905 resultados para Refus vaccinal parental


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Mammalian sex chromosomes stem from ancestral autosomes and have substantially differentiated. It was shown that X-linked genes have generated duplicate intronless gene copies (retrogenes) on autosomes due to this differentiation. However, the precise driving forces for this out-of-X gene "movement" and its evolutionary onset are not known. Based on expression analyses of male germ-cell populations, we here substantiate and extend the hypothesis that autosomal retrogenes functionally compensate for the silencing of their X-linked housekeeping parental genes during, but also after, male meiotic sex chromosome inactivation (MSCI). Thus, sexually antagonistic forces have not played a major role for the selective fixation of X-derived gene copies in mammals. Our dating analyses reveal that although retrogenes were produced ever since the common mammalian ancestor, selectively driven retrogene export from the X only started later, on the placental mammal (eutherian) and marsupial (metatherian) lineages, respectively. Together, these observations suggest that chromosome-wide MSCI emerged close to the eutherian-marsupial split approximately 180 million years ago. Given that MSCI probably reflects the spread of the recombination barrier between the X and Y, crucial for their differentiation, our data imply that these chromosomes became more widely differentiated only late in the therian ancestor, well after the divergence of the monotreme lineage. Thus, our study also provides strong independent support for the recent notion that our sex chromosomes emerged, not in the common ancestor of all mammals, but rather in the therian ancestor, and therefore are much younger than previously thought

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Primary Aims of this intervention are weight management and behaviour change of children 7-13 years.Secondary aims include parental weight management and increase in self esteem and confidence in both children and their family

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Primary aims of this intervention are weight management and behaviour change of children 7-16 years old and secondary aims include parental weight management and increase in self esteem and confidence in both children and their families. The Referred Child:Will understand the importance of healthy eating and physical activity.Be able to make informed choices.Will have increased confidence and self esteem. The Parents:Will understand the importance of healthy eating and physical activity.Be able to make informed choices for themselves and their children.Feel empowered to continue a healthy lifestyle. The Family:Will understand the importance of healthy eating and physical activity.Will be able to work as a team to encourage each other to make healthy choices.Will feel confident enough to continue activities together.

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Background: Recombinant viruses based on the attenuated vaccinia virus strain NYVAC are promising HIV vaccine candidates as phase I/II clinical trials have shown good safety and immunogenicity profiles. However, this NYVAC strain is non-replicating in most human cell lines and encodes viral inhibitors of the immune system. Methods: With the aim to increase the immune potency of the current NYVAC-C vector (expressing the codon optimized clade C HIV-1 genes encoding gp120 and Gag-Pol-Nef polyprotein), we have generated and characterized three NYVAC-C-based vectors by, 1) deletion of the viral type I IFN inhibitor gene (NYVAC-CdeltaB19R), 2) restoration of virus replication competence in human cells by re-inserting K1L and C7L host range genes (NYVAC-C-KC) and, 3) combination of both strategies (NYVACC- KC-deltaB19R). Results: Insertion of the KC fragment restored the replication competence of the viruses in human cells (HeLa cells and primary dermal fibroblasts and keratinocytes), increased the expression of HIV antigens by more than 3-fold compared to the non-replicating homologs, inhibited apoptosis induced by the parental NYVAC-C and retained attenuation in a newborn mouse model. In adult mice, replication-competent viruses showed a limited capacity to replicate in tissues surrounding the inoculation site (ovaries and lymph nodes). After infection of keratinocytes, PBMCs and dendritic cells these viruses induced differential modulation in specific host cell signal transduction pathways, triggering genes important in immune modulation. Conclusion: We have developed improved NYVAC-C-based vectors with enhanced HIV-1 antigen expression, with the ability to replicate in cultured human cells and partially in some tissues, with an induced expression of cellular genes relevant to immune system activation, and which trigger IFN-dependent and independent signalling pathways, while maintaining a safety phenotype. These new vectors are promising new HIV vaccine candidates. These studies were performed within the Poxvirus Tcell Vaccine Discovery Consortium (PTVDC) which is part of the CAVD program.

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Plasmid and chromosomal genes encode determinants of virulence for Yersinia pestis, the causative agent of plague. However, in vitro, Y. pestis genome is very plastic and several changes have been described. To evaluate the alterations in the plasmid content of the cultures in vitro and the impact of the alterations to their pathogenicity, three Y. pestis isolates were submitted to serial subculture, analysis of the plasmid content, and testing for the presence of characteristic genes in each plasmid of colonies selected after subculture. Different results were obtained with each strain. The plasmid content of one of them was shown to be stable; no apparent alteration was produced through 32 subcultures. In the other two strains, several alterations were observed. LD50 in mice of the parental strains and the derived cultures with different plasmid content were compared. No changes in the virulence plasmid content could be specifically correlated with changes in the LD50.

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A total of 190 research documents were identified in line with the criteria agreed between the researchers and the CAAB, and are included in the audit. The key findings from the analysis of the audit are as follows:    - Research identified in the audit has tended to focus on child protection and the child protection system generally, as well as sexual abuse. This research has primarily been undertaken by clinicians and academics, and spans across sectors.   - Over half, (110 or 58%) of the research falls under the heading of policy/practice reviews/analysis. This is further reflected in the fact that the research most commonly focused on operating procedures, followed by practice issues and the policy framework, both in studies with a single focus and those with multiple foci.   - The most common type of publication was peer reviewed article (74 or 39%), with commissioned research accounting for just 7% (13). This is in line with the findings that 68% (128) of commissioning/publishing bodies and 74% (139) of research bodies were in the academic sector.   - The research published and/or commissioned by the statutory sector follows the pattern found in the audit generally, with the most common type of study being policy/practice review/analysis (27 or 48%) and the most common focus being operating procedures (22 or 39%).   - Information sources rarely incorporated primary research with children, with only 14 studies (8%) citing direct contact with children and young people. Information on children was more commonly gathered from case files, professionals and family members.   - The topics covered in the identified research were very wide-ranging but closely related to the primary subject area (type of abuse) and the sector in which the research was located.   One conclusion stated that: There is a shortage of child protection-focused research on the factors that cause and perpetuate child abuse, such as homelessness, addiction, parental mental illness and domestic violence. The need for material on these areas is demonstrated by the nature and scale of reports to the child protection system and the removal of some children from their families into out of home care as a result of the above mentioned adversities.This resource was contributed by The National Documentation Centre on Drug Use.

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 The latest results from the study paint a picture of how these families are faring across a range of areas in their lives including their health, family life and financial and economic circumstances. In general the findings show that three-year-olds in Ireland are in good health with a few notable public health and related issues (including overweight and obesity), there is overall stability in family structures over the short term and that the recession has had a substantial effect on families with young children over the last number of years. These are the first longitudinal findings from the study. The first wave of fieldwork with the families of the Infant Cohort included approximately 11,100 nine-month-olds, their parents and carers. Interviews began in September 2008 and were completed in March 2009. Interviews for the second round of interviews with this cohort took place between January and August 2011. A total of 90% of the original sample of nine-month-olds were successfully re-interviewed. (A full download of the results released today, presented in three briefing documents can be found by clicking here. Key findings include: Health â?¢ Most of the children were described as being in good health; 75% were rated as very healthy and a further 23% were rated as healthy, but a few minor problems. Girls were more likely to be reported as very healthy (78%) compared with boys (72%). â?¢ One in four or almost one quarter of three-year-old children were overweight (19%) or obese (6%). â?¢ Childrenâ?Ts weight was related to household social class. 5% of children in families in the professional/managerial group were classified as obese at three years of age compared with 9% of those in the most disadvantaged social class group. However, at least one-fifth of children in every social class were overweight. â?¢ Childrens consumption of energy-dense foods such as crisps, sweets, chips, and non-diet fizzy drinks increased as parental education fell. 63% of children whose mother had a lower secondary education or less ate at least one portion of crisps compared with 36% of those from degree-level backgrounds, although consumption of biscuits/chocolates was over 70% for both groups of children. â?¢ Two-thirds (66%) of three-year-olds had received at least one course of antibiotics in the 12 months preceding the interview. Children with a full medical card (35% of the sample) or a GP-only medical card (5% of the sample) were more likely to have received a course of antibiotics than â?¢ Children with a full medical card received a higher number of antibiotic courses on average (2.6) compared with those without a medical card (2.1). â?¢ Just under 16% of three-year-old children were reported as having at least one longstanding illness, condition or disability. The most commonly reported illness types included Asthma (5.8%), Eczema/Skin allergies (3.9%) and Food/digestive allergies (1.2%) Family Life and Childcare â?¢ While the overall distribution of family structure was stable, there have been transitions from one-parent families to two-parent families and vice-versa over the 27 months between interview â?" approximately 2 to 3 percent in each direction. â?¢ 50% of three year olds were in some form of non-parental childcare for eight or more hours a week. The most common form used was centre-based childcare which almost tripled between nine months and three years, from 11% to 30%. â?¢ A similar percentage of grandparents were caring for children at both nine months and three years, 12% and 11% respectively. A total of 10% of three-year-olds were being minded by a childminder, an increase of 3 percentage points from when the children were nine months of age. â?¢ Children who were in some form of non-parental childcare were spending an average of 23 hours a week in their main type of childcare. â?¢ At time of interview the vast majority of mothers reported that they had regular contact with the Study Childâ?Ts grandparents (91%). In offering support to parents, grandparents were most likely to babysit (50%), and buy clothes (40%) at least on a monthly basis. One-parent families were more likely than two-parent families to receive financial support from grandparents with just under one-third (66%) of one-parent families receiving financial support from grandparents at least once every three months. â?¢ The most frequently used discipline technique was â?~discussing or explaining why the behaviour was wrongâ?T, with 63% of mothers saying they always did this. â?¢ 12% of mothers said they used â?~smackingâ?T as a form of discipline now and again and less than 1% used â?~smackingâ?T as a form of discipline more frequently. Over half reported that they never smacked the Study Child. Financial and Economic Circumstances â?¢ Just over half (53%) of mothers of three-year-olds worked outside the home, 38% said they were on home duties and 6% said they were unemployed. â?¢ The biggest change in terms of the work status of three-year-oldsâ?T parents was an increase in the percentage of unemployed fathers â?" 6% when the child was nine months rising to almost 14% when s/he was three years of age. â?¢ 61% of families of three-year-olds reported experiencing difficulties in making â?~ends meetâ?T. This was a substantial increase from 44% in the first round of interviews when the children were nine-months-old. â?¢ Almost two thirds (63%) of all families with three-year-olds reported that the recession had had a very significant or significant effect on them. â?¢ The most frequently recorded effects were: a reduction in wages (63%); canâ?Tt afford luxuries (54%), social welfare reduction (53%) and canâ?Tt afford/cut back on basics (32%). Growing Up in Ireland is a Government funded study tracking the development of two nationally representative cohorts of children: an Infant Cohort which was interviewed initially at nine months and subsequently at three years of age; and a Child Cohort which was interviewed initially at nine years and subsequently at 13 years of age. The study is being conducted by a consortium of researchers led by the Economic and Social Research Institute (ESRI) and Trinity College Dublin. For Further Information Please Contact: Jillian Heffernan Communications Officer, Growing Up in Ireland Tel: 01 896 3378 Mobile: 087 9016880This resource was contributed to our repository by the National Documentation Centre on Drug Use.

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The aim of the present work was to study parasitological, molecular, and genetic aspects in descendants of crossbreedings between a totally resistant Biomphalaria tenagophila strain (Taim, RS) and another one highly susceptible (Joinville, SC) to Schistosoma mansoni. Descendants F1 and F2 were submitted to S. mansoni infection (LE strain). The susceptibility rates for individuals from Group F1 were 0 to 0.6%, and from Group F2 was 7.2%. The susceptible individuals from Group F2 discharged a lower number of cercariae, when compared with the susceptible parental group, and in 2 out of 9 positive snails the cercarial elimination was discontinued. In order to identify genetic markers associated with resistance the genotype of parental snails and their offspring F1 and F2 were analyzed by means of the randomly amplified polymorphic DNA method. Nevertheless, it was not possible to detect any marker associated to resistance, but the results showed that in the mentioned species the resistance character is determined by two dominant genes.

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The study investigates associations between attachment cognitions and depression symptoms in 71 15-25-year-olds, 26 of whom have eating disorders, and 20 of whom are drug misusers. Attachment cognitions were measured with the CaMir Q-sort, which provides indexes for secure, avoidant, and preoccupied attachment, as well as scores on 13 dimensions. The BDI-13 was used to measure depressive symptomatology. Consistent with the literature, BDI scores were associated with cognitions of preoccupied attachment. They were also related to cognitions of avoidant attachment, confirming Bowlby's theory on defensive exclusion. For participants with eating disorders, depressive symptomatology was related to preoccupation and parental interference, whereas for drug misusers, it was negatively related to security, preoccupation, parental support, and lack of parental concern. These findings help understand how attachment cognitions may participate in depressive symptomatology, namely in youth whose behavior problems may be associated with specific attachment experiences.

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Introduction : DTI has proven to be an exquisite biomarker of tissue microstructure integrity. This technique has been successfully applied to schizophrenia in showing that fractional anisotropy (FA, a marker of white matter integrity) is diminished in several areas of the brain (Kyriakopoulos M et al (2008)). New ways of representing diffusion data emerged recently and achieved to create structural connectivity maps in healthy brains (Hagmann P et al. (2008)). These maps have the capacity to study alterations over the entire brain at the connection and network level. This is of high interest in complex disconnection diseases like schizophrenia. We report on the specific network alterations of schizophrenic patients. Methods : 13 patients with chronic schizophrenia were recruited from in-patient, day treatment, out-patient clinics. Comparison subjects were recruited and group-matched to patients on age, sex, handedness, and parental social economic-status. This study was approved by the local IRB and subjects had to give informed written consent. They were scanned with a 3T clinical MRI scanner. DTI and high-resolution anatomical T1w imaging were performed during the same session. The path from diffusion MRI to a multi-resolution structural connection matrices of the entire brain is a five steps process that was performed in a similar way as described in Hagmann P et al. (2008). (1) DTI and T1w MRI of the brain, (2) segmentation of white and gray matter, (3) white matter tractography, (4) segmentation of the cortex into 242 ROIs of equal surface area covering the entire cortex (Fig 1), (5) the connection network was constructed by measuring for each ROI to ROI connection the related average FA along the corresponding tract. Results : For every connection between 2 ROIs of the network we tested the hypothesis H0: "average FA along fiber pathway is larger or equal in patients than in controls". H0 was rejected for connections where average FA in a connection was significantly lower in patients than in controls. Threshold p-value was 0.01 corrected for multiple comparisons with false discovery rate. We identified consistently that temporal, occipito-temporal, precuneo-temporal as well as frontal inferior and precuneo-cingulate connections were altered (Fig 2: significant connections in yellow). This is in agreement with the known literature, which showed across several studies that FA is diminished in several areas of the brain. More precisely, abnormalities were reported in the prefrontal and temporal white matter and to some extent also in the parietal and occipital regions. The alterations reported in the literature specifically included the corpus callosum, the arcuate fasciculus and the cingulum bundle, which was the case here as well. In addition small world indexes are significantly reduced in patients (p<0.01) (Fig. 3). Conclusions : Using connectome mapping to characterize differences in structural connectivity between healthy and diseased subjects we were able to show widespread connectional alterations in schizophrenia patients and systematic small worldness decrease, which is a marker of network desorganization. More generally, we described a method that has the capacity to sensitively identify structure alterations in complex disconnection syndromes where lesions are widespread throughout the connectional network.

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Colombian strain of Trypanosoma cruzi, biodeme Type III (T. cruzi I), has been cloned by micromanipulation at two phases of the acute infection: early (10 days ) and advanced (30 days). Twelve clones were obtained therefrom. Characterization by their biological and biochemical behavior showed an identity among the several clones and their parental strain, albeit with different degrees of virulence. Molecular characterization of the kinetoplast DNA (kDNA) after amplification by polymerase chain reaction revealed identical profiles of the bands from the kDNA minicircle by the analysis of restriction fragment lenght polymorphism for the isolated clones, their parental strain, and to the clones isolated at two different phases of the infection. Results suggest the predominance of a "principal clone", in the composition of the Colombian strain, responsible for the biological and biochemical behavior. However, no relationship was detected between the molecular profile of kDNA and the degree of virulence presented by the several clones.

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This joint PHA/HSCB Hidden Harm Action Plan - Responding to the needs of children born to and living with parental alcohol and drug misuse in Northern Ireland, has been prepared for the DHSSPS in response to the PfA target on Hidden Harm. The plan was approved by DHSSPS in October 2009.

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Parental or professional concern regarding an infant/young child's hearing may be identified at any time.� Where such concern is identified, direct referral should be made, irrespective of newborn hearing screening outcomes and with parental agreement.�

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Informed consent – which can be either written or oral (depending on local Trust policy) – must be obtained and recorded in the notes at the time of each immunisation, after the child’s fitness and suitability have been established. It is important that the person giving consent is fully informed about the vaccine at the time they give consent. Written material is available to assist in this, but is not a substitute for an opportunity to discuss the issues with a health professional. Consent is given by the person with parental responsibility; however, this person does not necessarily need to be present at the time the immunisation is given. Although the decision to immunise must be taken by the person with parental responsibility, they can arrange for someone else (eg grandparent or childminder) to bring the child to be immunised. You do not need consent in writing – if they have received all the relevant information and arranged for another person to bring the child, the circumstances indicate they have consented. A child under 16 years may give consent provided he or she understands fully the benefits and risks involved. If a competent child consents to treatment, a parent cannot override that consent. Obviously they should be encouraged to involve the person with parental responsibility in the decision. Legally, a parent can consent if a competent child refuses �

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Cancer is the second leading cause of mortality worldwide. Cancer progression leads to metastasis formation, which accounts for more than ninety percent of cancer-related death. Metastases are more difficult to be surgically removed because of their invasive behavior and shape. In addition, during their transformation journey, they become more and more resistant to anticancer drugs. Significant improvements have been achieved in therapy against cancer in recent years but targeting the metastatic cascade remains the Achilles heel of the cure against cancer. A First step in the metastatic process is the escape of cancer cells from the primary tumor site. This involves an increase in cell motility and the concomitant ability to clear a path through the extracellular matrix. From a therapeutic point of view, inhibition of cell migration is a logical approach to develop anti-metastatic drugs. Our lab previously developed a cell permeable peptide derived from a caspase-3-generaied fragment of the RasGAP protein called TAT-RasGAP317-326. This peptide efficiently and specifically sensitizes cancer cells to chemotherapy- and radiotherapy-induced ceil death, which allows decreasing the anticancer drug doses and eventually their associated side- effects. In the present study we discovered that TAT-RasGAP317.326 also increases cell adhesion which was associated with inhibition of cell migration and invasion into the extracellular matrix. The ability of TAT-RasGAP317.326 to increase ceil adhesion involves the dramatic depolymerization of actin cytoskekton together with redistribution of focal adhesions. We found that the inhibitory effects on migration were mediated by a RhoGAP tumor and metastasis suppressor cailed DLC1 (Deleted in Liver Cancer 1). Moreover. DEC 1 was found to be a direct RasGAP-interacting protein and this interaction requires the RasGAP tryptophan 317 residue, the very first RasGAP residue of TAT-RasGAP317.326. We then evaluated the roie of RasGAP fragments in the in vivo metastatic cascade. We found that breast cancer cells overexpressing the parental RasGAP fragment, to which the TAT-RasGAP317.326 peptide belongs, have a markedly decreased ability to form lung metastases. Unfortunately, we were not able to recapitulate these an ti-metastatic effects when TAT-RasGAP317.326 was injected. However, we later understood that this was due to the fact that TAT-RasGAP317.326 was not properly delivered to the primary tumors. Further work, aimed at better understanding of how TAT-RasGAP317.326 functions, revealed that the ten amino acid TAT-RasGAP317.326 peptide could, be narrowed down to a three amino acid TAT-RasGAP317.329 peptide while keeping its sensitizer activity. In parallel, investigations on the RasGAP-DLCl binding indicated that the arginine linger of the DLC1 GAP domain is required for this interaction, which suggests that TAT-RasGAP317.326 modulates the GAP activity of DLC1. Additional work should be performed to fully elucidate its mechanism of action and render TAT-RasGAP317.326 usable as a tool to fight cancer on two fronts, by improving chemotherapy and preventing metastatic progression. - Le cancer est la deuxième cause de mortalité dans le monde. La formation de métastases est la dernière étape de la progression cancéreuse et représente plus du nonante pour cent des morts induites par le cancer. De par leur morphologie et comportement invasifs, ii est difficile d'avoir recours à la chirurgie pour exciser des métastases. De plus, les cellules cancéreuses en progression deviennent souvent de plus en plus résistantes aux drogues anticancéreuses. Ces dernières années, des avancements significatifs ont contribué à l'amélioration de la lutte contre le cancer. Néanmoins, pouvoir cibler spécifiquement la cascade métastatique demeure cependant le talon d'Achille des thérapies anticancéreuses. Une première étape dans ie processus métastatique est l'évasion des cellules cancéreuses du site de la tumeur primaire. Ceci requiert une augmentation de la motiliié cellulaire couplée à la capacité de se frayer un chemin au sein de la matrice extracelluiaire. D'un point de vue thérapeutique, inhiber la migration cellulaire est une approche attrayante. Notre laboratoire a développé un peptide, nommé TAT-RasGAP317.326 dérivé d'un fragment qui est lui-même le résultat du clivage de la protéine RasGAP par la caspase-3. Ce peptide est capable de pénétrer les cellules cancéreuses et de les sensibiliser spécifiquement à la mort induite par la radiothérapie et la chimiothérapie. La finalité des effets de ce peptide est de pouvoir diminuer les doses des traitements anti-cancéreux et donc des effets secondaires qu'ils engendrent. Dans cette étude, nous avons découvert que TAT-RasGAP317.326 augmente l'adhésion des cellules et inhibe la migration cellulaire ainsi que l'invasion des cellules à travers une matrice extracellulaire. La capacité de TAT-RasGAP317.326 à induire l'adhésion repose sur ia dépolymérisation du cytosquelette d'actine associée à une redistribution des points d'ancrage cellulaire. Nous avons découvert que l'inhibition de ia migration par TAT-RasGAP317.326 nécessitait la présence d'un suppresseur de tumeur et de métastases appelé DLC1 (Deleted in Liver Cancer l), qui par ailleurs s'avère aussi être une protéine RhoGAP. De plus, nous avons aussi trouvé que DLC1 était un partenaire d'interaction de RasGAP et que cette interaction s'effectuait via l'acide aminé tryptophane 317 de RasGAP. qui s'avère être le premier acide aminé du peptide TAT-RasGAP317.326. Nous avons ensuite évalué le rôle joué par certains fragments de RasGAP dans le processus de métastatisation. Dans ce contexte, des cellules de cancer du sein qui sur-expriment un fragment de RasGAP contenant la séquence TAT-RasGAP317.326 ont vu leur potentiel métastatique diminuer drastiquerment. Malheureusement, aucun effet anti-métastatique n'a été obtenu après injection de TAT-RasGAP317.326 dans les souris. Cependant, nous avons réalisé rétrospectivement que TAT-RasGAP317.326 n'était pas correctement délivré à la tumeur primaire, ce qui nous empêche de tirer des conclusions sur le rôle anti-métastatique de ce peptide. La suite de cette étude visant à mieux comprendre comment TAT-RasGAP317.326 agit, a mené à la découverte que les dix acides aminés de TAT-RasGAP317.326 pouvaient être réduits à trois acides aminés, TAT-RasGAP317.329, tout en gardant l'effet sensibilisateur à la chimiothérapie. En visant à élucider le mode d'interaction entre RasGAP et DLC1, nous avons découvert qu'un acide aminé nécessaire à l'activité GAP de DLC1 était requis pour lier RasGAP, ce qui laisse présager que TAT-RasGAp317.32c, module i'activité GAP de DLC1. Des travaux supplémentaires doivent encore être effectués pour complètement élucider les mécanismes d'action de TAT-RasGAP317.326 et afin de pouvoir l'utiliser comme un outil pour combattre le cancer sur deux fronts, en améliorant les chimiothérapies et en inhibant la formation de métastases.