The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe⁻/H₂Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O₂ consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H₂O₂), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.     

Structural Basis for The Recognition of Deaminated Nucleobases by An Archaeal DNA Polymerase

With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B-family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B-family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’-overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B-family DNA polymerases.     

Synchronous receiver initiated MAC protocol for long-lived sensor networks

In this paper, we discuss the design of a new Medium Access Control (MAC) protocol, SRI-MAC (Synchronous Receiver Initiated MAC), for wireless sensor networks whose goal is to extend the lifetime of the network by avoiding major energy waste causes, such as collisions, overhearing and idle listening.     

A Framework of Deep Optimal Features Selection for Apple Leaf Diseases Recognition

Identifying fruit disease manually is time-consuming, expert-required, and expensive; thus, a computer-based automated system is widely required. Fruit diseases affect not only the quality but also the quantity. As a result, it is possible to detect the disease early on and cure the fruits using computer-based techniques. However, computer-based methods face several challenges, including low contrast, a lack of dataset for training a model, and inappropriate feature extraction for final classification. In this paper, we proposed an automated framework for detecting apple fruit leaf diseases using CNN and a hybrid optimization algorithm. Data augmentation is performed initially to balance the selected apple dataset. After that, two pre-trained deep models are fine-tuning and trained using transfer learning. Then, a fusion technique is proposed named Parallel Correlation Threshold (PCT). The fused feature vector is optimized in the next step using a hybrid optimization algorithm. The selected features are finally classified using machine learning algorithms. Four different experiments have been carried out on the augmented Plant Village dataset and yielded the best accuracy of 99.8%. The accuracy of the proposed framework is also compared to that of several neural nets, and it outperforms them all.     

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

Angiotensin II stimulates cAMP production and protein tyrosine phosphorylation in mouse spermatozoa

Angiotensin II (AII), found in seminal plasma, has been shown to stimulate capacitation in uncapacitated mammalian spermatozoa. The present study investigated the location of AII receptors on spermatozoa and AII's mechanism of action. AT1 type receptors for AII are present on the acrosomal cap region and along the whole of the flagellum of both mouse and human spermatozoa. Because combinations of low concentrations of AII and either calcitonin or fertilization-promoting peptide (FPP), both known to regulate the adenylyl cyclase (AC)/cAMP signal transduction pathway, elicited a significant response, this study investigated the hypothesis that these peptides act on the same pathway. AII was shown to significantly stimulate cAMP production in both uncapacitated and capacitated mouse spermatozoa and this was associated with increases in protein tyrosine phosphorylation. Using an anti-phosphotyrosine antibody to visualize the location of tyrosine phosphoproteins within individual cells, AII significantly stimulated phosphorylation within 20 min in both the head, especially in the acrosomal cap region, and the flagellum, especially in the principal piece, of uncapacitated mouse spermatozoa; combined AII + FPP was stimulatory within 5 min. In addition, Western blotting revealed that AII stimulation increased phosphorylation in a number of tyrosine phosphoproteins in both uncapacitated and capacitated mouse spermatozoa, with some being altered only in the latter category of cells. These results support the hypothesis that AII stimulates AC/cAMP in mammalian spermatozoa.     

Near-infrared spectroscopy: theory and applications

In conclusion, NIRS appears to offer both a new monitoring modality and new information about cerebral oxygenation. Technical problems in the application of this technology persist, most notably determination of pathlength and the volume of tissue interrogated. Those familiar with the history of pulse oximetry will recall that although Millikan developed an ear oximeter in 1947, it was not until Aoyagi combined recognition of the pulse signal with spectroscopy in the 1970s that oximetry was transformed into a clinically applicable monitor. In much the same way, NIRS may find the same tremendous usefulness as a noninvasive monitor of cerebral oxygen utilization, pending resolution of the remaining technical problems.     

Survey on Wireless Sensor Network Applications and Energy Efficient Routing Protocols

Wireless sensor network (WSN) is a group of small power-constrained nodes that sense data and communicate it to the base station (BS). These nodes cover a vast region of interest (ROI) for several purposes according to the application need. The first challenge encountered in WSNs is how to cover the ROI perfectly and send the monitored data to the BS. Although the energy introduced during setup phase and the violation of energy fairness constraint of dynamic routing topologies, they achieve high network performance in terms of coverage and connectivity. In this paper, we categorize the applications of WSN based on different aspects to show the major protocol design issues. Thus, the energy efficiency of the recent proactive routing protocols is studied from different angles. The energy overhead and energy fairness of each protocol were carefully analyzed. The most energy efficient routing protocols for homogeneous proactive networks were studied and compared to highlight the research challenges and existing problems in this area. The results proved that energy overhead and route selection are the most effective aspects of network lifetime and network efficiency.

     

A new QoS aware and energy efficient opportunistic routing protocol for wireless sensor networks

Energy efficiency and Quality of Service (QoS) providing are known to be critical design concerns in routing protocols for Wireless Sensor Networks (WSNs). Recent studies, demonstrate that Opportunistic Routing (OR) can greatly improve the performance of WSNs by exploiting the broadcast nature of the wireless medium. In this paper, we propose a new QoS aware and Energy efficient Opportunistic Routing protocol (QEOR) to efficiently routing data under QoS and energy constraints for WSNs. QEOR uses a new multi-metric QoS based candidate selection method in order to accurately select and prioritise the candidate forwarders. The selection is focused on a QoS function that takes into consideration the reliabilty of buffers and links, while the prioritisation is established according to transmission delays. To achieve an obvious improvement on the energy consumption, QEOR uses an energy efficient coordination method and an implicit ACKnowledgement scheme for collision and redundancy avoidance. Simulation results show that QEOR provides best performances as compared to other OR protocols.