bluuebunny/crossref_metadata_2025 huggingface dataset:
Weathering, Sr fluxes, and controls on water chemistry in the Lake Qinghai catchment, NE Tibetan Plateau
Authors: Jin Zhangdong , Wang Sumin , Zhang Fei , Shi Yuewei
Published: January 2010

Strontium (Sr) concentrations and isotopic ratios have been measured in a series of water and rock samples from most of the major tributaries of the Lake Qinghai basin on the north‐eastern Tibetan Plateau. Dissolved Sr and 87Sr/86Sr show ranges of 488–12 240 nmol/l and 0·710497–0·716977, respectively. These data, together with measurements of major cations and anions in rivers and their tributaries and various lithologies of the catchment, were used to determine the contributions of Sr and its isotopic expense to rivers and lakes. Our results demonstrate that the chemical components and 87Sr/86Sr ratios of the alkaline waters are derived from mixing of carbonate and silicate sources, with the former contributing 72 ± 18% dissolved Sr to rivers. The difference in tributary compositions stems from the lithology of different river systems and low weathering intensity under a semi‐arid condition. Variation in 87Sr/86Sr ratios places constraint on the Sr‐isotopic compositions of the main tributaries surrounding Lake Qinghai. The water chemistry of the Buha River, the largest river within the catchment underlain by the late Paleozoic marine limestone and sandstones, dominates Sr isotopic composition of the lake water, being buffered by the waters from the other rivers and probably by groundwater. However, the characteristic chemical composition of the lake itself differs remarkably from the rivers, which can be attributed to precipitation of authigenic carbonates (low‐magnesium calcite, aragonite, and dolomite), though this does not impact the Sr isotope signature, which may remain a faithful indicator in paleo‐records. Regarding the potential role of groundwater input within the Lake Qinghai systems in the water budget and water chemistry, we have also determined the Sr concentration and 87Sr/S6Sr ratio of groundwater from diverse environments. This has allowed us to further constrain the Sr isotope systematic of this source. A steady‐state calculation gives an estimate for the groundwater flux of 0·19 ± 0·03 × 108 m3/yr, accounting for about 8% of contemporary lake Sr budget. Copyright © 2010 John Wiley & Sons, Ltd.
Lactational zinc deficiency‐induced hippocampal neuronal apoptosis by a BDNF‐independent TrkB signaling pathway
Authors: Xu He , Gao Hui‐Ling , Zheng Wei , Xin Na , Chi Zhi‐Hong , Bai Shu‐Ling , Wang Zhan‐You
Published: January 2010

It is well‐known that zinc deficiency leads to neuronal death in the brain. Here we tested the hypothesis that changes in the TrkB signaling pathway are involved in hippocampal neuronal apoptosis of suckling offspring with maternal zinc deficiency. Postpartum mice were fed a zinc‐deficient (0.85 ppm) diet and their offspring were used as a lactational zinc deficiency mouse model. At P7, P14, and P21, changes in hippocampal neuronal apoptosis were assessed by Nissl and TUNEL staining. BDNF levels and TrkB neurotrophic signaling were examined using immunoblotting assay. Lactational zinc deficiency resulted in lower levels of p‐TrkB and p‐ERK, and higher levels of Bax/Bcl‐2 and caspase‐3 in the hippocampus, suggesting that zinc deficiency‐induced low levels of TrkB phosphorylation would abrogate the downstream ERK signaling pathway, leading to hippocampal neuronal apoptosis. Most interestingly, our data showed that the activity of Src, a key molecule for zinc‐induced TrkB activation through the BDNF‐independent pathway, was inhibited significantly, and the expression levels of BDNF were significantly increased in the hippocampus of suckling mice. The present data indicate that zinc depletion‐induced hippocampal neuronal apoptosis is likely through modulation of the TrkB neurotrophic signaling pathway by a BDNF‐independent and Src‐dependent mechanism, whereas higher expression of BDNF is considered as a protective response, which cannot fully compensate for the injury caused by maternal zinc deficiency. © 2010 Wiley‐Liss, Inc.
When do high‐level managers believe they can influence the stock price? Antecedents of stock price expectancy cognitions
Authors: Dunford Benjamin B. , Boswell Wendy R. , Boudreau John W.
Published: January 2010

Stock based rewards are often used to motivate high‐level managers to take actions to increase the stock price of the firm. However, numerous constraints may weaken the perceived link between individual effort and stock price appreciation for many recipients. This study introduces a new construct, stock price expectancy, which we define as individuals' perceptions of influence over their firm's stock price. We examined its antecedents in a sample of 349 high‐level U.S. managers and found that employment at corporate headquarters, firm size, hierarchical level, and contact with investment analysts predicted stock price expectancy perceptions. © 2010 Wiley Periodicals, Inc.
Context‐bound configurations of corporate HR functions in multinational corporations
Authors: Farndale Elaine , Paauwe Jaap , Morris Shad S. , Stahl Günter K. , Stiles Philip , Trevor Jonathan , Wright Patrick M.
Published: January 2010

Considerable attention has focused on how multinational corporations (MNCs) deal with the simultaneous pressures of globalization and localization when it comes to human resource management (HRM). HR function activities in this process, however, have received less focus. The study presented here identifies configurations of the corporate HR function based on international HRM (IHRM) structures, exploring how issues of interdependency shape corporate HR roles. The study is based on 248 interviews in 16 MNCs based in 19 countries. The findings are applied to develop a contextually based framework outlining the main corporate HR function configurations in MNCs, including new insights into methods of IHRM practice design. © 2010 Wiley Periodicals, Inc.
Cross‐cultural differences on work‐to‐family conflict and role satisfaction: A Taiwanese‐British comparison
Authors: Lu Luo , Cooper Cary L. , Kao Shu‐Fang , Chang Ting‐Ting , Allen Tammy D. , Lapierre Laurent M. , O'Driscoll Michael P. , Poelmans Steven A. Y. , Sanchez Juan I. , Spector Paul E.
Published: January 2010

The aim of this research was to explore relations between work and family demands and resources, work‐to‐family conflict (WFC), and work and family outcomes in a cross‐cultural comparative context involving Taiwanese and British employees. Two‐hundred and sixty‐four Taiwanese employees and 137 British employees were surveyed using structured questionnaires. For both Taiwanese and British employees, work and family demands were positively related to WFC, whereas work resources were negatively related to WFC. Furthermore, WFC was negatively related to family satisfaction. More importantly, we found that nation moderated relationships between work resources and WFC, WFC and work, and family satisfaction. Specifically, work resources had a stronger protective effect for Taiwanese than British in reducing WFC, whereas WFC had a stronger detrimental effect on role satisfaction for British than Taiwanese. It is recommended that both culture‐general and culture‐specific effects should be taken into consideration in designing future WFC research and familyfriendly managerial practices. © 2010 Wiley Periodicals, Inc.
Exploring the ethicality of firing employees who blog
Authors: Valentine Sean , Fleischman Gary M. , Sprague Robert , Godkin Lynn
Published: January 2010

This exploratory study evaluates the ethical considerations related to employees fired for their blogging activities. Specifically, subject evaluations of two employee‐related blogging scenarios were investigated with established ethical reasoning and moral intensity scales, and a measure of corporate ethical values was included to assess perceptions of organizational ethics. The first scenario involved an employee who was fired because of innocuous blogging, while the second vignette involved an employee who was fired because of work‐related blogging. Survey data were collected from employed college students and working practitioners. The findings indicated that the subjects' ethical judgments that firing an employee for blogging was unethical were negatively related to unethical intentions to fire an employee for blogging. Moral intensity was positively related to ethical judgments and negatively related to unethical intentions to fire an employee for blogging, while individual perceptions of ethical values were negatively associated with unethical intentions. Finally, subjects perceived that terminating an employee for innocuous blogging that did not target an employer was more ethically intense than was firing an employee for work‐related blogging. The implications of the findings for human resource professionals are discussed, as are the study's limitations and suggestions for future research. © 2010 Wiley Periodicals, Inc.
Contingent workers' impact on standard employee withdrawal behaviors: Does what you use them for matter?
Authors: Way Sean A. , Lepak David P. , Fay Charles H. , Thacker James W.
Published: January 2010

Previous research has suggested that workforce mixing—simultaneously using contingent workers and standard employees—can negatively affect standard employee attitudes and behaviors. In this study, we consider the impact of two reasons employers choose to use contingent workers (to enhance standard employee employment stability and to reduce labor costs) on standard employee withdrawal behaviors (absenteeism and turnover). We posit that when the aim of using contingent labor is to enhance standard employee employment stability (employment stability contingent labor strategy or ESCLS), the effects on standard employee withdrawal behaviors will differ from when the aim is to reduce labor costs (labor cost contingent labor strategy, or LCCLS). Using a sample of 90 firms that employ a mixed workforce, we examine the influence of ESCLS, LCCLS, and high investment HR systems (HIHRS) on standard employee withdrawal behaviors at the firm level. In addition to supporting the hypothesized direct (positive) effect of LCCLS on standard employee withdrawal behaviors, this study's results support the hypothesized moderating effects of HIHRS on the negative relationship between ESCLS and standard employee withdrawal behaviors and the positive relationship between LCCLS and standard employee withdrawal behaviors. Implications for research and practice and suggestions for further research are discussed. © 2010 Wiley Periodicals, Inc.
CCA addition to tRNA: Implications for tRNA quality control
Authors: Hou Ya‐Ming
Published: January 2010

The CCA sequence is conserved at the 3′ end of all mature tRNA molecules to function as the site of amino acid attachment. This sequence is acquired and maintained by stepwise nucleotide addition by the ubiquitous CCA enzyme, which is an unusual RNA polymerase that does not use a nucleic acid template for nucleotide addition. Crystal structural work has divided CCA enzymes into two structurally distinct classes, which differ in the mechanism of template‐independent nucleotide selection. Recent kinetic work of the class II E. coli CCA enzyme has demonstrated a rapid and uniform rate constant for the chemistry of nucleotide addition at each step of CCA synthesis, although the enzyme uses different determinants to control the rate of each step. Importantly, the kinetic work reveals that, at each step of CCA synthesis, E. coli CCA enzyme has an innate ability to discriminate against tRNA backbone damage. This discrimination suggests the possibility of a previously unrecognized quality control mechanism that would prevent damaged tRNA from CCA maturation and from entering the ribosome machinery of protein synthesis. This quality control is relevant to cellular stress conditions that damage tRNA backbone and predicts a role of CCA addition in stress response. © 2010 IUBMB IUBMB Life, 62(4): 251–260, 2010
Integrin signaling through FAK in the regulation of mammary stem cells and breast cancer
Authors: Guan Jun‐Lin
Published: January 2010

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase identified as a key mediator of intracellular signaling by integrins, a major family of cell surface receptors for extracellular matrix, in the regulation of different cellular functions in a variety of cells. Upon activation by integrins through disruption of an autoinhibitory mechanism, FAK undergoes autophosphorylation and forms a complex with Src and other cellular proteins to trigger downstream signaling through its kinase activity or scaffolding function. A number of integrins are identified as surface markers for mammary stem cells (MaSCs), and both integrins and FAK are found to play crucial roles in the maintenance of MaSCs in studies using mouse models, suggesting that integrin signaling through FAK may serve as a functional marker for MaSCs. Consistent with previous studies linking increased expression and activation of FAK to human breast cancer, these findings suggest a novel cellular mechanism of FAK promotion of mammary tumorigenesis by maintaining the pools of MaSCs as targets of oncogenic transformation. Furthermore, FAK inactivation in mouse models of breast cancer also reduced the pool of mammary cancer stem cells (MaCSCs), decreased their self‐renewal in vitro, and compromised their tumorigenicity and maintenance in vivo, suggesting a potential role of integrin signaling through FAK in breast cancer growth and progression through its functions in MaCSCs. This review discusses these recent advances and future studies into the mechanism of integrin signaling through FAK in breast cancer through regulation of MaCSCs that may lead to development of novel therapies for this deadly disease. © 2010 IUBMB IUBMB Life, 62(4): 268–276, 2010
Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease
Authors: Chang Ta‐Yuan , Chang Catherine C. Y. , Bryleva Elena , Rogers Maximillian A. , Murphy Stephanie R.
Published: January 2010

Cholesterol has been implicated in various neurodegenerative diseases. Here we review the connection between cholesterol and Alzheimer's disease (AD), focusing on a recent study that links neuronal cholesterol esterification with biosynthesis of 24(S)‐hydroxycholesterol and the fate of human amyloid precursor protein in a mouse model of AD. We also briefly evaluate the potential of ACAT1 as a drug target for AD. © 2010 IUBMB IUBMB Life, 62(4): 261–267, 2010
Porcine induced pluripotent stem cells may bridge the gap between mouse and human iPS
Authors: Esteban Miguel A. , Peng Meixiu , Deli Zhang , Cai Jie , Yang Jiayin , Xu Jianyong , Lai Liangxue , Pei Duanqing
Published: January 2010

Recently, three independent laboratories reported the generation of induced pluripotent stem cells (iPSCs) from pig (Sus scrofa). This finding sums to the growing list of species (mouse, human, monkey, and rat, in this order) for which successful reprogramming using exogenous factors has been achieved, and multiple others are possibly forthcoming. But apart from demonstrating the universality of the network identified by Shinya Yamanaka, what makes the porcine model so special? On one side, pigs are an agricultural commodity and have an easy and affordable maintenance compared with nonhuman primates that normally need to be imported. On the other side, resemblance (for example, size of organs) of porcine and human physiology is striking and because pigs are a regular source of food the ethical concerns that still remain in monkeys are not applicable. Besides, the prolonged lifespan of pigs compared with other domestic species can allow exhaustive follow up of side effects after transplantation. Porcine iPSCs may thus fill the gap between the mouse model, which due to its ease is preferred for mechanistic studies, and the first clinical trials using iPSCs in humans. However, although these studies are relevant and have created significant interest they face analogous problems that we discuss herein together with potential new directions. © 2010 IUBMB IUBMB Life, 62(4): 277–282, 2010
Stochastic monotonicity in intergenerational mobility tables
Authors: Dardanoni Valentino , Fiorini Mario , Forcina Antonio
Published: January 2010

The aim of this paper is to test for stochastic monotonicity in intergenerational socio‐economic mobility tables. In other words, we question whether having a parent from a high socio‐economic status is never worse than having one with a lower status. Using existing inferential procedures for testing unconditional stochastic monotonicity, we first test a set of 149 intergenerational mobility tables in 35 different countries and find that monotonicity cannot be rejected in hardly any table. In addition, we propose new testing procedures for testing conditional stochastic monotonicity and investigate whether monotonicity still holds after conditioning on a number of covariates such as education, cognitive and non‐cognitive skills. Based on the NCDS cohort data from the UK, our results provide evidence that monotonicity holds, even conditionally. Moreover, we do not find large differences in our results when comparing social class and wage class mobility. Copyright © 2010 John Wiley & Sons, Ltd.
Pancytopenia with severe thrombocytopenia in a patient treated with twice‐weekly LDL‐apheresis by polyacrylate adsorption from whole blood
Authors: Nowack Rainer , Wiedemann Günther
Published: January 2010

Pancytopenia with severe thrombocytopenia occurred in a patient treated with low‐density lipoprotein (LDL)‐apheresis by polyacrylate adsorption from whole blood, after treatment frequency had been increased from once to twice a week. Cell counts recovered with discontinuation of LDL‐apheresis, but thrombocytopenia recurred after resumption of twice‐weekly treatments. Thrombocyte counts remained stable following the replacement of polyacrylate adsorption from whole blood by double‐filtration plasmapheresis. The complications' close coincidence with twice‐weekly polyacrylate adsorption from whole blood suggests a causal relationship, although by a still unknown mechanism. Monitoring of thrombocytes should be advised in patients treated with LDL‐apheresis by polyacrylate adsorption from whole blood. J. Clin. Apheresis 2010. © 2010 Wiley‐Liss, Inc.
Electro‐membrane process for the separation of amino acids by iso‐electric focusing
Authors: Kumar Mahendra , Tripathi Bijay P. , Shahi Vinod K.
Published: January 2010

BACKGROUND: Amino acids (AAs) are usually produced commercially using chemical, biochemical and microbiological fermentation methods. The product obtained from these methods undergoes various treatments involving extraction and electrodialysis (ED) for salt removal and AA recovery. This paper describes an electro‐membrane process (EMP) for the charge based separation of amino acids.

RESULTS: Iso‐electric separation of AAs (GLU–LYS) from their mixture, using ion‐ exchange membranes (IEMs) has been achieved by an efficient and indigenous EMP. It was observed that electro‐transport rate (flux) of glutamic acid (GLU) at pH 8.0 (above its pI) was extremely high, while that for lysine (LYS) (pH 9.6) across the anion‐exchange membrane (AEM) was very low, under similar experimental conditions. Under optimum experimental conditions, separation of GLU from GLU–LYS mixture was achieved with moderate energy consumption (12.9 kWh kg−1), high current efficiency (CE) (65%) and 85% recovery of GLU.

CONCLUSIONS: On the basis of the electro‐transport rate of AA and membrane selectivity, it was concluded that the separation of GLU–LYS mixture was possible at pH 8.0, because of the oppositely charged nature of the two amino acids due to their different pI values. Moreover, any type of membrane fouling and deterioration in membrane conductivity was ruled out under experimental conditions. This work clearly demonstrates the great potential of EMP for industrial applications. Copyright © 2010 Society of Chemical Industry
Improving adeno‐associated vector yield in high density insect cell cultures
Authors: Mena Jimmy A. , Aucoin Marc G. , Montes Johnny , Chahal Parminder S. , Kamen Amine A.
Published: January 2010

Background

Recombinant adeno‐associated virus (rAAV) are the most promising vectors for gene therapy. However, large‐scale rAAV production remains a challenge for the translation of rAAV‐based therapeutic strategies to the clinic. The baculovirus expression vector system (BEVS) has been engineered to produce high rAAV titers in serum‐free suspension cultures of insect cells.

Methods

The typical approach of rAAV production in BEVS has been based on a synchronous infection with three baculoviruses at high multiplicity of infection (MOI) [>3 plaque forming units (pfu)/cell]. An alternative approach is to co‐infect at low MOI (0.1 pfu/cell). Both strategies (high and low MOI) were compared at a cell density of 1.0 × 106 cells/ml in shake‐flask experiments. To increase the rAAV titer, a low MOI combined with an initial cell density at infection of 5.0 × 106 cells/ml, in fed‐batch mode, was evaluated. Subsequently, the production strategy was validated in 3‐l bioreactor runs.

Results

An increase of 210% in the rAAV titer (4.7 × 1011 enhanced transduction units/l) was observed when using low MOI, an effect primarily caused by the increase in cell density. The fed‐batch approach resulted in a seven‐fold increase of rAAV yield. Controlled operations in bioreactor contributed to further increase the rAAV yield (2.8 × 1014 vector genomes/l) by 25% in comparison to the shake flask results.

Conclusions

This high yield production process using low MOIs and a feeding strategy successfully addresses several limitations of current rAAV production in insect cells and contributes to position the BEVS system as one of the most efficient for large‐scale manufacturing of rAAV vectors. Copyright © 2010 John Wiley & Sons, Ltd. The copyright in Jimmy A. Mena's, Johnny Montes', Parminder S. Chahal's and Amine A. Kamen's contributions belongs to the Crown in right of Canada and such copyright material is reproduced with the permission of the Research Council of Canada.
Effective in‐service education requires more than subject expertise
Authors: Lynch Krishna , Buckner‐Hayden Gia
Published: January 2010

Several formal roles within the field of human performance and training are specifically responsible for ensuring that programs are designed and developed for maximum impact. Data show that education and training are essential functions of healthcare risk management professionals. For this, healthcare risk management professionals can maximize their training efforts by partnering with an instructional designer or developer to create a training program that promotes safe and trusted healthcare.
Reducing the new employee learning curve to improve productivity
Authors: Lynch Krishna , Buckner‐Hayden Gia
Published: January 2010

Effective onboarding is essential to the acclimation and socialization of new healthcare risk management professionals within their new organizations. This acclimation process is a natural extension of employee orientation training. Benefits of effective onboarding include maximizing new employees' full productivity in core functions, thereby recouping the organization's return on investment, and positioning them for enduring success.
Plaintiff's attorneys share perspectives on patient communication
Authors: Spector Richard A.
Published: January 2010

This article reports that malpractice attorneys representing plaintiffs accept a small percentage of the clients who request legal representation for medical liability claims. Of those cases they do not accept, these attorneys report that a significant motivator for patients seeking legal counsel is poor clinician‐patient communication. They cite poor listening skills; delegation of critical consent communication; failure to share timely information with colleagues and nursing personnel; failure to have meaningful, empathetic conversations when adverse outcomes occur; and defensive behavior when patients seek to learn more by questioning diagnoses and treatment options.
In healthcare, is the human being an asset or liability?
Authors: Latino Robert J.
Published: January 2010

This article contrasts the application of preventive and predictive technologies in industry to those in healthcare. For years, risk managers have been discussing the rationing of care. This article presents the perspective of an engineering professional from the manufacturing industry who now consults with healthcare risk managers. The human being is often referred to as an “asset” in our society. Do we actually treat people as assets or liabilities? When preventive maintenance is routinely performed on a piece of equipment, the benefits are more reliable operations, increased productivity, and lower life cycle costs. If these proactive concepts are applied to the human body within our current healthcare systems, will we see these same benefits?
Carbon‐14 radiosynthesis of 4‐(5‐chloro‐2‐hydroxyphenyl)‐3‐(2‐hydroxyethyl)‐6‐(trifluoromethyl)‐[4‐14C]quinolin‐2(1H)‐one (XEN‐D0401), A novel BK channel activator
Authors: Kitson Sean L. , Jones Stuart , Watters William , Chan Fiona , Madge David
Published: January 2010

A method has been developed for the carbon‐14 radiosynthesis of [14C]XEN‐D0401, a 4‐(2‐hydroxyphenyl)quinolin‐2(1H)‐one derivative. The radiosynthetic route involves a series of ortho‐lithiations directed by both 2‐methoxymethyl (MOM) and pivaloyl protecting groups. This is demonstrated in the first key radiochemical step between the reaction of 5‐chloro‐2‐methoxymethoxy‐[carboxyl‐14C]benzoic acid methyl ester [14C]‐3 and the ortho‐lithiated intermediate generated from 2,2‐dimethyl‐N‐(4‐trifluoromethylphenyl)‐propionamide (2) to afford the protected benzophenone [14C]‐4. The other key radiochemical step utilizes a variation of the Friedländer quinoline synthesis, which involves a base catalysed, one‐pot condensation process between (2‐amino‐5‐trifluoromethyl‐phenyl)‐(5‐chloro‐2‐methoxymethoxy‐phenyl)‐[14C]methanone [14C]‐5 and γ‐butyrolactone to give MOM‐protected [14C]‐6. On MOM deprotection, [14C]XEN‐D0401 was isolated with a radiochemical purity of >97%, with a specific activity of 55 mCi/mmol from seven radiochemical steps, starting from barium [14C]carbonate in a radiochemical yield of 10.5%. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of deuterium‐labelled fosamprenavir calcium
Authors: Shi Lei , Chen Liping , Chen Ryan , Chen Liqin
Published: January 2010

This study describes the synthesis of deuterium‐labelled fosamprenavir calcium. The stable isotopic‐labelled compound was prepared starting from L‐phenylalanine in 18 steps with a 9% overall yield. Copyright © 2010 John Wiley & Sons, Ltd.
Is the large size of the pinna of the ear of the European hare (Lepus europaeus) due to its role in thermoregulation or in anterior capital shock absorption?
Authors: Stott Philip , Jennings Nancy , Harris Stephen
Published: January 2010

Large pinnae are characteristic of the Leporids, and the pinna is known to have a thermoregulatory role. Another role has been hypothesized for the pinna of Lepus spp., as a part of a suspensory system for the greater portion of the head, absorbing shock that might otherwise interfere with vision during high‐speed locomotion. We compared the lengths of the pinnae of adult European hares Lepus europaeus from the source population in the cooler climate of England with those of the introduced population in the warmer climate of Australia, and we compared the lengths of the pinnae of hares that had grown in cooler weather with those that had grown in warmer weather. There were no significant differences between each of the comparisons, indicating that the size of the pinna is not determined by thermoregulatory requirements at rest. We compared the growth in length of the pinnae and the legs with growth in body mass, and growth in the mass of the pinnae with the masses of the head and the eyeballs, and found support for the suspension hypothesis. We suggest that the rapid growth of the pinna is because visual acuity is a function of absolute eye size, not relative eye size, yet juvenile hares are subject to the same predator pressure as adult hares, and equally need to maximize visual acuity while running at high speeds in dim light. We believe that the large size of the pinna is determined by its role in anterior capital suspension, not in thermoregulation. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
Ultrastructure of the ovarian follicles in the placentotrophic Andean lizard of the genus Mabuya (Squamata: Scincidae)
Authors: Vieira Simón , de Pérez Gloria Romero , Ramírez‐Pinilla Martha Patricia
Published: January 2010

We studied the ultrastructural organization of the ovarian follicles in a placentotrophic Andean lizard of the genus Mabuya. The oocyte of the primary follicle is surrounded by a single layer of follicle cells. During the previtellogenic stages, these cells become stratified and differentiated in three cell types: small, intermediate, and large globoid, non pyriform cells. Fluid‐filled spaces arise among follicular cells in late previtellogenic follicles and provide evidence of cell lysis. In vitellogenic follicles, the follicular cells constitute a monolayered granulosa with large lacunar spaces; the content of their cytoplasm is released to the perivitelline space where the zona pellucida is formed. The oolemma of younger oocytes presents incipient short projections; as the oocyte grows, these projections become organized in a microvillar surface. During vitellogenesis, cannaliculi develop from the base of the microvilli and internalize materials by endocytosis. In the juxtanuclear ooplasm of early previtellogenic follicles, the Balbiani's vitelline body is found as an aggregate of organelles and lipid droplets; this complex of organelles disperses in the ooplasm during oocyte growth. In late previtellogenesis, membranous organelles are especially abundant in the peripheral ooplasm, whereas abundant vesicles and granular material occur in the medullar ooplasm. The ooplasm of vitellogenic follicles shows a peripheral band constituted by abundant membranous organelles and numerous vesicular bodies, some of them with a small lipoprotein core. No organized yolk platelets, like in lecithotrophic reptiles, were observed. Toward the medullary ooplasm, electron‐lucent vesicles become larger in size containing remains of cytoplasmic material in dissolution. The results of this study demonstrate structural similarities between the follicles of this species and other Squamata; however, the ooplasm of the mature oocyte of Mabuya is morphologically similar to the ooplasm of mature oocytes of marsupials, suggesting an interesting evolutionary convergence related to the evolution of placentotrophy and of microlecithal eggs. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
Synergistic effect of oligochitosan and silicon on inhibition of Monilinia fructicola infections
Authors: Yang Lingyu , Zhao Pan , Wang Li , Filippus Itoolwa , Meng Xianghong
Published: January 2010

BACKGROUND: Oligochitosan has broad‐spectrum antimicrobial activity and shows an obvious inhibitory effect on phytopathogens. In addition, as an exogenous elicitor, it can induce various defence responses, including affecting the activities of several defence‐related enzymes and substances in some plants. Owing to this dual function of oligochitosan, it can be used to control postharvest diseases of fruits. Silicon, like oligochitosan, also has a dual function. In this study the synergistic effect of oligochitosan and silicon on the decay control of apple fruit was investigated.

RESULTS: In vitro, both oligochitosan and silicon significantly inhibited spore germination, germ tube elongation and mycelial growth of Monilinia fructicola, with higher concentrations having a greater effect. The synergistic effect of oligochitosan and silicon at half‐maximal inhibitory concentration on disease control at 25 °C was much better than the effect of oligochitosan or silicon alone, not only in vitro but also in vivo.

CONCLUSION: The results showed that a combination of oligochitosan and silicon had a synergistic effect on the control of disease caused by M. fructicola in apple fruit at 25 °C. Copyright © 2010 Society of Chemical Industry
Enzymatic hydrolysis of Alaska pollack (Theragra chalcogramma) skin and antioxidant activity of the resulting hydrolysate
Authors: Jia Jianping , Zhou Yangang , Lu Jianzhang , Chen Aiying , Li Yuezhong , Zheng Gaoli
Published: January 2010

BACKGROUND: Fish skin, a by‐product of the food industry, contains a large amount of collagen. However, only a small proportion of fish skin is used in the production of leather materials and animal feedstuffs, most of it being discarded. The aims of this study were to prepare peptides from Alaska pollack (Theragra chalcogramma) skin by enzymatic hydrolysis and to evaluate the antioxidant activity of the resulting hydrolysate.

RESULTS: Protamex was the most efficient enzyme for preparing antioxidant peptides from Alaska pollack skin. The optimal hydrolysis conditions were as follows: hydrolysis time 8 h; enzyme/substrate ratio 2:1000; skin/water ratio 1:6; temperature 55 °C; pH 6.0. Under these conditions the highest yield of peptides was 83.44%, with 85.95% of the hydrolysate being mainly composed of oligopeptides with molecular weights ranging from 180 to 1000 Da. The hydrolysate showed 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging activity, with an IC50 value of 2.5 mg mL−1, and its reducing power was 0.14 at 1 mg mL−1, 53.8% of that of reduced glutathione at the same concentration.

CONCLUSION: This study demonstrated that the hydrolysate of Alaska pollack skin was mainly composed of oligopeptides with two to eight amino acid residues and possessed antioxidant activity. Copyright © 2010 Society of Chemical Industry
Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs
Authors: Foxton Matthew R. , Al-Freah Mohammad A. B. , Portal Andrew J. , Sizer Elizabeth , Bernal William , Auzinger Georg , Rela Mohamed , Wendon Julia A. , Heaton Nigel D. , O'Grady John G. , Heneghan Michael A.
Published: January 2010

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P = 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P = 0.004 and P = 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P = not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay. Liver Transpl 16:668-677, 2010. © 2010 AASLD.
Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation
Authors: Nart Deniz , Yaman Banu , Yılmaz Funda , Zeytunlu Murat , Karasu Zeki , Kılıç Murat
Published: January 2010

Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail. Liver Transpl 16:621-630, 2010. © 2010 AASLD.
T Cell-mediated biliary epithelial-to-mesenchymal transition in liver allograft rejection
Authors: Rygiel Karolina A. , Robertson Helen , Willet Joseph D. P. , Brain John G. , Burt Alastair D. , Jones David E. J. , Kirby John A.
Published: January 2010

Loss of bile duct epithelium is characteristic of early chronic rejection following liver transplantation. Recent studies have suggested that intrahepatic biliary epithelial cells can transform into myofibroblasts. This study examines the induction and molecular regulation of this transition during allograft rejection. Immortalized human cholangiocytes were stimulated with either transforming growth factor β1 (TGFβ1) or a T cell line, and they were examined for morphological, proteomic, and functional features. Posttransplant liver biopsy sections were also examined. Treatment of cholangiocytes with TGFβ1 or TGFβ-presenting T cells induced a bipolar morphology, reduced expression of E-cadherin and zona occludens 1 (ZO-1), and increased vimentin, fibronectin, matrix metalloproteinase 2 (MMP-2), MMP-9, and S100 calcium binding protein A4 (S100A4); treated cells invaded a model basement membrane. Chemokines induced T cell penetration of 3-dimensional, cultured bile duct-like structures and bile ducts in liver biopsy sections. A spatial association was observed between duct-infiltrating T cells and cholangiocyte expression of mesenchymal markers, including S100A4. Inhibition of S100A4 expression in vitro blocked TGFβ1-mediated loss of E-cadherin and ZO-1 but did not reduce induction of fibronectin, MMP-2, or MMP-9. This study demonstrates the potential for T cells to induce an intrahepatic biliary epithelial-to-mesenchymal cell transition during chronic rejection. Furthermore, S100A4 expression by cholangiocytes was identified as a crucial regulator of this transition. Liver Transpl, 2010. © 2010 AASLD.
Calcineurin inhibitor tacrolimus does not interfere with the suppression of hepatitis C virus infection by interferon-α
Authors: Pan Qiuwei , Metselaar Herold J. , de Ruiter Petra , Kwekkeboom Jaap , Tilanus Hugo W. , Janssen Harry L. A. , van der Laan Luc J. W.
Published: January 2010

Immunosuppression considerably affects hepatitis C virus (HCV) recurrence and the outcome of antiviral treatment after liver transplantation. Recent findings have suggested that the calcineurin inhibitor tacrolimus (Tac), unlike cyclosporine A (CsA), interferes with the antiviral activity of interferon-α (IFN-α) in vitro. The aim of this study was to more extensively investigate the effects of calcineurin inhibitors on IFN-α signaling and antiviral activity in subgenomic and infectious HCV models. Treatment with Tac and CsA did not affect Huh7 cell proliferation at doses of 10 to 500 ng/mL; however, it completely inhibited T cell proliferation. In contrast to previous reports, Tac had no effect on IFN-α-stimulated reporter gene expression, even at the dose of 5 μg/mL. Furthermore, in Huh7 subgenomic HCV replicon cells, treatment with Tac had no significant effect on the suppression of viral replication by IFN-α. In the infectious HCV model, treatment with IFN-α effectively inhibited both viral RNA replication and de novo production of virus particles, and neither was attenuated at any concentration of Tac. CsA had no significant effect on IFN-α-stimulated reporter gene expression; however, as shown previously, a combination of CsA (at 500 ng/mL and higher) and IFN-α resulted in enhanced inhibition of viral replication in both the subgenomic and infectious HCV models. In conclusion, our study shows no evidence that Tac or CsA interferes with IFN-α-mediated inhibition of HCV replication and virion production in vitro. Therefore, no further mechanistic arguments have been found to break the clinical controversy about the choice of calcineurin inhibitors during posttransplantation antiviral therapy.
Portal inflow and pressure changes in right liver living donor liver transplantation including the middle hepatic vein
Authors: Chan See Ching , Lo Chung Mau , Ng Kelvin K.C. , Ng Irene O.L. , Yong Boon Hun , Fan Sheung Tat
Published: January 2010

The middle hepatic vein may be included in right liver living donor liver transplantation (LDLT) to optimize hepatic venous outflow. We studied the graft's ability to relieve portal hypertension and accommodate portal hyperperfusion with portal manometry and ultrasonic flowmetry. Surgical outcomes with respect to portal hemodynamometry were also investigated. The ages of the recipients and donors for 46 consecutive LDLT procedures were 50 (range, 16-66 years) and 31 years (range, 18-54 years), respectively. The graft to standard liver volume ratio was 47.4% (range, 32.4%-69.0%). The hospital mortality rate was 4.4% as 2 recipients died from a subarachnoid hemorrhage and sepsis. The portal pressure dropped by 8 mm Hg (range, −7 to 19 mm Hg) from 23 (range, 8-37 mm Hg) to 14 mm Hg (range, 10-26 mm Hg) after graft implantation. The portal inflow positively correlated with the portal pressure before native liver hepatectomy (R
2 = 0.305, P = 0.001) and not with the graft size. The portal inflow increased from 81 mL/minute/100 g (range, 35-210 mL/minute/100 g) before donor right hepatectomy to 318 mL/minute/100 g (range, 102-754 mL/minute/100 g) after graft implantation. The graft portal inflow had a positive linear correlation with the recipient portal pressure before native liver total hepatectomy (R
2 = 0.261, P = 0.001) but not after graft implantation, and it had a negative correlation with the graft to standard liver volume ratio (R
2 = 0.247, P = 0.001). Only 1 of the graft biopsies showed moderate sinusoidal congestion. Twelve recipients had Clavien grade 2+ complications that were not related to the portal inflow and pressure or graft size. Right liver LDLT including the middle hepatic vein effectively lowered the recipient portal pressure by allowing unimpeded venous outflow. Liver Transpl 17:115–121, 2011. © 2011 AASLD
Coronary artery disease in orthotopic liver transplantation: Pretransplant assessment and management
Authors: Ehtisham Javed , Altieri Mario , Salamé Ephrem , Saloux Eric , Ollivier Isabelle , Hamon Martial
Published: January 2010

The prevalence of coronary artery disease in end-stage liver disease is only now being recognized. Liver transplant patients are a high risk subgroup for coronary artery disease, even if asymptomatic. Coronary artery disease is a predictor of poor outcomes; therefore, identification of those at risk must be a key clinical priority. However, risk assessment is particularly difficult as many of the available diagnostic tools have either proven to be unhelpful or remain to be validated. Risk factor profiling has been unable to identify those at risk and commonly underestimates risk. The high negative predictive value of Dobutamine stress echo, when target heart rates are achieved, allows it to be used to identify a low risk group. For all other patients, proceeding to invasive coronary angiography is often necessary, and the risks of the procedure can be reduced by a transradial approach. Pharmacological reduction of the consequences of coronary artery disease can be limited by the underlying liver disease. Revascularization pre-transplantation is recommended in international guidelines but has demonstrated little evidence of benefit. Surgical revascularization carries an increased risk in these patients and is commonly performed pre-transplantation, although combined liver and cardiac surgery has been described. Percutaneous coronary intervention is increasingly used with patients requiring anti-platelet medication for up to one year after intervention. We present a review of all these issues and the evidence for assessing and managing these high-risk patients. Liver Transpl 16:550-557, 2010. © 2010 AASLD.
Direct Synthesis of Poly(dimethylsiloxane) Copolymers with TPE‐Properties via CuAAC (Click Chemistry)
Authors: Schmidt Udo , Zehetmaier Philip C. , Rieger Bernhard
Published: January 2010

Poly(dimethylsiloxane) copolymers were synthesized directly from AA/BB monomers employing a CuAAC reaction (click chemistry) in a polyaddition approach. Using organic dialkynes and oligo(siloxane)s end‐functionalized with azide moieties it was possible to obtain siloxane‐based copolymers with TPE properties by click chemistry for the first time. As seen from DSC experiments, properties were strongly dependent on the incorporated organic comonomer.

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