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Ghrelin exerts key effects on islet hormone secretion to regulate blood glucose levels. Here, we sought to determine whether ghrelin's effects on islets extend to the alteration of islet size and ß cell mass. We demonstrate that reducing ghrelin -- by ghrelin gene knockout (GKO), conditional ghrelin cell ablation, or high-fat diet (HFD) feeding -- was associated with increased mean islet size (up to 62%), percentage of large islets (up to 854%), and ß cell cross-sectional area (up to 51%). In GKO mice, these effects were more apparent in 10-to 12-week-old mice than in 4-week-old mice. Higher ß cell numbers from decreased ß cell apoptosis drove the increase in ß cell cross-sectional area. Conditional ghrelin cell ablation in adult mice increased the ß cell number per islet by 40% within 4 weeks. A negative correlation between islet size and plasma ghrelin in HFD-fed plus chow-fed WT mice, together with even larger islet sizes in HFD-fed GKO mice than in HFD-fed WT mice, suggests that reduced ghrelin was not solely responsible for diet-induced obesity-associated islet enlargement. Single-cell transcriptomics revealed changes in gene expression in several GKO islet cell types, including upregulation of Manf, Dnajc3, and Gnas expression in ß cells, which supports decreased ß cell apoptosis and/or increased ß cell proliferation. These effects of ghrelin reduction on islet morphology might prove useful when designing new therapies for diabetes. [ABSTRACT FROM AUTHOR]

Tobacco use continues to be a leading cause of death and morbidity globally. At the core of Australia's response to tobacco‐related harms is the National Tobacco Strategy which highlights a national collaborative framework to reduce prevalence, and associated health, social and economic impacts of tobacco use. A draft National Tobacco Strategy (2022–2030) has recently been released for consultation and as members of the Australasian Professional Society on Alcohol and other Drugs' Special Interest Group for Smoking Cessation Professionals we provide a commentary on key successes of the previous National Tobacco Strategy, and suggestions for improvement areas to strengthen Australia's policy response to tobacco and e‐cigarette‐related issues. [ABSTRACT FROM AUTHOR]

Smart sensing devices enabled hydroponics, a concept of vertical farming that involves soilless technology that increases green area. Although the cultivation medium is water, hydroponic cultivation uses 13 ± 10 times less water and gives 10 ± 5 times better quality products compared with those obtained through the substrate cultivation medium. The use of smart sensing devices helps in continuous real-time monitoring of the nutrient requirements and the environmental conditions required by the crop selected for cultivation. This, in turn, helps in enhanced year-round agricultural production. In this study, lettuce, a leafy crop, is cultivated with the Nutrient Film Technique (NFT) setup of hydroponics, and the growth results are compared with cultivation in a substrate medium. The leaf growth was analyzed in terms of cultivation cycle, leaf length, leaf perimeter, and leaf count in both cultivation methods, where hydroponics outperformed substrate cultivation. The results of the 'AquaCrop simulator also showed similar results, not only qualitatively and quantitatively, but also in terms of sustainable growth and year-round production. The energy consumption of both the cultivation methods is compared, and it is found that hydroponics consumes 70 ± 11 times more energy compared to substrate cultivation. Finally, it is concluded that smart sensing devices form the backbone of precision agriculture, thereby multiplying crop yield by real-time monitoring of the agronomical variables. [ABSTRACT FROM AUTHOR]

The current research article deals with the study of deformation in a non-homogeneous orthotropic micropolar medium. It is assumed that the functionally graded material has non-homogeneous mechanical properties in the x-direction. The exact analytical expressions for the displacement and stress components are obtained in the physical domain by using the normal mode analysis technique. These components are then computed numerically using MATLAB software for aluminum epoxy composite as micropolar material and are also depicted graphically to show the variations of physical quantities. The comparisons have been carried out to show the effect of anisotropy on all physical quantities. [ABSTRACT FROM AUTHOR]

Background:Body fluids including pleural, peritoneal, and pericardial fluids accumulated in pathologic conditions, including benign and nonneoplastic disorders, and benign and malignant neoplasms. The present study was clinico--cytopathologic study of pericardial effusion. Materials & Methods:37 pericardial effusion specimens of both genders was recorded. Parameters such as cytologic features and the cytologic diagnosis of PE was classified into five categories in accordance with ISRSFC. Results: Out of 37 specimens, males were 20 and females were 17. Diagnosis was negative for malignancy (NFM) in 30, atypia of undetermined significance (AUS) in 4, suspicious for malignancy (SFM) in 2 and positive for malignancy (MAL) in 1 case. The difference was significant (P< 0.05). Symptoms/signs were raised jugular venous pulse in 24, breathlessness in 12, tachycardia in 15, tachypnea in 23, fever in 8, hypotension in 4, cough in 10 and body swelling in 3. Etiology was unknown in 15, Tb pericarditis in 6, traumatic in 8, heart disease in 1, renal disease in 1, autoimmune in 3 and malignancy/Suspicion for malignancy in 3 cases. The difference was non-significant (P> 0.05). Conclusion: PF specimens are uncommon. Unknown etiology the most common cause to produce malignant PF in both males and females. [ABSTRACT FROM AUTHOR]

The world population is on the rise, which demands higher food production. The reduction in the amount of land under cultivation due to urbanization makes this more challenging. The solution to this problem lies in the artificial cultivation of crops. IoT and sensors play an important role in optimizing the artificial cultivation of crops. The selection of sensors is important in order to ensure a better quality and yield in an automated artificial environment. There are many challenges involved in selecting sensors due to the highly competitive market. This paper provides a novel approach to sensor selection for saffron cultivation in an IoT-based environment. The crop used in this study is saffron due to the reason that much less research has been conducted on its hydroponic cultivation using sensors and its huge economic impact. A detailed hardware-based framework, the growth cycle of the crop, along with all the sensors, and the block layout used for saffron cultivation in a hydroponic medium are provided. The important parameters for a hydroponic medium, such as the concentration of nutrients and flow rate required, are discussed in detail. This paper is the first of its kind to explain the sensor configurations, performance metrics, and sensor-based saffron cultivation model. The paper discusses different metrics related to the selection, use and role of sensors in different IoT-based saffron cultivation practices. A smart hydroponic setup for saffron cultivation is proposed. The results of the model are evaluated using the AquaCrop simulator. The simulator is used to evaluate the value of performance metrics such as the yield, harvest index, water productivity, and biomass. The values obtained provide better results as compared to natural cultivation. [ABSTRACT FROM AUTHOR]

The present research article deals with the study of surface wave propagation in hygrothermoelastic medium with hydrostatic initial stress. The coupled wave equations in terms of displacement, temperature and moisture concentration are solved analytically. The values of the penetration depth of different waves are obtained and depicted graphically against frequency. To explore some interesting results, the authors have also discussed deformation in the medium caused due to a mechanical force along the free surface of hygrothermoelastic solid with hydrostatic initial stress. The components of displacement, mechanical stresses, moisture concentration and temperature distribution in the medium are obtained and presented analytically. The graphical results of the variations of these quantities are presented graphically to show the effect of hydrostatic initial stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • AURK-B plays an essential role in chromosome segregation and onset of cell cycle events. • Overexpression of AURK-B has been linked with gastric cancer, oral cancer and lung cancer. • AURK-B maintained its native secondary and tertiary structure at pH 8.0 that is responsible for its optimum enzyme activity at pH 8.0. • Molecular dynamic simulations (MDS) on AURK-B by mimicking the diverse pH conditions indicate a strong correlation between insilico, spectroscopic and kinase activity assay studies. Aurora kinase B (AURK-B) is a serine/threonine kinase protein that plays an essential role in chromosomal separation during the cell cycle event. AURK-B is highly expressed in various types of cancer such as human seminoma, thyroid carcinoma, non-small cell lung carcinoma (NSCLC), oral carcinoma, and gastric cancer. Hence, it is a potential therapeutic target in the treatment of various cancers. The structure of AURK-B in complex with one of its substrate inner centromeric protein (INCENP) is present, but the structural and functional characterization of native AURK-B at different pH environment is still unexplored.This study determines the effect of different pH milieu on the structure and function of AURK-B protein wherein the influence of pH on the protein conformation was probed using Circular dichroism (CD) and fluorescence spectroscopy. The structural studies were further combined with functional activity assay to observe the change in kinase activity at various pH milieu (2.0–11.0). CD and fluorescence spectroscopy experiments dictate that at high acidic conditions (pH 2.0 – 5.0), the secondary and tertiary structures of AURK-B become distorted, leading to diminished activity. The protein, however, was observed to stabilize towards pH 7.0 – 8.0 with minimal structure alteration over the basic pH range (pH 9.0 –11.0). The measured spectroscopic structural features were found to be in-line with obtained experimental kinase activity assays. Further, in-vitro experiments indicate that the enzyme is maximally active at pH 8.0. More ordered conformation and compact structure was observed at this pH (pH 8.0) as compared to other pH values through molecular dynamics simulation studies (MDS). As AURK-B localizes itself in the intracellular compartment, this study may provide a clue about the role of different pH environments in enhancing cancer growth, proliferation, and invasion. [ABSTRACT FROM AUTHOR]

Supply chain management is implementing the standards of Industry 4.0 in order to enhance the trust and safety level in the system with invention of the latest technologies. At the same time, the customers are now more focused towards the product quality. Supply chain management is the demand of the era. However, it is difficult to trace and maintain the track data throughout the process during the supply of a product. The traditional solutions were based on centralized third party solutions, where the data is inclined to various security attacks and high risk of tempering. In this paper, a solution for the management of supply of a product has been proposed which is based on IoT with an amalgamation of blockchain so as to increase the transparency of the flow during the supply of the product. The solution will help to enhance the trust as the data will be shared among all participating nodes of the network in blockchain. It also makes instant traceability of the product and this can be done by both the end of the chain. Moreover, this solution will help the consumer to check whether the product is from a reliable source or not. For the implementation and testing of smart contracts the authors have used Remix IDE, MetaMask and RinkeyBy. [ABSTRACT FROM AUTHOR]

A population explosion has resulted in garbage generation on a large scale. The process of proper and automatic garbage collection is a challenging and tedious task for developing countries. This paper proposes a deep learning-based intelligent garbage detection system using an Unmanned Aerial Vehicle (UAV). The main aim of this paper is to provide a low-cost, accurate and easy-to-use solution for handling the garbage effectively. It also helps municipal corporations to detect the garbage areas in remote locations automatically. This automation was derived using two Convolutional Neural Network (CNN) models and images of solid waste were captured by the drone. Both models were trained on the collected image dataset at different learning rates, optimizers and epochs. This research uses symmetry during the sampling of garbage images. Homogeneity regarding resizing of images is generated due to the application of symmetry to extract their characteristics. The performance of two CNN models was evaluated with the state-of-the-art models using different performance evaluation metrics such as precision, recall, F1-score, and accuracy. The CNN1 model achieved better performance for automatic solid waste detection with 94% accuracy. [ABSTRACT FROM AUTHOR]

Aurora kinases (AURKs) are a family of serine /threonine protein kinases that have a crucial role in cell cycle process mainly in the event of chromosomal segregation, centrosome maturation and cytokinesis. The family consists of three members including Aurora kinase A (AURK-A), Aurora kinase B (AURK-B) and Aurora kinase C (AURK-C). All AURKs contain a conserved kinase domain for their activity but differ in their cellular localization and functions. AURK-A and AURK-B are expressed mainly in somatic cells while the expression of AURK-C is limited to germ cells. AURK-A promotes G2 to M transition of cell cycle by controlling centrosome maturation and mitotic spindle assembly. AURK-B and AURK-C form the chromosome passenger complex (CPC) that ensures proper chromosomal alignments and segregation. Aberrant expression of AURK-A and AURK-B has been detected in several solid tumours and malignancies. Hence, they have become an attractive therapeutic target against cancer. The first part of this review focuses on AURKs structure, functions, subcellular localization, and their role in tumorigenesis. The review also highlights the functional and clinical impact of selective as well as pan kinase inhibitors. Currently, >60 compounds that target AURKs are in preclinical and clinical studies. The drawbacks of existing inhibitors like selectivity, drug resistance and toxicity have also been addressed. Since, majority of inhibitors are Aurora kinase inhibitor (AKI) type-1 that bind to the active (DFG in and C in) conformation of the kinase, this information may be utilized to design highly selective kinase inhibitors that can be combined with other therapeutic agents for better clinical outcomes. [ABSTRACT FROM AUTHOR]

Since the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to > 233 million infections and > 4.7 million deaths as of Sept. 28th, 2021. SARS-CoV-2, Spike (S) protein binds to host cells by recognizing human angiotensin-converting enzyme 2 (hACE2) receptor. The viral S protein contains S1 and S2 domains that constitute the binding and fusion machinery, respectively. Structural analysis of viral S protein reveals that the virus undergoes conformational flexibility and dynamicity to interact with the hACE2 receptor. The SARS-CoV-2 variants and mutations might be associated with affecting the conformational plasticity of S protein, potentially linked to its altered affinity, infectivity, and immunogenicity. This review focuses on the current circulating variants of SARS-CoV-2 and the structure–function analysis of key S protein mutations linked with increased affinity, higher infectivity, enhanced transmission rates, and immune escape against this infection. [ABSTRACT FROM AUTHOR]

The increasing popularity and adoption of the Internet of Things (IoT) ecosystem in various domains has brought attention to the security breaches linked with this paradigm. As the number of IoT devices continues to grow, it is essential to ensure that they are secured to protect against potential threats and attacks. IoT network proliferation of interconnected devices has significantly raised security concerns making them attractive targets for cyber attackers seeking to gain unauthorized access to systems and cause disruptions. As IoT networks collect and transmit sensitive data using centralized architecture, ensuring security and integrity of these networks becomes paramount. Distributed Ledger Technology (DLT) has emerged as a promising solution for enhancing IoT security. Two prominent DLT platforms: Blockchain and Internet of Things Application (IOTA) technologies can provide a more secure and resilient foundation for IoT ecosystems, and also help to mitigate risks associated with central node vulnerabilities. DLT-based IoT systems can also enable the creation of decentralized marketplaces and autonomous agents that can operate without human intervention. The objective of this research is to offer a comprehensive as well as fundamental study of IoT ecosystems and its associated security risks. Moreover, this paper provides a holistic study of the DLT platform and bibliometric inspection using VoS viewer tool on generic DLT platform technologies i.e., Blockchain and IOTA for securing data in IoT ecosystem. By leveraging bibliometric insights resulting from both DLT technologies, this study identities the most promising areas for further investigation and contribute to advancing security in IoT ecosystems. This survey contributes to the ongoing discourse on IoT security by providing a thorough comprehensive comparison of DLT solutions i.e., Blockchain and IOTA technologies on various key metrics, revealing that IOTA technology is projected to offer significant improvements over blockchain in securing sustainable IoT ecosystems. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients. [ABSTRACT FROM AUTHOR]

Insulin-induced hypoglycemia leads to far-ranging negative consequences in patients with diabetes. Components of the counterregulatory response (CRR) system that help minimize and reverse hypoglycemia and coordination between those components are well studied but not yet fully characterized. Here, we tested the hypothesis that acyl-ghrelin, a hormone that defends against hypoglycemia in a preclinical starvation model, is permissive for the normal CRR to insulin-induced hypoglycemia. Ghrelin knockout (KO) mice and wild-type (WT) littermates underwent an insulin bolus-induced hypoglycemia test and a low-dose hyperinsulinemic-hypoglycemic clamp procedure. Clamps also were performed in ghrelin-KO mice and C57BL/6N mice administered the growth hormone secretagogue receptor agonist HM01 or vehicle. Results show that hypoglycemia, as induced by an insulin bolus, was more pronounced and prolonged in ghrelin-KO mice, supporting previous studies suggesting increased insulin sensitivity upon ghrelin deletion. Furthermore, during hyperinsulinemic-hypoglycemic clamps, ghrelin-KO mice required a 10-fold higher glucose infusion rate (GIR) and exhibited less robust corticosterone and growth hormone responses. Conversely, HM01 administration, which reduced the GIR required by ghrelin-KO mice during the clamps, increased plasma corticosterone and growth hormone. Thus, our data suggest that endogenously produced acyl-ghrelin not only influences insulin sensitivity but also is permissive for the normal CRR to insulin-induced hypoglycemia. [ABSTRACT FROM AUTHOR]

DNA gyrase, a type II topoisomerase maintains the topology of DNA by introducing negative supercoils using energy generated by ATP hydrolysis. It is composed of two subunits, GyrA and GyrB (GyrA 2 GyrB 2 hetero-tetramer). GyrB comprises two domains, a 43 kDa amino N-terminus (GBNTD) and 47 kDa carboxyl C- terminus (GBCTD). Till now no study has been reported in terms of stability of Gyrase B and its domains using chemical denaturants related to its function. To understand the role of each domain in GyrB subunit, we estimated the thermodynamic stability of GBF and its individual domains using urea and GdmCl. Changes in secondary and tertiary structures were monitored using circular dichroism and fluorescence spectroscopy. The Cm values for GBNTD, GBCTD and GBF proteins were found to be 2.25, 1.65 and 1.82 M during GdmCl-induced denaturation and 2.95, 2.25 and 2.67 M for urea-induced denaturation. It is observed that GBNTD is more stable than GBCTD and it contributes to overall stability of GyrB. The lower Cm and ΔG values reflect the flexibility of GBCTD to form the catalytic site along with GANTD for cleavage or religation reaction. Both GdmCl- and urea-induced denaturation of GyrB domains were reversible over the entire range of concentration. [ABSTRACT FROM AUTHOR]

The goal of positive development is the promotion of healthy physical, intellectual, psychosocial and emotional development. It equips young people with attributes, skills, competencies, and values that will contribute to their future role as productive, socially-minded, healthy citizens likely to succeed in areas of family, work, and society. This study investigates the relationship between civic engagement and subjective well-being. To serve this purpose the research designed consisted of300 participants, 150 females and 150 males, in the age range of 18 to28yrs from urban India. Purposive random sampling technique was used. The measurement tools used for the purpose of data collection were the Civic Engagement Scale (CES) by Amy Doolittle and Anna Faul (2013) and Satisfaction with Life Scale (SWLS) developed by Diener et al. (1985). The results reveal positive correlation between the scores on civic engagement status and subjective well-being (r=0.84, p=<.01). When civic engagement is entered in the regression model with subjective well-being as a criterion for the total sample, civic engagement itself contributed to 57.9% of the variance. Probability that the regression output is not by chance is seen by "significance F". Engagement as sense of belonging can foster participation in activities, communities, and institutions, and the process of participation can foster a sense of belonging. Civic engagement is critical to both positive youth development and to healthy societies and democracies. In these ways, engagement is both a process and an outcome. It is important to provide emerging adults with more opportunities to experience a sense of and promote prosocial behaviours in the community context. [ABSTRACT FROM AUTHOR]

5HT 3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic–pituitary–adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists. [ABSTRACT FROM AUTHOR]

Despite the presence of a multitudinous pharmacotherapy, diabetes-induced depressive disorder remains undertreated. Evidence suggests that brain serotonergic deficits are associated with depressive-like behavior in diabetes and that 5HT 3 receptor (5HT3R) antagonists have serotonergic facilitatory effects. This study examined the effects of a novel 5HT3R antagonist, 4i ( N -(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide), in diabetes-induced depressive phenotypes. Experimentally, (1) to evaluate the effects of 4i, mice with 8-weeks of diabetes (induced by streptozotocin, 200 mg/kg, i.p.) were treated with vehicle, 4i (0.5 and 1 mg/kg/day, i.p.), fluoxetine (10 mg/kg/day, i.p.) for 4-weeks and subjected to neurobehavioral assays, followed by biochemical estimation of serotonin levels in midbrain, prefrontal-cortex and cerebellum. (2) To evaluate the role of 5HT3R in the postulated effect of 4i, diabetic mice were given 4i (1 mg/kg/day, i.p.) after 1 h of 1-( m -chlorophenyl)-biguanide ( m CPBG, a 5HT3R agonist, 10 mg/kg/day, i.p.) treatment and subjected to the same protocol. The results showed that diabetic mice exhibited a significant behavioral deficit, including depression-like behavior in forced swim test, anxiety-like in open field test and sociability deficits in social interaction test, along with a significant decrease in serotonin level in these brain regions. 4i (1 mg/kg), similar to fluoxetine, prevented these behavioral abnormalities and normalized brain serotonin levels. 4i (0.5 mg/kg) ameliorated only diabetes-induced depressive-like behavior and serotonin deficits, but not anxiety-like effects. m CPBG blunted 4i-mediated behavioral response and increase in brain serotonin levels. Altogether, this study suggests that 4i prevents diabetes-induced depressive phenotypes in mice, which may involve antagonism of 5HT3Rs and increase in serotonin levels in discrete brain regions. [ABSTRACT FROM AUTHOR]

Background: The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites. Methods: Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively. Results: Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite. Conclusions: Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host. [ABSTRACT FROM AUTHOR]

Cloud computing plays an important role in every IT sector. Many tech giants such as Google, Microsoft, and Facebook as deploying their data centres around the world to provide computation and storage services. The customers either submit their job directly or they take the help of the brokers for the submission of the jobs to the cloud centres. The preliminary aim is to reduce the overall power consumption which was ignored in the early days of cloud development. This was due to the performance expectations from cloud servers as they were supposed to provide all the services through their services layers IaaS, PaaS, and SaaS. As time passed and researchers came up with new terminologies and algorithmic architecture for the reduction of power consumption and sustainability, other algorithmic anarchies were also introduced, such as statistical oriented learning and bioinspired algorithms. In this paper, an indepth focus has been done on multiple approaches for migration among virtual machines and find out various issues among existing approaches. The proposed work utilizes elastic scheduling inspired by the smart elastic scheduling algorithm (SESA) to develop a more energy-efficient VM allocation and migration algorithm. The proposed work uses cosine similarity and bandwidth utilization as additional utilities to improve the current performance in terms of QoS. The proposed work is evaluated for overall power consumption and service level agreement violation (SLA-V) and is compared with related state of art techniques. A proposed algorithm is also presented in order to solve problems found during the survey. [ABSTRACT FROM AUTHOR]

Objective: In the last few decades, serotonin type-3 (5-HT3) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.]) or diazepam (2 mg/kg, i.p.) or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP) (mCPP, a 5-HT2A/2C receptor agonist, 1 mg/kg, i.p.) and buspirone (BUS, a partial 5-HT1A agonist, 10 mg/kg, i.p.) were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05) increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT3 receptor antagonist with standard anxiolytics may improve therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic–pituitary–adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT 3 receptor, 4i was examined on CORT induced depression in mice. CORT (30 mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5–1 mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10 mg/kg), for the last 2-weeks of CORT dosing. Repeated CORT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CORT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CORT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CORT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT 3 antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation. [ABSTRACT FROM AUTHOR]

Diabetes associated depression is a largely understudied fi eld which nonetheless carries a signifi cant disease burden. The very low therapeutic effi cacy of the existing conventional drugs with poor outcome may be, in part, due to uncertainty of the mechanism involved that clearly explains the existing comorbidity. The main purpose of this review was to address the sophisticated mechanisms of this comorbidity with a view of developing potential novel targets with higher effi cacy and specifi city. Data were collected from database searches including PubMed, references from relevant English language research/review articles and other offi cial publications. Articles from 1990 to 2013 were included, and a broad search term criteria were followed for data mining so that relevant information was not missed out. Some of the search terms used included; diabetes-induced depression, diabetes and serotonin, hypothalamic-pituitary-adrenal (HPA) axis and diabetes and glucocorticoids in diabetes. Neuropathologically, depletion of brain monoaminergic activity specifi cally the serotonin (5-hydroxytryptamine [5-HT]) system, due to chronically persisting diabetic state may lead to the mood and behavioral complications that further add on worsening the quality life years. The 5-HT system through multifunctional tasks regulates neurogenesis and plasticity and by complex receptor mechanism controls the emotional and behavioral activity. Persisting hyperglycemia leads to impaired neurogenesis, decreased synaptic plasticity, undesired neuro-anatomical alterations, neurochemical defi cits, and reduced neurotransmitter activity. The neurotrophic factors and secondary messenger functions affected at molecular and genetic levels indicate the impact of diabetes-mediated dysregulation on neuronal circuits. HPA activity, glycogen synthase kinase 3, and insulin signaling controls were also found to be hampered, interlinked to 5-HT system following diabetic progression. [ABSTRACT FROM AUTHOR]

Increased prevalence and high comorbidity of depression-like mood disorders and diabetes have prompted investigation of new targets and potential contributing agents. There is considerable evidence supporting the inconsistent clinical efficacy and persistent undesirable effects of existing antidepressant therapy for depression associated with diabetes. Therefore, the present study was aimed at investigating the effect of ondansetron, a selective 5HT 3 receptor antagonist in attenuating depression and anxiety-like behavior comorbid with diabetes. Experimentally, Swiss albino mice were rendered diabetic by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg). After 8 weeks, diabetic mice received a single dose of vehicle/ondansetron (0.5 and 1 mg/kg, p.o.)/fluoxetine (the positive control, 10 mg/kg p.o.) for 28 days. Thereafter, behavioral studies were conducted to test depression-like behavior using forced swim test (FST) and anxiety-like deficits using hole-board and light–dark tests, followed by biochemical estimation of serotonin content in discrete brain regions. The results demonstrated that, STZ-induced diabetic mice exhibited increased duration of immobility and decreased swimming behavior in FST, reduced exploratory behavior during hole-board test and increased aversion to brightly illuminated light area in light–dark test as compared to non-diabetic mice, while ondansetron (similar to fluoxetine) treatment significantly reversed the same. Biochemical assay revealed that ondansetron administration attenuated diabetes-induced neurochemical impairment of serotonin function, indicated by elevated serotonin levels in discrete brain regions of diabetic mice. Collectively, the data indicate that ondansetron may reverse depression and anxiety-like behavioral deficits associated with diabetes in mice and modulation of serotonergic activity may be a key mechanism of the compound. [ABSTRACT FROM AUTHOR]

Anxiety disorders are widely spread psychiatric illnesses that are a cause of major concern. Despite a consistent increase in anxiolytics, the prevalence of anxiety is static; this necessitates the development of new compounds with potential activity and minimum unwanted effects. A serotonergic (5HT) system plays an important role in pathogenesis of anxiety and predominantly involves 5HT 1A receptor action in mediating anxiety-like behavior; the antagonism of 5HT 1A receptor has demonstrated to produce anxiolytic-like effects. Alverine citrate (AVC) is reported as a 5HT 1A antagonist; however, its effects on anxiety-like behavior are not investigated. Thus, the present study, by utilizing a neurobehavioral approach, examined the anxiolytic-like effects of AVC in experimental mouse models of anxiety. Mice were acutely treated with AVC (5–20 mg/kg, i.p.)/diazepam (DIA, 2 mg/kg, i.p.) and subjected to four validated anxiety models viz. elevated plus-maze (EPM), light/dark (L/D), hole-board (HB) and marble burying (MB) tests. AVC (15–20 mg/kg) and DIA significantly increased open arm activity in EPM, exploration in light chamber in L/D test, exploratory behavior in HB and reduced MB behavior in marble burying test. AVC (5 mg/kg) had no effect on all behavioral tests, while AVC (10 mg/kg) produced partial effects. It revealed anxiolytic-like effects of AVC. Furthermore, anxiolytic-like effects of AVC at higher doses (15–20 mg/kg) were more pronounced than lower doses (10 mg/kg) and were quite similar to the standard drug DIA. The present finding demonstrates, for the first time, the anxiolytic-like effects of AVC, which may be an alternative approach for management of anxiety-related disorders. [ABSTRACT FROM AUTHOR]

Clinical and preclinical data suggest that diabetes is often associated with anxiety. Insulin, a peptide hormone has been reported to have key functions in the brain and in alleviating several psychological impairments, occur as a consequence of diabetes. However, its effects in diabetes-induced anxiety are scanty. The present study examined whether; insulin can reverse the anxiety-like behavior in streptozotocin (STZ)-induced diabetes in mice. After 8-weeks of diabetes induced by STZ (200 mg/kg, intraperitoneally (i.p.)), mice were given insulin (1-2 IU/kg/day, i.p.)/ diazepam (1 mg/kg/day, i.p.)/ vehicle for 14 days and evaluated for behavioral effects in three validated models of anxiety viz. elevated plus maze (EPM), light-dark (L/D) and hole board (HB) tests. STZ-induced diabetic mice elicited significant behavioral effects which include, decreased percentage open arm entries and time in EPM, reduced latency and time spent in light chamber in L/D, decreased number of head dips, squares crossed and rearings in HB tests respectively. Insulin treatment attenuated the behavioral effects evoked by STZ-induced diabetes in mice as indicated by increased open arms activity in EPM, decreased aversion in light chamber during L/D test and increased exploratory behavior in HB test. In conclusion, this study revealed that insulin can reverse anxiety-like behavior in STZ-induced diabetes in mice. [ABSTRACT FROM AUTHOR]

Brain tumor diagnosis at an early stage can improve the chances of successful treatment and better patient outcomes. In the biomedical industry, non-invasive diagnostic procedures, such as magnetic resonance imaging (MRI), can be used to diagnose brain tumors. Deep learning, a type of artificial intelligence, can analyze MRI images in a matter of seconds, reducing the time it takes for diagnosis and potentially improving patient outcomes. Furthermore, an ensemble model can help increase the accuracy of classification by combining the strengths of multiple models and compensating for their individual weaknesses. Therefore, in this research, a weighted average ensemble deep learning model is proposed for the classification of brain tumors. For the weighted ensemble classification model, three different feature spaces are taken from the transfer learning VGG19 model, Convolution Neural Network (CNN) model without augmentation, and CNN model with augmentation. These three feature spaces are ensembled with the best combination of weights, i.e., weight1, weight2, and weight3 by using grid search. The dataset used for simulation is taken from The Cancer Genome Atlas (TCGA), having a lower-grade glioma collection with 3929 MRI images of 110 patients. The ensemble model helps reduce overfitting by combining multiple models that have learned different aspects of the data. The proposed ensemble model outperforms the three individual models for detecting brain tumors in terms of accuracy, precision, and F1-score. Therefore, the proposed model can act as a second opinion tool for radiologists to diagnose the tumor from MRI images of the brain. [ABSTRACT FROM AUTHOR]

Abstract: Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light–dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system. [Copyright &y& Elsevier]

Abstract: Diabetes is a persistent metabolic disorder, which often leads to depression as a result of the impaired neurotransmitter function. Insulin is believed to have antidepressant effects in depression associated with diabetes; however, the mechanism underlying the postulated effect is poorly understood. In the present study, it is hypothesized that insulin mediates an antidepressant effect in streptozotocin (STZ) induced diabetes in mice through modulation of the serotonin system in the brain. Therefore, the current study investigated the antidepressant effect of insulin in STZ induced diabetes in mice and insulin mediated modulation in the brain serotonin system. In addition, the possible pathways that lead to altered serotonin levels as a result of insulin administration were examined. Experimentally, Swiss albino mice of either sex were rendered diabetic by a single intraperitoneal (i.p.) injection of STZ. After one week, diabetic mice received a single dose of either insulin or saline or escitalopram for 14days. Thereafter, behavioral studies were conducted to test the behavioral despair effects using forced swim test (FST) and tail suspension test (TST), followed by biochemical estimations of serotonin concentrations and monoamine oxidase (MAO) activity in the whole brain content. The results demonstrated that, STZ treated diabetic mice exhibited an increased duration of immobility in FST and TST as compared to non-diabetic mice, while insulin treatment significantly reversed the effect. Biochemical assays revealed that administration of insulin attenuated STZ treated diabetes induced neurochemical alterations as indicated by elevated serotonin levels and decreased MAO-A and MAO-B activities in the brain. Collectively, the data indicate that insulin exhibits antidepressant effects in depression associated with STZ induced diabetes in mice through the elevation of the brain serotonin levels. [Copyright &y& Elsevier]

Background: Depression is a neurological disorder characterized by sad mood, loss of pleasure, agitation and retardation. Though most relevant neuronal pathophysiology is characterized by decrease in monoamine namely; serotonin (5-HT), dopamine, noradrenaline level in central areas regulating mood and behavior, it inadequately explains the exact mechanism involved. Buspirone (BUS), a partial 5-HT1A receptor agonist has shown promising anti-depressant and anxiolytic properties in various pre-clinical and clinical studies, but the molecular and cellular mechanisms are still unclear. Objective: The aim of this study was to investigate, in vivo, the role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in pathophysiology of depression-related disorders and the anti-depressant like activity of BUS. To simulate HPA axis dysregulation, rats were subjected to bilateral adrenalectomy (ADX). Materials and Methods: We have analyzed effect of BUS (10 mg/kg, i.p.) in ADX and sham rats using open field, sucrose consumption, elevated plus maze and hyper-emotionality tests. Results: In all animal models tested, ADX rats exhibited significant depressive and anxiogenic states while BUS was effective in reversing the psychological diseased condition developed. Conclusion: Taken together, these data showed a prominent role of HPA axis in depression and neuronal mechanism of BUS as anti-depressant and anxiolytic agent. Moreover, our findings suggest that BUS can be a better candidate for stress related depression and anxiety. [ABSTRACT FROM AUTHOR]

Depression is among the common psychiatric disorders, therefore the common pathways and pathogenesis associated with depression is required to be studied. In few years, role of 5-hydroxytryptamine-1A/B (5-HT1A/B) receptors in depressive disorders have been revealed. Both preclinical and clinical studies reported that the potential agonist and antagonist at 5-HT1A/B receptors have significant modulatory effects in depression. However, the collective details regarding the involvement of 5-HT1A/B receptors and the molecular pathways associated in depression is lacking. Thus, the present review evidence the link between 5-HT1A/B receptors in the brain and depression, the possible pathways involved and their alterations in depression. Further, it reviews the preclinical evidences of 5-HT1A/B receptor modulators as antidepressant agents and their effectiveness. The current review also details the clinical relevance of 5-HT1A/B receptors etiopathogenesis of major depression in humans. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID- 19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread over the world. Although there are minimal microbiological and antibiotic data on COVID-19, bacterial co-infections have been related to poor outcomes in respiratory viral infections. Adequate antibiotic use in conformity with antibiotic stewardship (ABS) recommendations is necessary during the pandemic. Material and procedure: We conducted a retrospective single-center cohort analysis of 140 adult hospitalised patients (ages 17-99) with confirmed COVID-19 who were admitted between February 16, 2021, and April 22, 2021, and who were discharged on May 6, 2021. From 140 COVID-19 participants, the following clinical data was gathered: Men made up 63.5 percent of the participants, with a median age of 63.5 years (range 17-99). Results: According to local ABS recommendations, the most commonly administered antibiotic regimen was ampicillin/sulbactam (41.5 percent) with a median length of 6 (range 1-13) days. Urine antigen testing for Legionella pneumophila and Streptococcus peumoniae was negative in all of the patients. In critically ill patients hospitalised to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were discovered. Blood cultures obtained at admission had a diagnostic yield of 4.2 percent. Conclusion: While bacterial and fungal co-infections are rare in COVID-19 patients, they are widespread in critically ill individuals. More investigation into the impact of antimicrobial therapy on therapeutic success in COVID-19 patients is essential to prevent antibiotic abuse.COVID-19 management might be improved with the aid of ABS standards. It's also necessary to look at the microbiological patterns of infectious consequences in COVID-19 individuals who are severely unwell. [ABSTRACT FROM AUTHOR]

The objectives of this study are to highlight the arthritic presentation of acute lymphoblastic leukemia (ALL) in children and to delineate features that could help differentiate it from juvenile idiopathic arthritis (JIA). We present a retrospective case control study based on records of the Pediatric Rheumatology Clinic, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India for the period January 2005–October 2008. We compared the clinical profile of 11 children referred to us with musculoskeletal complaints who were ultimately diagnosed to have ALL, with the clinical profile of an equal number of age and sex matched children with JIA. Important features that predicted a diagnosis of ALL and differentiated it from JIA were history of night pain ( P = 0.001), non-articular bony pain ( P = 0.001), presence of joint pain out of proportion to physical findings ( P = 0.0001), anemia ( P = 0.004), leucopenia ( P = 0.045), lymphocytic predominance ( P = 0.002) and thrombocytopenia ( P = 0.012). In conclusion, children with musculoskeletal complaints are often referred to the rheumatologist for evaluation. The treating physician should always exclude the possibility of an underlying ALL especially if there are atypical clinical features or subtle hematological abnormalities. [ABSTRACT FROM AUTHOR]

In solution, unsubstituted guanine (GH2) is in a tautomeric equilibrium between 1H,7H-keto and 1H,9H-keto forms. Upon coordination with (dien)PtII, N9-bound mononuclear complex is preferentially formed. With excess (dien)PtII, the dinuclear complex [{Pt(dien)}2(GH-N7,N9)]3+is formed at basic pH. The X-ray crystal structure analysis of mononuclear complexes [Pt(dien)(GH2-N9)](ClO4)2·2.25H2O (1a), [Pt(dien)(GH2-N9)](Cl)(ClO4) (1b), and the dinuclear complex [{Pt(dien)}2(GH-N7,N9)](ClO4)3(3) are reported. The N7 linkage isomer [Pt(dien)(GH2-N7)]2+(2) could not be isolated and was tentatively assigned in solution. In HCl-acidic medium, the dinuclear complex 3dissociates to form N9 bound mononuclear complex (1) as the major product and presumably the N7 linkage isomer (2) as a minor side product. Species 1and 3have been identified by the pD dependence of the 1H NMR guanine resonances. pKavalues (calculated for H2O) for deprotonation of the N9 linkage isomer (1a, 1b) are 6.51 ± 0.01 and 10.53 ± 0.05 as well as 0.52 ± 0.07 and 8.55 ± 0.06 for the dinuclear complex [{Pt(dien)}2(GH-N7,N9)]3+(3). Ab initiocalculations have been performed for [Pt(dien)(GH2-N7)]2+, [Pt(dien)(GH2-N9)]2+and [{Pt(dien)}2(GH-N7,N9)]3+. They reveal that in gas phase the N7 linkage isomer is more stable than the N9 linkage isomer by ΔE= 8.4 kcal mol−1. Reactions with (dien)PtIIand cis-(NH3)2PtIIwere also carried out to study the metal binding behaviour of the ligand, 7-methylguanine (7-MeGH). The complexes [Pt(dien)(7-MeGH-N9)](NO3)(ClO4) (4), cis-[Pt(NH3)2(7-MeGH-N9)2]Cl2·2H2O (5) and cis,cis-[{PtCl(NH3)2}2(7-MeGH-N3,N9)]Cl2·3H2O (6) have been characterized by X-ray crystallography. pKavalues for 4are < 2 and 8.16 ± 0.04, and for 51.86 ± 0.45 and 8.00 ± 0.08 (average for deprotonation of two 7-MeGH ligands). Structural peculiarities of N9 platinated guanine ligands are discussed and pKavalues of Pt complexes with related guanine nucleobases are compared. [ABSTRACT FROM AUTHOR]

Thrombocytosis is well described in children with Kawasaki disease (KD). We describe six children with KD who had thrombocytopenia at disease onset. This is an unusual finding and has clinical implications in the diagnosis of this condition. [ABSTRACT FROM AUTHOR]

The decomposition of peroxynitrite near neutral pH leads ultimately to the formation of dioxygen and nitrite viaan intermediate with an absorbance maximum at 284 nm. The intermediate oxidises I−with a rate constant of (78 ± 8) × 10 M−1s−1and decays near pH 7 with a rate constant of (0.58 ± 0.02) s−1at 22 °C, but is longer-lived at lower pH. On the basis of experiments performed with a tandem-quenching flow reactor, we tentatively identify this intermediate as peroxynitric acid, formed during the proposed reaction sequence ONOOH + ONOO−→ NO2−+ O2NOO−+ H+→ 2 NO2−+ O2. These products are those expected from a peracid. The rate constant for the first reaction is ca.3 × 104M−1s−1. Part of the dioxygen formed is in the 1Δgstate (S. Miyamoto, G. E. Ronsein, T. C. Corréa, G. R. Martinez, M. H. G. Medeiros and P. Di Mascio, Dalton Trans., 2009, DOI: 10.1039/b905560f). The decay of peroxynitrous acid at concentrations higher than 0.1 mM near neutral pH is best described by the simultaneous process of isomerisation (k= 1.2 s−1) and decomposition to peroxynitrate. The rate of formation and the amount of peroxynitrate formed are much larger than can be accounted for by homolysis reactions. [ABSTRACT FROM AUTHOR]

Metal binding to ligands with the potential of existing in different tautomeric structures can dramatically alter the tautomeric equilibrium by stabilizing a particular, frequently minor, tautomer. The assumption that metal complexation of a minor tautomer is chemically irrelevant because of its very low abundance is misleading and in many cases wrong. In fact, from available X-ray structural data on metal–nucleobase complexes it is evident that metal binding to rare, as opposed to preferred tautomers, is anything but an exception. This “promotion of rare tautomers” through metal coordination is of particular biological relevance in the case of nucleobases because any deviation from Watson–Crick base pairing is potentially mutagenic. In recent years models of “metal-stabilized rare nucleobase tautomers” have been characterized for all common DNA nucleobases, including by X-ray crystallography. Though metal binding causes relatively minor structural changes in the nucleobases, electronic changes as expressed by acid–base properties, for example, can be substantial. In this perspective article the biological consequences of the occupation of nucleobase sites by a metal entity and the altered acid–base chemistry of the nucleobase with regard to base mismatch formation, prevention of base pairing, and acid–base catalysis in nucleic acids are examined. Although not relevant to biology, the behaviour of the unsubstituted parent nucleobases is illuminating in this respect and therefore included. [ABSTRACT FROM AUTHOR]

In this paper, we study two types of approximate solutions for a vector optimization problem in Banach space setting. Our main concern is to define two new concepts of approximate saddle points and relate them to the above solution concepts. As a result, a dual is formulated, and duality results are established. [ABSTRACT FROM AUTHOR]

Abstract: 1-Methylisocytosine (1-MeIC) can be protonated at the endocyclic N(3) position (pK a of 1-MeICH+, 4.02±0.04) or complexed at this position with (dien)MII (M=Pt, Pd). X-ray crystal structures of the protonated species 1 as well as the Pd (2) and Pt (3) complexes are reported, and gas phase structures of the cation 2 and 3 have been calculated by ab initio methods. These results are compared with results from X-ray crystallography. At high pH, the Pt complex 3 undergoes deamination of the exocyclic N(2)H2 group to the 1-methyluracilate complex. As compared to the situation with 1-methylcytosine (1-MeC), the accelerating effect of (dien)PtII is much less pronounced, however. [Copyright &y& Elsevier]

The formation and crystal structure analysis of a cyclic trinuclear Pd complex with bridging 1-methylcytosinato model nucleobases is reported: [{(tmeda)Pd(1-MeC--N3,N4)}3] (ClO4)3·5.5H2O (tmeda = N,N,N′,N′-tetramethylethylenediamine; 1-MeC- = 1-methylcytosine deprotonated at exocyclic amino group) is obtained, among others, from the hydroxo-bridged dinuclear species [{(tmeda)Pd(OH)}2](ClO4)2, which likewise has been characterized by X-ray crystallography, and 1-MeC (1-MeC = neutral 1-methylcytosine) in aqueous solution. The usual head-tail dimer (HT1) appears not to be formed presumably because of the steric bulk of the tmeda ligand, which prevents a close approach of two tmeda ligands. There is also no evidence for formation of an alternative head-tail dimer structure (HT2) which, in principle, would not lead to any steric clash of ligands, but would require an orientation of the metal at N(4) that is almost perpendicular to the nucleobase plane. In the Pd3 compound, the bridging metals are approximately in an anti arrangement, thereby leading to Pd···Pd separations within the Pd3 triangle close to 5.2 Å. This arrangement is reflected in the ¹H NMR spectrum by a strongly deshielded H5 resonance of the nucleobase, occurring at 6.56 ppm (D2O). The overall structure of the Pd3 is that of a double cone, with ClO4- counterions approaching the cavities from either side. The trinuclear structure is also maintained in Me2SO-d6. In this solvent, Pd3 acts as a fluoride anion receptor, with F- binding to the N(4)H protons, as evident from large downfield shifts of these protons. The compound is compared with cyclic adeninato complexes of hexacoordinated metal ions, and a conceptional analogy with [12]metallacrown-3 species is outlined. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative condition of the brain that affects the memory and reasoning abilities of patients. Memory is steadily wiped out by this condition, which gradually affects the brain's ability to think, recall, and form intentions. In order to properly identify this disease, a variety of manual imaging modalities including CT, MRI, PET, etc. are being used. These methods, however, are time-consuming and troublesome in the context of early diagnostics. This is why deep learning models have been devised that are less time-intensive, require less high-tech hardware or human interaction, continue to improve in performance, and are useful for the prediction of AD, which can also be verified by experimental results obtained by doctors in medical institutions or health care facilities. In this paper, we propose a hybrid-based AI-based model that includes the combination of both transfer learning (TL) and permutation-based machine learning (ML) voting classifier in terms of two basic phases. In the first phase of implementation, it comprises two TL-based models: namely, DenseNet-121 and Densenet-201 for features extraction, whereas in the second phase of implementation, it carries out three different ML classifiers like SVM, Naïve base and XGBoost for classification purposes. The final classifier outcomes are evaluated by means of permutations of the voting mechanism. The proposed model achieved accuracy of 91.75%, specificity of 96.5%, and an F1-score of 90.25. The dataset used for training was obtained from Kaggle and contains 6200 photos, including 896 images classified as mildly demented, 64 images classified as moderately demented, 3200 images classified as non-demented, and 1966 images classified as extremely mildly demented. The results show that the suggested model outperforms current state-of-the-art models. These models could be used to generate therapeutically viable methods for detecting AD in MRI images based on these results for clinical prospective. [ABSTRACT FROM AUTHOR]

When it comes to software development, precise planning, proper documentation and proper process control, some errors are inevitable in the software environment. These software flaws can lead to quality deterioration, which can be the main reason behind system failure. As the whole world especially developing countries is dependent upon software systems, it is very important to focus on its reliability aspect. Nowadays sophisticated systems require concerted efforts for managing and reducing the shortcomings in software engineering. But, these efforts require more cost, more money and more time. Software error prediction is the most helpful step in the testing stage of the software development life cycle. It identifies components or parts of the code where an error may occur and requires broad testing, so the test resources can be efficiently used. Software error assessment reduces efforts of testing the software by helping the software testers locate the actual problem and classify different classes of errors in the system. Error estimators are majorly used in various organizations to evaluate the software to save time, improve the quality of software and testing and optimize resources to meet timelines. Machine learning provides support in fault projection by collecting the training data from various edge devices and thus helps in escalating the reliability of the software available on Kaggle. The multilayer perceptron shows better results in precision, recall, F1 score and accuracy as compared to decision tree and Gaussian Naive Bayes as it achieves an accuracy of 96.8%. [ABSTRACT FROM AUTHOR]

DNA Gyrase is a type II topoisomerase that utilizes the energy of ATP hydrolysis for introducing negative supercoils in DNA. The protein comprises two subunits GyrA and GyrB that form a GyrA 2 GyrB 2 heterotetramer. GyrB subunit contains the N-terminal domain (GBNTD) for ATPase activity and the C-terminal domain (GBCTD) for interaction with GyrA and DNA. Earlier structural studies have revealed three different conformational states for GBNTD during ATP hydrolysis defined as open, semi-open, and closed. Here we report, the three-dimensional structure of a new transient closed conformation of GBNTD from Salmonella Typhi (St GBNTD) at 1.94 Å resolution. Based on the structural analysis of this transient closed conformation, we propose the role of protein in the mechanism of ATP hydrolysis. We further explored the effect of pH on ATPase activity and structural stability of the GBNTD using CD and fluorescence spectroscopy at varying pH environment. Kinetic parameters obtained from the ATPase assay were correlated with its secondary and tertiary structure at their respective pH environment. The protein possessed maximum ATPase activity and structural stability at optimum pH 8. At acidic pH, a remarkable decrease in both enzymatic activity and structural stability was observed whereas at alkaline pH there was no significant change. The structural analysis of St GBNTD reveals the role of polar interactions in stabilizing the overall dimeric conformation of the protein. [Display omitted] • GyrB N-terminal domain (GBNTD), hydrolyzes ATP during the catalytic activity of DNA Gyrase • The three-dimensional structure of GBNTD from S almonella Typhi adopts transient closed conformation at pH 8.0. • Polar interactions observed at dimeric interface and ATP binding site stabilise the overall protein. • Role of ionization states of polar amino acids investigated at different pH milieu by kinetics and spectroscopic assays. [ABSTRACT FROM AUTHOR]

Nowadays, one of the most popular applications is cloud computing for storing data and information through World Wide Web. Since cloud computing has become available, users are rapidly increasing. Cloud computing enables users to obtain a better and more effective application at a lower cost in a more satisfactory way. Health services data must therefore be kept as safe and secure as possible because the release of this data could have serious consequences for patients. A framework for security and privacy must be employed to store and manage extremely sensitive data. Patients' confidential health records have been encrypted and saved in the cloud using cypher text so far. To ensure privacy and security in a cloud computing environment is a big issue. The medical system has been designed as a standard, access of records, and effective use by medical practitioners as required. In this paper, we propose a novel algorithm along with implementation details as an effective and secure E-health cloud model using identity-based cryptography. The comparison of the proposed and existing techniques has been carried out in terms of time taken for encryption and decryption, energy, and power. Decryption time has been decreased up to 50% with the proposed method of cryptography. As it will take less time for decryption, less power is consumed for doing the cryptography operations. [ABSTRACT FROM AUTHOR]

Objective: While expression of the ghrelin receptor, GHSR (growth hormone secretagogue receptor), by pancreatic islets has been investigated, data regarding the specific islet cell types that express GHSR are inconsistent and incomplete. For instance, transcriptomic studies indicate marked GHSR expression by somatostatin (SST)-secreting delta cells vs. little to no GHSR expression by alpha cells and beta cells, which contrasts studies suggesting direct actions of ghrelin on GHSRs expressed by alpha cells and beta cells. Also, to our knowledge, GHSR expression by pancreatic polypeptide (PP) cells has not previously been directly investigated. The aims of this study were to determine GHSR expression within the four principal islet endocrine cell types and the effects of ghrelin on circulating PP. Methods: Ghsr-IRES-Cre mice, which express Cre recombinase directed by the GHSR promoter, crossed to Cre-dependent ROSA26-YFP reporter mice were used to histologically identify GHSR expression in islets. Double and triple labeling for YFP-immunoreactivity (IR) with insulin-IR, glucagon-IR, SST-IR, and/or PP-IR was performed to determine GHSR co-expression with islet hormones. Pharmacological manipulations were used to examine in vivo effects of acyl-ghrelin on plasma PP. Results: Eighty-five % of YFP-IR cells expressed PP-IR, 50% expressed SST-IR, and none expressed insulin-IR or glucagon-IR. GHSR antagonist raised plasma PP in overnight-fasted C57BL/6N mice. However, acyl-ghrelin administration had no effect on plasma PP in C57BL/6N mice. Conclusions: These results suggest that within mouse pancreatic islets, GHSR expression occurs most abundantly in PP cells and that pharmacologic blockade of ghrelin action raises plasma PP. Disclosure: D. Gupta: None. B.K. Mani: None. K. Shankar: None. S. Osborne-Lawrence: None. N. Metzger: None. J.M. Zigman: Stock/Shareholder; Self; Medtronic. Funding: Diana and Richard C. Strauss Professorship in Biomedical Research; Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; Kent and Jodi Foster Distinguished Chair in Endocrinology; University of Texas Southwestern Medical Center (to J.M.Z.) [ABSTRACT FROM AUTHOR]