Identification of respiratory vagal feedback in awake normal subjects using pseudorandom unloading.

Evidence of the Hering-Breuer reflex has been found in humans during anesthesia and sleep but not during wakefulness. Cortical influences, present during wakefulness, may mask the effects of this reflex in awake humans. We hypothesized that, if lung volume were increased in awake subjects unaware of the stimulus, vagal feedback would modulate breathing on a breath-to-breath basis. To test this hypothesis, we employed proportional assist ventilation in a pseudorandom sequence to unload the respiratory system above and below the perceptual threshold in 17 normal subjects. Tidal volume, integrated respiratory muscle pressure per breath, and inspiratory time were recorded. Both sub- and suprathreshold stimulation evoked a significant increase in tidal volume and inspiratory flow rate, but a significant decrease in inspiratory time was present only during the application of a subthreshold stimulus. We conclude that vagal feedback modulates respiratory timing on a breath-by-breath basis in awake humans, as long as there is no awareness of the stimulus.     

Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2

The precise regulation of synapse maintenance is critical to the development and function of neuronal circuits. Using an in vivo RNAi screen targeting the Drosophila kinome and phosphatome, we identify 11 kinases and phosphatases controlling synapse stability by regulating cytoskeletal, phospholipid, or metabolic signaling. We focus on casein kinase 2 (CK2) and demonstrate that the regulatory (β) and catalytic (α) subunits of CK2 are essential for synapse maintenance. CK2α kinase activity is required in the presynaptic motoneuron, and its interaction with CK2β, mediated cooperatively by two N-terminal residues of CK2α, is essential for CK2 holoenzyme complex stability and function in vivo. Using genetic and biochemical approaches we identify Ankyrin2 as a key presynaptic target of CK2 to maintain synapse stability. In addition, CK2 activity controls the subcellular organization of individual synaptic release sites within the presynaptic nerve terminal. Our study identifies phosphorylation of structural synaptic components as a compelling mechanism to actively control the development and longevity of synaptic connections.     

Preadapted for invasiveness: do species traits or their plastic response to shading differ between invasive and non‐invasive plant species in their native range?

Aim Species capable of vigorous growth under a wide range of environmental conditions should have a higher chance of becoming invasive after introduction into new regions. High performance across environments can be achieved either by constitutively expressed traits that allow for high resource uptake under different environmental conditions or by adaptive plasticity of traits. Here we test whether invasive and non‐invasive species differ in presumably adaptive plasticity. Location Europe (for native species); the rest of the world and North America in particular (for alien species). Methods We selected 14 congeneric pairs of European herbaceous species that have all been introduced elsewhere. One species of each pair is highly invasive elsewhere in the world, particularly so in North America, whereas the other species has not become invasive or has spread only to a limited degree. We grew native plant material of the 28 species under shaded and non‐shaded conditions in a common garden experiment, and measured biomass production and morphological traits that are frequently related to shade tolerance and avoidance. Results Invasive species had higher shoot–root ratios, tended to have longer leaf‐blades, and produced more biomass than congeneric non‐invasive species both under shaded and non‐shaded conditions. Plants responded to shading by increasing shoot–root ratios and specific leaf area. Surprisingly, these shade‐induced responses, which are widely considered to be adaptive, did not differ between invasive and non‐invasive species. Main conclusions We conclude that high biomass production across different light environments pre‐adapts species to become invasive, and that this is not mediated by plasticities of the morphological traits that we measured.     

Termination of inspiration by phase-dependent respiratory vagal feedback in awake normal humans.

Imperceptible levels of proportional assist ventilation applied throughout inspiration reduced inspiratory time (TI) in awake humans. More recently, the reduction in TI was associated with flow assist, but flow assist also reaches a maximum value early during inspiration. To test the separate effects of flow assist and timing of assist, we applied a pseudorandom binary sequence of flow-assisted breaths during early, late, or throughout inspiration in eight normal subjects. We hypothesized that imperceptible flow assist would shorten TI most effectively when applied during early inspiration. Tidal volume, integrated respiratory muscle pressure per breath, TI, and TE were recorded. All stimuli (early, late, or flow assist applied throughout inspiration) resulted in a significant increase in inspiratory flow; however, only when the flow assist was applied during early inspiration was there a significant reduction in TI and the integrated respiratory muscle pressure per breath. These results provide further evidence that vagal feedback modulates breathing on a breath-by-breath basis in conscious humans within a physiological range of breath sizes.     

The major histocompatibility complex of primates

The major histocompatibility complex (MHC) encodes cell surface glycoproteins that function in self-nonself recognition and in allograft rejection. Among primates, the MHC has been well defined only in the human; in the chimpanzee and in two species of macaque monkeys the MHC is less well characterized. Serologic, biochemical and genetic evidence indicates that the basic organization of the MHC linkage group has been phylogenetically conserved. However, the number of genes and their linear relationship on the chromosomes differ between species. Class I MHC loci encode molecules that are the most polymorphic genes known. These molecules are ubiquitous in their tissue distribution and typically are recognized together with nominal antigens by cytotoxic lymphocytes. Class II MHC loci constitute a smaller family of serotypes serving as restricting elements for regulatory T lymphocytes. The distribution of class II antigens is limited mainly to cell types serving immune functions, and their expression is subject to up and down modulation. Class III loci code for components C2, C4 and Factor B (Bf) of the complement system.Interspecies differences in the extent of polymorphism occur, but the significance of this finding in relation to fitness and natural selection is unclear. Detailed information on the structure and regulation of MHC gene expression will be required to understand fully the biologic role of the MHC and the evolutionary relationships between species. Meanwhile, MHC testing has numerous applications to biomedical research, especially in preclinical tissue and organ transplantation studies, the study of disease mechanisms, parentage determination and breeding colony management. In this review, the current status of MHC definition in nonhuman primates will be summarized. Special emphasis is placed on the CyLA system of M. fascicularis which is a major focus in our laboratory. A highly polymorphic cynomolgus MHC has been partially characterized and consists of at least 14 A locus, 11 B locus, 7 C locus class I allelic specificities, 9 Ia-like class II antigens and 6 Bf (class III) variants.