Absence of Free Aldehydes in Fresh Tissues, as Shown with a Neutralized Schiff Reagent

A neutralized Schiff's reagent (pH 6.7) was prepared and used to investigate the role of the acidic nature of the routine Schiff's reagent (pH 2.6) in the plasmal reaction. The neutralized reagent was satisfactory as an aldehyde reagent in the nucleal reaction on gut and, although giving a less intense reaction than the routine reagent in the PAS reaction on the gut and plasmal reaction on the aorta, was satisfactory here in respect to localization and thus to aldehyde specificity. Control sections for the plasmal reaction of unfixed nerve and aorta gave positive results when placed in the routine Schiff's, this increasing with time left in the reagent. Similar control sections in the neutralized Schiff's reagent remained consistently negative even though left in this reagent for 0.5 hr. The positive reaction of such control sections is apparently due to acid hydrolysis of labile plasmalogens by the routine Schiff's reagent in myelin and elastin and not to the presence of “free” aldehydes in these tissue elements     

MA-[D-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Normalizes Glucose Tolerance and Episodic Memory in a Mouse Model of Type 2 Diabetes Mellitus and Alzheimer’s Disease-Like Cognitive Impairment

International Journal of Peptide Research and Therapeutics - In addition to its roles in regulating energy balance and glucose homeostasis, leptin greatly influences hippocampal learning and...     

Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Prevents or Slows the Progression of Obesity,Insulin Resistance,and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus

International Journal of Peptide Research and Therapeutics - Oral delivery of MA-[d-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic...     

The Insulin Receptor: Both a Prototypical and Atypical Receptor Tyrosine Kinase

Unlike prototypical receptor tyrosine kinases (RTKs), which are single-chain polypeptides, the insulin receptor (InsR) is a preformed, covalently linked tetramer with two extracellular α subunits and two membrane-spanning, tyrosine kinase-containing β subunits. A single molecule of insulin binds asymmetrically to the ectodomain, triggering a conformational change that is transmitted to the cytoplasmic kinase domains, which facilitates their trans-phosphorylation. As in prototypical RTKs, tyrosine phosphorylation in the juxtamembrane region of InsR creates recruitment sites for downstream signaling proteins (IRS [InsR substrate] proteins, Shc) containing a phosphotyrosine-binding (PTB) domain, and tyrosine phosphorylation in the kinase activation loop stimulates InsR’s catalytic activity. For InsR, phosphorylation of the activation loop, which contains three tyrosine residues, also creates docking sites for adaptor proteins (Grb10/14, SH2B2) that possess specialized Src homology-2 (SH2) domains, which are dimeric and engage two phosphotyrosines in the activation loop.Insulin is a highly potent anabolic hormone that is critical for tissue development and for glucose homeostasis (Taniguchi et al. 2006). Released from the β cells of the pancreas, insulin regulates glucose output from the liver and glucose uptake into (primarily) skeletal muscle and adipose tissue. In addition, insulin promotes the synthesis and storage of carbohydrates, lipids, and protein. Insulin’s actions are mediated by the insulin receptor (InsR), a plasma membrane-resident glycoprotein and member of the receptor tyrosine kinase (RTK) family. Other members of the InsR subfamily of RTKs include the insulinlike growth factor-1 receptor (IGF1R) and insulin receptor-related receptor, the latter of which has no known ligand. As an RTK, InsR is ligand-activated through mechanisms that are both prototypical and atypical of RTKs. These mechanisms will be the focus of this article.     

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.     

Phytochemical Analysis and Total Antioxidant Capacity of Rhizome,Above‐Ground Vegetative Parts and Flower of Three Iris Species

This study was aimed at investigating the phytochemical composition and antioxidant capacity of rhizomes, above‐ground vegetative parts and flowers of three Iris species: Iris humilis Georgi , Iris pumila L. and Iris variegata L. UHPLC‐Orbitrap MS analysis was used for determination of phytochemical profile. Total pigments, phenolics, flavonoids, soluble sugars and starch content as well as ABTS antioxidant capacity were also determined. In total, 52 phenolics compounds were identified with 9 compounds (derivatives of iriflophenone, apigenin C‐glycosides, luteolin O‐glycoside, isoflavones derivatives of iristectorigenin, dichotomitin, nigracin and irilone) never reported before in Iris spp. Differences in phenolic composition profile, pigments, soluble sugar, starch, total phenolics and flavonoids content and total antioxidant capacity were found among Iris species and different part of plants. Significant correlation between total phenolic content and antioxidant capacity was determined. The obtained results are comparable with those obtained for medical plants. These findings could be useful for fingerprinting characterization of Iris species and estimation of possible use in pharmaceutical industries.     

Evolutionary replacement of components in a salamander pheromone signaling complex: more evidence for phenotypic-molecular decoupling

In this article we explore the evolutionary history of a functional complex at the molecular level in plethodontid salamanders. The complex consists of a proteinaceous courtship pheromone, a pheromone-producing gland on the male's chin, and a set of behaviors for delivering the pheromone to the female. Long-term evolutionary stasis is the defining feature of this complex at both the morphological and behavioral levels. However, our previous assessment of the pheromone gene, plethodontid receptivity factor (PRF), revealed rapid evolution at the molecular level despite stasis at higher levels of organization. Analysis of a second pheromone gene, sodefrin precursor-like factor (SPF), now indicates that evolutionary decoupling in this complex is pervasive. The evolutionary profiles of SPF and PRF are remarkably similar in that: (a) both genes exhibit high levels of sequence diversity both within and across taxa, (b) genetic diversity has been driven by strong positive selection, and (c) the genes have evolved heterogeneously in different salamander lineages. The composition of the pheromone signal as a whole, however, has experienced an extraordinary evolutionary transition. Whereas SPF has been retained throughout the 100 MY radiation of salamanders, PRF has only recently been recruited to a pheromone function (27 million years ago). When SPF and PRF coexist in the same clade, they show contrasting patterns of evolution. When one shows rapid evolution driven by positive selection, the other shows neutral divergence restrained by purifying selection. In one clade, the origin and subsequent rapid evolution of PRF appear to have interfered with the evolution and persistence of SPF, leading to a pattern of evolutionary replacement. Overall, these two pheromone genes provide a revealing window on the dynamics that drive the evolution of multiple traits in a signaling complex.