Importance of Electronic Relaxation for Inter-Coulombic Decay in Aqueous Systems

Inspired by recent photoelectron spectroscopy experiments on hydroxide solutions, we have examined the conditions necessary for enhanced (and, in the case of solutions, detectable) inter-Coulombic decay (ICD)—Auger emission from an atomic site other than that originally excited. We present general guidelines, based on energetic and spatial overlap of molecular orbitals, for this enhancement of inter-Coulombic decay-based energy transfer in solutions. These guidelines indicate that this decay process should be exhibited by broad classes of biomolecules and suggest a design criterion for targeted radiooncology protocols. Our findings show that photoelectron spectroscopy cannot resolve the current hydroxide coordination controversy

Nuclear quantum effects in the structure and lineshapes of the N2 near-edge x-ray absorption fine structure spectrum

We study the relative ability of several models of x-ray absorption spectra to capture the Franck–Condon structure apparent from an experiment on gaseous nitrogen. In doing so, we adopt the Born–Oppenheimer approximation and a constrained density functional theory method for computing the energies of the x-ray-excited molecule. Starting from an otherwise classical model for the spectrum, we systematically introduce more realistic physics, first by substituting the quantum mechanical nuclear radial density in the bond separation R for the classical radial density, then by adding the effect of zero-point energy and other level shifts, and finally by including explicit rovibrational quantization of both the ground and excited states. The quantization is determined exactly, using a discrete variable representation (DVR). We show that the near-edge x-ray absorption fine structure (NEXAFS) spectrum can be predicted semiquantitatively within this framework. We also address the possibility of non-trivial temperature dependence in the spectrum. By using constrained density functional theory in combination with more accurate potentials, we demonstrate that it is possible to improve the predicted spectrum. Ultimately, we establish the predictive limits of our method with respect to vibrational fine structure in NEXAFS spectra

Importance of Electronic Relaxation for Inter-Coulombic Decay in Aqueous Systems

Inspired by recent photoelectron spectroscopy (PES) experiments on hydroxide solutions, we have examined the conditions necessary for enhanced (and, in the case of solutions, detectable) intercoulombic decay (ICD)--Auger emission from an atomic site other than that originally excited. We present general guidelines, based on energetic and spatial overlap of molecular orbitals, for this enhancement of ICDbased energy transfer in solutions. These guidelines indicate that this decay process should be exhibited by broad classes of biomolecules and suggest a design criterion for targeted radiooncology protocols. Our findings show that PES cannot resolve the current hydroxide coordination controversy

Bee‑safe peptidomimetic acaricides achieved by comparative genomics

The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey beesafe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa miteselective acaricides, hence, expedited translational processes

A comparison of alternative assays to measure DNA damage in stallion spermatozoa: TUNEL test versus ‘Nicoletti assay’

The aberrations of sperm DNA may cause various problems and have negative consequences on fertility. These influence embryonic development or might lead to early embryo loss. Sperm Chromatin Structure Assay (SCSA) is the flow cytometric method most often used for the detection of DNA lesions; however, some studies using that method reached confusing conclusions. The aim of this pilot study was to adjust and compare two alternative tests, namely the TUNEL test and the Nicoletti assay. The above-mentioned two flow cytometric methods capable of detecting the fragmented DNA of sperm were tested on 12 frozen-thawed stallion semen samples. The TUNEL test demonstrated much higher DNA fragmentation ratio than the Nicoletti assay (mean ± SD: 30.77 ± 13.03% vs. 1.93 ± 0.89%, respectively). A fluorescent microscopic check of the samples showed that TUNEL labelled the plasma membrane and the mitochondria in a nonspecific way, rather than detecting only the fragmented DNA, thus eventually resulting in a false positive sign. The Nicoletti assay is simpler, quicker and does not detect nonspecific binding; however, further analyses are required to determine its diagnostic value

A functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production

Bone morphogenetic proteins (BMP) are firmly implicated as intra-ovarian regulators of follicle development and steroidogenesis. Here we report a microarray analysis showing that treatment of cultured bovine theca cells (TC) with BMP6 significantly (>2-fold; P<0.01) up- or down-regulated expression of 445 genes. Insulin-like peptide 3 (INSL3) was the most heavily down-regulated gene (-43-fold) with CYP17A1 and other key transcripts involved in TC steroidogenesis including LHCGR, INHA, STAR, CYP11A1 and HSD3B1 also down-regulated. BMP6 also reduced expression of NR5A1 encoding steroidogenic factor-1 known to target the promoter regions of the aforementioned genes. Real-time PCR confirmed these findings and also revealed a marked reduction in expression of INSL3 receptor (RXFP2). Secretion of INSL3 protein and androstenedione were also suppressed suggesting a functional link between BMP and INSL3 pathways in controlling androgen synthesis. RNAi-mediated knockdown of INSL3 reduced INSL3 mRNA and secreted protein level (75 and 94%, respectively) and elicited a 77% reduction in CYP17A1 mRNA level and 83% reduction in androstenedione secretion. Knockdown of RXFP2 also reduced CYP17A1 mRNA level (81%) and androstenedione secretion (88%). Conversely, treatment with exogenous (human) INSL3 increased androstenedione secretion ~2-fold. The CYP17 inhibitor abiraterone abolished androgen secretion and reduced expression of both INSL3 and RXFP2. Collectively, these findings indicate a positive autoregulatory role for INSL3 signaling in maintaining thecal androgen production, and visa versa. Moreover, BMP6-induced suppression of thecal androgen synthesis may be mediated, at least in part, by reduced INSL3-RXFP2 signaling

Evolution of Precision Medicine and Surgical Strategies for Bicuspid Aortic Valve-Associated Aortopathy

Bicuspid aortic valve (BAV) is a common congenital cardiac malformation affecting 1–2% of people. BAV results from fusion of two adjacent aortic valve cusps, and is associated with dilatation of the aorta, known as bicuspid valve associated aortopathy. Bicuspid valve aortopathy is progressive and associated with catastrophic clinical events, such as aortic dissection and rupture. Therefore, frequent monitoring and early intervention with prophylactic surgical resection of the proximal aorta is often recommended. However, the specific pattern of aortopathy is highly variable among patients, with different segments of the ascending aorta being affected. Individual patient risks are sometimes difficult to predict. Resection strategies are informed by current surgical guidelines which are primarily based on aortic size and growth criteria. These criteria may not optimally reflect the risk of important aortic events. To address these issues in the care of patients with bicuspid valve aortopathy, our translational research group has focused on validating use of novel imaging techniques to establish non-invasive hemodynamic biomarkers for risk-stratifying BAV patients. In this article, we review recent efforts, successes, and ongoing challenges in the development of more precise and individualized surgical approaches for patients with bicuspid aortic valves and associated aortic disease