Fossil traces of the bone-eating worm Osedax in early Oligocene whale bones

Osedax is a recently discovered group of siboglinid annelids that consume bones on the seafloor and whose evolutionary origins have been linked with Cretaceous marine reptiles or to the post-Cretaceous rise of whales. Here we present whale bones from early Oligocene bathyal sediments exposed in Washington State, which show traces similar to those made by Osedax today. The geologic age of these trace fossils (∼30 million years) coincides with the first major radiation of whales, consistent with the hypothesis of an evolutionary link between Osedax and its main food source, although older fossils should certainly be studied. Osedax has been destroying bones for most of the evolutionary history of whales and the possible significance of this “Osedax effect” in relation to the quality and quantity of their fossils is only now recognized.     

In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens

Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.     

Comparison of metabolic adaptations between endurance‐ and sprint‐trained athletes after an exhaustive exercise in two different calf muscles using a multi‐slice 31P‐MR spectroscopic sequence

Measurements of exercise‐induced metabolic changes, such as oxygen consumption, carbon dioxide exhalation or lactate concentration, are important indicators for assessing the current performance level of athletes in training science. With exercise‐limiting metabolic processes occurring in loaded muscles, ³¹P‐MRS represents a particularly powerful modality to identify and analyze corresponding training‐induced alterations. Against this background, the current study aimed to analyze metabolic adaptations after an exhaustive exercise in two calf muscles (m. soleus – SOL – and m. gastrocnemius medialis – GM) of sprinters and endurance athletes by using localized dynamic ³¹P‐MRS. In addition, the respiratory parameters VO₂ and VCO₂, as well as blood lactate concentrations, were monitored simultaneously to assess the effects of local metabolic adjustments in the loaded muscles on global physiological parameters. Besides noting obvious differences between the SOL and the GM muscles, we were also able to identify distinct physiological strategies in dealing with the exhaustive exercise by recruiting two athlete groups with opposing metabolic profiles. Endurance athletes tended to use the aerobic pathway in the metabolism of glucose, whereas sprinters produced a significantly higher peak concentration of lactate. These global findings go along with locally measured differences, especially in the main performer GM, with sprinters revealing a higher degree of acidification at the end of exercise (pH 6.29 ± 0.20 vs. 6.57 ± 0.21). Endurance athletes were able to partially recover their PCr stores during the exhaustive exercise and seemed to distribute their metabolic activity more consistently over both investigated muscles. In contrast, sprinters mainly stressed Type II muscle fibers, which corresponds more to their training orientation preferring the glycolytic energy supply pathway. In conclusion, we were able to analyze the relation between specific local metabolic processes in loaded muscles and typical global adaptation parameters, conventionally used to monitor the training status of athletes, in two cohorts with different sports orientations.     

Real-Time Clustered Multiple Signal Classification (RTC-MUSIC)

Magnetoencephalography (MEG) and electroencephalography provide a high temporal resolution, which allows estimation of the detailed time courses of neuronal activity. However, in real-time analysis of these data two major challenges must be handled: the low signal-to-noise ratio (SNR) and the limited time available for computations. In this work, we present real-time clustered multiple signal classification (RTC-MUSIC) a real-time source localization algorithm, which can handle low SNRs and can reduce the computational effort. It provides correlation information together with sparse source estimation results, which can, e.g., be used to identify evoked responses with high sensitivity. RTC-MUSIC clusters the forward solution based on an anatomical brain atlas and optimizes the scanning process inherent to MUSIC approaches. We evaluated RTC-MUSIC by analyzing MEG auditory and somatosensory data. The results demonstrate that the proposed method localizes sources reliably. For the auditory experiment the most dominant correlated source pair was located bilaterally in the superior temporal gyri. The highest activation in the somatosensory experiment was found in the contra-lateral primary somatosensory cortex.     

Criteria for gauging response to sodium oxybate for narcolepsy

Our objective was to define responder criteria using an anchor‐based approach for frequency of cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo‐controlled, double‐blind, multicentre 4‐ and 8‐week trials of sodium oxybate for narcolepsy with cataplexy and analysed using receiver operator characteristics analysis. The percentage change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared with Clinical Global Impression of Change ratings, used as the anchor to define true response. Participants (n = 336) were 39% male, 89% white, with a mean age of 41.5 (15.3) years, reporting a median of 20.5 cataplexy attacks per week and a mean Epworth Sleepiness score of 17.5 at baseline. A majority (51%) were Much Improved or Very Much Improved based on Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%) supported response definition thresholds of 46% and 12%, respectively. Classification using either response definition agreed with the anchor for approximately 71% of participants. Cataplexy response definition was more sensitive (cataplexy = 0.77, Epworth Sleepiness Scale = 0.69), while sleepiness was more specific (cataplexy = 0.66, Epworth Sleepiness Scale = 0.75). Both responder definitions showed a dose–response relationship with sodium oxybate, demonstrating their validity using an external criterion. Weekly cataplexy attacks and Epworth Sleepiness Scale can be used to help document clinical response to narcolepsy treatment using criteria of 46% and 12% reductions, respectively.     

Altered GPM6A/M6 Dosage Impairs Cognition and Causes Phenotypes Responsive to Cholesterol in Human and Drosophila

Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol‐rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient‐derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient‐derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long‐term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes.     

Zur Katalyse der stereospezifischen Butadienpolymerisation mit den Katalysatorsystemen aus Nd(η3-C3H5)3 · dioxan und methylaluminoxan (MAO) sowie Hexaisobutylaluminoxan (HIBAO)

The activation of the tris(allyl)neodymium complex Nd(η³-C₃H₅)₃ · dioxane with alkylaluminoxanes (MAO or HIBAO) results in highly selective catalysts for the 1,4-cis-polymerization of butadiene (cis-selectivity up to 80%). Under standard conditions (50°C, toluene), the turnover frequency (TOF) of the catalyst/MAO system amounts to 10–15000 mol butadiene/(mol Nd · h). Molecular weight determinations indicate the formation of only one polymer chain per neodymium center as in a living polymerization reaction, and for the catalyst/HIBAO system the rate law r_p = k_p [Nd][C₄H₆] with k_p = 8,7 · 10^?2 mol/(L · s) (at 25°C) has been derived. As the catalytically active species, a cationic monobutenyl neodymium(III) complex is discussed, which is stabilized through coordinative interaction with the counter anion as well as the growing polybutadiene chain. This cationic complex reacts under insertion with butadiene in a bimolecular fashion.     

Serodiagnosis of Helicobacter hepaticus infection in mice by an enzyme-linked immunosorbent assay.

Helicobacter hepaticus is a newly recognized bacterium associated with chronic active hepatitis, hepatic carcinoma, and inflammatory bowel disease in mice. Currently, fecal or tissue PCR, fecal culture, or histologic examination of silver-stained liver sections is used to diagnose H. hepaticus infection. In this report, we describe an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of H. hepaticus infection in mice with a membrane digest preparation of H. hepaticus as the antigen. Sera from mice positive for H. hepaticus by PCR or histologic examination (n = 88), positive for Helicobacter bilis by PCR (n = 13), positive for other helicobacters (not identifiable to species level) by PCR (n = 25), or negative for all Helicobacter species by PCR (n = 162) were used to evaluate the ELISA. Results indicated that ELISA provided 93.2% sensitivity, 94% specificity, 87.2% positive predictive value, and 96.9% negative predictive value. Cross-reactive antibodies were detected in some mice infected with helicobacters not identifiable to species level. To further define ELISA sensitivity and specificity, groups of 10 C57BL/6 mice were inoculated per os with H. hepaticus, Helicobacter muridarum, or H. bilis. Sera were collected and examined by the ELISA. H. hepaticus-infected mice seroconverted by 2 weeks and maintained ELISA reactivity throughout the 18-week study, while mice infected with H. muridarum and H. bilis were negative by ELISA. These results indicate that this reported ELISA is highly sensitive and specific for the serodiagnosis of H. hepaticus infection in mice.