Strategy formation effects on managerial action: Strategy in the back of your head

This paper examines the interplay between top and middle level managers as strategy-making settles and in subsequent managerial action. It reports on an exploratory case study at a car service company that has an aggressive expansion strategy. The study examines the context and characteristics of the strategy-making process and the specific evolution of fourteen strategic initiatives. Of particular interest was that the interplay between top managers and middle managers was resolved through a legitimizing mechanism. This interplay took place through deliberation and agreement, with extensive participation, and developed into shared views of strategy which provided legitimation. Once settled, strategic initiatives were subsequently developed in harmony with the strategic intent. This agreement provided guidance to carry out strategic initiatives and was a source of resilient strategic conversation. From analysis of the case, a model presenting how strategic intent interacts with the creation of strategic initiatives is presented. This model aims at overcoming the mutually exclusive bottom-up and top-down sources of influence, integrating both in a process model.Strategy-making; middle management; top management; managerial action;

Sequence of thinking and acting in strategy making

This paper gives an answer to the continuing emergent-deliberate debate. Thinking and acting are two outstanding features of this controversy. What is needed in the field is a framework that can explain under what circumstances each of these two features takes place along the strategy-making process. The focus of the paper is on the sequence of thinking and acting in the strategy-making process. A framework is developed to show how thinking co-evolves with action in a succession of strategic activities. Within boundaries, strategic activities are carried forward by social automatic behaviour, following a set pattern. Yet, when an action crosses a certain threshold, a different condition of awareness is achieved. Similarly, thought can cross an equivalent threshold, giving rise to consciousness. Either condition enhances the organization's ability to make changes in the direction of its strategic activity.strategy-making process; strategic activities;

Subsidiary strategy: The embeddedness component

This paper inductively derives a model that develops the concept of subsidiary embeddedness as the canvas within which subsidiary strategy can take place. Our model identifies three hierarchical levels of embeddedness: Operational embeddedness relates to the interlocking day-to-day relations. Capability embeddedness deals with the development of competitive capabilities for the multinational as a whole. Strategic embeddedness deals with subsidiary participation in the MNC strategy setting. We deem these three types of embeddedness as ways to develop subsidiary strategic alternatives. In as such, different types of subsidiary embeddedness imply different subsidiary roles. Embeddedness, as it was inductively derived from a revelatory case study, is not merely an outcome of the institutional setting, but a resource a subsidiary can manage by means of manipulating dependencies or exerting influence over the allocation of critical resources. A subsidiary can modify its embeddedness to change its strategic restraints. Therefore, the development of subsidiary embeddedness becomes an integral part of subsidiary strategy.Multinational management; subsidiary; strategy; organization;

Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome

<p>Abstract</p> <p>Background</p> <p>Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (<it>RAI1</it>). Little is known about the function of human RAI1.</p> <p>Results</p> <p>We generated the full-length cDNA of the wild type protein and five mutated forms: <it>RAI1-HA </it>2687delC, <it>RAI1-HA </it>3103delC, <it>RAI1 </it>R960X, <it>RAI1-HA </it>Q1562R, and <it>RAI1-HA </it>S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity.</p> <p>Conclusion</p> <p>Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.</p

Ejercicio físico para personas con demencia y deterioro cognitivo leve: consideraciones metodológicas

The exponential worldwide increase in the number of older adults is causing a parallel rise in the number of cases of neurodegenerative diseases, such as mild cognitive impairment (MCI) and dementia. Exercise is a promising strategy for improving physical and cognitive function in healthy older adults, reducing the risk of developing MCI and dementia, and improving physical and cognitive function as well as decreasing neuropsychiatric symptoms in people with MCI and dementia. However, there are still some inconsistencies in the literature, especially in regards to the cognitive benefits, and there are currently no guidelines for prescribing exercise for older adults with cognitive impairment. In this article, a narrative review on the benefits of exercise for people with MCI and dementia was conducted, establishing some preliminary guidelines for prescribing exercise efficiently and safely in this population.El incremento exponencial del número de personas mayores a nivel mundial, está causando un aumento paralelo en el número de casos de enfermedades neurodegenerativas, como es el caso del deterioro cognitivo leve (DCL) o la demencia. El ejercicio físico es una estrategia prometedora para mejorar la función física y cognitiva de los adultos mayores sanos, reducir el riesgo de desarrollar un DCL o una demencia, así como mejorar la función física, cognitiva y los síntomas neuropsiquiátricos en personas con DCL o demencia. Sin embargo, existen todavía algunas inconsistencias en la literatura científica, especialmente acerca de los beneficios cognitivos, y faltan pautas metodológicas para prescribir ejercicio físico para personas mayores con deterioro cognitivo. En este artículo, se ha llevado a cabo una revisión narrativa de la literatura acerca de los beneficios del ejercicio físico para personas con DCL y demencia, estableciendo unas pautas metodológicas preliminares para prescribir ejercicio físico, de forma eficiente y segura en esta población.Miguel García-Jaén participated in this study supported by a pre-doctoral grant ACIF/2016/048 from the Generalitat Valenciana, Spain

Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors

Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.Fil: Dalvi, Maithili P.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Wang, Lei. University of Texas. Southwestern Medical Center; Estados UnidosFil: Zhong, Rui. University of Texas. Southwestern Medical Center; Estados UnidosFil: Kollipara, Rahul K.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Park, Hyunsil. University of Texas. Southwestern Medical Center; Estados UnidosFil: Bayo Fina, Juan Miguel. University of Texas. Southwestern Medical Center; Estados Unidos. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Yenerall, Paul. University of Texas. Southwestern Medical Center; Estados UnidosFil: Zhou, Yunyun. University of Texas. Southwestern Medical Center; Estados UnidosFil: Timmons, Brenda C.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Rodriguez Canales, Jaime. University of Texas; Estados UnidosFil: Behrens, Carmen. Md Anderson Cancer Center; Estados UnidosFil: Mino, Barbara. University of Texas; Estados UnidosFil: Villalobos, Pamela. University of Texas; Estados UnidosFil: Parra, Edwin R.. University of Texas; Estados UnidosFil: Suraokar, Milind. University of Texas; Estados UnidosFil: Pataer, Apar. University of Texas; Estados UnidosFil: Swisher, Stephen G.. University of Texas; Estados UnidosFil: Kalhor, Neda. University of Texas; Estados UnidosFil: Bhanu, Natarajan V.. University of Pennsylvania; Estados UnidosFil: Garcia, Benjamin A.. University of Pennsylvania; Estados UnidosFil: Heymach, John V.. University of Texas; Estados UnidosFil: Coombes, Kevin. University of Texas; Estados UnidosFil: Xie, Yang. University of Texas. Southwestern Medical Center; Estados UnidosFil: Girard, Luc. University of Texas. Southwestern Medical Center; Estados UnidosFil: Gazdar, Adi F.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Kittler, Ralf. University of Texas. Southwestern Medical Center; Estados UnidosFil: Wistuba, Ignacio I.. University of Texas; Estados UnidosFil: Minna, John D.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Martinez, Elisabeth D.. University of Texas. Southwestern Medical Center; Estados Unido

The genetic ancestry of American Creole cattle inferred from uniparental and autosomal genetic markers

Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development

Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

BACKGROUND: Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits

Podocyte-Specific Overexpression of Wild Type or Mutant Trpc6 in Mice Is Sufficient to Cause Glomerular Disease

Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2–3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes