SLC38A2 provides proline to fulfil unique synthetic demands arising during osteoblast differentiation and bone formation.

Cellular differentiation is associated with the acquisition of a unique protein signature which is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins including RUNX2, OSX, OCN and COL1A1 are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation.

Emerging Pandemic COVID 19 versus SARS-COV-1

Rising threat of the global pandemic COVID 19 has become the major cause of concern among nations worldwide. The appalling pandemic has aggravated the global health of people making normal life come to a virtual standstill. The purpose of this study is to investigate and compare the similarities and differences between the previous global pandemic outbreak SARS-COV-1 with that of COVID 19. It makes use of a bioinformatic approach to analyze why COVID 19 has made situations uncontrollable as opposed to that of SARS-COV-1 although both belong to the same coronavirus family. Discusses about the recent clinical trials that are being conducted to evaluate potential therapeutics to combat the deadly pandemic. There is currently no available vaccine for COVID 19. E The current status of COVID 19 research stands progressive in various areas of knowledge. Further studies based on emerging evidences are required to produce drugs which can slow down disease progression and improve survival.

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

In the last few years, microRNA-mediated regulation has been shown to be important in viral infections. In fact, viral microRNAs can alter cell physiology and act on the immune system; moreover, cellular microRNAs can regulate the virus cycle, influencing positively or negatively viral replication. Accordingly, microRNAs can represent diagnostic and prognostic biomarkers of infectious processes and a promising approach for designing targeted therapies. In the past 18 months, the COVID-19 infection from SARS-CoV-2 has engaged many researchers in the search for diagnostic and prognostic markers and the development of therapies. Although some research suggests that the SARS-CoV-2 genome can produce microRNAs and that host microRNAs may be involved in the cellular response to the virus, to date, not enough evidence has been provided. In this paper, using a focused bioinformatic approach exploring the SARS-CoV-2 genome, we propose that SARS-CoV-2 is able to produce microRNAs sharing a strong sequence homology with the human ones and also that human microRNAs may target viral RNA regulating the virus life cycle inside human cells. Interestingly, all viral miRNA sequences and some human miRNA target sites are conserved in more recent SARS-CoV-2 variants of concern (VOCs). Even if experimental evidence will be needed, in silico analysis represents a valuable source of information useful to understand the sophisticated molecular mechanisms of disease and to sustain biomedical applications.

Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study

Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, analysis of the results obtained from animal models of brain ischemia could be helpful. We have developed a bioinformatic approach exploring single nucleotide polymorphisms (SNPs) in human orthologues of rat genes expressed differentially under conditions of induced brain ischemia. Using this approach, we identified and analyzed nine SNPs in 553 Russian individuals (331 patients with IS and 222 controls). We explored the association of SNPs with both IS outcomes and with the risk of IS. SNP rs66782529 (LGALS3) was associated with negative IS outcomes (p = 0.048). SNPs rs62278647 and rs2316710 (PTX3) were associated significantly with IS (p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the PTX3 polymorphism. Thus, this research not only reveals some new genetic associations with IS and its outcomes but also shows how exploring variations in genes from a rat model of brain ischemia can be of use in searching for human genetic markers of this disorder.

A Dynamic Network of Proteins Facilitate Cell Envelope Biogenesis in Gram-Negative Bacteria

Bacteria must maintain the ability to modify and repair the peptidoglycan layer without jeopardising its essential functions in cell shape, cellular integrity and intermolecular interactions. A range of new experimental techniques is bringing an advanced understanding of how bacteria regulate and achieve peptidoglycan synthesis, particularly in respect of the central role played by complexes of Sporulation, Elongation or Division (SEDs) and class B penicillin-binding proteins required for cell division, growth and shape. In this review we highlight relationships implicated by a bioinformatic approach between the outer membrane, cytoskeletal components, periplasmic control proteins, and cell elongation/division proteins to provide further perspective on the interactions of these cell division, growth and shape complexes. We detail the network of protein interactions that assist in the formation of peptidoglycan and highlight the increasingly dynamic and connected set of protein machinery and macrostructures that assist in creating the cell envelope layers in Gram-negative bacteria.

Utilization of specific primers in legume allergens based polymorphism screening

Different types of allergies became a part of life of many people around the world. The research activities connecting to allergens are actually not oriented only for protein and immunological interactions, but to the genomic and transcriptomic background of them, too. Analysis and description of genomic variability of allergens in plant food resources will help to manage the allergen based strategies in the future. Here, the bioinformatic approach was used to develop and validate the specific primers for genomic screening of polymorphism of profilins (Profilin Based Amplicon Polymorphism; PBAP) and vicilins (Vicilin Based Amplicon Polymorphism; VBAP) among the legumes. The alignment of existing public databases data for these allergens in the group of legumes was performed. Subsequently, specific primers were designed and their ability to generate polymorphic amplicons were tested for three legumes – bean, lentil and chickpeas. In all cases, amplicons were generated and polymorphism was detected in all three species for profilin as well as for vicilin.

Clinical Significance of Long Non-Coding RNA HCG18, OIP5-AS1, FGD5-AS1 and LINC00657 Expression in Human Gastric Cancer

Background Gastric cancer (GC) is a major health problem and the third cause of cancer-induced deaths globally. Long non-coding RNAs (lncRNAs) are new cellular regulators in cancers whose contribution to GC carcinogenesis is still unknown to a large extent. This study aimed to investigate expression levels of bioinformatically ranked lncRNAs in GC tissues. Methods Using a bioinformatic approach, lncRNAs supposed to be involved in GC tumorigenesis were prioritized. Further, the top-ranked lncRNAs including HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 were selected for experimental validation. Moreover, qPCR was used to validate bioinformatics findings in 35 GC and 35 paired adjacent normal gastric tissue samples (ANGTs). Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were generated to assess the diagnostic values of the lncRNAs. Results lncRNA-HCG18 showed to be the top-ranked lncRNA involved in GC, as identified by bioinformatics analysis. Additionally, HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 expression levels significantly increased in GC tissue samples compared to ANGTs. The area under the curve (AUC) of HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 were 0.80, 0.74, 0.73, and 0.71, respectively. Considering the findings, it was concluded that HCG18, OIP5-AS1, FGD5-AS1, and LINC00657 lncRNAs may contribute to GC tumorigenesis. Conclusion This study also found that the bioinformatic approach could be applied as an efficient approach to finding candidate lncRNAs relevant to GC progression.