Antimicrobial peptides: key components of the innate immune system

Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs

Identification of a Contiguous 6-Residue Determinant in the MHV Receptor That Controls the Level of Virion Binding to Cells

AbstractMurine carcinoembryonic antigens serve as receptors for the binding and entry of the enveloped coronavirus mouse hepatitis virus (MHV) into cells. Numerous receptor isoforms are now known, and each has extensive differences in its amino terminal immunoglobulin-like domain (NTD) to which MHV binds via its protruding spike proteins. Some of these receptor alterations may affect the ability to bind viral spikes. To identify individual residues controlling virus binding differences, we have used plasmid and vaccinia virus vectors to express two forms of MHV receptor differing only in their NTD. The two receptors, designated biliary glycoproteins (Bgp) 1aand 1bNTD, varied by 29 residues in the 107 amino acid NTD. When expressed from cDNAs in receptor-negative HeLa cells, these two Bgp molecules were displayed on cell surfaces to equivalent levels, as both were equally modified by a membrane-impermeant biotinylation reagent. Infectious center assays revealed that the 1aisoform was 10 to 100 times more effective than 1bNTDin its ability to confer sensitivity to MHV (strain A59) infection. Bgp1awas also more effective than Bgp1bNTDin comparative virus adsorption assays, binding 6 times more MHV (strain A59) and 2.5 times more MHV (strain JHMX). Bgp1awas similarly more effective in promoting the capacity of viral spikes to mediate intercellular membrane fusion as judged by quantitation of syncytia following cocultivation of spike and receptor-bearing cells. To identify residues influencing these differences, we inserted varying numbers of 1bresidues into the Bgp1abackground via restriction fragment exchange and site-directed mutagenesis. Analysis of the resulting chimeric receptors showed that residues 38 to 43 of the NTD were key determinants of the binding and fusion differences between the two receptors. These residues map to an exposed loop (C-C′ loop) in a structural model of the closely related human carcinoembryonic antigen

Rhinacanthus nasutus

The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus

A study on the clinical manifestations and the incidence of benign and malignant tumors in a solitary thyroid nodule

Tumors are either benign or malignant. The thyroid nodule, which is usually a clinical manifestation of most of the thyroid disorders, is one among them which has been the subject of controversies with divergent opinions and views. Clinical presentation of thyroid nodules varies widely ranging from solitary nodules to benign and malignant tumors. Thyroid nodules accounts up to 8% of the adult population having palpable nodules. However studies on its incidence in the population residing near seacoast are limited. Hence, the present study is carried in an aim to evaluate the clinico-pathological correlation of solitary thyroid nodule and the incidence of malignancy in the population residing at sea coast. The study is conducted in the Narayana Medical College & Hospital (NMCH), which is situated within 10-15 km radius of the seacoast in Nellore district of Andhra Pradesh, India. In this study, 73 subjects were selected who presented with thyroid swelling which was clinically confirmed as solitary thyroid nodule. Out of 73 cases, 12 cases (16.5%) were found to have malignant lesions with remaining 61 cases (83.5%) being benign lesions. The incidence of malignancy among solitary thyroid nodule subjects is up to 16.5% in the population residing near seacoast. Thus the present study warrants people to consult surgeons for early diagnosis and adequate treatment without being passive as most of these swellings are asymptomatic for long duration

The Place of ARBs in Heart Failure Therapy: Is Aldosterone Suppression the Key?

Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (AT1R) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or ‘sartans’, short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT1 receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of AT1R, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the adrenal cortex, thirst-fluid intake (hypervolemia), etc., the ARBs are nowadays one of the most useful cardiovascular drug classes used in clinical practice. However, significant differences in their pharmacological and clinical properties exist that may favor use of particular agents over others within the class, and, in fact, two of these drugs, candesartan and valsartan, continuously appear to distinguish themselves from the rest of the ‘pack’ in recent clinical trials. The reason(s) for the potential superiority of these two agents within the ARB class are currently unclear but under intense investigation. The present short review gives an overview of the clinical properties of the ARBs currently approved by the United States Food and Drug Administration, with a particular focus on candesartan and valsartan and the areas where these two drugs seem to have a therapeutic edge. In the second part of our review, we outline recent data from our laboratory (mainly) on the molecular effects of the ARB drugs on aldosterone production and on circulating aldosterone levels, which may underlie (at least in part) the apparent clinical superiority of candesartan (and valsartan) over most other ARBs currently in clinical use

Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis

Objective: To evaluate the association between preeclampsia (PE) and eclampsia (E) on subsequent metabolic and biochemical outcomes. Methods: Systematic review and meta-analysis of observational studies. We searched five engines until November 2018 for studies evaluating the effects of PE/E on metabolic and biochemical outcomes after delivery. PE was defined as presence of hypertension and proteinuria at >20 weeks of pregnancy; controls did not have PE/E. Primary outcomes were blood pressure (BP), body mass index (BMI), metabolic syndrome (MetS), blood lipids and glucose levels. Random effects models were used for meta-analyses, and effects reported as risk difference (RD) or mean difference (MD) and their 95% confidence interval (CI). Subgroup analyses by time of follow up, publication year, and confounder adjustment were performed. Results: We evaluated 41 cohorts including 3300 PE/E and 13,967 normotensive controls. Women were followed up from 3 months after delivery up to 32 years postpartum. In comparison to controls, PE/E significantly increased systolic BP (MD = 8.3 mmHg, 95%CI 6.8 to 9.7), diastolic BP (MD = 6.8 mmHg, 95%CI 5.6 to 8.0), BMI (MD = 2.0 kg/m2; 95%CI 1.6 to 2.4), waist (MD = 4.3 cm, 95%CI 3.1 to 5.5), waist-to-hip ratio (MD = 0.02, 95%CI 0.01 to 0.03), weight (MD = 5.1 kg, 95%CI 2.2 to 7.9), total cholesterol (MD = 4.6 mg/dL, CI 1.5 to 7.7), LDL (MD = 4.6 mg/dL; 95%CI 0.2 to 8.9), triglycerides (MD = 7.7 mg/dL, 95%CI 3.6 to 11.7), glucose (MD = 2.6 mg/dL, 95%CI 1.2 to 4.0), insulin (MD = 19.1 pmol/L, 95%CI 11.9 to 26.2), HOMA-IR index (MD = 0.7, 95%CI 0.2 to 1.2), C reactive protein (MD = 0.05 mg/dL, 95%CI 0.01 to 0.09), and the risks of hypertension (RD = 0.24, 95%CI 0.15 to 0.33) and MetS (RD = 0.11, 95%CI 0.08 to 0.15). Also, PE/E reduced HDL levels (MD = –2.15 mg/dL, 95%CI –3.46 to −0.85). Heterogeneity of effects was high for most outcomes. Risk of bias was moderate across studies. Subgroup analyses showed similar effects as main analyses. Conclusion: Women who had PE/E have worse metabolic and biochemical profile than those without PE/E in an intermediate to long term follow up period. ©Revisión por pare

Handwashing Action Detection System for an Autonomous Social Robot

Young children are at an increased risk of contracting contagious diseases such as COVID-19 due to improper hand hygiene. An autonomous social agent that observes children while handwashing and encourages good hand washing practices could provide an opportunity for handwashing behavior to become a habit. In this article, we present a human action recognition system, which is part of the vision system of a social robot platform, to assist children in developing a correct handwashing technique. A modified convolution neural network (CNN) architecture with Channel Spatial Attention Bilinear Pooling (CSAB) frame, with a VGG-16 architecture as the backbone is trained and validated on an augmented dataset. The modified architecture generalizes well with an accuracy of 90% for the WHO-prescribed handwashing steps even in an unseen environment. Our findings indicate that the approach can recognize even subtle hand movements in the video and can be used for gesture detection and classification in social robotics

Meeting IMT 2030 Performance Targets: The Potential of OTFDM Waveform and Structural MIMO Technologies

The white paper focuses on several candidate technologies that could play a crucial role in the development of 6G systems. Two of the key technologies explored in detail are Orthogonal Time Frequency Division Multiplexing (OTFDM) waveform and Structural MIMO (S-MIMO)

Exploring the characteristics and most bothersome symptoms in MECP2 duplication syndrome to pave the path toward developing parent-oriented outcome measures

BACKGROUND: MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity. Studies using antisense oligonucleotides revealed a broad phenotypic rescue in transgenic mice. With human clinical trials on the horizon, there is a need to develop clinical outcome measures for MDS. METHODS: We surveyed caregivers of MDS individuals to explore the frequency and severity of MDS clinical features, and identify the most meaningful symptoms/domains that need to be included in the outcome measure scales. RESULTS: A total of 101 responses were eligible for the survey. The top six most meaningful symptoms to caregivers in descending order included epilepsy, gross motor, fine motor, communication, infection, and constipation problems. Epilepsy was present in 58.4% of the subjects and 75% were drug‐resistant, Furthermore, ~12% required intensive care unit (ICU) admission. Infections were present in 55% of the subjects, and one‐fourth of them required ICU admission. Constipation was present in ~85% of the subjects and one‐third required enemas/suppositories. CONCLUSION: Our study is one of the largest cohorts conducted on MDS individuals characterizing the frequency and severity of MDS symptoms. Additionally, these study results will contribute to establishing a foundation to develop parent‐reported outcomes in MDS

Optimal operation of stand-alone microgrid considering emission issues and demand response program using whale optimization Algorithm

Microgrids are new technologies for integrating renewable energies into power systems. Optimal operation of renewable energy sources in standalone micro-grids is an intensive task due to the continuous variation of their output powers and intermittant nature. This work addresses the optimum operation of an independent microgrid considering the demand response program (DRP). An energy management model with two different scenarios has been proposed to minimize the costs of operation and emissions. Interruptible/curtailable loads are considered in DRPs. Besides, due to the growing concern of the developing efficient optimization methods and algorithms in line with the increasing needs of microgrids, the focus of this study is on using the whale meta-heuristic algorithm for operation management of microgrids. The findings indicate that the whale optimization algorithm outperforms the other known algorithms such as imperialist competitive and genetic algorithms, as well as particle swarm optimization. Furthermore, the results show that the use of DRPS has a significant impact on the costs of operation and emissions