A zebrafish model for studying the mechanisms of newborn hyperbilirubinemia and bilirubin-induced neurological damage.

Unresolved neonatal hyperbilirubinemia may lead to the accumulation of excess bilirubin in the body, and bilirubin in neural tissues may induce toxicity. Bilirubin-induced neurological damage (BIND) can result in acute or chronic bilirubin encephalopathy, causing temporary or lasting neurological dysfunction or severe damage resulting in infant death. Although serum bilirubin levels are used as an indication of severity, known and unknown individual differences affect the severity of the symptoms. The mechanisms of BIND are not yet fully understood. Here, a zebrafish newborn hyperbilirubinemia model is developed and characterized. Direct exposure to excess bilirubin induced dose- and time-dependent toxicity linked to the accumulation of bilirubin in the body and brain. Introduced bilirubin was processed by the liver, which increased the tolerance of larvae. BIND in larvae was demonstrated by morphometric measurements, histopathological analyses and functional tests. The larvae that survived hyperbilirubinemia displayed mild or severe morphologies associated with defects in eye movements, body posture and swimming problems. Interestingly, a plethora of mild to severe clinical symptoms were reproduced in the zebrafish model.

Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv.

Single chain antibody fragments (scFvs) are favored in diagnostic and therapeutic fields thanks to their small size and the availability of various engineering approaches. Linker between variable heavy (VH) and light (VL) chains of scFv covalently links these domains and it can affect scFv's bio-physical/chemical properties and in vivo activity. Thus, scFv linker design is important for a successful scFv construction, and flexible linkers are preferred for a proper pairing of VH-VL. The flexibility of the linker is determined by length and sequence content and glycine-serine (GS) linkers are commonly preferred for scFvs based on their highly flexible profiles. Despite the advantage of this provided flexibility, GS linkers carry repeated sequences which can cause problems for PCR-based engineering approaches and immunogenicity. Here, two different linkers, a repetitive GS linker and an alternative non-repetitive linker with similar flexibility but lower immunogenicity are employed to generate anti-Vascular Endothelial Growth Factor scFvs derived from bevacizumab. Our findings highlight a better in vitro profile of the non-repetitive linker such as a higher monomer ratio, higher thermal stability while there was no significant difference in in vivo efficacy in a zebrafish embryonic angiogenesis model. This is the first study to compare in vivo efficacy of scFvs with different linkers in a zebrafish model.

Analysis of Gender Sensitivity of Turkey's Disaster Legislation to Create a Disaster-Resilient Society.

Disasters frequently occur in Turkey. Although there is comprehensive disaster legislation in Turkey, it has not been well studied in terms of gender sensitivity. This study aimed to evaluate the disaster legislation of Turkey in the context of gender equality. We investigated 17 non-technical disaster legislations to determine in what context and to what level disaster management is gender-sensitive in Turkey. We also carried out a workshop with experts from governmental bodies and nongovernmental organizations (NGOs), and academics to discuss the gender sensitivity of the legislations. We found that only two of the 17 legislations included a gender perspective. One legislation addressed gender equality and equity very well, while one was partially gender-sensitive and the others 5 were gender blind. The workshop was conducted in collaboration with the Disaster and Emergency Management Presidency (AFAD) and 33 participants from 19 organizations. The participants agreed that the disaster legislation did not include a gender perspective and acknowledged the importance of integrating a gender perspective into the disaster policies of Turkey. They recommended that the AFAD and emergency response units should have at least one female president or vice president, gender equality training should be provided to officers and managers of government and non-governmental disaster institutions, and a working group should be established to develop strategies that integrate gender perspectives into disaster and emergency policies. The disaster legislation of Turkey is not gender sensitive. It is important to incorporate language terminologies, understanding, and approaches that are sensitive to gender into disaster-related legislation and regulations.

The identification of small supernumerary marker chromosomes; the experiences of 15,792 fetal karyotyping from Turkey.

Small supernumerary marker chromosomes (sSMCs) are often associated with developmental abnormalities and malformations are de novo in approximately 60% of the cases. Fluorescence in situ hybridization (FISH) techniques using various probes provided the possibility to analyze and characterize sSMCs, which is highly important for prenatal diagnosis and genetic counseling. We now present the establishment of a specific strategy to identify the origin and structure of the sSMCs using a combination of conventional banding and classical FISH techniques. Based on this strategy, in a series of 15,792 prenatal karyotypes, 20 cases with sSMCs (prevalence 1.26 per 1000) were diagnosed. Eighteen of these cases were completely analyzed by FISH using commercial probes and Chromoprobe Multiprobe-I System. Out of 20 sSMCs 12 were satellited (10 bisatellited and two monosatellited) (60%) and eight were non-satellited (six ring-like and two isochromosomes) (40%). sSMCs were mostly derived from chromosome 15 (10/20) (50%). Euchromatin material was found in 13 cases by various banding and FISH techniques, while in six of 20 sSMCs there was no evidence of euchromatin material. Parental karyotypes could be evaluated in 15 cases and familial inheritance was found in only three of them (20%). We conclude that the proposed strategy for the identification and characterization of sSMCs is accurate and represents a good alternative to novel FISH techniques for modestly equipped cytogenetic laboratories.