Search results

1

Self-regulating genes. Exact steady state solution by using Poisson representation

100%

Sugár I., Simon I.

Open Physics

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2014

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vol. 12

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issue 9

615-627

EN

Systems biology studies the structure and behavior of complex gene regulatory networks. One of its aims is to develop a quantitative understanding of the modular components that constitute such networks. The self-regulating gene is a type of auto regulatory genetic modules which appears in over 40% of known transcription factors in E. coli. In this work, using the technique of Poisson Representation, we are able to provide exact steady state solutions for this feedback model. By using the methods of synthetic biology (P.E.M. Purnick and Weiss, R., Nature Reviews, Molecular Cell Biology, 2009, 10: 410–422) one can build the system itself from modules like this.

2

Molecular genetics of exfoliation syndrome

100%

Kasım B., Mocan M. C., İrkeç M.

OphthaTherapy

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2015

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vol. 2

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issue 1

13-20

EN

Exfoliation syndrome is an age-related disorder of the extracellular matrix, characterized by progressive accumulation of abnormal fibrillar material in several ocular and extraocular tissues. Although the exact etiopathogenesis is still unknown, several genetic and environmental factors appear to be involved in disease pathogenesis. Recently, single nucleotide polymorphisms in lysyl oxidase-like 1 have been found to be strongly associated with exfoliation syndrome. Dysregulation of lysyl oxidase-like 1 specifity and activity, an enzyme with a role in tropoelastin cross-linking and elastin homeostasis is thought to be involved in the development of exfoliation syndrome. This review aims to examine the recent genetic findings in the disease process.

PL

Zespół pseudoeksfoliacji to związane z wiekiem zaburzenie macierzy zewnątrzkomórkowej, charakteryzujące się postępującym odkładaniem się nieprawidłowego materiału fibrylarnego w różnych tkankach oka i poza nimi. Dokładna etiopatogeneza choroby pozostaje nieznana, jednak wydaje się, że istnieje kilka czynników genetycznych i środowiskowych w nią zaangażowanych. Niedawno wykazano, że polimorfizmy pojedynczego nukleotydu w obrębie oksydazy lizynowej 1 są silnie powiązane z zespołem pseudoeksfoliacji. Dysregulacja swoistości i aktywności oksydazy lizynowej 1, czyli enzymu odgrywającego rolę w sieciowaniu tropoelastyny i homeostazie elastyny, jest uważana za jeden z czynników rozwoju zespołu pseudoeksfoliacji. Celem niniejszej pracy jest przeanalizowanie najnowszych doniesień dotyczących genetyki wspomnianego procesu chorobowego.

3

Genetic Variation as a Possible Explanation for the Heterogeneity of Pain in Tendinopathy: What can we learn from other pain syndromes?

88%

Mkumbuzi N. S., Posthumus M., September A. V., Collins M.

Central European Journal of Sport Sciences and Medicine

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2021

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vol. 36

57-72

EN

The mechanisms of pain in tendinopathy are unclear. Current theories implicate tendon structural changes, neovascularisation, inflammation or changes in central pain processing. As with other types of musculoskeletal pain, tendon pain has high interindividual variability and, as with other types of pain, this could be attributed to genetic variation. Notably, the association between certain genetic polymorphisms and susceptibility to tendinopathy is well established in the literature. Therefore, the investigation of the mechanisms of tendon pain should also extend to include genetic variation as a possible explanation for the clinical features of tendon pain. This review summarises the current knowledge on genetic contributors to chronic pain and highlights findings that are relevant to chronic tendon pain. In particular, based on the current hypotheses on the possible sources of tendon pain, it focuses on findings that relate to genes that encode structural connective tissue components, inflammatory markers, ion channels and catecholamines and how they may relate to chronic tendon pain. In the absence of a definitive mechanism of tendon pain, an a priori genetic approach that is guided by these current hypotheses may help elucidate the mechanisms of tendon pain which may allow a more rational approach to research and treatment.

4

Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer

88%

Kabziński J., Walczak A., Mik M., Majsterek I.

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EN

Colorectal cancer (CRC) is one of the most common malignant tumors. One of the factors increasing the risk of its occurrence may be the reduced efficiency of repairing DNA damage, both nuclear and mitochondrial. The main mechanism for repairing oxidative damage is the BER system (in mitochondria mtBER), whose key proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 obtain full efficiency only at the appropriate level of acetylation. Sirtuin 3 is a key protein for mitochondrial homeostasis, regulating a number of metabolic processes related mainly to the control of the level of reactive oxygen species. Because Sirt3 possesses acetylase activity, it can modulate the level of activity of mtBER proteins by their deacetylation. The conducted study showed that the tested proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 are the substrate for the enzymatic deacetylation activity of Sirt3, which may lead to modulation of the risk of CRC, and in cancer cells may be a potential therapeutic target enhancing the action of cytostatic drugs.

5

Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model

75%

Pawlak M., Walkowska A., Mlącki M., Pistolic J., Wrzesiński T., Benes V., Jane S., Wesoły J., Kompanowska-Jezierska E., Wilanowski T.

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2015

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vol. 62

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issue 2

287-296

EN

Aim: The Grainyhead-like 1 (GRHL1) transcription factor is tissue-specific and is very highly expressed in the kidney. In humans the GRHL1 gene is located at the chromosomal position 2p25. A locus conferring increased susceptibility to essential hypertension has been mapped to 2p25 in two independent studies, but the causative gene has never been identified. Furthermore, a statistically significant association has been found between a polymorphism in the GRHL1 gene and heart rate regulation. The aim of our study was to investigate the physiological consequences of Grhl1 loss in a mouse model and ascertain whether Grhl1 may be involved in the regulation of blood pressure and heart rate. Experimental approach: In our research we employed the Grhl1 "knock-out" mouse strain. We analyzed renal gene expression, blood pressure and heart rate in the Grhl1-null mice in comparison with their "wild-type" littermate controls. Most important results: The expression of many genes is altered in the Grhl1-/- kidneys. Some of these genes have previously been linked to blood pressure regulation. Despite this, the Grhl1-null mice have normal blood pressure and interestingly, increased heart rate. Conclusions: Our work did not discover any new evidence to suggest any involvement of Grhl1 in blood pressure regulation. However, we determined that the loss of Grhl1 influences the regulation of heart rate in a mouse model.

6

Wpływ uwarunkowań genetycznych i czynników środowiskowych na zachorowalność na cukrzycę typu 2

75%

Cecot N., Boruczkowska B.

Innowacje w Pielęgniarstwie i Naukach o Zdrowiu

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2020

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vol. 5

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issue 3

55-68

EN

Admission. Diabetes mellitus is a chronic metabolic disease resulting from disturbed secretion or action of insulin, a hormone produced by the pancreas. It is genetically and multigene conditioned and by environmental factors, mainly obesity, bad eating habits and lack of physical activity. Aim. The aim of this study was to assess the influence of genetic conditions and environmental factors on the incidence of type 2 diabetes. Material and methods. In this work, the survey technique and classic qualitative analysis of documents were used. Research tools are used for the technical collection of data, such as: interview questionnaire, observation sheet, dictaphone, pen, etc. Patients from the CDL Barska Diabetes Clinic in Włocławek participated in the study. The condition was the patient's written consent. Patients received the questionnaire and it was conducted with their consent Results. One of the factors causing complications is alcohol consumption. Most respondents stated that they do not consume alcohol (45%), but a very large proportion of the respondents admitted that they drink alcohol occasionally (44%). Patients indicated that alcohol may induce hypoglycaemia (51%). Most of the respondents answered that alcohol is bad for the treatment of type 2 diabetes (88%). When indicating the type of physical activity, the respondents most often reported walking (48,4%) and cycling (25,8%). Patients admitted that they do physical activity once a week (34%) or not at all (27%). Conclusions. Genetic and environmental factors in the incidence of type 2 diabetes are playing the very important role.

PL

Wstęp. Cukrzyca jest przewlekłą chorobą metaboliczną wynikająca z zaburzonego wydzielania lub działania insuliny – hormonu produkowanego przez trzustkę. Jest ona uwarunkowana genetycznie-wielogenowo oraz poprzez czynniki środowiskowe, głównie otyłość, złe nawyki żywieniowe oraz brak aktywności fizycznej. Cel. Celem niniejszej pracy była ocena wpływu uwarunkowań genetycznych i czynników środowiskowych na zachorowalność na cukrzycę typu 2. Materiał i metody. W niniejszej pracy wykorzystano technikę ankietowania oraz klasyczną jakościową analizę dokumentów. Narzędzia badawcze służą technicznemu gromadzeniu danych i są nimi np.: kwestionariusz ankiety. W badaniu wzięli udział pacjenci Poradni Diabetologicznej CDL Barska we Włocławku. Warunkiem była pisemna zgoda pacjenta. Ankietę otrzymali pacjenci i przeprowadzono ją za ich zgodą. Wyniki. Jednym z czynników powodujących powikłania jest spożywanie alkoholu. Najwięcej badanych stwierdziło, że nie spożywa alkoholu (45%), ale bardzo duża część badanych przyznała, iż spożywa alkohol okazjonalnie (44%). Pacjenci wskazali, że alkohol może wywołać niedocukrzenie (51%). Najwięcej osób odpowiedziało, że alkohol źle wpływa na leczenie cukrzycy typu 2 (88%). Wskazując na rodzaj aktywności fizycznej badani najczęściej podawali spacery (48,4%) oraz jazdę na rowerze (25,8%). Pacjenci przyznali, iż aktywność fizyczną uprawiają raz w tygodniu (34%) lub nie uprawiają wcale (27%). Wnioski. Czynniki genetyczne i środowiskowe w zachorowalności cukrzycy typu 2 odgrywają bardzo ważną rolę.

7

Inclusion body myositis – pathomechanism and lessons from genetics

75%

Murnyák B., Bodoki L., Vincze M., Griger Z., Csonka T., Szepesi R., Kurucz A., Dankó K., Hortobágyi T.

Open Medicine

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2014

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vol. 10

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issue 1

EN

Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease.

8

SNARE proteins and schizophrenia: linking synaptic and neurodevelopmental hypotheses

75%

Johnson R. D., Oliver P. L., Davies K. E.

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2008

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vol. 55

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issue 4

619-628

EN

Much of the focus of neurobiological research into schizophrenia is based on the concept that disrupted synaptic connectivity underlies the pathology of the disorder. Disruption of synaptic connectivity is proposed to be a consequence of both disrupted synaptic transmission in adulthood and abnormalities in the processes controlling synaptic connectivity during development of the central nervous system. This synaptic hypothesis fits with neurodevelopmental models of schizophrenia and our understanding of the mechanisms of antipsychotic medication. This conceptual model has fostered efforts to define the exact synaptic pathology further. Synaptic proteins are obvious candidates for such studies, and the integral role of the SNARE complex, and SNARE-associated proteins, in synaptic transmission will ensure that it is the focus of much of this research. Significant new insights into the role of this complex are arising from new mouse models of human disease. Here the evidence from both animal and human clinical studies showing that the SNARE complex has a key role to play in the aetiology and pathogenesis of schizophrenia is discussed.

9

Agenezja trzecich zębów trzonowych

63%

Machorowska-Pieniążek A., Rojek U., Krukowska-Drozd O., Liśniewska-Machorowska B.

Annales Academiae Medicae Silesiensis

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2010

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vol. 64

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issue 1-2

22-28

EN

INTRODUCTION Teeth agenesis is the most common teeth developmental anomaly. It mostly aff ects third molars (5-58%). The intensity of this agenesis can be various (from one to four teeth). Hypodontia of third molars can co-exist with other teeth number disturbances. The aim of this study was to fi nd relation between agenesis of third molars and agenesis of other teeth. MATERIAL AND METHODS Medical documentation of 980 patients was analysed. The studied group were patients with absence of one or more third molars as confi rmed radiografi cally. The second condition was to obtain stadium G of germs formation (by Demirijan) by the second lower molars. Patients possessing all four third molars create a control group. Prevalence and type of agenesis in the studied and control group were examined. RESULTS 363 patients were qualifi ed to thestudy, 296 in the control group and 67 in the studied one. The agenesis of 133 third molars were found (62 in the upper jaw and 71 in the lower one). The prevalence of other teeth agenesis in the studied group was 20.9% and concerns mainly the lower second premolars (19.4%), upper (17.9%) and upper lateral incisors (10.5%). The prevalence of other teeth agenesis in the control group was 8.8%. CONCLUSIONS The most frequent form of agenesis was the absence of singular lower third molar. In the studied group prevalence of congenital lack of other teeth was higher than in the control group.

PL

WSTĘP Niedoliczbowość zębów należy do najczęściej występujących wad rozwojowych uzębienia i najczęściej dotyczy trzecich zębów trzonowych (5-58%). Agenezja tych zębów ma różne nasilenie i może współistnieć z innymi nieprawidłowościami liczby zębów. Celem podjętych badań było ustalenie zależności między agenezją trzecich zębów trzonowych a agenezją innych zębów. MATERIAŁ I METODY Przeanalizowano dokumentację medyczną 980 osób. Grupę badawczą stanowili pacjenci, u których stwierdzono agenezję trzecich zębów trzonowych przy jednoczesnym osiągnięciu przez drugi dolny stały ząb trzonowy stadium rozwoju „G” wg Demirijana. Pacjenci, u których obecne były zawiązki wszystkich trzecich zębów trzonowych, stanowili grupę kontrolną. Zbadano częstość i rodzaj niedoliczbowości zębów w grupie badawczej i kontrolnej. WYNIKI Do badań zakwalifi kowano 363 pacjentów: 296 do grupy kontrolnej, a 67 do grupy badawczej. Ujawniono agenezję 133 trzecich zębów trzonowych, w tym 62 górnych i 71 dolnych. U 20,9% pacjentów z agenezją trzecich zębów trzonowych występowały braki zawiązków innych zębów, wśród których dominowały braki zawiązków drugich zębów przedtrzonowych dolnych (19,4%) i górnych (17,9%) oraz górnych siekaczy bocznych (10,5%). W grupie kontrolnej niedoliczbowość zębów wyniosła 8,8%. WNIOSKI Agenezja najczęściej dotyczyła pojedynczego dolnego trzeciego zęba trzonowego. W grupie badawczej częstość agenezji pozostałych zębów była wyższa niż w grupie kontrolnej.

10

Regulation of the genes involved in neurotransmission in Attention Deficit/Hyperactivity Disorder

63%

Cuch B., Polaczek A., Idziak M., Kotuła L., Maciejewski R., Madej-Czerwonka B., Kocki J.

Current Issues in Pharmacy and Medical Sciences

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2015

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vol. 28

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issue 2

115-119

EN

Attention Deficit Hyperactivity Disorder is the full name of the disease commonly deemed ADHD. This disease is most frequently diagnosed in childhood, and it affects up to 12 % of all children world-wide. The current clinical criteria (the base for diagnosis) can be found in DSM -V. The core symptoms are divided in three groups: hyperactivity, impulsivity and impaired attention. The aetiology of the disorder is combined, including a wide range of factors, and the genetic, environmental, toxic, perinatal background is taken into account. Because, currently, more and more studies are seeking to explore the heritability of the disorder, the aim of this study is to review the information provided by different research centres which discuss the genetic background of the disease. Herein, we present the results of different studies gathered from the online database. Our findings indicate that the participation of genetic factors within this disorder is supported by family, twin and adoption studies. Indeed, in current literature, researchers estimate that there is a higher risk of developing ADHD among children from families with an ADHD history. Of particular note is that there are some studies indicating particular genes that determine the susceptibility to ADHD. Such studies make mention that most of these genes encode components of the dompaminergic and serotoninergic neurotransmission systems. Researchers in the field, thus, are attempting to link the presence of certain alleles in affected children with their response to treatment. Yet, while ADHD is now considered as being a disorder of genetic background, we cannot indicate a single gene or its mutation that would be crucial in the aetiology and diagnosis. Still, a number of candidate genes have been reported so far.

11

Atypowa postać mukowiscydozy u 14-letniego chłopca

63%

Stelmach I., Bal-Gierańczyk K., Szarkowska M.

Pediatria i Medycyna Rodzinna

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2016

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vol. 12

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issue 2

209-213

EN

The diagnosis of cystic fibrosis is based on the occurrence of clinical symptoms and evidence of two mutations in cystic fibrosis transmembrane conductance regulator. However, in cases of atypical cystic fibrosis, not all symptoms may be manifested and not all diagnostic tests may be positive. The World Health Organization has recognised the need for a category that covers patients with atypical (often single organ disease), who may or may not supply evidence for cystic fibrosis transmembrane conductance regulator dysfunction (sweat test) or two cystic fibrosis transmembrane conductance regulator mutations. The aim of this case report is to highlight the difficulties in cystic fibrosis diagnosis in some groups of patients who do not fit in the “gold standard” of the diagnostic scheme. Individuals with atypical cystic fibrosis might only have dysfunction in one organ system and of a much milder degree than those with typical cystic fibrosis. This may be the main reason for a diagnosis and treatment delay.

PL

Rozpoznanie mukowiscydozy opiera się na występowaniu objawów klinicznych oraz obecności dwóch mutacji genu odpowiedzialnego za syntezę błonowego kanału chlorkowego. Jednakże w przypadkach atypowej postaci mukowiscydozy nie wszystkie objawy mogą się ujawniać, a wyniki badań diagnostycznych nie zawsze muszą potwierdzać chorobę. Światowa Organizacja Zdrowia wskazała na potrzebę stworzenia nowej kategorii wśród pacjentów z atypową postacią choroby (często dotyczącą jednego organu), u których przebieg mukowiscydozy nie musi być manifestowany dysfunkcją błonowego kanału chlorkowego (test potowy) oraz obecnością dwóch mutacji genu odpowiedzialnego za jego syntezę. Niniejsza praca ma na celu zwrócenie uwagi na trudności w rozpoznaniu mukowiscydozy u pacjentów, którzy nie spełniają kryteriów diagnostycznych tej choroby – tzw. złotych standardów. Dzieci z atypową postacią mukowiscydozy mogą wykazywać dysfunkcję tylko jednego narządu danego układu, i to w stopniu znacznie łagodniejszym niż u pacjentów z typową postacią mukowiscydozy, co może stanowić główną przyczynę niepowodzeń diagnostycznych i terapeutycznych.

12

Compound heterozygous LDLR variant in severely affected familial hypercholesterolemia patient

63%

Al-Allaf F., Alashwal A., Abduljaleel Z., Taher M., Bouazzaoui A., Abalkhail H., Al-Allaf A., Athar M.

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2017

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vol. 64

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issue 1

75-79

EN

Familial hypercholesterolemia (FH) is most commonly caused by mutations in the LDL receptor (LDLR), which is responsible for hepatic clearance of LDL from the blood circulation. We described a severely affected FH proband and their first-degree blood relatives; the proband was resistant to statin therapy and was managed on an LDL apheresis program. In order to find the causative genetic variant in this family, direct exon sequencing of the LDLR, APOB and PCSK9 genes was performed. We identified a compound heterozygous mutation in the proband with missense p.(W577C) and frameshift p.(G676Afs33) variants at exons 12 and 14 of the LDLR gene respectively. DNA sequencing of LDLR gene from the parents demonstrated that the missense variant was inherited from the mother and frameshift variant was inherited from the father. The frameshift variant resulted in a stop signal 33 codons downstream of the deletion, which most likely led to a truncated protein that lacks important functional domains, including the trans-membrane domain and the cytoplasmic tail domain. The missense variant is also predicted to be likely pathogenic and affect EGF-precursor homology domain of the LDLR protein. The segregation pattern of the variants was consistent with the lipid profile, suggesting a more severe FH phenotype when the variants are in the compound heterozygous state. The finding of a compound heterozygous mutation causing severe FH phenotype is important for the genotype-phenotype correlation and also enlarges the spectrum of FH-causative LDLR variants in the Arab population, including the Saudi population.

Refine search results

Self-regulating genes. Exact steady state solution by using Poisson representation

Molecular genetics of exfoliation syndrome

Genetic Variation as a Possible Explanation for the Heterogeneity of Pain in Tendinopathy: What can we learn from other pain syndromes?

Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer

Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model

Wpływ uwarunkowań genetycznych i czynników środowiskowych na zachorowalność na cukrzycę typu 2

Inclusion body myositis – pathomechanism and lessons from genetics

SNARE proteins and schizophrenia: linking synaptic and neurodevelopmental hypotheses

Agenezja trzecich zębów trzonowych

Regulation of the genes involved in neurotransmission in Attention Deficit/Hyperactivity Disorder

Atypowa postać mukowiscydozy u 14-letniego chłopca

Compound heterozygous LDLR variant in severely affected familial hypercholesterolemia patient