Chronic smoke exposure is associated with autophagy in murine Peyer's patches

INTRODUCTION: Cigarette smoke causes oxidative stress, leading to smoke-induced autophagy in several organs. Autophagy is a homeostatic process regulating the turnover of proteins and cytoplasmatic organelles. However, recently it has also been associated with many autoimmune and inflammatory disorders, among which Crohn’s disease. The purpose of the present study was to investigate whether cigarette smoke exposure is associated with increased autophagy in Peyer’s patches and its epithelium. AIMS & METHODS: C57BL/6 mice were exposed to cigarette smoke or air. After 24 weeks, the animals were sacrificied and Peyer’s patches were collected. m RNA expression of autophagy-related genes was determined by RT-PCR. Transmission electron microscopy (TEM) was used to evaluate the presence of autophagic vesicles in the follicleassociated epithelium of Peyer’s patches. RESULTS: Expression of Beclin-1, a protein involved in the nucleation of autophagosomes, and of Atg5 and Atg7, which both play a role in the autophagosome vesicle elongation and completion, increased after chronic smoke exposure. Furthermore, electron microscopy of the follicle-associated epithelium demonstrated that the mean area of autophagic vesicles per epithelial cell increased considerably from 1.1 μm2 ± 0.4 μm2 in the air group to 2.4 μm2 ± 0.4 μm2 in the smoke group (p < 0.05). Epithelial cells had a significantly higher number of autophagic vesicles after smoke exposure (1.1 ± 0.1 after smoke exposure versus 0.5 ± 0.1 vesicles per cell after air exposure, p < 0.05), but the size of the vesicles did not differ between both groups. CONCLUSION: Here we provide the first evidence that chronic exposure to cigarette smoke is associated with autophagy in murine Peyer’s patches, and more in particular in the follicle-associated epithelium covering Peyer’s patches. Our findings can help to understand the role of smoking in the pathogenesis of inflammatory bowel disease, such as Crohn’s disease

The influence of dairy consumption, sedentary behaviour and physical activity on bone mass in Flemish children : a cross-sectional study

Background: This cross-sectional study aimed to look for an association in young children between whole body bone mineral content (BMC) and areal bone mineral density (aBMD) and dairy consumption as well as sedentary behaviour (SB) and physical activity (PA). Moreover, we investigated whether there was an interaction effect between dairy consumption and SB or PA on BMC and aBMD. Methods: Healthy children (6-12 years) were recruited from primary schools. Body composition and whole body bone mass were measured with dual-energy X-ray absorptiometry (DXA), dairy consumption was assessed with a food frequency questionnaire (FFQ) and PA and SB with an accelerometer. In total, 272 children underwent a DXA scan. Complete FFQ data were available for 264 children and 210 children had matching data from accelerometry recordings. Regression analyses were used to study the associations between (1) BMC and aBMD and (2) dairy consumption, SB and PA, adjusting for age, gender, pubertal stage, height and body composition. Results: Dairy consumption was positively associated with whole body BMC and aBMD (absolute value as well as z-score), after correction for relevant confounders. SB was negatively associated with aBMD z-score and light PA was positively associated with both BMC and aBMD z-score. No gender differences were found. Moreover, an interaction effect between vigorous PA (VPA) and dairy consumption on aBMD (z-score) and BMC z-score was found, indicating that children with both high VPA and high dairy consumption had higher values for BMC and aBMD of the whole body minus the head. Conclusion: Already at young age, PA and dairy consumption positively influence whole body bone mass assessed by DXA. Moreover, this study indicates clearly that SB is negatively associated with whole body bone density. Promoting regular PA and sufficient dairy consumption in young children and limiting SB can be expected to positively influence their bone mass accumulation, which can help in the prevention of osteoporosis later in life

Translational research into the effects of cigarette smoke on inflammatory mediators and epithelial TRPV1 in Crohn’s disease

Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increasedIL-8transcription in ileum of controls (p < 0,001; n = 18-20/group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p <0,001; n = 20/group). In the colon, TRPV1 mRNA levels were decreased (p = 0,046) in smoking healthy controls (n = 20/group). Likewise, healthy mice chronically exposed to cigarette smoke (n = 10/group) showed elevated ilealCxcl2(p = 0,0075) and colonicKcmRNA levels (p = 0,0186), whereas TRPV1 mRNA and protein levels were elevated in the ileum (p = 0,0315). Although cigarette smoke exposure prior to trinitrobenzene sulphonic acid administration did not alter disease activity, increased pro-inflammatory cytokine production was observed in the distal colon (Kc: p = 0,0273; Cxcl2: p = 0,104; Il1-beta: p = 0,0796), in parallel with the increase ofTrpv1mRNA (p < 0,001). We infer that CS affects pro-inflammatory cytokine expression in healthy and inflamed gut, and that the simultaneous modulation of TRPV1 may point to a potential involvement of TRPV1 in cigarette smoke-induced production of inflammatory mediators

CEP5 and XIP1/CEPR1 regulate lateral root initiation in Arabidopsis

Roots explore the soil for water and nutrients through the continuous production of lateral roots. Lateral roots are formed at regular distances in a steadily elongating organ, but how future sites for lateral root formation become established is not yet understood. Here, we identified C-TERMINALLY ENCODED PEPTIDE 5 (CEP5) as a novel, auxin-repressed and phloem pole-expressed signal assisting in the formation of lateral roots. In addition, based on genetic and expression data, we found evidence for the involvement of its proposed receptor, XYLEM INTERMIXED WITH PHLOEM 1 (XIP1)/CEP RECEPTOR 1 (CEPR1), during the process of lateral root initiation. In conclusion, we report here on the existence of a peptide ligand−receptor kinase interaction that impacts lateral root initiation. Our results represent an important step towards the understanding of the cellular communication implicated in the early phases of lateral root formation

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

The xerobranching response represses lateral root formation when roots are not in contact with water

Efficient soil exploration by roots represents an important target for crop improvement and food security [1, 2]. Lateral root (LR) formation is a key trait for optimising soil foraging for crucial resources such as water and nutrients. Here, we report an adaptive response termed xerobranching, exhibited by cereal roots, that represses branching when root tips are not in contact with wet soil. Non-invasive X-ray microCT imaging revealed that cereal roots rapidly repress LR formation as they enter an air space within a soil profile and are no longer in contact with water. Transcript profiling of cereal root tips revealed that transient water deficit triggers the abscisic acid (ABA) response pathway. In agreement with this, exogenous ABA treatment can mimic repression of LR formation under transient water deficit. Genetic analysis in Arabidopsis revealed that ABA repression of LR formation requires the PYR/PYL/RCAR-dependent signalling pathway. Our findings suggest that ABA acts as the key signal regulating xerobranching. We conclude that this new ABA-dependent adaptive mechanism allows roots to rapidly respond to changes in water availability in their local micro-environment and to use internal resources efficiently

Hamstring muscles: Architecture and innervation

Knowledge of the anatomical organization of the hamstring muscles is necessary to understand their functions, and to assist in the development of accurate clinical and biomechanical models. The hamstring muscles were examined by dissection in six embalmed human lower limbs with the purpose of clarifying their gross morphology. In addition to obtaining evidence for or against anatomical partitioning ( as based on muscle architecture and pattern of innervation), data pertaining to architectural parameters such as fascicular length, volume, physiological cross-sectional area, and tendon length were collected. For each muscle, relatively consistent patterns of innervation were identified between specimens, and each was unique with respect to anatomical organization. On the basis of muscle architecture, three regions were identified within semimembranosus. However, this was not completely congruent with the pattern of innervation, as a primary nerve branch supplied only two regions, with the third region receiving a secondary branch. Semitendinosus comprised two distinct partitions arranged in series that were divided by a tendinous inscription. A singular muscle nerve or a primary nerve branch innervated each partition. In the biceps femoris long head the two regions were supplied via a primary nerve branch which divided into two primary branches or split into a series of branches. Being the only muscle to cross a single joint, biceps femoris short head consisted of two distinct regions demarcated by fiber direction, with each innervated by a separate muscle nerve. Architecturally, each muscle differed with respect to parameters such as physiological cross-sectional area, fascicular length and volume, but generally all partitions within an individual muscle were similar in fascicular length. The long proximal and distal tendons of these muscles extended into the muscle bellies thereby forming elongated musculotendinous junctions. Copyright (C) 2005 S. Karger AG, Basel

The CEP5 Peptide Promotes Abiotic Stress Tolerance, As Revealed by Quantitative Proteomics, and Attenuates the AUX/IAA Equilibrium in Arabidopsis.

Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-TERMINALLY ENCODED PEPTIDE 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical, and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance