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Neurological disorders such as Alzheimer's disease, stroke and epilepsy are currently marred by the lack of effective treatments to prevent neuronal death. Erroneous cell cycle reentry (CCR) is hypothesized to have a causative role in neurodegeneration. We show that forcing S-phase reentry in cultured hippocampal neurons is sufficient to induce neurodegeneration. We found that kainic-acid treatment in vivo induces erroneous CCR and neuronal death through a Notch-dependent mechanism. Ablating Notch signaling in neurons provides neuroprotection against kainic acid-induced neuronal death. We further show that kainic-acid treatment activates Notch signaling, which increases the bioavailability of CyclinD1 through Akt/GSK3β pathway, leading to aberrant CCR via activation of CyclinD1-Rb-E2F1 axis. In addition, pharmacological blockade of this pathway at critical steps is sufficient to confer resistance to kainic acid-induced neurotoxicity in mice. Taken together, our results demonstrate that excitotoxicity leads to neuronal death in a Notch-dependent manner through erroneous CCR. [ABSTRACT FROM AUTHOR]

Abstract: We developed a phase retrieval algorithm that utilizes pre-determined partial phase information to overcome insufficient oversampling ratio in diffraction data. Implementing the Fourier modulus projection and the modified support projection manifesting the pre-determined information, a generalized difference map and HIO (Hybrid Input–Output) algorithms are developed. Optical laser diffraction data as well as simulated X-ray diffraction data are used to illustrate the validity of the proposed algorithm, which revealed the strength and the limitations of the algorithm. The proposed algorithm can expand the applicability of the diffraction based image reconstruction. [Copyright &y& Elsevier]

The effect of low-dose gamma irradiation (0.25–1.00 kGy) on pre-packed whole-wheat flour (atta) was assessed in terms of physico-chemical properties, nutritional quality, chapati-making quality and sensory attributes. Semi-pilot scale storage studies on irradiated pre-packed whole-wheat flour revealed that there was no adverse effect of irradiation and storage up to 6 months of whole-wheat flour treated at doses up to 1.00 kGy on total proteins, fat, carbohydrates, vitamin B1 and B2 content, colour index, sedimentation value, dough properties, total bacterial and mould count. Storage of wheat flour resulted in slight increase in moisture, free fatty acids, damaged starch, reducing sugars and slight decrease in gelatinization viscosity. However, irradiation as such had no effect on any of these parameters. Irradiation at 0.25 kGy was sufficient to extend the shelf-life of atta up to 6 months without any significant change in the nutritional, functional attributes. Chapaties made from irradiated atta (0.25 kGy) were preferred even after 6 months storage, compared with the control. [ABSTRACT FROM AUTHOR]

Recent studies have identified NOTCH signaling as a contributor of neurodegeneration including Alzheimer's disease' (AD) pathophysiology. As part of the efforts to understand molecular mechanisms and players involved in neurodegenerative dementia, we employed transgenic mouse models with Notch1 and Rbpjk loss of function (LOF) mutation in pyramidal neurons of the CA fields. Using RNA-seq, we have investigated the differential expression of NOTCH-dependent genes either upon environmental enrichment (EE) or upon kainic acid (KA) injury. We found a substantial genetic diversity in absence of both NOTCH1 receptor or RBPJK transcriptional activator. Among differentially expressed genes, we observed a significant upregulation of Gabra2a in both knockout models, suggesting a role for NOTCH signaling in the modulation of E/I balance. Upon excitotoxic stimulation, loss of RBPJK results in decreased expression of synaptic proteins with neuroprotective effects. We confirmed Nptx2 , Npy , Pdch8 , TncC as direct NOTCH1/RBPJK targets and Bdnf and Scg2 as indirect targets. Finally, we translate these findings into human entorhinal cortex containing the hippocampal region from AD patients performing targeted transcripts analysis. We observe an increased trend for RBPJK and the ligand DNER starting in the mild-moderate stage of the disease with no change of NOTCH1 expression. Alongside, expression of the Notch targets Hes5 and Hey1 tend to rise in the intermediate stage of the disease and drop in severe AD. Similarly the newly discovered NOTCH targets, NPTX2 , NPY , BDNF show an up-warding tendency during the mild-moderate stage, and decline in the severe phase of the disease. This study identifies NOTCH as a central signaling cascade capable of modulating synaptic transmission in response to excitatory insult through the activation of neuroprotective genes that have been associated to AD. • Loss of NOTCH1 signaling in pyramidal neurons of the hippocampal CA fields mainly affects the postsynaptic genes. • In both Rbpjk cKO and Notch1 cKO mouse models there is upregulation of GABAergic receptor subunit alpha2 (Gabra2a). • The plasticity genes: Npy , Nptx2 , Pcdh8 and TncC withknown association with AD are direct NOTCH1/RBPJK targets. • Neuroprotective NOTCH targets show an upgrading trend in mild-moderate AD, followed by a down scaling in severe AD. [ABSTRACT FROM AUTHOR]

We present a flyscan compatible acquisition scheme for three-modal X-Ray Computed Tomography (CT) with two-dimensional phase sensitivity. Our approach is demonstrated using a "beam tracking" setup, through which a sample's attenuation, phase (refraction) and scattering properties can be measured from a single frame, providing three complementary contrast channels. Up to now, such setups required the sample to be stepped at each rotation angle to sample signals at an adequate rate, to prevent resolution losses, anisotropic resolution, and under-sampling artefacts. However, the need for stepping necessitated a step-and-shoot implementation, which is affected by motors' overheads and increases the total scan time. By contrast, our proposed scheme, by which continuous horizontal and vertical translations of the sample are integrated with its rotation (leading to a "cycloidal-spiral" trajectory), is fully compatible with continuous scanning (flyscans). This leads to greatly reduced scan times while largely preserving image quality and isotropic resolution. [ABSTRACT FROM AUTHOR]

It is widely known that India holds a high burden of pneumococcal disease and studies related to the genetic variation in the penicillin-binding proteins (PBP), the principal target of beta-lactam drugs are sparse. Further, serotype 19F of Streptococcus pneumoniae was the predominant serotype among Indian children. The present study identifies the genetic variations and AMR patterns of PBP genes 1a, 2b, and 2x of S. pneumoniae 19F serotype in Indian children (≤5 years). A total of 97 S.pneumoniae serotype 19F clinical isolates collected across India from 2009-2018, were subjected to WGS on the Illumina platform. Multiple Sequence Alignment on MEGA-X-V10.0.3 was performed for extracted PBP sequence data, and the AMR pattern was determined. Of the 97, 19F serotype isolates, 62 belonged to the pediatric age. A total of 29 different substitution mutations in PBP 1a, 2b, and 2x genes were observed. In the conserved motifs of PBP genes, the following substitutions were observed: PBP1a-85.5% (P432T), 75.8% (T371A); PBP1b-85.5% (T446A), 83.9% (Q438E), 46.8% (A619G); PBP2x- 78.3% (T338A and L546V), respectively. Whereas in the protein, active sites 100% substitutions were detected in E388D (PBP1a), and S517A (PBP2b) regions. The genetic variations were correlated phenotypically and it was interesting to note that 53 of the 62 isolates conferred resistance to penicillin (MIC = 0.5 µg/ml to 4 µg/ml). About 9 isolates displayed sensitivity to penicillin (MIC = 0.03 µg/ml) without any mutations. There was a higher degree of genetic diversity detected in PBPs substitutions among the isolates, a few of which were on par with previously reported data, while the major substitution mutations observed in the study resulted in high-level resistance to beta-lactams. [ABSTRACT FROM AUTHOR]

Synthesis of Zinc oxide (ZnO) nanoparticles has been carried out using a chemical route. Stability of the size has been achieved using mercaptoethanol as surface capping molecules. Infra red spectroscopy and x-ray photoelectron spectroscopy analysis confirm the presence of capping molecules on the ZnO particle surface. Strong green photoluminescence was observed at ~534 nm from all the nanoparticles. [ABSTRACT FROM AUTHOR]

Semiconductor nanoparticles exhibit size dependent properties, when their size is comparable to the size of Bohr diameter for exciton. This can be exploited to increase fluorescence efficiency or increase the internal magnetic field strength in doped semiconductors. Nanoparticles are usually unstable and can aggregate. It is therefore necessary to protect them. Surface passivation using capping molecules or by making core–shell particles are some useful ways. Here synthesis and results on doped and un-doped nanoparticles of ZnS, CdS and ZnO will be discussed. We shall present results on core–shell particles using some of these nanoparticles and also discuss briefly the effect of Mn doping on hyperfine interactions in case of CdS nanoparticles. [ABSTRACT FROM AUTHOR]

Presents corrections to author information for the paper, "Effect of inhomogeneous medium on fields above GCPW PCB for near-field scanning probe calibration application," (Marathe, S., et al), IEEE Trans. Electromagn. Compat., vol. 61, no. 1, pp. 3–10, Feb. 2019. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen and is associated with serious infections, and treatment can be challenging. Rates of antimicrobial resistance (AMR), multidrug-resistant (MDR) infections are increasing. Our objective was to characterize the epidemiology and AMR mechanisms of this pathogen circulating in India using whole genome sequencing. 312 P.aeruginosa isolates recovered from 21 hospital sites in India between 2017–2022 were seqeunced. Isolates were subjected to antimicrobial susceptibility testing by Vitek-2 automated system, and their genomes were assembled from Illumina sequencing data. MLST type, virulence genes, AMR determinants, and relatedness between isolates were derived; and determined concordance between phenotypic and genotypic resistance. β-lactam resistance was high (99.6%), with 99.6%to Cephalosporins, 98.3%to Aminoglycosides, 96.4%to Phenicols, 54.8% to Fluroquinolones, 36% to carbapenem and 17.6% to Macrolides. Carbapenem resistance was associated mainly with acquisition of the MBLs- blaOXA genes and blaNDM1 gene. Loss of function of the OprD-porin was observed in 4 isolates. KPC-2 was detected in 5 isolates and blaVIM gene was not detected. Concordance between phenotypic and genotypic resistance was 99.5% overall. Virulence genes, toxA (94.8%), plcH (98.3%), lasA/B/I (99.6%), exoS (51.6%), exoT (97.1%), exoU (48%), exoX (90%) were detected. Genotyping by MLST revealed 80 different sequence types. The population of P.aeruginosa was diverse, with MLSTs ST357, ST308, ST235, ST244 and ST654 predominant. About 13.7%of STs were of novel types and were found to emerge from the high-risk clones, having 100% resistance to Beta lactams and Cephalosporins, 90% resistance to Aminoglycosides and harbouring diverse virulence genes. Most of the ST357 and Novel ST genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the India. The survey bridges the gap in genomic data from India. The association of resistance determinants with phylogenetic background displays the utility of WGS-monitoring AMR in P.aeruginosa. The presence of resistance and virulence determinants throughout phylogenetic tree shows that knowledge of local epidemiology is crucial for guiding potential treatment of MDR P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

K.pneumoniae is an urgent health concern due to the emergence of multidrug-resistant strains for which vaccination offers potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address high diversity of surface-exposed polysaccharides. For the success of K/O-antigenbased vaccine strategies, knowledge of serotype distribution and diversity among clinical isolates are mandatory. The study aimed to elucidate the genetic diveristy of K.pneumoniae capsular types in India. 1072 K.pneumoniae isolates collected during 2013-2022 from 38 hospitals were sequenced. The assembled data was uploaded to pathogen watch for analysis, using kleborate for typing K.pneumoniae The study defines the genetic diversity of O-and K-loci bearing isolates in India. 71 different K-loci were identified in the study. KL64 (25.5%), KL51 (23.2%) and K2 (8.2%) were predominant and 18 isolates had novel cps loci. Prevalence of internationally known KL-types K1 and K2 was 1.3% and 8.2% respectively. 37.2% of KL-64 strains and 85.1% of KL-51 strains belong to clonal lineage ST147 and ST231 respectively. Strikingly, virulence and antibiotic resistance genes were present in high proportion (70.3% virulence, 90.8% resistance) among KL51 strains where as their presence was 31.4% and 90.9% in KL64 strains. Serotypes-O1/O2v1 and-O1/O2v2 were most prevalent accounting for 43.9% and 32.9% respectively. 67% of O1/O2v2 strains harboured KL51 loci and were associated with ST231 clonal lineage, which is a predominant lineage in India. The distribution of virulence and resistance genes was 22.7% and 79.8% among O1/O2v1 strains where as their presence was 58.6% and 69.6% in O1/O2v2 strains The study reveals the existence of diverse population pool of Kantigens among the Indian circulating strains of K.pneumoniae which is different from other parts of the world. The study isolates in addition, displayed a high diverse STs, virulome and resistome. On the contrary, O-antigens were less diverse. The diversity of circulating population has to be considered while developing vaccines. [ABSTRACT FROM AUTHOR]

High pressure metal die casting is an extremely dynamic process with widely ranging cooling rates and intensifying pressures, resulting in a wide range of solid fractions and deformation rates simultaneously existing in the same casting. These process parameters and their complex interplay dictate the formation of microstructural solidification defects. In this study, fast synchrotron X-ray imaging experiments simulating high pressure die casting of aluminium alloys were conducted to investigate the effect of solid fraction, loading conditions and semisolid flow on local microstructural inhomogeneity. While most of the existing literature in this field reports speeds up to 10 µm/s for in situ deformation, the present work captures much faster filling and solidification, at speeds closer to 100 µm/s and at different solid fractions. Semisolid deformation of low solid fractions reveals two typical microstructural features: (i) coarser grains in the middle and finer ones near the walls, and (ii) remelting near the solid-liquid interface due to Cu enrichment in the liquid by the flow. Ex situ scans and digital image correlation analysis of the higher solid fraction samples reveal a porosity formation mechanism based on the local state of stresses, microstructure and feeding. Four different characteristics were identified: (i) plug flow, (ii) dead zone (densified mush), (iii) shear and (iv) bulk zones. These insights will be used to develop zone-specific strategies for the numerical modelling of defect formation during die casting. [Display omitted] [ABSTRACT FROM AUTHOR]

In the city of Mumbai (formerly Bombay), chloroquine (CQ) continues to be recommended as the drug of first choice for the treatment of Plasmodium vivax and P. falciparum infections, even though > 50% of local isolates of P. falciparum are resistant to it. Primaquine, an 8-aminoquinoline is also given to patients with falciparum malaria, in a single, 45-mg dose, to kill the gametocytes and so reduce transmission. The gametocytocidal activity of supervised primaquine (45 mg given on day 8) was investigated in 90 patients who had been treated with CQ. Of these, 15 were found to be CQ-sensitive patients, 61 were resistant (49, eight and four considered RI, RII and RIII, respectively) and 14 were lost before completion of the follow-up. The mean (S.D.) baseline gametocytaemias in the CQ-sensitive and RI-resistant cases were 665.1 (411.3) and 1537.4 (1045.5)/mul, respectively. Despite supervised primaquine treatment, four of the 15 CQ-sensitive patients and 32 of the 49 patients found to be RI-resistant had gametocytes on day 29. There therefore appears to be a need to review the current, gametocytocidal, primaquine-dosage schedule and to re-treat patients who remain gametocytaemic with higher doses of primaquine, as an important, transmission-blocking strategy. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of antimalarial treatments for chloroquine resistance in Plasmodium falciparum. Comparison between chloroquine and co-artemether treatment; Resistance of local P. falciparum to chloroquine; Use of double blinding in antimalarial clinical trials.