Discovery of bioactive small-molecule inhibitor of poly adp-ribose polymerase: implications for energy-deficient cells

Poly (ADP-ribose) polymerase (PARP1) is a nuclear protein that, when overactivated by oxidative stress-induced DNA damage, ADP ribosylates target proteins leading to dramatic cellular ATP depletion. We have discovered a biologically active small-molecule inhibitor of PARP1. The discovered compound inhibited PARP1 enzymatic activity in vitro and prevented ATP loss and cell death in a surrogate model of oxidative stress in vivo. We also investigated a new use for PARP1 inhibitors in energy-deficient cells by using Huntington's disease as a model. Our results showed that insult with the oxidant hydrogen peroxide depleted cellular ATP in mutant cells below the threshold of viability. The protective role of PARP1 inhibitors against oxidative stress has been shown in this model system.     

Comparing efficiency across markets: An extension and critique of the methodology

The use of non-parametric frontier methods for the evaluation of product market efficiency in heterogeneous markets seems to have gained some popularity recently. However, the statistical properties of these frontier estimators have been largely ignored. The main point is that non-parametric frontier estimators are biased and that the degree of bias depends on specific sample properties, most importantly sample size and number of dimensions of the model. To investigate the effect of this bias on comparing market efficiency, this contribution estimates the efficiency for several datasets for two main product categories. Following (Zhang, Y., Bartels, R., 1998. The effect of sample size on the mean efficiency in DEA with an application to electricity distribution in Australia, Sweden and New Zealand. Journal of Productivity Analysis, 9(3), 187-204.), these results comprise re-estimates for the larger samples limiting their size to that of the smaller samples when the model dimensions for different samples are identical. Furthermore, sample sizes are adjusted to mitigate the eventual differences in dimensions in specification. This allows comparing market efficiency for different markets on a more equal footing, since it reduces the bias effect to a minimum making the comparison of market efficiency possible. However, the article also points out the critical limitations of this [Zhang, Y., Bartels, R., (1998). The effect of sample size on the mean efficiency in DEA with an application to electricity distribution in Australia, Sweden and New Zealand. Journal of Productivity Analysis 9 (3), 187–204] approach in certain respects. Apart from reporting these negative results, we also offer some suggestions for future work.     

Stereoselective Base‐Catalyzed 1,1‐Silaboration of Terminal Alkynes

A base‐catalyzed reaction that enables stereoselective 1,1‐silaboration of terminal alkynes is described. This method not only offers a new strategy to functionalize simple and readily accessible alkynes beyond 1,2‐difunctionalization, but also provides an unconventional atom‐ and step‐economical approach to rapidly and reliably access versatile geminal silylboranes in the absence of transition metals and with exquisite stereoselectivity.     

On the density of foliations without algebraic solutions on weighted projective planes

We prove that a generic holomorphic foliation on a weighted projective plane has no algebraic solutions when the degree is big enough. We also prove an analogous result for foliations on Hirzebruch surfaces.     

Druggable exosites of the human kino-pocketome

Journal of Computer-Aided Molecular Design - Small molecules binding at any of the multiple regulatory sites on the molecular surface of a protein kinase may stabilize or disrupt the corresponding...     

Synthesis of ferrocenylpyrazole derivatives

Reactions of arene‐ and pyridinecarbaldehydes with ferrocenyl‐4,5‐dihydropyrazoles afforded 1‐arylmethyl‐ and 1‐pyridylmethyl‐3,5‐aryl(ferrocenyl)pyrazoles. Their structures were established based on spectroscopic methods and, for 4‐[(3,5‐diferrocenylpyrazol‐1‐yl)methyl]pyridine, based on X‐ray diffraction analysis.     

Excited‐State Charge Transfer in Covalently Functionalized MoS2 with a Zinc Phthalocyanine Donor–Acceptor Hybrid

The functionalization of MoS₂ is of paramount importance for tailoring its properties towards optoelectronic applications and unlocking its full potential. Zinc phthalocyanine (ZnPc) carrying an 1,2‐dithiolane oxide linker was used to functionalize MoS₂ at defect sites located at the edges. The structure of ZnPc‐MoS₂ was fully assessed by complementary spectroscopic, thermal, and microscopy imaging techniques. An energy‐level diagram visualizing different photochemical events in ZnPc‐MoS₂ was established and revealed a bidirectional electron transfer leading to a charge separated state ZnPc^{. +} ‐MoS₂^.?. Markedly, evidence of the charge transfer in the hybrid material was demonstrated using fluorescence spectroelectrochemistry. Systematic studies performed by femtosecond transient absorption revealed the involvement of excitons generated in MoS₂ in promoting the charge transfer, while the transfer was also possible when ZnPc was excited, signifying their potential in light‐energy‐harvesting devices.