Conserve Epitopes of Influenza Virus Induce Innate and Adaptive Immune Responses to Produce Specific Antibody Against M2e Protein

The existing vaccines against influenza are based onthe generation of neutralizing antibody primarilydirected against surface protein, haemagglutinin(HA) and neuraminidase (NA). However, antigenicdrift and occasional shift of these two membraneglycoproteins, HA and NA, make vaccine productioncumbersome and necessitate yearly revision ofthe vaccine seed strains by the World HealthOrganization. For these reasons, many investigatorshave often tried to look at the possibility of generatinga universal vaccine useful against more than oneinfluenza strain. The objective of research was toobtain an alternative antigen as vaccine candidatefor universal flu vaccination, instead of HA and NAcomponents. In this study, we use conserved epitopeM2e which is consist of three major componentsuch as N-terminal M2e2-24 (24 amino acids),transmembrane(59 amino acids) and C-terminal (19amino acids). We design two components of antigen,linier and branched structures. The antigens thenformulated with aluminium hydroxide gel comparedto FCA/IFA adjuvant. These vaccines were testedtheir immunogenicity, and the potency to mature thedendritic cells for stimulating either CD8+ T cell orantibody-mediated immune responses. The antibodytitre and the maturity of dendritic cell indicated bycytokines concentration such as; IFN-ã, IL2 and IL4were measured by ELISA test.The result of researchshowed that the conserved epitope of Me2 2-16 whenincorporated with P25 protein from canine distempervirus (linear structure) in alhydrogel adjuvant hasgreater potential to produce anti-M2e antibodiesthan in Freund adjuvant. Alhydrogel adjuvant hada stronger effect than Freund adjuvant. Alhydrogelalso stimulate the release of IL-2 and IL-4

The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities:A systematic review and meta-analysis

ObjectivesTo determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.MethodsA systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.ResultsOverall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).ConclusionThe likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.What is already known?Congenital heart abnormalities are the most commonly occurring congenital anomalies and can be associated with chromosomal or monogenic conditions. With the increasing use of fetal sequencing, there is a need to define the association between monogenic conditions and specific cardiac abnormalities, particularly when isolated to facilitate triaging for prenatal sequencing.What does this study add?The incremental yield of prenatal exome sequencing over and above chromosome microarray for congenital heart abnormalities is 9.3% in isolated lesions and 35.2% in the presence of complex lesions/heterotaxy. Clinicians should consider the clinical utility of offering prenatal exome sequencing in selected isolated cardiac lesions dependent on resources available

The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities:A systematic review and meta-analysis

ObjectivesTo determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.MethodsA systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.ResultsOverall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).ConclusionThe likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.What is already known?Congenital heart abnormalities are the most commonly occurring congenital anomalies and can be associated with chromosomal or monogenic conditions. With the increasing use of fetal sequencing, there is a need to define the association between monogenic conditions and specific cardiac abnormalities, particularly when isolated to facilitate triaging for prenatal sequencing.What does this study add?The incremental yield of prenatal exome sequencing over and above chromosome microarray for congenital heart abnormalities is 9.3% in isolated lesions and 35.2% in the presence of complex lesions/heterotaxy. Clinicians should consider the clinical utility of offering prenatal exome sequencing in selected isolated cardiac lesions dependent on resources available

Metal-responsive gene regulation and metal transport in Helicobacter species

Helicobacter species are among the most successful colonizers of the mammalian gastrointestinal and hepatobiliary tract. Colonization is usually lifelong, indicating that Helicobacter species have evolved intricate mechanisms of dealing with stresses encountered during colonization of host tissues, like restriction of essential metal ions. The recent availability of genome sequences of the human gastric pathogen Helicobacter pylori, the murine enterohepatic pathogen Helicobacter hepaticus and the unannotated genome sequence of the ferret gastric pathogen Helicobacter mustelae has allowed for comparitive genome analyses. In this review we present such analyses for metal transporters, metal-storage and metal-responsive regulators in these three Helicobacter species, and discuss possible contributions of the differences in metal metabolism in adaptation to the gastric or enterohepatic niches occupied by Helicobacter species

A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter

Writing Class In and Out: Constructions of Class in Elite Businesswomen's Autobiographies

The final version of this paper has been published in Sociology, November 2020 by SAGE Publications Ltd, All rights reserved. © The Authors, 2020. It is available at: https://journals.sagepub.com/home/socThis article explores how meanings of class are constructed in elite businesswomen’s autobiographies. It extends existing sociological studies of elites in two ways. First, by theorising the cultural mechanisms that contribute to the reproduction of business elites, and second, by examining the hitherto under-researched gendered aspects of the reproduction of business elites, and the legitimisation of wealth. We show how these autobiographical texts acknowledge class yet render it irrelevant through discursive repertoires of ordinariness, a universal gender struggle and the unimportance of wealth. We argue that in doing so the genre of elite businesswomen autobiographies contributes to the cultural erasure of class, perpetuating messages that contribute to the creation of a cultural milieu in which class and wealth inequalities remain unquestioned. In an economic context where social disparities continue to grow, the article importantly furthers our understanding of the cultural means by which a plutocratic elite holds on to power

Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation

External validation of prognostic models to predict stillbirth using the International Prediction of Pregnancy Complications (IPPIC) Network database: an individual participant data meta-analysis

Objective Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Peer reviewe

Incremental yield of whole genome sequencing over chromosome microarray and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis.

Publication status: PublishedOBJECTIVE: Primarily to determine the incremental yield of Whole Genome Sequencing (WGS) over Chromosome Microarray Assessment (CMA) and/or Exome Sequencing (ES) in fetuses and infants with a congenital anomaly that was or could have been detectable on ultrasound prenatally. Secondly, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways. METHODS: OVID MEDLINE(R), EMBASE, Medline (Web of Science), Cochrane Library, and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including fetuses/infants with ≥n=3 cases of: (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound and; (iii) exclusion of aneuploidy and pathogenic Copy Number Variants >50kb. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed statistically using Higgins' I2 . Sub-analyses were performed based on pre- or postnatal presentation, multi-system anomalies and classification based upon NHS England prenatal (R21) ES inclusion criteria. PROSPERO 2022 CRD42022380483 RESULTS: Eighteen studies incorporating n=1284 cases were included, of which n=8 (44.4%) incorporating n=754 (58.7%) cases were prenatal cohorts and the remainder representing postmortem (postnatal evaluation), neonatal or infants with congenital structural anomalies. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI 18-36%, I2 =86%), 16% (9-24%, I2 =85%) and 39% (95%CI 27-51%, I2 =53%) for all, prenatal and postnatal cases. The incremental yields were optimal where sequencing was performed in line with NHS England prenatal ES criteria; 32% (22%-42%, I2 =70%). The incremental yield of Variants of Uncertain Significance (VUS) was 18% (95% CI 7-33%, I2 =74%). The yield of WGS over ES was non-significant at 1% (95% CI 0%-4%, I2 =47%). The pooled median TAT for WGS was 18 days (range: 1-912 days) and the quantity of DNA required for WGS versus CMA and ES was 100ng (±0) and 350ng (±50) p=0.03 respectively. CONCLUSION: Whilst WGS investigation for congenital anomaly holds great promise, for the future, its' incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS (compared to sequential QF-PCR/CMA/ES) requires less DNA with a potentially faster TAT. There was a relatively high rate of VUS. This article is protected by copyright. All rights reserved