Impairment of chloroplast development and sink strength by blockade of light in chloroembryos of Cyamopsis Tetragonoloba (L.) Taub.

In many members of Fabaceae synthesis of chloroplast pigments takes place even when the embryo is deep inside the fruit. Blockade of light totally etiolated the embryos of developing Cyamopsis fruits upto 16-18 days after anthesis (DAA), whereas the pigments of the mature embryos, when shaded, were not significantly affected. Upon illuminatio resynthesis of green pigments by etiolated embryos occurred both l n v i v o and in vitro more significantly during the early stages of growth of the embryos (upto 18 DAA). Shading of developing fruits at different growth stages of embryos, reduced the growth of sink. The results are discussed in relation to the importance of light on embryo greening and dry matter production

Analysis, Design and Implementation of an End-to-End QKD Link

This manuscript discusses the most relevant aspects of the practical implementation of a long-range Quantum Key Distribution (QKD) link with trusted nodes, achieving the highest possible secret key rate generation within the security and system level constraints. To this purpose, we report on recent pilot studies for the measurements of detection efficiency and source photon statistics for validating the calibration facilities (i) at telecom wavelength for realistic quantum backbone implementation through standard telecommunications grade optical fiber, and (ii) for the telecom and VIS-NIR regime. In addition, since there are circumstances when a fiber optical link may not be available, we will also discuss the characterization of a Free Space Optics (FSO) QKD link. Finally, the manuscript also discusses the problem of information reconciliation in Continuous Variable QKD (CV-QKD) scenarios

Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach

Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT) derived from heterologous species (immunized animal or mouse hybridoma) together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R) domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa) is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH) that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80%) to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP), the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme

Copper effect on the protein composition of photosystem II

The definitive version is available at: http://www.blackwell-synergy.com/doi/full/10.1111/j.1399-3054.2000.1100419.xWe provide data from in vitro experiments on the polypeptide composition, photosynthetic electron transport and oxygen evolution activity of intact photosystem II (PSII) preparations under Cu(II) toxicity conditions. Low Cu(II) concentrations (Cu(II) per PSII reaction centre unit≤230) that caused around 50% inhibition of variable chlorophyll a fluorescence and oxygen evolution activity did not affect the polypeptide composition of PSII. However, the extrinsic proteins of 33, 24 and 17 kDa of the oxygen-evolving complex of PSII were removed when samples were treated with 300 μM CuCl2 (Cu(II) per PSII reaction centre unit=1 400). The LHCII antenna complex and D1 protein of the reaction centre of PSII were not affected even at these Cu(II) concentrations. The results indicated that the initial inhibition of the PSII electron transport and oxygen-evolving activity induced by the presence of toxic Cu(II) concentrations occurred before the damage of the oxygen-evolving complex. Indeed, more than 50% inhibition could be achieved in conditions where its protein composition and integrity was apparently preserved.This work was supported by the Dirección General de Investigación Científica y Técnica (Grant PB98-1632).Peer reviewe

Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies

Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A–G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay

Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy:Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2–78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020–2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.</p

Multivariate modeling of chromium-induced oxidative stress and biochemical changes in plants of Pistia stratiotes L.

Biochemical changes in the plants of Pistia stratiotes L., a free floating macrophyte exposed to different concentrations of hexavalent chromium (0, 10, 40, 60, 80 and 160 μM) for 48, 96 and 144 h were studied. Chromium-induced oxidative stress in macrophyte was investigated using the multivariate modeling approaches. Cluster analysis rendered two fairly distinct clusters (roots and shoots) of similar characteristics in terms of their biochemical responses. Discriminant analysis identified ascorbate peroxidase (APX) as discriminating variable between the root and shoot tissues. Principal components analysis results suggested that malondialdehyde (MDA), superoxide dismutase (SOD), APX, non-protein thiols (NP-SH), cysteine, ascorbic acid, and Cr-accumulation are dominant in root tissues, whereas, protein and guaiacol peroxidase (GPX) in shoots of the plant. Discriminant partial least squares analysis results further confirmed that MDA, SOD, NP-SH, cysteine, GPX, APX, ascorbic acid and Cr-accumulation dominated in the root tissues, while protein in the shoot. Three-way analysis helped in visualizing simultaneous influence of metal concentration and exposure duration on biochemical variables in plant tissues. The multivariate approaches, thus, allowed for the interpretation of the induced biochemical changes in the plant tissues exposed to chromium, which otherwise using the conventional approaches is difficult