HUMAN LUNG CANCER RISKS FROM RADON – PART III - EVIDENCE OF INFLUENCE OF COMBINED BYSTANDER AND ADAPTIVE RESPONSE EFFECTS ON RADON CASE-CONTROL STUDIES - A MICRODOSE ANALYSIS

Since the publication of the BEIR VI (1999) report on health risks from radon, a sig- nificant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m-3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid

Jackdaw nestlings can discriminate between conspecific calls but do not beg specifically to their parents

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Behavioral Ecology following peer review. The definitive publisher-authenticated version Lies Zandberg, Jolle W. Jolles, Neeltje J. Boogert, and Alex Thornton Jackdaw nestlings can discriminate between conspecific calls but do not beg specifically to their parents Behavioral Ecology (2014) 25 (3): 565-573 first published online February 28, 2014 doi:10.1093/beheco/aru026 is available online at: http://intl-beheco.oxfordjournals.org/content/25/3/565.The ability to recognize other individuals may provide substantial benefits to young birds, allowing them to target their begging efforts appropriately, follow caregivers after fledging, and establish social relationships later in life. Individual recognition using vocal cues is likely to play an important role in the social lives of birds such as corvids that provision their young postfledging and form stable social bonds, but the early development of vocal recognition has received little attention. We used playback experiments on jackdaws, a colonial corvid species, to test whether nestlings begin to recognize their parents’ calls before fledging. Although the food calls made by adults when provisioning nestlings were individually distinctive, nestlings did not beg preferentially to their parents’ calls. Ten-day-old nestlings not only responded equally to the calls of their parents, neighboring jackdaws whose calls they were likely to overhear regularly and unfamiliar jackdaws from distant nest boxes, but also to the calls of rooks, a sympatric corvid species. Responses to rooks declined substantially with age, but 20- and 28-day-old nestlings were still equally likely to produce vocal and postural begging responses to parental and nonparental calls. This is unlikely to be due to an inability to discriminate between calls, as older nestlings did respond more quickly and with greater vocal intensity to familiar calls, with some indication of discrimination between parents and neighbors. These results suggest that jackdaws develop the perceptual and cognitive resources to discriminate between conspecific calls before fledging but may not benefit from selective begging responses

Light Chain Separated from the Rest of the Type A Botulinum Neurotoxin Molecule Is the Most Catalytically Active Form

Botulinum neurotoxins (BoNT) are the most potent of all toxins. The 50 kDa N-terminal endopeptidase catalytic light chain (LC) of BoNT is located next to its central, putative translocation domain. After binding to the peripheral neurons, the central domain of BoNT helps the LC translocate into cytosol where its proteolytic action on SNARE (soluble NSF attachment protein receptor) proteins blocks exocytosis of acetyl choline leading to muscle paralysis and eventual death. The translocation domain also contains 105 Å -long stretch of ∼100 residues, known as “belt,” that crosses over and wraps around the LC to shield the active site from solvent. It is not known if the LC gets dissociated from the rest of the molecule in the cytosol before catalysis. To investigate the structural identity of the protease, we prepared four variants of type A BoNT (BoNT/A) LC, and compared their catalytic parameters with those of BoNT/A whole toxin. The four variants were LC + translocation domain, a trypsin-nicked LC + translocation domain, LC + belt, and a free LC. Our results showed that Km for a 17-residue SNAP-25 (synaptosomal associated protein of 25 kDa) peptide for these constructs was not very different, but the turnover number (kcat) for the free LC was 6-100-fold higher than those of its four variants. Moreover, none of the four variants of the LC was prone to autocatalysis. Our results clearly demonstrated that in vitro, the LC minus the rest of the molecule is the most catalytically active form. The results may have implication as to the identity of the active, toxic moiety of BoNT/A in vivo

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio

Differential Cerebral Cortex Transcriptomes of Baboon Neonates Consuming Moderate and High Docosahexaenoic Acid Formulas

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system (CNS). These nutrients are present in most infant formulas at modest levels, intended to support visual and neural development. There are no investigations in primates of the biological consequences of dietary DHA at levels above those present in formulas but within normal breastmilk levels. METHODS AND FINDINGS: Twelve baboons were divided into three formula groups: Control, with no DHA-ARA; “L”, LCPUFA, with 0.33%DHA-0.67%ARA; “L3”, LCPUFA, with 1.00%DHA-0.67%ARA. All the samples are from the precentral gyrus of cerebral cortex brain regions. At 12 weeks of age, changes in gene expression were detected in 1,108 of 54,000 probe sets (2.05%), with most showing <2-fold change. Gene ontology analysis assigns them to diverse biological functions, notably lipid metabolism and transport, G-protein and signal transduction, development, visual perception, cytoskeleton, peptidases, stress response, transcription regulation, and 400 transcripts having no defined function. PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only LCPUFA biosynthetic enzyme that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated by high DHA, while the mitochondrial proton carrier, UCP2, was upregulated. TIMM8A, also known as deafness/dystonia peptide 1, was among several differentially expressed neural development genes. LUM and TIMP3, associated with corneal structure and age-related macular degeneration, respectively, were among visual perception genes influenced by LCPUFA. TIA1, a silencer of COX2 gene translation, is upregulated by high DHA. Ingenuity pathway analysis identified a highly significant nervous system network, with epidermal growth factor receptor (EGFR) as the outstanding interaction partner. CONCLUSIONS: These data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across a wide array of processes, in addition to changes in visual and neural function normally associated with formula LCPUFA

Search for B_s --> mu+mu- and B_d --> mu+mu- Decays with CDF II

A search has been performed for B_s --> mu+mu- and B_d --> mu+mu- decays using 7/fb of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron collider. The observed number of B_d candidates is consistent with background-only expectations and yields an upper limit on the branching fraction of BF(B_d-->mu+mu-) < 6.0E-9 at 95% confidence level. We observe an excess of B_s candidates. The probability that the background processes alone could produce such an excess or larger is 0.27%. The probability that the combination of background and the expected standard model rate of B_s --> mu+mu- could produce such an excess or larger is 1.9%. These data are used to determine BF(B_s-->mu+mu-) = (1.8^{+1.1}_{-0.9})E-8 and provide an upper limit of BF(B_s -->mu+mu-) < 4.0E-8 at 95% confidence level.Comment: 7 pages, 1 figure; version accepted by PR