Double trouble:Bacillus depends on a functional Tat machinery to avoid severe oxidative stress and starvation upon entry into a NaCl-depleted environment

The widely conserved twin-arginine translocases (Tat) allow the transport of fully folded cofactor-containing proteins across biological membranes. In doing so, these translocases serve different biological functions ranging from energy conversion to cell division. In the Gram-positive soil bacterium Bacillus subtilis, the Tat machinery is essential for effective growth in media lacking iron or NaCl. It was previously shown that this phenomenon relates to the Tat-dependent export of the heme-containing peroxidase EfeB, which converts Fe2+ to Fe3+ at the expense of hydrogen peroxide. However, the reasons why the majority of tat mutant bacteria perish upon dilution in NaCl-deprived medium and how, after several hours, a sub-population adapts to this condition was unknown. Here we show that, upon growth in the absence of NaCl, the bacteria face two major problems, namely severe oxidative stress at the membrane and starvation leading to death. The tat mutant cells can overcome these challenges if they are fed with arginine, which implies that severe arginine depletion is a major cause of death and resumed arginine synthesis permits their survival. Altogether, our findings show that the Tat system of B. subtilis is needed to preclude severe oxidative stress and starvation upon sudden drops in the environmental Na+ concentration as caused by flooding or rain

Psychological Well-Being of Parents of Very Young Children With Type 1 Diabetes – Baseline Assessment

Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior. Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ). Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c. Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention

Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers

Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage

Psychological Well-Being of Parents of Very Young Children With Type 1 Diabetes – Baseline Assessment

Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior. Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ). Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c. Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements