Characterization for Binding Complex Formation with Site-Directly Immobilized Antibodies Enhancing Detection Capability of Cardiac Troponin I

The enhanced analytical performances of immunoassays that employed site-directly immobilized antibodies as the capture binders have been functionally characterized in terms of antigen-antibody complex formation on solid surfaces. Three antibody species specific to cardiac troponin I, immunoglobulin G (IgG), Fab, and F(ab′)2 were site-directly biotinylated within the hinge region and then immobilized via a streptavidin-biotin linkage. The new binders were more efficient capture antibodies in the immunoassays compared to randomly bound IgG, particularly, in the low antibody density range. The observed improvements could have resulted from controlled molecular orientation and also from flexibility, offering conditions suitable for binding complex formations

Influence of Calcium Sulfate Type on Evolution of Reaction Products and Strength in NaOH- and CaO-Activated Ground Granulated Blast-Furnace Slag

This study investigated the influences of CaSO4 type (i.e., anhydrite vs. gypsum) on strength development and reaction products in the activation of ground granulated blast-furnace slag (GGBFS) when different activators (i.e., CaO vs. NaOH) and sources of GGBFS were used. In the CaO-activation, the addition of calcium sulfates greatly enhanced 28-day strengths, regardless of the choice of CaSO4 or GGBFS source, through increasing the quantities of reaction products and reducing pore volume and size. However, in the NaOH-activation, the use of calcium sulfates showed the complex dependency of strength on the choice of CaSO4 type and GGBFS source, and it barely produced beneficial effects on the quantity of reaction products and reduction of pore volume and size. Thus, the results in this study indicate that the combination of CaO-activation and calcium sulfates is a more effective means of activating GGBFS to gain enhanced strength and significant quality control than the use of gypsum with NaOH-activation

Effects of informative and confirmatory feedback on brain activation during negative feedback processing

The current study compared the effects of informative and confirmatory feedback on brain activation during negative feedback processing. For confirmatory feedback trials, participants were informed that they had failed the task, whereas informative feedback trials presented task relevant information along with the notification of their failure. Fourteen male undergraduates performed a series of spatial-perceptual tasks and received feedback while their brain activity was recorded. During confirmatory feedback trials, greater activations in the amygdala, dorsal anterior cingulate cortex, and the thalamus (including the habenular) were observed in response to incorrect responses. These results suggest that confirmatory feedback induces negative emotional reactions to failure. In contrast, informative feedback trials elicited greater activity in the dorsolateral prefrontal cortex (DLPFC) when participants experienced failure. Further psychophysiological interaction (PPI) analysis revealed a negative coupling between the DLPFC and the amygdala during informative feedback relative to confirmatory feedback trials. These findings suggest that providing task-relevant information could facilitate implicit down-regulation of negative emotions following failure

Intracorporeal Anastomosis Using Linear Stapler in Laparoscopic Distal Gastrectomy: Comparison between Gastroduodenostomy and Gastrojejunostomy

Purpose: Intracorporeal anastomosis during laparoscopic gastrectomy is becoming increasingly prevalent. However, selection of the anastomosis method after laparoscopic distal gastrectomy is equivocal because of a lack of technical feasibility and safety. We compared intracorporeal gastroduodenostomy with gastrojejunostomy using linear staplers to evaluate the technical feasibility and safety of intracorporeal anastomoses as well as its' minimally invasiveness. Materials and Methods: Retrospective analyses of a prospectively collected database for gastric cancer revealed 47 gastric cancer patients who underwent laparoscopic distal gastrectomy with either intracorporeal gastroduodenostomy or gastrojejunostomy from March 2011 to June 2011. Perioperative outcomes such as operation time, postoperative complication, and hospital stay were compared according to the type of anastomosis. Postoperative inflammatory response was also compared between the two groups using white blood cell count and high sensitivity C-reactive protein. Results: Among the 47 patients, 26 patients received gastroduodenostomy, whereas 21 patients received gastrojejunostomy without open conversion or additional mini-laparotomy incision. There was no difference in mean operation time, blood loss, and length of postoperative hospital stays. There was no statistically significant difference in postoperative complication or mortality between two groups. However, significantly more staplers were used for gastroduodenostomy than for gastrojejunostomy (n=6) than for gastroduodenostomy and (n=5). Conclusions: Intracorporeal anastomosis during laparoscopic gastrectomy using linear stapler, either gastroduodenostomy or gastrojejunostomy, shows comparable and acceptable early postoperative outcomes and are safe and feasible. Therefore, surgeons may choose either anastomosis method as long as oncological safety is guaranteedope

Visfatin Induces Sickness Responses in the Brain

BACKGROUND/OBJECTIVE: Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity. METHODOLOGY: Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated. PRINCIPAL FINDINGS: Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity. CONCLUSIONS: Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain

Cellular Stress-Modulating Drugs Can Potentially Be Identified by in Silico Screening with Connectivity Map (CMap)

Accompanied by increased life span, aging-associated diseases, such as metabolic diseases and cancers, have become serious health threats. Recent studies have documented that aging-associated diseases are caused by prolonged cellular stresses such as endoplasmic reticulum (ER) stress, mitochondrial stress, and oxidative stress. Thus, ameliorating cellular stresses could be an effective approach to treat aging-associated diseases and, more importantly, to prevent such diseases from happening. However, cellular stresses and their molecular responses within the cell are typically mediated by a variety of factors encompassing different signaling pathways. Therefore, a target-based drug discovery method currently being used widely (reverse pharmacology) may not be adequate to uncover novel drugs targeting cellular stresses and related diseases. The connectivity map (CMap) is an online pharmacogenomic database cataloging gene expression data from cultured cells treated individually with various chemicals, including a variety of phytochemicals. Moreover, by querying through CMap, researchers may screen registered chemicals in silico and obtain the likelihood of drugs showing a similar gene expression profile with desired and chemopreventive conditions. Thus, CMap is an effective genome-based tool to discover novel chemopreventive drugs. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.1

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration.

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration