<i>Salmonella</i>succinate utilisation is inhibited by multiple regulatory systems

AbstractSuccinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these niches are colonised by the pathogenic bacteriumSalmonella entericaserovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source forin vitrocultivation,Salmonellaand other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we used an experimental evolution approach to isolate fast-growing mutants during growth ofS. Typhimurium on succinate containing minimal medium.Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA.The RNA chaperone Hfq, the exoribonuclease PNPase and their cognate sRNAs function together to repress succinate utilisationviaRpoS induction. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation.Our discoveries shed light on redundant regulatory systems that tightly regulate the utilisation of succinate. We propose that the control of central carbon metabolism by multiple regulatory systems inSalmonellagoverns the infection niche-specific utilisation of succinate.</jats:p

Conclusive quantum steering with superconducting transition edge sensors

Quantum steering allows two parties to verify shared entanglement even if one measurement device is untrusted. A conclusive demonstration of steering through the violation of a steering inequality is of considerable fundamental interest and opens up applications in quantum communication. To date all experimental tests with single photon states have relied on post-selection, allowing untrusted devices to cheat by hiding unfavourable events in losses. Here we close this "detection loophole" by combining a highly efficient source of entangled photon pairs with superconducting transition edge sensors. We achieve an unprecedented ~62% conditional detection efficiency of entangled photons and violate a steering inequality with the minimal number of measurement settings by 48 standard deviations. Our results provide a clear path to practical applications of steering and to a photonic loophole-free Bell test.Comment: Preprint of 7 pages, 3 figures; the definitive version is published in Nature Communications, see below. Also, see related experimental work by A. J. Bennet et al., arXiv:1111.0739 and B. Wittmann et al., arXiv:1111.076

Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa

Background:The ST313 sequence type ofSalmonellaTyphimurium causes invasive non-typhoidal salmonellosis and wasthought to be confined to sub-Saharan Africa. Two distinct phylogenetic lineages of African ST313 have been identified.Methods:We analysed the whole genome sequences ofS. Typhimurium isolates from UK patients that weregenerated following the introduction of routine whole-genome sequencing (WGS) ofSalmonella entericabyPublic Health England in 2014.Results:We found that 2.7% (84/3147) ofS. Typhimurium from patients in England and Wales were ST313 and wereassociated with gastrointestinal infection. Phylogenetic analysis revealed novel diversity of ST313 that distinguishedUK-linked gastrointestinal isolates from African-associated extra-intestinal isolates. The majority of genome degradationof African ST313 lineage 2 was conserved in the UK-ST313, but the African lineages carried a characteristic prophageand antibiotic resistance gene repertoire. These findings suggest that a strong selection pressure exists for certainhorizontally acquired genetic elements in the African setting. One UK-isolated lineage 2 strain that probably originatedin Kenya carried a chromosomally locatedblaCTX-M-15, demonstrating the continual evolution of this sequence type inAfrica in response to widespread antibiotic usage.Conclusions:The discovery of ST313 isolates responsible for gastroenteritis in the UK reveals new diversity in thisimportant sequence type. This study highlights thepower of routine WGS by public health agencies to makeepidemiologically significant deductions that would be missed by conventional microbiological methods. Wespeculate that the niche specialisation of sub-Saharan African ST313 lineages is driven in part by the acquisitionof accessory genome elements

A Basal Sauropodomorph (Dinosauria: Saurischia) from the Ischigualasto Formation (Triassic, Carnian) and the Early Evolution of Sauropodomorpha

BACKGROUND: The earliest dinosaurs are from the early Late Triassic (Carnian) of South America. By the Carnian the main clades Saurischia and Ornithischia were already established, and the presence of the most primitive known sauropodomorph Saturnalia suggests also that Saurischia had already diverged into Theropoda and Sauropodomorpha. Knowledge of Carnian sauropodomorphs has been restricted to this single species. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new small sauropodomorph dinosaur from the Ischigualsto Formation (Carnian) in northwest Argentina, Panphagia protos gen. et sp. nov., on the basis of a partial skeleton. The genus and species are characterized by an anteroposteriorly elongated fossa on the base of the anteroventral process of the nasal; wide lateral flange on the quadrate with a large foramen; deep groove on the lateral surface of the lower jaw surrounded by prominent dorsal and ventral ridges; bifurcated posteroventral process of the dentary; long retroarticular process transversally wider than the articular area for the quadrate; oval scars on the lateral surface of the posterior border of the centra of cervical vertebrae; distinct prominences on the neural arc of the anterior cervical vertebra; distal end of the scapular blade nearly three times wider than the neck; scapular blade with an expanded posterodistal corner; and medial lamina of brevis fossa twice as wide as the iliac spine. CONCLUSIONS/SIGNIFICANCE: We regard Panphagia as the most basal sauropodomorph, which shares the following apomorphies with Saturnalia and more derived sauropodomorphs: basally constricted crowns; lanceolate crowns; teeth of the anterior quarter of the dentary higher than the others; and short posterolateral flange of distal tibia. The presence of Panphagia at the base of the early Carnian Ischigualasto Formation suggests an earlier origin of Sauropodomorpha during the Middle Triassic

Antagonistic genetic correlations for milking traits within the genome of dairy cattle

Genome-wide association studies can be applied to identify useful SNPs associated with complex traits. Furthermore, regional genomic mapping can be used to estimate regional variance and clarify the genomic relationships within and outside regions but has not previously been applied to milk traits in cattle. We applied both single SNP analysis and regional genomic mapping to investigate SNPs or regions associated with milk yield traits in dairy cattle. The de-regressed breeding values of three traits, total yield (kg) of milk (MLK), fat (FAT), and protein (PRT) in 305 days, from 2,590 Holstein sires in Japan were analyzed. All sires were genotyped with 40,646 single-nucleotide polymorphism (SNP) markers. A genome-wide significant region (P < 0.01) common to all three traits was identified by regional genomic mapping on chromosome (BTA) 14. In contrast, single SNP analysis identified significant SNPs only for MLK and FAT (P < 0.01), but not PRT in the same region. Regional genomic mapping revealed an additional significant region (P < 0.01) for FAT on BTA5 that was not identified by single SNP analysis. The additive whole-genomic effects estimated in the regional genomic mapping analysis for the three traits were positively correlated with one another (0.830-0.924). However, the regional genomic effects obtained by using a window size of 20 SNPs for FAT on BTA14 were negatively correlated (P < 0.01) with the regional genomic effect for MLK (-0.940) and PRT (-0.878). The BTA14 regional effect for FAT also showed significant negative correlations (P < 0.01) with the whole genomic effects for MLK (-0.153), FAT (-0.172), and PRT (-0.181). These negative genomic correlations between loci are consistent with the negative linkage disequilibrium expected for traits under directional selection. Such antagonistic correlations may hamper the fixation of the FAT increasing alleles on BTA14. In summary, regional genomic mapping found more regions associated with milk production traits than did single SNP analysis. In addition, the existence of non-zero covariances between regional and whole genomic effects may influence the detection of regional effects, and antagonistic correlations could hamper the fixation of major genes under intensive selection

Reviewer agreement trends from four years of electronic submissions of conference abstract

BACKGROUND: The purpose of this study was to determine the inter-rater agreement between reviewers on the quality of abstract submissions to an annual national scientific meeting (Canadian Association of Emergency Physicians; CAEP) to identify factors associated with low agreement. METHODS: All abstracts were submitted using an on-line system and assessed by three volunteer CAEP reviewers blinded to the abstracts' source. Reviewers used an on-line form specific for each type of study design to score abstracts based on nine criteria, each contributing from two to six points toward the total (maximum 24). The final score was determined to be the mean of the three reviewers' scores using Intraclass Correlation Coefficient (ICC). RESULTS: 495 Abstracts were received electronically during the four-year period, 2001 – 2004, increasing from 94 abstracts in 2001 to 165 in 2004. The mean score for submitted abstracts over the four years was 14.4 (95% CI: 14.1–14.6). While there was no significant difference between mean total scores over the four years (p = 0.23), the ICC increased from fair (0.36; 95% CI: 0.24–0.49) to moderate (0.59; 95% CI: 0.50–0.68). Reviewers agreed less on individual criteria than on the total score in general, and less on subjective than objective criteria. CONCLUSION: The correlation between reviewers' total scores suggests general recognition of "high quality" and "low quality" abstracts. Criteria based on the presence/absence of objective methodological parameters (i.e., blinding in a controlled clinical trial) resulted in higher inter-rater agreement than the more subjective and opinion-based criteria. In future abstract competitions, defining criteria more objectively so that reviewers can base their responses on empirical evidence may lead to increased consistency of scoring and, presumably, increased fairness to submitters

Clearing the Backlog: Trichiasis Surgeon Retention and Productivity in Northern Ethiopia

Blindness from trachoma is caused by the abrasive effect of trichiasis (in-turned eyelashes). Surgery is performed to correct this anatomical abnormality, and prevent blindness. Despite the progress made in many regions in controlling the active/infectious stages of this disease, the global prevalence of trichiasis remains about the same. Current surgical activity is barely keeping abreast of incident trichiasis; this is undermining all the other efforts to control trachoma. We examine staff retention and productivity in Amhara Region, Ethiopia, where many hundreds of health care workers have been trained to perform the surgery. We found that the majority of people trained to do the surgery are now not in a position to do so. Amongst the sub-set that is still active within the programme, surgical productivity is low, with most surgery performed during “outreach campaigns” Insufficient surgical instruments and consumables were frequent problems. Strengthened health-systems management can overcome many of the problems that are holding back the delivery of an effective trichiasis surgical service

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

A New Basal Sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), Northwestern Argentina

BACKGROUND: Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. METHODOLOGY/PRINCIPAL FINDING: We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. CONCLUSIONS/SIGNIFICANCE: Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of Leyesaurus with the Lower Jurassic Massospondylus suggest a younger age for the Quebrada del Barro Formation than previously postulated