bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Growth Hormone Resistance After Acute Injury
Authors: Corrick Ryan M. , Li Li , Frank Stuart J. , Messina Joseph L. 
Published: February 2013

AbstractSevere injury and infection are often followed by accelerated protein catabolism and acute insulin resistance. This results in several effects that complicate and prolong recovery, including weakness, immobility, impaired wound healing, and organ dysfunction. Recent studies have demonstrated the development of GH resistance during severe inflammation, providing a potential mechanism for the protein loss that follows injury and infection. To understand this GH resistance, we recently developed a murine model of acute injury. Mice were subjected to soft-tissue injury, alone or combined with hemorrhage, and injected iv with GH 30, 60, or 90 minutes later. Hepatic GH signaling was measured via Western analysis. GH-induced signal transducer and activator of transcription 5 phosphorylation was decreased immediately after completion of the trauma procedure, and at 30 and 60 minutes, but further decreased by 90 minutes after trauma. Combined trauma and hemorrhage resulted in severely decreased GH-induced signal transducer and activator of transcription 5 phosphorylation compared with trauma alone, and this was true at all time points studied. Western analysis revealed an apparent decrease in the molecular weight of the hepatic GH receptor (GHR) after trauma and hemorrhage, but not trauma alone. Additional studies determined that the hemorrhage-induced decrease in receptor size was not due to changes in GHR N-linked glycosylation. These results suggest that GH sensitivity is rapidly impaired after acute injury and that trauma combined with hemorrhage results in a more severe form of GH resistance resulting from alteration or inactivation of hepatic GHR.
Ghrelin Restoration of Function In Vitro in Somatotropes from Male Mice Lacking the Janus Kinase (JAK)-Binding Site of the Leptin Receptor
Authors: Syed Mohsin , Cozart Michael , Haney Anessa C. , Akhter Noor , Odle Angela K. , Allensworth-James Melody , Crane Christopher , Syed Farhan M. , Childs Gwen V. 
Published: February 2013

Abstract
Deletion of the signaling domain of leptin receptors selectively in somatotropes, with Cre-loxP technology, reduced the percentage of immunolabeled GH cells and serum GH. We hypothesized that the deficit occurred when leptin's postnatal surge failed to stimulate an expansion in the cell population. To learn more about the deficiency in GH cells, we tested their expression of GHRH receptors and GH mRNA and the restorative potential of secretagogue stimulation in vitro. In freshly plated dissociated pituitary cells from control male mice, GHRH alone (0.3 nM) increased the percentage of immunolabeled GH cells from 27 ± 0.05% (vehicle) to 42 ± 1.8% (P &lt; .002) and the secretion of GH 1.8–3×. Deletion mutant pituitary cells showed a 40% reduction in percentages of immunolabeled GH cells (16.7 ± 0.4%), which correlated with a 47% reduction in basal GH levels (50 ng/mL control; 26.7 ng/mL mutants P = .01). A 50% reduction in the percentage of mutant cells expressing GHRH receptors (to 12%) correlated with no or reduced responses to GHRH. Ghrelin alone (10 nM) stimulated more GH cells in mutants (from 16.7–23%). When added with 1–3 nM GHRH, ghrelin restored GH cell percentages and GH secretion to levels similar to those of stimulated controls. Counts of somatotropes labeled for GH mRNA confirmed normal percentages of somatotropes in the population. These discoveries suggest that leptin may optimize somatotrope function by facilitating expression of membrane GHRH receptors and the production or maintenance of GH stores.
Phosphorylation of Threonine 333 Regulates Trafficking of the Human sst5 Somatostatin Receptor
Authors: Petrich Aline , Mann Anika , Kliewer Andrea , Nagel Falko , Strigli Anne , Märtens Jan Carlo , Pöll Florian , Schulz Stefan 
Published: February 2013

Abstract
The frequent overexpression of the somatostatin receptors sst2 and sst5 in neuroendocrine tumors provides the molecular basis for therapeutic application of novel multireceptor somatostatin analogs. Although the phosphorylation of the carboxyl-terminal region of the sst2 receptor has been studied in detail, little is known about the agonist-induced regulation of the human sst5 receptor. Here, we have generated phosphosite-specific antibodies for the carboxyl-terminal threonines 333 (T333) and 347 (T347), which enabled us to selectively detect either the T333-phosphorylated or the T347-phosphorylated form of sst5. We show that agonist-mediated phosphorylation occurs at T333, whereas T347 is constitutively phosphorylated in the absence of agonist. We further demonstrate that the multireceptor somatostatin analog pasireotide and the sst5-selective ligand L-817,818 but not octreotide or KE108 were able to promote a detectable T333 phosphorylation. Interestingly, BIM-23268 was the only sst5 agonist that was able to stimulate T333 phosphorylation to the same extent as natural somatostatin. Agonist-induced T333 phosphorylation was dose-dependent and selectively mediated by G protein-coupled receptor kinase 2. Similar to that observed for the sst2 receptor, phosphorylation of sst5 occurred within seconds. However, unlike that seen for the sst2 receptor, dephosphorylation and recycling of sst5 were rapidly completed within minutes. We also identify protein phosphatase 1γ as G protein-coupled receptor phosphatase for the sst5 receptor. Together, we provide direct evidence for agonist-selective phosphorylation of carboxyl-terminal T333. In addition, we identify G protein-coupled receptor kinase 2-mediated phosphorylation and protein phosphatase 1γ-mediated dephosphorylation of T333 as key regulators of rapid internalization and recycling of the human sst5 receptor.
Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase
Authors: Le Ly-Thuy-Tram , Vu Hong-Lien , Nguyen Chi-Hung , Molla Annie 
Published: February 2013

Summary
Histone H3 phosphorylation is the hallmark of mitosis deposited by aurora kinase B. Benzo[e]pyridoindoles are a family of potent, broad, ATP-competitive aurora kinase inhibitors. However, benzo[e]pyridoindole C4 only inhibits histone H3 phosphorylation in prophase but not in metaphase. Under the C4 treatment, the cells enter into mitosis with dephosphorylated histone H3, assemble chromosomes normally and progress to metaphase, and then to anaphase. C4 also induces lagging chromosome in anaphase but we demonstrated that these chromosome compaction defects are not related to the absence of H3 phosphorylation in prophase. As a result of C4 action, mitosis lasts longer and the cell cycle is slowed down.
We reproduced the mitotic defects with reduced concentrations of potent pan aurora kinase as well as with a specific aurora B ATP-competitive inhibitor; we therefore propose that histone H3 phosphorylation and anaphase chromosome compaction involve the basal activity of aurora kinase B. Our data suggest that aurora kinase B is progressively activated at mitosis entry and at anaphase onset. The full activation of aurora kinase B by its partners, in prometaphase, induces a shift in the catalytic domain of aurora B that modifies its affinity for ATP. These waves of activation/deactivation of aurora B correspond to different conformations of the chromosomal complex revealed by FRAP.
The presence of lagging chromosomes may have deleterious consequences on the daughter cells and, unfortunately, the situation may be encountered in patients receiving treatment with aurora kinase inhibitors.
Analysis of the shape fluctuations of reconstituted membranes using GUVs made from lipid extracts of invertebrates
Authors: Bouvrais Hélène , Holmstrup Martin , Westh Peter , Ipsen John H. 
Published: February 2013

Summary
Changes in the physical properties of the lipid matrix of cell membranes have repeatedly been proposed to underlie stresses associated with e.g. drought, cold and xenobiotics. Therefore, the ability to experimentally monitor such properties is central to the fundamental physiological understanding of adaptive changes. Here, we test the analysis of shape fluctuations in membranes composed of lipid extracts from two soil invertebrates, and show that theories and experimental approaches previously developed for simpler liposomes may be applied directly to reconstituted membrane lipids. Specifically, we show how the bending rigidity of giant unilamellar liposomes of lipid extracts can be determined precisely. We suggest that future measurements of this parameter could elucidate mechanisms of adaptive processes such as changes in lipid composition and accumulation of protective osmolytes.
Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery
Authors: Jorrisch Melissa H. , Shih Wenting , Yamada Soichiro 
Published: February 2013

Summary
Cell motility is a cornerstone of embryogenesis, tissue remodeling and repair, and cancer cell invasion. It is generally thought that migrating cells grab and exert traction force onto the extracellular matrix in order to pull the cell body forward. While previous studies have shown that myosin II deficient cells migrate efficiently, whether these cells exert traction forces during cell migration in the absence of the major contractile machinery is currently unknown. Using an array of micron-sized pillars as a force sensor and shRNA specific to each myosin II isoform (A and B), we analyzed how myosin IIA and IIB individually regulate cell migration and traction force generation. Myosin IIA and IIB localized preferentially to the leading edge where traction force was greatest, and the trailing edge, respectively. When individual myosin II isoforms were depleted by shRNA, myosin IIA deficient cells lost actin stress fibers and focal adhesions, whereas myosin IIB deficient cells maintained similar actin organization and focal adhesions as wild-type cells. Interestingly, myosin IIA deficient cells migrated faster than wild-type or myosin IIB deficient cells on both a rigid surface and a pillar array, yet myosin IIA deficient cells exerted significantly less traction force at the leading edge than wild-type or myosin IIB deficient cells. These results suggest that, in the absence of myosin IIA mediated force-generating machinery, cells move with minimal traction forces at the cell periphery, thus demonstrating the remarkable ability of cells to adapt and migrate.
Quantitative assay for TALEN activity at endogenous genomic loci
Authors: Hisano Yu , Ota Satoshi , Arakawa Kazuharu , Muraki Michiko , Kono Nobuaki , Oshita Kazuki , Sakuma Tetsushi , Tomita Masaru , Yamamoto Takashi , Okada Yasushi , Kawahara Atsuo 
Published: February 2013

Summary
Artificially designed nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can induce a targeted DNA double-strand break at the specific target genomic locus, leading to the frameshift-mediated gene disruption. However, the assays for their activity on the endogenous genomic loci remain limited. Herein, we describe a versatile modified lacZ assay to detect frameshifts in the nuclease target site. Short fragments of the genome DNA at the target or putative off-target loci were amplified from the genomic DNA of TALEN-treated or control embryos, and were inserted into the lacZα sequence for the conventional blue–white selection. The frequency of the frameshifts in the fragment can be estimated from the numbers of blue and white colonies. Insertions and/or deletions were easily determined by sequencing the plasmid DNAs recovered from the positive colonies. Our technique should offer broad application to the artificial nucleases for genome editing in various types of model organisms.
The KMN protein network – chief conductors of the kinetochore orchestra
Authors: Varma Dileep , Salmon E. D. 
Published: February 2013

Summary
Successful completion of mitosis requires that sister kinetochores become attached end-on to the plus ends of spindle microtubules (MTs) in prometaphase, thereby forming kinetochore microtubules (kMTs) that tether one sister to one spindle pole and the other sister to the opposite pole. Sites for kMT attachment provide at least four key functions: robust and dynamic kMT anchorage; force generation that can be coupled to kMT plus-end dynamics; correction of errors in kMT attachment; and control of the spindle assembly checkpoint (SAC). The SAC typically delays anaphase until chromosomes achieve metaphase alignment with each sister kinetochore acquiring a full complement of kMTs. Although it has been known for over 30 years that MT motor proteins reside at kinetochores, a highly conserved network of protein complexes, called the KMN network, has emerged in recent years as the primary interface between the kinetochore and kMTs. This Commentary will summarize recent advances in our understanding of the role of the KMN network for the key kinetochore functions, with a focus on human cells.
Perihilar branching patterns of renal artery and extrarenal length of arterial branches and tumour-feeding arteries on multidetector CT angiography
Authors: Kang W Y , Sung D J , Park B J , Kim M J , Han N Y , Cho S B , Kang C H , Kang S H 
Published: February 2013

Objective:
The purpose of our study was to assess the extrarenal length of renal arterial branches and tumour-feeding arteries on multidetector CT (MDCT) angiography, in addition to the perihilar branching patterns, with relevance to segmental artery clamping.

Methods:
MDCT angiograms of 64 patients with renal masses &lt;4 cm were retrospectively reviewed by 2 radiologists. The perihilar branching patterns of the single main renal artery were assessed according to the number of pre-segmental and segmental arteries. The extrarenal lengths of segmental plus pre-segmental arteries and the tumour-feeding arteries, measured on volume-rendered images, were compared according to the vascular segmentation and the tumour location, respectively.

Results:
In the 116 kidneys, 1 pre-segmental plus 5 segmental arteries (n=48) was the most common branching pattern. The mean extrarenal length of the inferior segmental plus pre-segmental arteries (33.05 mm) and the posterior segmental plus pre-segmental arteries (32.30 mm) was longer than any of the other segmental plus pre-segmental arteries (apical, 23.87 mm; superior, 26.80 mm; middle, 29.23 mm) (p&lt;0.05). The mean extrarenal length of the lower pole tumour-feeding arteries (35.94 mm) was longer than those of the upper and mid-pole tumour-feeding arteries (24.95 mm, 29.62 mm), with significant difference between the lower and the upper pole tumour-feeding arteries (p&lt;0.05).

Conclusion:
Tumours in the lower pole, supplied by the inferior or posterior segmental artery, may be more amenable to segmental artery clamping.

Advances in knowledge:
MDCT angiography with volume rendering can demonstrate the extrarenal length of tumour-feeding arteries and may help in determining the accessibility for segmental artery clamping.
The Stock Selection and Performance of Buy-Side Analysts
Authors: Groysberg Boris , Healy Paul , Serafeim George , Shanthikumar Devin 
Published: February 2013

Prior research on equity analysts focuses almost exclusively on those employed by sell-side investment banks and brokerage houses. Yet investment firms undertake their own buy-side research, and their analysts face different stock selection and recommendation incentives than their sell-side peers. We examine the selection and performance of stocks recommended by analysts at a large investment firm relative to those of sell-side analysts from mid-1997 to 2004. We find that the buy-side firm's analysts issue less optimistic recommendations for stocks with larger market capitalizations and lower return volatility than their sell-side peers, consistent with their facing fewer conflicts of interest and having a preference for liquid stocks. Tests with no controls for these effects indicate that annualized buy-side strong buy/buy recommendations underperform those for sell-side peers by 5.9% using market-adjusted returns and by 3.8% using four-factor model abnormal returns. However, these findings are driven by differences in the stocks recommended and their market capitalization. After controlling for these selection effects, we find no difference in the performance of the buy- and sell-side analysts' strong buy/buy recommendations.This paper was accepted by Mary Barth, accounting.
Guilt by Association: Strategic Failure Prevention and Recovery Capacity Investments
Authors: Kim Sang-Hyun , Tomlin Brian 
Published: February 2013

We examine technological systems that display the following characteristics: (i) unplanned outages incur significant costs, (ii) the system experiences an outage if one or more of its subsystems fails, (iii) subsystem failures may occur simultaneously, and (iv) subsystem recovery requires specific resources and capabilities that are provided by different firms. Firms may invest in two measures to enhance system availability—namely, failure prevention and recovery capacity. If recovery capacity investment is the only option, we find that the firms in a decentralized setting overinvest in capacity, resulting in higher system availability but at a higher cost. If both investments can be made, we find that the firms underinvest in failure prevention and overinvest in recovery capacity. That is, firms in a decentralized setting shift their focus from preventing failures to responding to failures. The net effect is lower system availability, reversing the conclusion above. We also find that, unexpectedly, firms are more willing to let their subsystems fail if a joint failure is more likely to occur. This paper was accepted by Martin Lariviere, operations management.
Designing Buyback Contracts for Irrational But Predictable Newsvendors
Authors: Becker-Peth Michael , Katok Elena , Thonemann Ulrich W. 
Published: February 2013

One of the main assumptions in research on designing supply contracts is that decision makers act in a way that maximizes their expected profit. A number of laboratory experiments demonstrate that this assumption does not hold. Specifically, faced with uncertain demand, decision makers place orders that systematically deviate from the expected profit maximizing levels. We have added to this body of knowledge by demonstrating that ordering decisions also systematically depend on individual contract parameters and by developing a behavioral model that captures this systematic behavior. We proceed to test our behavioral model using laboratory experiments and use the data to derive empirical model parameters. We then test our approach in out-of-sample validation experiments that confirm that, indeed, contracts designed using the behavioral model perform better than contracts designed using the standard model. This paper was accepted by Christian Terwiesch, operations management.
Mixed Bundling of Two Independently Valued Goods
Authors: Bhargava Hemant K. 
Published: February 2013

This paper develops analytical results and insights for the mixed bundling problem of pricing a product line consisting of two component goods (with valuations distributed uniformly and independently in [0, a1] and [0, a2], respectively, with a1≤ a2) and a bundle of the two goods. This setting has previously been considered analytically intractable. By deriving component good prices as exact algebraic functions of the optimal bundle price, I reduce the multiproduct pricing problem to a univariate nonlinear optimization problem in the bundle price. When the two component goods are sufficiently asymmetric in valuations, the optimal solution is partial mixed bundling (one component good is not sold separately), for which I derive exact conditions and optimal prices. An exact analytical solution is also given for mixed bundling of two information goods (component goods with zero marginal costs). For the general case, I derive a closed-form approximation of the optimal bundle price: pB= 0.5724w1+ 0.5695w2+ 0.3516a1+ 0.4889a2+ 0.0054(a2/a1)w1−0.0201(a2/a1)w2. The approximation is highly accurate (the resulting profit is within a percent of the exact optimal profit), efficient (instant solutions for specific problem instances), and useful in other applications where mixed bundling is a subproblem. I demonstrate this by applying the solution to the mixed bundle problem in a vertical channel where a retailer must bundle and price component goods from multiple independent manufacturers.This paper was accepted by Lorin Hitt, information systems.
Demand Uncertainty and Excess Supply in Commodity Contracting
Authors: Popescu Dana G. , Seshadri Sridhar 
Published: February 2013

We examine how different characteristics of product demand and market impact the relative sales volume in the forward and spot markets for a commodity whose aggregate demand is uncertain. In a setting where either the forward contracts are binding quantity commitments between buyers and suppliers or the forward production takes place before the uncertainty in demand is resolved, we find that a combination of factors that include market concentration, demand risk, and price elasticity of demand will determine whether a commodity will be sold mainly through forward contracts or in the spot market. Previous findings in the literature show that when participants are risk neutral, the ratio of forward sales to spot sales is a function of market concentration alone; also, the lower the concentration, the higher this ratio. These findings hold under the assumption that demand is either deterministic or, if demand is uncertain, all production takes place after uncertainty is fully resolved and production plans can be altered instantaneously and costlessly. In our setting, however, we find that even a low level of demand risk can reverse the nature of supply in a highly competitive (low concentration) market, by shifting it from predominantly forward-driven to predominantly spot-driven supply. In markets with high concentration, the price elasticity of demand will determine whether the supply will be predominantly spot-driven or forward-driven. Our analysis suggests various new hypotheses on the structure of supply in commodity markets. This paper was accepted by Martin Lariviere, operations management.
Customer-Driven Misconduct: How Competition Corrupts Business Practices
Authors: Bennett Victor Manuel , Pierce Lamar , Snyder Jason A. , Toffel Michael W. 
Published: February 2013

Competition among firms yields many benefits but can also encourage firms to engage in corrupt or unethical activities. We argue that competition can lead organizations to provide services that customers demand but that violate government regulations, especially when price competition is restricted. Using 28 million vehicle emissions tests from more than 11,000 facilities, we show that increased competition is associated with greater inspection leniency, a service quality attribute that customers value but is illegal and socially costly. Firms with more competitors pass customer vehicles at higher rates and are more likely to lose customers whom they fail, suggesting that competition intensifies pressure on facilities to provide illegal leniency. We also show that, at least in markets in which pricing is restricted, firms use corrupt and unethical practices as an entry strategy. This paper was accepted by Bruno Cassiman, business strategy.