Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria.

Differentiation of naïve CD4+ T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates

Synthesis, spectral, thermal and electrochemical studies of oxomolybdenum(V) and dioxomolybdenum(VI) complexes of an azo dye derived from 4-amino-2,3-dimethyl-1-phenyl pyrazol-5-one

1787-1792Some novel complexes of oxomolybdenum(V) and dioxomolybdenum(VI) with an azodye derived from 4-amino-antipyrine and 3-methoxyphenol have been synthesised and characterized by elemental analyses, molar conductance values, magnetic susceptibility measurements, IR, electronic, ESR, and ¹H NMR spectra and cyclic voltammetric studies. The physico-chemical studies and spectral data indicate that the ligand acts as neutral bidentate. All the complexes are found to be monomeric and neutral with distorted octahedral geometry. The X-ray diffraction studies of [MoO(MOPAAP)Cl₃] and [MoO₂(MOPAAP)Cl₂] indicate that the complexes are orthorhombic with the unit cell dimensions a = 7.3277 Å, b = 9.6663Å and c = 15.8897 Å; and a = 8.5534 Å, b = 9.5986 Å, c = 15.4056 Å respectively.. The CV profile of the complex [MoO(MOPAAP)Cl₃] shows a quasireversible peak, which indicates that the metal-ligand linkage is more covalent in nature. The thermal stabilities of the complexes have been compared and show that [MoO(MOPAAP)Cl₃] is more stable than [MoO₂(MOPAAP)Cl₂]

Studies on friction in cotton textiles: Part I—A study on the relationship between physical properties and frictional characteristics of cotton fibres and yarns

244-250<span style="mso-fareast-font-family:SimSun; mso-ansi-language:EN-US;mso-fareast-language:AR-SA" lang="EN-US">The present paper reports a study on the relationship between physical properties of cotton and the frictional characteristics at the fibre and yarn stages. It is observed that coarser fibres show higher coefficient of friction. With regard to yarns, coarser and more compressible yarns show higher coefficient of friction values. </span

Novel heterocyclic construction via dipolar cycloadditions to 1,2-dicarbonyl compounds

The reactivity of o-quinones and other 1,2-diones towards a variety of dipolar species viz-, nitrile oxides, carbonyl ylides, betaines and mesoionic compounds has been investigated. In most cases, these reactions occur with the participation of C=O group as the dipolarophile leading to the synthesis of novel heterocyclic compounds

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Not AvailableAntimicrobial resistance (AMR) burden in Escherichia coli along the 90 km stretch of Vembanad Lake, Kerala, India, was assessed. Seventy- seven percent of water samples drawn from 35 different stations of the lake harbored E. coli. Antibiotic susceptibility test performed on 116 E. coli isolates revealed resistance to ≥ one antibiotic with 39 AMR profiles in 81%, multidrug resistance in 30%, and extended spectrum β - lactamase (ESBL) producers in 32%. Of all the 15 antibiotics tested, the probability of isolating cefotaxime - resistant E. coli was the highest ( P ≤ 0.05) in the lake. Genetically diverse ESBL types, namely blaTEM -116, blaCTX - M -152, blaCTX - M -27, blaCTX - M - 55, blaCTX - M - 205, and blaSHV - 27, were identified in the lake. This is probably the first report in India for the presence of blaCTX - M - 205 (blaCTX - M - group 2) in the Vembanad Lake. ST11439 and single and double loci variants of ST443 and ST4533 were identified in multilocus sequence typing (MLST). Inc plasmids (B / O, F, W, I1, FIIA, HI1, P - 1α, K / B, and N) identified in the lake evidences the resistance transmission potential of the E. coli isolated from the lake. Molecular typing (ERIC - PCR, MLST, and PBRT) delineated diverse E. coli, both between and within the sampling stations. Low multiple antibiotic resistance index (average MAR < 0.2) indicates a lower risk of the lake to the human population, but the occurrence of genetically diverse ESBL E. coli in the Vembanad Lake signals health hazards and necessitates pragmatic control measures.Not Availabl

Quantification of host-mediated parasite clearance during blood-stage Plasmodium infection and anti-malarial drug treatment in mice

A major mechanism of host-mediated control of blood-stage Plasmodium infection is thought to be removal of parasitized red blood cells (pRBCs) from circulation by the spleen or phagocytic system. The rate of parasite removal is thought to be further increased by anti-malarial drug treatment, contributing to the effectiveness of drug therapy. It is difficult to directly compare pRBC removal rates in the presence and absence of treatment, since in the absence of treatment the removal rate of parasites is obscured by the extent of ongoing parasite proliferation. Here, we transfused a single generation of fluorescently-labelled Plasmodium berghei pRBCs into mice, and monitored both their disappearance from circulation, and their replication to produce the next generation of pRBCs. In conjunction with a new mathematical model, we directly estimated host removal of pRBCs during ongoing infection, and after drug treatment. In untreated mice, pRBCs were removed from circulation with a half-life of 15.1 h. Treatment with various doses of mefloquine/artesunate did not alter the pRBC removal rate, despite blocking parasite replication effectively. An exception was high dose artesunate, which doubled the rate of pRBC removal (half-life of 9.1 h). Phagocyte depletion using clodronate liposomes approximately halved the pRBC removal rate during untreated infection, indicating a role for phagocytes in clearance. We next assessed the importance of pRBC clearance for the decrease in the parasite multiplication rate after high dose artesunate treatment. High dose artesunate decreased parasite replication ∼46-fold compared with saline controls, with inhibition of replication contributing 23-fold of this, and increased pRBC clearance contributing only a further 2.0-fold. Thus, in our in vivo systems, drugs acted primarily by inhibiting parasite replication, with drug-induced increases in pRBC clearance making only minor contributions to overall drug effect