Temporal instability of climate signal in tree-ring width of the five dominant species (Pinus nigra, P. sylvestris, P. uncinata, Abies alba, Fagus sylvatica) growing under Mediterranean mountainous ...climate was studied over the last century (1910–2004). To disentangle the tree–climate–site complex, the effects of both soil water availability (SWA) (dry, mesic and humid sites) and altitude (from 430 to 1,690 m) were investigated on the response patterns. Responses to climate were analysed using bootstrapped correlation coefficients from 17 ring-width chronologies built from 293 trees sampled in 64 stands in South-Eastern France. Temporal analyses were performed considering forty-six 50-years intervals (from 1910–1959 to 1955–2004). May–June drought was the primary limiting factor. For P. sylvestris, summer precipitation also played a key role. F. sylvatica was the less responding species with no clear common pattern. Low SWA led to an increasing correlation with precipitation in May for P. nigra and A. alba. Precipitation from May to August prevailed on the driest conditions for P. sylvestris. Correlation analyses suggested that warm autumn or winter enhanced growth, except for F. sylvatica. For P. nigra, the importance of April temperature increased with increasing altitude. Temporal analyses revealed a stability of sensitivity for the highest contexts (P. uncinata and F. sylvatica). At lower altitudes, the correlation with minimum temperature in April increased while temperature more often exceeded the threshold of 0°C over the last decades. For precipitation, a decrease in the strength of correlation was observed without close relationships with local xericity.
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic ...acid–Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3–96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.
Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic ...precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarry-based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of 3 Hthymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth.
BAFF (B-cell–activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome ...(pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7 RNA was reengineered to deliver antisense sequences targeting BAFF splice regions. A major decrease of BAFF messenger RNA (mRNA) and protein secretion, concomitantly with the increase of ΔBAFF mRNA, was observed in vitro. In vivo, SG retrograd instillation of nonobese diabetic mice by the modified U7 cloned into an adeno-associated virus vector significantly decreased BAFF protein expression and lymphocytic infiltrates and improved salivary flow. This study offers a rationale for localized therapeutic BAFF inhibition in pSS and represents a proof of concept of the interest of exon skipping in autoimmune diseases.
Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report that VGLUT1 and VGLUT2, two subtypes of vesicular glutamate ...transporters, are expressed in rat spinal motoneurons. Both proteins are present in somato‐dendritic compartments as well as in axon terminals in primary cultures of immunopurified motoneurons and sections of spinal cord from adult rat. However, VGLUT1 and VGLUT2 are not found at neuromuscular junctions of skeletal muscles. After intracellular injection of biocytin in motoneurons, VGLUT2 is observed in anterogradely labelled terminals contacting Renshaw inhibitory interneurons. These VGLUT2‐ and VGLUT1‐positive terminals do not express VAChT, the vesicular acetylcholine transporter. Overall, our study establishes for the first time that (i) mammalian spinal motoneurons express vesicular glutamate transporters, (ii) these motoneurons have the potential to release glutamate (in addition to acetylcholine) at terminals contacting Renshaw cells, and finally (iii) the VGLUTs are not present at neuromuscular synapses of skeletal muscles.
Breakdown of the blood–brain barrier (BBB) and ensuing gliosis are common events following physical trauma to the central nervous system (CNS) or during autoimmune diseases such as experimental ...allergic encephalomyelitis (EAE). Some studies of EAE in rodents report that peripheral injections of complete Freund's adjuvant (CFA), which contains heat-inactivated Mycobacterium to provoke peripheral inflammation without adversely affecting the CNS, can itself lead to increased BBB permeability to small tracer molecules and certain serum proteins. To study the equivocal relationship between serum protein extravasation and reactive gliosis, we injected C57BL/6 mice with CFA and histologically assessed the permeability of various serum proteins and the reactivity of proximal microglia and astrocytes in the uninjured brainstem and spinal cord enlargements after 1–4 weeks. Our results confirm that CFA injections induce progressive increases in the perivascular extravasation of serum IgG, albumin, IgM, and exogenous horseradish peroxidase, all to varying degrees, most prominently in the brainstem and cervical spinal cord after 2–3 weeks. More importantly, neither microglial cells nor astrocytes in regions of focal serum protein leakage appeared morphologically reactive based on immunoreactivity for CR3 receptors (Mac-1) or glial fibrillary acidic protein (GFAP), respectively. Because we found no evidence of T cell infiltration accompanying the exudates, our results indicate that in the absence of physical trauma or inflammatory cells resident CNS neuroglia remain quiescent upon exposure to extravasated serum proteins.
Background: Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor‐β1 (TGF‐β1) plays an important ...role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF‐β1.
Methods: Basal, mucus, and ciliated cells were characterized by cytokeratin‐14, MUC5AC, and βIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF‐β1 supplementation. Using RT‐PCR, the effects of TGF‐β1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated.
Results: In situ, high TGF‐β1 expression was associated with low MUC5AC and βIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin‐14 expression was strong and decreased with time, while βIV tubulin expression increased. Transforming growth factor‐β1 supplementation downregulated MUC5AC and βIV tubulin expression as well as MUC5AC and DNAI1 transcripts.
Conclusion: After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF‐β1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.
The landscapes currently studied in ecology are either “discontinuous” (category-based or patch-based), as in the case of mosaics of agricultural units, or of more “continuous” type (raster ...lattices), as used for representing elevation or other ecological gradients. The main landscape models either involve explicit processes or are neutral, recreating spatial patterns in the absence of studied processes (using statistical rules). This article presents neutral models suitable for the creation and handling of patchy landscapes. These models (Patchy Landscape Neutral Models) adapt the Gibbs process already used successfully in forestry and biology to describe the local interactions between landscape units. These interactions can be either ecological, if justified, for example, by natural mechanisms of dispersal (plant species dynamics), or crop successions in anthropized landscapes, or statistical (geometrical). We define a global “cost function” representative of the landscape to be simulated by summing the “pair function” that expresses the interactions between units for the whole landscape. This generic approach makes it possible to reconstruct different kinds of patchy landscape compositions (land cover) and opens the way to study changes in landscape configuration (unit arrangements) as well as an analytical description of landscapes.
Objective To determine whether muscle precursor cells (MPCs) harvested from limb skeletal muscle can enhance the regeneration process of the striated urethral sphincter after injury.
Material and ...methods Striated urethral sphincters of male mice were injured by an injection of a myotoxic substance (notexin). In the experimental group, 2 days after injury, MPCs were enzymatically harvested from striated muscles of the lower limbs and labelled with PKH 26, then immediately re‐injected into the injured urethral sphincter of the same animal. In the control group, saline buffer was injected instead of MPCs. Animals were killed 7 days or 1 month after injury and the sphincters removed for histological study (the presence of PKH 26‐labelled myofibres, measurement of myofibre diameter and total number of myofibres).
Results MPC autografting accelerated sphincter muscle repair, as shown by a higher myofibre diameter (P = 0.03) and number (P = 0.01) in the experimental group than in the controls at 7 days. One month after their injection MPCs were still detectable in the regenerating sphincters and participated in the formation of new myofibres.
Conclusion This study provides the experimental basis for a new therapeutic approach to urethral sphincter insufficiency after surgical or obstetrical injury, based on MPC autografting.
This study was an epidemiological questionnaire survey of a representative sample of the French population that included 12 778 individuals and in which adapted DSM‐IV criteria for the definition of ...insomnia were used. Our goals were not only to assess the prevalence of ‘insomnia’ using these criteria, but also to compare the results obtained with those of prior studies using different definitions of ‘insomnia’. The aim of this study was also to identify where areas of agreement and disaggreement existed, as we believe that it is important to emphasize these points because DSM‐IV recommendations are supposedly reflected in clinical practice. Seventy‐three per cent of the individuals surveyed complained of a nocturnal sleep problem, but only 29% reported at least one sleep problem three times per week for a month, and 19% (2428 subjects) had at least one sleep problem three times per week for a month and complained of daytime consequences (DSM‐IV criteria). Only 9% had two or more nocturnal sleep problems with daytime consequences and were classified as ‘severe insomniacs’. Our study indicates that if DSM‐IV criteria are used, the diagnosis of ‘insomnia’ is lower than in other epidemiological studies. The DSM criteria have an advantage in that they emphasize the daytime consequences of nocturnal sleep disturbances, which seem to be responsible for the most important socio‐economic costs of the problem.
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