Empirical critical loads for N deposition effects and maps showing areas projected to be in exceedance of the critical load (CL) are given for seven major vegetation types in California. Thirty-five ...percent of the land area for these vegetation types (99,639
km
2) is estimated to be in excess of the N CL. Low CL values (3–8
kg
N
ha
−1
yr
−1) were determined for mixed conifer forests, chaparral and oak woodlands due to highly N-sensitive biota (lichens) and N-poor or low biomass vegetation in the case of coastal sage scrub (CSS), annual grassland, and desert scrub vegetation. At these N deposition critical loads the latter three ecosystem types are at risk of major vegetation type change because N enrichment favors invasion by exotic annual grasses. Fifty-four and forty-four percent of the area for CSS and grasslands are in exceedance of the CL for invasive grasses, while 53 and 41% of the chaparral and oak woodland areas are in exceedance of the CL for impacts on epiphytic lichen communities. Approximately 30% of the desert (based on invasive grasses and increased fire risk) and mixed conifer forest (based on lichen community changes) areas are in exceedance of the CL. These ecosystems are generally located further from emissions sources than many grasslands or CSS areas. By comparison, only 3–15% of the forested and chaparral land areas are estimated to be in exceedance of the NO
3
− leaching CL. The CL for incipient N saturation in mixed conifer forest catchments was 17
kg
N
ha
−1
yr
−1. In 10% of the CL exceedance areas for all seven vegetation types combined, the CL is exceeded by at least 10
kg
N
ha
−1
yr
−1, and in 27% of the exceedance areas the CL is exceeded by at least 5
kg
N
ha
−1
yr
−1. Management strategies for mitigating the effects of excess N are based on reducing N emissions and reducing site N capital through approaches such as biomass removal and prescribed fire or control of invasive grasses by mowing, selective herbicides, weeding or domestic animal grazing. Ultimately, decreases in N deposition are needed for long-term ecosystem protection and sustainability, and this is the only strategy that will protect epiphytic lichen communities.
We review the results of an extensive campaign to determine the physical, geological, and dynamical properties of asteroid (101955) Bennu. This investigation provides information on the orbit, shape, ...mass, rotation state, radar response, photometric, spectroscopic, thermal, regolith, and environmental properties of Bennu. We combine these data with cosmochemical and dynamical models to develop a hypothetical timeline for Bennu's formation and evolution. We infer that Bennu is an ancient object that has witnessed over 4.5 Gyr of solar system history. Its chemistry and mineralogy were established within the first 10 Myr of the solar system. It likely originated as a discrete asteroid in the inner Main Belt approximately 0.7–2 Gyr ago as a fragment from the catastrophic disruption of a large (approximately 100‐km), carbonaceous asteroid. It was delivered to near‐Earth space via a combination of Yarkovsky‐induced drift and interaction with giant‐planet resonances. During its journey, YORP processes and planetary close encounters modified Bennu's spin state, potentially reshaping and resurfacing the asteroid. We also review work on Bennu's future dynamical evolution and constrain its ultimate fate. It is one of the most Potentially Hazardous Asteroids with an approximately 1‐in‐2700 chance of impacting the Earth in the late 22nd century. It will most likely end its dynamical life by falling into the Sun. The highest probability for a planetary impact is with Venus, followed by the Earth. There is a chance that Bennu will be ejected from the inner solar system after a close encounter with Jupiter. OSIRIS‐REx will return samples from the surface of this intriguing asteroid in September 2023.
Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have ...reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.
Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.
The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac)-2 progressively increased.
Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease.
Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise ...mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.
Signaling by the transcription factor nuclear factor kappa B (NF-κB) involves its release from inhibitor kappa B (IκB) in the cytosol, followed by translocation into the nucleus. NF-κB regulation of ...IκBα transcription represents a delayed negative feedback loop that drives oscillations in NF-κB translocation. Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IκBα transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-κB signaling may thus depend on number, period, and amplitude of oscillations.
Bone marrow‐derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC ...transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC‐based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)‐positive bone marrow‐chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post‐SCI improved motor function and relieved SCI‐induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C‐γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p‐p38 mitogen‐activated protein kinase and extracellular signal‐regulated kinase (p‐ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double‐positive hematogenous macrophages without decreasing the CD11b‐positive and GFP‐negative activated spinal‐microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood‐spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor‐α, interleukin‐6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte–macrophage colony‐stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal‐resident microglia and the activity and recruitment of hematogenous macrophages. Stem Cells 2015;33:1902–1914
Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; ...hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date.
Background
Recurrent abdominal pain is a common and costly health‐care problem attributed, in part, to visceral hypersensitivity. Increasing evidence suggests that gut bacteria contribute to ...abdominal pain perception by modulating the microbiome‐gut‐brain axis. However, specific microbial signals remain poorly defined. γ‐aminobutyric acid (GABA) is a principal inhibitory neurotransmitter and a key regulator of abdominal and central pain perception from peripheral afferent neurons. Although gut bacteria are reported to produce GABA, it is not known whether the microbial‐derived neurotransmitter modulates abdominal pain.
Methods
To investigate the potential analgesic effects of microbial GABA, we performed daily oral administration of a specific Bifidobacterium strain (B. dentiumATCC 27678) in a rat fecal retention model of visceral hypersensitivity, and subsequently evaluated pain responses.
Key Results
We demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.
Conclusions & Inferences
The functional significance of microbial‐derived GABA was demonstrated by gadB‐dependent desensitization of colonic afferents in a murine model of visceral hypersensitivity. Visceral pain modulation represents another potential health benefit attributed to bifidobacteria and other GABA‐producing species of the intestinal microbiome. Targeting GABAergic signals along this microbiome‐gut‐brain axis represents a new approach for the treatment of abdominal pain.
Increasing evidence suggests that gut bacteria contribute to abdominal pain perception by modulating the microbiome‐gut‐brain axis. Here, we demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.
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