Slovenščina Janes: pogovorna, nestandardna, spletna ali spretna?

V sklopu konference Slovenščina na spletu in v novih medijih je 27. novembra 2015 v dvorani Zemljepisnega muzeja GIAM ZRC SAZU potekala okrogla miza z naslovom Slovenščina Janes: pogovorna, nestandardna, spletna ali spretna? K razpravi je bilo povabljenih pet strokovnjakov in strokovnjakinj s področja slovenskega jezikoslovja: dr. Helena Dobrovoljc (Inštitut za slovenski jezik Frana Ramovša ZRC SAZU in Fakulteta za humanistiko UNG), dr. Polona Gantar (Filozofska fakulteta UL), dr. Simon Krek (Inštitut Jožef Stefan, Filozofska fakulteta UL in Fakulteta za družbene vede UL), dr. Damjan Popič (Filozofska fakulteta UL) in dr. Marko Stabej (Filozofska fakulteta UL). Razpravo sem moderirala dr. Špela Arhar Holdt (Zavod za uporabno slovenistiko Trojina in Filozofska fakulteta UL). Povod za okroglo mizo so bile terminološke zadrege, zaznane pri poskusu poimenovanja jezika v korpusu Janes,[1] vendar so slednje zelo hitro razkrile širok spekter kompleksnih vzrokov. Vprašanje opredelitve »slovenščine Janes« se tako zastavlja kot rezultat sprememb v načinu človeške komunikacije, po katerih opredelitve in pojmi obstoječe slovenske (in ne le slovenske) zvrstnostne teorije izgubljajo uporabno vrednost. Je mogoče po pojavu spleta in razvoju različnih zvrsti računalniško posredovane komunikacije še govoriti o javnem in zasebnem, formalnem in neformalnem, knjižnem in pogovornem? Še več, so te kategorije v praksi – v šoli in izven nje – sploh kdaj funkcionirale? Debata se je dotaknila vprašanja, kako naj se jezikoslovje na spremembe v jezikovni rabi odzove: moramo zagotoviti predvsem novo zvrstnostno teorijo ali je potrebna tudi sprememba v odnosu do jezikovnih uporabnikov, slovenistične metodologije, izdelkov in storitev, ki jih jezikovna skupnost od nas pričakuje, jezika samega? In kakšna je v sliki sodobnih jezikoslovnih raziskav in projektov vloga gradiva Janes, kje so glavne možnosti in kaj omejitve? Na začetku debate je imel vsak od panelistov nekaj minut za predstavitev izhodiščnega mnenja, sledile so replike in na koncu še vprašanja oz. mnenja udeležencev. Zapis izjav je bil pripravljen po zvočnem posnetku, pri čemer so bile izjave za namene lažjega branja skladenjsko prilagojene značilnostim pisnega jezika, nato pa so avtorji posredovali še nekaj dodatnih pojasnil glede svojih prispevkov. Zapis začenjamo s predstavitvijo prvega panelista. [1] Gre za korpus računalniško posredovane komunikacije, ki zajema besedila tvitov, blogov, uporabniških komentarjev in forumov. Korpus predstavlja prispevek (Erjavec in dr. 2015), projektna stran pa je: http://nl.ijs.si/janes/

Nova slovnica: kje smo in kam gremo

6. junija 2018 je na Inštitutu Jožef Stefan potekal dogodek, na katerem so bili javnosti predstavljeni cilji in prvi rezultati projekta Nova slovnica sodobne standardne slovenščine: viri in metode (ARRS J6-8256). Namen projekta je razviti jezikoslovno metodologijo za računalniško podprto analizo sodobne slovenščine, kakršna je zajeta v referenčnih besedilnih korpusih slovenskega jezika. Z novo metodologijo bodo pripravljene baze jezikovnih podatkov, ki bodo po koncu projekta skupnosti odprto na voljo za raziskave, gradnjo jezikovnih priročnikov ter učnih gradiv, razvoj jezikovnotehnoloških orodij ipd. Omenjeno projektno financiranje izdelave nove slovnice sicer ne pokriva, vendar že priprava podatkovnih baz zahteva premisleke o trenutnih prioritetah slovenskega prostora. Sodobni slovnični opis je brez dvoma med cilji za prihodnost, ni pa še v konsenza, kako naj bo oblikovan, da bo odgovoril na (različne) potrebe sodobne družbe. Da odpremo razpravo, smo na projektnem dogodku organizirali strokovni posvet, opredeljen z naslednjimi vprašanji: kdo so deležniki, ki bi lahko projektne rezultate uporabljali; na kaj moramo pri pripravi paziti, da bodo podatki optimalno uporabni; kakšno oz. katero slovnico potrebujemo najprej; katere so metodološke in logistične premise njene priprave; kje je trenutno slovensko slovničarstvo in kakšen razvoj si lahko obetamo; kakšne so potrebe po slovničnih podatkih pri različnih uporabniških skupinah ter kaj bi trenutne vrzeli najbolje naslovilo

ZSWIM7 Is associated with human female meiosis and familial primary ovarian insufficiency

Background Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. A genetic cause for POI can be found in up to 30% of women, elucidating key roles for these genes in human ovary development. Objective We aimed to identify the genetic mechanism underlying early-onset POI in 2 sisters from a consanguineous pedigree. Methods Genome sequencing and variant filtering using an autosomal recessive model was performed in the 2 affected sisters and their unaffected family members. Quantitative reverse transcriptase PCR (qRT-PCR) and RNA sequencing were used to study the expression of key genes at critical stages of human fetal gonad development (Carnegie Stage 22/23, 9 weeks post conception (wpc), 11 wpc, 15/16 wpc, 19/20 wpc) and in adult tissue. Results Only 1 homozygous variant cosegregating with the POI phenotype was found: a single nucleotide substitution in zinc finger SWIM-type containing 7 (ZSWIM7), NM_001042697.2: c.173C > G; resulting in predicted loss-of-function p.(Ser58*). qRT-PCR demonstrated higher expression of ZSWIM7 in the 15/16 wpc ovary compared with testis, corresponding to peak meiosis in the fetal ovary. RNA sequencing of fetal gonad samples showed that ZSWIM7 has a similar temporal expression profile in the developing ovary to other homologous recombination genes. Main conclusions Disruption of ZSWIM7 is associated with POI in humans. ZSWIM7 is likely to be important for human homologous recombination; these findings expand the range of genes associated with POI in women

Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency

Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical and psychosocial sequelae. Approximately 10% of POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development and function. Recently, Ythdc2, an RNA helicase and N6-methyladenosine reader, has emerged as a regulator of meiosis in mice. Here, we describe homozygous pathogenic variants in YTHDC2 in 3 women with early-onset POI from 2 families: C. 2567C>G, p.P856R in the helicase-associated (HA2) domain and c.1129G>T, p.E377*. We demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosisassociated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377*variant truncated the helicase core. Taken together, our results reveal that YTHDC2 is a key regulator of meiosis in humans and pathogenic variants within this gene are associated with POI

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects’ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis

STAG3 truncating variant as the cause of primary ovarian insufficiency

Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI

Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency

Purpose We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. Methods We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. Results We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke’s pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. Conclusion Our findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function

Molecular genetics of dilated cardiomyopathy in the Dobermann dog

Canine dilated cardiomyopathy (DCM) is a disease of the myocardium associated with dilatation and impaired contraction of the ventricles. It primarily affects large and giant breed dogs with Dobermanns being one of the most frequently affected. The high prevalence of DCM in specific breeds suggests a genetic background, but causal mutations have not yet been identified. The main objective of the study described in this thesis was to identify the gene(s) involved in DCM in the Dobermann. For that purpose, the genes of interest were evaluated. Due to close similarities in human and canine DCM, mutated genes identified to cause DCM in the human are good candidate genes for DCM in dogs. At the outset of the DCM research project in 2001, most of the DCM candidate genes had not yet been mapped and the dog genome resources were limited. Therefore, bacterial artificial chromosome (BAC) clones carrying the genes of interest were isolated from the canine BAC library. Microsatellite markers isolated from the BAC clones were typed in the Dobermanns and evaluated for association with the DCM phenotype. While the genes encoding desmin, phospholamban, ?-tropomyosin and ?-sarcoglycan were excluded as DCM causing genes, the genotyping results of the titin markers point to a crucial role of titin in DCM susceptibility. The genetic markers and sequencing oligonucleotide primers reported in this thesis are tools that will enable fast evaluation of the DCM candidate genes in breeds other than the Dobermann. Further research into the role of the titin in canine DCM will also lead to better understanding of cardiomyocyte physiology and pathophysiology of DCM

Odziv na “Anketo o slovenščini” projekta Jezikovna politika Republike Slovenije in potrebe uporabnikov

Odziv na “Anketo o slovenščini” projekta Jezikovna politika Republike Slovenije in potrebe uporabniko