Violeta Dimitrova

To assess the impact of prepregnancy body mass index (P-BMI) and family history (FH) of diabetes on the prevalence of gestational diabetes mellitus (GDM) a

Understanding how chromosome 21 gene dosage contributes to neurodevelopmental phenotypes in trisomy 21 (T21) remains a fundamental challenge. Here, we perform transcriptome-wide RNA-sequencing of fetal cortical and hippocampal tissues from T21 cases and euploid controls collected during mid-gestation, a critical window for human brain development. We identify widespread gene expression dysregulation with significant enrichment for chromosome 21 genes and perturbation of neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes is ADARB1, a chromosome 21-encoded RNA editing enzyme, whose overexpression associates with increased adenosine-to-inosine RNA editing, with consistent over-editing at functionally important recoding sites in glutamate and GABA receptor-related genes, including GRIK2, GRIA2, GRIA3, and GABRA3, across cortex and hippocampus. Meta-analyses across independent transcriptomic datasets validate robust chromosome 21 dosage effects, including ADARB1 overexpression and over-editing at 3′UTRs and GRIA3. These findings implicate dysregulated RNA editing as a post-transcriptional mechanism contributing to fetal neuropathology in T21.

Rare loss-of-function (LoF) mutations in SETD1A are associated with schizophrenia (SCZ). However, how SETD1A haploinsufficiency leads to SCZ-associated phenotypes and its relevance to patients without these rare mutations is unknown. Here, we identify SETD1A bound loci and regulated genes in human prenatal cortex and isogenic pluripotent stem cell-derived neuronal models engineered with SETD1A LoF variants, including the most common patient mutation. SETD1A preferentially binds the promoters of polygenic risk loci for psychiatric disorders that regulate chromatin remodeling, DNA repair, and synaptic function. Additionally, SETD1A binds to DNA damage-prone sites in neural progenitor cells and postmitotic neurons. SETD1A haploinsufficiency causes accelerated neurogenesis, reduced neuronal complexity, and DNA damage accumulation in postmitotic neurons that is rescued by inhibiting the H3K4me2/3 demethylase KDM5. In postmortem SCZ cortical tissue, individuals who lack SETD1A mutations exhibit reduced SETD1A expression, associated with downregulation of SETD1A-regulated genes, implicating SETD1A-H3K4me dysfunction in sporadic SCZ cases. We demonstrate that SETD1A functions as a convergent upstream modulator of a gene network that underlies polygenic risk for psychiatric disorders, which suggests that restoring the SETD1A-H3K4 methylation epigenetic imbalance may benefit a broad psychiatric population.

Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in tissue homeostasis and repair. The variety of functions makes γδ T cells a particularly interesting population during pregnancy. In this study, we investigated the proportion, phenotype and TCR γ and δ repertoires of γδ T cells at the maternal–fetal interface and in the blood of pregnant women using FACS, immunohistochemistry and spectratyping. We found an enrichment of activated and terminally differentiated pro-inflammatory γδ T-cell effectors with specific location in the human decidua during early pregnancy, while no significant changes in their counterparts in the blood of pregnant women were observed. Our spectratyping data revealed polyclonal CDR3 repertoires of the δ1, δ2 and δ3 chains and γ2, γ3, γ4 and γ5 chains and oligoclonal and highly restricted CDR3γ9 repertoire of γδ T cells in the decidua and blood of pregnant women. Early pregnancy induces recruitment of differentiated pro-inflammatory γδ T-cell effectors with diverse TCR repertoires at the maternal–fetal interface.

While implementing the radical transformations, such as the business processes reengineering in the work of industrial enterprises, there is a need to increase the personnel operating efficiency in the business processes redesign. The urgent increase of control by the top management of companies is demanded for observing the procedure and standards of business processes reengineering at the enterprises in order to increase its cost effectiveness. Therefore, the relevance of the scientific research subject is indisputable. The research works of academic economists concerning the features of staffing for the business processes reengineering of companies are analyzed. The ways to overcome the resistance to organizational changes of industrial enterprises by the staff are developed. The description of the effective members of the reengineering team in the work of the company has been improved by forming special features of each member of the reengineering team. The personal and professional competencies of the personnel are shaped and offered as the most effective ones for successful realization of marketing activity reengineering at the industrial enterprises. A questionnaire was developed as part of the analysis and selection of personnel during the marketing activities reengineering at the industrial enterprises. The resulting component of the questionnaire was developed for making managerial decision on personnel selection in reengineering teams.

Congenital anomalies affect 1% to 2% of the newborns. The urinary tract and the kidneys are involved in 4-5% of the cases while upper-extremities abnormalities are present in 10%. Certain anomalies occur in isolation, whereas others are associated with systemic conditions. The prenatal detection of fetal anomalies compatible with life is a challenge for both the parents and the physician. The prognosis for the fetus/newborn and the reproductive decisions of the family largely depend on the causes underlying the disease. The reported case is of a G2P1 pregnant woman referred for routine ultrasound scan at 24 weeks of gestation (w.g.). The fetus had growth retardation, right kidney agenesis, bilateral absence of radial bones and thumbs, radial deviation of the wrists, and short humeri. Nuchal fold thickness was 5 mm and there was a single umbilical artery. After termination of pregnancy, SNP array genotyping and next-generation sequencing of targeted candidate-genes were performed trying to clarify the etiology of the fetal polymalformative syndrome. A new hypomorphic mutation inFANCD2gene was found to underlie this fetal anomaly. The case illustrates that patients/families affected by rare monogenic disorders may benefit from application of modern technologies like microarrays and NGS.