Lunar Outgassing, Transient Phenomena and The Return to The Moon, I: Existing Data

Herein the transient lunar phenomena (TLP) report database is subjected to a discriminating statistical filter robust against sites of spurious reports, and produces a restricted sample that may be largely reliable. This subset is highly correlated geographically with the catalog of outgassing events seen by the Apollo 15, 16 and Lunar Prospector alpha-particle spectrometers for episodic Rn-222 gas release. Both this robust TLP sample and even the larger, unfiltered sample are highly correlated with the boundary between mare and highlands, as are both deep and shallow moonquakes, as well as Po-210, a long-lived product of Rn-222 decay and a further tracer of outgassing. This offers another significant correlation relating TLPs and outgassing, and may tie some of this activity to sagging mare basalt plains (perhaps mascons). Additionally, low-level but likely significant TLP activity is connected to recent, major impact craters (while moonquakes are not), which may indicate the effects of cracks caused by the impacts, or perhaps avalanches, allowing release of gas. The majority of TLP (and Rn-222) activity, however, is confined to one site that produced much of the basalt in the Procellarum Terrane, and it seems plausible that this TLP activity may be tied to residual outgassing from the formerly largest volcanic ffusion sites from the deep lunar interior. With the coming in the next few years of robotic spacecraft followed by human exploration, the study of TLPs and outgassing is both promising and imperiled. We will have an unprecedented pportunity to study lunar outgassing, but will also deal with a greater burden of anthropogenic lunar gas than ever produced. There is a pressing need to study lunar atmosphere and its sources while still pristine. [Abstract abridged.]Comment: 35 pages, 3 figures, submitted to Icarus. Other papers in series found at http://www.astro.columbia.edu/~arlin/TLP

The organic geochemistry of ancient sediments, part II

Chemical analysis of sediment and oil hydrocarbon content by gas chromatography and mass spectrometry to establish inception period of bio-organic evolutio

Outcomes for 18 to 25-year-olds with borderline personality disorder in a dedicated young adult only DBT programme compared to a general adult DBT programme for all ages 18

Aim Targeting young adults with borderline personality disorder (BPD) for treatment may carry significant social and clinical benefits. We aimed to evaluate a community‐based Dialectical Behaviour Therapy (DBT) programme delivered exclusively to young adults with BPD. Methods We describe a naturally occurring non‐equivalent, quasi‐experimental comparison of outcomes for young adults (18‐25 years) with BPD following 1 year of treatment in either a young adult only DBT programme or a general adult DBT programme (18+ years). Twenty‐four young adults enrolled in a community‐based young adult DBT programme open only to 18‐ to 25‐year‐olds with BPD. Another 13 young adults, also 18‐25 years, enrolled in a general adult DBT programme open to all ages above 18 years. Both treatment conditions offered all modes of standard DBT for 1 year. Participants completed a battery of self‐report measures on mental health symptoms at baseline and again at treatment completion after 1 year. Discharge rates at 2 years post‐treatment completion were also recorded. Results Better outcomes were found on borderline symptom severity and general psychopathology among completers of young adult DBT, with a large effect size for treatment condition as well as greater clinically significant change. Discharge rates from mental health services 24 months later were also higher for completers of young adult DBT. Conclusions There may be advantages in delivering DBT to young adults in an age‐specific programme, possibly due to group cohesion. Methodological limitations apply, such as small sample size and non‐randomization. Further controlled research is needed

Statement on the safety of taxifolin-rich extract from Dahurian Larch (Larix gmelinii)

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to carry out a supplementary safety assessment for taxifolin by considering also those population groups which were originally excluded at the request of the applicant (i.e. infants, young children and children up to 9 years) for the food categories set out in the application, and by taking into the extension of use of taxifolin from yogurt to a wider range of dairy products. In 2016, the EFSA NDA Paneladopted the Scientific Opinion on the safety of taxifolin-rich extract from Dahurian Larch (Larix gmelinii) as a novel food ingredient in non-alcoholic beverages, yogurts, chocolate confectionery and food supplements pursuant to Regulation (EC) No 258/97. In order to address the present mandate, an intake assessment was carried out by taking into account all population groups (including now also children below 9years of age) and by considering the food intended categories for which the applicant provided maximum use levels of taxifolin. Intakes were estimated for all age groups of the general population. The highest 95 th percentile intakes per kg bw per day among all population groups are 0.94 and 1.54 mg, respectively, derived for toddlers. Noting that the no-observed-adverse effect level (NOAEL) of the subchronic study was 1,500 mg/kg body weight (bw), the resulting margin of exposure (MOE) would be almost 1,000. For adults weighing 70 kg, the MOE to the combined intake from fortified foods and food supplements would be about 772. For adolescents, taking into account a default mean body weight of 61 kg, the MOE to the combined intake (including 100 mg from food supplements) would be about 627. The Panelconsiders that these MOEs are sufficient. The Panelconcludes that the NF food, taxifolin-rich extract from Dahurian Larch, is safe under the proposed conditions of use

Safety of 1-methylnicotinamide chloride (1-MNA) as a novel food pursuant to Regulation (EC) No258/97

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on 1-methylnicotinamide chloride (1-MNA) as a novel food (NF) ingredient submitted pursuant to Regulation (EC) No258/97 of the European Parliament and of the Council, taking into account the comments and objections of a scientific nature raised by Member States. 1-MNA is a substance present naturally in the human body as a normal downstream product of niacin metabolism. The Panelconsiders that the information provided on the composition, the specification and the batch-to-batch variability of the NF is sufficient. The applicant intends to use 1-MNA in food supplements and proposes a maximum intake of 58mg/day. 1-MNA is not genotoxic. In a subchronic rat study, epithelium degeneration of the non-glandular stomach was observed at all dose levels with increasing frequency. The Panelnotes that the human stomach does not have non-glandular epithelium and considers this finding is toxicologically not relevant for humans. At doses of 500 and 1,000mg/kg body weight (bw), changes of the urine pH, that did not reverse in the recovery period, were reported. As adversity of this finding cannot be ruled out, the Panelselected 250mg/kg bw in this rat study as the reference point. The Margin of Exposure to humans weighing 70kg and consuming 58mg would be about 300. The Panelnotes the upper level for nicotinamide, i.e. 900mg/day for adults. Taking into account that 1-MNA is a main metabolite from nicotinamide, the Panelconsiders that it is unlikely that an intake of 58mg 1-MNA from food supplements would result in adverse health outcomes in humans. The Panelconcludes that the NF, 1-MNA, is safe under the proposed uses and use levels. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority

Promiscuous Aggregate-Based Inhibitors Promote Enzyme Unfolding

One of the leading sources of false positives in early drug discovery is the formation of organic small molecule aggregates, which inhibit enzymes nonspecifically at micromolar concentrations in aqueous solution. The molecular basis for this widespread problem remains hazy. To investigate the mechanism of inhibition at a molecular level, we determined changes in solvent accessibility that occur when an enzyme binds to an aggregate using hydrogen-deuterium exchange mass spectrometry. For AmpC beta-lactamase, binding to aggregates of the small molecule rottlerin increased the deuterium exchange of all 10 reproducibly detectable peptides, which covered 41% of the sequence of beta-lactamase. This suggested a global increase in proton accessibility upon aggregate binding, consistent with denaturation. We then investigated whether enzyme-aggregate complexes were more susceptible to proteolysis than uninhibited enzyme. For five aggregators, trypsin degradation of beta-lactamase increased substantially when beta-lactamase was inhibited by aggregates, whereas uninhibited enzyme was generally stable to digestion. Combined, these results suggest that the mechanism of action of aggregate-based inhibitors proceeds via partial protein unfolding when bound to an aggregate particle

Identification of a Novel Chromosomal Passenger Complex and Its Unique Localization during Cytokinesis in Trypanosoma brucei

Aurora B kinase is a key component of the chromosomal passenger complex (CPC), which regulates chromosome segregation and cytokinesis. An ortholog of Aurora B was characterized in Trypanosoma brucei (TbAUK1), but other conserved components of the complex have not been found. Here we identified four novel TbAUK1 associated proteins by tandem affinity purification and mass spectrometry. Among these four proteins, TbKIN-A and TbKIN-B are novel kinesin homologs, whereas TbCPC1 and TbCPC2 are hypothetical proteins without any sequence similarity to those known CPC components from yeasts and metazoans. RNAi-mediated silencing of each of the four genes led to loss of spindle assembly, chromosome segregation and cytokinesis. TbKIN-A localizes to the mitotic spindle and TbKIN-B to the spindle midzone during mitosis, whereas TbCPC1, TbCPC2 and TbAUK1 display the dynamic localization pattern of a CPC. After mitosis, the CPC disappears from the central spindle and re-localizes at a dorsal mid-point of the mother cell, where the anterior tip of the daughter cell is tethered, to start cell division toward the posterior end, indicating a most unusual CPC-initiated cytokinesis in a eukaryote

TLR Tolerance Reduces IFN-Alpha Production Despite Plasmacytoid Dendritic Cell Expansion and Anti-Nuclear Antibodies in NZB Bicongenic Mice

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.NZBc13) intervals develop anti-nuclear antibodies and mild glomerulonephritis (GN), together with increased T and B cell activation. Here, we produced B6.NZBc1c13 bicongenic mice with both intervals, and demonstrate several novel phenotypes including: marked plasmacytoid and myeloid dendritic cell expansion, and elevated IgA production. Despite these changes, only minor increases in anti-nuclear antibody production were seen, and the severity of GN was reduced as compared to B6.NZBc1 mice. Although bicongenic mice had increased levels of baff and tnf-α mRNA in their spleens, the levels of IFN-α-induced gene expression were reduced. Splenocytes from bicongenic mice also demonstrated reduced secretion of IFN-α following TLR stimulation in vitro. This reduction was not due to inhibition by TNF-α and IL-10, or regulation by other cellular populations. Because pDC in bicongenic mice are chronically exposed to nuclear antigen-containing immune complexes in vivo, we examined whether repeated stimulation of mouse pDC with TLR ligands leads to impaired IFN-α production, a phenomenon termed TLR tolerance. Bone marrow pDC from both B6 and bicongenic mice demonstrated markedly inhibited secretion of IFN-α following repeated stimulation with a TLR9 ligand. Our findings suggest that the expansion of pDC and production of anti-nuclear antibodies need not be associated with increased IFN-α production and severe kidney disease, revealing additional complexity in the regulation of autoimmunity in systemic lupus erythematosus