Peripheral regulation by ecdysteroids of olfactory responsiveness in male Egyptian cotton leaf worms, Spodoptera littoralis

Physiological and behavioral plasticity allows animals to adapt to changes in external (environmental) and internal (physiological) factors. In insects, the physiological state modulates adult behavior in response to different odorant stimuli. Hormones have the potential to play a major role in the plasticity of the olfactory responses. To explore if peripheral olfactory processing could be regulated by steroid hormones, we characterized the molecular, electrophysiological, and behavioral response to changes in endogenous hormone levels in adult male Spodoptera littoralis. The expression of the receptor complex (EcR/USP) was localized by in situ hybridization in the olfactory sensilla of antennae. Injections of 20-hydroxyecdysone (20E) induced an ecdysteroid signaling pathway in antennae and increased expression of the nuclear receptors EcR, USP and E75. Diacylglycerol kinase (DGK) and CaM expression were also up-regulated by 20E. Taken together, these molecular, electrophysiological, and behavioral results suggest a hormonal regulation of the peripheral olfactory processing in S. littoralis.     

Low plasma albumin levels are associated with increased plasma protein glycation and HbA1c in diabetes

Albumin is one of the most abundant plasma proteins and is heavily glycated in diabetes. In this study, we have addressed whether variation in the albumin levels influence glycation of plasma proteins and HbA1c. The study was performed in three systems: (1) streptozotocin (STZ)-induced diabetic mice plasma, (2) diabetic clinical plasma, and (3) in vitro glycated plasma. Diabetic mice and clinical plasma samples were categorized as diabetic high albumin plasma (DHAP) and diabetic low albumin plasma (DLAP) on the basis of their albumin levels. For the in vitro experiment, two albumin levels, high albumin plasma (HAP) and low albumin plasma (LAP), were created by differential depletion of plasma albumin. Protein glycation was studied by using a combination of two-dimensional electrophoresis (2DE), Western blotting, and LC-MS(E). In both mice and clinical experiments, an increased plasma protein glycation was observed in DLAP than in DHAP. Additionally, plasma albumin levels were negatively correlated with HbA1c. The in vitro experiment with differential depletion of albumin mechanistically showed that the low albumin levels are associated with increased plasma protein glycation and that albumin competes for glycation with other plasma proteins.     

Isocitrate dehydrogenase of Helicobacter pylori potentially induces humoral immune response in subjects with peptic ulcer disease and gastritis

Background

H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD), an important house keeping protein of H. pylori.

Methodology/Principal Findings

Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA) in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD.

Conclusions/Significance

ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1) and therefore, may not be a notable proinflammatory agent.     

Multistep Photoluminescence Decay Reveals Dissociation of Geminate Charge Pairs in Organolead Trihalide Perovskites

Charge carrier dynamics in organolead iodide perovskites is analyzed by employing time‐resolved photoluminescence spectroscopy with several ps time resolution. The measurements performed by varying photoexcitation intensity over five orders of magnitude enable separation of photoluminescence components related to geminate and nongeminate charge carrier recombination and to address the dynamics of an isolated geminate electron–hole pair. Geminate recombination dominates at low excitation fluence and determines the initial photoluminescence decay. This decay component is remarkably independent of the material structure and experimental conditions. It is demonstrated that dependences of the geminate and nongeminate radiative recombination components on excitation intensity, repetition rate, and temperature, are hardly compatible with carrier trapping and exciton dissociation models. On the basis of semiclassical and quantum mechanical numerical calculation results, it is argued that the fast photoluminescence decay originates from gradual spatial separation of photogenerated weakly bound geminate charge pairs.     

Chromatographic methods for large-scale preparation of immunoglobulin G2a monoclonal antibodies Lym-1 and TNT-1 F(ab')2 fragments

Lym-1 and TNT-1 are two murine immunoglobulin G_2a monoclonal antibodies (MAbs) which have been used for clinical trials in cancer patients. This paper describes methods for large-scale preparation of F(ab')₂ fragments from 50 mg to 4 g of MAbs Lym-1 and TNT-1. Digestion of MAbs with pepsin was optimized and performed at pH 3.8, a pepsin/antibody ratio of 1:250, and 3–4 h of incubation at 37°C. The F(ab')₂ fragments were purified by tandem column procedures using fast protein liquid chromatography. Quality control analyses of the products included protein purity, isoelectric point, immunoreactivity, and endotoxin level. The results revealed that the chromatographic procedures are practical, simple, and effective, and can be used to produce gram quantities of clinical-grade F(ab')₂ fragments for the diagnosis of cancer in patients.     

Adamantanes Enhance the Photovoltaic Performance and Operational Stability of Perovskite Solar Cells by Effective Mitigation of Interfacial Defect States

Passivation of electronic defects is an effective strategy to boost the performance and operational stability of perovskite solar cells (PSCs). Identifying molecular materials that achieve this purpose is a key target of current research efforts. Here, adamantane (AD) and 1‐adamantylamine (ADA) are introduced as molecular modulators to abate electronic defects present within the bulk and at the perovskite–hole conductor interface. To this effect, the modulator is added either into the antisolvent (AS) to precipitate it together with the perovskite (AS method) or they are spin coated (SC) onto its surface (SC method). Time‐resolved photoluminescence measurements show substantially longer lifetimes for perovskite films treated with AD and ADA compared to the reference sample. In line with this observation, it is found that the presence of AD and ADA molecules at the interface between the perovskite film and the hole conductor increases all photovoltaic metrics, in particular the open circuit photovoltage (V _oc) as well as the operational stability of the PSC.     

Imidacloprid impedes mitochondrial function and induces oxidative stress in cotton bollworm, <Emphasis Type="Italic">Helicoverpa armigera</Emphasis> larvae (Hubner: Noctuidae)

Neonicotinoids have high agonistic affinity to insect nicotinic acetylcholine receptors (nAChR) and are frequently used as insecticides against most devastating lepidopteran insect pests. Imidacloprid influenced dose-dependent decline in the state III and IV respiration, respiration control index (RCI), and P/O ratios, in vitro and in vivo. The bioassay indicated its LD₅₀ value to be 531.24 μM. The insecticide exhibited a dose-dependent inhibition on F₀F₁-ATPase and complex IV activity. At 600 μM, the insecticide inhibited 83.62 and 27.13% of F₀F₁-ATPase and complex IV activity, respectively, and induced the release of 0.26 nmoles/min/mg protein of cytochrome c. A significant dose- and time-dependent increase in oxidative stress was observed; at 600 μM, the insecticide correspondingly induced lipid peroxidation, LDH activity, and accumulation of H₂O₂ content by 83.33, 31.51 and 223.66%. The stress was the maximum at 48 h of insecticide treatment (91.58, 35.28, and 189.80%, respectively). In contrast, catalase and superoxide dismutase were reduced in a dose- and time-dependent manner in imidacloprid-fed larvae. The results therefore suggest that imidacloprid impedes mitochondrial function and induces oxidative stress in H. armigera, which contributes to reduced growth of the larvae along with its neurotoxic effect.     

Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents

Based on our previous results and literature precedence, a series of 2-anilinopyridinyl-benzothiazole Schiff bases were rationally designed by performing molecular modeling experiments on some selected molecules. The binding energies of the docked molecules were better than the E7010, and the Schiff base with trimethoxy group on benzothiazole moiety, 4y was the best. This was followed by the synthesis of a series of the designed molecules by a convenient synthetic route and evaluation of their anticancer potential. Most of the compounds have shown significant growth inhibition against the tested cell lines and the compound 4y exhibited good antiproliferative activity with a GI₅₀ value of 3.8 µM specifically against the cell line DU145. In agreement with the docking results, 4y exerted cytotoxicity by the disruption of the microtubule dynamics by inhibiting tubulin polymerization via effective binding into colchicine domain, comparable to E7010. Detailed binding modes of 4y with colchicine binding site of tubulin were studied by molecular docking. Furthermore, 4y induced apoptosis as evidenced by biological studies like mitochondrial membrane potential, caspase-3, and Annexin V-FITC assays.