Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome

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The Bacterial Cytoskeleton Modulates Motility,Type 3 Secretion,and Colonization in Salmonella

Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its importance to virulence. In this study we have explored the contribution of the bacterial cytoskeleton to the ability of Salmonella to express and assemble virulence factors and cause disease. The bacterial actin-like protein MreB polymerises into helical filaments and interacts with other cytoskeletal elements including MreC to control cell-shape. As mreB appears to be an essential gene, we have constructed a viable ΔmreC depletion mutant in Salmonella. Using a broad range of independent biochemical, fluorescence and phenotypic screens we provide evidence that the Salmonella pathogenicity island-1 type three secretion system (SPI1-T3SS) and flagella systems are down-regulated in the absence of MreC. In contrast the SPI-2 T3SS appears to remain functional. The phenotypes have been further validated using a chemical genetic approach to disrupt the functionality of MreB. Although the fitness of ΔmreC is reduced in vivo, we observed that this defect does not completely abrogate the ability of Salmonella to cause disease systemically. By forcing on expression of flagella and SPI-1 T3SS in trans with the master regulators FlhDC and HilA, it is clear that the cytoskeleton is dispensable for the assembly of these structures but essential for their expression. As two-component systems are involved in sensing and adapting to environmental and cell surface signals, we have constructed and screened a panel of such mutants and identified the sensor kinase RcsC as a key phenotypic regulator in ΔmreC. Further genetic analysis revealed the importance of the Rcs two-component system in modulating the expression of these virulence factors. Collectively, these results suggest that expression of virulence genes might be directly coordinated with cytoskeletal integrity, and this regulation is mediated by the two-component system sensor kinase RcsC.     

Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population

ObjectiveTo compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population.DesignRandomised controlled trial.SettingObstetric unit of teaching hospitalParticipantsPregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour.InterventionWomen were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour.ResultsThere were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65).ConclusionsCompared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery.

What is already known on this topic

The admission cardiotocogram is a short recording of the fetal heart rate immediately after admission to the labour wardOpinion varies about its value in identifying a potentially compromised fetusIn low risk women, the incidence of intrapartum fetal compromise is low

What this study adds

Compared with Doppler auscultation of the fetal heart, admission cardiotocography has no benefit on neonatal outcome in low risk womenAdmission cardiotocography results in increased obstetric intervention, including operative delivery     

Olfactory search-image use by a mosquito-eating predator

By choosing blood-carrying mosquitoes as prey, Evarcha culicivora, an East African salticid spider, specializes at feeding indirectly on vertebrate blood. It also has an exceptionally complex mate-choice system. An earlier study revealed that search-image use assists E. culicivora in finding prey and mates when restricted to using vision alone. Here we show that search-image use assists E. culicivora in finding prey and mates when restricted to using olfaction alone. After being primed with prey odour or mate odour (control: not primed with odour), spiders were transferred to an olfactometer designed to test ability to find a prey-odour or mate-odour source that was either ‘cryptic’ (i.e. accompanied by a masking odour source, Lantana camara) or ‘conspicuous’ (no L. camara odour). When tested with conspicuous odour, the identity of the priming odour had no significant effect on how many spiders found the odour source. However, when tested with cryptic odour, significantly more spiders found the odour source when primed with congruent odour and significantly fewer spiders found the odour source when primed with incongruent odour.     

The peanut lectin-binding glycoproteins of human epidermal keratinocytes

Peanut lectin (PNA) is known to bind more strongly to keratinocytes that are undergoing terminal differentiation than to proliferating keratinocytes, both in intact epidermis and in culture. In order to investigate the significance of this change in cell-surface carbohydrate we have identified the PNA-binding glycoproteins of cultured human keratinocytes and raised antibodies against them. Two heavily glycosylated bands of 110 and 250 kDa were resolved by PAGE of [14C]galactose- or [14C]mannose- and [14C]glucosamine-labeled cell extracts eluted with galactose from PNA affinity columns. The higher molecular weight band was also detected on PNA blots of unlabeled cell extracts transferred to nitrocellulose. Both bands were sensitive to Pronase digestion, but only the 250-kDa band was digested with trypsin. A rabbit antiserum that we prepared (anti-PNA-gp) immunoprecipitated both bands from cell extracts. In contrast to PNA, anti-PNA-gp bound equally to proliferating and terminally differentiating cells, indicating that some epitope(s) of the PNA-binding glycoproteins is present on the cell surface prior to terminal differentiation. When keratinocytes grown as a monolayer in low-calcium medium (0.1 mM calcium ions) were switched to medium containing 2 mM calcium ions in order to induce desmosome formation and stratification, there was a dramatic redistribution of the PNA-binding glycoproteins, which became concentrated at the boundaries between cells. This may suggest a role for the glycoproteins in cell-cell interactions during stratification.