Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure

In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT(7) receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively. 5-HT(7) immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT(7) immunoreactivity. The selective 5-HT(7) receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently. Our in vitro experiments suggest an involvement of the 5-HT(7) receptor subtype in contractility of equine intestine. While the 5-HT(7) receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT(7) receptor ligand SB-269970, suggesting it exerting inverse agonist properties.

Is the Market Eroding Moral Norms? A Micro-Analytical Validation of Some Ideas of Anomie Theory

Anomie theorists have been reporting the suppression of shared welfare orientations by the overwhelming dominance of economic values within capitalist societies since before the outset of neoliberalism debate. Obligations concerning common welfare are more and more often subordinated to the overarching aim of realizing economic success goals. This should be especially valid with for social life in contemporary market societies. This empirical investigation examines the extent to which market imperatives and values of the societal community are anchored within the normative orientations of market actors. Special attention is paid to whether the shape of these normative orientations varies with respect to the degree of market inclusion. Empirical analyses, based on the data of a standardized written survey within the German working population carried out in 2002, show that different types of normative orientation can be distinguished among market actors. These types are quite similar to the well-known types of anomic adaptation developed by Robert K. Merton in “Social Structure and Anomie” and are externally valid with respect to the prediction of different forms of economic crime. Further analyses show that the type of normative orientation actors adopt within everyday life depends on the degree of market inclusion. Confirming anomie theory, it is shown that the individual willingness to subordinate matters of common welfare to the aim of economic success—radical market activism—gets stronger the more actors are included in the market sphere. Finally, the relevance of reported findings for the explanation of violent behavior, especially with view to varieties of corporate violence, is discussed.

Cow-Calf Production from Alfalfa-Grass or Smooth Bromegrass Pastures Rotationally Grazed at Three Stocking Rates

Pastures containing alfalfa-grass or smooth bromegrass were stocked with .6, .8, or 1.0 cow-calf units per acre to compare cow and calf production in rotational grazing systems managed for optimum forage quality. To remove excess forage early in the grazing season, yearling heifers or steers grazed with the cows in each pasture at a stocking rate of .6 ccu per acre for the first 28, 37, and 40 days of grazing in years one, two, and three. Live forage density and days of grazing per paddock were estimated by sward height. Cows, calves, and yearlings were weighed and cows condition scored every 28 days. All cows grazed for 140 days unless forage became limiting. The cows on the smooth bromegrass pasture stocked at 1.0 cow-calf units per acre were removed after 119 days in 1994, 129 days in 1995, and 125 days in 1996. Cows on one of the alfalfagrass pastures stocked at 1.0 ccu per acre were removed after 136 days of grazing in 1996 because of lack of forage. Alfalfa-grass pastures tended to have a more consistent supply of forage over the grazing season than the bromegrass pastures. Cows grazing the alfalfa-grass pastures had greater seasonal weight gains and body condition score increases and lower yearling weight gains than the smooth bromegrass pastures. Daily and total calf weight gains and total animal production also tended to be greater in alfalfa-cool season grass pastures. Increasing stocking rates resulted in significantly lower cow body condition increases and yearling weight gains, and also increased the amounts of calf and total growing animal produced.

Cow-Calf Production from Alfalfa-grass or Smooth Bromegrass Pastures Rotationally Grazed at Different Stocking Rates

Pastures containing alfalfa-smooth bromegrass or smooth bromegrass were stocked with .6, .8, or 1.0 cow-calf units per acre to compare cow and calf production in rotational grazing systems managed for optimum forage quality. To remove excess forage early in the grazing season, yearling heifers grazed with the cows in each pasture at a stocking rate of .6 heifers per acre for the first 28 days of grazing. Live forage density and days of grazing per paddock were estimated by sward height. Cows, calves, and heifers were weighed and cows condition scored every 28 days. All cows grazed for 140 days except those grazing the smooth bromegrass pasture stocked at 1.0 cow-calf units per acre; these were removed after 119 days in 1994 and 129 days in 1995 because of lack of forage. Alfalfa-grass pastures tended to have a more consistent supply of forage over the grazing season than the bromegrass pastures. Cows grazing the alfalfa-cool season grass pastures had greater seasonal weight gains and body condition score increases and lower heifer weight gains than the smooth bromegrass pastures. Daily and total calf weight gains and total animal production also tended to be greater in alfalfa-cool season grass pastures. Increasing stocking rates resulted in significantly lower condition increases and heifer weight gains, while increasing the amounts of calf and total growing animal produced.

Potential Value of Ultrasound to Sort Feeder Cattle into More Uniform Groups for Finishing and Marketing

Cattle in three experiments were scanned with ultrasound as feeders to measure ribeye area and thickness of fat cover to determine if cattle could be sorted into outcome groups with respect to carcass yield. Sorting the cattle into low fat cover or large ribeye groups resulted in improved carcass yield grades. There were no effects on carcass quality grades related to sorting of the cattle. Cattle with greater fat cover at the beginning of the feeding period were heavier, seemed to be more mature and had less muscle growth during the finishing period. There were no significant differences in gain among the groups, but cattle with more fat cover had poorer feed efficiency. Ultrasound seems to have potential to sort feeder cattle, but before it can be used in practice, growth curves need to be developed to predict final end points of individual cattle.

Consumer Behavior in Moral Markets. On the Relevance of Identity, Justice Beliefs, Social Norms, Status and Trust in Ethical Consumption

This article addresses ethical consumer behavior and uses the purchase of Fair Trade (FT) coffee to gain insights into determinants of ‘moral behavior’ in the marketplace. Our primary concern is to clarify which theoretical concepts and determinants are more useful than others in explaining FT consumption. We compare the explanatory power of consumer budget restrictions, consumer identity, social and personal norms, social status, justice beliefs, and trust. Our second aim is methodological; we contrast data on self-reported consumption of FT coffee with experimental data on hypothetical choices of different coffee products. To gain insights into the robustness of our measurement and findings, we test our propositions using two samples of undergraduate students from Germany and the United States. Our data show that consumer identity and personal norms are the major determinants of FT consumption in both samples, the results from survey-based data and from our experimental data are similar in this regard. Further, we demonstrate that studies based on a limited number of determinants might overestimate effects; the effect of justice beliefs for instance vanishes if other determinants are taken into account.

Norms on the gender perception of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak

We collected norms on the gender stereotypicality of an extensive list of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak, to be used as a basis for the selection of stimulus materials in future studies. We present a Web-based tool (available at https://www.unifr.ch/lcg/) that we developed to collect these norms and that we expect to be useful for other researchers, as well. In essence, we provide (a) gender stereotypicality norms across a number of languages and (b) a tool to facilitate cross-language as well as cross-cultural comparisons when researchers are interested in the investigation of the impact of stereotypicality on the processing of role nouns.

Delta like ligand 4 is a critical regulator of bone marrow cell differentiation into pericytes/vascular smooth muscle cells and is essential for the vasculogenesis that supports the growth of Ewing’s sarcoma

We have previously shown that vasculogenesis, the process by which bone marrow-derived cells are recruited to the tumor and organized to form a blood vessel network de novo, is essential for the growth of Ewing’s sarcoma. We further demonstrated that these bone marrow cells differentiate into pericytes/vascular smooth muscle cells(vSMC) and contribute to the formation of the functional vascular network. The molecular mechanisms that control bone marrow cell differentiation into pericytes/vSMC in Ewing’s sarcoma are poorly understood. Here, we demonstrate that the Notch ligand Delta like ligand 4 (DLL4) plays a critical role in this process. DLL4 is essential for the formation of mature blood vessels during development and in several tumor models. Inhibition of DLL4 causes increased vascular sprouting, decreased pericyte coverage, and decreased vessel functionality. We demonstrate for the first time that DLL4 is expressed by bone marrow-derived pericytes/vascular smooth muscle cells in two Ewing’s sarcoma xenograft models and by perivascular cells in 12 out of 14 patient samples. Using dominant negative mastermind to inhibit Notch, we demonstrate that Notch signaling is essential for bone marrow cell participation in vasculogenesis. Further, inhibition of DLL4 using either shRNA or the monoclonal DLL4 neutralizing antibody YW152F led to dramatic changes in blood vessel morphology and function. Vessels in tumors where DLL4 was inhibited were smaller, lacked lumens, had significantly reduced numbers of bone marrow-derived pericyte/vascular smooth muscle cells, and were less functional. Importantly, growth of TC71 and A4573 tumors was significantly inhibited by treatment with YW152F. Additionally, we provide in vitro evidence that DLL4-Notch signaling is involved in bone marrow-derived pericyte/vascular smooth muscle cell formation outside of the Ewing’s sarcoma environment. Pericyte/vascular smooth muscle cell marker expression by whole bone marrow cells cultured with mouse embryonic stromal cells was reduced when DLL4 was inhibited by YW152F. For the first time, our findings demonstrate a role for DLL4 in bone marrow-derived pericyte/vascular smooth muscle differentiation as well as a critical role for DLL4 in Ewing’s sarcoma tumor growth.

Smooth Muscle Hyperplasia due to ACTA2/MYH11 Mutations: Identification of Novel Pathology and Pathways Leading to Aneurysms and Diverse Vascular Occlusive Diseases

Missense mutations in smooth muscle cell (SMC) specific ACTA2 (á-actin) and MYH11 (â-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs and myofibroblasts were assessed and found to not form á-actin filaments whereas control cells did, suggesting a dominant negative effect of ACTA2 mutations on filament formation. A loss of á-actin filaments would be predicted to cause decreased SMC contractility. Histological examination of vascular tissues from patients revealed SMC hyperplasia leading to arterial stenosis and occlusion, supporting a gain of function associated with the mutant gene. Furthermore, ACTA2 mutant SMCs and myofibroblasts proliferated more rapidly in static culture than control cells (p<0.05). We also determined that Acta2-/- mice have ascending aortic aneurysms. Histological examination revealed aortic medial SMC hyperplasia, but minimal features of medial degeneration. Acta2-/- SMCs proliferated more rapidly in culture than wildtype (p<0.05), and microarray analysis of Acta2-/- SMCs revealed increased expression of Actg2, 15 collagen genes, and multiple focal adhesion genes. Acta2-/- SMCs showed altered localization of vinculin and zyxin and increased phosphorylated focal adhesion kinase (FAK) in focal adhesions. A specific FAK inhibitor decreased Acta2-/- SMC proliferation to levels equal to wildtype SMCs (p<0.05), suggesting that FAK activation leads to the increased proliferation. We have described a unique pathology associated with ACTA2 and MYH11 mutations, as well as an aneurysm phenotype in Acta2-/- mice. Additionally, we identified a novel pathogenic pathway for vascular occlusive disease due to loss of SMC contractile filaments, alterations in focal adhesions, and activation of FAK signaling in SMCs with ACTA2 mutations.

Multicentric hepatic EBV-associated smooth muscle tumors in an AIDS patient: a case report, investigation of mTOR activation and review of the literature.

Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS patients, and discuss their biologies and possible therapeutic strategies.

Expression of the neural stem cell markers NG2 and L1 in human angiomyolipoma: are angiomyolipomas neoplasms of stem cells?

Angiomyolipomas are benign tumors of the kidney which express phenotypes of smooth muscle, fat, and melanocytes. These tumors appear with increased frequency in the autosomal dominant disorder tuberous sclerosis and are the leading cause of morbidity in adults with tuberous sclerosis. While benign, these tumors are capable of provoking life threatening hemorrhage and replacement of the kidney parenchyma, resulting in renal failure. The histogenesis of these tumors is currently unclear, although currently, we believe these tumors arise from "perivascular epithelioid cells" of which no normal counterpart has been convincingly demonstrated. Recently, stem cell precursors have been recognized that can give rise to smooth muscle and melanocytes. These precursors have been shown to express the neural stem cell marker NG2 and L1. In order to determine whether angiomyolipomas, which exhibit smooth muscle and melanocytic phenotypes, express NG2 and L1, we performed immunocytochemistry on a cell line derived from a human angiomyolipoma, and found that these cells are uniformly positive. Immunohistochemistry of human angiomyolipoma specimens revealed uniform staining of tumor cells, while renal cell carcinomas revealed positivity only of angiogenic vessels. These results support a novel histogenesis of angiomyolipoma as a defect in differentiation of stem cell precursors.

The Function of Norms and Values in the Construction of Social Identity in Groups who experienced intergroup Conflicts

I present my explorative research about conflict and social identity. The Social Identity Approach of Henri Tajfel and John Turner is used as theoretical frame in the study. The main question is how the construction of social identity of group members is influenced by an inter-group conflict. The research project consists of two parts: 1. An empirical study conducted with qualitative research methods to investigate a today’s congregation of the Swiss reformed Church who experienced a conflict about twenty years ago. This conflict ended by the separation of a sub-group from the congregations. This group forms an independent community today. Members of both congregations where interviewed about the meaning which membership has for them and about their interpretation of the conflict. 2. An analysis of the Gospel of Matthew with questions who where developed out of the empirical study and the Social Identity Approach to better understand the separation conflict between the Matthean community and the synagogue.

A genetically engineered, adherent smooth muscle cell lining for left ventricular assist devices

Due to the clinical success of left ventricular assist devices (LVADs) used for short term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, a nonthrombogenic cellular lining was developed from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate$\sp{\rm TM}$ LVAD. SMCs have been transduced with the genes for endothelial nitric oxide synthase (NOS III) and GTP cyclohydrolase (GTPCH) with subsequent stable expression of the NOS III protein via an Epstein Barr based DNA expression vector. Transduced SMCs produce nitric oxide at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In addition, the adhesive capabilities of GE-SMC linings were also examined, and optimized in physical environments mimicking typical in vivo LVAD operation. Preliminary investigations examining cell adhesion during constant shear stress exposure demonstrated an acute phase of cell loss corresponding to cytoskeletal F-actin rearrangement. Subsequently, an in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies. ^