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Author Posor, Y.; Eichhorn-Grünig, M.; Haucke, V. url  openurl
  Title Phosphoinositides in endocytosis Type Journal Article
  Year 2015 Publication Abbreviated Journal Biochim Biophys Acta  
  Volume 1851 Issue 6 Pages 794-804  
  Keywords Jhu, Cme, Pip2  
  Abstract The internalization and subsequent endosomal trafficking of proteins and membrane along the endocytic pathway is a fundamental cellular process. Over the last two decades, this pathway has emerged to be subject to extensive regulation by phosphoinositides (PIs), phosphorylated derivatives of the minor membrane phospholipid phosphatidylinositol. Clathrin-mediated endocytosis (CME) is the endocytic mechanism characterized in most detail. It now represents a prime example of a process spatiotemporally organized by the interplay of PI metabolizing enzymes. The most abundant PI, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂], serves as a denominator of plasma membrane identity and together with cargo proteins is instrumental for the initiation of clathrin-coated pit (CCP) formation. During later stages of the process, the generation of phosphatidylinositol-3,4-bisphosphate [PI(3,4)P₂] and the dephosphorylation of PI(4,5)P₂regulate CCP maturation and vesicle uncoating. Here we provide an overview of the mechanisms by which PIs are made and consumed to regulate CME and other endocytic pathways and how conversion of PIs en route to endosomes may be accomplished. Mutations in PI converting enzymes are linked to multiple diseases ranging from mental retardation and neurodegeneration, to inherited muscle and kidney disorders suggesting that the tight control of PI levels along the endocytic pathway plays a critical role in cell physiology. This article is part of a Special Issue entitled Phosphoinositides.  
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  ISSN (up) 0006-3002 ISBN Medium  
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  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 46813  
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Author Varma, V.; Ratnam, J.; Viswanathan, V.; Osuri, A.M.; Biesmeijer, J.C.; Madhusudan, M.D.; Sankaran, M.; Krishnadas, M.; Barua, D.; Budruk, M.; Isvaran, K.; Jayapal, R.; Joshi, J.; Karanth, K.K.; Krishnaswamy, J.; Kumar, R.; Mukherjee, S.; Nagendra, H.; Niphadkar, M.; Owen, N.; Page, N.; Prasad, S.; Quader, S.; Nandini, R.; Robin, V.V.; Sait, S.M.; Shah, M.A.; Somanathan, H.; Srinivasan, U.; Sundaram, B. url  openurl
  Title Perceptions of priority issues in the conservation of biodiversity and ecosystems in India Type Journal Article
  Year 2015 Publication Abbreviated Journal Biological Conservation  
  Volume 187 Issue Pages 201-211  
  Keywords biodiversity; Conservation; Ecosystems; India; Perceptions  
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  ISSN (up) 0006-3207 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number CES @ dilipnaidu.gt @ Serial 42955  
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Author Al-Nouri, Z.L.; Reese, J.A.; Terrell, D.R.; Vesely, S.K.; George, J.N. url  openurl
  Title Drug-induced thrombotic microangiopathy: a systematic review of published reports Type Journal Article
  Year 2015 Publication Abbreviated Journal Blood  
  Volume 125 Issue 4 Pages 616-618  
  Keywords  
  Abstract Many patients with syndromes of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, have been reported to have a drug-induced etiology, and many different drugs have been suspected as a cause of TMA. We established criteria to assess the strength of evidence for a causal association of a drug with TMA and systematically searched for all published reports of drug-induced TMA. We identified 1569 articles: 604 were retrieved for review, 344 reported evaluable data for 586 individual patients, 43 reported evaluable data on 46 patient groups. Seventy-eight drugs were described; 22 had evidence supporting a definite causal association with TMA. Three drugs accounted for 61 of the 104 patient reports with definite evidence (quinine, 34; cyclosporine, 15; tacrolimus, 12). Twenty additional drugs had evidence supporting a probable association with TMA. These criteria and data can provide support for clinicians evaluating patients with suspected TMA.  
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  ISSN (up) 0006-4971 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45847  
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Author Holterbach, L.; Baumann, C.; Andreani, B.; Desre, D.; Auxemery, Y. url  doi
openurl 
  Title [Correlation between specific and nonspecific posttraumatic stress disorder symptoms with healthcare consumption among 340 French soldiers] Type Journal Article
  Year 2015 Publication L'Encephale Abbreviated Journal Encephale  
  Volume 41 Issue 5 Pages 444-453  
  Keywords Army; Armees; Consommation de soins; Detection; Depistage; Epidemiology; Healthcare consumption; Militaires; Pcls; Posttraumatic stress disorder; Psychopathologie; Psychopathology; Soldiers; Epidemiologie; Etat de stress post-traumatique  
  Abstract BACKGROUND: The psychotraumatic disorders are often difficult to diagnose because the specific symptoms of posttraumatic stress disorder (revival, hyperarousal, avoidance) are rarely a direct demand for health care: for reasons determined by the psychopathological structure of trauma, its symptomatology and course, the psychotraumatised subjects seek a care system for nonspecific psychological or somatoform symptoms: depressive episode, cognitive disorders, other anxiety disorders, histrionic and obsessive symptoms, changes in personality, pain disorders and somatization. Somatic pain may also result from a war injury and psychosomatic complications, addictive or consequences of risk behaviours during the evolution of posttraumatic stress disorder. OBJECTIVES: To establish a correlation between the PCLS and the evaluation of the healthcare consumption in a military population. METHODS: We conducted a multicenter epidemiological study analyzing the PCLS and a questionnaire assessing health care consumption. The PCLS has been studied in various forms: quantitative (17 to 85), in qualitative classes (<33, 33 to 43 and >/=44), and in five sub-dimensions (flashbacks, avoidance, dissociation, depression and hyperactivity). The sub-dimension revival was then studied item by item. The criteria used care consumption over the last twelve months is the numbers of days of sick leave, days of unavailability (of certain jobs or military activities) and consultations. RESULTS: Our population of 340 subjects cannot be considered representative of the French military population even if only a few characteristics differ. Sixteen of 340 subjects show a positive PCLS is 4.70% of our sample. PCLS average of 23 (+/-9.4) with a median of 19 objectifying much of PCLS have almost zero score. Validating our main hypothesis, we found a statistically significant relationship between elements of the PCLS and variables care consumption: this link exists mainly between the score, classes and sub-dimensions of the PCLS in one hand and number of days of sick leave and unavailability on the other hand. DISCUSSION: Towards a strategy for tracking psychotraumatic disorders, could be developed a score of health care consumption which would include the number of days of sick leave and unavailability, the number and quality of medical consultations, the number and quality of drug and laboratory requirements, the number of hospitalisations. To the identification of posttraumatic stress disorder, the PCLS score as well as the consumer healthcare score are valuable tools but do not replace the subjectivity of the clinical relationship: return to this shared subjectivity with the practitioner remains a diagnostic dimension, but also therapeutic, fundamental.  
  Address HIA Percy, 101, avenue Henri-Barbusse, BP 406, 92140 Clamart, France. Electronic address: yann.auxemery@hotmail.fr  
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  Language French Summary Language Original Title Etat de stress post-traumatique et consommation de soins sur l'annee ecoulee : etude menee aupres de 340 militaires francais de cinq unites combattantes de l'armee de terre  
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  Series Volume Series Issue Edition  
  ISSN (up) 0013-7006 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26049671 Approved no  
  Call Number UU @ jana.mullerova @ Serial 42181  
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Author Auxemery, Y. url  doi
openurl 
  Title [Clinical forms of post-traumatic depression] Type Journal Article
  Year 2015 Publication L'Encephale Abbreviated Journal Encephale  
  Volume 41 Issue 4 Pages 346-354  
  Keywords Deuil post-traumatique; Deuil traumatique; Depression masquee; Depression post-traumatique; Depression traumatique; Post-concussive syndrome; Posttraumatic depression; Posttraumatic grief; Psychic trauma; Psychopathologie; Psychopathology; Psychopharmacologie; Psychopharmacology; Syndrome post-commotionnel; Traumatic depression; Traumatic grief; Traumatisme psychique  
  Abstract INTRODUCTION: As a result of determinants specific to the psychopathological structure of the psychological trauma, psycho-traumatised patients very rarely solicit the health care system directly with a request for treatment centred on their trauma. The medical profession is consulted for non-specific symptoms and complications, which are mainly somatoform, addictions and depressive disorders. After a few epidemiological reminders followed by a discussion concerning contemporary depressive and post-traumatic nosographic features, we define, through our clinical experience collated with the data in the literature, different clinical and etiopathogenic contexts of post-traumatic depression in order to control their therapeutic treatment. CLINICAL FINDINGS: Burnout post-traumatic depression in response to re-experiencing is the most common: it is a reactive psycho-physiological burnout in response to the emotional distress re-experienced during flashbacks, insomnia, a constant feeling of insecurity and the deleterious consequences of this symptomatology in terms of social adaptation. A common genetic predisposition affecting serotoninergic regulation seems to be a vulnerability marker of both depressive and psychotraumatic symptoms. In this case, SSRI will be effective on sadness. In addition, these antidepressants have been widely prescribed for the first-line treatment of depressive and psychotraumatic symptoms. However, this pharmacological class is often insufficient in relieving autonomic hyperactivity such as re-experiencing which are mediated more by noradrenergic hyperactivity. SNRI such as venlafaxine can be used as a first-line treatment. Post-traumatic depression with psychotic features congruent with mood is dominated by a feeling of incurability; the subject blames himself and feels guilty about the traumatic event and its consequences. Symptoms of denial of identity are sometimes observed: confined by an intense depersonalization, the psycho-traumatised subject evokes that he is “no longer himself” and that his mind “is disconnected”. Confronted with the psychological emptiness of the traumatic scene, the psycho-traumatised subject remains devoid of thought as if their mind has left him. In addition to antidepressant therapy, an atypical antipsychotic drug must be prescribed to relieve the melancholic symptoms as well as the concomitant psychotraumatic symptoms. Post-traumatic depression masked by peripheral physical injuries is the result of accidents combining psychological and physical impairment. The physical pain resulting from the accident regularly recalls the drama in the same way as traumatic re-experiencing. Depression masked by this somatic suffering is difficult to diagnose, but the repeated somatic complaints at the forefront of the request for treatment, the breakdown of self-esteem as well as the level of subjective strain due to pain and dysesthesia are all indications. The psychotherapy will focus on the symbolic reconstruction of the organs that have been damaged or destroyed, with the aim of healing the extensive narcissistic impairment. Post-concussive depression is diagnosed following a head trauma, however severe. It is sometimes assigned to neurological lesions and at other times recognised as the expression of a purely psychological reaction. Antidepressant therapy, or possibly trial therapy, is often indicated. The terms traumatic grief and post-traumatic grief are often used synonymously in publications: a conceptual opposition must however been recalled. If the traumatic grief is the result of the loss of an object that holds much psychological importance for the individual, the subject has not however been traumatised by this event and is not suffering and will not suffer from re-experiencing. The therapy will include methods used in the psychotherapeutic treatment of grief; antidepressants are often insufficient. Differently, post-traumatic grief takes shape when the loss of another is concomitant with the confrontation with the reality of the death witnessed in a moment of peri-traumatic dissociation. This grief is often observed following the discovery of the body of a close friend or family member who has committed suicide, or when part of a family has been decimated by an accident whilst the survivors watch their close relations die pending the arrival of the emergency services, or when a military comrade is wounded in combat in front of his partner. The mourning process cannot really begin until the flashbacks cease. CONCLUSIONS: Clinical depression or even melancholia, possibly masked by somatic or post-concussive complaints, is often the initial mode of contact with the health care system for the psycho-traumatised subject. The different clinical and etiopathogenic contexts of post-traumatic depression that we have developed in this work use specific therapies which need to be clarified by further research based on this nosography.  
  Address Service medical de psychologie clinique appliquee a l'aeronautique, hopital d'instruction des Armees Percy, 101, avenue Henri-Barbusse, BP406, 92141 Clamart, France. Electronic address: yann.auxemery@hotmail.fr  
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  Language French Summary Language Original Title Formes cliniques des depressions post-traumatiques  
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  ISSN (up) 0013-7006 ISBN Medium  
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  Notes PMID:25238908 Approved no  
  Call Number UU @ jana.mullerova @ Serial 42198  
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Author Nash, W.P.; Boasso, A.M.; Steenkamp, M.M.; Larson, J.L.; Lubin, R.E.; Litz, B.T. url  doi
openurl 
  Title Posttraumatic stress in deployed Marines: prospective trajectories of early adaptation Type Journal Article
  Year 2015 Publication Journal of Abnormal Psychology Abbreviated Journal J Abnorm Psychol  
  Volume 124 Issue 1 Pages 155-171  
  Keywords  
  Abstract We examined the course of PTSD symptoms in a cohort of U.S. Marines (N = 867) recruited for the Marine Resiliency Study (MRS) from a single infantry battalion that deployed as a unit for 7 months to Afghanistan during the peak of conflict there. Data were collected via structured interviews and self-report questionnaires 1 month prior to deployment and again at 1, 5, and 8 months postdeployment. Second-order growth mixture modeling was used to disaggregate symptom trajectories; multinomial logistic regression and relative weights analysis were used to assess the role of combat exposure, prior life span trauma, social support, peritraumatic dissociation, and avoidant coping as predictors of trajectory membership. Three trajectories best fit the data: a low-stable symptom course (79%), a new-onset PTSD symptoms course (13%), and a preexisting PTSD symptoms course (8%). Comparison in a separate MRS cohort with lower levels of combat exposure yielded similar results, except for the absence of a new-onset trajectory. In the main cohort, the modal trajectory was a low-stable symptoms course that included a small but clinically meaningful increase in symptoms from predeployment to 1 month postdeployment. We found no trajectory of recovery from more severe symptoms in either cohort, suggesting that the relative change in symptoms from predeployment to 1 month postdeployment might provide the best indicator of first-year course. The best predictors of trajectory membership were peritraumatic dissociation and avoidant coping, suggesting that changes in cognition, perception, and behavior following trauma might be particularly useful indicators of first-year outcomes.  
  Address VA Boston Healthcare System  
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  Language English Summary Language Original Title  
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  ISSN (up) 0021-843X ISBN Medium  
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  Notes PMID:25419860 Approved no  
  Call Number UU @ jana.mullerova @ Serial 42197  
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Author Yogurtcu, O.N.; Johnson, M.E. url  openurl
  Title Theory of bi-molecular association dynamics in 2D for accurate model and experimental parameterization of binding rates Type Journal Article
  Year 2015 Publication Abbreviated Journal J Chem Phys  
  Volume 143 Issue 8 Pages 084117  
  Keywords Jhu, Fpr, Cme  
  Abstract The dynamics of association between diffusing and reacting molecular species are routinely quantified using simple rate-equation kinetics that assume both well-mixed concentrations of species and a single rate constant for parameterizing the binding rate. In two-dimensions (2D), however, even when systems are well-mixed, the assumption of a single characteristic rate constant for describing association is not generally accurate, due to the properties of diffusional searching in dimensions d ≤ 2. Establishing rigorous bounds for discriminating between 2D reactive systems that will be accurately described by rate equations with a single rate constant, and those that will not, is critical for both modeling and experimentally parameterizing binding reactions restricted to surfaces such as cellular membranes. We show here that in regimes of intrinsic reaction rate (ka) and diffusion (D) parameters ka/D > 0.05, a single rate constant cannot be fit to the dynamics of concentrations of associating species independently of the initial conditions. Instead, a more sophisticated multi-parametric description than rate-equations is necessary to robustly characterize bimolecular reactions from experiment. Our quantitative bounds derive from our new analysis of 2D rate-behavior predicted from Smoluchowski theory. Using a recently developed single particle reaction-diffusion algorithm we extend here to 2D, we are able to test and validate the predictions of Smoluchowski theory and several other theories of reversible reaction dynamics in 2D for the first time. Finally, our results also mean that simulations of reactive systems in 2D using rate equations must be undertaken with caution when reactions have ka/D > 0.05, regardless of the simulation volume. We introduce here a simple formula for an adaptive concentration dependent rate constant for these chemical kinetics simulations which improves on existing formulas to better capture non-equilibrium reaction dynamics from dilute to dense systems.  
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  ISSN (up) 0021-9606 ISBN Medium  
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  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 46618  
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Author Gulbahar, O.; Konca Degertekin, C.; Akturk, M.; Yalcin, M.M.; Kalan, I.; Atikeler, G.F.; Altinova, A.E.; Yetkin, I.; Arslan, M.; Toruner, F. url  doi
openurl 
  Title A Case With Immunoassay Interferences in the Measurement of Multiple Hormones Type Journal Article
  Year 2015 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab  
  Volume 100 Issue 6 Pages 2147-2153  
  Keywords Adult; Antibodies, Heterophile/*blood; *Artifacts; Cross Reactions; *Diagnostic Techniques, Endocrine/standards; False Positive Reactions; Female; Hormones/*analysis; Humans; Immunoassay/methods; Postpartum Period/blood/immunology  
  Abstract CONTEXT: Commonly used immunoassays are not free from interference, which can be a confounder in the interpretation of test results. We present a case with extremely high multiple hormone levels due to such interference. CASE DESCRIPTION: A 33-year-old woman with no specific symptoms had markedly elevated TSH with normal free T4 and free T3 levels. Repeated measurements revealed discordantly high TSH, ACTH, FSH, PTH, IGF-1, prolactin, beta-human chorionic gonadotropin, and calcitonin levels without the associated clinical pictures. The measurements were repeated with the same patient sample on four different analytical platforms using chemiluminescence immunoassays/electrochemiluminescence immunoassays, and the results were divergent on each platform. Serial dilutions of serum samples revealed nonlinearity, suggesting assay interference. All hormonal measurements were in the normal range when heterophile antibody blocking tubes were used. The serum of the patient was then subjected to polyethylene glycol precipitation. The post-polyethylene glycol recovery resulted in hormone levels in the normal range. The patient did not receive any medications and has been under follow-up without any signs and symptoms for 24 months. CONCLUSIONS: This report illustrates a rare case of falsely elevated hormone levels due to assay interference caused by heterophile antibodies. We point out the importance of a close collaboration between clinicians and the laboratory to avoid unnecessary clinical investigations as well as inappropriate treatments.  
  Address Departments of Biochemistry (O.G., G.F.A.) and Endocrinology and Metabolism (C.K.D., M.A., M.M.Y., I.K., A.E.A., I.Y., M.A., F.T.), Gazi University Faculty of Medicine, 06100 Ankara, Turkey  
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  ISSN (up) 0021-972X ISBN Medium  
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  Notes PMID:25897621 Approved no  
  Call Number QEHB @ isla.wootton @ Serial 42160  
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Author Al-Awqati, Q. url  openurl
  Title Kidney growth and hypertrophy: the role of mTOR and vesicle trafficking Type Journal Article
  Year 2015 Publication Abbreviated Journal J Clin Invest  
  Volume 125 Issue 6 Pages 2267-2270  
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  Abstract The kidney, like other organs, grows in constant proportion to the rest of the body. When one kidney is removed, the remaining one hypertrophies. In a comprehensive series of studies, Chen et al. show that growth during maturation is mediated by the mTORC1 signaling pathway, which is induced by EGF-like peptides, and requires PI3K, PDK, AKT, mTORC2, and activation of mTORC1 through the combined effects of TSC and RHEB as part of a multiprotein complex localized on lysosomes. However, compensatory growth is mediated by amino acids, which act on mTORC1 independently of the previous pathway, and requires a class III PI3K (VPS34) that is known to be involved in vesicle trafficking to the lysosomes.  
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  ISSN (up) 0021-9738 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45804  
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Author Albers, J.; Danzer, C.; Rechsteiner, M.; Lehmann, H.; Brandt, L.P.; Hejhal, T.; Catalano, A.; Busenhart, P.; Gonçalves, A.F.; Brandt, S.; Bode, P.K.; Bode-Lesniewska, B.; Wild, P.J.; Frew, I.J. url  openurl
  Title A versatile modular vector system for rapid combinatorial mammalian genetics Type Journal Article
  Year 2015 Publication Abbreviated Journal J Clin Invest  
  Volume 125 Issue 4 Pages 1603-1619  
  Keywords Animals; Apoptosis; Caspase 9; Cells, Cultured; Cloning, Molecular; Clustered Regularly Interspaced Short Palindromic Repeats; Doxycycline; Drug Resistance; Gene Deletion; Gene Knockdown Techniques; Genetic Vectors; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lentivirus; Mice; Mice, SCID; PTEN Phosphohydrolase; Recombination, Genetic; research support, non-u.s. gov’t; Retinoblastoma Protein; RNA, Small Interfering; Sarcoma, Experimental; Transduction, Genetic; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays; Cas9/CRIPSR; Journal club  
  Abstract Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.  
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  ISSN (up) 0021-9738 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45848  
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