The N-Terminus of GalE Induces tmRNA Activity in Escherichia coli

BACKGROUND: The tmRNA quality control system recognizes stalled translation complexes and facilitates ribosome recycling in a process termed 'ribosome rescue'. During ribosome rescue, nascent chains are tagged with the tmRNA-encoded SsrA peptide, which targets tagged proteins for degradation. In Escherichia coli, tmRNA rescues ribosomes arrested on truncated messages, as well as ribosomes that are paused during elongation and termination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a new translational pausing determinant that leads to SsrA peptide tagging of the E. coli GalE protein (UDP-galactose 4-epimerase). GalE chains are tagged at more than 150 sites, primarily within distinct clusters throughout the C-terminal domain. These tagging sites do not correspond to rare codon clusters and synonymous recoding of the galE gene had little effect on tagging. Moreover, tagging was largely unaffected by perturbations that either stabilize or destabilize the galE transcript. Examination of GalE-thioredoxin (TrxA) fusion proteins showed that the GalE C-terminal domain is no longer tagged when fused to an N-terminal TrxA domain. Conversely, the N-terminus of GalE induced tagging within the fused C-terminal TrxA domain. CONCLUSIONS/SIGNIFICANCE: These findings suggest that translation of the GalE N-terminus induces subsequent tagging of the C-terminal domain. We propose that co-translational maturation of the GalE N-terminal domain influences ribosome pausing and subsequent tmRNA activity

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Male hatchling production in sea turtles from one of the world’s largest marine protected areas, the Chagos Archipelago

Incubation temperatures at turtle nest depths and implications for hatchling sex ratios of hawksbill turtles (Eretmochelys imbricata) and green turtles (Chelonia mydas) nesting in the Chagos Archipelago, Western Indian Ocean are reported and compared to similar measurements at rookeries in the Atlantic and Caribbean. During 2012-2014, temperature loggers were buried at depths and in beach zones representative of turtle nesting sites in Diego Garcia. Data collected for 12,546 days revealed seasonal and spatial patterns of sand temperature. Depth effects were minimal, perhaps modulated by shade from vegetation. Coolest and warmest temperatures were recorded in the sites heavily shaded in vegetation during the austral winter and in sites partially shaded in vegetation during summer respectively. Overall, sand temperatures were relatively cool during the nesting seasons of both species which would likely produce fairly balanced hatchling sex ratios of 53% and 63% male hatchlings, respectively, for hawksbill and green turtles. This result contrasts with the predominantly high female skew reported for offspring at most rookeries around the globe and highlights how local beach characteristics can drive incubation temperatures. Our evidence suggests that sites characterized by heavy shade associated with intact natural vegetation are likely to provide conditions suitable for male hatchling production in a warming world

Parametric study of 15Cr / 15Ni austenitic steels swelling behavior under irradiation using cluster dynamics

International audienceAs part of the research program on generation IV reactors, CEA is developing new grades of austen-itic steels for the fuel cladding of Sodium Fast Reactors (SFR). Austenitic stainless steels show ex-cellent properties in SFR’s extreme operating conditions: corrosive environment, high operating tem-perature (400-700 ° C) and highly energetic neutron flux. However, the appearance of the swelling phenomenon under irradiation limits cladding lifespan. The most optimized French grade is AIM1, a 15Cr-15Ni austenitic stabilized steel, which sustain doses up to 100 displacements per atom (dpa)