DPYD IVS14+1G>A and 2846A>T genotyping for the prediction of severe fluoropyrimidine-related toxicity: a meta-analysis.

Aim: In the present study we conducted a systematic review and meta-analysis of published data to quantify the impact of the DPYD IVS14+1G>A and 2846A>T variants on the risk of fluoropyrimidine-related toxicities and to determine sensitivity and specificity testing for DPYD variants. Methods: Relevant studies were identified through PubMed and Web of Knowledge databases, studies included were those published up until to May 2012. Study quality was assessed according to the HuGENET guidelines and Strengthening the Reporting of Genetic Association (STREGA) recommendations. Results: Random-effects meta-analysis provided evidence that carriers of DPYD IVS14+1G>A are at higher risk of ≥3 degrees of overall grade toxicity, hematological toxicity, mucositis and diarrhea. In addition, a strong association was also found between carriers of the DPYD 2846T allele and overall grade ≥3 toxicity or grade ≥3 diarrhea. An inverse linear relationship was found in prospective studies between the odds ratio of DPYD IVS14+1G>A and the incidence of overall grade ≥3 toxicity, indicating an higher impact in cohorts in which the incidence of severe toxicity was lower. Conclusion: The results of this meta-analysis confirm clinical validity of DPYD IVS14+1G>A and 2846A>T as risk factors for the development of severe toxicities following fluoropyrimidine treatment. Furthermore, the sensitivity and specificity estimates obtained could be useful in establishing the cost-effectiveness of testing for DPYD variants. Original submitted 4 March 2013; Revision submitted 17 June 2013

Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice

Adolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity

Orbital magnetoelectric effect in zigzag nanoribbons of p-band systems

Profiles of the spin and orbital angular momentum accumulations induced by a longitudinally applied electric field are explored in nanoribbons of $p$-band systems with a honeycomb lattice. We show that nanoribbons with zigzag borders can exhibit orbital magnetoelectric effects. More specifically, we have found that purely orbital magnetization oriented perpendicularly to the ribbon may be induced in these systems by means of the external electric field, when sublattice symmetry is broken. The effect is rather general and may occur in other multi-orbital materials.Comment: 10 pages, 4 figure

Disentangling orbital and valley Hall effects in bilayers of transition metal dichalcogenides

It has been recently shown that monolayers of transition metal dichalcogenides (TMDs) in the 2H structural phase exhibit relatively large orbital Hall conductivity plateaus within their energy band gaps, where their spin Hall conductivities vanish. However, since the valley Hall effect (VHE) in these systems also generates a transverse flow of orbital angular momentum it becomes experimentally challenging to distinguish between the two effects in these materials. The VHE requires inversion symmetry breaking to occur, which takes place in the TMD monolayers, but not in the bilayers. We show that a bilayer of 2H-MoS$_2$ is an orbital Hall insulator that exhibits a sizeable OHE in the absence of both spin and valley Hall effects. This phase can be characterised by an orbital Chern number that assumes the value $\mathcal{C}_{L}=2$ for the 2H-MoS$_2$ bilayer and $\mathcal{C}_{L}=1$ for the monolayer, confirming the topological nature of these orbital-Hall insulator systems. Our results are based on density functional theory (DFT) and low-energy effective model calculations and strongly suggest that bilayers of TMDs are highly suitable platforms for direct observation of the orbital Hall insulating phase in two-dimensional materials. Implications of our findings for attempts to observe the VHE in TMD bilayers are also discussed.Comment: 7 pages, 4 figures + Supplementary materia