PDE8 controls CD4(+) T cell motility through the PDE8A-Raf-1 kinase signaling complex

The levels of cAMP are regulated by phosphodiesterase enzymes (PDEs), which are targets for the treatment of inflammatory disorders. We have previously shown that PDE8 regulates T cell motility. Here, for the first time, we report that PDE8A exerts part of its control of T cell function through the V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase signaling pathway. To examine T cell motility under physiologic conditions, we analyzed T cell interactions with endothelial cells and ligands in flow assays. The highly PDE8-selective enzymatic inhibitor PF-04957325 suppresses adhesion of in vivo myelin oligodendrocyte glycoprotein (MOG) activated inflammatory CD4(+) T effector (Teff) cells to brain endothelial cells under shear stress. Recently, PDE8A was shown to associate with Raf-1 creating a compartment of low cAMP levels around Raf-1 thereby protecting it from protein kinase A (PKA) mediated inhibitory phosphorylation. To test the function of this complex in Teff cells, we used a cell permeable peptide that selectively disrupts the PDE8A-Raf-1 interaction. The disruptor peptide inhibits the Teff-endothelial cell interaction more potently than the enzymatic inhibitor. Furthermore, the LFA-1/ICAM-1 interaction was identified as a target of disruptor peptide mediated reduction of adhesion, spreading and locomotion of Teff cells under flow. Mechanistically, we observed that disruption of the PDE8A-Raf-1 complex profoundly alters Raf-1 signaling in Teff cells. Collectively, our studies demonstrate that PDE8A inhibition by enzymatic inhibitors or PDE8A-Raf-1 kinase complex disruptors decreases Teff cell adhesion and migration under flow, and represents a novel approach to target T cells in inflammation

Adaptive capacity of female rabbits submitted to a change in breeding practices

[EN] The aim of this study was to test the consequences of a change in breeding practices on 219 multiparous rabbit does over 2 reproductive cycles (5th and 6th insemination). Three rabbit breeding systems were defined I: intensive, S: semi-intensive and E: extensive), which varied for the females in terms of reproductive rhythm (RR: 35, 42 and 49 d, respectively) and age at first insemination (20.6, 19.6 and 16.6 wk, respectively), and for kits in terms of age at weaning (32, 35 and 30 d, respectively) and age at slaughter (63, 70 and 70 d, respectively). Females were submitted to one of the 3 systems from the 1st to the 4th artificial insemination (AI), and to another system from the 5th to the 6th AI, before returning to the initial system at the 7th AI. Consequently, they were allocated to 4 groups: I-S-I, S-I-S, S-E-S and E-S-E. Because of poor reproductive performance in the I system and despite a high growth of kits before weaning due to a more energetic diet for does, a sudden change from an I system to an S system significantly increased productivity at 28 d, from 3.37 to 5.04 kg/AI. Conversely, in the S and E systems, the females were not very sensitive to an intensification (groups S-I-S and E-S-E) or an extensification (S-E-S) of the breeding system, leading to similar productivity at 63 d (14.4 and 14.3 kg/AI, 14.4 and 13.5 kg/AI, 16.5 and 16.2 kg/AI, respectively, for groups S-I-S, E-S-E and S-E-S). The consequences of a return to the initial system deserve to be tested over a longer period.This work was supported by the CAS DAR (Cunipalm n° 9023) and by the French rabbit Interprofessional Association (CLIPP).Theau.clément, M.; Galliot, P.; Souchet, C.; Bignon, L.; Fortun-Lamothe, L. (2016). Adaptive capacity of female rabbits submitted to a change in breeding practices. World Rabbit Science. 24(4):267-273. https://doi.org/10.4995/wrs.2016.5155SWORD267273244Blanc F., Dumont B., Brunschwig G., Bocquier F., Agabriel J. 2010. Extensive ruminant farming systems highlight animal coping processes based on robustness, flexibility and plasticity. In: Robustesse, rusticité, flexibilité, plasticité, résilience, les nouveaux critères de qualité des animaux et des systèmes d'élevage. Sauvant D., Perez J.M. (Eds). Dossier INRA Prod. Anim., 23, 65-80.Maertens, L., Perez, J.M., Villamide, M., Cervera, C., Gidenne, T., Xiccato, G., 2002. Nutritive value of raw materials for rabbits: EGRAN tables 2002. World Rabbit Sci., 10: 157-166.Theau-Clément M., Boiti C., Mercier P., Falières J. 2000. Description of the ovarian status and fertilising ability of primiparous rabbit does at different lactation stage, In Proc.: 7th World Rabbit Congress, 4-7 July 2000, Valencia, Spain, Vol A: 259-266

Luminosity indicators in dusty photoionized environments

The luminosity of the central source in ionizing radiation is an essential parameter in a photoionized environment, and one of the most fundamental physical quantities one can measure. We outline a method of determining luminosity for any emission-line region using only infrared data. In dusty environments, grains compete with hydrogen in absorbing continuum radiation. Grains produce infrared emission, and hydrogen produces recombination lines. We have computed a very large variety of photoionization models, using ranges of abundances, grain mixtures, ionizing continua, densities, and ionization parameters. The conditions were appropriate for such diverse objects as H II regions, planetary nebulae, starburst galaxies, and the narrow and broad line regions of active nuclei. The ratio of the total thermal grain emission relative to H$\beta$ (IR/H$\beta$) is the primary indicator of whether the cloud behaves as a classical Str\"{o}mgren sphere (a hydrogen-bounded nebula) or whether grains absorb most of the incident continuum (a dust-bounded nebula). We find two global limits: when $IR/H\beta<100$ infrared recombination lines determine the source luminosity in ionizing photons; when $IR/H\beta\gg100$ the grains act as a bolometer to measure the luminosity.Comment: 12 pages 3 figures. Accepted ASP Sept.9

A log analysis study of 10 years of ebook consumption in academic library collections

Even though libraries have been offering eBooks for more than a decade, very little is known about eBook access and consumption in academic library collections. This paper addresses this gap with a log analysis study of eBook access at the library of the University of Waikato. This in-depth analysis covers a period spanning 10 years of eBook use at this university. We draw conclusions about the use of eBooks at this institution and compare the results with other published studies of eBook usage at tertiary institutes

The distribution and movement patterns of four woodland caribou herds in Quebec and Labrador

Recent studies of woodland caribou (Rangifer tarandus caribou) in northern Quebec and central Labrador have demonstrated similar patterns of seasonal movements and distribution among four herds. Aerial surveys and radio-telemetry indicated that animals occupied forest-wetland habitat at densities of 0.03 caribou km2, or lower, for most of the year. Although females were widely dispersed at calving individuals demonstrated fidelity toward specific calving locations, in successive years. Caribou did not form large post-calving aggregations. Movement was greatest in the spring, prior to calving, and in the fall, during or immediately after rutting. Caribou were generally sedentary during summer and winter, although some moved relatively long distances to late-winter range. Although the herds occupy continuous range across Quebec and Labrador, our data indicate that the herds are largely discreete and should be managed individually

Effects of parity order and reproductive management on the efficiency of rabbit productive systems.

The aim of this work was to study the effect of parity order and reproductive management systems on rabbit production performance. A total of 73 rabbit does (I group) were submitted to a 35-day intensive rhythm [artificial insemination (AI) on day 4 post-partum (pp) and weaning at 25 days of lactation], and 108 rabbit does (SI group) were submitted to a 42-day semi-intensive rhythm (AI on day 11 pp and weaning at 35 days of lactation) during 9 months. Primiparous does had the lowest live body weight at parturition (P < 0.0001) and at 21 days of lactation (P < 0.0001). They also had lower milk production (P < 0.0001) than does with later parities. I group animals needed a higher number of AI than SI group to become pregnant (1.70 ± 0.03 vs. 1.39 ± 0.03; P < 0.0001: especially after the third). Prolificacy was not affected by the management system. Parturition interval (PI) was longer than expected in both groups [56.0 ± 1.4 and 50.9 ± 1.38 days in I and SI groups, respectively (P < 0.05)]. Mean productivity, estimated as number of weaned rabbits per female and year, was 12 kits higher in rabbit does of the SI group (P < 0.05). From the third parturition onward, an increase in live body weight of kits at different ages was observed. At 21 (P < 0.05) and 25 days of age (P < 0.01), kits from the I group rabbit does weighed more than those from the SI group; however, the latter showed a higher weight at 35 (P < 0.05) and 60 days of age (P < 0.05). Rabbit does with two or three parturitions had higher litter size at 21 and 25 days of age (P < 0.0001 and P < 0.001, respectively). Kit mortality between 21 and 25 days of age and between 35 and 60 days of age was not affected by treatments but was higher in the I group between 25 and 35 days (18.2 vs. 5.03% in the I and SI groups, respectively; P < 0.0001) and as age of does increased (P < 0.05). In light of these results, we could conclude that long term doe reproductive performance is negatively affected and litter viability decreased when using intensive compared to a semi-intensive reproductive management

COMPARING GC×GC-TOFMS-BASED METABOLOMIC PROFILING AND WOOD ANATOMY FOR FORENSIC IDENTIFICATION OF FIVE MELIACEAE (MAHOGANY) SPECIES

Illegal logging and associated trade have increased worldwide. Such environmental crimes represent a major threat to forest ecosystems and society, causing distortions in market prices, economic instability, ecological deterioration, and poverty. To prevent illegal imports of forest products, there is a need to develop wood identification methods for identifying tree species regulated by the Convention on International Trade in Species of Wild Fauna andFlora in Trade (CITES) and other look-alike species. In this exploratory study, we applied metabolomic profiling of five species (Swietenia mahagoni, Swietenia macrophylla, Cedrela odorata, Khaya ivorensis, and Toona ciliata) using two-dimensional gas chromatog- raphy combined with time-of-flight mass spectrometry (GC3GC-TOFMS). We also performed qualitative, quantitative (based on the measurement of vessel area, tangential vessel lumina diameter,vessel element length, ray height, and ray width), and machine-vision aided (XyloTron) wood anatomy on a subsample of wood specimens to explore thepotential and limits of each approach. Fifty dried xylaria wood specimens were ground, extracted with methanol, and subsequently analyzed by GC3GC-TOFMS. In this study, the four genera could easily be identified using qualitative wood anatomy and chemical profiling. At the spe- cies level, Swietenia macrophylla and Swietenia mahagoni specimens were found to share many major metabolites and could only be differentiated after feature selection guided by cluster resolution (FS-CR) and visualization using Principal Component Analysis (PCA). Expectedly, specimens from the two Swiete- nia spp. could not be distinguished based on qualitative wood anatomy. However, significant differences in quantitative anatomical features were obtained for these two species. Excluding T. ciliata that was not included in the reference database of end grain images at the time of testing (2021), the XyloTron could successfully identify the majority of the specimens to the right genus and 50% of the specimens to the right species. The machine-vision tool was particularly successful at identifying Cedrela odorata samples, where all samples were correctly identified. Despite the limited number of specimens available for thisstudy, our preliminary results indicate that GC3GC-TOFMS-based metabolomic profiles could be used as comple- mentary method to differentiate CITES-regulated wood specimens at the genus and species levels.

Effect of late weaning and use of alternative cages on performance of does, suckling and fattening rabbits under extensive reproductive management

The effects of the combined use of long lactation periods (46 days) with alternative cages on the reproductive and growth performance of 104 rabbit does and their litters during five consecutive reproductive cycles were studied. Half of does were housed in conventional polyvalent cages (39 cm×100 cm×30 cm) and the other half in alternative polyvalent cages (39 cm×100 cm×60 cm), with a raised platform. Half of the rabbit does in each type of cage were weaned at 32 and the other half at 46 days after parturition. Longer lactation negatively affected the body weight (P<0.001), fat and energy content (P<0.05) of rabbit does at the end of the lactation period, but this effect decreased with the number of parturitions. Fertility, prolificacy and doe mortality were not affected by lactation length. Late weaning led to higher litter size (by 8.9%) and litter weight (by 11.3%) at the end of growing period (P<0.001) and lower feed conversion ratio per cage during the experimental period (13.5%) than weaning at 32 day (P<0.001). These results were paralleled by lower mortality (12.6 vs. 17.6%; P<0.01) of young rabbits weaned later during the overall experimental period. Differences in performance as a result of different weaning ages were only observed during cycles with worst health status (third and fifth cycles) in which late weaning decreased mortality. Type of cage did not affect doe body weight and body condition, mortality, fertility, prolificacy and litter size during the five reproductive cycles. Nevertheless, at day 21 litter weight and feed conversion ratio between 3 and 21 day were 4.2% higher (P<0.01) and 5.0% lower (P<0.05), respectively, in animals housed in alternative rather than in conventional cages. Alternative cages also led to heavier litters at 59 days (P<0.01). It was concluded that the combined use of longer lactations and cages with higher available surface with a raised platform could be alternatives to improve animal welfare in farmed rabbit