The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular ...organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.
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•TLRs are first described PRRs that revolutionized the biology of host-pathogen interaction and immune response•The discovery of different TLRs in humans proved milestone in the field of innate immunity and inflammation•The pattern of expression of all the TLRs expressed by human immune cells•An association of various TLR SNPs with different inflammatory diseases•Currently available drugs or vaccines based on TLRs and their future in drug targeting along with the role in reproduction, and regeneration
The lung is a primary organ for gas exchange in mammals that represents the largest epithelial surface in direct contact with the external environment. It also serves as a crucial immune organ, which ...harbors both innate and adaptive immune cells to induce a potent immune response. Due to its direct contact with the outer environment, the lung serves as a primary target organ for many airborne pathogens, toxicants (aerosols), and allergens causing pneumonia, acute respiratory distress syndrome (ARDS), and acute lung injury or inflammation (ALI). The current review describes the immunological mechanisms responsible for bacterial pneumonia and sepsis-induced ALI. It highlights the immunological differences for the severity of bacterial sepsis-induced ALI as compared to the pneumonia-associated ALI. The immune-based differences between the Gram-positive and Gram-negative bacteria-induced pneumonia show different mechanisms to induce ALI. The role of pulmonary epithelial cells (PECs), alveolar macrophages (AMs), innate lymphoid cells (ILCs), and different pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs) and inflammasome proteins) in neutrophil infiltration and ALI induction have been described during pneumonia and sepsis-induced ALI. Also, the resolution of inflammation is frequently observed during ALI associated with pneumonia, whereas sepsis-associated ALI lacks it. Hence, the review mainly describes the different immune mechanisms responsible for pneumonia and sepsis-induced ALI. The differences in immune response depending on the causal pathogen (Gram-positive or Gram-negative bacteria) associated pneumonia or sepsis-induced ALI should be taken in mind specific immune-based therapeutics.
The immune system has evolved to protect the host from the pathogens and allergens surrounding their environment. The immune system develops in such a way to recognize self and non-self and develops ...self-tolerance against self-proteins, nucleic acids, and other larger molecules. However, the broken immunological self-tolerance leads to the development of autoimmune or autoinflammatory diseases. Pattern-recognition receptors (PRRs) are expressed by immunological cells on their cell membrane and in the cytosol. Different Toll-like receptors (TLRs), Nod-like receptors (NLRs) and absent in melanoma-2 (AIM-2)-like receptors (ALRs) forming inflammasomes in the cytosol, RIG (retinoic acid-inducible gene)-1-like receptors (RLRs), and C-type lectin receptors (CLRs) are some of the PRRs. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) is another PRR present in the cytosol and the nucleus. The present review describes the role of ALRs (AIM2), TLR9, and cGAS in recognizing the host cell DNA as a potent damage/danger-associated molecular pattern (DAMP), which moves out to the cytosol from its housing organelles (nucleus and mitochondria). The introduction opens with the concept that the immune system has evolved to recognize pathogens, the idea of
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and its failure due to the emergence of autoimmune diseases (ADs), and the discovery of PRRs revolutionizing immunology. The second section describes the cGAS-STING signaling pathway mediated cytosolic self-DNA recognition, its evolution, characteristics of self-DNAs activating it, and its role in different inflammatory conditions. The third section describes the role of TLR9 in recognizing self-DNA in the endolysosomes during infections depending on the self-DNA characteristics and various inflammatory diseases. The fourth section discusses about AIM2 (an ALR), which also binds cytosolic self-DNA (with 80-300 base pairs or bp) that inhibits cGAS-STING-dependent type 1 IFN generation but induces inflammation and pyroptosis during different inflammatory conditions. Hence, this trinity of PRRs has evolved to recognize self-DNA as a potential DAMP and comes into action to guard the cellular galaxy. However, their dysregulation proves dangerous to the host and leads to several inflammatory conditions, including sterile-inflammatory conditions autoinflammatory and ADs.
Properties of nanosilicon in the form of nanoparticles, nanowires, nanotubes, and as porous material are of great interest. They can be used in finding suitable components for future miniature ...devices, and for the more exciting possibilities of novel optoelectronic applications due to bright luminescence from porous silicon, nanoparticles and nanowires. New findings from research into metal encapsulated clusters, silicon fullerenes and nanotubes have opened up a new paradigm in nanosilicon research and this could lead to large scale production of nanoparticles with control on size and shape as well as novel quasi one-dimensional structures. There are possibilities of using silicon as an optical material and in the development of a silicon laser. In this book leading experts cover state-of-the-art experimental and theoretical advances in the different forms of nanosilicon. Furthermore, applications of nanosilicon to single electron transistors, as photonic material, chemical and biological sensors at molecular scale, and silicon nanowire devices are also discussed. Self-assemblies of silicon nanoforms are important for applications. These developments are also related to cage structures of silicon in clathrates. With an interesting focus on the bottlenecks in the advancement of silicon based technology, this book provides a much-needed overview of the current state of understanding of nanosilicon research.
* Latest developments in nanoparticles, nanowires and nanotubes of silicon * Focus on nanosilicon - a very timely subject attracting large interest * Novel chapters on metal encapsulated silicon clusters and nanotubes
Dielectric polymer nanocomposites are rapidly emerging as novel materials for a number of advanced engineering applications. In this Review, we present a comprehensive review of the use of ...ferroelectric polymers, especially PVDF and PVDF-based copolymers/blends as potential components in dielectric nanocomposite materials for high energy density capacitor applications. Various parameters like dielectric constant, dielectric loss, breakdown strength, energy density, and flexibility of the polymer nanocomposites have been thoroughly investigated. Fillers with different shapes have been found to cause significant variation in the physical and electrical properties. Generally, one-dimensional and two-dimensional nanofillers with large aspect ratios provide enhanced flexibility versus zero-dimensional fillers. Surface modification of nanomaterials as well as polymers adds flavor to the dielectric properties of the resulting nanocomposites. Nowadays, three-phase nanocomposites with either combination of fillers or polymer matrix help in further improving the dielectric properties as compared to two-phase nanocomposites. Recent research has been focused on altering the dielectric properties of different materials while also maintaining their superior flexibility. Flexible polymer nanocomposites are the best candidates for application in various fields. However, certain challenges still present, which can be solved only by extensive research in this field.
Genre theory in the past few years has contributed immensely to our understanding of the way discourse is used in academic, professional and institutional contexts. However, its development has been ...constrained by the nature and design of its applications, which have invariably focused on language teaching and learning, or communication training and consultation. This has led to the use of simplified and idealised genres. In contrast to this, the real world of discourse is complex, dynamic and unpredictable. This tension between the real world of written discourse and its representation in applied genre-based literature is the main theme of this book. The book addresses this theme from the perspectives of four rather different worlds: the world of reality, the world of private intentions, the world of analysis and the world of applications. Using examples from a range of situations including advertising, business, academia, economics, law, book introductions, reports, media and fundraising, Bhatia uses discourse analysis to move genre theory away from educational contexts and into the real world. Introduction Overview: Perspectives on Discourse The World of Reality The World of Private Intentions The World of Analysis The World of Applications References
The COVID-19 pandemic has brought to light the lacunae in the preparedness of healthcare systems across the globe. This preparedness also includes the safety of healthcare providers (HCPs) at various ...levels. Sudden spread of COVID-19 infection has created threatening and vulnerable conditions for the HCPs. The current pandemic situation has not only affected physical health of HCPs but also their mental health.
This study aims to understand the prevalence and severity of secondary traumatic stress, optimism parameters, along with states of mood experienced by the HCPs, viz., doctors, nurses and allied healthcare professionals (including Physiotherapist, Lab technicians, Phlebotomist, dieticians, administrative staff and clinical pharmacist), during the COVID-19 lockdown in India.
The assessment of level of secondary traumatic stress (STS), optimism/pessimism (via Life Orientation Test-Revised) and current mood states experienced by Indian HCPs in the present COVID-19 pandemic situation was done using a primary data of 2,008 HCPs from India during the first lockdown during April-May 2020. Data was collected through snow-ball sampling technique, reaching out to various medical health care professionals through social media platforms.
Amongst the study sample 88.2% of doctors, 79.2 of nurses and 58.6% of allied HCPs were found to have STS in varying severity. There was a female preponderance in the category of Severe STS. Higher optimism on the LOTR scale was observed among doctors at 39.3% followed by nurses at 26.7% and allied health care professionals 22.8%. The mood visual analogue scale which measures the "mood" during the survey indicated moderate mood states without any gender bias in the study sample.
The current investigation sheds light on the magnitude of the STSS experienced by the HCPs in the Indian Subcontinent during the pandemic. This hitherto undiagnosed and unaddressed issue, calls for a dire need of creating better and accessible mental health programmes and facilities for the health care providers in India.
Vessel segmentation of retinal images is a key diagnostic capability in ophthalmology. This problem faces several challenges including low contrast, variable vessel size and thickness, and presence ...of interfering pathology such as micro-aneurysms and hemorrhages. Early approaches addressing this problem employed hand-crafted filters to capture vessel structures, accompanied by morphological post-processing. More recently, deep learning techniques have been employed with significantly enhanced segmentation accuracy. We propose a novel domain enriched deep network that consists of two components: 1) a representation network that learns geometric features specific to retinal images, and 2) a custom designed computationally efficient residual task network that utilizes the features obtained from the representation layer to perform pixel-level segmentation. The representation and task networks are jointly learned for any given training set. To obtain physically meaningful and practically effective representation filters, we propose two new constraints that are inspired by expected prior structure on these filters: 1) orientation constraint that promotes geometric diversity of curvilinear features, and 2) a data adaptive noise regularizer that penalizes false positives. Multi-scale extensions are developed to enable accurate detection of thin vessels. Experiments performed on three challenging benchmark databases under a variety of training scenarios show that the proposed prior guided deep network outperforms state of the art alternatives as measured by common evaluation metrics, while being more economical in network size and inference time.
Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination ...strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes. Further, the physiochemical characterization was performed to check the aliphatic index, theoretical PI, molecular weight, and thermostable nature of vaccine construct. The allergenicity and antigenicity were also predicted to ensure the safety and immunogenic behavior of final vaccine construct. Moreover, homology modeling, followed by molecular docking and molecular dynamics simulation study was also performed to evaluate the binding affinity and stability of receptor (TLR-4) and ligand (vaccine protein) complex. This study warrants the experimental validation to ensure the immunogenicity and safety profile of presented vaccine construct which may be further helpful to control VL infection.
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