Sequence-Level Analysis of the Major European Huntington Disease Haplotype

Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HTT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that ∼50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches. Consequently, we performed whole-genome sequencing of HD and control subjects from four independent families in whom the major European HD haplotype segregates with the disease. Analysis of the full-sequence-based HTT haplotype indicated that these four families share a common ancestor sufficiently distant to have permitted the accumulation of family-specific variants. Confirmation of new CAG-expansion mutations on this haplotype suggests that unlike most founders of human disease, the common ancestor of HD-affected families with the major haplotype most likely did not have HD. Further, availability of the full sequence data validated the use of SNP imputation to predict the optimal variants for capturing heterozygosity in personalized allele-specific gene-silencing approaches. As few as ten SNPs are capable of revealing heterozygosity in more than 97% of European HD subjects. Extension of allele-specific silencing strategies to the few remaining homozygous individuals is likely to be achievable through additional known SNPs and discovery of private variants by complete sequencing of HTT. These data suggest that the current development of gene-based targeting for HD could be extended to personalized allele-specific approaches in essentially all HD individuals of European ancestry.     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Optimization of Pre-transplantation Conditions to Enhance the Efficacy of Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are considered a potential tool for cell based regenerative therapy due to their immunomodulatory property, differentiation potentials, trophic activity as well as large donor pool. Poor engraftment and short term survival of transplanted MSCs are recognized as major limitations which were linked to early cellular ageing, loss of chemokine markers during ex vivo expansion, and hyper-immunogenicity to xeno-contaminated MSCs. These problems can be minimized by ex vivo expansion of MSCs in hypoxic culture condition using well defined or xeno-free media i.e., media supplemented with growth factors, human serum or platelet lysate. In addition to ex vivo expansion in hypoxic culture condition using well defined media, this review article describes the potentials of transient adaptation of expanded MSCs in autologous serum supplemented medium prior to transplantation for long term regenerative benefits. Such transient adaptation in autologous serum supplemented medium may help to increase chemokine receptor expression and tissue specific differentiation of ex vivo expanded MSCs, thus would provide long term regenerative benefits.     

Identifying qualitative effects of different grazing types on below‐ground communities and function in a long‐term field experiment

Herbivory is an important modulator of plant biodiversity and productivity in grasslands, but our understanding of herbivore‐induced changes on below‐ground processes and communities is limited. Using a long‐term (17 years) experimental site, we evaluated impacts of rabbit and invertebrate grazers on some soil functions involved in carbon cycling, microbial diversity, structure and functional composition. Both rabbit and invertebrate grazing impacted soil functions and microbial community structure. All functional community measures (functions, biogeochemical cycling genes, network association between different taxa) were more strongly affected by invertebrate grazers than rabbits. Furthermore, our results suggest that exclusion of invertebrate grazers decreases both microbial biomass and abundance of genes associated with key biogeochemical cycles, and could thus have long‐term consequences for ecosystem functions. The mechanism behind these impacts are likely to be driven by both direct effects of grazing altering the pattern of nutrient inputs and by indirect effects through changes in plant species composition. However, we could not entirely discount that the pesticide used to exclude invertebrates may have affected some microbial community measures. Nevertheless, our work illustrates that human activity that affects grazing intensity may affect ecosystem functioning and sustainability, as regulated by multi‐trophic interactions between above‐ and below‐ground communities.     

Bio-separation, speciation and determination of chromium in water using partially pyrolyzed olive pomace sorbent

Speciation of Cr(III)/Cr(VI) from water using olive pomace (OP) was improved by partial pyrolysis of OP. The sorbents were characterized by physicochemical techniques. Sorption of Cr(III) on raw and partially pyrolyzed OP sorbents followed Freundlich isotherm and second-order rate kinetics. OP pyrolyzed at 150 °C (sorbent OP-150) exhibited maximum sorption capacity, favorability and the lowest sorption energy. Sorption was exothermic and spontaneous for the raw-OP and OP pyrolyzed at 100 or 150 °C; but endothermic and non-spontaneous for OP pyrolyzed at 200, 250, 300 or 400 °C. A speciation method of chromium was proposed, in which Cr(III) was selectively retained at pH 3 on sorbent OP-150; while total Cr was determined after reduction of Cr(VI). The method was selective with a detection limit for Cr(III) of 1.58 μg L⁻¹. The method was applied on natural and industrial waters (recoveries >97.7%, RSD’s <9%) and on tobacco leaves certified reference material (INCT-PVTL-6).