Un Mateix camí amb dreceres diferents en funció del sexe: gametogènesi femenina

En humans, les aneuploïdies s'originen principalment a causa d'errors en la gametogènesi femenina. Aquest fenomen fa de l'oogènesi un tema d'estudi atractiu, tot i que per la dificultat que comporta l'obtenció de mostres no existeixen molts estudis al respecte. En aquest treball, es resumeix l'estat actual del problema, i es para especial atenció a les diferències existents entre la gametogènesi masculina i femenina que puguin explicar l'origen d'aquest important problema per a la societat actual.In humans, aneuploidy is mainly originated by errors produced during female gametogenesis. This phenomenon makes oogenesis such an attractive research topic, but due to the difficulties involving sample collection, not many studies have been performed in human oocytes. In this paper, a summary of the current knowledge about human female meiosis is provided, specially focusing on the differences between male and female gametogenesis that may explain the origin of such an important topic for Western society

Turvapaikkatutkinnan sanasto

Sanglakhi, Fahima. Turvapaikkatutkinnan sanasto, suomi-persia-englanti. Helsinki, kevät 2015, 37 s., liitteitä 1. Diakonia-ammattikorkeakoulu, Diak Etelä. Asioimistulkkauksen koulutusohjelma, Tulkki (AMK) Kaksikielisten sanastojen puutteen vuoksi, varsinkin kieliparilla suomi-persia, tunsin tarvetta sanaston laatimiseen. Opinnäytetyö on kehittämispainotteinen eli toiminnallinen, jonka tuloksena syntyy uusi tuote. Tämän opinnäytetyön tavoitteena oli tehdä suppea turvapaikkatutkinnan sanasto työkielissä suomi-persia-englanti. Sanasto voi auttaa persian- ja darinkielistä tulkkia valmistautumisessa toimeksiantoihin. Uudistetun asioimistulkkien ammattisäännöstön viidennen kohdan mukaan valmistautumisella tarkoitetaan sitä, että tulkin on perehdyttävä tulkkausaiheeseen ja sen edellyttämään sanastoon ja terminologiaan molemmilla työkielillä. Opinnäytetyön tarkoitus oli helpottaa persian ja darin kielen tulkkien työtä turvapaik-katutkinnassa ja auttaa heitä välittämään viestiä paremmin vaikeista termeistä huolimatta. Opinnäytetyössä aineistona on käytetty Suomen maahanmuuttoviraston kotisivuilla olevaa sanastoa ja pakolaisneuvonnan ja maahanmuuttoviraston yhteistyössä julkistamaa Opas tulkeille -kirjan sanastoa. Sanastoa laadin ensin keräämällä suomenkielisiä termejä ja myöhemmin etsimällä niiden vastineita persiaksi ja englanniksi. Aineisto koostu 157 suomenkielisestä termistä ja niiden vastineista persian ja englannin kielellä. Sanastosta on hyötyä tulkeille, kääntäjille ja opiskelijoille, jotka työskentelevät maahanmuuttoalalla tai ovat muutenkin kiinnostuneita tästä aiheesta. Asiasanat: sanastotyö, persian kieli, suomen kieli, sanastot, maahanmuutto, turvapaikanhakijat, asioimistulkkausSanglakhi, Fahima. Asylum investigation glossary in Finnish, Persian and English. Helsinki, spring 2015, p 37, 1 appendix Diaconia University of Applied Sciences, Diak South. Degree Programme in Community Interpreting, Degree: Interpreter Due to the lack of multilingual glossaries especially in the language pairs of Finnish- Persian, it was necessary to draft a glossary in the field of migration. Aim of this thesis was to make a concise asylum investigation glossary in language pairs of Finnish-Persian-English, which could help Persian and Dari language interpreters in preparing for their assignments. The purpose of this thesis was to facilitate Persian and Dari language interpreters' work in asylum investigation field and help them to forward the messages better, despite the tough terms. The thesis material consisted of glossary of Finnish immigration website and glossary of Interpretation in the asylum processes which were published by collaboration of the Finnish Immigration and Refugee advice centre. I found 157 terms. The glossary was compiled first by collecting Finnish terms and later looking for their equivalents in Persian and English. A glossary is useful for all Persian and Dari language interpreters, translators and students who work and study in the field of immigration or are otherwise interested in this topic

Pairing and recombination features during meiosis in Cebus paraguayanus (Primates: Platyrrhini)

Background: Among neotropical Primates, the Cai monkey Cebus paraguayanus (CPA) presents long, conserved chromosome syntenies with the human karyotype (HSA) as well as numerous C+ blocks in different chromosome pairs. In this study, immunofluorescence (IF) against two proteins of the Synaptonemal Complex (SC), namely REC8 and SYCP1, two recombination protein markers (RPA and MLH1), and one protein involved in the pachytene checkpoint machinery (BRCA1) was performed in CPA spermatocytes in order to analyze chromosome meiotic behavior in detail. Results: Although in the vast majority of pachytene cells all autosomes were paired and synapsed, in a small number of nuclei the heterochromatic C-positive terminal region of bivalent 11 remained unpaired. The analysis of 75 CPA cells at pachytene revealed a mean of 43.22 MLH1 foci per nucleus and 1.07 MLH1 foci in each CPA bivalent 11, always positioned in the region homologous to HSA chromosome 21. Conclusion: Our results suggest that C blocks undergo delayed pairing and synapsis, although they do not interfere with the general progress of pairing and synapsis

ATR is required to complete meiotic recombination in mice

Precise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination.We thank M. A. Handel (The Jackson Laboratory, Bar Harbor, USA) for the anti-H1T antibody; E. Marcon for the anti-RPA antibody (University of Toronto, Canada); A. Toth for the anti-pHORMAD2 antibody (U. Dresden, Germany) and N. Hunter for the anti- RNF212 antibody (UC Davis, USA); J. Turner (National Institute for Medical Research,London, UK) for assistance in the RNA-FISH experiments, for the X chromosome probe,for providing AtrFL/−testis samples and for sharing unpublished data; L. Kauppi(University of Helsinki, Finland) for providing us with protocols for the testis cultures;and members of the Roig lab and the Spanish Ministerio de Ciencia e Innovación-funded Network of Spanish groups working on Meiosis (MeioNet, BFU201‐71786‐REDT) and Enrique Martínez Pérez (Imperial College, London, UK) for helpful discussions. M.M.O. was supported by a FPI fellowship from the Ministerio de Ciencia e Innovación (BES-2011-045381). J.L. was supported in part by American Cancer Society post-doctoral fellowship (PF-12-157-01-DMC). S.K. is an Investigator of the Howard Hughes Medical Institute. This work was supported by the Ministerio de Ciencia e Innovación (BFU2010-18965, BFU2013-43965-P and BFU2016-80370-P, I.R.), by the UAB-Aposta award to young investigators (APOSTA2011-03, I.R.) and by the NIH (R35 GM118175, to M.J.and R35 GM118092 to S.K.).S

European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

The 2017 European LeukemiaNet (ELN 2017) guidelines for the diagnosis and management of acute myeloid leukemia (AML) have become fundamental guidelines to assess the prognosis and postremission therapy of patients. However, they have been retrospectively validated in few studies with patients included in different treatment protocols. We analyzed 861 patients included in the Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, whereas it recommends allogeneic stem cell transplantation (alloSCT) as a postremission strategy for the ELN 2017 intermediateand adverse-risk groups. We retrospectively classified patients according to the ELN 2017, with 327 (48%), 109 (16%), and 245 (36%) patients allocated to the favorable-, intermediate-, and adverse-risk group, respectively. The 2- and 5-year overall survival (OS) rates were 77% and 70% for favorable-risk patients, 52% and 46% for intermediate-risk patients, and 33% and 23% for adverse-risk patients, respectively. Furthermore, we identified a subgroup of patients within the adverse group (inv(3)/t(3;3), complex karyotype, and/or TP53 mutation/17p abnormality) with a particularly poor outcome, with a 2-year OS of 15%. Our study validates the ELN 2017 risk stratification in a large cohort of patients treated with an ELN-2017 risk-adapted protocol based on alloSCT after remission for nonfavorable ELN subgroups and identifies a genetic subset with a very poor outcome that warrants investigation of novel strategies

Genome-wide association study of germline variants and breast cancer-specific mortality.

BackgroundWe examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.MethodsMeta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).ResultsWe did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.ConclusionsWe uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4

Genome-wide association study of germline variants and breast cancer-specific mortality

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers