A novel homozygous truncating variant in PPFIBP1 further delineates PPFIBP1-associated neurodevelopmental disorder.

Neurodevelopmental disorders (NDDs) are classified as a group of disorders affecting function and development of the brain and having wide clinical variability. Herein, we describe two affected individuals segregating a recessive NDD. The affected individuals exhibited phenotypes such as global developmental delay (GDD), intellectual disability (ID), microcephaly and speech delay. Whole-exome sequencing (WES) followed by bidirectional Sanger sequencing techniques identified a homozygous nonsense variant (c.466C > T; p.Gln156*) in the PPFIBP1 gene (NM_003622.4) that segregated with the disease phenotype. Further, to elucidate the effect of the variant on protein structure, 3D protein modelling was performed for the mutant and normal protein that suggested substantial reduction of the mutant protein. Our data support the evidence that PPFIBP1 has a pivotal role in neurodevelopment in humans, and loss-of-function variants cause clinically variable neurodevelopmental phenotypes.

Toxicological effects of the chemical and green ZnO NPs on Cyprinus carpio L. observed under light and scanning electron microscopy.

Nanoparticles in aquatic bodies cause serious harm to the aquatic organisms when accumulated in high amounts. However, green nanoparticles synthesized using plants can be less toxic as compared to chemical nanoparticles. Hence, we designed our study to investigate the toxicological effects of chemical and green zinc oxide nanoparticles (ZnO NPs) on the biological activity of juvenile Cyprinus carpio. The green ZnO NPs were synthesized from Solieria robusta, and chemical ZnO NPs were synthesized using zinc chloride solution and ammonium hydroxide. Characterization was done by using light microscopy, scanning electron microscope (SEM), Fourier transmission infrared radiation, and X-ray diffraction (XRD) techniques. The highest absorbance of nanoparticles was observed at 360 which confirmed the synthesis of ZnO. The SEM analysis showed that green nanoparticles were hexagonal while the chemical nanoparticles were spherical to cubic in shape. Definite peaks were observed in XRD of green and chemical NPs at 2θ angles 45.84° and 32.18°, respectively. Oxidative stress was determined by chemical analysis of catalase, glutathione S-transferase (GST), glutathione (GSH), and lipid peroxidation (LPO) activities. The toxicological effects of chemical ZnO NPs on the catalase, LPO, GST, and GSH activities were more than green ZnO NPs. The histopathological investigation proved that the effect of chemical nanoparticles was worse than green ZnO NPs. More tissue damage was found in chemical nanoparticles than green synthesized nanoparticles. It was concluded that chemical nanoparticles can be replaced by green nanoparticles, as green nanoparticles are eco-friendly with less toxicological effects. This replacement can limit the toxic effect of nanoparticles when they get accumulated in high amounts in water bodies.

Case Report: Biallelic Variant in the tRNA Methyltransferase Domain of the AlkB Homolog 8 Causes Syndromic Intellectual Disability.

Intellectual disability (ID) has become very common and is an extremely heterogeneous disorder, where the patients face many challenges with deficits in intellectual functioning and adaptive behaviors. A single affected family revealed severe disease phenotypes such as ID, developmental delay, dysmorphic facial features, postaxial polydactyly type B, and speech impairment. DNA of a single affected individual was directly subjected to whole exome sequencing (WES), followed by Sanger sequencing. Data analysis revealed a novel biallelic missense variant (c.1511G>C; p.(Trp504Ser)) in the ALKBH8 gene, which plays a significant role in tRNA modifications. Our finding adds another variant to the growing list of ALKBH8-associated tRNA modifications causing ID and additional phenotypic manifestations. The present study depicts the key role of the genes associated with tRNA modifications, such as ALKBH8, in the development and pathophysiology of the human brain.

A review on polysaccharides from Artemisia sphaerocephala Krasch seeds, their extraction, modification, structure, and applications.

Artemisia sphaerocephala Krasch (ASK) is an important member of Compositae (Asteraceae) family. Its seeds have been widely used as traditional medicine and to improve the quality of food. Water soluble and water insoluble polysaccharides are found in the seeds of this plant. Research has been conducted on the extraction of polysaccharides, their modification and determination of their structure. To date different techniques for extraction purposes have been applied which are reviewed here. Antioxidant, antidiabetic, anti-obesogenic, antitumor, and immunomodulatory activities have been explored using in vivo and in vitro methods. Moreover, these polysaccharides have been used as packaging material and as a sensing component for monitoring the freshness of packaged food. Some experimental results have shown that the quality of foods is also improved by using them as a food additive. We have also indicated some of the potential areas that are needed to be explored.

SGCD Homozygous Nonsense Mutation (p.Arg97∗) Causing Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F) in a Consanguineous Family, a Case Report.

Background: Limb-girdle muscular dystrophy (LGMD) is an increasingly heterogeneous category of inherited muscle diseases, mainly affecting the muscles of shoulder areas and the hip, segregating in both autosomal recessive and dominant manner. To-date, thirty-one loci have been identified for LGMD including seven autosomal dominant (LGMD type 1) and twenty four autosomal recessive (LGMD type 2) inherited loci. Methodology/Laboratory Examination: The present report describes a consanguineous family segregating LGMD2F in an autosomal recessive pattern. The affected individual is an 11-year-old boy having two brothers and a sister. Direct targeted next generation sequencing was performed for the single affected individual (VI-1) followed by Sanger sequencing. Results: Targeted next generation sequencing revealed a novel homozygous nonsense mutation (c.289C>T; p.Arg97∗) in the exon 3 of the delta-sarcoglycan (SGCD) gene, that introduces a premature stop codon (TCA), resulting in a nonsense mediated decay or a truncated protein product. Discussion and Conclusion: This is the first report of LGMD2F caused by an SGCD variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SGCD in causing LGMD2F and might help in genetic counseling, which is more important to deliver the risk of carrier or affected in the future pregnancies.

Knowledge of Medicinal Plants for Children Diseases in the Environs of District Bannu, Khyber Pakhtoonkhwa (KPK).

Medicinal plants are important treasures for the treatment of different types of diseases. Current study provides significant ethnopharmacological information, both qualitative and quantitative on medical plants related to children disorders from district Bannu, Khyber Pakhtunkhwa (KPK) province of Pakistan. The information gathered was quantitatively analyzed using informant consensus factor, relative frequency of citation and use value method to establish a baseline data for more comprehensive investigations of bioactive compounds of indigenous medicinal plants specifically related to children disorders. To best of our knowledge it is first attempt to document ethno-botanical information of medicinal plants using quantitative approaches. Total of 130 informants were interviewed using questionnaire conducted during 2014-2016 to identify the preparations and uses of the medicinal plants for children diseases treatment. A total of 55 species of flowering plants belonging to 49 genera and 32 families were used as ethno-medicines in the study area. The largest number of specie belong to Leguminosae and Cucurbitaceae families (4 species each) followed by Apiaceae, Moraceae, Poaceae, Rosaceae, and Solanaceae (3 species each). In addition leaves and fruits are most used parts (28%), herbs are most used life form (47%), decoction method were used for administration (27%), and oral ingestion was the main used route of application (68.5%). The highest use value was reported for species Momordica charantia and Raphnus sativus (1 for each) and highest Informant Consensus Factor was observed for cardiovascular and rheumatic diseases categories (0.5 for each). Most of the species in the present study were used to cure gastrointestinal diseases (39 species). The results of present study revealed the importance of medicinal plant species and their significant role in the health care of the inhabitants in the present area. The people of Bannu own high traditional knowledge related to children diseases. In conclusion we recommend giving priority for further phytochemical investigation to plants that scored highest FIC, UV values, as such values could be considered as good indicator of prospective plants for discovering new drugs and attract future generations toward traditional healing practices.