I acknowledge all students, student teachers and expert teachers

I acknowledge all students, student teachers and expert teachers involved in the project: Nastassia Racenet, Carmen Page, Samuel Bellani, Nadine Sommer, Felix Stürner, Sigismond, Roduit, Claire Dumas, Aurélia Mercier, Selleck ABT-737 Laetitia Cuccuru Biasse, Joëlle Schreiber-Orso, Stéphanie Bocion, Catherine Veuthey. “
“La didactique s’est constituée initialement en s’appuyant sur d’autres champs en sciences humaines (psychologie du développement, psychologie sociale, sociologie, anthropologie, épistémologie, philosophie…) avant d’essayer de se constituer comme une discipline spécifique. Les didactiques se sont construites sur des questions d’apprentissage disciplinaire

qui en ont déterminé leur spécificité et leur structuration. Les courants actuels en France relèvent d’ancrages théoriques plus ou moins homogènes et ont produit des notions ou concepts différents ou complémentaires en partageant des principes constructivistes et socio-constructivistes. On peut observer des hybridations entre les courants1. Les recherches en didactique

ont démarré en mathématiques, puis les didactiques des sciences se sont développées autour des associations ou groupes de chercheurs tant nationaux (ARDIST2) qu’européens (ERIDOB3, ESERA4) ou mondiaux (NARST5, AERA6, ASERA7). A partir des années 80, les travaux fondateurs de Chevallard (1985), notamment avec la notion de transposition http://www.selleckchem.com/products/ly2157299.html didactique, ont initié la Théorie Anthropologique du Didactique (TAD) et l’on doit la théorie dite des situations à Brousseau (1998). En prolongement de ces cadres, Mercier et al. (2002), Sensevy (2007) ont développé la Théorie de

l’Action Conjointe en Didactique (TACD) sur laquelle se sont fondés des travaux en didactique comparée. Parallèlement la didactique professionnelle a émergé à partir des travaux de Pastré (1999), inspiré par Vergnaud (l994), lui-même disciple de Piaget, et qui s,est également intéressé à l,enseignement des mathématiques dès les années 70. Des travaux en didactiques des sciences (biologie, physique-chimie) et des techniques se sont appuyés sur ces courants Fossariinae nés en didactique des mathématiques, d׳autres se sont davantage inspirés de la psychologie sociale (Giordan et al., 1994 and Astolfi and Develay, 1989), d’autres ont pris le parti de développer une didactique curriculaire (Lebeaume, 1999), tandis que d’autres se sont fondés sur une approche bachelardienne en développant le courant de la problématisation (Orange, 1997 and Fleury and Fabre, 2005). Nous situerons dans cet article ces différents courants ainsi que le courant de la didactique des Questions Socialement Vives (QSV) auquel nous contribuons et les filiations qui l’ont enrichi au niveau national et international (Fig. 1).

They observed that different provinces harbored distinct flavobac

They observed that different provinces harbored distinct flavobacterial communities which displayed distinct niches and different lifestyle strategies, revealing basin scale taxonomy and trait biogeographic patterns. Tanespimycin This highlights another factor complicating marine microbial biogeography: specific biogeographical patterns may emerge at some scales but not others. Indeed the geographic distribution of samples collected (e.g. micro, local, regional, basin, global),

the number of samples examined and the depth of interrogation (e.g. number of sequences obtained per samples) may determine which patterns are revealed, and this effect is particularly pronounced for taxa belonging to the rare biosphere (Woodcock et al., 2006 and Zinger et al., 2014). It has been shown that much of the microbial diversity

in the marine system can be determined present at a single given site if enough sequences are examined (Gibbons et al., 2013) so biogeographic patterns may be the result of “shallow” sequencing. However, determination of presence should not negate the importance of patterns in the abundance of microorganisms, especially the relative Fulvestrant abundance of different ecotypes within a given taxa. Hence, the taxonomic scale of sampling is a critical component to consider. To date, most microbial biogeography studies rely on comparison of 16S rRNA gene sequences. Due to a lack of a consensus model for what constitutes a bacterial species, patterns are derived from comparison of operational taxonomic units (OTU’s) (e.g. Schloss and Handelsman, 2005). Using next generation sequencing technology these OTU’s are generally based on sequence similarity of a small variable region of the ribosomal operon (e.g. Caporaso et al., 2012a). What

divergence in these variable regions means in terms of historically defined 97% 16S rRNA gene sequence similarity or 70% DNA/DNA hybridization (Stakebrandt and Goebel, 1994), or in terms of organismal GBA3 ecology (e.g. Eren et al., 2013), is rarely considered. For example, Synechococcus clades IV and III which proliferate under distinctly different oceanic conditions (temperate versus subtropical oligotrophic oceans respectively, discussed below) cannot be resolved on the basis of the V6 hypervariable region of the SSU rRNA gene ( Post et al., 2011). Moreover, there can be much phylogenetic and ecological heterogeneity obscured within OTU’s, even those that are highly stringent ( Brown et al., 2009 and Koeppel and Wu, 2013). Some of this heterogeneity may be resolved using higher resolution molecular markers such as the internal transcribed spacer region (e.g. Brown et al., 2012), while some requires whole genome sequencing to unmask. For instance, in the marine Synechococcus clade III, genes found on genomic islands ( Dufresne et al.

The surprisal   (or ‘self information’) of

the outcome of

The surprisal   (or ‘self information’) of

the outcome of a random variable is defined as the negative logarithm of the outcome’s probability, which in this case is the probability of the actual next word wt+1wt+1 given the sentence so far: equation(1) surprisal(wt+1)=-logP(wt+1|w1…t),where the base of the logarithm forms an arbitrary scaling factor (we use base-e). Informally, the surprisal of a word can be viewed as a measure of the extent to which its occurrence was unexpected. The symbols w in Eq. (1) do not need to stand for actual words. Instead, they may represent the words’ syntactic categories (i.e., their parts-of-speech; PoS), in which case Eq. (1) formalizes the unexpectedness of the encountered PoS www.selleckchem.com/products/pf-562271.html given the PoS-sequence corresponding to the sentence so far. This does away with any (lexical) semantics and may thereby reveal purely syntactic effects (cf. Frank & Bod, 2011). Several authors have put forth theoretical arguments for surprisal as a measure of cognitive processing effort or predictor of word reading time (Hale, 2001, Levy, 2008, Smith and Levy, 2008 and Smith and Levy, 2013) and it is indeed well established by now that reading times correlate positively with the surprisal of words (Fernandez Monsalve et al., 2012, Fossum and Levy, MS-275 price 2012, Frank, 2014, Frank and Thompson, 2012, Mitchell et al., 2010,

Roark et al., 2009 and Smith and Levy, 2013) as well as with the surprisal of parts-of-speech (Boston et al., 2008, Boston et al., 2011, Demberg and Keller, 2008 and Frank and Bod, 2011). A second important concept from information theory is entropy   ( Shannon, 1948), a measure of the uncertainty about the outcome of a random variable. For example, after

processing w1…tw1…t, the uncertainty about the remainder of the sentence is quantified by the entropy of the distribution of probabilities over the possible continuations wt+1…kwt+1…k (with k>tk>t). This entropy www.selleck.co.jp/products/Adrucil(Fluorouracil).html is defined as equation(2) H(Wt+1…k)=-∑wt+1…kP(wt+1…k|w1…t)logP(wt+1…k|w1…t),where Wt+1…kWt+1…k is a random variable with the particular sentence continuations wt+1…kwt+1…k as its possible outcomes. When the next word or part-of-speech, wt+1wt+1, is encountered, this will usually decrease the uncertainty about the rest of the sentence, that is, H(Wt+2…k)H(Wt+2…k) is generally smaller than H(Wt+1…k)H(Wt+1…k). The difference between the two is the entropy reduction  , which will be denoted ΔHΔH. Entropy is strongly reduced when moving from a situation in which there exists many possible, low-probability continuations to one in which there are few, high-probability continuations. Informally, entropy reduction can be said to quantify how much ambiguity is resolved by the current word or PoS, at least, to the extent that disambiguation reduces the number of possible sentence continuations.

Por sua vez, a administração de contraste endovenoso (hexafluoret

Por sua vez, a administração de contraste endovenoso (hexafluoreto de enxofre,

Sonovue®) ( fig. 1) permite analisar o padrão de microvascularização das lesões. O ADC tem uma aparência hipovascular, contrariamente aos TNE e às lesões de pancreatite crónica e autoimune, que têm aparência hiper ou isovascular 33. O achado de uma massa hipocaptante exibe uma sensibilidade de 94% e especificidade de 89% no diagnóstico de ADC do pâncreas 34. A análise quantitativa da captação de contraste pode vir a aumentar a acuidade da técnica, particularmente no diagnóstico diferencial entre ADC e pancreatite crónica 34. Outras aplicações possíveis dos agentes de contraste incluem a avaliação das estruturas vasculares perilesionais, permitindo melhorar click here a acuidade da EE no estadiamento T, e a deteção de lesões de pequenas dimensões não identificadas por EE em modo B, particularmente nos doentes com pancreatite crónica

ou com próteses biliares. Embora não possam substituir a PAAF-EE, estas 2 modalidades podem contribuir para a tomada de decisões IWR-1 clínicas na abordagem de casos com cito-histologia negativa para malignidade e podem ser utilizadas para guiar e potenciar os resultados da PAAF–EE de lesões pancreáticas e de gânglios linfáticos, permitindo selecionar as áreas suspeitas a puncionar 35 and 36. O ADC compreende 90% das neoplasias sólidas do pâncreas. Localiza-se mais frequentemente na região cefálica. O aspeto ecomorfológico mais representativo deste tumor é o de uma massa heterogénea, hipoecóica e com margens irregulares (fig. 2), tendo como achados preditivos a dilatação do ducto pancreático principal e a presença de um halo hipoecóico periductal (sinal hipoecóico periductal)37. Dada a elevada sensibilidade da angio–TC na avaliação da invasão arterial, a EE deve ter o papel de confirmar o grau de envolvimento vascular já determinado por este método de imagem, após exclusão de metastização à distância38. Os tumores irressecáveis ou borderline ressectable podem ser incluídos em protocolos de terapêutica

Forskolin mouse neoadjuvante em validação e com diferentes finalidades 39. Nestes casos é mandatório o diagnóstico cito-histopatológico prévio obtido por PAAF-EE. Igualmente, a presença de linfadenopatias malignas pode justificar a realização de terapêutica neoadjuvante. As características ecomorfológicas dos gânglios linfáticos associadas a malignidade são a forma arredondada, dimensão superior a 5 mm, ecotextura hipoecóica e margens bem definidas. Quando presentes em conjunto, apresentam uma acuidade diagnóstica de 80%, o que ocorre em apenas 25% dos gânglios malignos, podendo ser necessário recorrer à PAAF para confirmação cito-histológica 37. A EE possibilita, também, a identificação e punção de bolsas de efusões peritoneais e pleurais, lesões nodulares hepáticas e adenopatias à distância.

Shewanella putrefaciens and Pseudomonas fluorescens have long bee

Shewanella putrefaciens and Pseudomonas fluorescens have long been associated with the spoilage of raw fish and its presence is characterised by ammoniacal, spoilt and hydrogen sulphide-type odours ( Whitifield, 2003). Simultaneously, metallic odours in the skin were perceptible, probably due to, among other factors, lipid oxidation, commonly associated with odours at this degradation phase (Ashton, 2002, chap. 14; Undeland & Lingnert, 1999). During the later stages, lipid oxidation occurred, presumptively initiated

by the presence of reactive oxygen species generated by autolytic reactions and products of microbiological growth. Taking into consideration all sensory data, rejection was found to occur on day 12–13 in ice, mainly due to the presence of unpleasant odours in skin and gills. According to Barbosa, Bremner & Vaz-Pires (2002, chap. buy GSK2118436 11) the total see more bacterial count just after catch is variable between 101 and 104 cfu/g or cm2 but, at the time of sensorial rejection, it can be as high as 106 or 107 cfu/g or/cm2, levels which are in accordance with the counts of microorganisms obtained in the present work. If we consider the values suggested by these authors as rejection indicators, the results of sensory aspects are confirmed, since on day 12 of ice storage the

values from microbiological analyses were 106 cfu/cm2 for H2S-producing bacteria and 107 cfu/cm2 for Pseudomonas and TVC. Dalgaard (2000, p. 31) reported that different QIM schemes provide different scores at the end of product shelf-life; however, this drawback is reduced by expressing the sensory score in relation to the maximum number of demerit points used for the scheme. Pearson correlation and linear regression were significant between the QI and storage time, while the three best-fit equations were coincidental (Table 3). The quality index of whole raw blackspot seabream during ice storage can be seen in Fig. 3. In Table 4 one can observe that a significant Pearson correlation and a linear regression between the Torrymeter values and the time of ice storage was found in three experiments. The best

linear equations for the three experiments are coincident, Bumetanide having the same intercept and slope. Considering all data, the equation as well as the slope and intercept are also coincident with data from the three experiments. The values of Torrymeter measurements were interpreted as follows: Absolutely fresh fish is given a score of 10; good quality fish receives a score of 6 or more, while scores below 4 indicates fish unfit for consumption (Distell, 2007, p. 87). Torrymeter values of whole raw blackspot seabream during ice storage are shown in Fig. 4. Considering the value 4 as limit, the moment of rejection occurs at around day 13. Once the rate of change in the spoilage indicators had been monitored, models were developed in which the measured parameters could be used to predict remaining storage life.

Os autores declaram que para esta investigação não se realizaram

Os autores declaram que para esta investigação não se realizaram experiências em seres humanos e/ou animais. Os autores declaram ter seguido os protocolos de seu centro de trabalho acerca da publicação dos dados de pacientes e que todos os pacientes incluídos no estudo receberam informações suficientes e deram o seu consentimento informado por escrito para participar nesse estudo. Os autores declaram ter

selleck compound recebido consentimento escrito dos pacientes e/ ou sujeitos mencionados no artigo. O autor para correspondência deve estar na posse deste documento. Os autores declaram não haver conflito de interesses. “
“A 74-year-old man attended our gastroenterology outpatient clinic with hipogastric aching pain for the past 5 years associated with recent worsening of chronic constipation. Physical examination as well as abdomino-pelvic ultrasound and colonoscopy was unremarkable. Anti-antispasmodics and dietary measures did not improve the clinical condition. For this reason, this website we performed an abdomino-pelvic computed tomography (CT) scan which showed thickening of the terminal ileum. The patient repeated colonoscopy with ileoscopy and regular hogback in the terminal ileum was observed that could not be overcome, lined by normal mucosa. It was biopsed, but histologic examination was normal. The entero-resonance was suggestive of nonspecific mesenteritis,

but did not reveal changes in small bowel. Serologies to Crohn’s disease and celiac disease were negative. A video capsule enteroscopy was performed which revealed diffuse pattern of linfagiectasia and segmental pseudopolypoid whitish areas in jejunum and ileum (Fig. 1). Through push enteroscopy (Fig. 2) with a pediatric colonoscope, biopsies of proximal jejunum were taken. Microscopic examination demonstrated neoplastic proliferation of lymphoid tissue with follicular pattern (Fig. 3). The tumor cells were positive for CD20, CD10, BCL2, BCL6 and negative for CD3, CD5, CD23, and 5 blasts per high power field were observed. Based on these findings, a diagnosis of follicular ADAM7 lymphoma grade 1 was established. After performing thoraco-abdomino-pelvic

CT scan and osteomedullar biopsy, the disease was classified at stage II2 (Lugano classification). He was referred to the Hematology Department, who adopted the “watch and wait” strategy. He is now in the sixth month of surveillance, without clinical worsening. Primary extranodal follicular lymphoma (FL) is uncommon, constituting less than 7% of GI tract lymphomas.1 The most common site in the small intestine is the duodenum followed by the ileum.2 FL of the gastrointestinal tract most frequently occurs in middle-aged adults with a slight female predominance (2:1).3 The clinical presentation of small intestinal lymphoma is non-specific and the patients may have symptoms such as abdominal pain, nausea, vomiting, and weight loss.

The results were expressed as hazard ratios and the corresponding

The results were expressed as hazard ratios and the corresponding 95% CIs. In addition to the relative mortality between Sirolimus the 2 FITs, the absolute mortality reduction for each FIT was estimated and compared with nonparticipants with the adjustment of self-selection bias.14 The following equation was applied: RRadjustedforself-selectionbias=Screeningrate(SR)×RRparticipants/uninvited+(1-SR)×RRnon-participants/uninvited The calculation is detailed

in Supplementary Tables 2–4. Because the stage and location of screen-detected and interval cancers are of clinical significance,15 a subsidiary analysis was performed and a comparison was made between the 2 tests using the χ2 test. Cancer was staged according to the American Joint Committee on Cancer 7th staging system.16 The colon above the level of the splenic flexure (including the splenic flexure) was defined as the proximal colon. When concurrent proximal and distal cancers were present, subjects were placed into the distal colon category. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). All P values were 2-sided and P < .05 was considered to indicate statistical significance. Between January 1, 2004 and December 31, 2009, selleck compound a total of 956,005 subjects underwent screening. Among them, 747,076 (78%) and

208,929 (22%) received the OC-Sensor and HM-Jack tests, respectively; their baseline data according to demographic characteristics, geography, and temperature, and characteristics of the confirmatory diagnosis are presented in Table 1. Small differences, which were statistically significant owing to the large sample size, were observed with respect to sex, follow-up time, confirmatory examination tool, colonoscopy adenoma detection rate, and colonoscopy advanced adenoma detection rate. Differences were more prominent in the geographic areas and the hospital levels where ADP ribosylation factor confirmatory diagnoses were performed. As shown in Table 2, positivity rates were similar between the 2 tests (3.8% vs 3.9%), but the confirmatory examination rate was higher for those who received

HM-Jack (80.9% vs 85.3%). As expected, positivity rates were higher for males and those of older age as compared with the total population group. These findings were unchanged regardless of adjustments for sex and age distributions (data not shown). The effect of ambient temperature on FIT positivity was also evaluated. For the temperature ranges of 10–14°C, 15–19°C, 20–24°C, and ≥25°C, the positivity rates for OC-Sensor were 5.6%, 4.4%, 3.9%, and 3.6%, respectively, and for HM-Jack were 5.5%, 3.8%, 4.7%, and 3.6%, respectively, revealing an inverse association (P < .001) between FIT positivity and ambient temperature. The OC-Sensor test detected CRC in 0.21% of patients, with a positive predictive value of 6.8%.

Hanahan and Weinberg [32] and [33] have proposed six biological h

Hanahan and Weinberg [32] and [33] have proposed six biological hallmarks necessary for tumor development, Overexpression of iNOS acts on three of these six

markers. This occurs when overexpressed iNOS interacts on two important molecular pathways, IKK/NF-kappaB and RAS/ERK. Activation of these pathways triggers the transcription of genes that control cell growth, angiogenesis, and inhibition of cell death [34] and [35]. Regarding the role eNOS in carcinoma, Decker et al. [36] demonstrated that eNOS overexpression was associated with fewer and smaller tumor lesions as well as increased animal survival. buy DAPT However, eNOS-/- knockout animals developed larger tumors and had worse survival. This vascular dysfunction in chronic liver disease is an important sign that precedes carcinoma [36]. After determination of proteins classically involved in chronic liver diseases, we assessed oxidative stress, by measuring the cytosolic concentration of TBARS and quantifying SOD activity. TBARS was already increased in the PL groups compared to controls. DEN is hydrolyzed in nitrosamine, AZD8055 supplier generating the ethyl radical, responsible for an

increase in intensification of oxidative stress. Many studies have linked oxidative stress to pathogenesis and disease prognosis [37], [38] and [39]. One of the key factors in carcinogenesis is an imbalance of the redox state, favoring the formation of several toxic products such as malondialdehyde and 4-hydroxynonenal, which can attack lipids, proteins and DNA, leading to carcinogenicity and mutagenicity [40] and [41]. In this study, SOD activity was reduced in advanced HCC, whereas increased in early HCC, signaling the presence of the superoxide anion. Similar results, showing increases in oxidative stress and reduction in SOD levels in animals with HCC have

been previously reported, indicating that the decrease of SOD activity intensifies with the disease progression [8] and [42]. In addition to SOD activity, NQO1 expression was also determined. While SOD activity was significantly reduced in animals with advanced HCC, NQO1 protein expression increased significantly. Most solid tumors express for high levels of NQO1 [43], and biochemical studies have shown that NQO1 is induced by numerous chemicals, including polycyclic aromatic hydrocarbons and azo dyes. Two regulatory elements responsible for the NQO1 gene are the antioxidant response element (ARE) and the xenobiotic response element (XRE) [44]. According to Venugopal and Jaiswal [45] an increase in NQO1 expression occurs in response to the generation of ROS caused by inflammation or xenobiotic exposure. Conversely, precancerous lesions showed augmented SOD activity with no increase in NOQ1 protein expression. These findings suggest that NQO1 acts directly as a superoxide anion scavenger, although less efficiently than SOD [46].

, 1998) Lactobacillus

paracasei subsp paracasei NTU 101

, 1998). Lactobacillus

paracasei subsp. paracasei NTU 101 was isolated from human feces, and it is resistant to gastric juice and bile salt in the natural environment ( Lin et al., 2004). It also has probiotic characteristics that are effective in reducing cholesterol in blood and in the liver ( Chiu et al., 2006). L. paracasei subsp. paracasei NTU 101 can upregulate the antigen-presenting ability of dendritic cells and expression of natural killer group 2 D molecules capable of triggering natural killer cell-mediated cytotoxicity in BALB/c mice ( Tsai et al., 2008). Hydrolysates of L. paracasei subsp. paracasei NTU 101 can induce proliferation of macrophages and splenocytes and a release of the cytokines IL-10 and IL-12 that modulate the innate and adaptive immunity buy Ceritinib and an inflammatory response ( Chiang et al., 2012a). Soy skim milk fermented by L. paracasei subsp. paracasei NTU 101 (NTU 101F milk), with or without

a Momordica charantia supplement, is effective at preventing and retarding hyperlipidemia-induced oxidative stress and atherosclerosis in hyperlipidemic hamsters ( Tsai et al., 2009). This type of milk is also useful for prevention of acute gastric ulcers induced by pylorus ligation and acidified ethanol (via prostaglandin E2), and it significantly enhances superoxide dismutase (SOD) activity ( Liu et al., 2009). Moreover, NTU 101F milk can attenuate bone loss in ovariectomized (OVX) mice ( Chiang and Pan, 2011) and aging-induced bone loss in BALB/c mice and can Endonuclease lower the risk of osteoporosis ( Chiang et al., 2012b). In addition, NTU 101F milk can upregulate and PF-562271 mw downregulate lipolysis and

heparin-releasable lipoprotein lipase, respectively, in 3T3-L1 cells and can reduce obesity in Wistar rats fed a high-fat diet ( Lee et al., 2013). Taken together, the above data show that intake of cultured probiotic L. paracasei subsp. paracasei NTU 101 is likely to have various beneficial effects on the health of humans and animals. Hence, the safety of L. paracasei subsp. paracasei NTU 101 must be evaluated. Accordingly, the aim of this study was to assess the possible genotoxicity and mutagenicity of Vigiis 101 powder made from L. paracasei subsp. paracasei NTU 101. In addition, we performed a 28-day oral toxicity assay in Wistar rats. Sodium azide, benzo[α]pyrene, mitomycin C, 2-aminofluorene, 2-amino-anthracene, 4-nitro-o-phenylenediamine, 9-aminoacridine, acridine orange, and cyclophosphamide monohydrate were purchased from Sigma (St. Louis, MO, USA). The main media, including McCoy’s 5A medium with 10% fetal bovine serum and penicillin-streptomycin solution, minimal glucose agar plates, master plates, soft agar, and nutrient broth, were obtained from Biological Industries (Kibbutz Beit-HaEmek, North District, Israel). The probiotic used in this study was Vigiis 101 (SunWay Biotecn Co., Ltd., Taipei, Taiwan). Vigiis 101 is a dry powder which contains 6 billion bacteria of L.

It remains to be determined whether other anabolic therapies besi

It remains to be determined whether other anabolic therapies besides mechanical loading, when used in conjunction Saracatinib order with an anti-resorptive agent, have a negative, additive or synergistic effect on the skeleton. Clinical evidence has shown that there can be a negative interaction between alendronate and intermittent parathyroid hormone, the only anabolic drug currently licensed for osteoporosis treatment [47] and [48]. This interaction seems to be less for risedronate than alendronate [49] and [50].

On the other hand, mechanical loading in rodents has been shown to suppress sclerostin expression in osteocytes [39] and [51], and sclerostin neutralizing monoclonal www.selleckchem.com/products/byl719.html antibody also increases bone formation independently of bone resorption in humans as well as rats [52] and [53]. Further elucidation of the osteogenic pathways induced by mechanical loading will therefore offer the potential for developing potent anabolic approaches which can act independently of bone resorption. In conclusion, mechanical loading-related increases in both trabecular and cortical bone mass are not reduced by even high doses of risedronate in almost skeletally mature female mice. This experimental evidence suggests that osteogenic exercise can have beneficial effects on bone health independently of those derived

from the anti-resorptive effects of bisphosphonates in patients with osteoporosis. This study was supported by the Wellcome Trust and Warner Chilcott (Ireland) Ltd. Lee Meakin and Gabriel Galea are recipients of Integrated Training Fellowships for Veterinarians from the Wellcome Trust. “
“Bone mass and architecture are thought to adapt to be appropriate for the mechanical loading they experience by a mechanism in which load-induced strains, within the bone tissue, influence resident bone cells to control modelling and remodelling to achieve and maintain

target levels of strain. The mechanism(s) by which resident bone cells respond to their strain environment is complex and involves the activation Resveratrol of a number of signalling pathways including the canonical Wnt pathway, prostaglandins, nitric oxide, extracellular signal-related kinases and oestrogen receptor-α [1], [2], [3], [4], [5] and [6]. The involvement of the Wnt pathway in strain-related regulation of bone architecture was predicted from the discovery that two unrelated families of Caucasian origin, with bones of essentially normal appearance but BMD z scores ranging from 4 to 7, had an autosomal dominant mutation mapped to the gene for the low-density lipoprotein receptor-related protein 5 (Lrp5) [7] and [8]. It is through the Lrp5/Frizzled co-receptor that extracellular Wnts activate the Wnt pathway.