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Depletion of intracellular polyamines reduced GATA3 expression but increased IL-9-producing CD4+ T cells under both Th2 and Th9-skewing conditions. Furthermore, oral administration of DFMO increased IL-9-producing CD4+ T cells in small intestine in mice. Thus, our data indicate that polyamines play a critical role in the regulation of the Th2/Th9 balance.The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
In the absence of a licensed vaccine, Clostridioides (formerly Clostridium) difficile infection represents a substantial health burden. The aim of this study was to evaluate the efficacy, immunogenicity, and safety of a toxoid vaccine candidate.

We did a phase 3 multicentre, observer-blind, randomised, controlled trial at 326 hospitals, clinics, and clinical research centres in 27 countries in the USA, Canada, Latin America, Europe, and the Asia-Pacific region. We included adults aged 50 years or older who were considered to be at an increased risk of C difficile infection because they had previously had two hospital stays (each ≥24 h in duration) and had received systemic antibiotics in the previous 12 months (risk stratum 1), or because they were anticipating being admitted to hospital for 72 h or more for elective surgery within 60 days of enrolment (risk stratum 2). Eligible participants were stratified by geographical region and the two risk strata, and randomly assigned (21), with a fixed block sizei Pasteur.Conjugated proteins and enzymes are often formed using N-hydroxysuccinimide (NHS) chemistry, which reacts with free primary amines resulting in a loss of charge and a reduction in isoelectric point (pI). Measurement of the extent of reaction of these conjugates is critical for biopharmaceutical developers. Due to this change in protein charge state, denaturing capillary isoelectric focussing (cIEF) offers a potentially straightforward and convenient approach for extent-of-reaction quantification. Here, we demonstrate the potential of this technique with poly(ethylene glycol) (PEG) conjugates of Erwinia chrysanthemil-asparaginase (ErA). Development of an appropriate sample preparation technique is critical to achieving reproducible cIEF electropherograms, particularly for denaturation-resistant proteins such as ErA, and an emphasis was placed on this during development of the PEG-ErA cIEF method. cIEF electropherograms demonstrating a distribution of PEGylation states in a bell-shaped curve were obtained, and assignment of PEGylation states to these peaks was critical to routine use of the method. The method is sensitive enough to resolve non-lysine adducts of PEG (such as those conjugated to histidine residues) and was shown to give reproducible results over a 2 year period. Biopharmaceutical developers should consider cIEF for extent of reaction monitoring and measurement for conjugates of free amine groups.
DNA-binding proteins perform important roles in cellular processes and are involved in many biological activities. These proteins include crucial protein-DNA binding domains and can interact with single-stranded or double-stranded DNA, and accordingly classified as single-stranded DNA-binding proteins (SSBs) or double-stranded DNA-binding proteins (DSBs). Computational prediction of SSBs and DSBs helps in annotating protein functions and understanding of protein-binding domains.

Performance is reported using the DNA-binding protein dataset that was recently introduced by Wang et al., [1]. The proposed method achieved a sensitivity of 0.600, specificity of 0.792, AUC of 0.758, MCC of 0.369, accuracy of 0.744, and F-measure of 0.536, on the independent test set.

The proposed method with the hidden Markov model (HMM) profiles for feature extraction, outperformed the benchmark method in the literature and achieved an overall improvement of approximately 3%. The source code and supplementary information of the proposed method is available at https//github.com/roneshsharma/Predict-DNA-binding-proteins/wiki.
The proposed method with the hidden Markov model (HMM) profiles for feature extraction, outperformed the benchmark method in the literature and achieved an overall improvement of approximately 3%. The source code and supplementary information of the proposed method is available at https//github.com/roneshsharma/Predict-DNA-binding-proteins/wiki.Malaria disproportionately affects children younger than 5 years. Falciparum malaria is responsible for more than 200 000 child deaths per year in Africa and vivax malaria is well documented as a cause of severe anaemia and excess mortality in children in Asia and Oceania. For the treatment of malaria in children, paediatric dosing recommendations for several agents, including parenteral artesunate and dihydroartemisinin-piperaquine, have belatedly been shown to be suboptimal. Worsening antimalarial resistance in Plasmodium falciparum in the Greater Mekong Subregion threatens to undermine global efforts to control malaria. Triple antimalarial combination therapies are being evaluated to try to impede this threat. The RTS,S/AS01 vaccine gives partial protection against falciparum malaria and is being evaluated in large, pilot studies in Ghana, Malawi, and Kenya as a complementary tool to other preventive measures. Seasonal malaria chemoprevention in west Africa has resulted in declines in malaria incidence and deaths and there is interest in scaling up efforts by expanding the age range of eligible recipients. Preventing relapse in Plasmodium vivax infection with primaquine is challenging because treating children who have G6PD deficiency with primaquine can cause acute haemolytic anaemia. The safety of escalating dose regimens for primaquine is being studied to mitigate this risk.All malaria infections are harmful to both the pregnant mother and the developing fetus. One in ten maternal deaths in malaria endemic countries are estimated to result from Plasmodium falciparum infection. Malaria is associated with a 3-4 times increased risk of miscarriage and a substantially increased risk of stillbirth. Current treatment and prevention strategies reduce, but do not eliminate, malaria's damaging effects on pregnancy outcomes. Reviewing evidence generated from meta-analyses, systematic reviews, and observational data, the first paper in this Series aims to summarise the adverse effects of malaria in pregnancy on the fetus and how the current drug treatment and prevention strategies can alleviate these effects. Although evidence supports the safety and treatment efficacy of artemisinin-based combination therapies in the first trimester, these therapies have not been recommended by WHO for the treatment of malaria at this stage of pregnancy. check details Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine is contraindicated in the first trimester and provides imperfect chemoprevention because of inadequate dosing, poor (few and late) antenatal clinic attendance, increasing antimalarial drug resistance, and decreasing naturally acquired maternal immunity due to the decreased incidence of malaria.
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