To Link or Not to Link? Multiple Team Membership and Unit Performance

Multiple team membership is common in today’s team-based organizations, but little is known about its relationship with collective effectiveness across teams. We adopted a microfoundations framework utilizing existing individual- and team-level research to develop a higher-level perspective on multiple team membership’s relationship with performance of entire units of teams. We tested our predictions with data collected from 849 primary care units of the Veterans Health Administration serving over 4.2 million patients. In this context, we found multiple team membership is negatively associated with unit performance, and this negative relationship is exacerbated by task complexity

THOSE WITH THE MOST FIND IT HARDEST TO SHARE: EXPLORING LEADER RESISTANCE TO THE IMPLEMENTATION OF TEAM-BASED EMPOWERMENT

We use a convergent parallel mixed methods approach to explore barriers to the successful implementation of a team-based empowerment initiative within the Veterans Health Administration. Although previous research has suggested that leaders often actively obstruct empowerment initiatives, little is known about the reasons behind and effects of such hindering. Using a longitudinal quasi-experimental design, we support a hypothesis that higher-status physician leaders are less successful than lower-status nonphysician leaders in implementing team-based empowerment. In parallel, we analyze qualitative data obtained through interviews conducted during early months of the teambased empowerment initiative to identify common themes for why and how leaders facilitated or obstructed implementation. Leader identity work and leader delegation were identified as themes explaining (1) why higher-status leaders struggled with the new empowering role and (2) how specific leader actions either facilitated or inhibited sharing of tasks and leadership. Results suggest that team-based empowerment creates a status threat for high-status leaders who then struggle to protect their old identity as someone with distinct professional capabilities, which in turn leads to improper delegation behavior. Therefore, in order for team-based empowerment to succeed, leaders may need to change their perceptions of who they are before they will change what they do

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation

Ion microprobe determination of sulfur isotope variations in iron sulfides from the Post/ Betze sediment-hosted disseminated gold deposit, Nevada, USA

Secondary ion mass spectrometric analyses of ore samples from the Post/Betze sedimenthosted disseminated gold deposit were utilized to constrain elemental distribution of Au and As in iron sulfide phases. Most of the Au was deposited very early in the paragenetic sequence. Although Au and As are covariant in arsenian pyrite, Au apparently was depleted much more rapidly from the hydrothermal solutions than was As.Sensitive high-resolution ion microprobe (SHRIMP) sulfur isotope analyses of iron sulfides from the Post/Betze deposit vary widely from [delta]34S = -29 to 23[per mille sign] and provide important information on the origin of sulfur and constraints on depositional mechanisms. Ore solutions had high [delta]34S values and were most likely derived, at least in part, from thermochemical reduction of lower Paleozoic seawater-derived sulfate, possibly bedded barite. Late-stage ore fluids ([delta]34Ssulfide = -12 to -29[per mille sign]) are extremely depleted in 34S relative to main-stage ore fluids ([delta]34Ssulfide = 16-23[per mille sign]). Although such low [delta]34S values can be generated hypothetically from the original ore fluids by oxidation (possibly boiling), the stability of pyrite is compromised. Introduction of and mixing with Fe-rich fluids is necessary to deposit pyrite having low isotopic values.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30896/1/0000565.pd

Gas Accretion is Dominated by Warm Ionized Gas in Milky Way-Mass Galaxies at z ~ 0

We perform high-resolution hydrodynamic simulations of a Milky Way-mass galaxy in a fully cosmological setting using the adaptive mesh refinement code, Enzo, and study the kinematics of gas in the simulated galactic halo. We find that the gas inflow occurs mostly along filamentary structures in the halo. The warm-hot (10^5 K 10^6 K) ionized gases are found to dominate the overall mass accretion in the system (with dM/dt = 3-5 M_solar/yr) over a large range of distances, extending from the virial radius to the vicinity of the disk. Most of the inflowing gas (by mass) does not cool, and the small fraction that manages to cool does so primarily close to the galaxy (R <~ 20 kpc), perhaps comprising the neutral gas that may be detectable as, e.g., high-velocity clouds. The neutral clouds are embedded within larger, accreting filamentary flows, and represent only a small fraction of the total mass inflow rate. The inflowing gas has relatively low metallicity (Z/Z_solar < 0.2). The outer layers of the filamentary inflows are heated due to compression as they approach the disk. In addition to the inflow, we find high-velocity, metal-enriched outflows of hot gas driven by supernova feedback. Our results are consistent with observations of halo gas at low z.Comment: 10 pages including 5 figures, submitted to Ap

Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation

Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation

Human Cancer Long Non-Coding RNA Transcriptomes

Once thought to be a part of the ‘dark matter’ of the genome, long non-coding RNAs (lncRNAs) are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE) libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described &lt;10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation

Rapid Enzyme-linked Immunosorbent Assay for Detection of the Algal Toxin Domoic Acid

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range from 0.1–3 ppb and was used successfully to measure DA in razor clams, mussels, scallops, and phytoplankton. The assay requires approximately 1.5 h to complete and has a standard 96-well format where each strip of eight wells is removable and can be stored at 4°C until needed. The first two wells of each strip serve as an internal control eliminating the need to run a standard curve. This allows as few as 3 or as many as 36 duplicate samples to be run at a time enabling real-time sample processing and limiting degradation of DA, which can occur during storage. There was minimal cross-reactivity in this assay with glutamine, glutamic acid, kainic acid, epi- or iso-DA. This accurate, rapid, cost-effective, assay offers environmental managers and public health officials an effective tool for monitoring DA concentrations in environment samples