NCube/papyrus huggingface dataset:
Early growth response protein 1 (Egr-1) expression by Insulin-like growth factor 1 (IGF-1) involves MAPKs and PKB pathways

Aberrant vascular remodelling underlies the pathogenesis of major cardiovascular diseases (CVD), such as atherosclerosis and hypertension. Abnormal growth, migration and proliferation of vascular smooth muscle cells (VSMC) are believed to play a critical role in vascular remodelling. IGF-1, potent mitogen, is believed to contribute to the development of CVD through the hyperactivation of proliferative and growth promoting pathways including mitogen-activated protein kinase (MAPK) and protein kinase B (PKB) pathways. It has also been implicated in modulating the expression of multiple transcription factors, including the early growth response protein-1 (Egr-1). Egr-1 upregulation has been observed in different models of vascular diseases implicating growth and redox signalling such as observed in response to IGF-1. However, modulation of Egr-1 expression by IGF-1 in VSMC, more specifically the signaling pathways involved in this process remain poorly characterized. Therefore, in the present studies, we investigated the implication of MAPK, PKB and ROS in IGF-1-induce Egr-1 expression in VSMC. IGF-1 induced a marked increase in Egr-1 protein level in a time and dose-dependent fashion. This increase was dose dependently inhibited by different pharmacological inhibitors targeting MAPK, PKB and reactive oxygen species (ROS) generation. Furthermore, pharmacological inhibitors of RNA and protein synthesis also attenuated IGF-1-induce response on Egr-1 expression. In conclusion, we showed that IGF-1 stimulates the expression of Egr-1 through ERK1/2/JNK and PI3K/PKB. We also propose that ROS generation plays an important role in this response. Overall, we propose a novel mechanism through which IGF-1 may exert its deleterious responses in vascular abnormalities.

Keyphrases: Egr-1, IGF-1, IGF-1R, ERK1/2, JNK, PKB, VSMC
Le diagnostic des tuméfactions latérales solides cervicales chez l'enfant

Introduction: Histological studies are often required to establish the etiology of solid lateral cervical masses (SLCM) in children since diagnostic tools are lacking accuracy. We evaluated the diagnostic tools available in order to develop a systematic and standardized diagnostic approach.   Methods: After etiologies and diagnostic tools were described, a review of the scientific literature on the topic was performed. A retrospective study between 2002 and 2012 of SLCM was conducted. A case report showing the feasibility of Fine Needle Aspiration (FNA) is presented. Finally, a decision algorithm integrating our results and the scientific opinion of an expert group is proposed.  Results: Differential diagnosis for SLCM is wide. The scientific literature regarding their diagnosis is weak, outdated and comparison is difficult. The 42 children studied had a median age of seven year old. They had inflammatory masses in 59% (26/44 biopsies) with mostly Atypical Mycobacteria (13/26), which has been shown to be difficult to confirm and often requires multiple diagnostic tests. The benefit of biopsy is questionable in 39% (17/44) of biopsies. Ultrasound-guided FNA appears to be a feasible technique and less invasive than biopsy. The algorithm proposes a standardized approach based on scientific facts that we want to evaluate through a prospective study.  Conclusion: SLCM in children represent a diagnostic challenge and the algorithm intends to guide the clinician’s diagnostic approach. A prospective study on the algorithm created is at its final step for acceptance through the CHU Sainte-Justine authorities.

Keyphrases: Diagnostic, Diagnosis, Surgical biopsy, Fine-needle aspiration, Neck mass, Child, Atypical Mycobacteria
Altération de l’interaction entre la PTH et LRP6 dans les ostéoblastes humains arthrosiques via DKK2

Osteoarthritis (OA) is characterized by loss of articular cartilage, bone sclerosis and synovial membrane inflammation. In vivo and in vitro studies indicate that the changes in bone tissue are responsible for the loss of articular cartilage. OA Osteoblasts (Ob) show a reduced response to parathyroid hormone (PTH), an important anabolic signal for bone tissue, versus normal Ob. The PTH receptor (PTH-R) interacts with LRP6, a receptor of Wnt ligands, and DKK antagonists block this interaction. Since DKK2 production is high in OA Ob whereas DKK2 is increased in normal Ob in response to TGF-β1, we propose that DKK2 alters the LRP6/PTH-R interaction, PTH-R recycling and inhibits the response to PTH. We used human OA and normal osteoblasts in primary culture. PTH-R, DKK2 and LRP6 expression were measured by RT-PCR. LRP6, PTH-R and DKK2 protein levels were determined by immunoblotting. Inhibition of DKK2 levels in OA Ob was performed by DKK2-siRNA, and cAMP production was measured by ELISA. The effect of TGF-β1 on DKK2, PTH-R and cAMP production was tested in osteosarcoma cells SaOS-2. In OA Ob, PTH-R and LRP6 mRNA levels were not changed following DKK2 siRNA treatment. However, PTH-R protein expression increased while that for LRP-6 remained unchanged after treatment with DKK2-siRNA. Compared to control, the distribution of PTH-R was higher in the membrane fraction and lower in the intracellular fraction in OA Ob following DKK2 inhibition. In contrast, LRP6 levels remained almost unchanged following these treatments. The results of the inhibition of the clathrin pathway by triflupromazin showed an increased expression of the PTH receptor in the membrane fraction that may be due to inhibition of their degradation by clathrin pathway. In OA Ob, DKK2 inhibition stimulated cAMP production in response to PTH. DKK2 induction by TGF-β1 in SaOS-2 cells, as assessed by qRT-PCR, caused the inhibition of PTH-R protein expression but not of LRP6. In addition, TGF-β1 treatment in SaOS-2 cells reduced cAMP production in response to PTH. These results demonstrate that high levels of DKK2 in OA Ob are responsible for the altered response to PTH. DKK2 antagonists decrease specifically PTH-R membrane display while they do not affect LRP6 recycling. These results suggest an altered cross-talk between LRP6 and PTH-R in OA Ob due to high levels of DKK2 in these cells.

Keyphrases: PTH-R, DKK2, LRP-6, Osteoarthritis, subchondral bone, osteoblast, Wnt signaling
The potential utility of age, triage score, and disposition data contained in emergency department electronic records for influenza-like illness surveillance in Montreal

Surveillance of influenza relies on a wide array of data, including emergency department based syndromic surveillance data. An increasing number of variables are recorded in emergency department electronic records and are available for surveillance. The main objective of this research is to evaluate the potential utility of age, triage scores, and disposition data for enhanced monitoring of the burden of severe influenza cases. Data from a subset of Montreal hospitals was used, from April 2006 to January 2011. Pneumonia and influenza hospitalizations were taken as a measure of the burden of severe influenza cases, and were modeled using a negative binomial regression approach, taking into account seasonal and secular trends. Age-, triage score-, and disposition-stratified influenza-like illness visits improved the fit of predictive models for pneumonia and influenza hospitalization, as compared to overall influenza-like illness visits. Before integration of these variables into the Montreal surveillance system, additional steps are suggested, including the optimization of an influenza-like illness syndrome definition, the confirmation of the value of these predictors using new data, and the evaluation of their practical utility.

Keyphrases: Influenza, Surveillance, Emergency department, Electronic records, Influenza-like illness, Public health, Syndromic surveillance
L’Office des Nations Unies contre la drogue et le crime et la lutte internationale contre la corruption : perceptions des professionnels

In addition to the social changes associated with the end of communism, the 1990s also marked a growing interest in corruption and its harmful effects on development. Due to pressure from the United States and the increasing visibility of corruption, several international organizations have seen the interest to get involved in the fight against corruption. Nevertheless, the literature supports that the United Nations Convention against Corruption represents the quintessential anti-corruption international document. Adopted in 2003, it now has 144 signatories. Despite the importance of the document, professionals’ perceptions remain hidden behind the institutional discourse. Therefore, this case study focuses on the perceptions of the employees working in the UNODC’s Corruption and Economic Crime Branch. They reveal several technical difficulties related to their work. Among others, professionals evoke workload, financial resources and consideration of their judgments during the evaluation process. Their functions are also limited by challenges associated with the implementation of the Convention: the absence of surveillance and sanctions mechanisms for non compliant countries, the access to data, the application of the Convention and the difference between working in the headquarters and working on the field. The professionals also mention some issues characterizing anticorruption international cooperation and the technical assistance provided to Member States.

Keyphrases: Corruption, CNUCC, Anticorruption, UNCAC, Fight against corruption, United Nations Convention against Corruption, UNODC, CEB, Corruption and Economic Crime Branch
Further characterization and determination of the single amino acid change in the tsI138 reovirus thermosensitive mutant

Many temperature-sensitive mutants have been isolated in early studies of mammalian reovirus. However, the bio- logical properties and nature of the genetic alterations remain incompletely explored for most of these mutants. The mutation harbored by the tsI138 mutant was already assigned to the L3 gene encoding the l1 protein. In the present study, this mu- tant was further studied as a possible tool to establish the role of the putative l1 enzymatic activities in viral multiplication. It was observed that synthesis of viral proteins is only marginally reduced, while it was difficult to recover viral particles at the nonpermissive temperature. A single nucleotide substitution resulting in an amino acid change was found; the position of this amino acid is consistent with a probable defect in assembly of the inner capsid at the nonpermissive temperature.

Keyphrases: reovirus, virus
The Hygiene Hypothesis and the risk of Crohn’s disease : a case-control study utilizing prospectively-collected exposure data from an administrative database

Crohn’s disease (CD) poses specific challenges in the paediatric population (growth failure, depression, etc).  The environmental contributors to CD aetiology remain largely unknown. There are suggestions that sanitary living conditions prevailing in developed countries prevent antigen exposure and impede the development of immunological tolerance amongst children, resulting in abnormally heightened immunological responses with subsequent exposures (hygiene hypothesis). Evidence for the hygiene hypothesis in CD aetiology remains unclear.  Objectives: To assess the role of the frequency, timing and type of childhood infections (measures of antigen exposure) on the risk of paediatric CD.  A case-control study was carried out. Confirmed cases of CD were recruited from a tertiary care paediatric hospital.  Controls matched to the cases on calendar age, gender, and area of residence, were selected using the provincial health insurance files.  Infection exposure was ascertained using ICD-9 diagnostic codes provided by the provincial insurer’s administrative databases. Conditional logistic regression analysis was used to assess the relationship between childhood infections and CD.  Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated.  409 cases and 1621 controls were recruited. A diagnosis of infection was associated with reduced risks for paediatric CD (OR=0.67, 95% CI:[0.48-0.93], p=0.018), attributable to infection exposures primarily during the first 5 years since birth [OR=0.74, 95% CI=0.57-0.96, p=0.025]. Infections affecting the kidney and urinary tract, oral tract and viral CNS infections, were most significantly associated with protective effects.  Our study provides support for the hygiene hypothesis in CD whereby exposure to infections in early childhood could potentially reduce risks for CD.

Keyphrases: infections, paediatric Crohn's disease, hygiene hypothesis, case-control study
L’association entre la marche utilitaire et le diabète : une étude transversale des adultes montréalais

Background: Type 2 diabetes is an important public health problem. Regular involvement in physical activity contributes to the prevention of this chronic disease. However, limited research has examined associations between transportation physical activity, especially utilitarian walking, and diabetes. Purpose: To examine the association between utilitarian walking and the prevalence of diabetes in a cross-sectional sample. Methods: Secondary analysis of data from a research project on the reach and potential impact of the implementation of a public bicycle share program was conducted. A sample of 7012 adults were recruited to telephone surveys in spring 2009, fall 2009, and fall 2010 via random-digit dialing with oversampling in locations where the public bike share was available. Utilitarian walking was estimated using questions adapted from the International Physical Activity Questionnaire (IPAQ). Multivariable logistic regression models examined the association between utilitarian walking and diabetes. The influence of socio- demographic covariates, involvement in other physical activities, and body mass index were controlled and sensitivity analyses were performed. Sensitivity analyses were performed using a different cut-off for utilitarian walking time. Results: In final models, utilitarian walking was associated with a lower likelihood of self-reporting diabetes (OR=0.721; 95% CI: 0.547, 0.950). Conclusion: Adoption of utilitarian walking is associated with a lower likelihood of reporting diabetes. Replication of these results in longitudinal studies could have implications for strategies to encourage people to incorporate more walking into their daily routine.

Keyphrases: Type 2 diabetes, utilitarian walk, cross-sectional study
The role of interleukin-1beta on the expression of nestin in cardiac neural stem cells following myocardial infarction

The underlying biological event(s) implicated in the increased expression of nestin in cardiac resident neural stem cells (NSC) following myocardial infarction (MI) remain unknown. Past studies have shown that dexamethasone treatment, a synthetic glucocorticoid with potent anti-inflammatory properties, abolished the upregulation of nestin in the non-infacted left ventricle (NILV) following MI. This suggests an association with the inflammatory response. The present study tested the hypothesis that the inflammatory cytokine interleukin-1beta (IL-1beta) can influence the neural stem cell phenotype. A secondary goal of the study was to assess impact of IL-1beta signalling inhibition on cardiac function and wound healing following MI. Following complete coronary artery ligation of the adult male rat heart, left ventricular contractile dysfunction was associated with the upregulation of the pro-apoptotic protein bax, the anti-apoptotic protein Bcl-2 and nestin in the non-infarcted myocardium. Xoma 052 (1 mg/kg), an IgG antibody directed against IL-1beta, was administred 24 hrs after ischemic injury and subsequently injected 2x over a period of 21 days. Treatment did not alter infarct size or improve left ventricular contractility. In addition, it failed to abolish the increased expression of nestin and Bcl-2, and modestly reduced bax protein levels. To directly assess the relationship between inflammation and the expression of nestin in the absence of an ischemic insult, adult male rats were injected with lipopolysaccharide (LPS) (10mg/kg;18 hrs). In the heart of LPS- treated rats, IL-1beta mRNA levels were significantly increased and associated with elevated nestin protein expression. The pre-treatment with Xoma 052 (10mg/kg) abolished the increased expression of nestin in the heart of LPS-treated rats. These data indicate that neural stem cells may represent a target for IL-1beta. However, futher investigation is required to elucidate the role of IL-1beta on NSC following MI.

Keyphrases: Nestin, Neural Stem Cells, Interleukin-1beta, Xoma 052, Nestin, Interleukin-1beta, Xoma 052
Effect of knockdown of Giα proteins using antisense oligodeoxynucleotides encapsulated in cationic liposomes on the development of hypertension in spontaneously hypertensive rats

Hypertension is one of the leading causes of morbidity and mortality in the world. Understanding the mechanisms underlying the development of hypertension will provide new insights into better control of hypertension. We have previously shown that the levels of Giα-2 and Giα-3 proteins were augmented in SHR before the onset of hypertension. Antihypertensive (ACE) inhibitor is associated with decreased Gi-proteins. In addition, intrapertoneal injection of pertussis toxin (PTX) inactivated both Giα proteins and prevented the development of hypertension in SHR. However, the specific contribution of Giα-2 and Giα-3 proteins in hypertension development is still not known. In the present study, Giα-2 and Giα-3 Antisense oligodeoxynuleotide (AS-ODN) (1 mg/Kg body weight) encapsulated in PEG/DOTAP/DOPE cationic liposomes were administrated intravenously to three-week-old pre-hypertensive SHR and their age-matched WKY while control WKY and SHR were injected with sterile PBS, empty liposomes or sense oligomer. Blood pressure (BP) was monitored weekly using tail-cuff technique. The rats were sacrificed at the age of six weeks and nine weeks. Heart and aorta were used to study Gi proteins expression. The knockdown of Giα-2 protein by Giα-2-AS injection prevented the development of hypertension up to the age of six weeks; thereafter the BP began to increase rapidly and reached the same level found in control groups at the age of nine weeks. On the other hand, the BP of the Giα-3-AS treated group began to increase at the age of four weeks. The SHR Giα-3-AS had augmented BP at six weeks but lower than that of SHR-CTL. The heart and aorta obtained from six week-old SHR Giα-2-AS and Giα-3-AS had significant decrease in Giα-2 and Giα-3 proteins expression respectively. WKY Giα-2-AS and Giα-3-AS had decreased in Giα-2 and Giα-3 protein expression respectively despite having no change in BP compared to CTL WKY. At the age of nine weeks, the SHR Giα-2-AS and Giα-3-AS had the same BP and Gi protein expression as the control SHR. These results suggest that both Giα-2 and Giα-3 proteins are implicated in the development of hypertension in SHR but the knockdown of Giα-2 not Giα-3 has prevented the development of hypertension.

Keyphrases: Liposomes, rats SHR, Hypertension, Giα-2 proteins, Giα-3 proteins, Antisense, Liposomes, SHR
Étude structurale et fonctionnelle du canal potassium dépendant du voltage KvAP

Voltage-gated ion channels are responsible for the initiation and propagation of action potentials in excitable cells. Several hereditary diseases (channelopathies) are associated with a defective voltage control by these channels, leading to arrhythmias, epilepsy, etc. Hence, establishing the exact structure/function relation for ion channels is crucial for the development of new specific therapeutic agents. Here, the bacterial voltage-gated potassium channel KvAP served as a model to study i) electromechanical coupling, ii) influence of lipids on the voltage dependent activity and iii) closed-state inactivation. To overcome the lack of structural information on the cytosolic side and of crystal structure in the closed state, we determined the S4-S5 linker movement during gating using fluorescence spectroscopy (LRET). We were able to control the conformational state of the channels by using lipids (phospholipids and non phospholipids) instead of voltage clamp. Based on these experimental constraints, a model in the closed state was produced, showing that a small 4Å radial displacement of the S4-S5 linker is sufficient to close the conduction pore. Interactions between lipids and membrane proteins play an important role in the regulation of ion channels activity but are not well characterized. We studied the influence of different lipids on KvAP voltage-dependent activation and showed two distinct effects related to different interactions sites: one bound to the voltage sensor, leading to a shift of the conductance-voltage curve, and another at the intracellular side near the pore region, affecting the steepness of this curve. We also showed that the exchange of lipids is very limited around KvAP and seems to be state dependent, occuring only when the channels are kept in the open state. KvAP has a slow inactivation atypical, accessible from the open state. We studied the effects of lipid composition and temperature on entry into inactivation and recovery. We also used voltage-clamp fluorometry in bilayers to investigate closed-state inactivation molecular basis. We identified a position at the bottom of the S4 helix that seems involved in the mechanism for slow inactivation and the extremely slow recovery from inactivation typically displayed by KvAP.

Keyphrases: Kv, KvAP, LRET, DOTAP, ion channel, voltage-clamp fluorometry, electromechanical coupling, voltage sensing domain, inactivation, lipids
Effets de plantes réputées antidiabétiques sur un modèle cellulaire hépatique de résistance à l’insuline induite par le palmitate

Cree pharmacopeia is rich in medicinal plants and many of them are studied by our laboratory for their antidiabetic potential. Some of the species tested have shown to activate the AMP-activated protein kinase (AMPK), an enzyme responsible for the translocation of glucose transporters to the cell membrane (hypoglycaemic activity). AMPK is also known to activate other cellular functions, like fat oxidation, in order to restore cell energy loss. The objectives of this study are, first, to measure the metabolic stress induced by eight of the species in muscular and liver cells, an effect believed to be responsible for the AMPK activation. Metabolic stress is evaluated by measuring extracellular medium acidification and cellular ATP depletion. The second objective is to assess the capacity of the extracts to clear intracellular fat (fat oxidation) and, by doing this, restore insulin sensitivity in insulin-resistant driven hepatocytes. To become insulin-resistant (a condition strongly linked to obesity), the hepatocytes are treated with a saturated fatty acid, palmitate. The results show that most of the extracts seem to increase the metabolic stress in muscular cells and hepatocytes for a short period of time. Among all extracts, only one has significantly reduced intracellular triglycerides in palmitate treated hepatocytes, an effect not followed by an increase in insulin sensitivity. In conclusion, the species tested in this study seem to exert their hypoglycaemic potential by affecting mitochondrial respiration (metabolic stress). However, the experimentations have not clearly shown the capacity of the species to restore insulin sensitivity in insulin-resistant liver cells.

Keyphrases: Type II diabetes, Populations autochtones, Aboriginal populations, Medicinal plants, AMPK, AMPK, Metabolic stress, Obesity, Palmitate, Palmitate, Insulin resistance, Fat oxidation