OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.     

The evaluation and prognosis of the psychophysiological status of a human operator

In experiments on 56 healthy subjects (18-20 years old) the quality of their activity was determined during compensatory watching the mark at complicating regimes of work. Depending on the difficulty of the task five groups of subjects were singled out with optimum working capacity in one of four working conditions: normal, ordinary and strenuous work, model of stress situation. It is established that the change of the number of significant correlative connections between main parameters of psychophysiological state of man-operator reflects the condition of his functional systems. On the basis of computation of total range of organization values of both R-R intervals of the ECG and duration of expiration, the success of the man-operator work in complex conditions of activity is predicted.     

α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.     

How to Make a Beetle Out of Wood: Multi-Elemental Stoichiometry of Wood Decay,Xylophagy and Fungivory

The majority of terrestrial biomass is wood, but the elemental composition of its potential consumers, xylophages, differs hugely from that of wood. This causes a severe nutritional imbalance. We studied the stoichiometric relationships of 11 elements (C, N, P, K, Ca, Mg, Fe, Zn, Mn, Cu, Na) in three species of pine-xylem-feeding insects, Stictoleptura rubra, Arhopalus rusticus (Coleoptera, Cerambycidae) and Chalcophora mariana (Coleoptera, Buprestidae), to elucidate their mechanisms of tissue growth and to match their life histories to their dietary constraints. These beetles do not differ from other Coleoptera in their absolute elemental compositions, which are approximately 1000 (N), 100 (P, Cu) and 50 (K, Na) times higher than in dead but undecayed pine wood. This discrepancy diminishes along the wood decay gradient, but the elemental concentrations remain higher by an order of magnitude in beetles than in highly decayed wood. Numerical simulation of the life history of S. rubra shows that feeding on nutrient-poor undecayed wood would extend its development time to implausible values, whereas feeding on highly decomposed wood (heavily infected with fungi) would barely balance its nutritional budget during the long development period of this species. The changes in stoichiometry indicate that the relative change in the nutrient levels in decaying wood cannot be attributed solely to carbon loss resulting from decomposer respiration: the action of fungi substantially enriches the decaying wood with nutritional elements imported from the outside of the system, making it a suitable food for wood-eating invertebrates.     

Highly specialized Cretaceous beetle parasitoids (Ripiphoridae) identified with optimized visualization of microstructures

Extremely miniaturized longipedes insects (body length c. 0.3 mm) embedded in two pieces of Cretaceous amber from Myanmar are described and interpreted. Using inverted fluorescence and light microscopy for detailed analysis of microstructures, the inclusions were identified as primary larvae of the beetle family Ripiphoridae, subfamily Ripidiinae. While the structure of thoracic and abdominal segments including appendages corresponds well with the groundplan known in recent members of Ripidiinae, a curved prosternal ridge with prominent spines (each c. 5 μm), the reduced condition of stemmata and antennae and the lack of sharp mandibles are unique features within the entire family, apparently apomorphies of the longipedes larvae. A sinuate prosternal edge with a dense row of spines (prosternoctenidium) might be homologous with ‘head ctenidia’ in some previously described miniaturized conicocephalate larvae, but further investigation is needed. The morphological differences between the head of longipedes larvae and extant Ripidiinae are interpreted as adaptations to different groups of hosts and life strategies. Palaeoethology of the longipedes larvae is briefly discussed. In addition, the systematic placement of conicocephalate larvae from Canadian, Myanmar and Russian Cretaceous ambers, already interpreted by various authors as primary instars within Coleopterida (assigned to either Strepsiptera or to the coleopteran Tenebrionoidea: Ripiphoridae), is discussed.     

Fine Mapping the Spatial Distribution and Concentration of Unlabeled Drugs within Tissue Micro-Compartments Using Imaging Mass Spectrometry

Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.