6 results on '"Da’as, Sahar"'
Search Results
2. Microinjection quality control in zebrafish model for genetic manipulations
- Author
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Abdelrahman, Doua, Hasan, Waseem, and Da'as, Sahar I.
- Published
- 2021
- Full Text
- View/download PDF
3. A recessive variant in SIM2 in a child with complex craniofacial anomalies and global developmental delay.
- Author
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Al-Kurbi, Alya A., Da'as, Sahar Isa, Aamer, Waleed, Krishnamoorthy, Navaneethakrishnan, Poggiolini, Ilaria, Abdelrahman, Doua, Elbashir, Najwa, Al-Shabeeb Akil, Ammira, Glass, Graeme E., and Fakhro, Khalid A.
- Subjects
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DEVELOPMENTAL delay , *WHOLE genome sequencing , *PROTEIN structure , *MISSENSE mutation , *FACIAL abnormalities , *CHROMOSOME duplication , *FETAL brain - Abstract
Rare deletions and duplications on the long arm of Chromosome 21 have previously been reported in many patients with craniofacial and developmental phenotypes. However, this Down Syndrome Critical Region (DSCR) contains multiple genes, making identifying a single causative gene difficult. Here, we report a case of a boy with bicoronal craniosynostosis, facial dysmorphism, developmental delay, and intellectual impairment who was found by whole genome sequencing to have a homozygous missense mutation in the Single-Minded Homolog 2 (SIM2) gene (c.461 A > G, p.Tyr154Cys) within the DSCR. SIM2 encodes an essential bHLH and PAS domain transcription factor expressed during fetal brain development and acts as a master regulator of neurogenesis. This variant is globally very rare, segregates in the family, and is predicted to be highly deleterious by in silico analysis, 3D molecular modeling of protein structure, and functional analysis of zebrafish models. Zebrafish expressing the human SIM2p.Y154C variant displayed a progressed microcephaly-like phenotype and head shape abnormalities. When combined with careful phenotyping of the patient vis-à-vis previously reported cases harboring structural variants in this critical 21q22 region, the data support a pathogenic role of SIM2 in this complex syndrome and demonstrates the utility of next-generation sequencing in prioritizing genes in contiguous deletions/duplications syndromes and diagnosing microarray-negative patients in the craniofacial clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Zebrafish mast cells possess an FcɛRI-like receptor and participate in innate and adaptive immune responses
- Author
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Da’as, Sahar, Teh, Evelyn M., Dobson, J. Tristan, Nasrallah, Gheyath K., McBride, Eileen R., Wang, Hao, Neuberg, Donna S., Marshall, Jean S., Lin, Tong-Jun, and Berman, Jason N.
- Subjects
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MAST cells , *IMMUNE response , *AEROMONAS salmonicida , *ANAPHYLAXIS , *KETOTIFEN , *IMMUNOGLOBULINS - Abstract
Abstract: We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p =0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p =0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FcɛRIγ) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish FcɛRI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p =0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
5. Biocompatibility and toxicity of novel iron chelator Starch-Deferoxamine (S-DFO) compared to zinc oxide nanoparticles to zebrafish embryo: An oxidative stress based apoptosis, physicochemical and neurological study profile.
- Author
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Nasrallah, Gheyath K., Salem, Rola, Da'as, Sahar, Al-Jamal, Ola Loay Ahmad, Scott, Mark, and Mustafa, Ibrahim
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IRON chelates , *DEFEROXAMINE , *ZINC oxide , *NANOPARTICLES , *ZEBRA danio embryos , *CLINICAL trials - Abstract
Abstract Objectives Clinically approved iron chelators are effective in decreasing significant transfusional iron accumulation. Starch-Deferoxamine (S-DFO), a novel high molecular weight iron chelator, was produced to increase binding capacity to iron and reduce toxicity. Although its efficacy was established in one small cohort clinical trial, its potential adverse effect was not adequately addressed. Methods We utilized zebrafish model to assess S-DFO toxicity using following assays: mortality, teratogenicity, hatching rate, tail flicking, Acridine Orange staining for apoptosis detection, o -dianisidine staining for hemoglobin synthesis, and the level of Hsp70 as a general stress indicator. Embryos were exposed to different concentrations of S-DFO, Zinc Oxide nanoparticle (ZnO) (positive control), along with untreated control (UC). Results S-DFO showed no significant mortality nor deformities at all tested concentrations (0.0–1000 μM). Thus, the LC50 is expected to >1000 μM. 100 μM S-DFO treatment did not affect embryo development (as judged by hatching rate); neuromuscular activity (as judged by tail flicking); and hemoglobin synthesis. Neither apoptosis, nor increase in Hsp70 level was noticed upon S-DFO treatment. Conclusion Our assays demonstrate that S-DFO does not induce cellular or biochemical stress and has no adverse effect on organ development of zebrafish embryos, suggesting its safe use as an iron chelator. Graphical abstract Unlabelled Image Highlights • Biocompatible high molecular weight iron chelators • No adverse effect of neurological functions of zebrafish • There is no adverse effect on hemoglobin synthesis. • No adverse effect on protein synthesis and expression • Potential better iron chelator to be used in clinical practice [ABSTRACT FROM AUTHOR]
- Published
- 2019
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6. Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos.
- Author
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Al-Jamal, Ola, Al-Jighefee, Hadeel, Younes, Nadin, Abdin, Roba, Al-Asmakh, Maha A., Radwan, A. Bahgat, Sliem, Mostafa H., Majdalawieh, Amin F., Pintus, Gianfranco, Yassine, Hadi M., Abdullah, Aboubakr M., Da'as, Sahar I., and Nasrallah, Gheyath K.
- Abstract
Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC 50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC 50 of 2.3 mg/L. Thus, based on the LC 50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as "moderately toxic". The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies. Unlabelled Image • According to the USFWS acute toxicity rating scale, SAPDMA is classified as "moderately toxic" surfactant. • Embryos exposure to SAPDMA caused mortality in a dose-dependent manner with calculated LC50 of 2.3 mg/L and NOEC at 0.1 mg/L. • SAPDMA induces cardiotoxicity by decreasing the Aortic pulse and blood flow velocity at concentration higher than the NOEC. • Starting from 0.8 mg/L, SAPDMA severely affects the hematopoiesis process and locomotive activity. • SAPDMA at the NOEC (0.1 mg/L) might cause hepatomegaly without significantly affecting the normal function of the liver. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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