Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies

How Agile Workers Make Sense of Managerial Communication

TITLE How Agile Workers Make Sense of Managerial Communication AUTHORS Anna Hagberg, Yang Li & Farah Khanjar SUPERVISOR Katie Sullivan DATE 23rd May 2014 PURPOSE The purpose of the research project is to contribute to agile communication theory with insights about how agile workers make sense of managerial communication. RELEVANCE Due to the rapid changes organizations in the software development industry are now facing, the use of agile practices has become popular. Also, taking the agile workers perspective has a tendency to be neglected in literature on agile practices. METHODOLOGY This qualitative research has been conducted with an interpretative approach, using an abductive method when working with data and theory. In total, we conducted 12 semi-structured interviews and analyzed them using hermeneutics. FINDINGS We discovered that there is a tension between agile workers and management and also that managers should use a mix of communication channels when communicating with agile workers. CONTRIBUTIONS We contributed with an in-depth understanding of how agile workers make sense of managerial communication. We also contributed to literature on agile practices by identifying the tension between the self-organized teams and management, specifically in large-sized companies. KEY-WORDS Agile workers, agile communication, agile practices, self-organized teams, managers, SCRUM, managerial communicatio

Volumetric combustion of biomass for CO 2 and NOx reduction in coal-fired boilers

To meet the urgent environmental targets, substituting coal with biomass has been considered to be an effective and promising method over the last decades. In this paper, a new concept of volumetric combustion is proposed and further developed to achieve 100% fuel switching to biomass in large scale coal-fired boilers. Volumetric combustion not only changes the in-furnace flow but also affects the combustion reactions by the intensive mixing and internal recirculation of the flue gases. Firstly, the volumetric combustion properties of the wood pellets were investigated experimentally. An Aspen model was then used to thermodynamically describe and study the volumetric combustion with three different types of fuel, and the emission properties of CO 2 and NOx were compared. Finally, two applications of volumetric combustion were discussed. It is concluded that the wood pellets ignited and combusted much faster than the coal pellets and had a larger combustion volume when combusted under lower oxygen concentration conditions, and the ignition time was almost independent of the oxygen concentration when the oxidizer was preheated to 1000 °C. In addition, the NOx emissions decreased as the recirculation ratio of the flue gas increased, and as the percentage of biomass used in co-firing increased, the amount of flue gas that needs to be recycled for reduction of NOx decreased. Thus, the volumetric combustion is beneficial as it reduces the operation cost of NOx reduction. The volumetric combustion would be an attractive technology for co-firing a large proportion of biomass in coal-fired boilers with high boiler efficiency and effective emissions reduction

Galaxy Groups in the SDSS DR4: I. The Catalogue and Basic Properties

We use a modified version of the halo-based group finder developed by Yang et al. to select galaxy groups from the Sloan Digital Sky Survey (SDSS DR4). In the first step, a combination of two methods is used to identify the centers of potential groups and to estimate their characteristic luminosity. Using an iterative approach, the adaptive group finder then uses the average mass-to-light ratios of groups, obtained from the previous iteration, to assign a tentative mass to each group. This mass is then used to estimate the size and velocity dispersion of the underlying halo that hosts the group, which in turn is used to determine group membership in redshift space. Finally, each individual group is assigned two different halo masses: one based on its characteristic luminosity, and the other based on its characteristic stellar mass. Applying the group finder to the SDSS DR4, we obtain 301237 groups in a broad dynamic range, including systems of isolated galaxies. We use detailed mock galaxy catalogues constructed for the SDSS DR4 to test the performance of our group finder in terms of completeness of true members, contamination by interlopers, and accuracy of the assigned masses. This paper is the first in a series and focuses on the selection procedure, tests of the reliability of the group finder, and the basic properties of the group catalogue (e.g. the mass-to-light ratios, the halo mass to stellar mass ratios, etc.). The group catalogues including the membership of the groups are available at http://gax.shao.ac.cn/data/Group.html and http://www.astro.umass.edu/~xhyang/Group.htmlComment: 19 pages, 12 figures, Accepted for publication in ApJ. Group catalogues are available at http://gax.shao.ac.cn/data/Group.html and http://www.astro.umass.edu/~xhyang/Group.htm

Live calcium imaging of Aedes aegypti neuronal tissues reveals differential importance of chemosensory systems for life-history-specific foraging strategies.

BackgroundThe mosquito Aedes aegypti has a wide variety of sensory pathways that have supported its success as a species as well as a highly competent vector of numerous debilitating infectious pathogens. Investigations into mosquito sensory systems and their effects on behavior are valuable resources for the advancement of mosquito control strategies. Numerous studies have elucidated key aspects of mosquito sensory systems, however there remains critical gaps within the field. In particular, compared to that of the adult form, there has been a lack of studies directed towards the immature life stages. Additionally, although numerous studies have pinpointed specific sensory receptors as well as responding motor outputs, there has been a lack of studies able to monitor both concurrently.ResultsTo begin filling aforementioned gaps, here we engineered Ae. aegypti to ubiquitously express a genetically encoded calcium indicator, GCaMP6s. Using this strain, combined with advanced microscopy, we simultaneously measured live stimulus-evoked calcium responses in both neuronal and muscle cells with a wide spatial range and resolution.ConclusionsBy coupling in vivo live calcium imaging with behavioral assays we were able to gain functional insights into how stimulus-evoked neural and muscle activities are represented, modulated, and transformed in mosquito larvae enabling us to elucidate mosquito sensorimotor properties important for life-history-specific foraging strategies

Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.

Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses

Three Different Types of Galaxy Alignment within Dark Matter Halos

Using a large galaxy group catalogue based on the Sloan Digital Sky Survey Data Release 4 we measure three different types of intrinsic galaxy alignment within groups: halo alignment between the orientation of the brightest group galaxies (BGG) and the distribution of its satellite galaxies, radial alignment between the orientation of a satellite galaxy and the direction towards its BGG, and direct alignment between the orientation of the BGG and that of its satellites. In agreement with previous studies we find that satellite galaxies are preferentially located along the major axis. In addition, on scales r < 0.7 Rvir we find that red satellites are preferentially aligned radially with the direction to the BGG. The orientations of blue satellites, however, are perfectly consistent with being isotropic. Finally, on scales r < 0.1 \Rvir, we find a weak but significant indication for direct alignment between satellites and BGGs. We briefly discuss the implications for weak lensing measurements.Comment: 4 pages, 4 figures, ApJL accepte

A concise and straightforward approach to total synthesis of (+)-Strictifolione and formal synthesis of Cryptofolione via a unified strategy

YesWe describe a concise and straightforward approach to the total syntheses of (+)-Strictifolione and Cryptofolione in the longest linear sequences of four steps and six steps from 3-phenyl propanal and trans-cinnamaldehyde, respectively. The route utilized a titanium tetraisopropoxide/(R)-[1,1'-binaphthalene]-2,2'-diol catalyzed Mukaiyama aldol reaction, indium(0)-promoted Barbier reaction, and olefin cross-metathesis as the key reactions.National Science Foundation of China [21062088, 21562020, and 21462004], the Science and Technology Plan Project of Jiangxi Province [No. 20151BBG70028, 20142BBE50006] and State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources [CMEMR2014-A04] for the funding support

Inverse tuning of metal binding affinity and protein stability by altering charged coordination residues in designed calcium binding proteins

Ca2+ binding proteins are essential for regulating the role of Ca2+ in cell signaling and maintaining Ca2+ homeostasis. Negatively charged residues such as Asp and Glu are often found in Ca2+ binding proteins and are known to influence Ca2+ binding affinity and protein stability. In this paper, we report a systematic investigation of the role of local charge number and type of coordination residues in Ca2+ binding and protein stability using de novo designed Ca2+ binding proteins. The approach of de novo design was chosen to avoid the complications of cooperative binding and Ca2+-induced conformational change associated with natural proteins. We show that when the number of negatively charged coordination residues increased from 2 to 5 in a relatively restricted Ca2+-binding site, Ca2+ binding affinities increased by more than 3 orders of magnitude and metal selectivity for trivalent Ln3+ over divalent Ca2+ increased by more than 100-fold. Additionally, the thermal transition temperatures of the apo forms of the designed proteins decreased due to charge repulsion at the Ca2+ binding pocket. The thermal stability of the proteins was regained upon Ca2+ and Ln3+ binding to the designed Ca2+ binding pocket. We therefore observe a striking tradeoff between Ca2+/Ln3+ affinity and protein stability when the net charge of the coordination residues is varied. Our study has strong implications for understanding and predicting Ca2+-conferred thermal stabilization of natural Ca2+ binding proteins as well as for designing novel metalloproteins with tunable Ca2+ and Ln3+ binding affinity and selectivity