In Vitro Identification of Gold Nanorods through Hyperspectral Imaging

Due to their unique plasmonic and optical properties, gold nanorods (GNR) have shown tremendous potential for nano-based applications extending into a variety of fields including bioimaging, sensor development, electronics, and cancer therapy. These distinctive, shape-specific properties are strongly dependent upon the GNR aspect ratio, thus producing the ability to be targeted for an application by fine-tuning their physical parameters. It is owing to their characteristic spectral signature, which is vastly different from that of a cellular setting, that GNRs are emerging as an ideal candidate for nano-based imaging applications. However, one challenge that has emerged in the field of bioimaging is the need to account for the observed plasmon coupling effect that arises from GNR agglomeration in a physiological environment. In this study, GNRs with aspect ratios of 2.5 and 6.0 were actively identified in an in vitro setting through a hyperspectral imaging (HSI) analysis; which successfully recognized and separated the light scattering pattern of these particles from that of the surrounding cells. Through inclusion of agglomerated GNR spectral patterns in the HSI spectral library, this imaging technique was able to overcome the complication of plasmon coupling, though to varying degrees. These results demonstrate the tremendous potential of GNRs coupled with HSI analysis to advance the field of nano-based sensing and imaging mechanisms.     

Opposite Roles of NMDA Receptors in Relapsing and Primary Progressive Multiple Sclerosis

Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms.     

Introduction to the Special Issue on Savanna Chimpanzees

International Journal of Primatology -     

The relationship of hemolymph osmotic pressure to spermatogenesis in the tobacco budworm,Heliothis virescens

The hemolymph osmotic pressure of male Heliothis virescens last instar larvae and pupae can be correlated with the state of spermatogenesis: intermediate (approx. 325 mOsm/kg) osmotic pressures are found in pre-meiotic animals, low (approx. 300 mOsm/kg) osmotic pressures characterize meiosis and elongation, and high (approx. 370 mOsm/kg) osmotic pressures, characterize the tests of diapausing pupae, where mature sperm have disappeared and only pre-meiotic sperm are found. In vitro studies show that, as the osmotic pressure of the medium is increased, spermatogenesis is inhibited and the survival of pre-meiotic cysts is enhanced. It is proposed that the osmotic pressure of the hemolymph plays a role in spermatogenesis and in the preservation of immature cysts during diapause.     

Development of low-linolenic acid Brassica oleracea lines through seed mutagenesis and molecular characterization of mutants

Designing the fatty acid composition of Brassica napus L. seed oil for specific applications would extend the value of this crop. A mutation in Fatty Acid Desaturase 3 (FAD3), which encodes the desaturase responsible for catalyzing the formation of α-linolenic acid (ALA; 18:3 ^cisΔ9,12,15), in a diploid Brassica species would potentially result in useful germplasm for creating an amphidiploid displaying low ALA content in the seed oil. For this, seeds of B. oleracea (CC), one of the progenitor species of B. napus, were treated with ethyl-methane-sulfonate to induce mutations in genes encoding enzymes involved in fatty acid biosynthesis. Seeds from 1,430 M₂ plants were analyzed, from which M₃ seed families with 5.7–6.9 % ALA were obtained. Progeny testing and selection for low ALA content were carried out in M₃–M₇ generations, from which mutant lines with <2.0 % ALA were obtained. Molecular analysis revealed that the mutation was due to a single nucleotide substitution from G to A in exon 3 of FAD3, which corresponds to an amino acid residue substitution from glutamic acid to lysine. No obvious differences in the expression of the FAD3 gene were detected between wild type and mutant lines; however, evaluation of the performance of recombinant Δ-15 desaturase from mutant lines in yeast indicated reduced production of ALA. The novelty of this mutation can be inferred from the position of the point mutation in the C-genome FAD3 gene when compared to the position of mutations reported previously by other researchers. This B. oleracea mutant line has the potential to be used for the development of low-ALA B. napus and B. carinata oilseed crops.     

The maize lipoxygenase,ZmLOX10, mediates green leaf volatile,jasmonate and herbivore‐induced plant volatile production for defense against insect attack

Fatty acid derivatives are of central importance for plant immunity against insect herbivores; however, major regulatory genes and the signals that modulate these defense metabolites are vastly understudied, especially in important agro‐economic monocot species. Here we show that products and signals derived from a single Zea mays (maize) lipoxygenase (LOX), ZmLOX10, are critical for both direct and indirect defenses to herbivory. We provide genetic evidence that two 13‐LOXs, ZmLOX10 and ZmLOX8, specialize in providing substrate for the green leaf volatile (GLV) and jasmonate (JA) biosynthesis pathways, respectively. Supporting the specialization of these LOX isoforms, LOX8 and LOX10 are localized to two distinct cellular compartments, indicating that the JA and GLV biosynthesis pathways are physically separated in maize. Reduced expression of JA biosynthesis genes and diminished levels of JA in lox10 mutants indicate that LOX10‐derived signaling is required for LOX8‐mediated JA. The possible role of GLVs in JA signaling is supported by their ability to partially restore wound‐induced JA levels in lox10 mutants. The impaired ability of lox10 mutants to produce GLVs and JA led to dramatic reductions in herbivore‐induced plant volatiles (HIPVs) and attractiveness to parasitoid wasps. Because LOX10 is under circadian rhythm regulation, this study provides a mechanistic link to the diurnal regulation of GLVs and HIPVs. GLV‐, JA‐ and HIPV‐deficient lox10 mutants display compromised resistance to insect feeding, both under laboratory and field conditions, which is strong evidence that LOX10‐dependent metabolites confer immunity against insect attack. Hence, this comprehensive gene to agro‐ecosystem study reveals the broad implications of a single LOX isoform in herbivore defense.     

Design and synthesis of tricyclic cores for kinase inhibition

Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest.