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PurposeAlthough most research considers organizational learning as an antecedent of innovation, the relationship is complex and could be reciprocal. Therefore, more research is needed on the profit gained from the learning and organization acquires from its innovation activities. Using the concept of fit, this paper aims to investigate whether organizational learning increases when an organization’s technical innovation level exceeds that of its competitors (positive misfit), theorizing the curvilinear effect of positive technical innovation misfit on organizational learning.Design/methodology/approachThis paper uses regression analysis with survey data gathered from 202 European firms.FindingsThe findings support the argument that positive technical innovation misfit has an inverted-U shaped effect on organizational learning.Practical implicationsThe findings obtained should orient firm managers to developing a work environment that enables optimal levels of technical innovation and learning – levels at which the technical innovation developed drives learning among the organization’s members but avoids becoming trapped in the organizational complexity involved in very high levels of positive technical innovation misfit.Originality/valueThis study resolves conflicting views of the relationship between organizational learning and technical innovation and adds to the existing literature that indicates that proactive innovative firms can fail when becoming learners.

Metabolic and immune mediators activate many of the same signal transduction pathways. Therefore, molecules that regulate metabolism often affect immune responses. Leptin is an adipokine that exemplifies this interplay. Leptin is the body's major nutritional status sensor, but it also plays a key role in immune system regulation. To provide an in vitro tool to investigate the link between leptin and innate immunity, we immortalized and characterized a leptin receptor-deficient macrophage cell line, DB-1. The cell line was created using bone marrow cells from leptin receptor-deficient mice. Bone marrow cells were differentiated into macrophages by culturing them with recombinant mouse macrophage colony stimulating factor, and passaged when confluent for 6 months. The cells spontaneously immortalized at approximately passage 20. Cells were cloned twice by limiting dilution cloning prior to characterization. The macrophage cell line is diploid and grows at a linear rate for 4-5 days before reaching the growth plateau. The cells are MAC-2 and F4/80 positive and have phagocytic activity similar to primary macrophages from wild-type and leptin receptor-deficient mice. DB-1 cells were responsive to stimulation with interferon-γ as measured by increase in Nos2 transcript levels. In addition, DB-1 macrophages are not responsive to the chemotactic signaling of adipocyte conditioned media nor leptin when compared to primary WT macrophages. We believe that DB-1 cells provide a dependable tool to study the role of leptin or the leptin receptor in obesity-associated inflammation and immune system dysregulation.

Purpose – The purpose of this paper is to analyze how the presence of communication and knowledge flows influences the creation of a work context that supports innovation, and how this relationship is moderated by labor externalization. Design/methodology/approach – To study these relationships, the authors use a sample of 249 workers from five organizations. The different hypotheses proposed are contrasted using hierarchical regression analysis. Findings – The results obtained show the authors that, when communication flows exist, workers’ orientation to innovation is greater; likewise, knowledge transfer influences workers’ innovative attitude positively. However, the results are different when externalization of workers acts as a moderating variable. Practical implications – The firm's management should make decisions and foster the production of information flows between employees, as the results obtained indicate that communication and knowledge transfer encourage employee attitudes and behavior favorable to innovation. Originality/value – The main contribution of this study is to provide new empirical evidence on the influence of communication and knowledge flows on workers’ orientation to innovation. The authors also analyze how these relationships are affected by the presence of externalization. The evidence obtained in this study permits to deduce what actions foster or inhibit organizations in creating a work context that supports innovation and thus encourages the generation of innovation.

We differentiated mouse bone marrow cells in the presence of recombinant macrophage colony stimulating (rM-CSF) factor for 14 days during the flight of space shuttle Space Transportation System (STS)-126. We tested the hypothesis that the receptor expression for M-CSF, c-Fms was reduced. We used flow cytometry to assess molecules on cells that were preserved during flight to define the differentiation state of the developing bone marrow macrophages; including CD11b, CD31, CD44, Ly6C, Ly6G, F4/80, Mac2, c-Fos as well as c-Fms. In addition, RNA was preserved during the flight and was used to perform a gene microarray. We found that there were significant differences in the number of macrophages that developed in space compared to controls maintained on Earth. We found that there were significant changes in the distribution of cells that expressed CD11b, CD31, F4/80, Mac2, Ly6C and c-Fos. However, there were no changes in c-Fms expression and no consistent pattern of advanced or retarded differentiation during space flight. We also found a pattern of transcript levels that would be consistent with a relatively normal differentiation outcome but increased proliferation by the bone marrow macrophages that were assayed after 14 days of space flight. There also was a surprising pattern of space flight influence on genes of the coagulation pathway. These data confirm that a space flight can have an impact on the in vitro development of macrophages from mouse bone marrow cells.

[EN] Benjamin Kennicott (1718-1783), important Hebraist and librarian at the Radcliffe Library, gathered a number of Hebrew Bible manuscripts, kept nowadays in the Bodleian library. It is a collection of nine bibles, being seven of them of Sephardic origin; only two were copied in Ashkenaz and one in Italy. Until the present days, the only complete catalogue of those manuscripts in Neubauer's, dated in 1886, which obviously foes not include codicological aspects. The present work is focused in a detailed study of the bibles in this collection copied in the Iberian Peninsula, excluding the famous Kennicott Bible, which has been already described and studied. The work on each manuscript is two folded: the first part correspond to the description and in the second part textual aspects of the manuscript are presented., [ES] Benjamín Kennicott (1718-1783) fue un destacado hebraísta y bibliotecario en la Radcliffe Library de Oxford. A lo largo de su vida reunió un importante número de manuscritos hebreos bíblicos, que hoy se conservan en la Biblioteca Bodleiana. Se trata de una colección de nueve biblias, de las cuales siete son de origen sefardí; una de ellas fue copiada en Askenaz y otra en Italia.Hasta el momento, el único catálogo que existe de ellas es el de Neubauer, fechado en 1886 y que, obviamente, no incluye aspectos codicológicos. EL presente trabajo ofrece un detallado estudio de las biblias sefardíes de esta colección, excluyendo la famosa Biblia de Kennicott (Ms. Kennicott 1), que ya ha sido objeto de numerosos estudios de forma independiente.La descripción de cada manuscrito comprende dos partes: la primera ofrece la descripción codicológica y la segunda ofrece un análisis más detallado de sus aspectos textuales., Research project "Legado de Sefarad. La producción material e intelectual del judaismo sefardí bajomedieval" (Ref. FFI2012-38451) and "Patrimonio Cultural Escrito de los Judios en la Península Ibérica" (Ref. FFI2012-33809)

We examined the cell-mediated immune response against the obligate intracellular bacterium Ehrlichia chaffeensis after single or multiple experimental antigen exposures. We confirmed that CD4 knock-out mice had longer delays in clearance of bacteria from the site of injection compared to wild-type B6 mice. However, the absence of CD8+ T cells did not affect clearance. We found that there was effective mobilization of splenic effector memory cells after primary and secondary experimental challenges. We designed several IAb-binding peptides using established algorithms and tested them for their ability to stimulate T-cell proliferation. Several of the IAb-binding peptides were immunogenic. The most stimulatory epitope was conserved between p28-OMP 14 and p28-OMP 19. Several E. chaffeensis p28-OMP 14 and p28-OMP 19H-2Kb binding peptides including IGGHFHKV, IGNEFRDI, and EAHRYCAL were also identified as epitopes for H-2b-restricted CD19−CD8+ T cells.

Cathelicidins, a group of cationic peptides found in leukocytes and epithelial cells, play a central role in the early innate immune defense against infection. Although these host defense peptides have been reported in several mammalian species, including primates, no cathelicidins have been identified in carnivores. Here we report the cloning, tissue expression and biological activity of a novel canine cathelicidin (K9CATH). The full-length cDNA sequence of K9CATH encodes a predicted 172 amino acid pre-propeptide that is 60–70% similar to other mammalian cathelicidins. Mass spectrometry analysis confirmed that the 38 aa mature K9CATH peptide was present in neutrophil granule contents. Synthetic K9CATH displayed broad antimicrobial activity against Gram-positive bacteria ( Listeria monocytogenes , and Staphylococcus aureus ; MICs (minimal inhibitory concentrations) 0.5 and 50 μM, respectively), Gram-negative bacteria ( Escherichia coli , Klebsiella pneumoniae , Salmonella serotype Typhimurium, Pseudomonas aeruginosa , Proteus mirabilis ; MICs 1.25 μM, Salmonella serotype Enteritidis; MIC 0.5 μM, and Neisseria gonorrhoeae ; MIC 0.06 μM), and yeast ( Candida albicans ; MIC 12.5–50 μM). K9CATH demonstrated high antimicrobial activity against Ureaplasma canigenitalium , and lower activity against Ureaplasma urealyticum (MIC 0.06 and 50 μM, respectively). Similar to its ovine congener SMAP-29, K9CATH possesses salt-independent antimicrobial activity and LPS binding capacity. K9CATH displayed minimal hemolytic activity against human, dog and chicken erythrocytes. The potency and broad antimicrobial activity of K9CATH suggest that this peptide may act as a fundamental contributor to the innate immune responses in this carnivore species

Obesity is characterized by an increased recruitment of proinflammatory macrophages to the adipose tissue (AT), leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimeric C57BL/6J mice reconstituted with either leptin receptor-deficient (db/db) or wild-type (WT) bone marrow and challenged them with a high-fat diet (HFD) for 16 weeks. Mice reconstituted with db/db bone marrow (WT/db), had significantly lower body weight and adiposity compared with mice with WT bone marrow (WT/WT). Gonadal AT in WT/db mice displayed a 2-fold lower expression of the inflammatory genes Tnfa, Il6, and Ccl2. In addition, gonadal fat of WT/db mice contained significantly fewer crown-like structures compared with WT/WT mice, and most of their AT macrophages expressed macrophage galactose-type C type lectin 1 (MGL1) and were C-C chemokine receptor type 2 (CCR2)-negative, indicative of an anti-inflammatory phenotype. Moreover, WT/db mice exhibited greater insulin sensitivity compared with WT/WT mice. These data show that disrupted leptin signaling in bone marrow-derived cells attenuates the proinflammatory conditions that mediate many of the metabolic complications that characterize obesity. Our findings establish a novel mechanism involved in the regulation of obesity-associated systemic inflammation and support the hypothesis that leptin is a proinflammatory cytokine.

An important number of manuscripts reproduce Rashi’s commentary on the Torah. Among them, we can found in Spain a codex with particular characteristics: the codex is divided in two parts kept in two different libraries: the Lázaro Galdiano museum in Madrid and the Colombina Library in Seville. A systematic study of both fragments at one side and the comparison between its decorations and illuminations with those of other similar manuscripts allows us to make some considerations and remarks to the partial studies published until now. The codex, written in different stages and different periods, reflects diverse cultural traditions existing in Iberian Peninsula during the Middle Ages., Existen numerosos manuscritos hebreo que copian el comentario de Rashi a la Biblia. Pero hay un ejemplar en España que reúne unas características especiales. El códice se encuentra dividido en dos fragmentos conservados en dos bibliotecas distintas: la del museo Lázaro Galdiano de Madrid y la Biblioteca Colombina de Sevilla. Un estudio sistemático de ambos fragmentos al mismo tiempo y la comparación de varias de sus decoraciones e ilustraciones con otros manuscritos similares permiten hacer algunas puntualizaciones a los estudios parciales ya hechos sobre el códice, realizado en varias fases y en épocas distintas, reflejo de diversas tradiciones culturales existentes en la Europa judía medieval.

Ehrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on Drosophila melanogaster S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to support Ehrlichia replication. Three additional D. melanogaster fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes CG6479 , separation anxiety , chitinase 11 , CG6364 ( Uck2 ), CG6543 ( Echs1 ), withered ( whd ), CG15881 ( Ccdc58 ), CG14806 ( Apop1 ), CG11875 ( Nup37 ), and dumpy ( dp ) had increased resistance to infection with Ehrlichia . Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes ( san , Cht11 , Uck2 , Echs1 , whd , C cdc58 , and Apop1 ) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human UCK2 gene indicates that the disruption of the uridine-cytidine kinase affects E. chaffeensis replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for E. chaffeensis replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides.

Obesity is associated with a proinflammatory state, with macrophage infiltration into adipose tissue. We tested the hypothesis that communication between macrophages and adipocytes affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function. To test this hypothesis, we cocultured 3T3-L1 adipocytes with C2D macrophages or primary peritoneal mouse macrophages and examined the impacts of macrophages and adipocytes on each other. Adipocytes and preadipocytes did not affect C2D macrophageTNF-α,IL-6, orIL-1βtranscript concentrations relative to those obtained when C2D macrophages were incubated alone. However, preadipocytes and adipocytes increased PEC-C2D macrophageIL-6transcript levels, while preadipocytes inhibitedIL-1βtranscript levels compared to those obtained when PEC-C2D macrophages were incubated in medium alone. We found that adipocyte coculture increased macrophage consumption of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and, in some cases, IL-6. C2D macrophages increasingly downregulatedGLUT4transcript levels in differentiated adipocytes. Recombinant TNF-α, IL-1β, and IL-6 also downregulatedGLUT4transcript levels relative to those for the control. However, only IL-6 was inhibitory at concentrations detected in macrophage-adipocyte cocultures. IL-6 and TNF-α, but not IL-1β, inhibited Akt phosphorylation within 15 min of insulin stimulation, but only IL-6 was inhibitory 30 min after stimulation. Lastly, we found that adipocyte differentiation was inhibited by macrophages or by recombinant TNF-α, IL-6, and IL-1β, with IL-6 having the most impact. These data suggest that the interaction between macrophages and adipocytes is a complex process, and they support the hypothesis that the macrophage-adipocyte interaction affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function.

There are still questions about whether macrophage differentiation is predetermined or is induced in response to tissue microenvironments. C2D macrophage cells reside early in the macrophage lineage in vitro, but differentiate to a more mature phenotype after adoptive transfer to the peritoneal cavity (PEC-C2D). Since C2D macrophage cells also traffic to adipose tissue after adoptive transfer, we explored the impact of white adipose tissue (WAT), brown adipose tissue (BAT) and in vitro cultured adipocytes on C2D macrophage cells. When PEC-C2D macrophage cells were cultured with preadipocytes the cells stretched out and CD11b and Mac-2 expression was lower compared to PEC-C2D macrophage cells placed in vitro alone. In contrast, PEC-C2D cells co-cultured with adipocytes maintained smaller, round morphology and more cells expressed Mac-2 compared to PEC-C2D co-cultured with preadipocytes. After intraperitoneal injection, C2D macrophage cells migrated into both WAT and BAT. A higher percentage of C2D macrophage cells isolated from WAT (WAT-C2D) expressed Ly-6C (33%), CD11b (11%), Mac-2 (11%) and F4/80 (29%) compared to C2D macrophage cells isolated from BAT (BAT-C2D). Overall, BAT-C2D macrophage cells had reduced expression of many cytokine, chemokine and receptor gene transcripts when compared to in vitro grown C2D macrophages, while WAT-C2D macrophage cells and PEC-C2D up-regulated many of these gene transcripts. These data suggest that the C2D macrophage phenotype can change rapidly and distinct phenotypes are induced by different microenvironments.

Bone marrow cells were isolated from the humeri of C57BL/6 mice after a 13-day flight on the space shuttle Space Transportation System (STS)-118 to determine how spaceflight affects differentiation of cells in the granulocytic lineage. We used flow cytometry to assess the expression of molecules that define the maturation/activation state of cells in the granulocytic lineage on three bone marrow cell subpopulations. These molecules included Ly6C, CD11b, CD31 (platelet endothelial cell adhesion molecule-1), Ly6G (Gr-1), F4/80, CD44, and c-Fos. The three subpopulations were small agranular cells [region (R)1], larger granular cells (R2), which were mostly neutrophils, and very large, very granular cells (R3), which had properties of macrophages. Although there were no composite phenotypic differences between total bone marrow cells isolated from spaceflight and ground-control mice, there were subpopulation differences in Ly6C (R1 and R3), CD11b (R2), CD31 (R1, R2, and R3), Ly6G (R3), F4/80 (R3), CD44high(R3), and c-Fos (R1, R2, and R3). In particular, the elevation of CD11b in the R2 subpopulation suggests neutrophil activation in response to landing. In addition, decreases in Ly6C, c-Fos, CD44high, and Ly6G and an increase in F4/80 suggest that the cells in the bone marrow R3 subpopulation of spaceflight mice were more differentiated compared with ground-control mice. The presence of more differentiated cells may not pose an immediate risk to immune resistance. However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights.