Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1–2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines

Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean

Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning

Extension of the core map of common bean with EST-SSR, RGA, AFLP, and putative functional markers

Microsatellites and gene-derived markers are still underrepresented in the core molecular linkage map of common bean compared to other types of markers. In order to increase the density of the core map, a set of new markers were developed and mapped onto the RIL population derived from the ‘BAT93’ × ‘Jalo EEP558’ cross. The EST-SSR markers were first characterized using a set of 24 bean inbred lines. On average, the polymorphism information content was 0.40 and the mean number of alleles per locus was 2.7. In addition, AFLP and RGA markers based on the NBS-profiling method were developed and a subset of the mapped RGA was sequenced. With the integration of 282 new markers into the common bean core map, we were able to place markers with putative known function in some existing gaps including regions with QTL for resistance to anthracnose and rust. The distribution of the markers over 11 linkage groups is discussed and a newer version of the common bean core linkage map is proposed

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The XXL Survey . IV. Mass-temperature relation of the bright cluster sample

Part of the first data release of the XXL Survey. Associated data is accessible via CDS and via the XXL Database hosted at IASF-MIContext. The XXL Survey is the largest survey carried out by XMM-Newton. Covering an area of 50 deg2, the survey contains ~450 galaxy clusters out to a redshift ~2 and to an X-ray flux limit of ~ 5 × 10-15 erg s-1 cm-2. This paper is part of the first release of XXL results focussed on the bright cluster sample. Aims: We investigate the scaling relation between weak-lensing mass and X-ray temperature for the brightest clusters in XXL. The scaling relation discussed in this article is used to estimate the mass of all 100 clusters in XXL-100-GC. Methods: Based on a subsample of 38 objects that lie within the intersection of the northern XXL field and the publicly available CFHTLenS shear catalog, we derive the weak-lensing mass of each system with careful considerations of the systematics. The clusters lie at 0.1 Results: The mass-temperature relation fit (M ∝ Tb) to the XXL clusters returns a slope and intrinsic scatter σlnM|T≃ 0.53; the scatter is dominated by disturbed clusters. The fit to the combined sample of 96 clusters is in tension with self-similarity, b = 1.67 ± 0.12 and σlnM|T ≃ 0.41. Conclusions: Overall our results demonstrate the feasibility of ground-based weak-lensing scaling relation studies down to cool systems of ~1 keV temperature and highlight that the current data and samples are a limit to our statistical precision. As such we are unable to determine whether the validity of hydrostatic equilibrium is a function of halo mass. An enlarged sample of cool systems, deeper weak-lensing data, and robust modelling of the selection function will help to explore these issues further. Based on observations obtained with XMM-Newton, an ESA sci- ence mission with instruments and contributions directly funded by ESA Member States and NASA. Based on observations made with ESO Telescopes at the La Silla Paranal Observatory under programme 089.A-0666 and LP191.A-0268.The Master catalogue is available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/592/A

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Intraerythrocyte And Serum Magnesium Concentration In The Metabolic Pathology Of Adults.

Intraerythrocyte And Serum Magnesium Concentration In The Metabolic Pathology Of Adults. 31° Congresso Nazionale S.I.S.A. PALERMO 19-21 novembre 2017

Molecular markers linked to the fin gene controlling determinate growth habit in common bean

Bulked segregant analysis (BSA) was used to identify molecular markers linked to determinate growth habit (Wn gene) in a F2 population derived from the cross Andecha (FinFin) £ BRB130 (WnWn). Fourteen RAPD markers and one microsatellite (BMd45-AIA) were linked to the Wn gene when tested on the entire population. The SCAR, SI19b, designed from the RAPD marker OI19385 (linked to the Wn gene at a recombination fraction, RF = 0.14; LOD = 5.29), showed a codominant segregation in the F2 population Andecha £ BRB130 consistent with that of the corresponding RAPD. The microsatellite BMd45-AIA showed a codominant segregation in this population and was also linked to the Wn gene (RF = 0.11; LOD = 10.73). The DNA sequences of markers SI19b and BMd45-AIA present in Andecha and BRB130 were analyzed. The two alleles of marker SI19b diVer in 4 single base pairs and in a deletion of 30 bp, whereas the two alleles of marker BMd45-AIA diVer in a single base pair and in a deletion of 38 bp. In both cases, speciWc short sequences (CTGAAGA for SI19b and ACAGAGAGA for BMd45-AIA) were repeated at the beginning and the end of the deleted segments, suggesting that “looping” structures during replication could have caused these deletions. Linkage between the Wn gene and the molecular markers SI19b and BMd45-AIA was investigated in two other segregating populations: a F2 population derived from the cross MDRK (WnWn) £ V225 (FinFin), and a RIL population derived from the cross Xana (WnWn) £ Cornell 49242 (FinFin). SI19b was polymorphic (codominant segregation) only in the RIL population Xana £ Cornell 49242, and showed a weak linkage with the Wn gene (26.9 cM; LOD = 2.34). BMd45-AIA showed codominant segregation in both populations, and was tightly linked to the Wn gene, at 4.1 cM (LOD = 9.2) in the F2 population MDRK £ V225, and at 3.3 cM (LOD = 16.2) in the RIL population Xana £ Cornell 49242