Residue-specific orientation of arrestin in 5-HTR1B (Serotonin Receptor)- βArrestin-1 interaction

Physiologically G protein-coupled receptors (GPCRs) are an important class of cell surface proteins capable of sensing the exogenous signals across the cell membrane through G-protein-dependent and independent pathways. Activated GPCRs initiate diverse G-protein-independent signalling through interaction with arrestin. Arrestins comprise a family of four proteins that act as signal regulators of GPCRs. Arrestin specificity and assembly orientation with a particular GPCR depend on the finger loop's residues. Recent cryo-EM structural elucidation of neurotensin receptor-1(NTSR1)-β-arrestin1complex reveals its striking difference from Rhodopsin-visual-Arrestin by a 90˚ rotation of β-Arrestin1 concerning the receptor. Alignment of neurotensin receptor 1(NTSR1)-β-Arrestin1 assembly with 5-HTR1B (Serotonin receptor) structure shows an ionic interaction mediated complex formation between receptor binding cleft and finger loop of arrestin. Mutational analysis of finger loop residues R65, D67, and D69 of β-Arrestin1 by tango assay confirms its possible interaction with an electropositive pocket of K79 and R161 in 5-HTR1B

Monkeypox Outbreak: Wastewater and Environmental Surveillance Perspective

Monkeypox disease (MPXD), a viral disease caused by monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022, 92% (68/74) of the countries with reported MPXD cases had no historical MPXD case reports. From the One Health perspective, the spread of MPXV in the environment poses a risk not only to humans but also to small mammals and may, ultimately, spread to potent novel host populations. Wastewater-based surveillance (WBS), has been extensively utilized for monitoring communicable diseases, particularly during the ongoing coronavirus disease, the COVID-19 pandemic It helped to monitor infectious disease caseloads as well as specific viral variants circulating in communities. The detection of MPXV DNA in various body fluids, including respiratory and nasal secretions, saliva, urine, feces, and semen of infected individuals, supports the possibility of using WBS as an early proxy for the detection of MPXV infections. WBS of MPXV DNA can be used to monitor MPXV activity/trends in sewerage network areas even before detecting laboratory-confirmed clinical cases within a community. However, several factors affect the detection of MPXV in wastewater including, but not limited to, routes and duration time of virus shedding by infected individuals, infection rates in the relevant affected population, environmental persistence, the processes and analytical sensitivity of the used methods. Further research is needed to identify the key factors that impact the detection of MPXV biomarkers in wastewater and improve the utility of WBS of MPXV as an early warning and monitoring tool for safeguarding human health. In this review, we shortly summarize aspects of MPXV outbreak relevant to wastewater monitoring and discuss the challenges associated with WBS.Peer reviewe

Monkeypox outbreak : Wastewater and environmental surveillance perspective

Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no historical MPXD case reports. From the One Health perspective, the spread of MPXV in the environment poses a risk not only to humans but also to small mammals and may, ultimately, spread to potent novel host populations. Wastewater-based surveillance (WBS) has been extensively utilized to monitor communicable diseases, particularly during the ongoing COVID-19 pandemic. It helped in monitoring infectious disease caseloads as well as specific viral variants circulating in communities. The detection of MPXV DNA in lesion materials (e.g. skin, vesicle fluid, crusts), skin rashes, and various body fluids, including respiratory and nasal secretions, saliva, urine, feces, and semen of infected individuals, supports the possibility of using WBS as an early proxy for the detection of MPXV infections. WBS of MPXV DNA can be used to monitor MPXV activity/trends in sewerage network areas even before detecting laboratory-confirmed clinical cases within a community. However, several factors affect the detection of MPXV in wastewater including, but not limited to, routes and duration time of virus shedding by infected individuals, infection rates in the relevant affected population, environmental persistence, the processes and analytical sensitivity of the used methods. Further research is needed to identify the key factors that impact the detection of MPXV biomarkers in wastewater and improve the utility of WBS of MPXV as an early warning and monitoring tool for safeguarding human health. In this review, we shortly summarize aspects of the MPXV outbreak relevant to wastewater monitoring and discuss the challenges associated with WBS.publishedVersionPeer reviewe

Control Scheme of a Designed Step Climbing Wheeled Robot

This following article presents a control scheme of a step climbing wheeled robot which can traverse through uneven terrain. The main thrust of this article is on developing the control idea of a simple step climbing wheeled robot with simple micro-switch, which is used as sensor. The controller of the designed robot is programmed with microcontroller

Design and Development of a Step Climbing Wheeled Robot

This paper presents a design of Step Climbing Robot that can move in uneven environment and traverse a slope or staircase. The condition imposed on this new system of robot is that it will move only in linear fashion, which will reduce the demands on the physical complexity of the robot unit. A summary of the current state of research in the field of mobile robots as it relates to robot stair climbing and moving in uneven surfaces. The architecture of the robot is developed and compared with the previous design

Dynamic Modeling of Step Climbing Wheeled Robot

This following article presents the dynamic modeling of the developed step-climbing robot. The main idea is to develop the mathematical representation of the developed model. In this article the inverse arm model of a Newton-Euler analysis of free body motion is shown. The purpose of this model is to allow to compute the motor voltage required to produce given accelerations when the current is known and state of the arm and all of its parameters

Capturing Obstructed Nonverbal Cues in Augmented Reality Interactions: A Short Survey

We present a short survey on recovering nonverbal communication cues that are hidden by head-mounted devices while interacting in augmented reality. The focus is on recovering facial expressions and gaze behavior by using various kinds of sensors that are attached to or integrated with these devices. The nonverbal cues can be made visible for other co-located or remote interactants on devices or avatars

A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron’s viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron’s transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic

ChatGPT and large language models in orthopedics: from education and surgery to research

Abstract ChatGPT has quickly popularized since its release in November 2022. Currently, large language models (LLMs) and ChatGPT have been applied in various domains of medical science, including in cardiology, nephrology, orthopedics, ophthalmology, gastroenterology, and radiology. Researchers are exploring the potential of LLMs and ChatGPT for clinicians and surgeons in every domain. This study discusses how ChatGPT can help orthopedic clinicians and surgeons perform various medical tasks. LLMs and ChatGPT can help the patient community by providing suggestions and diagnostic guidelines. In this study, the use of LLMs and ChatGPT to enhance and expand the field of orthopedics, including orthopedic education, surgery, and research, is explored. Present LLMs have several shortcomings, which are discussed herein. However, next‐generation and future domain‐specific LLMs are expected to be more potent and transform patients’ quality of life

The landscape of neoantigens and its clinical applications: From immunobiology to cancer vaccines

Since millions of cancer-related deaths and diagnoses exist yearly, malignant tumors are a primary worldwide health concern. A promising method for treating cancer is tumor immunotherapy, which focuses on neoantigens. Neoantigens are tumor-specific antigens expressed on cancer cells due to genetic changes, viral infections, or other biological processes. They serve as excellent immune system targets to identify and attack cancerous cells. Neoantigens are more immunogenic than tumor-associated antigens (TAAs) because they lack central tolerance. Successful clinical trials of neoantigen-based vaccines have raised interest in individualized tumor immunotherapy. Furthermore, neoantigens represent a significant advancement in cancer immunotherapy, offering the potential for personalized and effective tumor treatments. The identification, synthesis, and application of neoantigen-based vaccines hold promise for improving patient outcomes and revolutionizing cancer treatment approaches. This review focuses on the significance of neoantigens in cancer immunotherapy, their classification and identification, the synthesis of neoantigen vaccines, clinical trials and the principles underlying their therapeutic efficacy