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Amaç: Ateroskleroz sürecinde endotelyal hücrelerde enflamatuvar tepkimeleri aktive eden sinyal yolaklarını uyaran okside LDL, kardiyovasküler hastalıkların gelişiminde önemli bir patojenik faktör olarak tanımlanmaktadır. Endotel hücrelerinde okside LDL için başlıca reseptör olan okside LDL reseptörü (LOX1), okside LDL’leri endotel hücrelerinde özgül olarak bağlayabilme, hücre içine alabilme ve degrade edebilme özelliğine sahiptir. Bu çalışmada LOX-1’i kodlayan OLR1 geninde 3’UTR188C>T polimorfizminin koroner arter hastaları ve sağlıklı kontrollerden oluşan çalışma gruplarında serum okside LDL ve lipid düzeylerine etkisinin araştırılarak KAH hastalarında lipid parametrelerle ilişkisinin belirlenmesi amaçlanmıştır. Yöntem: Çalışmaya katılan 50 KAH hastası ve 34 sağlıklı kontrolden oluşan gruplarda OLR1 geni 3’UTR188C>T polimorfizminin tespiti için Polimeraz Zincir Reaksiyonu ve Restriksiyon Fragman Uzunluk Polimorfizmi yöntemleri kullanılmıştır. İstatistiksel analiz SPSS 20.0 ile yapılmıştır. Bulgular: KAH grubunda okside LDL (pT genotip ve allel dağılımları gruplar arasında benzer bulunmuştur (p>0,05). 188T alleli hem KAH (pT polimorfizminin hem proaterojenik bir molekül olan serum okside LDL hem de aterojenik lipid profili lehine etkileriyle KAH gelişimiyle ilişkili olabileceğine işaret etmektedir., Aim: Oxidized LDL, which stimulates signaling pathways that activate inflammatory reactions in endothelial cells during atherosclerosis, is defined as an important pathogenic factor in the development of cardiovascular diseases. The oxidized LDL receptor (LOX-1), which is the main receptor for oxidized LDL in endothelial cells, has the ability to specifically bind, internalize and degrade oxidized LDLs in endothelial cells. In this study, it was aimed to investigate the effect of 3'UTR188C>T polymorphism in the OLR1 gene encoding LOX-1 on serum oxidized LDL and lipid levels in the study groups consisting of coronary artery disease (CAD) patients and healthy controls, and to determine its relationship with lipid parameters in patients with CAD. Methods: Polymerase Chain Reaction and Restriction Fragment Length Polymorphism methods were used to detect the OLR1 gene 3'UTR188C>T polymorphism in groups of 50 CAD patients and 34 healthy controls. Statistical analyzes were performed with SPSS 20.0. Results: In the CAD group, oxidized LDL (pT genotype and allele distributions were found to be similar between the groups (p>0.05). The 188T allele was associated with higher oxidized LDL levels in both CAD (pT polymorphism may be associated with the development of CAD with its effects in favor of both serum oxidized LDL, which is a proatherogenic molecule, and an atherogenic lipid profile.

Background: Cardiac-urogenital syndrome [MIM # 618280] is a newly described very rare syndrome associated with pathogenic variants in the myelin regulatory factor (MYRF) gene that leads to loss of protein function. MYRF is a transcription factor previously associated only with the control of myelin-related gene expression. However, it is also highly expressed in other tissues and associated with various organ anomalies. The clinical picture is primarily dominated by complex congenital cardiac developmental defects, pulmonary hypoplasia, congenital diaphragmatic hernia, and urogenital malformations. Case Presentation: We present case reports of two siblings of unrelated parents in whom whole-exome sequencing was indicated due to familial occurrence of extensive developmental defects. A new, previously undescribed splicing pathogenic variant c.1388+2T>G in the MYRF gene has been identified in both patients. Both parents are unaffected, tested negative, and have another healthy daughter. The identical de novo event in siblings suggests gonadal mosaicism, which can mimic recessive inheritance. Conclusions: To our knowledge, this is the first published case of familial cardiac-urogenital syndrome indicating gonadal mosaicism. Úvod: Kardio-urogenitální syndrom [MIM # 618280] je nově popsaný velmi vzácný syndrom spojený s patogenními variantami v genu myelinového regulačního faktoru (MYRF), který vede ke ztrátě funkce proteinů. MYRF je transkripční faktor dříve spojený pouze s kontrolou genové exprese související s myelinem. Je však také vysoce exprimován v jiných tkáních a je spojen s různými anomáliemi orgánů. Klinickému obrazu dominují především komplexní vrozené srdeční vývojové vady, plicní hypoplazie, vrozená brániční kýla a urogenitální malformace. Prezentace případů: Prezentujeme kazuistiky dvou sourozenců nepříbuzných rodičů, u kterých bylo indikováno celoexomové sekvenování z důvodu rodinného výskytu rozsáhlých vývojových vad. Nová, dosud nepopsaná sestřihová patogenní varianta c.1388+2T>G v genu MYRF byla identifikována u obou pacientů. Oba rodiče jsou nedotčeni, testy jsou negativní a mají další zdravou dceru. Identická událost de novo u sourozenců naznačuje gonadální mozaicismus, který může napodobovat recesivní dědičnost. Závěr: Pokud je nám známo, jedná se o první publikovaný případ familiárního kardio-urogenitálního syndromu indikujícího gonádový mosaicismus. Background: Cardiac-urogenital syndrome [MIM # 618280] is a newly described very rare syndrome associated with pathogenic variants in the myelin regulatory factor (MYRF) gene that leads to loss of protein function. MYRF is a transcription factor previously associated only with the control of myelin-related gene expression. However, it is also highly expressed in other tissues and associated with various organ anomalies. The clinical picture is primarily dominated by complex congenital cardiac developmental defects, pulmonary hypoplasia, congenital diaphragmatic hernia, and urogenital malformations. Case Presentation: We present case reports of two siblings of unrelated parents in whom whole-exome sequencing was indicated due to familial occurrence of extensive developmental defects. A new, previously undescribed splicing pathogenic variant c.1388+2T>G in the MYRF gene has been identified in both patients. Both parents are unaffected, tested negative, and have another healthy daughter. The identical de novo event in siblings suggests gonadal mosaicism, which can mimic recessive inheritance. Conclusions: To our knowledge, this is the first published case of familial cardiac-urogenital syndrome indicating gonadal mosaicism.

Behavioral flexibility is an important cornerstone for the ecological success of animals. Social Cataglyphis nodus ants with their age-related polyethism characterized by age-related behavioral phenotypes represent a prime example for behavioral flexibility. We propose neuropeptides as powerful candidates for the flexible modulation of age-related behavioral transitions in individual ants. As the neuropeptidome of C. nodus was unknown, we collected a comprehensive peptidomic data set obtained by transcriptome analysis of the ants' central nervous system combined with brain extract analysis by Q-Exactive Orbitrap mass spectrometry (MS) and direct tissue profiling of different regions of the brain by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS. In total, we identified 71 peptides with likely bioactive function, encoded on 49 neuropeptide-, neuropeptide-like, and protein hormone prepropeptide genes, including a novel neuropeptide-like gene (fliktin). We next characterized the spatial distribution of a subset of peptides encoded on 16 precursor proteins with high resolution by MALDI MS imaging (MALDI MSI) on 14 µm brain sections. The accuracy of our MSI data were confirmed by matching the immunostaining patterns for tachykinins with MSI ion images from consecutive brain sections. Our data provide a solid framework for future research into spatially resolved qualitative and quantitative peptidomic changes associated with stage-specific behavioral transitions and the functional role of neuropeptides in Cataglyphis ants.

Rad donosi pregled pojmova i spoznaja o genetičkom inženjerstvu te njegova razvoja u drugoj polovici XX. stoljeća do danas u svijetu i u Hrvatskoj. Genetičko inženjerstvo je naziv koji je pretrpio najveće pojmovne deformacije u biologiji i stoga su u radu jednoznačno objašnjeni važni pojmovi. Kako podatci i dokumentacija o genetičkom inženjerstvu u širem opsegu nisu dostupni javnosti, u radu se donosi sustavan pregled njegova razvoja u Hrvatskoj te su prikazane uloge pojedinaca, njihove interakcije i doprinosi. Već su u 1970-ima hrvatska farmaceutska industrija, kao i istraživačke institucije u Hrvatskoj, bile poprište zamaha biotehnologije i genetičkoga inženjerstva u istraživanju i razvoju proizvoda. Različite istraživačke grupe, većinom okupljene oko sastavnica Sveučilišta u Zagrebu (napose Prehrambeno-biotehnološkoga fakulteta i Prirodoslovno-matematičkoga fakulteta), Instituta Ruđer Bošković i PLIVE, rabe tehnologiju rekombinantne DNA za svoja osnovna istraživanja. Osim kronologije zbivanja povezanih s temom genetičkoga inženjerstva, rad opisuje i zasluge znanstvenika (M. Demereca, V. Johanides, M. Alačević, Ž. Trgovčevića, Ž. Kućana, S. Jelaske, V. Gamulin, V. Delića, I. Weygand-Đurašević, Z. Zgage, S. Jelenića, i dr.) u području genetičkoga inženjerstva., The paper provides an overview of concepts and knowledge about genetic engineering and its development in Croatia and abroad from the second half of the 20th century to the present day. Genetic engineering is the biological term that has undergone the greatest conceptual deformations, and therefore some important concepts are unambiguously explained in the paper. As data and documentation on this are not widely available to the public, a systematic overview of the development of genetic engineering in Croatia as well as the roles of individuals, their interactions and contributions is also presented. As early as the 1970s, the Croatian pharmaceutical industry and research institutions in Croatia produced a wave of biotechnological and genetic engineering research and product development. Various research groups, mostly gathered around the constituents of the University of Zagreb (especially the Faculty of Food Technology and Biotechnology and the Faculty of Science), the Ruđer Bošković Institute and PLIVA, use recombinant DNA technology for their basic research. In addition to a chronology of events related to genetic engineering, the paper also describes the work and merits of scientists M. Demerec, V. Johanides, M. Alačević, Ž. Trgovčević, Ž. Kućan, S. Jelaska, V. Gamulin, V. Delić, I. Weygand-Đurašević, Z. Zgaga, S. Jelenić, and others in the field of genetic engineering.

Publisher's version (útgefin grein), Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10− 9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes., 1000BRAINS: 1000BRAINS is a population-based cohort based on the Heinz-Nixdorf Recall Study and is supported in part by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their generous support in terms of the Heinz Nixdorf Study. The HNR study is also supported by the German Ministry of Education and Science (FKZ 01EG940), and the German Research Council (DFG, ER 155/6-1). The authors are supported by the Initiative and Networking Fund of the Helmholtz Association (Svenja Caspers) and the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 7202070 (Human Brain Project SGA1; Katrin Amunts, Sven Cichon). This work was further supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A to M.M.N. and S.C.), and by the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). 16p.11.2 European Consortium: B.D. is supported by the Swiss National Science Foundation (NCCR Synapsy, project grant Nr 32003B_159780) and Foundation Synapsis. LREN is very grateful to the Roger De Spoelberch and Partridge Foundations for their generous financial support. This work was supported by grants from the Simons Foundation (SFARI274424) and the Swiss National Science Foundation (31003A_160203) to A.R. and S.J. Betula: The relevant Betula data collection and analyses were supported by a grant from the Knut & Alice Wallenberg (KAW) to L. Nyberg. Brainscale: the Brainscale study was supported by the Netherlands Organization for Scientific Research MagW 480-04-004 (Dorret Boomsma), 51.02.060 (Hilleke Hulshoff Pol), 668.772 (Dorret Boomsma & Hilleke Hulshoff Pol); NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council (ERC-230374) (Dorret Boomsma), High Potential Grant Utrecht University (Hilleke Hulshoff Pol), NWO Brain and Cognition 433-09-220 (Hilleke Hulshoff Pol). Brain Imaging Genetics (BIG): This work makes use of the BIG database, first established in Nijmegen, The Netherlands, in 2007. This resource is now part of Cognomics (www.cognomics.nl), a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud university medical centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received supported from the participating departments and centres and from external grants, i.e., the Biobanking and Biomolecular Resources Research Infrastructure (the Netherlands) (BBMRI-NL), the Hersenstichting Nederland, and the Netherlands Organisation for Scientific Research (NWO). The research leading to these results also receives funding from the NWO Gravitation grant ‘Language in Interaction’, the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreements n° 602450 (IMAGEMEND), n°278948 (TACTICS), and n°602805 (Aggressotype) as well as from the European Community’s Horizon 2020 programme under grant agreement n° 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross-NIH partnership. COBRE: This work was supported by a NIH COBRE Phase I grant (1P20RR021938, Lauriello, PI and 2P20GM103472, Calhoun, PI) awarded to the Mind Research Network. We wish to express our gratitude to numerous investigators who were either external consultants to the Cores and projects, mentors on the projects, members of the external advisory committee and members of the internal advisory committee. Decode: The research leading to these results has received financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007–2013), EU-FP7 funded grant no. 602450 (IMAGEMEND) as well as support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no.115300 (EUAIMS). DemGene: Norwegian Health Association and Research Council of Norway. Dublin: Work was supported by Science Foundation Ireland (SFI grant 12/IP/1359 to Gary Donohoe and SFI08/IN.1/B1916-Corvin to Aidan C Corvin) and the European Research Council (ERC-StG-2015-677467). EPIGEN-UK (SMS, CL): The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health’s NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner, and the Epilepsy Society for supporting CL. Haavik: The work at the K.G.Jebsen center for neuropsychiatric disorders at the University of Bergen, Norway, was supported by Stiftelsen K.G. Jebsen, European Community’s Seventh Framework Program under grant agreement no 602805 and the H2020 Research and Innovation Program under grant agreement numbers 643051 and 667302. HUNT: The HUNT Study is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. HUNT-MRI was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian National Advisory Unit for functional MRI. IMAGEN: The work received support from the European Union-funded FP6Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. MCIC: This work was supported primarily by the Department of Energy DE-FG02-99ER62764 through its support of the Mind Research Network and the consortium as well as by the National Association for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (to SE) as well as through the Blowitz-Ridgeway and Essel Foundations, and through NWO ZonMw TOP 91211021, the DFG research fellowship (to SE), the Mind Research Network, National Institutes of Health through NCRR 5 month-RR001066 (MGH General Clinical Research Center), NIMH K08 MH068540, the Biomedical Informatics Research Network with NCRR Supplements to P41 RR14075 (MGH), M01 RR 01066 (MGH), NIBIB R01EB006841 (MRN), R01EB005846 (MRN), 2R01 EB000840 (MRN), 1RC1MH089257 (MRN), as well as grant U24 RR021992. NCNG: this sample collection was supported by grants from the Bergen Research Foundation and the University of Bergen, the Dr Einar Martens Fund, the K.G. Jebsen Foundation, the Research Council of Norway, to SLH, VMS and TE. The Bergen group was supported by grants from the Western Norway Regional Health Authority (Grant 911593 to AL, Grant 911397 and 911687 to AJL). NESDA: Funding for NESDA was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health.Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. NTR: The NTR study was supported by the Netherlands Organization for Scientific Research (NWO), MW904-61-193 (Eco de Geus & Dorret Boomsma), MaGW-nr: 400-07- 080 (Dennis van ‘t Ent), MagW 480-04-004 (Dorret Boomsma), NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council, ERC-230374 (Dorret Boomsma), and Amsterdam Neuroscience. OATS: OATS (Older Australian Twins Study) was facilitated by access to Twins Research Australia, which is funded by a National Health and Medical Research Council (NHMRC) Enabling Grant 310667. OATS is also supported via a NHMRC/Australian Research Council Strategic Award (401162) and a NHMRC Project Grant (1045325). DNA extraction was performed by Genetic Repositories Australia, which was funded by a NHMRC Enabling Grant (401184). OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. PAFIP: PAFIP data were collected at the Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Carlos III Health Institute PIE14/00031 and SAF2013-46292-R and SAF2015-71526-REDT. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement and analysis.We want to particularly acknowledge the patients and the BioBankValdecilla (PT13/0010/0024) integrated in the Spanish National Biobanks Network for its collaboration. QTIM: The QTIM study was supported by grants from the US National Institute of Child Health and Human Development (R01 HD050735) and the Australian National Health and Medical Research Council (NHMRC) (486682, 1009064). Genotyping was supported by NHMRC (389875). Lachlan Strike is supported by an Australian Postgraduate Award (APA). AFM is supported by NHMRC CDF 1083656. We thank the twins and siblings for their participation, the many research assistants, as well as the radiographers, for their contribution to data collection and processing of the samples. SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, 01ZZ0403 and 01ZZ0701), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. Whole-body MR imaging was supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. StrokeMRI: StrokeMRI has been supported by the Research Council of Norway (249795), the South-Eastern Norway Regional Health Authority (2014097, 2015044, 2015073) and the Norwegian ExtraFoundation for Health and Rehabilitation. TOP: TOP is supported by the Research Council of Norway (223273, 213837, 249711), the South East Norway Health Authority (2017-112), the Kristian Gerhard Jebsen Stiftelsen (SKGJ‐MED‐008) and the European Community’s Seventh Framework Programme (FP7/2007–2013), grant agreement no. 602450 (IMAGEMEND). We acknowledge the technical support and service from the Genomics Core Facility at the Department of Clinical Science, the University of Bergen

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and pathologically characterized by the presence of neurofibrillary tangles (tau aggregation) and amyloid plaques (amyloid-beta (A) aggregation). PSEN1 protein with 9 transmembrane helices acts as aspartyl protease and is one of the catalytic components of γ secretase complex, that cleaves amyloid precursor protein (APP). Furthermore, PSEN1 protein plays a significant role in the process of APP and in the generation of amyloid beta (Aβ). In the present study, it was aimed to estimate the probable deleterious effects of missense SNPs in PSEN1 gene that is associated with AD on protein stability and structure by using bioinformatics tools. SIFT, PolyPhen-2, PROVEAN, PhD-SNP, and PANTHER PSEP software were used to estimate the deleterious SNPs, whereas I-Mutant 3.0 and MUpro web tools were used to determine the effects of amino acid substitution on protein stability. Additionally, the effects of wild type and mutant amino acids on protein three-dimensional structure via modeling were predicted by Project HOPE webserver. The phylogenetic conservation of amino acid residues of PSEN1 protein was analyzed by ConSurf. In total, 386 missense SNPs were found in the human PSEN1 gene from the National Center for Biotechnology Information Single Nucleotide Polymorphism (NCBI dbSNP) database and 65 SNPs of which were determined to be deleterious or damaging. In the present study, 8 significant missense SNPs- rs63749891 (R278T), rs63750301 (P264L), rs63750353 (N135D), rs63750524 (R278S), rs63750772 (E273A), rs63751229 (P267S), rs121917807 (G266S), and rs201617677 (R157S)- were determined as high-risk pathogenic. Some differences between wild-type amino acids and mutant amino acids such as hydrophobicity, charge, size, and folding properties were determined according to the modeling findings. Our study demonstrates that high-risk pathogenic missense SNPs have the potential to alter the catalytic activity of the γ secretase complex and subsequently the amount of Aβ40 and Aβ42. Therefore, these missense SNPs may contribute to AD pathogenesis studies., Alzheimer Hastalığı (AH), progresif nörodejeneratif hastalıktır ve patolojik olarak nörofibriler yumaklar (tau agregasyonu) ve amiloid plakların (amiloid beta (A) agregasyonu) varlığı ile karakterize edilir. 9 transmembran heliks içeren PSEN1 proteini, aspartil proteaz olarak işlev görmektedir ve amiloid öncü proteini (APP) parçalayan γ sekretaz kompleksinin katalitik bileşenlerinden biridir. Ayrıca, PSEN1 proteini APP sürecinde ve amiloid beta (A) oluşumunda önemli rol oynamaktadır. Bu çalışmada, AH ile ilişkili PSEN1 genindeki missense (yanlış anlamlı) SNP’lerin protein stabilitesi ve yapısı üzerindeki olası zararlı etkilerinin biyoinformatik araçlar kullanılarak tahmin edilmesi amaçlanmıştır. Zararlı SNP’lerin tahmin edilmesinde SIFT, PolyPhen-2, PROVEAN, PhD-SNP ve PANTHER PSEP yazılımları kullanılırken, amino asit değişiminin protein stabilitesi üzerindeki etkilerini belirlemek için I-Mutant 3.0 ve MUpro web araçları kullanıldı. Ek olarak, yabanıl tip ve mutant amino asitlerin proteinin üç boyutlu yapısı üzerindeki etkileri ise modelleme yoluyla Project HOPE programı ile tahmin edilmiştir. PSEN1 proteininin amino asit kalıntılarının filogenetik korunumu ConSurf ile analiz edildi. NCBI dbSNP veritabanında insan PSEN1 geninde toplam 386 missense SNP bulunduğu ve 65 SNP’nin ise zararlı veya zarar verici olduğu belirlendi. Bu çalışmada, 8 önemli missense SNP- rs63749891 (R278T), rs63750301 (P264L), rs63750353 (N135D), rs63750524 (R278S), rs63750772 (E273A), rs63751229 (P267S), rs121917807 (G266S), ve rs201617677 (R157S)- yüksekli riskli patojenik olarak belirlendi. Yabanıl tip ve mutant amino asitler arasındaki hidrofobiklik, yük, boyut ve katlanma özellikleri gibi bazı farklılıklar modelleme bulgularına göre belirlenmiştir. Çalışmamız, yüksek riskli patojenik missense SNP’lerin γ sekretaz kompleksinin katalitik aktivitesini ve akabinde Aβ40 ve Aβ42 miktarını değiştirme potansiyelinin olduğunu göstermektedir. Bu nedenle, bu missense SNP'ler, AH patogenez çalışmalarına katkı sağlayabilir.

Revista CientíficaVol. 21 N° 36, p 42 - 48 / junio 2021ISSN 1998 – 8850https://lacalera.una.edu.nihttps://doi.org/10.5377/calera.v21i36.11470CIENCIA ANIMALCIENCIA ANIMALFrecuencias alélicas y genotípicas del gen Kappa Caseína y βeta Lactoglobulina en ganado Pardo SuizoAllelic and genotypic frequencies of the Kappa Casein and βeta Lactoglobulin gene in Brown Swiss cattleSonaira Gabriela Andrade Ortega1, Julio Omar López Flores2, Isaías Ezequiel Sánchez Gómez 31 MV. Graduado Universidad Nacional Agraria, ORCID: https://orcid.org/0000-0002-7396-9846/ sonairaortega@gmail.com2 MV. MSc. en Biotecnología, Facultad de Ciencia Animal, ORCID: https://orcid.org/0000-0002-7325-4912/ julio.lopez@ci.una.edu.ni 3 MSc. en Sanidad vegetal, Facultad de Agronomía, ORCID: https://orcid.org/0000-0002-6604-1660 / isanchez@ci.una.edu.ni Universidad Nacional AgrariaRESUMENLa raza Pardo Suizo es una de las razas con gran desarrollo genético orientada a la producción de mayores volúmenes de leche. El objetivo de este estudio fue determinar las frecuencia alélicas y genotípicas del gen de Κappa caseína y βeta Lactoglobulina en ganado con encaste Pardo Suizo y Brahaman. Se seleccionaron 20 hembras bovinas, ubicadas en la finca Santa Rosa de la Facultad de Ciencia Animal de la Universidad Nacional Agraria (UNA). Se extrajo el ADN a partir de sangre total con EDTA. Con la técnica PCR se amplifico fragmentos del gen de Kappa caseína de 351pb y fragmentos de 262pb para el gen Beta lactoglobulina. La genotipificación se realizó con la técnica PCR-FRLP y la separación de fragmentos para ambos genes se realizó en un gel de agarosa al 2 %. Las frecuencias genotípicas encontradas para Κappa caseína fueron de 0.25 (5/20), 0.65 (13/20), 0.10 (2/20), para los genotipos AA, AB y BB respectivamente, resultando más frecuente el heterocigoto AB. Las frecuencias alélicas para este mismo gen fueron de 0.575 y 0.425 para el alelo A y B. Las frecuencias genotípicas para βeta Lactoglobulina fueron 0.05 (1/20), 0.1 (2/20), 0.85 (17/20) para los genotipos AA, AB y BB respectivamente, resultando más frecuente los individuos homocigóticos BB. Las frecuencias alélicas resultaron ser de 0.1 y 0.9 para los alelos A y B de βeta Lactoglobulina. Los individuos evaluados para Κappa caseína presentaron baja proporción del genotipo deseable BB, mientras que para βeta Lactoglobulina la proporción de individuos con genotipo deseable BB fue mayor.

Studies of Trochila (Leotiomycetes, Helotiales, Cenangiaceae) are scarce. Here, we describe two new species based on molecular phylogenetic data and morphology. Trochila bostonensis was collected at the Boston Harbor Islands National Recreation Area, Massachusetts. It was found on the stem of Asclepias syriaca, representing the first report of any Trochila species from a plant host in the family Apocynaceae. Trochila urediniophila is associated with the uredinia of the rust fungus Cerotelium fici. It was discovered during a survey for rust hyperparasites conducted at the Arthur Fungarium, in a single sample from 1912 collected in Trinidad. Macro- and micromorphological descriptions, illustrations, and molecular phylogenetic analyses are presented. The two new species are placed in Trochila with high support in both our six-locus (SSU, ITS, LSU, rpb1, rpb2, tef1) and two-locus (ITS, LSU) phylogenetic reconstructions. In addition, two species are combined in Trochila: Trochila colensoi (formerly placed in Pseudopeziza) and T. xishuangbanna (originally described as the only species in Calycellinopsis). This study reveals new host plant families, a new ecological strategy, and a new country record for the genus Trochila. Finally, our work emphasizes the importance of specimens deposited in biological collections such as fungaria.

En este Trabajo Fin de Grado se ha desarrollado un demostrador de la utilidad de las tecnologías semánticas, especialmente del Linked Data, en el mundo de las Ciencias de la Vida. Para el desarrollo de este demostrador, se han analizado en profundidad los repositorios que se encuentran disponibles en Linked Open Data Cloud y tienen relación con enfermedades genéticas, genes y proteínas. Se han estudiado los mecanismos por los que se han creado esos repositorios en RDF para poder replicarlos de manera local. Para aquellas bases de datos para las que no existe repositorio en RDF o este se encuentra muy desactualizado, hemos analizado la forma en la que se pueden usar estas tecnologías con los datos públicos ya existentes. Se ha desarrollado, finalmente, una aplicación Web para que los usuarios finales (científicos) puedan aprovechar estas tecnologías y obtener información de interés sobre enfermedades genéticas, proteínas y genes.

Pericardial adipose tissue (PAT), a visceral fat depot enveloping the heart, is an active endocrine organ and a source of free fatty acids and inflammatory cytokines. As in other fat adult tissues, PAT contains a population of adipose stem cells; however, whether these cells and/or their environment play a role in physiopathology is unknown. We analyzed several stem cell-related properties of pericardial adipose stem cells (PSCs) isolated from obese and ex-obese mice. We also performed RNA-sequencing to profile the transcriptional landscape of PSCs isolated from the different diet regimens. Finally, we tested whether these alterations impacted on the properties of cardiac mesoangioblasts isolated from the same mice. We found functional differences between PSCs depending on their source: specifically, PSCs from obese PSC (oPSC) and ex-obese PSC (dPSC) mice showed alterations in apoptosis and migratory capacity when compared with lean, control PSCs, with increased apoptosis in oPSCs and blunted migratory capacity in oPSCs and dPSCs. This was accompanied by different gene expression profiles across the cell types, where we identified some genes altered in obese conditions, such as BMP endothelial cell precursor-derived regulator (BMPER), an important regulator of BMP-related signaling pathways for endothelial cell function. The importance of BMPER in PSCs was confirmed by loss- and gain-of-function studies. Finally, we found an altered production of BMPER and some important chemokines in cardiac mesoangioblasts in obese conditions. Our findings point to BMPER as a potential new regulator of PSC function and suggest that its dysregulation could be associated with obesity and may impact on cardiac cells. Ministerio de Ciencia e Innovación (SAF2015‐67911‐R) 6.513 JCR (2021) Q1, 10/81 Physiology 1.308 SJR (2021) Q1, 15/119 Clinical Biochemistry No data IDR 2021 UEM

Hans-Jörg Rheinberger und Staffan Müller-Wille erörtern in ihrem Beitrag das aktuelle wissenschaftliche Verständnis von Genen und ihrer Rolle in Stoffwechsel, biologischer Entwicklung und Evolution komplexer Organismen. Ausgehend von der Beobachtung, dass die Sonderstellung der Gene als bestimmende Faktoren in den genannten Prozessen im gegenwärtigen Zeitalter der Postgenomik weitgehend relativiert worden sei, untersuchen sie mit diesem Wandel verbundene konzeptuelle Probleme. Zudem diskutieren sie, wie sich die gegenwärtige „Deflation“ des Genbegriffs in Wissenschaftsphilosophie und theoretischer Biologie mit dessen tragender Rolle im vergangenen „Jahrhundert des Gens“ sowie in gegenwärtigen Diskursen und biotechnologischen Zukunftsvisionen vermitteln lässt. Die Autoren stellen zunächst die Debatte um die Reduzierbarkeit der klassischen Genetik mit ihrem abstrakten Genbegriff, der die materielle Grundlage der Vererbungserscheinungen offenlässt, auf die molekulare Genetik dar. Jüngere Forschungsergebnisse zeigten, dass molekulare Veränderungen kontextabhängige, nicht einfach direkt ableitbare Unterschiede auf der organismischen Ebene bewirken. Dies stellte die kategorische Unterscheidung von Genotyp und Phänotyp sowie von genetischen und epigenetischen Faktoren mit Verweis auf die kausale Rolle ersterer in Reproduktion, Entwicklung und Stoffwechsel infrage, lasse sich aber in das Informationsparadigma integrieren. Im Anschluss zeichnen die Autoren die Verengung des Bedeutungshorizontes des Vererbungsbegriffs im 20. Jahrhundert und dessen erneute Ausweitung im Zeitalter der Postgenomik nach. Angesichts der Dekonstruktion und Verabschiedung des Konzepts von Genen als „ultimativen Determinanten“ in Wissenschaftsphilosophie und Theorie der Biologie fragen Hans-Jörg Rheinberger und Staffan Müller-Wille nach den Gründen für dessen kaum gemindertes Fortleben in der öffentlichen Kommunikation und nicht zuletzt auch in der wissenschaftlichen Forschungspraxis. Sie argumentieren, dass Gene nicht aufgrund eines ontologischen Sonderstatus oder einer herausragenden Erklärungskraft, sondern aufgrund ihrer heuristischen Funktion als Untersuchungsinstrumente und somit aus epistemologischen und forschungspraktischen Gründen eine zentrale Rolle in der Wissenschaft gespielt haben und weiterhin spielen. Die Autoren zeigen Parallelen auf zwischen der Rolle von Genen als „Angriffspunkt“ für wissenschaftliche und technologische Verfahren in der Entwicklung des Forschungsprozess einerseits und ihrer instrumentellen Rolle in der Evolution der Organismen, die einen „Mittelweg zwischen Stabilitäts- und Plastizitätsanforderungen“ (S. 271) biete, andererseits.

[Resumen]: El término Trastornos del Espectro Alcohólico Fetal (FASD), se refiere al conjunto de efectos perjudiciales resultantes de la exposición embrionaria al etanol. En esta revisión recapitulo información sobre cómo los modelos animales, específicamente el pez cebra (Danio rerio), han facilitado nuestra comprensión del FASD y, en concreto, del Síndrome Alcohólico Fetal (FAS), el nivel de afectación más grave producido por la teratógenesis del alcohol, incluido en el término FASD, mediante revisión bibliográfica. Primero proporciono una breve introducción acerca de la biología del pez cebra y su importancia como organismo modelo. Posteriormente proporciono una introducción al FASD y a la importancia de comprender los mecanismos teratógenos del alcohol dada su elevada incidencia en la población. Para finalizar, evalué la capacidad del pez cebra como organismo modelo para el FASD y FAS. Detallando cómo se ha utilizado el pez cebra para modelar algunos de los principales defectos presentes en FAS y proporcionando información sobre cómo la investigación en el pez cebra nos ha ayudado a comprender los mecanismos teratógenos del alcohol y cómo nos puede ayudar a caracterizar las interacciones gen-etanol que pueden ser la base del FASD. [Resumo]: O termo Trastornos do Espectro Alcohólico Fetal (FASD) refírese ao conxunto de efectos nocivos resultantes da exposición embrionaria ao etanol. Nesta revisión recupero información sobre como os modelos animais, especialmente o peixe cebra (Danio rerio), facilitaron a comprensión do FASD e, específicamente, a do Síndrome Alcohólico Fetal (FAS), o nivel máis grave de afectación causado pola teratoxénese alcohólica, incluido no termo FASD, mediante revisión bibliográfica. Primeiro ofrezo unha breve introdución á bioloxía do peixe cebra e a súa importancia como organismo modelo. Posteriormente proporciono unha introdución ao FASD e a importancia de comprender os mecanismos teratoxénicos do alcol dada a súa alta incidencia na poboación. Finalmente, avaliei a capacidade do peixe cebra como organismo modelo para o FASD e FAS. Detallando como se usou o peixe cebra para modelar algúns dos maiores defectos presentes no FAS e proporcionando información sobre como a investigación sobre o peixe cebra nos axudou a comprender os mecanismos teratoxénicos do alcol. [Abstract]: The term Fetal Alcohol Spectrum Disorders (FASD) refers to the entire suite of deleterious outcomes resulting from embryonic exposure to ethanol. In this review I recap information on how animal models, specifically zebrafish (Danio rerio), have informed our understanding of FASD and specifically Fetal Alcohol Syndrome (FAS), the most serious level of involvement caused by alcohol teratogenesis, included in the term FASD, through bibliographic review. I first provide a brief introduction to the biology of the zebrafish and its importance as a model organism. Later I provide an introduction to FASD and the importance of understanding the teratogenic mechanisms of alcohol given its high incidence in the population. Finally, evaluating the capacity of the zebrafish as a model organism for the FASD and FAS. Detailing how zebrafish has been used to model some of the major defects present in FAS and providing information on how research on zebrafish has helped us understand the teratogenic mechanisms of alcohol and how it can help us characterize the gene-ethanol interactions that can be the basis of FASD. Traballo fin de grao (UDC.CIE). Bioloxía. Curso 2019/2020

RESUMEN : La medicina personalizada es una nueva manera de tratar y prevenir enfermedades. Este tipo de medicina tiene en cuenta factores que hasta ahora no se consideraban fundamentales para un correcto diagnóstico y tratamiento, como la variabilidad genética, el estilo de vida o el medio ambiente. El presente Trabajo Fin de Grado explora este concepto a través de la descripción del caso de una paciente de 17 años con un síndrome extremadamente raro causado por una mutación genética escasamente descrita. Tras un estudio genético exhaustivo, se objetiva una mutación en el gen XPO5; gen fundamental para un correcto desarrollo glomerular, pudiendo explicar así la aparición del síndrome nefrótico resistente a esteroides de la paciente. Tras un seguimiento clínico de 15 años, y diversos tratamientos diferentes, se ha conseguido la correcta estabilización de la paciente, logrando no solamente disminuir la proteinuria, sino adecuando su tratamiento a otros factores con posibles repercusiones en distintas etapas vitales, como un posible embarazo. La relación entre esta mutación y el síndrome no había sido descrita nunca anteriormente. Este trabajo no es solo la descripción de un caso clínico extremadamente raro, sino una iniciación a la investigación y a la publicación de artículos científicos. ABSTRACT : Personalized medicine is a new approach for disease treatment and prevention. This kind of medicine takes into account various factors that have not been traditionally considered to be fundamental for a successful diagnosis and treatment, such as gene variability, lifestyle and environment. The following Final Project explores this concept by describing the case of a 17-year-old woman, with an extremely rare syndrome caused by an exceptionally described genetic mutation. After an exhaustive genetic study, a mutation in XPO5 gene was discovered, being this gene fundamental for a satisfactory glomerular development, explaining the steroid-resistant nephrotic syndrome that she presents. After a long 15 year follow up, and a few different treatments, the patient is currently stable, with a significant reduction in proteinuria levels, as well as a satisfactory and safe treatment for all possible stages of development, for example a possible pregnancy. The link between the mutation and the syndrome she presents has never been described before. This Final Project is not only a description of an exceptionally rare clinical case, but an initiation to the processes of investigating and publishing scientific articles. Grado en Medicina

Publisher's version (útgefin grein)., Aims Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland. Methods and results Using a large resource of whole-genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that we examined for association with HDL-C (n = 136 672). Three rare SCARB1 mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency = 0.2%) associate with elevated levels of HDL-C (p.G319V: β = 11.1 mg/dL, P = 8.0 × 10 -7; p.V111M: β = 8.3 mg/dL, P = 1.1 × 10 -6; p.V32M: β = 10.2 mg/dL, P = 8.1 × 10 -4). These mutations do not associate with CAD (36 886 cases/306 268 controls) (odds ratio = 0.90, 95% confidence interval 0.67-1.22, P = 0.49), despite effects on HDL-C comparable to that reported for p.P376L, both in terms of direction and magnitude. Furthermore, HDL-C raising alleles of three common SCARB1 non-coding variants, including one previously unreported (rs61941676-C: β = 1.25 mg/dL, P = 1.7 × 10 -18), and of one low frequency coding variant (p.V135I) that independently associate with higher HDL-C, do not confer increased risk of CAD. Conclusion Elevated HDL-C due to genetically compromised SR-BI function is not a marker of CAD risk., The authors thank all the individuals who participated in this study and whose contribution made this work possible. We also thank our valued colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. Funding This work was supported by deCODE genetics/Amgen.

Phytoestrogens are polyphenol compounds which have similar structure to 17β-estradiol (E2), a kind of main estrogen in women. Thus, phytoestrogens may affect the reproductive and endocrine systems, leading to the development of estrogen-related cancers. The effect of genistein (Gen), one of the most studied phytoestrogens, on human cervical cancer cells (HeLa) was investigated in this study. It was found that Gen at concentrations of 0.001, 0.01, 0.1 and 1 µmol·L-1 promoted the proliferation of HeLa cells in a dose-dependent manner. Gen increased the portion of HeLa cells in S phase and decreased the portion of the cells in G1 phase. Besides, apoptosis rate of the cells was significantly lower when treated with Gen compared with the control group. It was also found that the expression of ERα, Akt or nuclear NF-κB p65 protein was activated by Gen. The correlation between these three proteins may be as following: ERα was the upstream, followed by Akt, and then nuclear NF-κB p65 protein. In addition, the downstream genes of activated nuclear NF-κB p65 were found to be associated with cell cycle and apoptosis of cancer cells. Our results suggested that Gen may stimulate cell proliferation partially through the estrogen receptor-mediated PI3K/Akt-NF-κB pathway and the further activation of the downstream genes of nuclear NF-κB p65.

Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function. Evidence supports the hypothesis that there is a link between GSH metabolism and the control of epigenetic mechanisms at different levels (i.e., substrate availability, enzymatic activity for DNA methylation, changes in the expression of microRNAs, and participation in the histone code). However, little is known about the molecular pathways by which GSH can control epigenetic events. Studying mutations in enzymes involved in GSH metabolism and the alterations of the levels of cofactors affecting epigenetic mechanisms appears challenging. However, the number of diseases induced by aberrant epigenetic regulation is growing, so elucidating the intricate network between GSH metabolism, oxidative stress and epigenetics could shed light on how their deregulation contributes to the development of neurodegeneration, cancer, metabolic pathologies and many other types of diseases. Sin financiación 6.020 JCR (2017) Q1, 39/292 Biochemistry and Molecular Biology, 17/143 Endocrinology and Metabolism UEV

Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments. Sin financiación 6.308 JCR (2017) Q1, 24/261 Neurosciences UEM

Recurrent neural networks have been widely used to generate millions of de novo molecules in defined chemical spaces. Reported deep generative models are exclusively based on LSTM and/or GRU units and frequently trained using canonical SMILES. In this study, we introduce Generative Examination Networks (GEN) as a new approach to train deep generative networks for SMILES generation. In our GENs, we have used an architecture based on multiple concatenated bidirectional RNN units to enhance the validity of generated SMILES. GENs autonomously learn the target space in a few epochs and are stopped early using an independent online examination mechanism, measuring the quality of the generated set. Herein we have used online statistical quality control (SQC) on the percentage of valid molecular SMILES as examination measure to select the earliest available stable model weights. Very high levels of valid SMILES (95–98%) can be generated using multiple parallel encoding layers in combination with SMILES augmentation using unrestricted SMILES randomization. Our trained models combine an excellent novelty rate (85–90%) while generating SMILES with strong conservation of the property space (95–99%). In GENs, both the generative network and the examination mechanism are open to other architectures and quality criteria.

Introducción: el melanoma representa el 4 % de todos los tumores malignos de la piel, pero es responsable del 80 % de las muertes por cáncer en este sitio. El surgimiento de las terapias dirigidas contra la mutación de BRAF ha cambiado el pronóstico, de allí, la importancia de identificar esta mutación en los pacientes con diagnóstico histológico de melanoma maligno ya que la tasa de mutaciones del oncogén BRAF es alta. Objetivo: describir las implicaciones diagnósticas, terapéuticas y pronósticas de la determinación de la mutación del gen BRAF V600E en el melanoma maligno cutáneo. Método: revisión bibliográfica vía PUBMED con la introducción de los siguientes términos de búsqueda: melanoma, melanoma AND genetics, melanoma AND BRAF mutation, melanoma AND BRAF V600E AND prognosis. Se identificaron 72 publicaciones. Resultados: múltiples estudios han corroborado la alta frecuencia del oncogén BRAF V600E mutado en el melanoma cutáneo, ofreciendo la posibilidad de que a través de la identificación de dicha alteración se pueda contribuir a mejorar el diagnóstico y a garantizar un tratamiento dirigido específicamente contra la actividad de BRAF. Conclusiones: la identificación de la mutación del oncogén BRAF representa un factor pronóstico y puede representar una diana terapéutica eficaz.

La mobilité entre Bruxelles et sa périphérie est une problématique multidimensionnelle qui soulève des enjeux socioéconomiques, environnementaux et politiques. Pourtant, les données précises à son sujet sont relativement limitées. Dans ce cadre, cet article propose d’aborder la question par le biais d’une analyse géographique empirique. Apparaissent ainsi les conditions et façons différenciées de se déplacer vers Bruxelles depuis son aire métropolitaine, qui sont synthétisées au sein d’une typologie. De mobiliteit tussen Brussel en de rand is een belangrijke multidimensionale problematiek die uitdagingen op sociaal-economisch, ecologisch en politiek vlak meebrengt. En toch zijn er relatief weinig nauwkeurige gegevens terug te vinden over dit onderwerp. Tegen die achtergrond gaat dit artikel dieper in op deze kwestie aan de hand van een empirische geografische analyse. Het resultaat zijn uiteenlopende omstandigheden en manieren om zich vanuit het grootstedelijk gebied naar Brussel te verplaatsen, die in een typologie worden samengevat. Mobility between Brussels and its outskirts is a multidimensional issue involving socioeconomic, environmental and political challenges. However, precise data on this issue are relatively limited. In this context, this article proposes to address the issue through an empirical geographical analysis. Thus, the differentiated conditions and ways of travelling to Brussels from its metropolitan area emerge, and are summarised within a typology.

De mobiliteit tussen Brussel en de rand is een multidimensionale problematiek die uitdagingen op sociaal-economisch, ecologisch en politiek vlak meebrengt. En toch zijn er relatief weinig nauwkeurige gegevens terug te vinden over dit onderwerp. Tegen die achtergrond gaat dit artikel dieper in op de kwestie aan de hand van een empirische geografische analyse. Het resultaat zijn uiteenlopende omstandigheden en manieren om zich vanuit het grootstedelijk gebied naar Brussel te verplaatsen, die in een typologie worden samengevat. La mobilité entre Bruxelles et sa périphérie est une problématique multidimensionnelle qui soulève des enjeux socioéconomiques, environnementaux et politiques. Pourtant, les données précises à son sujet sont relativement limitées. Dans ce cadre, cet article propose d’aborder la question par le biais d’une analyse géographique empirique. Apparaissent ainsi les conditions et façons différenciées de se déplacer vers Bruxelles depuis son aire métropolitaine, qui sont synthétisées au sein d’une typologie. Mobility between Brussels and its outskirts is a multidimensional issue involving socioeconomic, environmental and political challenges. However, precise data on this issue are relatively limited. In this context, this article proposes to address the issue through an empirical geographical analysis. Thus, the differentiated conditions and ways of travelling to Brussels from its metropolitan area emerge, and are summarised within a typology.

Publisher's version (útgefin grein)., Epithelial to mesenchymal transition (EMT) is a developmental event that is hijacked in some diseases such as fibrosis and cancer. In cancer, EMT has been linked to increased invasion and metastasis and is generally associated with a poor prognosis. In this study, we have compared phenotypic and functional differences between two isogenic cell lines with an EMT profile: D492M and D492HER2 that are both derived from D492, a breast epithelial cell line with stem cell properties. D492M is non-tumorigenic while D492HER2 is tumorigenic. Thus, the aim of this study was to analyze the expression profile of these cell lines, identify potential oncogenes, and evaluate their effects on cellular phenotype. We performed transcriptome and secretome analyses of D492M and D492HER2 and verified expression of selected genes at the RNA and protein level. One candidate, YKL-40 (also known as CHI3L1), was selected for further studies due to its differential expression between D492M and D492HER2, being considerably higher in D492HER2. YKL-40 has been linked to chronic inflammation diseases and cancer, yet its function is not fully understood. Knock-down experiments of YKL-40 in D492HER2 resulted in reduced migration and invasion as well as reduced ability to induce angiogenesis in an in vitro assay, plus changes in the EMT-phenotype. In summary, our data suggest that YKL-40 may provide D492HER2 with increased aggressiveness, supporting cancer progression and facilitating angiogenesis., This work was supported by Grants from Landspitali University Hospital Science Fund, University of Iceland Research Fund, and Icelandic Science and Technology Policy—Grant of Excellence: 152144051. ‘Göngum saman,’ a supporting group for breast cancer research in Iceland ( www.gongumsaman.is ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher's version (útgefin grein), Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D). Objectives: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal. Methods: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D. Results: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D. Conclusions: Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.

Urologic malignancies are some of the commonest tumors often curable when diagnosed at early stage. However, accurate diagnostic markers and faithful predictors of prognosis are needed to avoid over-diagnosis leading to overtreatment. Many promising exploratory studies have identified epigenetic markers in urinary malignancies based on DNA methylation, histone modification and non-coding ribonucleic acid (ncRNA) expression that epigenetically regulate gene expression. We review and discuss the current state of development and the future potential of epigenetic biomarkers for more accurate and less invasive detection of urological cancer, tumor recurrence and progression of disease serving to establish diagnosis and monitor treatment efficacies. The specific clinical implications of such methylation tests on therapeutic decisions and patient outcome and current limitations are also discussed. Fondo de Investigaciones Sanitarias, Ministerio de Sanidad, Gobierno de España (FIS11/608) 1.909 JCR (2016) Q3, 110/167 Genetics & Heredity, 171/257 Pharmacology & Pharmacy UEM

Publisher's version (útgefin grein), Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective: To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019. Exposures: Genetic variants (615643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples. Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography. Results: The mean (SD) age of the 44703 GERA participants was 69.7 (8.4) years, and 22019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P =.03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P =.04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]). Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target., This study was supported by grant R01 HL128550 from the NHLBI of the NIH (Dr Thanassoulis); the Ellison Medical Foundation, Robert Wood Johnson Foundation, Wayne and Gladys Valley Foundation, Kaiser Permanente Northern California, and the Kaiser Permanente National and Regional Community Benefit Programs (The Kaiser Permanente Research Program on Genes, Environment and Health); a grant from the NIH (The Genetic Epidemiology Research on Adult Health and Aging cohort); a strategic partnership between the MRC and the University of Oxford (University of Oxford MRC Population Health Research Unit); application 24281 from the UK Biobank Resource; contracts NO1-HC-25195 and HHSN268201500001I, R01 HL 089590, and the SHARe project from the NHLBI (Framingham Heart Study); the NHLBI in collaboration with Multi-Ethnic Study of Atherosclerosis (MESA) investigators (MESA and the MESA SHARe project); contracts HHSN268201500003I from the NIH, contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the NHLBI, contracts UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences, and contract DK063491 from the National Institute of Diabetes and Digestive and Kidney Diseases (MESA); contract N02-HL-64278 from the NHLBI (SHARe genotyping); shared instrumentation grant s10rr025141 from the NIH, awards UL1TR002243 and UL1TR000445 from the National Center for Clinical and Translational Science, and award UL1RR024975 from the National Center for Research Resources (Vanderbilt University Medical Center’s Vanderbilt DNA Biobank projects); and investigator-led projects U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, and R01HD07471 from the NIH (genomic data).

En este proyecto se presenta la importancia del cabello como estigma social, enfocado concretamente hacia la variación tonal del color pelirrojo. Partiendo de esta propuesta, la intención del proyecto es mostrar la importancia que tiene el cabello en la sociedad y la identidad que se crea según sus características, conllevando así a la creación de un estigma social, todo ello partiendo de la retrospectiva y condición genética del artista.

Tinaz, Ekrem ( Aksaray, Yazar ), Objective: The dopaminergic system, especially variations in the catechol-O-methyltransferase (COMT) gene, is of major interest in the etiology of schizophrenia. The rs4680 (Val108/158Met), rs165599, and P2 promoter rs2075507 single nucleotide polymorphisms (SNPs) in the COMT gene have been shown to be associated with alteration of COMT gene expression and COMT enzyme activity. The aim of this study was to investigate a possible association between schizophrenia and the haplotypes of these polymorphisms. Methods: The sample was comprised of 181 patients with schizophrenia and 368 healthy controls. The patients' psychotic symptoms were rated using the Positive and Negative Symptom Scale (PANSS). COMT rs2075507, rs4680, and rs165599 SNPs were evaluated by a polymerase chain reaction, followed by restriction fragment length polymorphism analysis. These SNPs in the COMT gene were subjected to haplotype analyses using Haploview ver. 4.2. Results: No significant differences were found between COMT rs2075507, rs4680, and rs165599 SNPs in schizophrenic patients and controls. The patients' PANSS results were not associated with these SNPs. No associations were obtained between 2 and 3-haplotypes of rs2075507, rs4680, rs165599 SNPs and schizophrenia. Conclusion: COMT rs2075507, rs4680, rs165599 SNPs and haplotypes do not appear to be risk factors for schizophrenia in this population.

BACKGROUND: DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. METHODS: A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. RESULTS: A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. CONCLUSIONS: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV. Sin financiación 9.117 JCR (2017) Q1, 11/155 Immunology, 3/88 Infectious Diseases, 11/125 Microbiology UEM

Los seres vivos compartimos parte de nuestro código genético entre distintas especies. Estudiar la similitud del código genético del ser humano con otras especies animales permite extrapolar conclusiones de experimentos con animales, e incluso conocer el carácter evolutivo de una enfermedad. Este proyecto ayuda a realizar este tipo de investigación ofreciendo una aplicación web que permite comparar el código genético de los genomas de todos los seres vivos. En la aplicación web se pueden comparar genomas de eucariota, bacterias y arquea. La aplicación web muestra un árbol filogenético para cada tipo de organismos. Este árbol representa visualmente la similitud entre distintas especies de eucariotas, bacterias y arqueas, así como su ascendencia común. Posteriormente, una vez seleccionados en el árbol los genomas que se quieren comparar, el visor en detalle permite ver qué partes de un genoma se conservan en el resto de genomas. We, living creatures, share out genetic code between species. Studying the similitude between the genetic code of the human being and other animal species makes it easier to extract conclusions from animal testing, and grants information about the origin of some diseases. This project helps this type of investigation offering a web application that allow for the comparison of the genomes of all living creatures. In this web application, genomes of eukaryote, bacteria and archaea can be compared. The web application shows a phylogenetic tree for each type of organism. This phylogenetic tree visually represents the similitude between species of eukaryote, bacteria and archaea, and also shows their shared ancestors. The genomes in the tree can be selected to open the detailed view of the comparison between the selected genomes. The detailed view allows for the viewing of parts of the genomes that are conserved in other genomes. Els éssers vius compartim part del nostre codi genètic entre diferents espècies. Estudiar la similitud del codi genètic de l'ésser humà amb altres espècies permet extrapolar conclusions d'experiments amb animals, i també conèixer el caràcter evolutiu d'una malaltia. Aquest projecte ajuda a realitzar aquest tipus d'investigació oferint una aplicació web que permet comparar el codi genètic dels genomes de tots els éssers vius. A l'aplicació web es poden comparar genomes d'eucariota, bacteri i arqueu. L'aplicació web mostra un arbre filogenètic per a cada tipus d'organisme. Aquest arbre representa visualment la similitud entre distintes espècies d'eucariotes, bacteris i arqueus, i també la seva ascendència comú. Posteriorment, un cop seleccionats a l'arbre els genomes que es vulguin comparar el visor en detall permet veure quines parts d'un genoma es conserven a la resta de genomes.

Deraeocorinae gen. sp. Unpublished record: [12], 13.i. 2015, 1&female;, coll. AK., Published as part of Krüger, Andreas & Deckert, Jürgen, 2016, True bugs (Hemiptera-Heteroptera) of Botswana — Bibliographical inventory and new records, pp. 33-63 in Zootaxa 4114 (1) on page 42, DOI: 10.11646/zootaxa.4114.1.2, http://zenodo.org/record/256012

Deraeocorinae gen. sp. Unpublished record: [12], 13.i. 2015, 1&female;, coll. AK.

Publisher's version (útgefin grein)., Mutations in BRCA1 result in predisposal to breast and ovarian cancers, but many variants exist with unknown clinical significance (VUS). One is BRCA1 c.4096+3A>G, which affects production of the full-length BRCA1 transcript, while augmenting transcripts lacking most or all of exon 11. Nonetheless, homozygosity of this variant has been reported in a healthy woman. We saw this variant cosegregate with breast and ovarian cancer in several family branches of four Icelandic pedigrees, with instances of phenocopies and a homozygous woman with lung cancer. We found eight heterozygous carriers (0.44%) in 1820 unselected breast cancer cases, and three (0.15%) in 1968 controls (p = 0.13). Seeking conclusive evidence, we studied tumors from carriers in the pedigrees for wild-type-loss of heterozygosity (wtLOH) and BRCA1-characteristic prevalence of estrogen receptor (ER) negativity. Of 15 breast and six ovarian tumors, wtLOH occurred in nine breast and all six ovarian tumours, and six of the nine breast tumors with wtLOH were ER-negative. These data accord with a pathogenic BRCA1-mutation. Our findings add to the current knowledge of BRCA1, and the role of its exon 11 in cancer pathogenicity, and will be of use in clinical genetic counselling., This research was funded by the Landspitali University Hospital Research Fund, grant A-2019-001, and by the Icelandic association "Walking for Breast Cancer Research" (Göngum saman).

Mitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c). Although more research is needed, we suggest that the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people. 5.760 JCR (2015) Q1, 36/187 Cell biology, 3/49 Geriatrics & gerontology UEM

ResumenEl cáncer es una patología con prevalencia en alza y cuyo origen se encuentra en el DNA, más específicamente en las alteraciones que lo afectan, y que finalmente se traducen en la desregulación del ciclo celular y de los mecanismos celulares reparadores del DNA. La desregulación del ciclo celular se traduce finalmente en la formación de tumores, que pueden invadir tejidos u órganos distantes, provocando la muerte del paciente. Conocer y entender las alteraciones y/o daños que puede sufrir el DNA permite comprender el proceso de carcinogénesis a escala molecular, pero también a escala humana. Esta revisión pretende actualizar y/o clarificar algunos conceptos moleculares básicos del cáncer, cómo éstos pueden estudiarse en un laboratorio de biología molecular y cómo pueden ayudar a mejorar la práctica clínica con un paciente oncológico.SummaryCancer prevalence is rising worldwide. The main pathogenic events of this devastating disease are alterations in the DNA, which eventually result in the dysregulation of both the cell cycle and DNA repair mechanisms. This dysregulation of the cell cycle results in the formation of a tumor, from which cancer cells disseminate to distant organs, finally bringing about patient death. Knowledge and understanding of the nature of the DNA alterations is essential to the comprehension of the carcinogenic process at both a molecular and human scale. This review aims to update and clarify some basic molecular concepts in cancer, focusing principally on how alterations can be studied within the molecular biology lab, and how this discipline can improve clinical cancer practice.

The characteristics of seven pea varieties of different groups of ripening are described. These cultivars provide the sustainable row material input in canning factories of Krasnodar region. In bogharic agriculture it takes 24,26 days. When using the irrigation system and different time of sowing it takes 35,40 days.

Psodogenler, gen benzeri olan fakat genlerden farkli olarak fonksiyonel urununu kodlayamayan, sahte gen bolgeleridir. Promotor bolgelerindeki delesyon, insersiyon, cerceve kaymasi gibi mutasyon veya zamanindan once stop kodonu bulundurma sonucu meydana gelirler. Insan genomu, yaklasik olarak 20.000 psodogen icermektedir. Psodogenler uretildikleri mekanizmalara gore tek kopya, tekrarlayan ve islenmis olmak uzere uc gruba ayrilmaktadir. Son yillarda yapilan molekuler calismalara gore, herhangi bir gorevi olmadigi zannedilen psodogenlerin bazi gorevlerinin oldugu, hatta bazilarininda kisa peptid ve protein uretebildigi gosterilmistir. mRNA stabilitesini, gen ekspresyonunu duzenledigi ve genomun evriminde rol oynadigi bildirilmistir. Bu raporlardan biri de psodogenlerin mikroRNA tuzaklari ile tumor supresor genler ve onkogenlerin duzenlenmesi yetenegine sahip oldugunu gostermektedir. Su ana kadar psodogenlerin olusum mekanizmalari ve gorevleri, hatta psodogenin yapisi ile ilgili hic Turkce bir kaynak bulunmamaktadir. Bu nedenle, biz bu derlemede psodogenler hakkinda okuyucuyu bilgilendirmeyi amacladik. Sonuc olarak ise bu genlerin ‘sahte’ ismini hak etmedigini, molekuler calismalar ile bu genlerin hucrede gen ekspresyonunda onemli rol oynadigi tespit edilmistir. Bu yuzden bilim camiasinda bu genlerin fonksiyonlari dogrultusunda yeniden isimlendirilmeleri gerektigi dusunulmektedir. Anahtar Kelimeler: Psodogen, Sahte gen, Gen, mikroRNA

La comparación de genomas proporciona información sobre los procesos evolutivos que se han llevado a cabo en la aparición de los diversos seres vivos que habitan el planeta tierra. A partir de la comparación entre los genomas, se puede obtener un árbol evolutivo entre las diferentes especies. En el caso de comparación de genomas de bacterias el principal problema es el gran número de genomas a comparar. Este gran número hace que la comparación entre todos los genomas secuenciados de bacteria pueda tardar más de un año. Para superar esta barrera se ha adaptado el sistema existente para obtener el árbol filogenético. En primer lugar se lanzarán las comparaciones entre genomas en paralelo. Por otro lado, se generará el árbol evolutivo cada vez que un genoma es comparado con el resto de genomas previamente comparados, sin necesidad de esperar que se realice la comparación entre todos los genomas. Por último, el sistema dejará de guardar los resultados de las comparaciones entre genomas. En su lugar, cada vez que el usuario requiera estudiar esas comparaciones via web se relanzará el cálculo de la comparación y solo se guardarán los resultados de las comparaciones más consultadas. The comparison of genomes provides information about the evolutionary processes that have taken place in the appearance of the various living beings that inhabit our planet. From the comparison between the genomes, you can obtain an evolutionary tree among the different species. In the case of the comparison between the bacteria genomes the main problem is the big amount of genomes to be compared. This huge number of genomes makes the comparison between all the sequenced bacteria genomes take longer than a year. To overtake this barrier, we have adapted the existing system to obtain the phylogenetic tree. Firstly, the comparisons between the genomes will be made in a parallel way. On the other side, the evolutionary tree will be generated every time that a genome is compared to the rest of previously compared genomes, with no need to wait for the comparison to be made between the genomes. Finally, the system will stop saving the results of the comparisons between the genomes. Instead, every time that the user requires analyzing those comparisons via web, the calculation of the comparison will be thrown and only the results of the most consulted comparisons will be saved. La comparació de genomes proporciona informació sobre els processos evolutius que s'han dut a terme en l'aparició dels diversos éssers vius que viuen a la terra. A partir de la comparació entre els genomes, es pot obtenir l'arbre evolutiu entre les diferents espècies. En les comparacions de genomes de bacteris el principal problema és el gran nombre de genomes a comparar. Aquest gran nombre fa que les comparacions entre tots els genomes seqüenciats de bacteri puguin trigar més d'un any. Per superar aquesta limitació s'ha adaptat el sistema existent per obtenir l'arbre filogenètic. En primer lloc és llançaran les comparacions entre genomes en paral·lel. Per altra banda, es generarà l'arbre evolutiu cada cop que un genoma és comparat amb la resta de genomes prèviament comparats sense necessitat d'esperar que es realitzi la comparació entre tots els genomes. Per últim, el sistema deixarà de guardar els resultats de les comparacions entre genomes. En el seu lloc, cada cop que l'usuari requereix estudiar les comparacions via web es rellançarà el calcul de la comparació i només és guardaran els resultats de les comparacions més consultades.

La esencia y los orígenes de la genética hay que buscarlos en los principales experimentos que Gregor Mendel publicó por los años 1866. A partir de ellos es cuando la misma genética empieza a tomar forma y se desarrolla diferentes ramas de estudio con técnicas y metodología más avanzadas que nos permiten avanzar en el conocimiento y la aplicación de los mismos en diversos ámbitos, muchos de los cuales permiten mejorar nuestra calidad de vida, especialmente en la medicina. Se abordan los contenidos fundamentales de la Teoría cromosómica de la herencia y del concepto, utilidad y tipos de mutaciones. The essence and origins of genetics are to be found in the main experiments that Gregor Mendel published by the years 1866. From them it is when the same genetic begins to take shape and different branches of study techniques and methodology most advanced develops that allow us to advance the knowledge and application thereof in various fields, many of which can improve our quality of life, especially in medicine. The fundamental contents of the chromosomal theory of inheritance and concept, utility and types of mutations are addressed.

RESUMEN: INTRODUCCIÓN: La telangiectasia hemorrágica hereditaria o HHT es una enfermedad hereditaria rara que afecta a varios órganos en forma de telangiectasias y malformaciones arteriovenosas. Hay pocos trabajos publicados en cuanto a la afectación ocular. MATERIAL Y MÉTODOS: Hemos realizado un estudio transversal con 206 pacientes registrados en la base de datos de la Unidad de HHT del Hospital Comarcal Sierrallana de Torrelavega (Cantabria, España), explorados por oftalmología entre los años 2003 y 2013. RESULTADOS: Todas las lesiones que hemos encontrado son telangiectasias conjuntivales sin ninguna malformación vascular retiniana, con una prevalencia del 50,95%. Los pacientes con lesiones oculares presentan mayor edad media, sin diferencias entre sexos ni grupos de edad. La afectación ocular está asociada a mutaciones en el gen ENG. Hay asociación entre las telangiectasias conjuntivales y las localizadas en dedos, y con resultados positivos en capilaroscopia. También están asociadas a sangrado de la mucosa oral y piel de la nariz, grado II de frecuencia en epistaxis según criterios de Sadick y MAVp grado III y IV según TTCE. CONCLUSIONES: La afectación ocular más frecuente en la HHT consiste en telangiectasias conjuntivales, asociadas al subtipo HHT1. Su presencia carece de gravedad y no sirve como indicador en la valoración clínica de los pacientes, por lo que no es necesaria la exploración oftalmológica de rutina. ABSTRACT: BACKGROUND: Hereditary hemorrhagic telangiectasia is a rare hereditary disorder with several organs involved causing telangiectasias and arteriovenous malformations. There are few published works about ocular involvement. MATERIAL AND METHODS: We have made a cross-sectional study with 206 patients included in HHT Unit database at Sierrallana Hospital in Torrelavega (Cantabria, Spain). These patients had been explored by ophthalmologist between 2003 and 2013. RESULTS: All lesions that we have found are conjunctival telangiectasias without any vascular retinal malformations. The prevalence of conjunctival telangiectasias is 50,95%. The average age of patients with ocular lesions is higher regardless of their sex and there no differences among patients into the same age group. Ocular involvement is linked to ENG gene mutations. Conjunctival and finger telangiectasias are related, and there is an association between conjuntival lessions and positive capilaroscopy, oral mucous and nose skin hemorrhage, II Sadick´s degree of epistaxis and III and IV VAMp degree according to TTCE. CONCLUSIONS: The most common ocular lesions in HHT are conjunctival telangiectasias, specifically HHT1 subtype. They are not a serious problem and they are not useful as a sign in these patients´ clinical evaluation, that´s why no ophthalmologic examination is necessary.

El objetivo general de este trabajo es revelar por primera vez los cambios en la expresión génica que se producen durante el desarrollo y la maduración de la pulpa de los frutos cítricos, y en particular aquellos asociados a los mecanismos de regulación de la acidez, identificando el conjunto de genes inducidos y reprimidos que regulan la síntesis y la degradación del ácido cítrico durante la maduración interna de los frutos cítricos. Desde un punto de vista metabólico se ha estudiado la evolución de los principales ácidos de los frutos en cuatro variedades que presentan diferencias en su periodo de maduración, con la intención de determinar los correspondientes patrones de acumulación y degradación. Por otra parte, atendiendo a la expresión de los principales genes implicados en el metabolismo de los ácidos se incide sobre los mecanismos de regulación de su síntesis durante las fases I y II del desarrollo del fruto, y de su degradación en las fases II y III de maduración del fruto. De este modo se ha comprobado que el ácido cítrico se metaboliza vía 2-oxoglutarato a glutamina y a succinato, en la ruta de derivación del GABA, por lo que esta ruta parece ser una vía prioritaria de catabolismo del ácido cítrico. Además, se ha comprobado que la acumulación de ácido cítrico en los frutos se encuentra directamente relacionada con una disminución del nivel de transcrito de la ATP citrato liasa, la cual reduce la degradación de citrato en el citosol quedando más cantidad de citrato disponible para ser almacenado en la vacuola., Soler Fayos, G. (2009). Cambios en la expresión génica asociados a la maduración interna del fruto de los cítricos: identificación de rutas metabólicas implicadas en la acumulación y eliminación de ácidos [Tesis doctoral no publicada]. Universitat Politècnica de València. doi:10.4995/Thesis/10251/6068.

Documento PDF de 5 páginas con ilustraciones a color. material didáctico del portal Web KIDS.CSIC Aprender ciencia es divertido. http://www.kids.csic.es/, Guía para el docente que acompaña a la película "Los guisantes informan". película para escolares en la que se describen los experimentos de Gregor Johann Mendel y las leyes que enunció.El material esta concebido como un recurso educativo para los docentes. La guía y la película están publicadas en el portal WEB "KIDS.CSIC Aprender ciencia es divertido" del Proyecto El CSIC y la Fundación BBVA en la Escuela., Fundación BBVA Consejo Superior de Investigaciones Científicas

Several studies have been conducted to analyze the role of short polymorphism of serotonin transporter (5-HTTLPR) in response to psy-chosocial stress mediated by cortisol, having found inconsistent results. In order to synthesize and analyze available information about the role of short polymorphisms of 5-HTTLPR gen in the stress response, this meta-analysis has been carried out. A meta-analysis of studies published until November 2011 without language restrictions, which analyzed the effect of the short polymorphisms of 5-HTTLPR in the cortisol response during a stress-inducing protocol was conducted. Published F or p genotype values were collected as estimators of the difference between groups as well as the sign of this difference for analysis. The global meta-analysis showed no significant association between the presence of the short allele and a different response to psychosocial stress. After comparing the subgroups of studies where participants underwent an emotionally neutral intervention versus an emotionally negative intervention, significant differences were found. The subgroup of studies where patients underwent an emotionally negative intervention showed a significantly greater cortisol release by those individuals carrying the short allele. This association was not seen in the neutral subgroup.

Varios estudios han sido llevados a cabo para analizar el papel del polimorfismo corto del transportador de la serotonina (5-HTTLPR) en la respuesta al estrés psicosocial mediado por cortisol, habiéndose encontrado resultados contradictorios. Con el fin de sintetizar y analizar la información disponible acerca del papel del polimorfismo corto del gen 5-HTTLPR en la respuesta al estrés se ha realizado este meta-análisis. Se realizó un meta-análisis de estudios publicados hasta noviembre de 2011 sin restricción de idioma, donde se analizaba el efecto del polimorfismo corto del 5-HTTLPR en la respuesta de cortisol durante un protocolo inductor de estrés. Se recogieron los valores F o p genotipo publicados como estimadores de la diferencia entre grupos, así como el signo de esta diferencia para su análisis. El meta-análisis global no mostró asociación significativa entre la presencia del alelo corto y una diferente respuesta al estrés psicosocial. Tras comparar los subgrupos de estudios donde sometía a los participantes a una intervención emocionalmente neutral frente a una intervención emocionalmente negativa, se encontraron diferencias significativas. En el subgrupo de estudios donde los pacientes fueron sometidos durante la intervención a un ambiente emocionalmente negativo, se observó una significativamente mayor liberación de cortisol por parte de aquellos sujetos portadores del alelo corto. Esta asociación no se observó en el subgrupo neutral. Several studies have been conducted to analyze the role of short polymorphism of serotonin transporter (5 HTTLPR) in response to psychosocial stress mediated by cortisol, having found inconsistent results. In order to synthesize and analyze available information about the role of short polymorphisms of 5-HTTLPR gen in the stress response, this metaanalysis has been carried out. A meta-analysis of studies published until November 2011 without language restrictions, which analyzed the effect of the short polymorphisms of 5-HTTLPR in the cortisol response during a stress-inducing protocol was conducted. Published F or p genotype values were collected as estimators of the difference between groups as well as the sign of this difference for analysis. The global meta-analysis showed no significant association between the presence of the short allele and a different response to psychosocial stress. After comparing the subgroups of studies where participants underwent an emotionally neutral intervention versus an emotionally negative intervention, significant differences were found. The subgroup of studies where patients underwent an emotionally negative intervention showed a significantly greater cortisol release by those individuals carrying the short allele. This association was not seen in the neutral subgroup.

Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a different response to fasting, we investigated the effects of preoperative fasting on renal IRI in aged-overweight male and female mice. Male and female F1-FVB/C57BL6-hybrid mice, average age 73 weeks weighing 47.2 grams, were randomized to preoperative ad libitum feeding or 3 days fasting, followed by renal IRI. Body weight, kidney function and survival of the animals were monitored until day 28 postoperatively. Kidney histopathology was scored for all animals and gene expression profiles after fasting were analyzed in kidneys of young and aged male mice. Preoperative fasting significantly improved survival after renal IRI in both sexes compared with normal fed mice. Fasted groups had a better kidney function shown by lower serum urea levels after renal IRI. Histopathology showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. A mRNA analysis indicated the involvement of metabolic processes including fatty acid oxidation and retinol metabolism, and the NRF2-mediated stress response. Similar to young-lean, healthy male mice, preoperative fasting protects against renal IRI in aged-overweight mice of both genders. These findings suggest a general protective response of fasting against renal IRI regardless of age, gender, body weight and genetic background. Therefore, fasting could be a non-invasive intervention inducing increased oxidative stress resistance in older and overweight patients as well. © 2014 Jongbloed et al.

An overview of the present knowledge of the family Stenasellidae (Asellota; Aselloidea) is presented, focusing on the success of recent investigations of the underground waters of Oman (S.E. Arabian Peninsula). We take up the discovery of four new species of the genus Stenasellus: small species adapted to interstitial biotopes and larger ones typical of karstic aquifers. These species cohabit in ecotones between interstitial and karstic water systems. The putative presence of stenasellids in hypogean waters of Yemen and South Iran is suggested. The taxonomic status of the genus Stenasellus auct. needs to be reconsidered in the future. A scenario to explain the origin and the presence of these isopods in continental underground waters is advanced.

El objetivo general de este trabajo de Tesis Doctoral es evaluar los efectos de dietas ricas en diferentes tipos de ácidos grasos (saturados, poli-insaturados omega 6 y omega 3) sobre el transcriptoma de grasa abdominal, hígado y músculo esquelético en pollos de engorde mediante el uso de GeneChip microarrays. En concreto se investiga que genes y vías metabólicas, de las conocidas hasta el momento, se ven afectadas en el pollo de carne al ingerir raciones con distinto grado de insaturación y se comprueba si los cambios en la expresión de determinados genes y vías metabólicas, descritos en experimentos previos, también se observan mediante el uso de GeneChip microarrays. En una segunda fase, se estudia la evolución con la edad del pollo del nivel de expresión de diferentes genes seleccionados a partir de los resultados obtenidos del experimento anterior y de la bibliografía existente en esta área para pollos de carne. Se diseñó un ensayo con pollos de carne alimentados con 4 piensos experimentales, una dieta baja en grasa (0,5% de grasa añadida) y 3 raciones suplementadas con 10% de diferentes grasas: sebo, como fuente de AGS de cadena larga, aceite n-3 (70% aceite de linaza + 30% aceite de pescado) rico en AGPI n-3 y aceite de girasol, rico en AGPI n-6. Dentro de este ensayo se desarrollaron dos estudios en paralelo. Uno para estudiar las variaciones producidas por las dietas experimentales en el transcriptoma de la grasa abdominal, el hígado y el músculo esquelético de pollos de carne de 50 días. Otro para estudiar la evolución en el tiempo de la expresión de genes seleccionados. Para ello se tomaron muestras de estos mismos tejidos (grasa abdominal, hígado y músculo) a lo largo del crecimiento de los pollos, tras 0, 10, 21, 35 y 45 días de administración de los piensos experimentales. Los piensos experimentales se suministraron a los animales desde el día 14 de vida. Cambios fenotípicos. Los rendimientos productivos de los animales se registraron como una comprobación previa de que se producían los cambios fenotípicos esperados. Así, efectivamente, los animales alimentados con la dieta rica en ácidos grasos omega-3 presentaron un menor depósito de grasa abdominal comparados con aquellos alimentados con dietas ricas en ácidos grasos saturados. Los cambios en la composición de los diferentes tejidos también fueron los esperados con composiciones que reflejaban los perfiles de ácidos grasos de las dietas. Los animales alimentados con dietas bajas en grasa, y con menor contenido en energía, tal y como se había comprobado en experimentos previos, presentaron rendimientos completamente diferentes al resto de grupos. Estudio del transcriptoma. La dieta rica en ácidos grasos poli-insaturados omega-3 fue la que indujo mayores cambios en los transcriptomas estudiados, sobretodo en el caso de grasa abdominal y músculo esquelético. En el caso de la grasa abdominal la dieta rica en ácidos grasos poli-insaturados omega-3 produjo cambios respecto a todas las otras dietas y, sobre todo, con variaciones en vías metabólicas poco específicas o relacionadas con la metabolización de diferentes moléculas. En el caso del músculo las diferencias de expresión se encontraron fundamentalmente entre la dieta rica en ácidos grasos poli-insaturados omega-3 en comparación con la dieta rica en ácidos grasos saturados, y la mayoría de las vías afectadas estaban relacionadas con el sistema inmune. Estudio de genes seleccionados. En este estudio se seleccionaron genes de interés según los resultados obtenidos en el estudio del transcriptoma y la bibliografía disponible. No todos los genes seleccionados mostraron cambios en respuesta a las diferentes dietas o al tiempo de consumo de estas. Los genes ITGB2, FABP7, LIPA, GSTA3, LITAF mostraron diferencias en su expresión en grasa abdominal entre los pollos alimentados con la dieta rica en ácidos grasos insaturados omega-3 y los alimentados con omega-6 o saturados. El gen CYP2C18 mostró mayores niveles de expresión en hígado en animales alimentados dietas ricas en ácidos grasos poli-insaturados n-3 y n-6 en comparación con aquellos alimentados con saturados. Los genes CLU y ITGB2 en grasa abdominal, CYP2C18, PCK1, PPARa, PPARg y FASN en hígado y ITGB2 y FABP4 en músculo mostraron cambios en su expresión con la edad del animal. De estos estudios podemos concluir que el transcriptoma de la grasa abdominal es mucho más sensible a cambios en la composición de la grasa de la dieta que el transcriptoma del hígado o del músculo esquelético. Además, dietas ricas en ácidos grasos poli-insaturados omega-3 producen transcriptomas muy diferentes a aquellos producidos por dietas ricas en ácidos grasos omega-6, saturados o incluso por dietas bajas en grasa en la grasa abdominal y el músculo esquelético. Los genes que presentaron cambios debido a las dietas o a la edad identificados en el presente trabajo, están principalmente relacionados con la metabolización de lípidos y otras moléculas y con la respuesta inmune, y son de interés para futuros estudios en pollos de engorde relacionados con el metabolismo lipídico o el desarrollo de los animales., The general aim of this PhD thesis is to assess the effects that diets rich in different fatty acid families (saturated, poly-unsaturated omega-6, or omega-3) have on the transcriptome of adipose tissue, liver, and skeletical muscle in broiler chickens, using GeneChip microarrays. In particular, this work wants to describe differences in gene/pathway expression in broiler chickens fed diets differing in their unsaturation degree, and want to verify those differences in genes/pathways expression previously described in literature. In a second part of this PhD Thesis, we describe the time-evolution of the expression of genes selected from those found important in the microarray data and in literature on broiler chickens. In this work, broiler chickens were fed 4 different experimental diets, a low-fat diet (0.5% added fat) and 3 diets supplemented with 10% of three different fats: tallow, rich in saturated fatty acids, a mixture of n3 oils (70% linseed oil + 30% fih oil) rich in poly-unsaturated omega-3 fatty acids, and sunflower oil rich in poly-unsaturated omega-6 fatty acids. This work includes two experiments that were developed parallel in time. First experiment studies the effects of the experimental diets on transcriptomes of abdominal fat, liver, and skeletical muscle in 50 days old broiler chicken; second experiment describes time-evolution of the expression of selected genes depending on the diets. Abdominal fat, liver, and skeletical muscle were sampled in broiler chickens on days 0, 10, 21, 35, and 45 after experimental feeds were introduced to the animals on day 14 of age. Phenotype changes. Productive performance was registered as a pre-requisite before we could proceed to run microarray analysis. Chickens fed the diet rich in poly-unsaturated omega-3 fatty acids showed lower deposition of abdominal compared to those fed the diet rich in saturated fatty acids. The different studied tissues also showed the expected changes in composition mimicking fatty acid profile of the respective diets. Broiler chickens fed low fat diet, and so with lower energy levels, showed productive performance records completely different to all other treatments, as expected. Study of transcriptome. Diet rich in poly-unsaturated omega-3 fatty acids induced most of the important observed changes in expression, especially in abdominal fat and skeletical muscle. For abdominal fat, diet rich in poly-unsaturated omega-3 fatty acids induced changes compared to all other diets, affecting several unspecific pathways related to metabolism of different molecules. For skeletical muscle, differential expression was mainly found between the diet rich in poly-unsaturated omega-3 fatty acids and diet rich in saturated fatty acids. Most of the pathways affected in this case were related to immune response. Study of selected genes. A group of genes were selected based on results obtained from the microarray experiment and previous results available on literature. Not all selected genes were differentially expressed among diets or time points. Genes ITGB2, FABP7, LIPA, GSTA3, LITAF showed differences on expression in abdominal fat of broiler chickens fed the diet rich in poly-unsaturated omega-3 fatty acids compared to those fed diets rich in poly-unsaturated omega-6 or saturated fatty acids. Gene CYP2C18 showed increased expression levels in liver of broiler chickens fed diets rich in poly-unsaturated omega-3 or omega-6 fatty acids compared to those fed saturated fatty acids. Genes CLU and ITGB2, in abdominal fat, genes CYP2C18, PCK1, PPARa, PPARg and FASN in liver and genes ITGB2 and FABP4 in skeletical muscle were affected by the age of the broiler chicken. As conclusions, we can say the transcriptome of the adipose tissue is more sensible to changes in the composition of the fat included in the diet than liver or muscle transcriptomes. Moreover, diets rich in poly-unsaturated omega-3 fatty acids resulted in very different transcriptomes when compared to diets rich in saturated or poly-unsaturated omega-6 fatty acids, or even when compared to low fat diet. Genes differencialy expressed among diets or sampling days were mainly related to metabolism of different molecules and to immune response. These are genes of interest for future studies related to lipid metabolism or development in broiler chickens.

Introducción: Los probióticos son conocidos como microrganismos vivos, que favorecen el equilibrio microbiano en el tracto gastrointestinal, sus metabolitos (ácidos orgánicos, ácido láctico, entre otros) inhiben el crecimiento de patógenos, a nivel de sistema inmune activan la respuesta humoral (IL 2) y activan la fagocitosis. Diferentes estudios han demostrado que la utilización de probióticos en el sector avícola como suplemento, relegaría el uso de antibióticos, puesto que la utilización de los mismos, ha generado casos de resistencia bacteriana, afectando al consumidor final y convirtiéndose en un problema de salud pública. El uso de probióticos según la FAO, encaminaría en estrategias de mejoramiento global del rendimiento y bienestar animal en países en desarrollo. Objetivo: Identificar fenotípicamente el comportamiento de las cepas Enterorococcus faecium, Enterococcus faecalis aisladas del intestino de pollo de engorde y gallina comercial (Gallus gallus) frente a antibacterianos. Metodología: estudio descriptivo de corte transversal. Se tomaron muestras del mucus intestinal de las aves (íleon, yeyuno y duodeno) aisladas en medio MRS el cual permite evidenciar el crecimiento de bacterias ácido lácticas, se realizaron pruebas microbiológicas y bioquímicas utilizando el sistema semiautomatizado Crystal para Gram positivos (BBLTM CrystalTM Gram-PositiveID Kit) posteriormente estas cepas fueron evaluadas en algunas características como potenciales probióticos: resistencia a pH bajo, concentraciones biliares de 0.1% a 0.3%, producción de hemolisinas, prueba de antagonismo; posteriormente se evaluó un factor de virulencia, la presencia de genes de resistencia a ciertos antibióticos; se realizó la caracterización fenotípica mediante difusión en disco Kirby Bauer , para evaluar la resistencia y/o sensibilidad, se seleccionaron los antibióticos de las familias Glicopetidos (Vancomicina), Inh folato (Trimetropim sulfa), Betalactamicos (Ampicilina),Fenicol (Cloramfenicol y Florfenicol) Fluroquinolonas (Ciprofloxacina) del laboratorio Oxoid. Resultados: para el caso de las cepas de E. faecium 94,1% muestran sensibildad frente a glucopeptidos (Vancomicina), 95% a inhibidores de folato (Trimetropim sulfa),76% a fenicol(Clorafenicol), 100% a los Betalactamicos (ampicilina), 19% a Fluoroquinolonas (Ciprofloxacina) y un 95% a Fenicol ( Florfenicol). Se obtuvo una resistencia de 5 % para Trimetropim sulfa, 19% para Clorafenicol, 52,3% a la Ciprofloxacina, para E. faecalis se observó una sensibilidad del 100% frente a los antibióticos usados, excepto para la Ciprofloxacina un 50% de cepas sensibles. Conclusiones: Tres cepas de Enterococcus cumplen con los criterios de cepas seguras como potenciales probióticos. Posteriormente se determinará presencia y/ o ausencia del gen Van A mediante pruebas moleculares.

Made available in DSpace on 2016-08-29T15:08:50Z (GMT). No. of bitstreams: 1 tese_5602_Dissertação Lorena Gonçalves.pdf: 5279865 bytes, checksum: 9aa8e3d3f38b0ce2b85dfc6416018ab5 (MD5) Previous issue date: 2012-04-05 Depoimento é um gênero do site de relacionamentos Orkut em que a interação entre os participantes constitui-se a partir de um fator em comum: o dono do perfil. Este é tomado como objeto de discurso do depoente e (re)categorizado de forma que o efeito da construção textual desse gênero corporifique a elaboração de face tanto do dono do perfil, quanto do amigo que cria o depoimento. A partir desse pressuposto, nesta pesquisa, tratamos da relação entre a (re)categorização de objeto de discurso e a construção de imagem social em depoimentos de Orkut. Nesse contexto, a categorização é entendida como um importante elemento da linguagem, que contribui com a representação da imagem social. Para entender questões relacionadas à imagem pública, nos apoiamos em teorias pragmáticas que desenvolvem esse tema a partir da noção de face e polidez linguística; autores fundamentais para nós são Goffman (1980, 1992), Lakoff (1973, 1975), Leech (1983) e Brown & Levinson (1975), que desenvolvem suas teorias em um viés considerado tradicional, pois centram sua atenção na intenção do falante, que almeja sempre salvar sua face, a partir do uso de atos de polidez. Na esteira desse estudo, para entender questões relacionadas à referenciação e à construção de objeto de discurso, damos enfoque a autores que contribuíram de forma memorável aos estudos da linguística textual, são eles: Mondada & Dubois (2003), Koch (2004, 2005b, 2008a, 2008b), Marcuschi (2007, 2008) e Cavalcante (2011). A partir da interface desses dois campos de estudo, propomos a análise da construção de face positiva em depoimentos de Orkut, os quais foram divididos em 3 categorias: Elogio, Rememorações e Agradecimento.