem depresji (Skala depresji Becka 8,7 vs 4,9, t = 2,18, p < 0,05. U ojców zaobserwo‑ wano wyższe subiektywne uczucie kontrolowania własnych reakcji w porównaniu z matkami – wyższy wynik CECS, suma u ojców (55,1 vs 47,2, t = 2,53, p < 0,05. U matek odnotowano wyższe wskaźniki zarówno w ska‑ lach mierzących poziom lęku jako cechy (STAI – cecha 45,7 vs 36,1, t = 3,19, p < 0,05 i stanu (STAI – stan 42,8 vs 33,4, t = 2,8, p < 0,05, jak i w kwestionariuszu badającym poziom depresji (10,62 vs 4,86, t = 2,66, p < 0,05. Rodzice, którzy wykazywali tendencję do obwiniania się o chorobę dziecka, podczas jej pierwszego epizodu uzyskali statystycznie istotny wyższy wynik w testach badających poziom depresji. Wnioski: Rodzice dzieci cierpiących na zespół nerczycowy charakteryzowali się istotnie wyższym poziomem depresji niż rodzice dzieci zdrowych. Ważne wydaje się objęcie szczególną opieką matek, mającą na celu obniżenie poziomu lęku i objawów depresji, oraz ojców skłonnych do tłumienia przeżywanych emocji.

mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

International Nuclear Information System (INIS)

Wang Chengye; Kong Qingpeng; Yao Yonggang; Zhang Yaping

2006-01-01

Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL

Digitalizacja zbiorów bibliotecznych - forma ochrony i szansa na upowszechnianie informacji

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Bartosz Spadło

2013-12-01

Full Text Available W artykule omówiono różne zastosowania digitalizacji zbiorów bibliotecznych. Są to przede wszystkim: archiwizacja i ochrona zbiorów, ułatwianie dostępu do informacji oraz ochrona środowiska. Przeanalizowane zostały wady i zalety przekształcania dokumentów na postać cyfrową, z uwzględnieniem aspektu politycznego, ekonomicznego, kulturalnego i ekologicznego.

Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets.

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Erhard van der Vries

2011-09-01

Full Text Available Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltamivir, zanamivir and peramivir. However, the ability of this virus to cause disease and spread in the human population is unknown. Therefore, this clinical isolate (NL/2631-R223 was compared with a well-characterized reference virus (NL/602. In vitro experiments showed that NL/2631-I223R replicated as well as NL/602 in MDCK cells. In a ferret pathogenesis model, body weight loss was similar in animals inoculated with NL/2631-R223 or NL/602. In addition, pulmonary lesions were similar at day 4 post inoculation. However, at day 7 post inoculation, NL/2631-R223 caused milder pulmonary lesions and degree of alveolitis than NL/602. This indicated that the mutant virus was less pathogenic. Both NL/2631-R223 and a recombinant virus with a single I223R change (recNL/602-I223R, transmitted among ferrets by aerosols, despite observed attenuation of recNL/602-I223R in vitro. In conclusion, the I223R mutated virus isolate has comparable replicative ability and transmissibility, but lower pathogenicity than the reference virus based on these in vivo studies. This implies that the 2009 pandemic influenza A/H1N1 virus subtype with an isoleucine to arginine change at position 223 in the neuraminidase has the potential to spread in the human population. It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza.

Raul Meele meeldivad 65

Index Scriptorium Estoniae

2006-01-01

2. märtsil tähistab oma 65. sünnipäeva kunstnik Raul Meel. R. Meel kirjutas-joonistas 2005. a. kaks raamatut. Seoses juubeliga toimub tema loomingut käsitlev konverents Shotimaal Dundee ülikoolis. USA New Jersey Rutgers'i ülikooli juures kirjutatakse Meele-keskselt kaht doktoritööd

Effect of mutations on the thermostability of <i>Aspergillus aculeatusi> β-1,4-galactanase

DEFF Research Database (Denmark)

Torpenholt, Søs Katja; De Maria, Leonardo; Olsson, Mats Henrik Mikael

2015-01-01

New variants of β-1,4-galactanase from the mesophilic organism Aspergillus aculeatus were designed using the structure of β-1,4-galactanase from the thermophile organism Myceliophthora thermophila as a template. Some of the variants were generated using PROPKA 3.0, a validated pKa prediction tool......, to test its usefulness as an enzyme design tool. The PROPKA designed variants were D182N and S185D/Q188T, G104D/A156R. Variants Y295F and G306A were designed by a consensus approach, as a complementary and validated design method. D58N was a stabilizing mutation predicted by both methods. The predictions...... were experimentally validated by measurements of the melting temperature (Tm) by differential scanning calorimetry. We found that the Tm is elevated by 1.1 °C for G306A, slightly increased (in the range of 0.34 to 0.65 °C) for D182N, D58N, Y295F and unchanged or decreased for S185D/Q188T and G104D/A156...

Ocena rozwoju fizycznego i stanu odżywienia dzieci rozpoczynających edukację w szkole podstawowej o profilu sportowym

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Zbigniew Krenc

2013-12-01

Full Text Available Wprowadzenie: Szkoły sportowe odgrywają ważną rolę w promowaniu istotnego dla zdrowia ruchu, w jego najbardziej aktywnej formie, czyli sportu wyczynowego. Cel pracy: Celem podjętych badań była próba określenia, na podstawie oceny stanu odżywienia oraz rozwoju fizycznego, potencjału zdrowotnego dzieci rozpoczynających edukację w szkole podstawowej o profilu sportowym. Materiał i metody: Badania przeprowadzono u dzieci rozpoczynających naukę w szkołach podstawowych, w tym u 41 uczniów ze szkoły sportowej i 46 ze szkoły powszechnej. U wszystkich badanych wykonano pomiary antropometryczne (wzrostu, masy ciała oraz grubości fałdów skórno-tłuszczowych. Wyniki: Pod‑ stawowe parametry rozwoju fizycznego (wzrost, masa ciała, BMI nie wykazywały istotnych statystycznie różnic w obu analizowanych grupach uczniów. U dzieci ze szkoły sportowej częściej niż w grupie kontrolnej występowała wysokorosłość (wzrost powyżej 95. centyla, a także otyłość (BMI powyżej 95. centyla. Niedobór masy ciała (poniżej 5. centyla, niskorosłość (poniżej 5. centyla oraz niedożywienie (BMI poniżej 5. centyla obserwowano wyłącznie u uczniów ze szko‑ ły sportowej. Grubość fałdów skórno-tłuszczowych w okolicy podłopatkowej, nad talerzem biodrowym i na podudziu była istotnie statystycznie mniejsza u dzieci ze szkoły sportowej. Wnioski: Analiza podstawowych parametrów rozwoju fizycznego nie wykazywała istotnych różnic w obu badanych grupach uczniów, chociaż skrajne wartości tych parame‑ trów częściej były obserwowane u dzieci ze szkoły sportowej. Grubość fałdów skórno-tłuszczowych w okolicy podłopat‑ kowej, nad talerzem biodrowym i na podudziu była istotnie statystycznie mniejsza u uczniów ze szkoły sportowej.

Short communication: Phenotypic protease inhibitor resistance and cross-resistance in the clinic from 2006 to 2008 and mutational prevalences in HIV from patients with discordant tipranavir and darunavir susceptibility phenotypes.

Science.gov (United States)

Bethell, Richard; Scherer, Joseph; Witvrouw, Myriam; Paquet, Agnes; Coakley, Eoin; Hall, David

2012-09-01

To test tipranavir (TPV) or darunavir (DRV) as treatment options for patients with phenotypic resistance to protease inhibitors (PIs), including lopinavir, saquinavir, atazanavir, and fosamprenavir, the PhenoSense GT database was analyzed for susceptibility to DRV or TPV among PI-resistant isolates. The Monogram Biosciences HIV database (South San Francisco, CA) containing 7775 clinical isolates (2006-2008) not susceptible to at least one first-generation PI was analyzed. Phenotypic responses [resistant (R), partially susceptible (PS), or susceptible (S)] were defined by upper and lower clinical cut-offs to each PI. Genotypes were screened for amino acid substitutions associated with TPV-R/DRV-S and TPV-S/DRV-R phenotypes. In all, 4.9% (378) of isolates were resistant to all six PIs and 31.0% (2407) were resistant to none. Among isolates resistant to all four first-generation PIs, DRV resistance increased from 21.2% to 41.9% from 2006 to 2008, respectively, and resistance to TPV remained steady (53.9 to 57.3%, respectively). Higher prevalence substitutions in DRV-S/TPV-R isolates versus DRV-R/TPV-S isolates, respectively, were 82L/T (44.4% vs. 0%) and 83D (5.8% vs. 0%). Higher prevalence substitutions in DRV-R/TPV-S virus were 50V (0.0% vs. 28.9%), 54L (1.0% vs. 36.1%), and 76V (0.4% vs. 15.5%). Mutations to help predict discordant susceptibility to DRV and TPV in isolates with reduced susceptibility to other PIs were identified. DRV resistance mutations associated with improved virologic response to TPV were more prevalent in DRV-R/TPV-S isolates. TPV resistance mutations were more prevalent in TPV-R and DRV-S isolates. These results confirm the impact of genotype on phenotype, illustrating how HIV genotype and phenotype data assist regimen optimization.

Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.

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Mehul Mistri

Full Text Available Tay Sachs disease (TSD is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients. Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K, c.964 G>A (p.D322N, c.964 G>T (p.D322Y, c.1178C>G (p.R393P and c.1385A>T (p.E462V, c.1432 G>A (p.G478R and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W. The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.

Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.

Science.gov (United States)

Mistri, Mehul; Tamhankar, Parag M; Sheth, Frenny; Sanghavi, Daksha; Kondurkar, Pratima; Patil, Swapnil; Idicula-Thomas, Susan; Gupta, Sarita; Sheth, Jayesh

2012-01-01

Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.

Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor.

Science.gov (United States)

McBride, Christie M; Smith, Ashley M; Smith, Jennifer L; Reloj, Allison R; Velasco, Ellyn J; Powell, Jonathan; Elayi, Claude S; Bartos, Daniel C; Burgess, Don E; Delisle, Brian P

2013-05-01

KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (I Kr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing I Kr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (I Kv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients' genotypes) mostly corrected the changes in I Kv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing I Kr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease I Kr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient.

Low prevalence of CHEK2 gene mutations in multiethnic cohorts of breast cancer patients in Malaysia.

Science.gov (United States)

Mohamad, Suriati; Isa, Nurismah Md; Muhammad, Rohaizak; Emran, Nor Aina; Kitan, Nor Mayah; Kang, Peter; Kang, In Nee; Taib, Nur Aishah Mohd; Teo, Soo Hwang; Akmal, Sharifah Noor

2015-01-01

CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.

Null missense ABCR (ABCA4) mutations in a family with stargardt disease and retinitis pigmentosa.

Science.gov (United States)

Shroyer, N F; Lewis, R A; Yatsenko, A N; Lupski, J R

2001-11-01

To determine the type of ABCR mutations that segregate in a family that manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the functional consequences of the underlying mutations. Direct sequencing of all 50 exons and flanking intronic regions of ABCR was performed for the STGD- and RP-affected relatives. RNA hybridization, Western blot analysis, and azido-adenosine triphosphate (ATP) labeling was used to determine the effect of disease-associated ABCR mutations in an in vitro assay system. Compound heterozygous missense mutations were identified in patients with STGD and RP. STGD-affected individual AR682-03 was compound heterozygous for the mutation 2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals AR682-04 and-05 were compound heterozygous for the complex allele [W1408R; R1640W] and the missense mutation V767D. Functional analysis of the mutation V767D by Western blot and ATP binding revealed a severe reduction in protein expression. In vitro analysis of ABCR protein with the mutations W1408R and R1640W showed a moderate effect of these individual mutations on expression and ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in protein expression. These data reveal that missense ABCR mutations may be associated with RP. Functional analysis reveals that the RP-associated missense ABCR mutations are likely to be functionally null. These studies of the complex allele W1408R; R1640W suggest a synergistic effect of the individual mutations. These data are congruent with a model in which RP is associated with homozygous null mutations and with the notion that severity of retinal disease is inversely related to residual ABCR activity.

Revision of the genus-group Hystricella R. T. Lowe, 1855 from Porto Santo (Madeira Archipelago), with descriptions of new recent and fossil taxa (Gastropoda, Helicoidea, Geomitridae).

Science.gov (United States)

Mattia, Willy De; Neiber, Marco T; Groh, Klaus

2018-01-01

The genus-group Hystricella R. T. Lowe, 1855 is revised on the basis of conchological, anatomical and genetic characteristics. A new genus Wollastonia gen. n. , two recent species, W. jessicae sp. n. and W. klausgrohi sp. n ., and one recent subspecies, W. jessicae monticola ssp. n. are described as new to science, as well as five fossil taxa, H. microcarinata sp. n. , W. beckmanni sp. n. , W. falknerorum sp. n. , W. ripkeni sp. n. , and W. inexpectata sp. n. For Helix vermetiformis R. T. Lowe, 1855, H. leacockiana Wollaston, 1878, H. oxytropis R. T. Lowe, 1831, H. duplicata R. T. Lowe, 1831 and H. oxytropis var. ß subcarinulata Wollaston, 1878 lectotypes are designated. For the taxa Helix bicarinata G. B. Sowerby I, 1824, Helix bicarinata var. ß aucta Wollaston, 1878 and Discula bulverii W. Wood, 1828 neotypes are selected. The taxa aucta and subcarinulata are elevated to specific rank. For the hitherto monospecific (sub-) genus Callina R. T. Lowe, 1855 it is shown that it is not closely related to the genus Discula but to the Hystricella -group and its generic rank is confirmed. The taxon D. bulverii W. Wood, 1828 is transferred from the genus Discula s. str. to the genus Callina . A further fossil taxon C. waldeni sp. n. is described as new to science.

Pyrosequencing-Based Assays for Rapid Detection of HER2 and HER3 Mutations in Clinical Samples Uncover an E332E Mutation Affecting HER3 in Retroperitoneal Leiomyosarcoma

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Paula González-Alonso

2015-08-01

Full Text Available Mutations in Human Epidermal Growth Factor Receptors (HER are associated with poor prognosis of several types of solid tumors. Although HER-mutation detection methods are currently available, such as Next-Generation Sequencing (NGS, alternative pyrosequencing allow the rapid characterization of specific mutations. We developed specific PCR-based pyrosequencing assays for identification of most prevalent HER2 and HER3 mutations, including S310F/Y, R678Q, L755M/P/S/W, V777A/L/M, 774-776 insertion, and V842I mutations in HER2, as well as M91I, V104M/L, D297N/V/Y, and E332E/K mutations in HER3. We tested 85 Formalin Fixed and Paraffin Embbeded (FFPE samples and we detected three HER2-V842I mutations in colorectal carcinoma (CRC, ovarian carcinoma, and pancreatic carcinoma patients, respectively, and a HER2-L755M mutation in a CRC specimen. We also determined the presence of a HER3-E332K mutation in an urothelial carcinoma sample, and two HER3-D297Y mutations, in both gastric adenocarcinoma and CRC specimens. The D297Y mutation was previously detected in breast and gastric tumors, but not in CRC. Moreover, we found a not-previously-described HER3-E332E synonymous mutation in a retroperitoneal leiomyosarcoma patient. The pyrosequencing assays presented here allow the detection and characterization of specific HER2 and HER3 mutations. These pyrosequencing assays might be implemented in routine diagnosis for molecular characterization of HER2/HER3 receptors as an alternative to complex NGS approaches.

Związek pomiędzy typem alergenu a rozwojem choroby atopowej w grupie pacjentów leczonych w Klinice Pediatrii, Nefrologii i Alergologii Dziecięcej WIM w Warszawie

Directory of Open Access Journals (Sweden)

Bolesław Kalicki

2011-07-01

Full Text Available Punktowe testy skórne to jedna z najpowszechniej stosowanych metod diagnostycznych we współczesnej alergologii, dzięki niej rozpoznajemy alergię natychmiastową, IgE-zależną. Diagnostycznie alergeny są stosowane w postaci standaryzowanych roztworów. Oceniana jest średnica powstałych bąbli, a także ich wielkość wzglę- dem kontroli dodatniej i ujemnej. W prezentowanej pracy przedstawiono wyniki punktowych testów skórnych przeprowadzonych w grupie 225 dzieci z objawami alergii w postaci astmy, alergicznego nieżytu nosa (ANN oraz atopowego zapalenia skóry (AZS. Oceniano związek pomiędzy typem alergenu a chorobą atopową oraz wiekiem dziecka. Najczęściej uczulającym alergenem w całej badanej grupie były roztocza kurzu domowego, stwierdzone u 81% pacjentów. Drugą co do częstości występowania alergię stanowiło uczulenie na pyłki traw (u 43%. W dalszej kolejności uczulały pyłki drzewa (33% i alergeny sierści kota (27%. Kolejność ta zmienia się w poszczególnych grupach wiekowych. Dla najmłodszej grupy pacjentów najczęściej stwierdzanym alergenem były pleśnie (54,3%, rzadziej odnotowywano – w równym stopniu – roztocza kurzu domowego oraz alergeny traw (po 43,5%. W grupie między 5. a 12. rokiem życia dominującym alergenem były roztocza kurzu domowego (90,7%, następnie pleśnie (50,4% i trawy (36%. U dzieci powyżej 12. roku życia również dominowały roztocza kurzu domowego (92%, rzadziej stwierdzano uczulenie – w równym stopniu – na trawy i pleśnie (po 58%. Najczęstszą manifestacją kliniczną był zespół współwystępowania astmy i ANN, rzadziej wystę- powały objawy astmy, a jeszcze rzadziej objawy ANN oraz zespół współwystępowania astmy i AZS. Najmniej liczną grupę stanowiły dzieci z objawami AZS. Rozkład najczęściej występujących alergenów w odniesieniu do manifestacji choroby atopowej wykazał, że wśród pacjentów z astmą oraz współistniejącymi astmą i ANN

Wybór najskuteczniejszej metody rekultywacji zbiorników wodnych z wykorzystaniem metody AHP

OpenAIRE

Joanna Chmist; Mateusz Hämmerling

2016-01-01

Problem z jakością wód w zamkniętych zbiornikach jest znany od lat. Poprawa parametrów jakości wody w jeziorze zwiększa możliwości jego wykorzystania. Obecnie istnieje wiele metod rekultywacji zbiorników wodnych. Wybór odpowiedniej uwarunkowany jest zarówno oddziaływaniem różnorodnych czynników powodujących stopniową degradację jezior, jak i kosztami rekultywacji czy typem zbiornika. W artykule zaprezentowano praktyczne zastosowanie metody AHP w rozwiązaniu wielokryterialnych problemów rekult...

Effects of Mutations in the Substrate-Binding Domain of Poly[(R)-3-Hydroxybutyrate] (PHB) Depolymerase from Ralstonia pickettii T1 on PHB Degradation▿

OpenAIRE

Hiraishi, Tomohiro; Hirahara, Yoko; Doi, Yoshiharu; Maeda, Mizuo; Taguchi, Seiichi

2006-01-01

Poly[(R)-3-hydroxybutyrate] (PHB) depolymerase from Ralstonia pickettii T1 (PhaZRpiT1) adsorbs to denatured PHB (dPHB) via its substrate-binding domain (SBD) to enhance dPHB degradation. To evaluate the amino acid residues participating in dPHB adsorption, PhaZRpiT1 was subjected to a high-throughput screening system consisting of PCR-mediated random mutagenesis targeted to the SBD gene and a plate assay to estimate the effects of mutations in the SBD on dPHB degradation by PhaZRpiT1. Genetic...

<i>phuR i>intergenic mutation results in pleiotropic effects on global gene expression

DEFF Research Database (Denmark)

Khademi, Seyed Mohammad Hossein; Wassermann, Tina; Ciofu, Oana

2015-01-01

We have previously found a positive selection for promoter mutations in Pseudomonas aeruginosa DK2 leading to increased expression of the phu (Pseudomonas heme utilization) system. By mimicking conditions of the CF airways in vitro, we experimentally demonstrated that increased expression of phu......R confers a growth advantage in the presence of hemoglobin, thus suggesting that P. aeruginosa evolves towards iron acquisition from hemoglobin....

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

Energy Technology Data Exchange (ETDEWEB)

O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, III, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim; (OHSU- Cancer Instit.); (ARIAD)

2010-09-07

Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.

Czy praktyczny profil studiów wymaga nowej organizacji programów nauczania i innowacyjnych metod edukacji?

Directory of Open Access Journals (Sweden)

Kinga Kurowska

2017-12-01

Full Text Available Zmiany społeczno-gospodarcze, jakie zachodzą we współczesnym świecie, związane z rozwojem nauki i technologii, wymagają nowych, innowacyjnych podejść do edukacji, a w tym do szkolnictwa wyższego. Egalitaryzm przejawia sięprzede wszystkim masową dostępnością do szkolnictwa wyższego. Proces ten zmusza szkoły wyższe do rozwijania, nie tylko elitarnych kursów akademickich, lecz także programów zorientowanych zawodowo. Konieczność wykorzystania nowych narzędzi i metod edukacyjnych staje się oczywistością. W artykule przedstawiono podstawy prawne profilu studiów praktycznych na kierunki akademickie w Polsce po reformie szkolnictwa wyższego w 2014 r., a także kontekst kształcenia i szkolenia zawodowego w zakresie europejskich oraz polskich ram kwalifikacji odnośnie uczenia się przez całe życie (LLL. Przedstawiono także przykłady nowych form edukacji przydatnych w rozwijaniu kompetencji i umiejętności wymaganych od dzisiejszych absolwentów szkół wyższych.

T cells to a dominant epitope of GAD65 express a public CDR3 motif.

Science.gov (United States)

Quinn, Anthony; McInerney, Marcia; Huffman, Donald; McInerney, Brigid; Mayo, Stella; Haskins, Kathryn; Sercarz, Eli

2006-06-01

Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes, and serve as a model for type 1 diabetes (T1D) and natural autoimmunity. T cell responses to the pancreatic islet antigen glutamic acid decarboxylase 65 (GAD65) can be detected in the spleens of young prediabetic NOD mice, which display a unique MHC class II molecule. Here, we report that a distinct TcR beta chain and CDR3 motif are utilized by all NOD mice in response to a dominant determinant on GAD65, establishing a public repertoire in the spontaneous autoimmunity to an important islet cell antigen. GAD65 530-543 (p530)-reactive T cells preferentially utilize the Vbeta4, Dbeta2.1 and Jbeta2.7 gene segments, with a CDR3 that is characterized by a triad of amino acids, DWG, preceded by a polar residue. In addition, we used CDR3 length spectratyping, CDR3-specific reverse transcriptase-PCR and direct TcR sequencing to show that the TcR beta chain structural patterns associated with p530-specific T cells consistently appeared in the islets of young NOD mice with insulitis, but not in the inflamed islets of streptozotocin-treated C57BL/6 mice, or in inflamed NOD salivary glands. To our knowledge, this is the first report to demonstrate that a public T cell repertoire is used in spontaneous autoimmunity to a dominant self-determinant. These findings suggest that defined clonotypes and repertoires may be preferentially selected in haplotypes predisposed to spontaneous autoimmunity.

Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.

Science.gov (United States)

Nemec, Antonia A; Bush, Korie B; Towle-Weicksel, Jamie B; Taylor, B Frazier; Schulz, Vincent; Weidhaas, Joanne B; Tuck, David P; Sweasy, Joann B

2016-11-01

Repair of DNA damage is critical for maintaining the genomic integrity of cells. DNA polymerase lambda (POLL/Pol λ) is suggested to function in base excision repair (BER) and nonhomologous end-joining (NHEJ), and is likely to play a role in damage tolerance at the replication fork. Here, using next-generation sequencing, it was discovered that the POLL rs3730477 single-nucleotide polymorphism (SNP) encoding R438W Pol λ was significantly enriched in the germlines of breast cancer patients. Expression of R438W Pol λ in human breast epithelial cells induces cellular transformation and chromosomal aberrations. The role of estrogen was assessed as it is commonly used in hormone replacement therapies and is a known breast cancer risk factor. Interestingly, the combination of estrogen treatment and the expression of the R438W Pol λ SNP drastically accelerated the rate of transformation. Estrogen exposure produces 8-oxoguanine lesions that persist in cells expressing R438W Pol λ compared with wild-type (WT) Pol λ-expressing cells. Unlike WT Pol λ, which performs error-free bypass of 8-oxoguanine lesions, expression of R438W Pol λ leads to an increase in mutagenesis and replicative stress in cells treated with estrogen. Together, these data suggest that individuals who carry the rs3730477 POLL germline variant have an increased risk of estrogen-associated breast cancer. The Pol λ R438W mutation can serve as a biomarker to predict cancer risk and implicates that treatment with estrogen in individuals with this mutation may further increase their risk of breast cancer. Mol Cancer Res; 14(11); 1068-77. ©2016 AACR. ©2016 American Association for Cancer Research.

Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation

International Nuclear Information System (INIS)

Zhao, Fuxin; Guan, Minqiang; Zhou, Xiangtian; Yuan, Meixia; Liang, Ming; Liu, Qi; Liu, Yan; Zhang, Yongmei; Yang, Li; Tong, Yi; Wei, Qi-Ping; Sun, Yan-Hong; Qu, Jia

2009-01-01

We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

Effect of T- and C-loop mutations on the Herbaspirillum seropedicae GlnB protein in nitrogen signalling.

Science.gov (United States)

Bonatto, Ana C; Souza, Emanuel M; Pedrosa, Fábio O; Yates, M Geoffrey; Benelli, Elaine M

2005-01-01

Proteins of the PII family are found in species of all kingdoms. Although these proteins usually share high identity, their functions are specific to the different organisms. Comparison of structural data from Escherichia coli GlnB and GlnK and Herbaspirillum seropedicae GlnB showed that the T-loop and C-terminus were variable regions. To evaluate the role of these regions in signal transduction by the H. seropedicae GlnB protein, four mutants were constructed: Y51F, G108A/P109a, G108W and Q3R/T5A. The activities of the native and mutated proteins were assayed in an E. coli background constitutively expressing the Klebsiella pneumoniae nifLA operon. The results suggested that the T-loop and C-terminus regions of H. seropedicae GlnB are involved in nitrogen signal transduction.

Agresja i przemoc w rodzinie a rozwój psychofizyczny i funkcjonowanie społeczne dzieci

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Norbert Dera

2013-04-01

Full Text Available Wstęp: Przemoc zdarza się w każdej grupie społecznej i to z porównywalną częstotliwością. Różnice środowi‑ skowe dotyczą jedynie sposobu przejawiania przemocy, a nie jej natężenia. Jest ona procesem, który stale przy‑ biera na sile, natomiast skutki stosowanej przez sprawcę przemocy zależą od wieku i stadium rozwojowego dziecka. Celem pracy było poznanie negatywnych skutków wpływu agresji i przemocy w rodzinie na rozwój psy‑ chofizyczny i funkcjonowanie społeczne dzieci. Materiał i metoda: Badanie przeprowadzono wśród 237 uczniów klas II, w wieku 14 lat, trzech gimnazjów województwa warmińsko-mazurskiego. Do badań użyto opracowanych ankiet dla rodziców, dzieci oraz nauczycieli i pedagogów. Przeprowadzono analizę dokumen‑ tacji z ośrodków zdrowia, pedagogiczno-wychowawczej, psychologicznej z placówek zajmujących się proble‑ mami dzieci (policyjne, ośrodki wychowawcze, poradnie psychologiczne etc.. Wykorzystano również dwa testy psychologiczne. Za metodę analizy statystycznej przyjęto metodę sondażu diagnostycznego. Wyniki: W bada‑ nej populacji u niemal połowy dzieci stwierdzono przejawy przemocy i agresji w rodzinie, przy czym tylko poło‑ wa z tej grupy bezpośrednio wskazała na obecność tych zjawisk. Ofiarami przemocy i agresji w rodzinie dwu‑ krotnie częściej stają się dziewczęta niż chłopcy. Przemoc często współwystępuje z problemem alkoholowym. Zauważono korelacje pomiędzy częstością stosowania przemocy wobec dziecka i współmałżonka. Przemoc powoduje zaburzenie wszystkich aspektów życia dziecka, zwiększając chorobowość i pogarszając funkcjono‑ wanie społeczne. Wykazano często występowanie przemocy w środowisku wiejskim oraz w rodzinach o niskim statusie socjoekonomicznym bądź takich, w których występuje bezrobocie. Wnioski: Wyniki badań wykazały jednoznacznie, że agresja i przemoc w rodzinie wywiera znamienny i negatywny wpływ na

Identification of a c.544C>T mutation in WDR34 as a deleterious recessive allele of short rib-polydactyly syndrome

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Shu-Han You

2017-12-01

Conclusion: This study was the first to identify c.544C > T [p.Arg182Trp] mutation in WDR34 in a patient with SRPS. According to the database, the homozygous mutation of c.544C > T in WDR34 was deleterious and the prevalence of heterozygous mutation was relatively higher in Asian population. More studies of this mutation in patients with SRPS are required.

Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis.

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Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Cuadrado-Grande, Nuria; Alvarez-Sala-Walther, Luis-Antonio; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2012-10-15

Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype. Copyright © 2012. Published by Elsevier B.V.

Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex.

Science.gov (United States)

Ritchie, Jacob; Pantazatos, Spiro P; French, Leon

2018-07-01

Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, we lack a comprehensive understanding of the macromolecular correlates of MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is considered to be a useful proxy for myelin content. As expected, we found enrichment of positive correlations between myelin-associated genes and the ratio image, supporting its use as a myelin marker. Genome-wide, there was an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated genes. Mitochondrial genes exhibit the strongest relationship, showing higher expression in regions with low T1-w/T2-w ratio. This may be due to the pH gradient in mitochondria as genes up-regulated by pH in the brain were also highly correlated with the ratio. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and pH. We evaluate correlations between AHBA transcriptomic measurements and a group averaged T1-w/T2-w ratio image, showing agreement with in-sample results. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w correlations for immune system, inflammatory disease, and microglia marker genes. Genes with negative correlations were enriched for neuron markers and synaptic plasticity genes. Lastly, our findings are similar when performed on T1-w or inverted T2-w intensities alone

W poszukiwaniu emancypacyjno-transformacyjnego wymiaru badań pedagogicznych i antropologicznych

OpenAIRE

Gołębniak, Bogusława D.; Červinková, Hana

2010-01-01

Zbiór Badania w działaniu. Pedagogika i antropologia zaangażowane, który mamy przyjemność zaprezentować polskim Czytelnikom, stanowi autorskie przedsięwzięcie redakcyjne, podjęte w kontekście, który można, za Wygotskim, nazwać epizodem wspólnego zaangażowania. Doświadczenie wyniesione z udziału w projektach badawczo-rozwojowych realizowanych w ciągu ostatnich lat pod auspicjami Dolnośląskiej Szkoły Wyższej we Wrocławiu pokazało – po pierwsze, że z perspektywy reprezentowanych przez nas różnyc...

Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

Science.gov (United States)

Sharma, Sonia; Grandvaux, Nathalie; Mamane, Yael; Genin, Pierre; Azimi, Nazli; Waldmann, Thomas; Hiscott, John

2002-09-15

IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3 associated with hypertrophic cardiomyopathy among Indians

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Rani Deepa

2012-08-01

Full Text Available Abstract Background Troponin I (TNNI3 is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7% in this gene had been reported in hypertrophic cardiomyopathy patients (HCM. However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study. Methods We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM, along with 160 healthy controls, inhabited in the same geographical region of southern India. Results Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM. The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++. The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85% with a rare codon (GAA: 14%. Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing. Conclusion Our study has provided valuable information regarding the prevalence of TNNI3 mutations in

Methylenetetrahydrofolate reductase C677T mutation and risk of retinal vein thrombosis.

Science.gov (United States)

Soltanpour, Mohammad Soleiman; Soheili, Zahra; Shakerizadeh, Ali; Pourfathollah, Ali Akbar; Samiei, Shahram; Meshkani, Reza; Shahjahani, Mohammad; Karimi, Abbas

2013-06-01

Elevated plasma homocysteine (Hcy) level has been established as a significant risk factor for venous thrombosis and cardiovascular disease. Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been associated with elevated plasma Hcy concentration and may contribute to retinal vein thrombosis (RVT) development. The aim of the present study was to investigate whether the hyperhomocysteinemia and/or homozygosity for the MTHFR C677T mutation are associated with an increased risk for RVT. Our study population consisted of 73 consecutive patients (50-78 years old) with RVT and 73 control subjects (51-80 years old), matched for age and sex. Genotyping for the MTHFR C677T mutation was performed by polymerase chain reaction-restriction fragment length polymorphism technique and Hcy level was determined by an enzyme immunoassay kit. The prevalence of 677TT genotype was higher in patients than control subjects, but the difference in frequency didn't reach a significant value (P = 0.07). The frequency of the 677T allele was 26% and 21.2% in patients and controls, respectively and did not differ significantly between the two groups (odds ratio = 1.3, 95% confidence interval (0.75-2.24), P = 0.33). Fasting plasma total Hcy level was significantly higher in patients than controls (P = 0.001). Our study demonstrated that hyperhomocysteinemia, but not the MTHFR C677T mutation, is associated with RVT.

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

DEFF Research Database (Denmark)

Bode, Anna; Wood, Sian-Elin; Mullins, Jonathan G L

2013-01-01

Hyperekplexia is a syndrome of readily provoked startle responses, alongside episodic and generalized hypertonia, that presents within the first month of life. Inhibitory glycine receptors are pentameric ligand-gated ion channels with a definitive and clinically well stratified linkage...... a structural mechanism for channel activation. Receptors incorporating p.P230S (which is heterozygous with p.R65W) desensitized much faster than wild type receptors and represent a new TM1 site capable of modulating desensitization. The recessive mutations p.R72C, p.R218W, p.L291P, p.D388A, and p.E375X...... precluded cell surface expression unless co-expressed with α1 wild type subunits. The recessive p.E375X mutation resulted in subunit truncation upstream of the TM4 domain. Surprisingly, on the basis of three independent assays, we were able to infer that p.E375X truncated subunits are incorporated...

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence

Science.gov (United States)

Zucker-Franklin, Dorothea; Pancake, Bette A.; Marmor, Michael; Legler, Patricia M.

1997-01-01

In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities. PMID:9177230

Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

Science.gov (United States)

Beltrán-Valero de Bernabé, D; Granadino, B; Chiarelli, I; Porfirio, B; Mayatepek, E; Aquaron, R; Moore, M M; Festen, J J; Sanmartí, R; Peñalva, M A; de Córdoba, S R

1998-01-01

Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles. PMID:9529363

Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency

DEFF Research Database (Denmark)

Alatzoglou, Kyriaki S; Turton, James P; Kelberman, Daniel

2009-01-01

mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology...... or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR...

B-Cell Activation and Tolerance Mediated by B-Cell Receptor, Toll-Like Receptor and Survival Signal Crosstalk in SLE Pathogenesis

Science.gov (United States)

2015-10-01

H. Wagner, K. Takeda, and S. Akira. 2000 . A Toll-like receptor recognizes bacterial DNA. Nature 408: 740–745. 2. Kawai, T., and S. Akira. 2010. The...I. M. Carr , J. C. Fuller, R. M. Jackson, T. Lamb, T. A. Briggs, et al. 2009. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as...Moreover, recent studies from Riley and colleagues (27) suggest that ABCs negatively influence B-lineage commitment or development of bone marrow

The Prevalence of Transmitted Drug Resistance in Newly Diagnosed HIV-Infected Individuals in Croatia: The Role of Transmission Clusters of Men Who Have Sex with Men Carrying the T215S Surveillance Drug Resistance Mutation

Science.gov (United States)

Grgic, Ivana; Lunar, Maja M.; Poljak, Mario; Vince, Adriana; Vrakela, Ivana Baca; Planinic, Ana; Seme, Katja; Begovac, Josip

2013-01-01

Abstract The aim of this study was to determine the prevalence of transmitted drug resistance (TDR) in newly diagnosed and treatment-naive HIV-infected patients from Croatia and evaluate a possible contribution of transmission clusters to the spread of resistant virus. The study enrolled treatment-naive HIV-infected patients that entered clinical care at the Croatian Reference Center for HIV/AIDS between 2006 and 2008. The protease gene and a part of the reverse transcriptase gene of the HIV-1 genome were sequenced by using the Trugene HIV-1 Genotyping System. The prevalence of transmitted drug resistance was analyzed by using the surveillance drug resistance mutations (SDRM) list recommended by the WHO in 2009. We report findings for 118 of 180 eligible patients (65.6% coverage). SDRM were detected in 26 of 118 patients (22.0%) who were infected with subtype B and belonged mostly to the men having sex with men (MSM). The majority of patients with primary resistance carried SDRM associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs, 23 of 118 patients, 19.5%). The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). SDRM associated with resistance to nonnucleoside reverse transcriptase inhibitors were detected in three (2.5%) patients and primary resistance to protease inhibitors was not detected. Non-B subtypes were detected in 13/118 patients (11%). A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. This study showed a high prevalence of TDR in newly diagnosed MSM from Croatia and is an important contribution concerning the relationship between local transmission clusters and the spread of resistant virus. PMID:22906365

MTHFR Gene C677T Mutation and ACE Gene I/D Polymorphism in Turkish Patients with Osteoarthritis

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Ahmet Inanir

2013-01-01

Full Text Available Osteoarthritis is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in osteoarthritis. The aim of the current study was to examine the influence of methylenetetrahydrofolate reductase (MTHFR gene C677T mutation and angiotensin converting enzyme (ACE gene insertion/deletion (I/D variations on the risk of osteoarthritis.

Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

Science.gov (United States)

da Costa, Marianges Zadrozny Gouvêa; Pires, Júlia Glória Lucatelli; Nasser, Paulo Dominguez; Ferreira, Camila da Silva; Teixeira, Ana Cristina de Sá; Paranaguá-Vezozzo, Denise Cerqueira; Guarita, Dulce Reis; Carrilho, Flair José; Ono, Suzane Kioko

2016-10-01

This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

Funkcje gospodarcze i znaczenie przyrodnicze rzeki Supraśl i jej obszarów dolinowych

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Aleksander Kiryluk

2016-01-01

Full Text Available Doliny rzeczne wraz z występującymi na nich rzekami i ciekami spełniają różnorodne funkcje w krajobrazie i w środowisku przyrodniczym. Położona na północ od Puszczy Knyszyńskiej, rozległa dolina rzeki Supraśli, ze względu na położenie pełni ważne funkcje przyrodnicze jest siedliskiem wielu gatunków flory. Bliska odległość od aglomeracji białostockiej stanowi także o jej walorach rekreacyjno-wypoczynkowych. Waloryzacja przyrodnicza wykazała występowanie procesu synantropizacji w zbiorowiskach roślinnych w dolinie i zmniejszenie walorów przyrodniczych tego ekosystemu. Przepływy bieżące rzeki Supraśli, a także wody podziemne doliny stanowią główne źródło zaopatrzenia w wodę mieszkańców aglomeracji białostockiej. Z tego też względu rolnicze użytkowanie i ochrona środowiska w tej dolinie powinny być zrównoważone.

Novel growth hormone receptor gene mutation in a patient with Laron syndrome.

Science.gov (United States)

Arman, Ahmet; Yüksel, Bilgin; Coker, Ajda; Sarioz, Ozlem; Temiz, Fatih; Topaloglu, Ali Kemal

2010-04-01

Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation.

T I Eldho

Indian Academy of Sciences (India)

Home; Journals; Sadhana. T I Eldho. Articles written in Sadhana. Volume 31 Issue 6 December 2006 pp 743-754. Hydrodynamic modelling of flow over a spillway using a two-dimensional finite volume-based numerical model · M R Bhajantri T I Eldho P B Deolalikar · More Details Abstract Fulltext PDF. Spillway flow, a ...

The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes

Energy Technology Data Exchange (ETDEWEB)

Estrada, Paola; Manandhar, Miglena; Dong, Shi-Hui; Deveryshetty, Jaigeeth; Agarwal, Vinayak; Cronan, John E.; Nair, Satish K.

2017-04-17

Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor. Proper position of reactive groups for the two half-reactions is achieved solely through movements of active site residues, as confirmed by site-directed mutational analysis. The ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent of pre-transfer proofreading observed in some tRNA synthetases, and we show that this activity can be abolished by mutation of a single residue. These studies illustrate how BioW can carry out three different biologically prevalent chemical reactions (adenylation, thioesterification, and proofreading) in the context of a new protein fold.

First study of C2491T FV mutation with ischaemic stroke risk in ...

Indian Academy of Sciences (India)

Faculty of Medicine and Pharmacy, Department of Genetic and Molecular Pathology Laboratory (LGPM),. Tarek Ibn Ziad, QH, Hassan II University, 9154 Casablanca, Morocco. [Diakite B., Hamzi K., Hmimech W., Nadifi S. and GMRAVC 2015 First study of C2491T FV mutation with ischaemic stroke risk in Morocco. J. Genet.

Helicity of the $W$ boson in single - lepton $t \\bar{t}$ events

Energy Technology Data Exchange (ETDEWEB)

Canelli, Maria Florencia [Rochester U.

2003-08-01

We have applied a general approach for extracting information from data to a study of top quarks produced in proton-antiproton (pp) collisions in the process pp ! tt. This reaction can be calculated in the Standard Model (SM), in which the top (or antitop) quarks decay into b quarks and W bosons: t ! W+ b, t ! W b. We examine the decays of the W boson in these events in order to establish how the spin of the W correlates with its momentum vector. This is dened by the helicity of the W boson (pro jection of its spin along its line of ight), which is also predicted by the SM. The analysis is based on a direct calculation of a probability for each event as a function of the helicity of the W bosons in top-antitop events in the lepton+jets nal state. These events correspond to one W decaying into a lepton and its neutrino, and the other W into a quark-antiquark pair, with the quarks from the W and the two b quarks evolving into jets of particles. The probability is calculated by convoluting the dierential cross section with the resolution and acceptance of the detector. This measurement uses top quarks collected by the D experiment in 125 events/pb of data in pp collisions at p s=1.8 TeV during Run I of the Fermilab TeVatron. Assuming the \\V{A" coupling of the SM decay, we obtain a longitudinal helicity fraction of F0=0.560.31(stat)0.07(syst) for the W, which is consistent with the prediction of the Standard Model of F0=0.70 for a top-quark mass of 175 GeV/c2 . The method employed in this analysis oers the possibility of increasing statistical precision by using both of the decays of W bosons in these events. Also Monte Carlo studies indicate that the approach provides an unbiased result in the limit of poor statistics. Although our measurement is severely limited by the small event sample of Run I, this powerful technique will provide far greater sensitivity to any departures from the SM in the data anticipated from Run II.

Characterization of mutations causing rifampicin and isoniazid resistance of Mycobacterium tuberculosis in Syria.

Science.gov (United States)

Madania, Ammar; Habous, Maya; Zarzour, Hana; Ghoury, Ifad; Hebbo, Barea

2012-01-01

In order to characterize mutations causing rifampicin and isoniazid resistance of M. tuberculosis in Syria, 69 rifampicin resistant (Rif(r)) and 72 isoniazid resistant (Inh(r)) isolates were screened for point mutations in hot spots of the rpoB, katG and inhA genes by DNA sequencing and real time PCR. Of 69 Rif(r) isolates, 62 (90%) had mutations in the rifampin resistance determining region (RRDR) of the rpoB gene, with codons 531 (61%), 526 (13%), and 516 (8.7%) being the most commonly mutated. We found two new mutations (Asp516Thr and Ser531Gly) described for the first time in the rpoB-RRDR in association with rifampicin resistance. Only one mutation (Ile572Phe) was found outside the rpoB-RRDR. Of 72 Inh(r) strains, 30 (41.6%) had a mutation in katGcodon315 (with Ser315Thr being the predominant alteration), and 23 (32%) harbored the inhA(-15C-->T) mutation. While the general pattern of rpoB-RRDR and katG mutations reflected those found worldwide, the prevalence of the inhA(-15C-->T mutation was above the value found in most other countries, emphasizing the great importance of testing the inhA(-15C-->T) mutation for prediction of isoniazid resistance in Syria. Sensitivity of a rapid test using real time PCR and 3'-Minor groove binder (MGB) probes in detecting Rif(r) and Inh(r) isolates was 90% and 69.4%, respectively. This demonstrates that a small set of MGB-probes can be used in real time PCR in order to detect most mutations causing resistance to rifampicin and isoniazid.

Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

NARCIS (Netherlands)

van den Hoek, J. A.; Al, E. J.; Huisman, J. G.; Goudsmit, J.; Coutinho, R. A.

1991-01-01

The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three

Prevalent mutations in fatty acid oxidation disorders

DEFF Research Database (Denmark)

Gregersen, N; Andresen, B S; Bross, P

2000-01-01

UNLABELLED: The mutational spectrum in a given disease-associated gene is often comprised of a large number of different mutations, of which a single or a few are present in a large proportion of diseased individuals. Such prevalent mutations are known in four genes of the fatty acid oxidation...... of the disease in question and determination of the carrier frequency in the general population may help in elucidating the penetrance of the genotype. This is exemplified in disorders of mitochondrial fatty acid oxidation....

Strategie tłumaczy wobec zjawiska obcości kulturowej w przekładach dwudziestowiecznej prozy nowogreckiej na język polski

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Natalia Jędraszak

2015-09-01

óre mogą u odbiorcy tłumaczenia wywoływać poczucie obcości. Wybór pomiędzy tymi strategiami zależy od tłumacza oraz jego wizji czytelnika docelowego. Przedmiotem tego artykułu jest analiza przekładów trzech wybranych powieści nowogreckich na język polski, ze szczególnym uwzględnieniem rozwiązań zastosowanych przez tłumaczy w obliczu dwóch głównych problemów tłumaczeniowych, które wynikają z kulturowej specyfiki tekstu: problemów leksykalnych oraz odniesień do wydarzeń historycznych i faktów społecznych, jak również wiedzy, którą te rozwiązania dostarczają nam na temat wyobrażeń tłumaczy o czytelnikach docelowych przekładanych tekstów.

The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber's hereditary optic neuropathy and hearing loss

International Nuclear Information System (INIS)

Wei Qiping; Zhou Xiangtian; Yang Li; Sun Yanhong; Zhou Jian; Li Guang; Jiang, Robert; Lu Fan; Qu Jia; Guan Minxin

2007-01-01

We report here the clinical, genetic and molecular characterization of one three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON) and hearing loss. Four of 14 matrilineal relatives exhibited the moderate central vision loss at the average age of 12.5 years. Of these, one subject exhibited both LHON and mild hearing impairment. Sequence analysis of the complete mitochondrial genomes in the pedigree showed the presence of homoplasmic LHON-associated ND6 T14484C mutation, deafness-associated 12S rRNA A1555 mutation and 47 other variants belonging to Eastern Asian haplogroup H2. None of other mitochondrial variants was evolutionarily conserved and functional significance. Therefore, the coexistence of the A1555G mutation and T14484C mutations in this Chinese family indicate that the A1555G mutation may play a synergistic role in the phenotypic manifestation of LHON associated ND6 T14484C mutation. However, the incomplete penetrance of vision and hearing loss suggests the involvement of nuclear modifier genes and environmental factors in the phenotypic expression of these mtDNA mutations

Methylenetetrahydrofolate reductase C677T mutation and risk of retinal vein thrombosis

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Mohammad Soleiman Soltanpour

2013-01-01

Full Text Available Background: Elevated plasma homocysteine (Hcy level has been established as a significant risk factor for venous thrombosis and cardiovascular disease. Homozygosity for the methylenetetrahydrofolate reductase (MTHFR C677T mutation has been associated with elevated plasma Hcy concentration and may contribute to retinal vein thrombosis (RVT development. The aim of the present study was to investigate whether the hyperhomocysteinemia and/or homozygosity for the MTHFR C677T mutation are associated with an increased risk for RVT. Materials and Methods: Our study population consisted of 73 consecutive patients (50-78 years old with RVT and 73 control subjects (51-80 years old, matched for age and sex. Genotyping for the MTHFR C677T mutation was performed by polymerase chain reaction-restriction fragment length polymorphism technique and Hcy level was determined by an enzyme immunoassay kit. Results: The prevalence of 677TT genotype was higher in patients than control subjects, but the difference in frequency didn′t reach a significant value (P = 0.07. The frequency of the 677T allele was 26% and 21.2% in patients and controls, respectively and did not differ significantly between the two groups (odds ratio = 1.3, 95% confidence interval (0.75-2.24, P = 0.33. Fasting plasma total Hcy level was significantly higher in patients than controls (P = 0.001. Conclusion: Our study demonstrated that hyperhomocysteinemia, but not the MTHFR C677T mutation, is associated with RVT.

Locally rotationally symmetric Bianchi type I cosmology in f(R, T) gravity

Energy Technology Data Exchange (ETDEWEB)

Shamir, M.F. [National University of Computer and Emerging Sciences, Department of Sciences and Humanities, Lahore (Pakistan)

2015-08-15

This manuscript is devoted to the investigation of the Bianchi type I universe in the context of f(R, T) gravity. For this purpose, we explore the exact solutions of locally rotationally symmetric Bianchi type I spacetime. The modified field equations are solved by assuming an expansion scalar θ proportional to the shear scalar σ, which gives A = B{sup n}, where A, B are the metric coefficients and n is an arbitrary constant. In particular, three solutions have been found and physical quantities are calculated in each case. (orig.)

Phenylalanine hydroxylase gene mutations in the United States: Report from the maternal PKU collaborative study

Energy Technology Data Exchange (ETDEWEB)

Guldberg, P.; Henriksen, K.F.; Guettler, F. [John F. Kennedy Inst., Glostrup (Denmark)] [and others

1996-07-01

The major cause of hyperphenylalaninemia is mutations in the gene encoding phenylalanine hydroxylase (PAH). The known mutations have been identified primarily in European patients. The purpose of this study was to determine the spectrum of mutations responsible for PAH deficiency in the United States. One hundred forty-nine patients enrolled in the Maternal PKU Collaborative Study were subjects for clinical and molecular investigations. PAH gene mutations associated with phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) were identified on 279 of 294 independent mutant chromosomes, a diagnostic efficiency of 95%. The spectrum is composed of 71 different mutations, including 47 missense mutations, 11 splice mutations, 5 nonsense mutations, and 8 microdeletions. Sixteen previously unreported mutations were identified. Among the novel mutations, five were found in patients with MHP, and the remainder were found in patients with PKU. The most common mutations were R408W, IVS12nt1g{r_arrow}a, and Y414C, accounting for 18.7%, 7.8% and 5.4% of the mutant chromosomes, respectively. Thirteen mutations had relative frequencies of 1%-5%, and 55 mutations each had frequencies {le}1%. The mutational spectrum corresponded to that observed for the European ancestry of the U.S. population. To evaluate the extent of allelic variation at the PAH locus within the United States in comparison with other populations, we used allele frequencies to calculate the homozygosity for 11 populations where >90% ascertainment has been obtained. The United States was shown to contain one of the most heterogeneous populations, with homozygosity values similar to Sicily and ethnically mixed sample populations in Europe. The extent of allelic heterogeneity must be a major determining factor in the choice of mutation-detection methodology for molecular diagnosis in PAH deficiency. 47 refs., 1 fig., 5 tabs.

Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

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Alexandra V Stavropoulou

Full Text Available Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24. In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6% of familial cancer cases and in 27/592 (4.6% of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%. The majority of BRCA1 carriers (71.2% presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.

Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

Science.gov (United States)

Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

2013-02-15

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 270 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all patients. We screened 90 individuals with Rett syndrome phenotype. A total of 19 different MECP2 mutations and polymorphisms were identified in 27 patients. Of the 19 mutations, we identified 7 (37%) frameshift, 6 (31%) nonsense, 14 (74%) missense mutations and one duplication (5%). The most frequent pathogenic changes were: missense p.T158M (11%), p.R133C (7.4%), and p.R306C (7.4%) and nonsense p.R168X (11%), p.R255X (7.4%) mutations. We have identified two novel mutations namely p.385-388delPLPP present in atypical patients and p.Glu290AlafsX38 present in a classical patient of Rett syndrome. Sequence homology for p.385-388delPLPP mutation revealed that these 4 amino acids were conserved across mammalian species. This indicated the importance of these 4 amino acids in structure and function of the protein. A novel variant p.T479T has also been identified in a patient with atypical Rett syndrome. A total of 62 (69%) patients remained without molecular genetics diagnosis that necessitates further search for mutations in other genes like CDKL5 and FOXG1 that are known to cause Rett phenotype. The majority of mutations are detected in exon 4 and only one mutation was present in exon 3. Therefore, our study suggests the need for screening exon 4 of MECP2 as first line of diagnosis in these patients. Copyright © 2012 Elsevier B.V. All rights reserved.

1 r urT log ),( r t lim ),( ) ( , urT urrT r r

African Journals Online (AJOL)

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dθ where u+(z) = max(u(z), 0). The lower order λ of u is given by λ = lim r. urT log. ),(. A sequence {rn} of positive numbers is said to be a sequence of Pólya peaks for T(r, u) of order λ > 0 if there is a sequence {∈n}, ∈n > 0 such that ∈n → 0.

Leki przeciwdepresyjne i przeciwpsychotyczne zarejestrowane u dzieci i młodzieży. Trudności prawne i etyczne związane z zakresem rejestracji leków

Directory of Open Access Journals (Sweden)

Piotr Niwiński

2017-11-01

Full Text Available Wstęp: Wykonując swój zawód, lekarz jest zobowiązany do przestrzegania nie tylko zasad sztuki lekarskiej, lecz także przepisów prawa. Regulacje prawne dotyczą m.in. zgody na leczenie i zasad rejestracji leków. Leki są zarejestrowane w ściśle określonych wskazaniach, dla konkretnych grup pacjentów. Zastosowanie leku poza rejestracją może zostać zinterpretowane jako przeprowadzenie eksperymentu medycznego. Podstawą stosowania leków są zalecenia towarzystw naukowych. W psychiatrii dzieci i młodzieży wiele leków nie ma rejestracji do stosowania u osób poniżej 18. roku życia, w związku z czym lekarz po udzieleniu odpowiednich informacji musi uzyskać pisemną zgodę na leczenie od rodzica lub opiekuna prawnego. Cel: Celem pracy był przegląd leków stosowanych w terapii zaburzeń depresyjnych i psychotycznych w populacji dzieci i młodzieży pod kątem wieku pacjentów zgodnego ze wskazaniami rejestracyjnymi. Metoda: Bazując na Indeksie Leków Medycyny Praktycznej, przeanalizowano charakterystyki produktów leczniczych. Wyniki: Spośród 226 leków przeciwpsychotycznych i przeciwdepresyjnych zarejestrowanych w Polsce 149 jest niewskazanych lub przeciwwskazanych do podawania pacjentom poniżej 18. roku życia. Kolejnych 29 leków zostało zarejestrowanych u dzieci, ale we wskazaniach innych niż leczenie zaburzeń depresyjnych i psychotycznych. Ponadto różne postacie leków lub postacie wytwarzane przez różne firmy farmaceutyczne mogą mieć odmienną rejestrację. Wnioski: Brak rejestracji leków stosowanych w psychiatrii dzieci i młodzieży stanowi zagrożenie prawne i finansowe dla lekarza, a także może powodować nieufność rodzica.

Textiles: Some technocal information and data II: Conversion factors, fibre properties, spinning limits, typical twist factors, weaving performannce and transfer printing temperatures.

CSIR Research Space (South Africa)

Hunter, L

1978-07-01

Full Text Available OF THE CSIR P.O. B O X 1 1 2 4 P O R T E L I Z A B E T H R E P U B L I C O F S O U T H A F R I C A WOL 47 ISBN 0 7988 1360 1 Contents INTRODUCTION ........................................................... Page .; ... 1 CONVERSION FACTORSAND... ........................................................................................ 118 REFERENCES TEXTILES: SOME TECHNICAL INFORMATION AND DATA 11: CONVERSION FACTORS, FIBRE PROPERTIES, SPINNING L I M I T S , T Y P I C A L T W I S T F A C T O R S , W E A V I N G PERFORMANCE A N D TRANSFER PRINTING TEMPERATURES 6.5, L...

Acute Respiratory Tract Toxicity of the Trichothecene Mycotoxin, T-2 Toxin.

Science.gov (United States)

1987-03-31

to 10-week-old, castrated , e male, cross-bred, specific pathogen-free pigs were exposed to an aerosol of T-2 toxin for 45 to 61 minutes with 8 mg of... castrated , crossbred, specific pathogen-free swine to aerosols of T-2 toxin for 42 to 65 minutes with 9 mg of the toxin nebulized per kilogram of body... cattle , Ph.D. Thesis, University of Illinois, Urbana, IL, 1983. 28. Lorenzana, R.M., Beasley, V.R., Buck, W.B., Ghent, A.W., Lundeen, G.R., and

Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation

International Nuclear Information System (INIS)

Wang Qiuju; Li Qingzhong; Han Dongyi; Zhao Yali; Zhao Lidong; Qian Yaping; Yuan Hu; Li Ronghua; Zhai Suoqiang; Young Wieyen; Guan Minxin

2006-01-01

We report here the clinical, genetic, and molecular characterization of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Five of nine matrilineal relatives had aminoglycoside-induced hearing loss. These matrilineal relatives exhibited variable severity and audiometric configuration of hearing impairment, despite sharing some common features: being bilateral and having sensorineural hearing impairment. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified 16 variants and the homoplasmic 12S rRNA C1494T mutation, which was associated with hearing loss in the other large Chinese family. In fact, the occurrence of the C1494T mutation in these genetically unrelated pedigrees affected by hearing impairment strongly indicated that this mutation is involved in the pathogenesis of aminoglycoside-induced and nonsyndromic hearing loss. However, incomplete penetrance of hearing loss indicated that the C1494T mutation itself is not sufficient to produce a clinical phenotype but requires the involvement of modifier factors for the phenotypic expression. Those mtDNA variants, showing no evolutional conservation, may not have a potential modifying role in the pathogenesis of the C1494T mutation. However, nuclear background seems to contribute to the phenotypic variability of matrilineal relatives in this family. Furthermore, aminoglycosides modulate the expressivity and penetrance of deafness associated with the C1494T mutation in this family

RPE65 gene: multiplex PCR and mutation screening in patients from ...

Indian Academy of Sciences (India)

Unknown

The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the ... PCR and mutation screening in patients from India with retinal degenerative diseases. ..... Bennett J. 2001 Gene therapy restores vision in a canine.

Xeroderma Pigmentosum: Low Prevalence of Germline XPA Mutations in a Brazilian XP Population

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Karina Miranda Santiago

2015-04-01

Full Text Available Xeroderma pigmentosum (XP is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

Xeroderma pigmentosum: low prevalence of germline XPA mutations in a Brazilian XP population.

Science.gov (United States)

Santiago, Karina Miranda; França de Nóbrega, Amanda; Rocha, Rafael Malagoli; Rogatto, Silvia Regina; Achatz, Maria Isabel

2015-04-22

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter) was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada.

Science.gov (United States)

Han, Fabin; Grimes, David A; Li, Fang; Wang, Ting; Yu, Zhe; Song, Na; Wu, Shichao; Racacho, Lemuel; Bulman, Dennis E

2016-01-01

Mutations in the β-glucocerebrosidase gene (GBA) have been implicated as a risk factor for Parkinson's disease (PD). However, GBA mutations in PD patients of different ethnic origins were reported to be inconsistent. We sequenced all exons of the GBA gene in 225 PD patients and 110 control individuals from Eastern Canada. Two novel GBA variants of c.-119 A/G and S(-35)N, five known GBA mutations of R120W, N370S, L444P, RecNciI and RecTL mutation (del55/D409H/RecNciI) as well as two non-pathological variants of E326K and T369M were identified from PD patients while only one mutation of S13L and two non-pathological variants of E326K and T369M were found in the control individuals. The frequency of GBA mutations within PD patients (4.4%) is 4.8 times higher than the 0.91% observed in control individuals (X(2) = 2.91, p = 0.088; odds ratio = 4.835; 95% confidence interval = 2.524-9.123). The most common mutations of N370S and L444P accounted for 36.0% (9/25) of all the GBA mutations in this Eastern Canadian PD cohort. The frequency (6.67%) of E326K and T369M in PD patients is comparable to 7.27% in control individuals (X(2) = 0.042, p = 0.8376), further supporting that these two variants have no pathological effects on PD. Phenotype analysis showed that no significant difference in family history, age at onset and cognitive impairment was identified between the GBA mutation carriers and non-GBA mutation carriers. GBA mutations were found to be a common genetic risk factor for PD in Eastern Canadian patients.

Problemy medyczne agresji i przemocy w rodzinie u dzieci

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Norbert Dera

2011-10-01

Full Text Available Przemoc jest procesem ponadczasowym, wykraczającym poza granice i uwarunkowania etniczne, rasowe, wiekowe, narodowościowe i socjoekonomiczne. Dane CBOS wskazują, że co piąty Polak bije swoje dzieci raz w miesiącu lub częściej. Ponad 25% młodzieży spotyka się z przemocą w swoich rodzinach. Podstawowym problemem, niepozwalającym w pełni oszacować rozmiaru zjawiska, jest niska zgłaszalność przypadków przemocy organom porządkowym – tylko co siódme zdarzenie zgłaszane jest na policję w Stanach Zjednoczonych, w Polsce zgłaszalność jest jeszcze mniejsza. Skutki krzywdzenia dziecka pozostają na długie lata w sferze fizycznej i psychicznej. U dzieci takich obserwuje się zwykle opóźnienie rozwoju mowy, płaczliwość, lękliwość, drażliwość lub obojętność, brak reakcji na uśmiech i głos dorosłych, a także opóźnienie rozwoju motorycznego, zaburzenia snu i łaknienia. Dzieci doznające przemocy znacznie częściej skarżą się na dolegliwości pod postacią bólów brzucha, głowy, zakażeń układu moczowego (z.u.m., urazów, astmy, nawracających infekcji dróg oddechowych (n.i.d.o., wymiotów, moczenia nocnego, zaburzeń miesiączkowania. Zaburzenia emocjonalne wywołane przemocą są określane również jako zespół zaburzeń stresu pourazowego (PTSD. Z punktu widzenia psychiatrycznego u dziecka lub młodocianego doświadczającego długotrwałej wieloletniej traumy dochodzi z czasem do tzw. złożonego zespołu stresu pourazowego (disorders of extreme stress not otherwise specified, DESNOS. Z kolei przeżyte w dzieciństwie traumatyczne wydarzenia związane z problemem alkoholowym rodziców wywołują zespół objawów psychopatologicznych i zaburzeń zachowania o nazwie dorosłe dzieci alkoholików (DDA.

Insight on Mutation-Induced Resistance from Molecular Dynamics Simulations of the Native and Mutated CSF-1R and KIT.

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Priscila Da Silva Figueiredo Celestino Gomes

Full Text Available The receptors tyrosine kinases (RTKs for the colony stimulating factor-1, CSF-1R, and for the stem cell factor, SCFR or KIT, are important mediators of signal transduction. The abnormal function of these receptors, promoted by gain-of-function mutations, leads to their constitutive activation, associated with cancer or other proliferative diseases. A secondary effect of the mutations is the alteration of receptors' sensitivity to tyrosine kinase inhibitors, compromising effectiveness of these molecules in clinical treatment. In particular, the mutation V560G in KIT increases its sensitivity to Imatinib, while the D816V in KIT, and D802V in CSF-1R, triggers resistance to the drug. We analyzed the Imatinib binding affinity to the native and mutated KIT (mutations V560G, S628N and D816V and CSF-1R (mutation D802V by using molecular dynamics simulations and energy calculations of Imatinib•target complexes. Further, we evaluated the sensitivity of the studied KIT receptors to Imatinib by measuring the inhibition of KIT phosphorylation. Our study showed that (i the binding free energy of Imatinib to the targets is highly correlated with their experimentally measured sensitivity; (ii the electrostatic interactions are a decisive factor affecting the binding energy; (iii the most deleterious impact to the Imatinib sensitivity is promoted by D802V (CSF-1R and D816V (KIT mutations; (iv the role of the juxtamembrane region, JMR, in the imatinib binding is accessory. These findings contribute to a better description of the mutation-induced effects alternating the targets sensitivity to Imatinib.

Texture analysis of T1-w and T2-w MR images allows a quantitative evaluation of radiation-induced changes of internal obturator muscles after radiotherapy for prostate cancer.

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Scalco, Elisa; Rancati, Tiziana; Pirovano, Ileana; Mastropietro, Alfonso; Palorini, Federica; Cicchetti, Alessandro; Messina, Antonella; Avuzzi, Barbara; Valdagni, Riccardo; Rizzo, Giovanna

2018-04-01

To investigate the potential of texture analysis applied on T2-w and postcontrast T1-w images acquired before radiotherapy for prostate cancer (PCa) and 12 months after its completion in quantitatively characterizing local radiation effect on the muscular component of internal obturators, as organs potentially involved in urinary toxicity. T2-w and postcontrast T1-w MR images were acquired at 1.5 T before treatment (MRI1) and at 12 months of follow-up (MRI2) in 13 patients treated with radiotherapy for PCa. Right and left internal obturator muscle contours were manually delineated upon MRI1 and then automatically propagated on MRI2 by an elastic registration method. Planning CT images were coregistered to both MRIs and dose maps were deformed accordingly. A high-dose region receiving >55 Gy and a low-dose region receiving evaluated. A signal increase was highlighted in both T2-w and T1-w images in the portion of the obturators near the prostate, i.e., in the region receiving medium-high doses. A change in the spatial organization was identified, as an increase in homogeneity and a decrease in contrast and complexity, compatible with an inflammatory status. In particular, the region receiving medium-high doses presented more significant or, at least, stronger differences. Texture analysis applied on T1-w and T2-w MR images has demonstrated its ability in quantitative evaluating radiation-induced changes in obturator muscles after PCa radiotherapy. © 2018 American Association of Physicists in Medicine.

[677T mutation of the MTHFR gene in adenomas and colorectal cancer in a population sample from the Northeastern Mexico. Preliminary results].

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Delgado-Enciso, I; Martínez-Garza, S G; Rojas-Martínez, A; Ortiz-López, R; Bosques-Padilla, F; Calderón-Garcidueñas, A L; Zárate-Gómez, M; Barrera-Saldaña, H A

2001-01-01

Adequate intake of folates has been associated to low prevalence of colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an important role in folate metabolism. The role of the 677 mutation at the MTHFR gene in the risk for colorectal cancer remains controversial. A recent report established that this mutation has a high prevalence in the healthy Mexican population. To analyze the prevalence of 677T MTHFR mutation in patients with colorectal cancer and controls without chronic gastrointestinal disorders. Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were analyzed. Patients and controls were matched for sex and age. For each sample, DNA isolation, PCR, and mutation detection by restriction enzyme digestion were performed to determine the allele at the 677 position in the MTHFR gene. Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions and controls, respectively. Frequencies of the 677C/677T genotype were 59.4, 56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively. Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer lesions, and controls, respectively. The odds ratio between genotypes carrying the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3), chi 2 = 3.5, p = 0.06. Our results showed that persons who carry the 677T mutation at MTHFR locus have a tendency for an increased risk for colorectal cancer. This study supports the basic concept that low levels of folic acid contribute with the colorectal cancer pathogenesis. Our lack of statistic significance may be due to reduced sample size.

Assessment of CD4+ T cell responses to glutamic acid decarboxylase 65 using DQ8 tetramers reveals a pathogenic role of GAD65 121-140 and GAD65 250-266 in T1D development.

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I-Ting Chow

Full Text Available Susceptibility to type 1 diabetes (T1D is strongly associated with MHC class II molecules, particularly HLA-DQ8 (DQ8: DQA1*03:01/DQB1*03:02. Monitoring T1D-specific T cell responses to DQ8-restricted epitopes may be key to understanding the immunopathology of the disease. In this study, we examined DQ8-restricted T cell responses to glutamic acid decarboxylase 65 (GAD65 using DQ8 tetramers. We demonstrated that GAD65 121-140 and GAD65 250-266 elicited responses from DQ8+ subjects. Circulating CD4+ T cells specific for these epitopes were detected significantly more often in T1D patients than in healthy individuals after in vitro expansion. T cell clones specific for GAD65 121-140 and GAD65 250-266 carried a Th1-dominant phenotype, with some of the GAD65 121-140-specific T cell clones producing IL-17. GAD65 250-266-specific CD4+ T cells could also be detected by direct ex vivo staining. Analysis of unmanipulated peripheral blood mononuclear cells (PBMCs revealed that GAD65 250-266-specific T cells could be found in both healthy and diabetic individuals but the frequencies of specific T cells were higher in subjects with type 1 diabetes. Taken together, our results suggest a proinflammatory role for T cells specific for DQ8-restricted GAD65 121-140 and GAD65 250-266 epitopes and implicate their possible contribution to the progression of T1D.