Housekeeping and other metabolic functions of the Plasmodium plastid

The malaria parasite carries a plastid called the apicoplast that has been the subject of intense study in the last 15 years. Having originated from red-algal plastids, the apicoplast has lost its ability to photosynthesize, but carries out other essential functions such as type-II fatty acid synthesis, biosynthesis of haem and isoprenoid synthesis; the DOXP pathway for isoprenoid synthesis has recently been demonstrated to be the only pathway critical for parasite survival in the erythrocytic stage. The apicoplast also has a functional Suf system for assembly of (Fe–S) complexes on target proteins. The organelle has a 35 kb, double-stranded DNA genome that encodes a set of RNAs and proteins, the latter being translated from organellar mRNA by an active translation machinery, a major component of which is encoded by the nucleus. This article reviews current knowledge of housekeeping functions of the Plasmodium apicoplast and its (Fe–S) assembly system and discusses these components as sites for drug intervention against malaria

A study on wire breakage and parametric efficiency of the wire electro chemical discharge machining process 1

Abstract: -The Wire Electrochemical Discharge Machining (WECDM) is a nonconventional process, typically used in cutting brittle and hard non-conductive materials. The WECDM is relatively new research area compared to its principle process-'Electro Chemical Discharge Machining (ECDM). In the current investigation, the wire breakage problem, commonly encountered while machining fine slots has been addressed. The aim was to reduce the wire breakage through optimum parametric settings, to understand the wire breaking voltages at different electrolytic concentrations along with its effect on the MRR, length of cut and width of cut. In this study, zinc diffused brass wire of fine diameter (0.20 mm) was used in experiments and the results of the same are being reported in the paper. The response parameters used in the investigation were MRR and width of cut; while the process parameters were workpiece feed rate, electrolyte concentrations and applied voltage

Coupling dynamics of a geared multibody system supported by Elastohydrodynamic lubricated cylindrical joints

A comprehensive computational methodology to study the coupling dynamics of a geared multibody system supported by ElastoHydroDynamic (EHD) lubricated cylindrical joints is proposed throughout this work. The geared multibody system is described by using the Absolute-Coordinate-Based (ACB) method that combines the Natural Coordinate Formulation (NCF) describing rigid bodies and the Absolute Nodal Coordinate Formulation (ANCF) characterizing the flexible bodies. Based on the finite-short bearing approach, the EHD lubrication condition for the cylindrical joints supporting the geared system is considered here. The lubrication forces developed at the cylindrical joints are obtained by solving the Reynolds’ equation via the finite difference method. For the evaluation of the normal contact forces of gear pair along the Line Of Action (LOA), the time-varying mesh stiffness, mesh damping and Static Transmission Error (STE) are utilized. The time-varying mesh stiffness is calculated by using the Chaari’s methodology. The forces of sliding friction along the Off-Line-Of-Action (OLOA) are computed by using the Coulomb friction models with a time-varying coefficient of friction under the EHD lubrication condition of gear teeth. Finally, two numerical examples of application are presented to demonstrate and validate the proposed methodology.National Natural Science Foundations of China under Grant 11290151, 11221202 and 11002022, Beijing Higher Education Young Elite Teacher Project under Grant YETP1201

Rapid growth and high cloud-forming potential of anthropogenic sulfate aerosol in a thermal power plant plume during COVID lockdown in India

The COVID lockdown presented an interesting opportunity to study the anthropogenic emissions from different sectors under relatively cleaner conditions in India. The complex interplays of power production, industry, and transport could be dissected due to the significantly reduced influence of the latter two emission sources. Here, based on measurements of cloud condensation nuclei (CCN) activity and chemical composition of atmospheric aerosols during the lockdown, we report an episodic event resulting from distinct meteorological conditions. This event was marked by rapid growth and high hygroscopicity of new aerosol particles formed in the SO2 plume from a large coal-fired power plant in Southern India. These sulfate-rich particles had high CCN activity and number concentration, indicating high cloud-forming potential. Examining the sensitivity of CCN properties under relatively clean conditions provides important new clues to delineate the contributions of different anthropogenic emission sectors and further to understand their perturbations of past and future climate forcing

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era