Hypersensitivity to the Moderna COVID-19 vaccine caused by tromethamine: PEG is not always the culprit excipient

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are considered the cornerstone of the solution to the current global pandemic. The first vaccines to receive authorization for emergency use in humans were the BNT162b2 Pfizer-BioNTech and the mRNA-1273 Moderna vaccines. Both contain synthetic mRNA that codes for the SARS-CoV-2 spike (S) protein, which is encased in a lipid nanoparticle envelope. Anaphylaxis and immediate hypersensitivity reactions were noted in only 1 case during phase III trials for BNT162b2, while no immediate hypersensitivity reactions were noted for the mRNA-1273 vaccine. However, a history of hypersensitivity to any component of the vaccines was an exclusion criterion. Nonetheless, cases of anaphylaxis were reported shortly after initiation of the vaccination campaign

A highly specific tool for identification of Xanthomonas vasicola pv. musacearum based on five Xvm-specific coding sequences

This is the final version. Available on open access from Elsevier via the DOI in this recordXanthomonas vasicola pv. musacearum (Xvm) is a bacterial pathogen responsible for the economically important Xanthomonas wilt disease on banana and enset crops in Sub-Saharan Africa. Given that the symptoms are similar to those of other diseases, molecular diagnosis is essential to unambiguously identify this pathogen and distinguish it from closely related strains not pathogenic on these hosts. Currently, Xvm identification is based on polymerase chain reaction (PCR) with GspDm primers, targeting the gene encoding general secretory protein D. Experimental results and examination of genomic sequences revealed poor specificity of the GspDm PCR. Here, we present and validate five new Xvm-specific primers amplifying only Xvm strains.Agropolis Fondatio

Cognitive impact of neuronal antibodies: encephalitis and beyond.

Cognitive dysfunction is a common feature of autoimmune encephalitis. Pathogenic neuronal surface antibodies are thought to mediate distinct profiles of cognitive impairment in both the acute and chronic phases of encephalitis. In this review, we describe the cognitive impairment associated with each antibody-mediated syndrome and, using evidence from imaging and animal studies, examine how the nature of the impairment relates to the underlying neuroimmunological and receptor-based mechanisms. Neuronal surface antibodies, particularly serum NMDA receptor antibodies, are also found outside of encephalitis although the clinical significance of this has yet to be fully determined. We discuss evidence highlighting their prevalence, and association with cognitive outcomes, in a number of common disorders including cancer and schizophrenia. We consider mechanisms, including blood-brain barrier dysfunction, which could determine the impact of these antibodies outside encephalitis and account for much of the clinical heterogeneity observed

Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis

Background: When psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods: Sera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell–based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride. Results: At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p =.031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects. Conclusions: These data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy

A parallel implementation of sequential minimal optimization on FPGA

This paper proposes a parallel FPGA implementation of the training phase of a Support Vector Machine (SVM). The training phase of the SVM is implemented using Sequential Minimal Optimization (SMO), which enables the resolution of a complex convex optimization problem using simple steps. The SMO implementation is also highly parallel and uses some acceleration techniques, such as the error cache. Moreover, the Hardware Friendly Kernel (HFK) is used in order to reduce the kernel’s area, enabling an increase in the number of kernels per area. After the parallel implementation in hardware, the SVM is validated by bit-accurate simulation. Finally, analysis associated with the temporal performance of the proposed structure, as well as analysis associated with FPGAs area usage is performed

Comparative genomics of the type VI secretion systems of Pantoea and Erwinia species reveals the presence of putative effector islands that may be translocated by the VgrG and Hcp proteins

<p>Abstract</p> <p>Background</p> <p>The Type VI secretion apparatus is assembled by a conserved set of proteins encoded within a distinct locus. The putative effector proteins Hcp and VgrG are also encoded within these loci. We have identified numerous distinct Type VI secretion system (T6SS) loci in the genomes of several ecologically diverse <it>Pantoea </it>and <it>Erwinia </it>species and detected the presence of putative effector islands associated with the <it>hcp </it>and <it>vgrG </it>genes.</p> <p>Results</p> <p>Between two and four T6SS loci occur among the <it>Pantoea </it>and <it>Erwinia </it>species. While two of the loci (T6SS-1 and T6SS-2) are well conserved among the various strains, the third (T6SS-3) locus is not universally distributed. Additional orthologous loci are present in <it>Pantoea </it>sp. aB-valens and <it>Erwinia billingiae </it>Eb661. Comparative analysis of the T6SS-1 and T6SS-3 loci showed non-conserved islands associated with the <it>vgrG </it>and <it>hcp</it>, and <it>vgrG </it>genes, respectively. These regions had a G+C content far lower than the conserved portions of the loci. Many of the proteins encoded within the <it>hcp </it>and <it>vgrG </it>islands carry conserved domains, which suggests they may serve as effector proteins for the T6SS. A number of the proteins also show homology to the C-terminal extensions of evolved VgrG proteins.</p> <p>Conclusions</p> <p>Extensive diversity was observed in the number and content of the T6SS loci among the <it>Pantoea </it>and <it>Erwinia </it>species. Genomic islands could be observed within some of T6SS loci, which are associated with the <it>hcp </it>and <it>vgrG </it>proteins and carry putative effector domain proteins. We propose new hypotheses concerning a role for these islands in the acquisition of T6SS effectors and the development of novel evolved VgrG and Hcp proteins.</p

Proteomic profiling of Burkholderia cenocepacia clonal isolates with different virulence potential retrieved from a cystic fibrosis patient during chronic lung infection

Respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) are associated with a worse prognosis and increased risk of death. In this work, we assessed the virulence potential of three B. cenocepacia clonal isolates obtained from a CF patient between the onset of infection (isolate IST439) and before death with cepacia syndrome 3.5 years later (isolate IST4113 followed by IST4134), based on their ability to invade epithelial cells and compromise epithelial monolayer integrity. The two clonal isolates retrieved during late-stage disease were significantly more virulent than IST439. Proteomic profiling by 2-D DIGE of the last isolate recovered before the patient's death, IST4134, and clonal isolate IST439, was performed and compared with a prior analysis of IST4113 vs. IST439. The cytoplasmic and membrane-associated enriched fractions were examined and 52 proteins were found to be similarly altered in the two last isolates compared with IST439. These proteins are involved in metabolic functions, nucleotide synthesis, translation and protein folding, cell envelope biogenesis and iron homeostasis. Results are suggestive of the important role played by metabolic reprogramming in the virulence potential and persistence of B. cenocepacia, in particular regarding bacterial adaptation to microaerophilic conditions. Also, the content of the virulence determinant AidA was higher in the last 2 isolates. Significant levels of siderophores were found to be secreted by the three clonal isolates in an iron-depleted environment, but the two late isolates were more tolerant to low iron concentrations than IST439, consistent with the relative abundance of proteins involved in iron uptake.This work was supported by FEDER and FCT – Fundação para a Ciência e a Tecnologia (contract PEst-OE/EQB/LA0023/2011_ research line: Systems and Synthetic Biology; PhD grant to A.M. – SFRH/BD/37012/2007, and PD grants to S.S. – SFRH/BPD/75483/2010 and C.C. – SFRH/BPD/ 81220/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Manson's schistosomiasis in the undernourished mouse: some recent findings

This paper deals with current knowledge of the interrelationships between Schistosoma infection and malnutrition. It emphasizes the relevance of these investigations in the face of dynamic and evolving changes occurring in population diets and changes in the epidemiological patterns of schistosomiasis in endemic countries. The paper further discusses the basis for continuing the studies on this subject and the reasons why it represents a misunderstood association. This review also focuses on the cellular and humoral immune responses in the undernourished mouse model infected with Schistosoma mansoni, with updated information on the immune response in wild-type and iNOS knockout mice concerning soluble egg antigen specific antibodies and kinetics of IFN-&#947;, IL-4, IL-10 and IL-13 cytokines, in the chronic phase of Manson's schistosomiasis. There is indication that schistosome-infected undernourished mice are able to develop a humoral immune response, but antibody titres are much lower than in the control animals. Cytokine production (IFN-&#947;, IL-4, IL-10) is lower in the undernourished mice, but as infection progresses to the chronic phase its kinetics run an antagonistic course when compared to that of well-nourished animals. Marked variation in the secretion of IL-13 (a fibrogenic cytokine) could explain why undernourished mice do not develop liver "pipe-stem" fibrosis described in previous papers on well-nourished animals

In vitro synthesis of heparosan using recombinant Pasteurella multocida heparosan synthase PmHS2

In vertebrates and bacteria, heparosan the precursor of heparin is synthesized by glycosyltransferases via the stepwise addition of UDP-N-acetylglucosamine and UDP-glucuronic acid. As heparin-like molecules represent a great interest in the pharmaceutical area, the cryptic Pasteurella multocida heparosan synthase PmHS2 found to catalyze heparosan synthesis using substrate analogs has been studied. In this paper, we report an efficient way to purify PmHS2 and to maintain its activity stable during 6 months storage at −80 °C using His-tag purification and a desalting step. In the presence of 1 mM of each nucleotide sugar, purified PmHS2 synthesized polymers up to an average molecular weight of 130 kDa. With 5 mM of UDP-GlcUA and 5 mM of UDP-GlcNAc, an optimal specific activity, from 3 to 6 h of incubation, was found to be about 0.145 nmol/μg/min, and polymers up to an average of 102 kDa were synthesized in 24 h. In this study, we show that the chain length distribution of heparosan polymers can be controlled by change of the initial nucleotide sugar concentration. It was observed that low substrate concentration favors the formation of high molecular weight heparosan polymer with a low polydispersity while high substrate concentration did the opposite. Similarities in the polymerization mechanism between PmHS2, PmHS1, and PmHAS are discussed