DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2 catalyze the interconversion of inactive and active glucocorticoids. Impaired regulation of these enzymes has been associated with obesity, diabetes, hypertension, and cardiovascular disease. Previous studies in animals and humans suggested that dehydroepiandrosterone (DHEA) has antiglucocorticoid effects, but the underlying mechanisms are unknown. In this study, DHEA treatment markedly increased mRNA expression and activity of 11beta-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. DHEA-treated rats tended to have reduced urinary corticosterone to 11-dehydrocorticosterone ratios. It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-beta mRNA and protein expression. Moreover, it is shown that C/EBP-alpha and C/EBP-beta differentially regulate the expression of 11beta-HSD1 and 11beta-HSD2. In conclusion, DHEA induces a shift from 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA.

Single Molecular Conductance of Tolanes: Experimental and Theoretical Study on the Junction Evolution Dependent on the Anchoring Group

Employing a scanning tunneling microscopy based beak junction technique and mechanically controlled break junction experiments, we investigated tolane (diphenylacetylene)-type single molecular junctions having four different anchoring groups (SH, pyridyl (PY), NH2, and CN) at a solid/liquid interface. The combination of current–distance and current–voltage measurements and their quantitative statistical analysis revealed the following sequence for junction formation probability and stability: PY > SH > NH2 > CN. For all single molecular junctions investigated, we observed the evolution through multiple junction configurations, with a particularly well-defined binding geometry for PY. The comparison of density functional theory type model calculations and molecular dynamics simulations with the experimental results revealed structure and mechanistic details of the evolution of the different types of (single) molecular junctions upon stretching quantitatively.

Lions-type compactness and Rubik actions on the Heisenberg group

In this paper we prove a Lions-type compactness embedding result for symmetric unbounded domains of the Heisenberg group. The natural group action on the Heisenberg group TeX is provided by the unitary group U(n) × {1} and its appropriate subgroups, which will be used to construct subspaces with specific symmetry and compactness properties in the Folland-Stein’s horizontal Sobolev space TeX. As an application, we study the multiplicity of solutions for a singular subelliptic problem by exploiting a technique of solving the Rubik-cube applied to subgroups of U(n) × {1}. In our approach we employ concentration compactness, group-theoretical arguments, and variational methods.

Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany – Austria – Switzerland)

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

Uniqueness of the Embedding Continuous Convolution Semigroup of a Gaussian Probability Measure on the Affine Group and an Application in Mathematical Finance

Let {μ(i)t}t≥0 ( i=1,2 ) be continuous convolution semigroups (c.c.s.) of probability measures on Aff(1) (the affine group on the real line). Suppose that μ(1)1=μ(2)1 . Assume furthermore that {μ(1)t}t≥0 is a Gaussian c.c.s. (in the sense that its generating distribution is a sum of a primitive distribution and a second-order differential operator). Then μ(1)t=μ(2)t for all t≥0 . We end up with a possible application in mathematical finance.

Inference of evolutionary forces acting on human biological pathways

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.

Sequential female assessment drives complex sexual selection on bower shape in a cichlid fish

In many animals, sexual selection on male traits results from female mate choice decisions made during a sequence of courtship behaviors. We use a bower-building cichlid fish, Nyassachromis cf. microcephalus, to show how applying standard selection analysis to data on sequential female assessment provides new insights into sexual selection by mate choice. We first show that the cumulative selection differentials confirm previous results suggesting female choice favors males holding large volcano-shaped sand bowers. The sequential assessment analysis reveals these cumulative differentials are the result of selection acting on different bower dimensions during the courtship sequence; females choose to follow males courting from tall bowers, but choose to engage in premating circling with males holding bowers with large diameter platforms. The approach we present extends standard selection analysis by partitioning the variances of increasingly accurate estimates of male reproductive fitness and is applicable to systems in which sequential female assessment drives sexual selection on male traits.

Peculiarities of cell death mechanisms in neutrophils

Analyses of neutrophil death mechanisms have revealed many similarities with other cell types; however, a few important molecular features make these cells unique executors of cell death mechanisms. For instance, in order to fight invading pathogens, neutrophils possess a potent machinery to produce reactive oxygen species (ROS), the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Evidence is emerging that these ROS are crucial in the execution of most neutrophil cell death mechanisms. Likewise, neutrophils exhibit many diverse granules that are packed with cytotoxic mediators. Of those, cathepsins were recently shown to activate pro-apoptotic B-cell lymphoma-2 (Bcl-2) family members and caspases, thus acting on apoptosis regulators. Moreover, neutrophils have few mitochondria, which hardly participate in ATP synthesis, as neutrophils gain energy from glycolysis. In spite of relatively low levels of cytochrome c in these cells, the mitochondrial death pathway is functional. In addition to these pecularities defining neutrophil death pathways, neutrophils are terminally differentiated cells, hence they do not divide but undergo apoptosis shortly after maturation. The initial trigger of this spontaneous apoptosis remains to be determined, but may result from low transcription and translation activities in mature neutrophils. Due to the unique biological characteristics of neutrophils, pharmacological intervention of inflammation has revealed unexpected and sometimes disappointing results when neutrophils were among the prime target cells during therapy. In this study, we review the current and emerging models of neutrophil cell death mechanisms with a focus on neutrophil peculiarities.

The impact of social presence on team performance in social networking platforms

Next to the extensive use of social networking platforms (SNPs) for communication and relationship building with friends and relatives, SNPs are also increasingly used for enhancing collaboration at work. SNP usage at the workplace is fundamentally different and it is unclear how SNPs can improve collaboration as well as in what way their designs should be modified and adapted to collaboration settings. This research identifies specific SNP functions that enhance social presence as particularly beneficial for collaboration. Consequently, two designs of SNPs, one with high social presence and one with low social presence, are outlined and its impacts on collaboration are discussed. A framework is constructed that illustrates how social presence in SNPs can improve team performance through enhancing transactive memory within teams (intra-group collaboration) and relational capital across teams (inter-group collaboration). In addition, it is outlined how this framework could be evaluated in an experimental setting of teams working on a complex group task.

In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows

OBJECTIVE: To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction. SAMPLE POPULATION: Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows. PROCEDURES: Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (A(max)), and area under the curve (AUC) were evaluated. RESULTS: Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M(3) antagonists (more commonly for basal tone than for A(max) and AUC). The M(2) receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M(3) receptor antagonists were generally more potent than the M(2) receptor antagonists. In a protection experiment, an M(3) receptor antagonist was less potent than when used in combination with an M(2) receptor antagonist. Receptor antagonists for M(1) and M(4) did not affect contractility variables. CONCLUSIONS AND CLINICAL RELEVANCE: Bethanechol acting on muscarinic receptor sub-types M(2) and M(3) may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.

Effects of Carnoy's solution on blood vessels of the axillary fossa of rats

Carnoy's solution is applied to reduce the recurrence of odontogenic keratocysts and unicystic ameloblastomas. The deleterious action of this fixative on nerves has been studied but no attention has been paid to its effects on nearby vessels. The aim of this study was to investigate the effects of Carnoy's solution on blood vessels. The rat axillary artery and vein were surgically exposed, soaked with Carnoy's solution and kept in place for 2, 5 or 10 min, depending on the treatment group. The 5-min group was followed for 1, 2 and 3 weeks postoperatively. The vessels in the 2-min and 5-min exposure groups showed histological changes to the vessels, represented by focal loss of the endothelium and hyalinization of the wall. These alterations increased in the 10-min group. The vessels in the 3-week observation period revealed signs of recovery. It is concluded that Carnoy's solution can damage blood vessels but the process is reversible for exposure times less than 5 min.

The influence of bedrock orientation on the landscape evolution, surface morphology and denudation (10Be) at the Niesen, Switzerland

Landscape evolution and surface morphology in mountainous settings are a function of the relative importance between sediment transport processes acting on hillslopes and in channels, modulated by climate variables. The Niesen nappe in the Swiss Penninic Prealps presents a unique setting in which opposite facing flanks host basins underlain by identical lithologies, but contrasting litho-tectonic architectures where lithologies either dip parallel to the topographic slope or in the opposite direction (i.e. dip slope and non-dip slope). The north-western facing Diemtigen flank represents such a dip slope situation and is characterized by a gentle topography, low hillslope gradients, poorly dissected channels, and it hosts large landslides. In contrast, the south-eastern facing Frutigen side can be described as non-dip slope flank with deeply incised bedrock channels, high mean hillslope gradients and high relief topography. Results from morphometric analysis reveal that noticeable differences in morphometric parameters can be related to the contrasts in the relative importance of the internal hillslope-channel system between both valley flanks. While the contrasting dip-orientations of the underlying flysch bedrock has promoted hillslope and channelized processes to contrasting extents and particularly the occurrence of large landslides on the dip slope flank, the flank averaged beryllium-10 (10Be)-derived denudation rates are very similar and range between 0.20 and 0.26 mm yr−1. In addition, our denudation rates offer no direct relationship to basin's slope, area, steepness or concavity index, but reveal a positive correlation to mean basin elevation that we interpret as having been controlled by climatically driven factors such as frost-induced processes and orographic precipitation. Our findings illustrate that while the landscape properties in this part of the northern Alpine border can mainly be related to the tectonic architecture of the underlying bedrock, the denudation rates have a strong orographic control through elevation dependent mean annual temperature and precipitation.

Ethnography of a Land-Deal. Local Perceptions and Vertical Perspectives of a Large Scale Land Acquisition Project in Northern Sierra Leone

Despite an increased scientific interest in the relatively new phenomenon of large-scale land acquisition (LSLA), data on processes on the local level remain sparse and superficial. However, knowledge about the concrete implementation of LSLA projects and the different impacts they have on the heterogeneous group of project affected people is indispensable for a deepened understanding of the phenomenon. In order to address this research gap, a team of two anthropologists and a human geographer conducted in-depth fieldwork on the LSLA project of Swiss based Addax Bioenergy in Sierra Leone. After the devastating civil war, the Sierra Leonean government created favourable conditions for foreign investors willing to lease large areas of land and to bring “development” to the country. Being one of the numerous investing companies, Addax Bioenergy has leased 57’000 hectares of land to develop a sugarcane plantation and an ethanol factory to produce biofuel for the export to the European market. Based on participatory observation, qualitative interview techniques and a network analysis, the research team aimed a) at identifying the different actors that were necessary for the implementation of this project on a vertical level and b) exploring various impacts of the project in the local context of two villages on a horizontal level. The network analysis reveals a complex pattern of companies, institutions, nongovernmental organisations and prominent personalities acting within a shifting technological and discursive framework linking global scales to a unique local context. Findings from the latter indicate that affected people initially welcomed the project but now remain frustrated since many promises and expectations have not been fulfilled. Although some local people are able to benefit from the project, the loss of natural resources that comes along with the land lease affects livelihoods of vulnerable groups – especially women and land users – considerably. However, this research doesn’t only disclose impacts on local people’s previous lives but also addresses strategies they adopt in the newly created situation that has opened up alternative spaces for renegotiations of power and legitimatisation. Therewith, this explorative study reveals new aspects of LSLA that have not been considered adequately by the investing company nor by the general academic discourse on LSLA.

Ethnography of a Land Grab and Gendered Coping Strategies in Northern Sierra Leone

Despite an increased scientific interest in the relatively new phenomenon of large-scale land acquisition (LSLA), data on the implementation of such projects and their impacts on the heterogeneous group of project-affected people are still sparse and superficial. Our ethnographic in-depth research on a Swiss-based bioenergy project in Sierra Leone generates well-documented data and provides insights into gendered access to land and wage employment. In the area where the project is located, customary land tenure applies. Thereby, women are structurally discriminated since they are not entitled to own land. However, user rights grant women and non-landowning men access to land and associated resources. Following the investing development banks’ guidelines, the company considered the local customary law when implementing its project. Nevertheless, the company only consulted and compensated landowners although women and non-landowning men could previously benefit from acquired land as well. Moreover, the company’s policy to enhance employment possibilities for women is barely implemented, and only few local women are hired. In order to cope with the transformed situation some women and non-landowning men continue to engage in subsistence farming on a reduced area of land. Others are involved in informal petty-trade or cooking food for the labourers whereby they subsidize the capitalist production of the company. In one village, women resisted additional land takes of the company. Acting within the framework of a specific power constellation on community level and simultaneously accommodating their claims within policy paradigms on transnational level, they were able to force a landowner to refuse leasing land to the company.

The influence of striking object characteristics on the impact energy.

A common form of violence investigated in legal medicine is blunt trauma caused by striking with different objects. The injuries and medical consequences have been widely examined, whereas the forces and especially the energies acting on impact have rarely been analyzed. This study focuses on how the impact energy of different striking objects depends on their characteristics. A total of 1170 measurements of horizontal strikes against a static and relatively heavy pendulum have been acquired with 13 volunteers. The main focus was laid on how the weight, the length, and the center of mass of the different striking objects influenced the striking energy. The results show average impact energies in the range of 67.3 up to 311.5 J for men with an optimum weight of about 1.3 kg with its center of mass in the far end quarter for a 1-m-long striking object. The average values for women range from 30 to 202.6 J, with an optimum weight between 1.65 and 2.2 kg and similar settings for the center of mass as the men. Also, the impact energies are getting higher with shorter object lengths and reach a maximum at a length of about 0.3 to 0.4 m. The male volunteers' impact energy was on average by 84.2 % higher than the values of the female volunteers, where the impact masses were very similar and the impact velocities played the key role.