miRNA-155 and miRNA-181a as prognostic biomarkers for pediatric acute lymphoblastic leukemia

Mortality rates of acute lymphoblastic leukemia (ALL) have improved over the past 20 years; however, a significant portion of deaths stems from the lack of prognostic biomarkers, which can direct therapy and overcome drug resistance. microRNA-155a (miRNA-155a) and miRNA-181a are two single-stranded miRNAs involved in the pathogenesis of many types of leukemia and lymphoma and is linked to drug resistance. We investigated their expression levels in 55 patients, 45 diagnosed with ALL and 10 as a control group. We found that miRNA-155a and miRNA-181a were significantly upregulated in the ALL group with both being linked to high levels of minimal residual disease and poor prognosis. miRNA-155a cutoff value was significant in discriminating between high- and low-risk ALL patients as well as between ALL patients and healthy controls, miRNA-181a cutoff value, however, was not significant. Both markers levels were significantly downregulated after therapy. We conclude that miR-155 is correlated with poor prognosis in ALL, whereas we couldn’t link miRNA-181a to the prognosis in ALL. Moreover, the marked decrease in their expression after therapy could reflect their impact on disease outcome.     

Alkaliphilic and halophilic hydrocarbon-utilizing bacteria from Kuwaiti coasts of the Arabian Gulf

Green animate materials from the intertidal zone of the Arabian Gulf coast accommodated more alkaliphilic and halophilic bacteria than inanimate materials. The alkaliphilic oil-utilizing bacteria, as identified by their 16S ribonucleic acid sequences, belonged to the following genera arranged in decreasing frequences: Marinobacter, Micrococcus, Dietzia, Bacillus, Oceanobacillus, and Citricoccus. The halophilic oil-utilizing bacteria belonged to the genera: Marinobacter, Georgenia, Microbacterium, Stappia, Bacillus, Isoptericola, and Cellulomonas. Most isolates could grow on a wide range of pure n-alkanes and aromatic compounds, as sole sources of carbon and energy. Quantitative gas liquid chromatographic analysis showed that individual isolates attenuated crude oil and representative pure hydrocarbons in culture. The optimum pH for most of the alkaliphilic genera was pH 10, and the optimum salinity for the halophiles ranged between 2.5 and 5% NaCl (w/v). It was concluded that as far as their microbial makeup is concerned, oily alkaline and saline intertidal areas of the Kuwaiti coasts have a self-cleaning potential.     

Ammonia channeling in bacterial glucosamine-6-phosphate synthase (Glms): molecular dynamics simulations and kinetic studies of protein mutants

Ammonia transfer from the glutamine site to the fructose-6P site of bacterial glucosamine-6-phosphate synthase was studied by molecular dynamics simulations. The studies suggest a key role for Trp74, in the sealing of the hydrophobic channel connecting the two binding sites, as well as for the two Ala602 and Val605 residues, which form a narrow passage whose opening/closing constitutes an essential event in ammonia transfer. Kinetic analyses of the corresponding protein mutants confirmed our predictions. The efficiency of ammonia transfer which was close to zero in the W74A mutant was partially restored by increasing the size of the corresponding side-chain; the simulations performed on the W74A mutant suggested the formation of a hole in the channel. In the case of A602L and V605L mutants, the efficiency of ammonia transfer decreased to approximately 50% of the value of the native protein. None of the mutants were, however, able to use exogenous ammonia as a substrate.     

Synthesis of some novel dimethine,bis-dimethine cyanine dyes and octacosamethine cyanine dyes endowed with promising biological potency against (HepG2), (Hela), (MCF-7), (MIA), (SN12C) and (H358) cell lines

Successfully, one step two component synthesis of dimethine cyanine dyes, bis-dimethine cyanine dyes and icosamethine cyanine dyes 2–10via reaction of pyridinium salt 1 with some different aldehydes hope to obtain these compounds with enhanced biological potency as antitumor agents against spontaneous liver (HepG2), cervical (Hela), breast (MCF-7), pancreas (MIA), kidney (SN12C) and lung (H358). The impact of substituted drugs on the tumor cells was reflected by means of structure activity relationship (SAR). Among these dyes, icosamethine cyanine dye 8 recorded an excellent activity toward all the tested cell lines. The newly destined drugs were identified and emphasized by spectroscopy and elemental analyses.     

Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle

Relatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n?=?35) and resistant group (n?=?35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.     

Rescue of αB Crystallin (HSPB5) Mutants Associated Protein Aggregation by Co-Expression of HSPB5 Partners

HSPB5 (also called αB-crystallin) is a ubiquitously expressed small heat shock protein. Mutations in HSPB5 have been found to cause cataract, but are also associated with a subgroup of myofibrillar myopathies. Cells expressing each of these HSPB5 mutants are characterized by the appearance of protein aggregates of primarily the mutant HSPB5. Like several members of the HSPB family, HSPB5 can form both homo-oligomeric and hetero-oligomeric complexes. Previous studies showed that co-expression of HSPB1 and HSPB8 can prevent the aggregation associated with the HSPB5 (R120G) mutant in cardiomyocytes and in transgenic mice. In this study, we systematically compared the effect of co-expression of each of the members of the human HSPB family (HSPB1-10) on the aggregation of three different HSPB5 mutants (R120G, 450 Δ A, 464 Δ CT). Of all members, co-expression of HSPB1, HSPB4 and HSPB5 itself, most effectively prevent the aggregation of these 3 HSPB5 mutants. HSPB6 and HSPB8 were also active but less, whilst the other 5 HSPB members were ineffective. Co-expression of Hsp70 did not reduce the aggregation of the HSPB5 mutants, suggesting that aggregate formation is most likely not related to a toxic gain of function of the mutants per se, but rather related to a loss of chaperone function of the oligomeric complexes containing the HSPB5 mutants (dominant negative effects). Our data suggest that the rescue of aggregation associated with the HSPB5 mutants is due to competitive incorporation of its partners into hetero-oligomers hereby negating the dominant negative effects of the mutant on the functioning of the hetero-oligomer.