Current Genomics - Volume 20, Issue 3, 2019

Background: Protein phosphorylation is an important reversible post-translational modification, which regulates a number of critical cellular processes. Phosphatases and kinases work in a concerted manner to act as a “molecular switch” that turns-on or - off the regulatory processes driving the growth and development under normal circumstances, as well as responses to multiple stresses in plant system. The era of functional genomics has ushered huge amounts of information to the framework of plant systems. The comprehension of who’s who in the signaling pathways is becoming clearer and the investigations challenging the conventional functions of signaling components are on a rise. Protein phosphatases have emerged as key regulators in the signaling cascades. PP2A phosphatases due to their diverse holoenzyme compositions are difficult to comprehend. Conclusion: In this review, we highlight the functional versatility of PP2A members, deciphered through the advances in the post-genomic era.

Background: Substantial substance use disorders and related health conditions emerged during the mid-20th century and continue to represent a remarkable 21st century global burden of disease. This burden is largely driven by the substance-dependence process, which is a complex process and is influenced by both genetic and environmental factors. During the past few decades, a great deal of progress has been made in identifying genetic variants associated with Substance Use and Dependence (SUD) through linkage, candidate gene association, genome-wide association and sequencing studies. Methods: Various statistical methods and software have been employed in different types of SUD genetic studies, facilitating the identification of new SUD-related variants. Conclusion: In this article, we review statistical methods and software that are currently available for SUD genetic studies, and discuss their strengths and limitations.

Background: Microgravity (μG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. μG effects on bone metabolism has been an extensive field of study in recent years, due to the challenges presented by space flight. Methods: We systematically reviewed research data from genomic studies performed in real or simulated μG, on osteoblast and osteoclast cells. Our search yielded 50 studies, of which 39 concerned cells of the osteoblast family and 11 osteoclast precursors. Results: Osteoblastic cells under μG show a decreased differentiation phenotype, proved by diminished expression levels of Alkaline Phosphatase (ALP) and Osteocalcin (OCN) but no apoptosis. Receptor Activator of NF-ΚB Ligand (RANKL)/ Osteoprotegerine (OPG) ratio is elevated in favor of RANKL in a time-dependent manner, and further RANKL production is caused by upregulation of Interleukin- 6 (IL-6) and the inflammation pathway. Extracellular signals and changes in the gravitational environment are perceived by mechanosensitive proteins of the cytoskeleton and converted to intracellular signals through the Mitogen Activated Protein Kinase pathway (MAPK). This is followed by changes in the expression of nuclear transcription factors of the Activator Protein-1 (AP-1) family and in turn of the NF-ΚB, thus affecting osteoblast differentiation, cell cycle, proliferation and maturation. Pre-osteoclastic cells show increased expression of the marker proteins such as Tryptophan Regulated Attenuation Protein (TRAP), cathepsin K, Matrix Metalloproteinase-9 (MMP-9) under μG conditions and become sensitized to RANKL. Conclusion: Suppressing the expression of fusion genes such as syncytine-A which acts independently of RANKL, could be possible future therapeutic targets for microgravity side effects.

Background: In recent years, tRFs(transfer RNA-Derived Fragments) and transfer RNADerived Stress-induced RNAs (or tRNA halves) have been shown to have vital roles in cancer biology. We aimed to reveal the expression profile of tRNA-derived fragments in breast cancer tissues in the study, and to explore their potential as biomarkers of breast cancer. Methods: We characterized the tRNA-derived fragments expression profile from 6 paired clinical breast cancer tissues and adjacent normal samples. Then we selected 6 significantly expressed tRNAderived fragments and screened the genes for validation by using Quantitative Real-time PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway were finally analyzed. Results: We found 30 differentially expressed tRNA-derived fragments across our dataset, out of which 17 were up-regulated, and 13 were down-regulated. Compared with 16 clinical breast cancer tissues and adjacent normal tissues by qPCR, the results demonstrated that tRF-32-Q99P9P9NH57SJ (FC = -2.6476, p = 0.0189), tRF-17-79MP9PP (FC = -4.8984, p = 0.0276) and tRF-32- XSXMSL73VL4YK (FC = 6.5781, p = 0.0226) were significantly expressed in breast cancer tissues (p < 0.001). tRF-32-XSXMSL73VL4YK was significantly up-regulated, and tRF-32- Q99P9P9NH57SJ and tRF-17-79MP9PP were significantly down-regulated in which the expression patterns were similar to the sequencing results. The top ten significant results of GO and KEGG pathways enrichment analysis were presented. Conclusion: Our studies have demonstrated that there were significantly expressed tRNA-derived fragments in breast cancer tissues. They are hopefully to become biomarkers and would be valuable researches in this area.

Background: Nanoparticles derived from plant viruses possess fascinating structures, versatile functions and safe properties, rendering them valuable for a variety of applications. Papaya mosaic Virus-Like Particles (VLPs) are nanoparticles that contain a repetitive number of virus capsid proteins (PMV-CP) and are considered to be promising platforms for vaccine design. Previous studies have reported the antigenicity of PMV nanoparticles in mammalian systems. Materials and Methods: As experiments that concern vaccine development require careful design and can be time consuming, computational experiments are of particular importance. Therefore, prior to expressing PMV-CP in E. coli and producing nanoparticles, we performed an in silico analysis of the virus particles using software programs based on a series of sophisticated algorithms and modeling networks as useful tools for vaccine design. A computational study of PMV-CP in the context of the immune system reaction allowed us to clarify particle structure and other unknown features prior to their introduction in vitro. Results: The results illustrated that the produced nanoparticles can trigger an immune response in the absence of fusion with any foreign antigen. Conclusion: Based on the in silico analyses, the empty capsid protein was determined to be recognised by different B and T cells, as well as cells which carry MHC epitopes.

Background: Split-hand/foot malformation syndrome is a rare, clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. It may occur as an isolated abnormality or it may be associated with a genetic syndrome. Case Report: In the present case, isolated split-hand/split-foot malformation was diagnosed by prenatal ultrasound at 24 weeks in a male singleton fetus, with deep median cleft of the right hand, syndactyly and hypoplasia of phalanges in both hands, and oligodactyly of the right foot. During consultation, the father of the fetus revealed that he also had an isolated right foot dysplasia. The parents chose elective termination and autopsy confirmed prenatal ultrasound findings. Genetic testing of the aborted fetus with QF-PCR analysis for common aneuploidies and array comparative genomic hybridization (aCGH) showed a male genomic pattern, without aneuploidies or chromosomal imbalances. Further investigation with next generation sequencing of 49 clinically relevant genes revealed a novel heterozygous FGFR1 mutation c.787_789del (p.Ala263del) in the fetus; the father was heterozygous to the same mutation. Conclusion: A novel heterozygous FGFR1 mutation causing split-hand/foot malformation syndrome is reported. Accurate genetic diagnosis allowed detailed counseling to be provided to the couple, including the underlying cause, recurrence risks, and detailed management plan with preimplantation genetic diagnosis for future pregnancies.