Showing papers in "Journal of the Indian Institute of Science in 2018"
TL;DR: In this article, the authors present an overview of research on flow in microconfinements with deformable boundaries, including electrokinetics, diffusion and porous flow, with a brief discussion about the cross-correlation between the works presented based on the phenomena studied.
Abstract: In this article,
we present an overview of research on flow in microconfinements with deformable boundaries. The time frame of focus is the last decade (2007–2017). The article is arranged into sections based on the geometry of the problem studied,
which fall under five major categories—microchannels, tubes, squeeze flow, cylinder near wall and thin structures (membranes, sheets, etc.).
The modelling of various coupled phenomena such as electrokinetics, diffusion and porous flow is discussed, maintaining the study of deformable boundaries as a common underlying theme. The article concludes with a brief discussion about the cross-correlation between the works presented based on the phenomena studied, constitutive models considered and methodologies employed.
33 citations
TL;DR: The configuration of the Greater Indian Landmass was achieved during the late Proterozoic era (Grenvillian-age) through tectonic cycles involving cratonic blocks of India and East Antarctica in the broad framework of the assembly of the supercontinent Rodinia.
Abstract: The configuration of the Greater Indian Landmass was achieved during the late Proterozoic era (Grenvillian-age) through tectonic cycles involving cratonic blocks of India and East Antarctica in the broad framework of the assembly of the supercontinent Rodinia. Geological evidences are recorded from orogenic belts separating southern, northern and western cratonic blocks of India and its transcontinental neighbor East Antarctica. Eastern Ghats Belt of India played a pivotal role in the continental amalgamation process and it evolved in tandem with the Central Indian Tectonic Zone and the Aravalli Delhi Mobile Belt. We have collated geological and geochronological evidences from the cratonic blocks and the bounding orogenic belts to trace back the Grenvillian-age tectonics surrounding India and its eventual manifestation as the configuration of the Greater Indian Landmass. The status of the Greater Indian Landmass as a part of Rodinia is debated and unresolved issues are highlighted.
30 citations
TL;DR: In this review, computational methods that can be used to study quadruplex–ligand interactions are explored to provide interpretation of experimental data and generate information that cannot be accessed by experimental methods.
Abstract: Quadruplexes are four-stranded DNA or RNA structures formed from tandem repeats of guanine-rich sequences. They are present throughout the genome, namely at telomeres, in promoter and untranslated regions of important genes. Quadruplexes are thermodynamically stable structures and once formed can be a hindrance to cellular processes like transcription, translation, replication among others. Based on these findings, it has been proposed that small molecules can be used to selectively bind and stabilise quadruplexes. In this review, we explore computational methods that can be used to study quadruplex–ligand interactions. These methods not only provide interpretation of experimental data but also generate information that cannot be accessed by experimental methods.
15 citations
TL;DR: It is indicated that not many microdevices for platelet separation are currently available, pointing to an important void that needs to be urgently filled.
Abstract: One of the major areas of active research in microfluidics is in biological applications. These applications often require complex analysis of biological fluids for clinical diagnostics. One such complex multicomponent suspension is blood, a mixture of cells suspended in plasma. The cellular components constitute RBCs, WBCs, and platelets. Platelets play a fundamental role in blood clotting mechanism and their efficient functioning is of utmost importance. Platelet separation is necessary for disease diagnostics, transfusion, and research purposes. Centrifugation is commonly employed for platelet separation. However, researchers are developing techniques to enable platelet separation using microfluidics as a tool, primarily due to the various advantages offered while working at microscale. In this review, we investigate and highlight various microscale platelet separation techniques currently available, focusing on their design, working principle, and performance aspects. The issues, challenges, and further possibilities of research and development are also underscored. Our review indicates that not many microdevices for platelet separation are currently available, pointing to an important void that needs to be urgently filled. A brief discussion on the conventional method of platelet separation and platelet dynamics is also included.
13 citations
TL;DR: Under the current trends of hyperspectral sensing from different platforms and instruments for various applications, mobile platforms are discussed which include spaceborne, airborne, ground-based sensing, unmanned aerial system, and underwater vehicle-based.
Abstract: Hyperspectral imaging is one of the promising remote sensing techniques. This technique records the spatial and spectral information of the object under study. Consequently, it has been gaining momentum in a number of Earth observing applications. The aim of this paper is to present the current trends of hyperspectral sensing from different platforms and instruments for various applications. For Earth observation, mobile platforms are discussed which include spaceborne, airborne, ground-based sensing, unmanned aerial system, and underwater vehicle-based. Under these different sensing platforms, hyperspectral imaging instruments are presented that have been developed by various public and private organizations in the past with some specific goals.
12 citations
TL;DR: A review of microfluidic membrane mimics can be found in this article, where a special focus is given to the filtration of colloidal fouling in a micro-fluid device.
Abstract: This review provides an overview of the recent improvements of microfluidic membrane mimics. A special focus is given to the filtration of colloids in this device. Methods for on-chip membrane filtration have undergone significant development and improvement over the past two decades. Many efforts have been made to develop a single chip microfluidic platform that integrates the benefits of microfluidics and membrane science and technology. This review addresses the potential for microfluidic devices to serve as microfiltration membranes for separation purposes, as well as, micro-sized tools to study colloidal fouling phenomena at the pore scale.
11 citations
TL;DR: Paper microfluidic devices as discussed by the authors are a new class of micro-fluidics devices in which flow channels are composed of multidimensional (2D or 3D) shapes of porous materials, making them portable, low-cost and ideal for use in low-resource settings.
Abstract: Since Andreas Manz first introduced the microchip technology for chemical applications back in the 1990s, the field of ‘microfluidics’ has expanded widely and microfluidic tools have become ubiquitous in life sciences research. However, pumps and controllers associated with most current microfluidic chips continue to be bulky and costly. A new class of microfluidic devices in which flow channels are composed of multidimensional (2D or 3D) shapes of porous materials is becoming increasingly popular. The ability of porous materials to wick fluids obviates the need for pumps, making such devices portable, low-cost, and ideal for use in low-resource settings. Such devices are broadly referred to as “paper microfluidic devices”. The ability to manipulate fluids in paper microfluidics has progressively increased over the past decade and such devices are currently being used to develop highly sensitive and multiplexed low-cost diagnostic/sensing devices. In this article, we review the area of paper microfluidics covering the basic fluid physics, methods of fabrication, flow control tools, applications in diagnostics/sensing, and applications in other emerging areas like tissue engineering and power storage. This review is targeted to a broad audience that does not have prior exposure to the field of paper-based microfluidics. Through this article, we wish to invite researchers from multiple backgrounds to contribute to further development in this new and exciting area of research.
10 citations
TL;DR: In this article, the authors report contrasting magmatic conditions in the generation of anorogenic (A-type) felsic rocks from the Phenai Mata hill of Deccan Large Igneous Province.
Abstract: We report contrasting magmatic conditions in the generation of anorogenic (A-type) felsic rocks from the Phenai Mata hill of Deccan Large Igneous Province. The felsic units in the present study area can be classified as granite, monzonite, quartz monzonite and granodiorite. The field as well as the geochemical evidences collectively indicate the mixing and mingling of contrasting magma compositions which were widely involved in the genesis of these anorogenic intrusions. Based on the anorogenic granite classification diagrams, it has been observed that the granite shows A1 type character whereas the monzonite, quartz monzonite and granodiorite exhibit A2 type characters. Both A1 and A2 type intrusions were compared with the associated basaltic andesites in the variation diagrams and found that the A1 type rocks exhibit a well-defined trend pointing towards a fractional crystallization process. The A2 type rocks do not exhibit any particular geochemical relation with the mafic rocks. Moreover, the A2 type rocks are characterized by negative Nb and Ta anomalies in the normalized diagrams indicating the involvement of crustal components. From the field and geochemical evidence, it can be presumed that the A1 type rocks represent the fractional crystallization sequence from a basaltic magma, whereas the A2 rocks might have been produced by the melting of the pre-existing crust or by the assimilation of crustal components into the mafic magma during ascent. These contrasting magmas along with the mafic magma variably interacted in the shallow crustal levels to form present-day field features in the Phenai Mata Igneous complex.
8 citations
TL;DR: In this paper, a high-resolution zircons at high resolution separated from metamorphosed rocks of igneous origin of the four tectonic domains of Sri Lanka by Lu-Hf and U-Pb isotope systematics have shed light upon its tectono-magmatic history.
Abstract: Recent studies on zircons at high resolution separated from metamorphosed rocks of igneous origin of the four tectonic domains of Sri Lanka by Lu–Hf and U–Pb isotope systematics have shed light upon its tectono-magmatic history. While providing better insights, the new dataset is not contradictory with Nd-model ages and U–Pb zircon dates discovered from Sri Lanka in early 90s. These new data suggest that both Wanni (WC) and Vijayan (VC) Complexes were magmatic arcs with the former being relatively older than the latter, and the Kadugannawa Complex (KC) is a marginal arc magmatic suite in the vicinity of WC. The oldest Highland Complex (HC) has been derived of Mesoproterozoic to Archean crustal and subducted sedimentary components. The Lu–Hf systematics of rocks from the HC record the oldest Hf-crustal model age of ~ 3.5 Ga and highly negative eHf(t)(t) values (up to − 30) inferring contribution of older subducted sediments and/or crustal components. In the WC and KC tectonic units, variable eHf(t) of zircon from negative to positive values from gneisses indicate the involvement of both juvenile mantle components and older continental materials in the generation of the arc-related magma with Hf-model ages from ~ 700 to 2800 Ma. On the other hand, the meta igneous rocks of the VC have distinct positive eHf(t) data with Hf-modal ages in the range of ~ 700–1600 Ma supporting entirely a juvenile origin. During the Neoproterozoic to Cambrian (ca. 700–500 Ma), the HC has predominantly served as a suture zone for the collision of the WC and VC arcs. This suggests that the Sri Lankan terrains were juxtaposed at an active continental margin setting associated with two-staged subduction during the Gondwana amalgamation. The metamorphism took place during the Neoproterozoic in the entire basement up to the granulite facies conditions reaching intermittently ultrahigh temperature (UHT) conditions.
8 citations
TL;DR: In this article, preliminary geochemical data for the dykes in the Tiptur area, WDC and compare them with the dyke swarms in the EDC are presented, and the difference in petrography, major, trace and rare earth element geochemistry between the dolerites and meta-dolerites lead to a preliminary inference that these two suits of rocks might not be cogenetic.
Abstract: Mafic dyke swarms are abundantly distributed in the Archean Dharwar craton. Previous studies have focused mainly on the major mafic dyke swarms in EDC; however, those in the WDC are yet to be studied in detail. Here we present preliminary geochemical data for the dykes in the Tiptur area, WDC and compare them with the dyke swarms in the EDC. Petrological studies indicate that the dykes in the Tiptur area fall into two distinct groups. The NW–SE trending dolerite dykes are unaltered, with characteristic ophitic textures and are geochemically comparable to 2.3 Ga EDC dykes. In contrast, the NE–SW trending meta-doleritic dykes showed high degree of alteration. The difference in petrography, major, trace and rare earth element geochemistry between the dolerites and meta-dolerites lead to a preliminary inference that these two suits of rocks might not be co-genetic. Meta-dolerites have not been reported from the EDC and it is possible to assume that they are a part of an earlier event, restricted in WDC, that might have emplaced prior to the amalgamation of WDC and EDC. In a global perspective, we compare our results with those reported in Archean cratons during late Archean to early Proterozoic around the world to constrain similarities that can lead to understanding the global scale magmatic activity and to aid in correlations between cratons.
8 citations
TL;DR: This review seeks to highlight the mechanistic details of ion-coupled transport and delve into the biophysical tools and methods that help in understanding these fascinating molecules.
Abstract: Cell membranes, despite providing a barrier to protect intracellular constituents, require selective gating for influx of important metabolites including ions, sugars, amino acids, neurotransmitters and efflux of toxins and metabolic end-products. The machinery involved in carrying out this gating process comprises of integral membrane proteins that use ionic electrochemical gradients or ATP hydrolysis, to drive concentrative uptake or efflux. The mechanism through which ion-coupled transporters function is referred to as alternating-access. In the recent past, discrete modes of alternating-access have been described with the elucidation of new transporter structures and their snapshots in altered conformational states. Despite X-ray structures being the primary sources of mechanistic information, other biophysical methods provide information related to the structural dynamics of these transporters. Methods including EPR and smFRET, have extensively helped validate or clarify ion-coupled transport mechanisms, in a near-native environment. This review seeks to highlight the mechanistic details of ion-coupled transport and delve into the biophysical tools and methods that help in understanding these fascinating molecules.
TL;DR: Individual components of the immune system are described, followed by a discussion of the recent advances in biomaterial-based strategies for the modulation of immune responses.
Abstract: The last few decades have seen rapid progress in the fields of drug delivery systems, implantable scaffolds, and tissue engineering. Broadly referred to as biomaterials, these inter-related areas of research have many diverse applications. One such application is in the area of immunology, where biomaterials may be used as tools to modify specific immune responses. Here, individual components of the immune system are described, followed by a discussion of the recent advances in biomaterial-based strategies for the modulation of immune responses.
TL;DR: In this article, a review of in-vivo-grown protein crystals and the new approaches towards micro-crystallography are summarized, and some of the diverse examples of in vivo crystals and their new approaches toward microcrystallization are summarized.
Abstract: The function of a protein dictates its physical state in a cell. Evolution has imparted selection pressure on proteins to maximize their function and minimize cell death. Most of the proteins exist in their soluble form inside or outside the cells. However, a small fraction of proteins in the total protein pool crystallizes with functional consequence. These in vivo-grown protein crystals perform a diversity of functions, ranging from food storage to defense. Sometimes limited by the volume of the cells and the cellular concentration of proteins, these crystals are very small in size. Hence, it has been difficult to carry out conventional X-ray crystallography on these crystals. With the advent of microcrystallography, it is now possible to study the structures of these tiny crystals. In this review, some of the diverse examples of in vivo crystals and the new approaches towards microcrystallography are summarized.
TL;DR: This work has shown that peptide-based biomaterials have emerged as a powerful immune-modulating strategy that can enlist the adaptive immune system in mounting a cellular or humoral immune response to a presented epitope or antigen.
Abstract: The versatility of supramolecular design in creating biomaterials and drug delivery devices for applications in medicine has gained considerable traction in recent years. The design of peptide-based self-assembling materials is one example of a highly useful and biomimetic approach to the generation of supramolecular biomaterials. One exciting area where designed supramolecular biomaterials created from peptides have demonstrated promise is in the field of immunoengineering.
Specifically, peptide-based biomaterials have been used in several different contexts to modify the host immune system through the controlled release of active signaling proteins, pharmaceutical agents, or gasotransmitters. In a separate approach, this class of materials has emerged as a powerful immune-modulating strategy that can enlist the adaptive immune system in mounting a cellular or humoral immune response to a presented epitope or antigen. The ease with which these materials are synthesized, their alignment with injection-based procedures, their low toxicity, and their rapid biodegradation make these useful materials for application in immunoengineering.
TL;DR: The lamprophyre xenoliths are distinct in texture (grain size) as well as in mineralogy from those of their host rock as mentioned in this paper, and they are inferred to represent an earlier pulse of lamp-phyre emplacement.
Abstract: We report rare occurrence of lamprophyre xenoliths within a host lamprophyre from the Dongargaon area, Deccan Large Igneous Province, NW India. The lamprophyre xenoliths are distinct in texture (grain size) as well in mineralogy from those of their host rock. The clinopyroxene (diopside) in the xenoliths is depleted in Ca and Mg but substantially enriched in Fe compared to those in the host lamprophyre. Mica in the xenoliths is a phlogopite whereas that present in the host rock is compositionally a biotite; spinels in the host lamprophyre are relatively enriched in TiO2. As the host lamprophyre dyke has been dated to be of Eocene (ca. 55 Ma) age, the entrained lamprophyre xenoliths are inferred to represent an earlier pulse of lamprophyre emplacement. The recurrent lamprophyre emplacement in this domain is consistent with the recently brought out polychronous nature of Late Cretaceous alkaline magmatism at the Mundwara and Sarnu Dandali complexes in the NW India and is related to the extensional events linked with the reactivation of the Narmada rift zone.
TL;DR: The fascinating details of the mechanistic variation of these enzymes and the molecular determinants that define the chain-length specificity have been discussed herewith.
Abstract: Fatty acyl-AMP ligases (FAAL) are enzymes that establish the crosstalk between fatty acid synthases and polyketide synthases or non-ribosomal peptide synthetases by activating newly synthesized fatty acids, shuttling them towards polyketide synthesis. These enzymes are unique as they have evolved a strict rejection mechanism for the coenzyme-A but can recognize and react with the phosphopantetheine of acyl-carrier proteins. A strategically placed insertion in the N-terminal domain and the rigidity of the hydrophobic anchor holding the insertion is at the heart of such a discrimination mechanism, the molecular details of which is yet to be clearly understood. The unique structural features of the insertion have been exploited to filter out FAALs from other members of the superfamily, in silico. Interestingly, several independent studies have characterized FAALs from different organisms such as Legionella, Myxococcus, Ralstonia, Pseudoalteromonas, Sorangium, etc. to name a few, laying emphasis on the usage of a FAAL-specific biochemistry in these organisms, particularly for the production of important bioactive molecules. These bioactive molecules help in improving the fitness of these systems to tide over the competition for nutritional resources in their local niche. Substrate specificity of these enzymes is another interesting aspect, which may hint at their potential roles in the cell. Various substrate-bound crystal structures have been used to identify the determinants of chain-length specificity and predict the preferences for different FAALs (both mycobacterial and non-mycobacterial). The fascinating details of the mechanistic variation of these enzymes and the molecular determinants that define the chain-length specificity have been discussed herewith.
TL;DR: Rapid electrokinetic patterning (REP) is a hybrid optoelectrokinetic technique that simultaneously uses a laser illumination and a uniform AC electric field to yield programmable, dynamic, and non-invasive manipulation of colloidal particles as mentioned in this paper.
Abstract: The dynamic manipulation and assembly of colloids enables the advancement of analytical techniques in biotechnology and the development of self-assembled materials. Rapid electrokinetic patterning (REP) is a hybrid optoelectrokinetic technique that simultaneously uses a laser illumination and a uniform AC electric field to yield programmable, dynamic, and non-invasive manipulation of colloidal particles. Since it was introduced, the technique has been applied to microengineering and biological research fields, showing its promising capabilities as a great tool for trapping, aggregating, translating, and sorting single and multiple micro- and nanoparticles, including bacteria. To effectively leverage and enhance these applications, this review paper will highlight its versatility and capability, including REP’s principles, governing physics, different experimental setups, fabrications, applications, and future prospects.
TL;DR: A detailed three-dimensional structure of macromolecular assemblies is necessary to understand their function which in turn helps to understand life Cryo-electron microscopy (cryo-EM) is a powerful method for structural studies of a wide range of different sizes biological macromoles and their complexes as discussed by the authors.
Abstract: A detailed three-dimensional structure of macromolecular assemblies is necessary to understand their function which in turn helps to understand life Cryo-electron microscopy (cryo-EM) is a powerful method for structural studies of a wide range of different sizes biological macromolecules and their complexes Cryo-EM has three different imaging modalities based on specimen and imaging condition: single particle analysis (SPA), cryo-electron tomography (cryo-ET) plus sub-tomogram averaging (STA)/sub-volume averaging (SVA) and electron diffraction Richard Henderson and Nigel Unwin revealed the structure of the first membrane protein bacteriorhodopsin from electron diffraction data This led to the beginning of understanding molecular structures of biomolecules in three-dimension Soon after that, a unique vitrification method of biomolecules has been successfully developed by Jacques Dubochet more than two decades ago Ordered 2D array or biomolecules with internal symmetry have long been considered for structure determination to achieve better resolution But structure calculation by electron microscopy was at that time known as blobology to others due to low resolution Images with small number of pixels and less information and less detail
(image with less information) compared to X-ray Since then imaging and software technologies have steadily improved and after 2013, with the development and success of direct detectors, the world witnessed a resolution revolution in cryo-EM Now cryo-EM more specifically single particle analysis has achieved the resolution at which protein complex can be studied at near-atomic level This once a highly skilled and difficult technique has now become a widely accepted biophysical technique in structural biology Here the two methods of cryo-EM (SPA and cryo-ET) and recent studies are reviewed
[...]
TL;DR: Sajeev et al. as discussed by the authors investigated the mafic dyke swarms in the Dharwar Craton to gain insights on the Archean-to-early Paleoproterozoic evolution.
Abstract: Planet Earth is unique in terms of its dynamic nature driven by the movement of lithospheric plates through what Earth Scientists term as plate tectonics which is the fundamental driver for continent building, life evolution and extinction, natural hazards, as well all the evolution of natural resources and environment. The history of our planet over its 4.6 billion years since birth is mostly shrouded in mystery except for our direct knowledge on ongoing processes from which we attempt to build the jigsaw puzzles of the past. In this special issue of the IISc Journal, we assemble five contributions that address some of the key evidence gathered from the Indian subcontinent and the adjacent Sri Lankan region that provide insights in various Earth processes in relation to the geological evolution through various tectonic processes. The opening paper by Bose and Dasgupta focuses on the Eastern Ghats Belt and its implications on the Proterozoic evolution of the Greater Indian landmass. They correlate tectonic cycles involving cratonic blocks of India and East Antarctica in the broad framework of the assembly of the supercontinent Rodinia. The conclude that the Eastern Ghats Belt of India played a pivotal role in the continental amalgamation process and it evolved in tandem with the Central Indian Tectonic Zone and the Aravalli Delhi Mobile Belt. In the next paper, Silpa and Satish-Kumar investigate the mafic dyke swarms in the Dharwar Craton to gain insights on the Archean-to-early Paleoproterozoic evolution. They present petrological and geochemical data on dyke rocks from the Western and Eastern Dharwar Cratonic blocks and bring out their distinctions. The authors conclude that the dykes were emplaced prior to the amalgamation of the Western and Eastern Dharwar blocks. They compare their results in a global perspective to understand the global-scale magmatic activity and inter-craton correlations. Hari et al. investigate the granitoids from the Phenai Mata Igneous complex in the Deccan Large Igneous Province of central India. They M. Santosh1,2* and K. Sajeev3 J. Indian Inst. Sci.
TL;DR: The present review is aimed at introducing various NMR isotope labeling strategies and discusses their impact in widening the scope of biomolecular NMR spectroscopy driven structural biology.
Abstract: NMR spectroscopy has become an indispensable tool for high-resolution structure determination of biomolecules at physiological conditions both in solutions and solids. Currently, NMR is routinely used to study the structure and dynamics of high molecular weight biomolecules in sizes ranging up to ~ 50–100 kDa and to evaluate complexes as large as 500–1 MDa. The latest advances in spectrometer technology, methodologies and advents in newer and highly innovative NMR active isotope-labeling strategies now enable us to overcome an earlier speculated size barrier of ~ 20 kDa for de novo structure determination. Of these, developments in NMR active isotope-labeling strategies are of great significance as they allow reduction in spectral crowding and yield selective spin correlations. Moreover, NMR isotope enrichment schemes permit exploitation of heteronuclear magnetization transfer pathways for enhanced sensitivity and selectivity. Functionally relevant sites or domains in very large complexes can also be selectively evaluated by specific labeling strategies in which other regions are masked. Further, labeling schemes can be effectively used to favourably overcome deleterious relaxation effects. Recently evolved labeling strategies include uniform labeling, perdeuteration, specific labeling of an amino acid or a side chain, selective deuteration or protonation, segmental labeling and biosynthesis of biomolecules in various organisms, cell lines and cell-free systems. The present review is aimed at introducing various NMR isotope labeling strategies and discusses their impact in widening the scope of biomolecular NMR spectroscopy driven structural biology.
TL;DR: This review recaps a few state-of-the-art tools and technologies that have helped harness the power of human immunology for vaccine design, evaluation, and testing.
Abstract: Our understanding of human immune responses is increasing at an unprecedented scale. Cutting edge new technologies are allowing us to disregard a piecemeal approach and analyze human immune responses in a comprehensive and cohesive manner. Innovative approaches to analyze immune cell phenotype, genotype, function, and associated soluble factors have provided us with a new hope for making vaccines against diseases that have been historically impossible. This review recaps a few state-of-the-art tools and technologies that have helped us harness the power of human immunology for vaccine design, evaluation, and testing.
TL;DR: For many years, X-ray crystallography has been exclusively used by structural biologists for resolving virus structures and viral proteins at atomic resolution level However, the discovery of electron microscopy, especially Cryo-electron microscopy (cryoEM), has enabled us to visualise the detailed structural features of biological macromolecules in a more accurate way.
Abstract: For many years, X-ray crystallography has been exclusively used by structural biologists for resolving virus structures and viral proteins at atomic resolution level However, the discovery of electron microscopy, especially Cryo-electron microscopy (cryoEM), has enabled us to visualise the detailed structural features of biological macromolecules in a more accurate way In recent years, cryoEM has made sudden progress in its use due to high-end microscopes, improved detectors and modernised software It is now possible to get near-atomic resolution three-dimensional viral maps using cryoEM Among viruses, the bacterial viruses or bacteriophages are the most fascinating objects for the structural biologists as they are highly symmetrical particles The development of cryoEM has also made it easy to determine the structures of these highly symmetrical macromolecules at near-atomic resolution
TL;DR: This review examines the different factors involved in CAR-T cell design such as design of the synthetic receptor, choice of T-cell subset and tumor target, and the use of safety circuits designed inCAR-T cells to minimize off-tumor toxicity.
Abstract: Chimeric antigen receptors (CAR) are synthetic receptors consisting of recognition domains derived from antibodies coupled to the signaling domains of T cells. CAR-modified T-cell therapies have shown dramatic remissions in the treatment of B-cell-derived malignancies. This review examines the different factors involved in CAR-T cell design such as design of the synthetic receptor, choice of T-cell subset and tumor target. Further, we discuss the promise of the initial clinical trials in hematological malignancies and the obstacles for translation of CAR-T cell therapies in solid tumors. The review also describes the use of safety circuits designed in CAR-T cells to minimize off-tumor toxicity. The combination of these approaches will help facilitate effective translation of CAR-T cell therapies.