Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

BACKGROUND: The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. METHODS: We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. RESULTS: Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. CONCLUSION: In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity

Effects of GLP-1 Receptor Polymorphisms on Adolescent Obesity

Obesity is becoming a concerning disease in developing countries. Like other multifactorial diseases, genetics plays a substantial role in the development of this disease. We tried to investigate genetic variations (mutation/polymorphism) of GLP-1R gene in children diagnosed with obesity and to identify their possible connections with obesity and other conditions. Genomic DNA was extracted from 162 overweight/obese patients and 100 controls. Later, full exon sequencing and association studies were carried out. Three polymorphisms and one mutation were detected in the fourth and fifth exons of the GLP-1R gene. Some variations were detected in three cases from which 1/3 had non-alcoholic fatty liver disease (NAFLD) but none showed insulin resistance (IR). There were also statistically meaningful results for ‘Odds Ratio’ among different genotypes and allele frequencies in groups with NAFLD and/or IR. In addition, there was an increase in risk for NAFLD and a decrease in risk for IR. In the homozygous group, also the prospect of IR was double declined. Patients with the A allele of this polymorphism showed a drop in risk for IR as well. GLP-1R polymorphisms could influence obesity and diabetes and thus the functional analysis of the GLP-1R polymorphisms is benevolent

A Large-Scale Study of Machine Translation in Turkic Languages

Recent advances in neural machine translation (NMT) have pushed the quality of machine translation systems to the point where they are becoming widely adopted to build competitive systems. However, there is still a large number of languages that are yet to reap the benefits of NMT. In this paper, we provide the first large-scale case study of the practical application of MT in the Turkic language family in order to realize the gains of NMT for Turkic languages under high-resource to extremely low-resource scenarios. In addition to presenting an extensive analysis that identifies the bottlenecks towards building competitive systems to ameliorate data scarcity, our study has several key contributions, including, i) a large parallel corpus covering 22 Turkic languages consisting of common public datasets in combination with new datasets of approximately 1.4 million parallel sentences, ii) bilingual baselines for 26 language pairs, iii) novel high-quality test sets in three different translation domains and iv) human evaluation scores. All models, scripts, and data will be released to the public.Peer reviewe

The Multilingual Picture Database

Publisher Copyright: © 2022, The Author(s).The growing interdisciplinary research field of psycholinguistics is in constant need of new and up-to-date tools which will allow researchers to answer complex questions, but also expand on languages other than English, which dominates the field. One type of such tools are picture datasets which provide naming norms for everyday objects. However, existing databases tend to be small in terms of the number of items they include, and have also been normed in a limited number of languages, despite the recent boom in multilingualism research. In this paper we present the Multilingual Picture (Multipic) database, containing naming norms and familiarity scores for 500 coloured pictures, in thirty-two languages or language varieties from around the world. The data was validated with standard methods that have been used for existing picture datasets. This is the first dataset to provide naming norms, and translation equivalents, for such a variety of languages; as such, it will be of particular value to psycholinguists and other interested researchers. The dataset has been made freely available.Peer reviewe

Türkçede anlam belirsizliği barındıran biçimbirimlerin işlemlenmesi.

Studies investigating the processing of linguistic ambiguity have to date mostly focused on lexical ambiguity. Morphemic ambiguity, on the other hand, has been less frequently studied in spite of its cross-linguistic prevalence. An intermediate level of representation (i.e. the lemma level) between form and meaning has been claimed to successfully account for the processing of ambiguous morphemes in English and Chinese. Moreover, meaning frequency has been found to affect the processing of these morphemes. Dwelling on this background, this thesis investigated whether an intermediate level of representation could be used to explain the processing of morphemic ambiguity in derived homonymous words (i.e. yan, Eng., side or to burn, in yanıcı, Eng., flammable) in Turkish. The second aim was to examine whether the relative meaning frequencies of the ambiguous morphemes would modulate the processing of morphemic ambiguity in Turkish. A masked priming lexical decision task (SOA: 50 ms) designed with four prime types (i.e. dominant, subordinate, opaque, unrelated) and two target types (i.e. dominant and subordinate) was run with adult Turkish native speakers. The results showed that no significant morpho-semantic priming was obtained, and the effect of the meaning frequency was not significant, which could imply that no intermediate level of representation is necessary. However, a statistically non-significant trend in the data indicated a different pattern of processing for the dominant and the subordinate targets, which could still be explained by an intermediate level of representation and the effect of the meaning frequency.Thesis (M.S.) -- Graduate School of Social Sciences. English literature

Düşük materyallerinde matriks metalloproteinaz 2 ve 9 gen polimorfizmlerinin araştırılması

Spontan abortus, gebeliğin 20. gebelik haftasından önce herhangi bir müdahale olmaksızın sonlanması olarak tanımlanır ve üreme çağındaki kadınların en yaygın problemlerinden biridir. Özellikle erken spontan abortusların etiyopatogenezinde %50-60 oranında kromozomal anormallikler tespit edilirken, olguların önemli bir kısmında herhangi bir sebep bulunamamaktadır. Matriks metallopreoteinazlar, ekstrasellüler matriks morfogenez ve gelişim esnasında gerekli olan hücresel çevre oluşumu için önemli makromoleküllerdir. MMP'ler pek çok normal biyolojik sürece (embriyonik gelişim, blastokist implantasyonu, organ morfogenezi, sinir büyümesi, ovülasyon, servikal dilatasyon, doğum sonrası uterus involüsyonu, endometrial siklus, saç folükülü döngüsü, kemik remodelingi, yara iyileşmesi, angiogenez apopitoz vb) ve patolojik sürece (artrit, kanser, kardiyovasküler hastalık, nefrit, nörolojik hastalık, kan-beyin bariyerinin yıkımı, periodontal hastalık, cilt ülserasyonu, gastrik ülser, korneal ülserasyon, karaciğer fibrozisi, amfizem, fibrotik akciğer hastalığı vb) katılır. Bu çalışmada, Ege Üniversitesi Tıp Fakültesi Hastanesi Kadın Hastalıkları ve Doğum Kliniği'nden, Tıbbi Genetik Anabilim Dalı'na gönderilen spontan abortus materyalleri arasından karyotipi normal saptanan 80 örnekte, etiyopatogenezden sorumlu olabileceğine dair önemli kanıtları bulunan MMP2 ve MMP9 genlerine ait fonksiyonel olduğu daha önce gösterilmiş -735 C>T, -1306 C>T ve -1562 C>T polimorfizmlerinin rolü araştırıldı. Kontrol grubu olarak sağlıklı 50 kadın ve 50 erkek çalışmaya alındı. -1306 C>T polimorfizminin, abortus örneklerinde kontrol grubuna göre riski arttırdığı saptandı. -735 C>T ve -1562 C>T polimorfizmlerinin ise abortus ve kontrol grubunda anlamlı bir farkı olmadığı, birleşik genotipler karşılaştırıldığında hepsinin abortus için riski arttırdığı gösterildi. Ancak, ileride yapılacak daha geniş kapsamlı çalışmalarla bu verilerin desteklenmesi gereklidir

Oral vocabulary and learning to read morphologically complex words: mechanisms of influence

It is well-established that there is a causal relationship between oral vocabulary and written word reading. However, it is not clear in what ways oral vocabulary facilitates reading and how morphological information interacts with this facilitation. This thesis aims to examine a cognitive mechanism recently proposed to explain the facilitatory role of oral vocabulary on reading and the potential role of morphology on the use of this cognitive mechanism.  Chapter I consists of a literature review in order to present an overview of the relevant evidence for oral vocabulary being causally associated with reading. Possible cognitive mechanisms are discussed. One such mechanism, the orthographic skeleton hypothesis, which is tested in the present study, is described in detail. The chapter further overviews the evidence on how readers use their morphological knowledge while reading and how orthographic skeletons could be linked with reading morphologically complex words. The type of morphological complexity (inflection and derivation) as well as their relevance to skeletons and reading in general are discussed.  Chapter II is an empirical investigation of the skeleton hypothesis for two types of morphologically complex novel words (inflected and derived) using a novel oral word learning paradigm, followed by one of two written tasks: self-paced reading or lexical recognition. The first aim was to test whether orthographic skeletons were formed for the stems (i.e., bases) of morphologically complex words upon oral training of these complex words, whereas the second aim was to investigate whether orthographic skeletons were formed independently of affix type. The main findings relate to lexical recognition and indicated that orthographic skeletons are built for the stems of complex words, and this is not dependent on the type of affix. Interactions between phonology, orthography and morphology during the process of reading new words are discussed. </p