Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle

Association between congenital toxoplasmosis and parent-reported developmental outcomes, concerns, and impairments in 3 year old children

Background: Information is lacking on the effects of congenital toxoplasmosis on development, behavior, and impairment in later childhood, as well as on parental concerns and anxiety. This information is important for counselling parents about the prognosis for an infected child and for policy decisions on screening. Methods: We prospectively studied a cohort of children identified by screening for toxoplasmosis in pregnant women or neonates between 1996 and 2000 in ten European centers. At 3 years of age, parents of children with and without congenital toxoplasmosis were surveyed about their child's development, behavior, and impairment, and about parental concerns and anxiety, using a postal questionnaire. Results: Parents of 178/223 (80%) infected, and 527/821 (64%) uninfected children responded. We found no evidence that impaired development or behavior were more common in infected children, or that any potential effect of congenital toxoplasmosis was masked by prenatal treatment. Parents of infected children were significantly more anxious and reported more visual problems in their children. Conclusion: On average, children aged three to four years with congenital toxoplasmosis identified by screening and treated during infancy in this European setting had risks of abnormal development and behavior similar to uninfected children. Parental anxiety about infected children needs to be addressed by clinicians. Future studies with longer follow up and clinician-administered assessments may be better able to detect any subtle differences in child outcomes

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.

Background: We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres. Methods: Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks. Results: The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres. Conclusion: Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies

Predicting aged pork quality using a portable Raman device

The utility of Raman spectroscopic signatures of fresh pork loin (1 d & 15 d postmortem) in predicting fresh pork tenderness and slice shear force (SSF) was determined. Partial least square models showed that sensory tenderness and SSF are weakly correlated (R2 = 0.2). Raman spectral data were collected in 6 s using a portable Raman spectrometer (RS). A PLS regression model was developed to predict quantitatively the tenderness scores and SSF values from Raman spectral data, with very limited success. It was discovered that the prediction accuracies for day 15 post mortem samples are significantly greater than that for day 1 postmortem samples. Classification models were developed to predict tenderness at two ends of sensory quality as “poor” vs. “good”. The accuracies of classification into different quality categories (1st to 4th percentile) are also greater for the day 15 postmortem samples for sensory tenderness (93.5% vs 76.3%) and SSF (92.8% vs 76.1%). RS has the potential to become a rapid on-line screening tool for the pork producers to quickly select meats with superior quality and/or cull poor quality to meet market demand/expectations

First πK\pi K atom lifetime and πK\pi K scattering length measurements

The results of a search for hydrogen-like atoms consisting of $\pi^{\mp}K^{\pm}$ mesons are presented. Evidence for $\pi K$ atom production by 24 GeV/c protons from CERN PS interacting with a nickel target has been seen in terms of characteristic $\pi K$ pairs from their breakup in the same target ($178 \pm 49$) and from Coulomb final state interaction ($653 \pm 42$). Using these results the analysis yields a first value for the $\pi K$ atom lifetime of $\tau=(2.5_{-1.8}^{+3.0})$ fs and a first model-independent measurement of the S-wave isospin-odd $\pi K$ scattering length $\left|a_0^-\right|=\frac{1}{3}\left|a_{1/2}-a_{3/2}\right|= \left(0.11_{-0.04}^{+0.09} \right)M_{\pi}^{-1}$ ($a_I$ for isospin $I$).Comment: 14 pages, 8 figure

Contribution of Early-Postmortem Proteome and Metabolome to Ultimate pH and Pork Quality

This study's objectives were to identify how subtle differences in ultimate pH relate to differences in pork quality and to understand how early-postmortem glycolysis contributes to variation in ultimate pH. The hypothesis was that elements in early-postmortem longissimus thoracis et lumborum proteome and metabolome could be used to predict quality defects associated with pH decline. Temperature and pH of the longissimus thoracis et lumborum were measured at 45 min, 24 h, and 14 d postmortem. Quality measurements were made after 14 d of aging. Groups were classified as normal pH (NpH; x̄ = 5 . 59 [5.53–5.67]; NpH, n = 10) and low pH (LpH; x̄ = 5 . 42 [5.38–5.45]; LpH, n = 10) at 14 d postmortem. Metabolites from 45 min postmortem were identified using GC-MS. Relative differences between proteins were quantified with two-dimensional difference in gel electrophoreses, and spots were identified with MALDI-MS. Western blot analyses were used to measure phosphofructokinase, peroxiredoxin-2, and reduced and non-reduced adenosine monophosphate deaminase-2 at 45 min and 14 d postmortem. Ultimate pH classification did not affect 45-min-postmortem pH (P = 0.64); 14-d pH was different between groups (P < 0.01). NpH had less purge loss (P < 0.01), was darker (P < 0.01), had lower star probe (P < 0.01), and had less intact day-7 desmin (P = 0.02). More pyruvate (P = 0.01) and less lactate (P = 0.09) was observed in NpH, along with more soluble lactate dehydrogenase (P = 0.03) and pyruvate kinase (P < 0.10). These observations indicate that differences in enzyme abundance or solubility may produce more pyruvate and less lactate. Fructose 6-phosphate was more abundant (P = 0.08) in the LpH group, indicating that phosphofructokinase may be involved in glycolytic differences. Furthermore, greater abundance of heat shock proteins, peroxiredoxin-2 (P = 0.02), and malate (P = 0.01) early postmortem all suggest differences in mitochondrial function and oxidative stability that contribute to quality differences. These results show that even subtle changes in ultimate pH can influence pork quality. The proteome and metabolome at 45 min postmortem are associated with variation in the extent of pH decline