Evaluation of deleted in malignant brain tumors 1 (DMBT1) gene expression in bladder carcinoma cases: preliminary study

This study was undertaken to evaluate the expression of DMBT1 in bladder cancer and its correlation with clinico-pathological parameters analyzed in bladder carcinoma patients. We investigated DMBT1 in 56 paraffin embedded specimens of transitional cell carcinoma of the urinary bladder. We assessed DMBT1 gene expression at mRNA level by RT-PCR. Our results show 100% expression of DMBT1 in bladder carcinoma samples. Due to this preliminary results; gene expression was compared to tumor grade, and a significant difference was detected between grade 1 and 3 (p?=?0.028). The down-regulation of DMBT1 gene expression in carcinomas suggests the possible role in bladder cancer.     

Effect of Encapsulated Lactobacillus bulgaricus on Innate Immune System and Hematological Parameters in Rainbow Trout (Oncorhynchus mykiss), Post-Administration of Pb

Probiotics and Antimicrobial Proteins - The present study was conducted to investigate the effects of probiotic and encapsulated Lactobacillus bulgaricus on hematological and immunological factors...     

gamma-Turn types prediction in proteins using the support vector machines

Recently, two different models have been developed for predicting gamma-turns in proteins by Kaur and Raghava [2002. An evaluation of beta-turn prediction methods. Bioinformatics 18, 1508-1514; 2003. A neural-network based method for prediction of gamma-turns in proteins from multiple sequence alignment. Protein Sci. 12, 923-929]. However, the major limitation of previous methods is inability in predicting gamma-turns types. Thus, there is a need to predict gamma-turn types using an approach which will be useful in overall tertiary structure prediction. In this work, support vector machines (SVMs), a powerful model is proposed for predicting gamma-turn types in proteins. The high rates of prediction accuracy showed that the formation of gamma-turn types is evidently correlated with the sequence of tripeptides, and hence can be approximately predicted based on the sequence information of the tripeptides alone.     

Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets

Advances in our understanding of the synthesis, regulation and function of prostanoids have led to a new appreciation of their actions in health and disease. Prostanoid synthesis is essential for the generation of inflammatory pain and this depends not only on prostanoid production at the site of inflammation, but also on the actions of prostanoids synthesized within the central nervous system (CNS). Moreover, central prostanoid synthesis is controlled both by neural and humoral signals, the latter being a novel form of input to the CNS. Diverse compounds that act along the pathway of prostanoid synthesis and action, both in the periphery and in the CNS, might provide increased benefit for treating inflammatory pain hypersensitivity and its associated sickness syndrome, with a reduced risk of adverse effects.     

Elucidating the protein cold-adaptation: Investigation of the parameters enhancing protein psychrophilicity

To investigate the role of the critical parameters in adaptation of proteins to low temperatures, a comparative systematic analysis was performed. Several parameters were proposed to have contribution to cold adaptation of proteins. Among proposed parameters, total values of residual structure states, secondary structure states and oligomeric states were alike in both psychrophilic and mesophilic proteins. In addition, our results provided new quantitative information about the trends in the substitution preference of Ile, Phe, Tyr, Lys, Arg, His, Glu and Leu with most of amino acids and substitution avoidance of Gly, Thr and Ala with most of amino acids. These findings would help future efforts propose a strategy for designing psychrophilic proteins.     

Focus: Health Equity: Financial Protection Indexes and the Iranian Health Transformation Plan: A Systematic Review

Background: On May 5, 2014, the Iranian Ministry of Health and Medical Education launched the Health Transformation Plan (HTP) as a major healthcare reform to curb out-of-pocket (OOP) expenses and protect people from catastrophic health expenditures (CHEs). Therefore, in this study, we conducted a comprehensive literature search with the aim of systematically investigating the impacts of HTP on OOP and CHE after the implementation of the plan. Method: Web of Science, PubMed, Scopus, Embase, and Iranian bibliographic thesauri and repositories such as MagIran, Elmnet, and Scientific Information Database were searched. Studies published between May 2014 and December 2020 that reported the impact of HTP on the financial indicators under investigation in this study (OOP and CHEs) that were conducted in Iran. Estimated pooled change both for OOP and CHEs was calculated as effect size utilizing meta-analytical techniques. Also, heterogeneity among studies was assessed with the I² statistics. Results: Seventeen studies were included, nine of which evaluated the OOP index, six studies assessed the CHEs index, and two studies examined both the OOP and CHEs indexes. The OOP was found to decrease after the implementation of the HTP (with an estimated decrease of 13.02% (95% CI: 9.09-16.94). Also, CHEs experienced a decrease of 5.80% (95% CI: 3.85-7.74). Conclusion: The findings show that the implementation of HTP has reduced health costs. In this regard and in order to keep reducing the costs that many people are unable to pay, the government and other organizations involved in the health system should provide sustainable financial resources in order to continue running HTP. However, there remain gaps and weaknesses that can be solved through discussion with all the actors involved.     

Woodland strawberry axillary bud fate is dictated by a crosstalk of environmental and endogenous factors

Plant architecture is defined by fates and positions of meristematic tissues and has direct consequences on yield potential and environmental adaptation of the plant. In strawberries (Fragaria vesca L. and F. × ananassa Duch.), shoot apical meristems can remain vegetative or differentiate into a terminal inflorescence meristem. Strawberry axillary buds (AXBs) are located in leaf axils and can either remain dormant or follow one of the two possible developmental fates. AXBs can either develop into stolons needed for clonal reproduction or into branch crowns (BCs) that can bear their own terminal inflorescences under favorable conditions. Although AXB fate has direct consequences on yield potential and vegetative propagation of strawberries, the regulation of AXB fate has so far remained obscure. We subjected a number of woodland strawberry (F. vesca L.) natural accessions and transgenic genotypes to different environmental conditions and growth regulator treatments to demonstrate that strawberry AXB fate is regulated either by environmental or endogenous factors, depending on the AXB position on the plant. We confirm that the F. vesca GIBBERELLIN20-oxidase4 (FvGA20ox4) gene is indispensable for stolon development and under tight environmental regulation. Moreover, our data show that apical dominance inhibits the outgrowth of the youngest AXB as BCs, although the effect of apical dominance can be overrun by the activity of FvGA20ox4. Finally, we demonstrate that the FvGA20ox4 is photoperiodically regulated via FvSOC1 (F. vesca SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) at 18°C, but at higher temperature of 22°C an unidentified FvSOC1-independent pathway promotes stolon development.

Environmental conditions and apical dominance dictate woodland strawberry plant architecture by regulating axillary bud fate.     

Plasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1α

The ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α. Both monoclonal antibodies and polyclonal IgG, that bound to epitopes in the SD3-loop, stained the surface of pRBC, disrupted rosettes and blocked direct binding of recombinant NTS-DBL1α to RBC. Depletion of polyclonal IgG raised to NTS-DBL1α on a SD3 loop-peptide removed the anti-rosetting activity. Immunizations with recombinant subdomain 1 (SD1), subdomain 2 (SD2) or SD3 all generated antibodies reacting with the pRBC-surface but only the sera of animals immunized with SD3 disrupted rosettes. SD3-sequences were found to segregate phylogenetically into two groups (A/B). Group A included rosetting sequences that were associated with two cysteine-residues present in the SD2-domain while group B included those with three or more cysteines. Our results suggest that the SD3 loop of PfEMP1-DBL1α is an important target of anti-rosetting activity, clarifying the molecular basis of the development of variant-specific rosette disrupting antibodies.     

Circadian gene variants and susceptibility to type 2 diabetes: a pilot study

Background

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants.

Methodology/Principal Findings

The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66–0.86], p = 3.18×10⁻⁵), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07–1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01–1.08], p = 0.008 and OR = 0.95 [0.91–0.99], p = 0.015 respectively).

Conclusions/significance

None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.     

Synthesis of Injectable Shear‐Thinning Biomaterials of Various Compositions of Gelatin and Synthetic Silicate Nanoplatelet

Injectable shear‐thinning biomaterials (iSTBs) have great potential for in situ tissue regeneration through minimally invasive therapeutics. Previously, an iSTB was developed by combining gelatin with synthetic silicate nanoplatelets (SNPs) for potential application to hemostasis and endovascular embolization. Hence, iSTBs are synthesized by varying compositions of gelatin and SNPs to navigate their material, mechanical, rheological, and bioactive properties. All compositions (each component percentage; 1.5–4.5%/total solid ranges; 3–9%) tested are injectable through both 5 Fr general catheter and 2.4 Fr microcatheter by manual pressure. In the results, an increase in gelatin contents causes decrease in swellability, increase in freeze‐dried hydrogel scaffold porosity, increase in degradability and injection force during iSTB fabrication. Meanwhile, the amount of SNPs in composite hydrogels is mainly required to decrease degradability and increase shear thinning properties of iSTB. Finally, in vitro and in vivo biocompatibility tests show that the 1.5–4.5% range gelatin–SNP iSTBs are not toxic to the cells and animals. All results demonstrate that the iSTB can be modulated with specific properties for unmet clinical needs. Understanding of mechanical and biological consequences of the changing gelatin–SNP ratios through this study will shed light on the biomedical applications of iSTB on specific diseases.