A Gestão de Stock: O Fornecimento de OutPut como factor de redução de custo

O presente trabalho tem como objectivo mostrar a importância que a Gestão económica de Stock tem no processo de redução de custo, por via da implementação de um modelo. E para isso far-se-á um estudo de caso numa empresa inserida no ramo de transformação de pescado – FRESCOMAR. A metodologia adoptada para alcançar os objectivos propostos passou pela pesquisa bibliográfica, recolha de dados e de informação relevante junto da empresa e tratamento dos dados numa folha de Excel. O modelo de gestão de Stock a ser implementado depende essencialmente da componente procura, onde que para uma empresa com procura constante utiliza-se os modelos determinísticos e para uma com procura aleatória utiliza-se os modelos estocásticos (Nível de Encomenda e Revisão Cíclica). Nos modelos determinísticos temos 4 modelos diferenciados pela forma de reposição e a admissibilidade da procura. Com as informações recolhidas junto da empresa em estudo escolhemos implementar o modelo de reposição não instantânea com ruptura não permitida e obtivemos a optimização do Stock com níveis reduzidos de produção e consequentemente houve uma diminuição do custo. Com resultados obtiveram-se ainda valores da Quantidade Óptima a ser Produzida, do Stock Máximo e do Custo Total Óptimo por unidade de tempo. Devido a diversidade de produtos propomos à empresa a utilização da análise ABC para classificar os produtos reagrupando-os em classes A, B e C, conforme o peso no consumo de Stock.

Leaf-litter amount as a factor in the structure of a ponerine ants community (Hymenoptera, Formicidae, Ponerinae) in an eastern Amazonian rainforest, Brazil

Leaf-litter amount as a factor in the structure of a ponerine ants community (Hymenoptera, Formicidae, Ponerinae) in an eastern Amazonian rainforest, Brazil. Leaf-litter may be an important factor in structuring ponerine ant communities (Hymenoptera, Formicidae, Ponerinae) in tropical rainforests. We specifically examined how leaf-litter affects the structure of a ponerine ant community in primary Amazonian rainforest sites at the Ferreira Penna Scientific Station, Pará, Brazil. A total of 53 species belonging to eight genera of three ponerine tribes were collected with mini-Winkler extractors. The amount of leaf-litter positively affected the abundance and richness of the ponerine ant community, and also influenced species composition. Nearby samples often had low species similarity, especially when adjacent samples differed in the amount of leaf-litter. Leaf-litter availability in Amazonian primary forests is a key factor for distribution of ground-dwelling ponerine species, even at small scales.

The social value of health programs: Is age a relevant factor?

In cost-effectiveness analysis (CEA) it is usually assumed that a QALY is of equal value to everybody, irrespective of the patient's age. However, it is possible that society assigns different social values to a QALY according to who gets it. In this paper we discuss the possibility of weighting health benefits for age in CEA. We also examinethe possibility that age-related preferences depend on the size of the health gain. An experiment was performedto test these hypotheses. The results assessing suggest that the patient's age is a relevant factor when assessing health gains.

A liderança como factor de sucesso empresarial O caso da empresa Anjos Mundilar

O desempenho da empresa é influenciado pelas competências dos seus funcionários. A competência humana aliada a outros recursos empresariais dá origem e sustentação à competência empresarial. A participação dos funcionários no processo de gestão de competências expondo as suas expectativas, motivações e também, percepções a respeito do seu superior e da estratégia de negócios da empresa é fundamental para o sucesso empresarial.

Auditoria interna como factor de promoção da qualidade do serviço educativo – sua aplicação no controlo dos sumários na Universidade Jean Piaget de Cabo Verde

Este trabalho aborda a auditoria como um meio para a promoção da qualidade de ensino praticado na Universidade Jean Piaget de Cabo Verde, tendo como referências os resultados das análises efectuadas aos sumários. De referir que, para esse efeito, tivemos que partir de extracto amostral de 25% dos 16 cursos de graduação que vêm sendo ministrados, procurando fazer jus à metodologia inicialmente escolhida que, para além da pesquisa bibliográfica, inclui, igualmente, o tratamento estatístico dos dados recolhidos. No tocante à recolha, ao tratamento e à análise dos dados, recorremos a duas abordagens, isto é, a abordagem quantitativa e a abordagem qualitativa. Na verdade, a abordagem quantitativa aparece já no momento do extracto da amostra; todavia, passa a estar mais evidenciada depois de termos elaborado grelhas que, com efeito, nos permitiram recolher e, consequentemente, fazer o tratamento dos dados relacionados com o cumprimento da carga horária e dos itens apontados nos programas pelo docente de cada disciplina, bem como no que toca ao cumprimento das exigências formais exigidas pela UniPiaget, com auxílio dos programas Excel e SPSS versão 11.0 for Windows.

Human immunodeficiency virus type 1 fitness is a determining factor in viral rebound and set point in chronic infection.

Human immunodeficiency virus type 1 (HIV-1) isolates from 20 chronically infected patients who participated in a structured treatment interruption (STI) trial were studied to determine whether viral fitness influences reestablishment of viremia. Viruses derived from individuals who spontaneously controlled viremia had significantly lower in vitro replication capacities than viruses derived from individuals that did not control viremia after interruption of antiretroviral therapy (ART), and replication capacities correlated with pre-ART and post-STI viral set points. Of note, no clinically relevant improvement of viral loads upon STI occurred. Virus isolates from controlling and noncontrolling patients were indistinguishable in terms of coreceptor usage, genetic subtype, and sensitivity to neutralizing antibodies. In contrast, viruses from controlling patients exhibited increased sensitivity to inhibition by chemokines. Sensitivity to inhibition by RANTES correlated strongly with slower replication kinetics of the virus isolates, suggesting a marked dependency of these virus isolates on high coreceptor densities on the target cells. In summary, our data indicate that viral fitness is a driving factor in determining the magnitude of viral rebound and viral set point in chronic HIV-1 infection, and thus fitness should be considered as a parameter influencing the outcome of therapeutic intervention in chronic infection.

Can the trabecular bone score (TBS) be considered as a major clinical risk factor (CRF) of osteoporotic fractures? A meta-like analysis

Abstract: To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist.Out of these factorsmany of themare indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50 years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 crosssectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest comparedwith themiddle TBS tertilewas 1.55[1.46- 1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF (Fig 1) and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

Liderança como factor de sucesso na gestão escolar O caso da Escola Secundária “Amor de Deus”

O presente trabalho de investigação destina-se a obtenção do grau de licenciatura em ciências de educação e praxis educativa, variante administração escolar na Universidade Jean Piaget de Cabo Verde, O trabalho de investigação intitula-se liderança como factor de sucesso na gestão escolar: O caso da escola secundária ―Amor de Deus‖ (cidade da praia), local de incidência de estudo. A metodologia utilizada permitiu-nos fazer consulta bibliográfica e sitografica sobre o tema. No que refere ao inquérito por questionário, uma amostra de 20 professores deram os seus contributos no universo de 43 docentes efectivo da escola, e a entrevista foi feita à directora da escola. Constatamos que a gestão das instituições do ensino secundário Amor de Deus que consideramos que uma escola nova está a atingir o nível alto de democratização uma vez que com os dirigentes aceitam as opiniões (quando relevante) dos diferentes elementos das organizações dando-lhes a autonomia e conferindo um vasto leque de competências aos seus diversos órgãos de gestão, nos planos administrativos, pedagógicos e disciplinar. O presente trabalho estudou o ciclo de gestão escolar das escolas secundárias a luz de do Decreto-Lei n° 20/2002 de 19 de Agosto, com vista a compreender os modelos de gestão escolar e a autonomia da escola como condição indispensável à prestação de um serviço educativo de qualidade. Muito são os problemas que se tem colocado às escolas secundárias de Cabo Verde nesse momento, como por exemplo os objectivos da escola, sua forma de actuação perante os dilemas gerado nessa sociedade em transformação e a sua forma de gestão. Neste sentido o tema em estudo é sem dúvida, polémico e de grande importância para as organizações educativas em geral, e em particular para a escola secundária em estudo.

A liderança como Factor de Motivação para o Trabalho em Equipa

A liderança constitui, hoje, um tema muito debatido pela sua importância no seio das organizações. Este factor é considerado por todas as organizações que têm objectivos e metas a alcançar. Quando falamos no alcance dos objectivos e metas, torna-se necessário mencionar a equipa que vai trabalhar para este fim. Daí a importância de referirmos a “Liderança como Factor de Motivação para o Trabalho em Equipa”. Visando contribuir para análise desta temática e a obtenção do grau de licenciatura, escolhemos o contexto da instituição Centro de Emprego e Formação Profissional da Praia (CEFPP), para fazer o nosso estudo. Ela que é uma organização que promove a formação, orientação e inserção na vida profissional, e tal como outras organizações necessita do exercício da liderança para motivação de sua equipa, á obtenção de resultados satisfatórios. O objectivo principal do nosso estudo é saber se o estilo de liderança predominantemente adoptado no CEFP da Praia incentiva o trabalho em equipa. Para atingir esse objectivo, apoiamos teoricamente, em autores que têm trabalhado a temática em questão e empiricamente, no estudo de caso realizado no “Centro de Emprego e Formação Profissional da Praia”, situado em Chão de Areia, Cidade da Praia. De referir que a recolha de dados foi efectuada mediante a aplicação de um questionário aos colaboradores e realização de uma entrevista ao Director do Centro. Quanto ao tratamento dos dados recolhidos através do questionário, recorremos ao Método Estatístico e dos dados da entrevista o Método Descritivo. Dos dados obtidos concluímos que o estilo de liderança predominante é o estilo Democrático e este incentiva os colaboradores a trabalharem em equipa.

The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors.

Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy.

Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

PURPOSE: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. PATIENTS AND METHODS: All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. RESULTS: With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). CONCLUSION: In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor.

The homeodomain protein PDX-1, referred as IPF-1/STF-1/IDX-1, is a transcriptional factor that plays a critical role in the control of several genes expressed in the pancreatic islet. PDX-1 gene expression has been previously shown to be reduced in cultured beta-cell lines chronically exposed to high glucose concentrations. As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. We have identified a repeat of a TAAT motif (5'-TAATA-ATAACA-3') conserved in the sequence of the human and murine GLUT2 promoters. Recombinant PDX-1 binds to this GLUT2TAAT motif in electrophoretic mobility shift experiments. PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. The GLUT2TAAT motif was mutated in the murine GLUT2 promoter (-1308/+49 bp) linked to a luciferase reporter gene and transfected into beta TC3 cells. Compared with the transcriptional activity of the wild type promoter, that of the mutated promoter decreases by 41%. Multiple copies of the GLUT2TAAT motif were ligated 5' to a heterologous promoter and transfected into a PDX-1-expressing cell line (beta TC3) and into cell lines lacking the homeobox factor (InR1-G9 and JEG-3). The GLUT2TAAT motif mediates the activation of the heterologous promoter in the PDX-1-expressing cell line but not in InR1-G9 or JEG-3 cell lines. Furthermore, cotransfection in a PDX-1-deficient cell line with the expression vector encoding PDX-1 transactivates specifically the heterologous promoter containing the multimerized GLUT2TAAT motif. These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif.

Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

Canine distemper virus : persistence and pathology in the central nervous system

Résumé : Le virus de la maladie de Carré (en anglais: canine distemper virus, CDV) qui est pathogène pour les chiens et autres carnivores, est très semblable au virus de la rougeole humaine (en anglais MV). Ces deux virus font partie du genre des Morbillivirus qui appartient à la famille des Paramyxoviridae. Ils induisent des complications dans le système nerveux central (SNC). Au stade précoce et aigu de l'infection du SNC, le CDV induit une démyélinisation (1). Ce stade évolue dans certains cas vers une infection chronique avec progression de la démyélinisation. Pendant le stade précoce, qui suit en général de trois semaines les premiers symptômes, le processus de démyélinisation est associé à la réplication du virus et n'est pas considéré comme inflammatoire (1). Par contre, au stade chronique, la progression des plaques de démyélinisation semble être plutôt liée à des processus immunogènes caractéristiques (2), retrouvés également dans la sclérose en plaques (SEP) chez les humains. Pour cette raison, le CDV est considéré comme un modèle pour la SEP humaine et aussi pour l'étude des maladies et complications induites par les Morbillivirus en général (3). Dans notre laboratoire, nous avons utilisé la souche A75/17-CDV, qui est considérée comme le modèle des souches neurovirulentes de CDV. Nous avons cherché en premier lieu à établir un système robuste pour infecter des cultures neuronales avec le CDV. Nous avons choisi les cultures primaires de l'hippocampe du nouveau-né de rat (4), que nous avons ensuite infecté avec une version modifiée du A75/17, appelée rgA75/17-V (5). Dans ces cultures, nous avons prouvé que le CDV infecte des neurones et des astrocytes. Malgré une infection qui se diffuse lentement entre les cellules, cette infection cause une mort massive aussi bien des neurones infectés que non infectés. En parallèle, les astrocytes perdent leur morphologie de type étoilé pour un type polygonal. Finalment, nous avons trouvé une augmentation importante de la concentration en glutamate dans le milieu de culture, qui laisse présumer une sécrétion de glutamate par les cultures infectées (6). Nous avons ensuite étudié le mécanisme des effets cytopathiques induits par le CDV. Nous avons d'abord démontré que les glycoprotéines de surface F et H du CDV s'accumulent massivement dans le réticulum endoplasmique (RE). Cette accumulation déclenche un stress du RE, qui est caractérisé par une forte expression du facteur de transcription proapoptotique CHOP/GADD 153 et de le la calreticuline (CRT). La CRT est une protéine chaperonne localisée dans le RE et impliquée dans l'homéostasie du calcium (Ca2+) et dans le repliement des protéines. En transfectant des cellules de Vero avec des plasmides codant pour plusieurs mutants de la glycoprotéine F de CDV, nous avons démontré une corrélation entre l'accumulation des protéines virales dans le RE et l'augmentation de l'expression de CRT, le stress du RE et la perte de l'homéostasie du Ca2+. Nous avons obtenu des résultats semblables avec des cultures de cellules primaires de cerveau de rat. Ces résultats suggèrent que la CRT joue un rôle crucial dans les phénomènes neurodégénératifs pendant l'infection du SNC, notamment par le relazgage du glutamate via le Ca2+. De manière intéressante, nous démontrons également que l'infection de CDV induit une fragmentation atypique de la CRT. Cette fragmentation induit une re-localisation et une exposition sélective de fragments amino-terminaux de la CRT, connus pour êtres fortement immunogènes à la surface des cellules infectées et non infectées. A partir de ce résultat et des résultats précédents, nous proposons le mécanisme suivant: après l'infection par le CDV, la rétention dans le RE des protéines F et H provoque un stress du RE et une perte de l'homéostasie du Ca2+. Ceci induit la libération du glutamate, qui cause une dégénération rapide du SNC (sur plusieurs jours ou semaines) correspondant à la phase aiguë de la maladie chez le chien. En revanche, les fragments amino-terminaux de la CRT libérés à la surface des cellules infectées peuvent avoir un rôle important dans l'établissement d'une démyélinisation d'origine immunogène, typique de la phase chronique de l'infection de CDV. Summary : The dog pathogen canine distemper virus (CDV), closely related to the human pathogen measles virus (MV), belongs to the Morbillivirus genus of the Paramyxoviridae family. Both CDV and NIV induce complications in the central nervous system (CNS). In the acute early stage of the infection in CNS, the CDV infection induces demyelination. This stage is sometimes followed by a late persistent stage of infection with a progression of the demyelinating lesions (1). The acute early stage occurs around three weeks after the infection and demyelinating processes are associated with active virus replication and are not associated to inflammation (1). In contrast during late persistent stage, the demyelination plaque progression seems to be mainly due to an immunopathological process (2), which characteristics are shared in many aspects with the human disease multiple sclerosis (MS). For these reasons, CDV is considered as a model for human multiple sclerosis, as well as for the study of Morbillivirus-mediated pathogenesis (3). In our laboratory, we used the A75/17-CDV strain that is considered to be the prototype of neurovirulent CDV strain. We first sought to establish a well characterized and robust model for CDV infection of a neuronal culture. We chose primary cultures from newborn rat hippocampes (4) that we infected with a modified version of A75/17, called rgA75/17-V (5). In these cultures, we showed that CDV infects both neurons and astrocytes. While the infection spreads only slowly to neighbouring cells, it causes a massive death of neurons, which includes also non-infected neurons. In parallel, astrocytes undergo morphological changes from the stellate type to the polygonal type. The pharmacological blocking of the glutamate receptors revealed an implication of glutamatergic signalling in the virus-mediated cytopathic effect. Finally, we found a drastic increase concentration of glutamate in the culture medium, suggesting that glutamate was released from the cultured cells (6). We further studied the mechanism of the CDV-induced cytopathic effects. We first demonstrated that the CDV surface glycoprotein F and H markedly accumulate in the endoplasmic reticulum (ER). This accumulation triggers an ER stress, which is characterized by increased expression of the proapoptotic transcription factor CHOP/GADD 153 and calreticulin (CRT). CRT is an ER resident chaperon involved in the Ca2+ homeostasis and in the response to misfolded proteins. Transfections of Vero cells with plasmids encoding various CDV glycoprotein mutants reveal a correlation between accumulation of viral proteins in the ER, CRT overexpression, ER stress and alteration of ER Ca2+ homeostasis. Importantly, similar results are also obtained in primary cell cultures from rat brain. These results suggest that CRT plays a crucial role in CNS infection, particularly due to CRT involvement in Ca2+ mediated glutamate releases, and subsequent neurodegenerative disorders. Very intriguingly, we also demonstrated that CDV infection induces an atypical CRT fragmentation, with relocalisation and selective exposure of the highly immunogenic CRT N-terminal fragments at the surface of infected and neighbouring non-infected cells. Altogether our results combined with previous findings suggest the following scenario. After CDV infection, F and H retention alter Ca2+ homeostasis, and induce glutamate release, which in turn causes rapid CNS degeneration (within days or a week) corresponding to the acute phase of the disease in dogs. In contrast, the CRT N-terminal fragments released at the surface of infected cells may rather have an important role in the establishment of the autoimmune demyelination in the late stage of CDV infection.

Connexin26 is regulated in rat urothelium by the scaffold protein IB1/JIP-1.

Proper function of the wall of bladder requires gap junctional communication for coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial cells, whereas Cx26 expression is restricted to the epithelium. We used a model of bladder outlet obstruction, in which a ligature is placed around the urethra to increase voiding pressure. Increased fluid pressure was associated with increased Cx43 and Cx26 mRNA expression and with the activation of a signaling cascade including the transcription factor c-Jun, which is a component of the AP-1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine retention, we have found a reduced content of IB1/JIP-1 in urothelial cells, which in turn induced a drastic increase of JNK and AP-1 binding activities. The stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using a viral gene transfer approach, a condition which also resulted in a decrease in Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that urothelial Cx26 may be directly regulated by the AP-1 complex.