On the Correlation between the Oxygen in Hydrogen Content and the Catalytic Activity of Cathode Catalysts in PEM Water Electrolysis

Altogether five platinum group metal (PGM) and PGM-free cathode catalysts were investigated in full PEM water electrolysis cells regarding their polarisation behaviour and their hydrogen and oxygen recombination properties. It was shown that the recombination activity of permeated oxygen and evolved hydrogen within the cathodic catalyst layer correlates with the activity of the oxygen reduction reaction (ORR) which was determined ex situ with linear sweep voltammetry. We found that the investigated PGM-free cathode catalysts had a low activity for the ORR resulting in higher measurable oxygen in hydrogen volume fractions compared to the PGM catalysts, which are more active for the ORR. Out of the three investigated PGM-free catalysts, only one commercially available material based on a Ti suboxide showed a similar good polarisation behaviour as the state of the art cathode catalyst platinum, while its recombination activity was the lowest of all catalysts. In addition to the recombination of hydrogen and oxygen on the electrocatalysts, we found that the prevalent carbon-based cathodic porous transport layers (PTL) also offer catalytically active recombination sites. In comparison to an inactive PTL, the measurable oxygen flux using carbon-based PTLs was lower and the recombination was enhanced by microporous coatings with high surface areas.

Synergistic Effect of Simultaneous versus Sequential Combined Treatment of Histone Deacetylase Inhibitor Valproic Acid with Etoposide on Melanoma Cells

Melanoma is the most lethal form of skin cancer, which is intrinsically resistant to conventional chemotherapy. Combination therapy has been developed to overcome this challenge and show synergistic anticancer effects on melanoma. Notably, the histone deacetylase inhibitor, valproic acid (VPA), has been indicated as a potential sensitizer of chemotherapy drugs on various metastatic cancers, including advanced melanoma. In this study, we explored whether VPA could serve as an effective sensitizer of chemotherapy drug etoposide (ETO) on B16-F10 and SK-MEL-2-Luc melanoma cell lines in response to drug-induced DNA damages. Our results demonstrated that the VPA-ETO simultaneous combined treatment and ETO pretreated sequential combined treatment generated higher inhibitory effectivities than the individual treatment of each drug. We found the VPA-ETO simultaneous combined treatment contributed to the synergistic inhibitory effect by the augmented DNA double-strand breaks, accompanied by a compromised homologous recombination activity. In comparison, the ETO pretreated sequential combined treatment led to synergistic inhibitory effect via enhanced apoptosis. Surprisingly, the enhanced homologous recombination activity and G2/M phase arrest resulted in the antagonistic effect in both cells under VPA pretreated sequential combined treatment. In summary, our findings suggested that sequential order and effective dose of drug administration in VPA-ETO combination therapy could induce different cellular responses in melanoma cells. Such understanding might help potentiate the effectiveness of melanoma treatment and highlight the importance of sequential order and effective dose in combination therapy.

Genome-wide variability in recombination activity is associated with meiotic chromatin organization

Background: Recombination enables reciprocal exchange of genomic information between parental chromosomes and successful segregation of homologous chromosomes during meiosis. Errors in this process lead to negative health outcomes, while variability in recombination rate affects genome evolution. In mammals, most crossovers occur in hotspots defined by PRDM9 motifs, though PRDM9 binding sites are not all equally hot. We hypothesize that dynamic patterns of meiotic genome folding are linked to recombination activity. Results: We apply an integrative bioinformatics approach to analyze how three-dimensional (3D) chromosomal organization during meiosis relates to rates of double-strand-break (DSB) and crossover formation at PRDM9 hotspots. We show that active, spatially accessible genomic regions during meiotic prophase are associated with DSB-favoured hotspots, which further adopt a transient locally active configuration in early prophase. Conversely, crossover formation is depleted among DSBs in spatially accessible regions during meiotic prophase, particularly within gene bodies. We also find evidence that active chromatin regions have smaller average loop sizes in mammalian meiosis. Collectively, these findings establish that differences in chromatin architecture along chromosomal axes are associated with variable recombination activity. Conclusions: We propose an updated framework describing how 3D organization of brush-loop chromosomes during meiosis may modulate recombination.

First cases of Recombinant Noroviruses in Cameroon

Noroviruses have been reported as being a common cause of acute gastroenteritis both in children and adults worldwide. Genotyping and nomenclature of noroviruses was based on the partial capsid gene of the ORF2. Due to frequent reported recombination activities in the ORF1/ORF2 junction, a new dual nomenclature has been proposed based on genotyping of two genes – the capsid and polymerase genes. This study identified recombinant noroviruses circulating in Cameroon between 2010 and 2013. RT-PCR –based methods, next generation sequencing and phylogenetic analysis were used to genotype samples from hospitalized children. The combined RdRp/capsid dual genotype was determined for 19 GII strains including 5 RdRp genotypes (GII.P4, GII.P7, GII.P17, GII.P21, and GII.P31) and 5 capsid genotypes (GII.2, GII.3, GII.4, GII.6, GII.17). They had 17(89.5%) recombinants and 2 (112.5%) non recombinants. 17 were recombinants. The most prevalent noroviruses were GII.4 (76.5%) consisting of GII.4 Sydney [P31] (41.2%) and GII.4 Sydney [P4 New Orleans] (35.3%), followed by GII.6 [P7] (11.8%), GII.2 [P21] (5.9%) and GII.3 [P21] (5.9%). This is the first study of norovirus dual genotyping and recombinants in Cameroon. Recombination activity is high and contributes to ongoing evolution of circulating noroviruses in Cameroon.