bluuebunny/crossref_metadata_2025 huggingface dataset:
The intracellular dynamic of protein palmitoylation
Authors: Salaun Christine , Greaves Jennifer , Chamberlain Luke H.
Published: December 2010

S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond. This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning. Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation. In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates. In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation.
Culling sick mitochondria from the herd
Authors: Pallanck Leo J.
Published: December 2010

The PINK1–Parkin pathway plays a critical role in mitochondrial quality control by selectively targeting damaged mitochondria for autophagy. In this issue, Tanaka et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201007013) demonstrate that the AAA-type ATPase p97 acts downstream of PINK1 and Parkin to segregate fusion-incompetent mitochondria for turnover. p97 acts by targeting the mitochondrial fusion-promoting factor mitofusin for degradation through an endoplasmic reticulum–associated degradation (ERAD)-like mechanism.
Massive calcium–activated endocytosis without involvement of classical endocytic proteins
Authors: Lariccia Vincenzo , Fine Michael , Magi Simona , Lin Mei-Jung , Yaradanakul Alp , Llaguno Marc C. , Hilgemann Donald W.
Published: December 2010

We describe rapid massive endocytosis (MEND) of >50% of the plasmalemma in baby hamster kidney (BHK) and HEK293 cells in response to large Ca transients. Constitutively expressed Na/Ca exchangers (NCX1) are used to generate Ca transients, whereas capacitance recording and a membrane tracer dye, FM 4–64, are used to monitor endocytosis. With high cytoplasmic adenosine triphosphate (ATP; >5 mM), Ca influx causes exocytosis followed by MEND. Without ATP, Ca transients cause only exocytosis. MEND can then be initiated by pipette perfusion of ATP, and multiple results indicate that ATP acts via phosphatidylinositol-bis 4,5-phosphate (PIP2) synthesis: PIP2 substitutes for ATP to induce MEND. ATP-activated MEND is blocked by an inositol 5-phosphatase and by guanosine 5′-[γ-thio]triphosphate (GTPγS). Block by GTPγS is overcome by the phospholipase C inhibitor, U73122, and PIP2 induces MEND in the presence of GTPγS. MEND can occur in the absence of ATP and PIP2 when cytoplasmic free Ca is clamped to 10 µM or more by Ca-buffered solutions. ATP-independent MEND occurs within seconds during Ca transients when cytoplasmic solutions contain polyamines (e.g., spermidine) or the membrane is enriched in cholesterol. Although PIP2 and cholesterol can induce MEND minutes after Ca transients have subsided, polyamines must be present during Ca transients. MEND can reverse over minutes in an ATP-dependent fashion. It is blocked by brief β-methylcyclodextrin treatments, and tests for involvement of clathrin, dynamins, calcineurin, and actin cytoskeleton were negative. Therefore, we turned to the roles of lipids. Bacterial sphingomyelinases (SMases) cause similar MEND responses within seconds, suggesting that ceramide may be important. However, Ca-activated MEND is not blocked by reagents that inhibit SMases. MEND is abolished by the alkylating phospholipase A2 inhibitor, bromoenol lactone, whereas exocytosis remains robust, and Ca influx causes MEND in cardiac myocytes without preceding exocytosis. Thus, exocytosis is not prerequisite for MEND. From these results and two companion studies, we suggest that Ca promotes the formation of membrane domains that spontaneously vesiculate to the cytoplasmic side.
Linear representations of soluble groups of finite Morley rank
Authors: Altınel Tuna , Wilson John
Published: December 2010

Sufficient conditions are given for groups of finite Morley rank having nontrivial torsion-free nilpotent normal subgroups to have linear representations with small kernels. In particular, centreless connected soluble groups of finite Morley rank with torsion-free Fitting subgroups have faithful linear representations. Along the way, using a notion of definable weight space, we prove that certain connected soluble groups of finite Morley rank with torsion-free derived subgroup can be embedded in groups of finite Morley rank whose Fitting subgroups have definable abelian supplements.
Subspaces of almost Daugavet spaces
Authors: Lücking Simon
Published: December 2010

We study the almost Daugavet property, a generalization of the Daugavet property. We analyze what kind of subspaces and sums of Banach spaces with the almost Daugavet property have this property as well. The main result of the paper is that if

Z
Z

is a closed subspace of a separable almost Daugavet space

X
X

such that the quotient space

X

/

Z

X/Z

contains no copy of

ℓ
1

\ell _1

, then

Z
Z

has the almost Daugavet property too.
On asymptotic stability of ground states of NLS with a finite bands periodic potential in 1D
Authors: Cuccagna Scipio , Visciglia Nicola
Published: December 2010

We consider a nonlinear Schrödinger equation
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="i u Subscript t Baseline minus h 0 u plus beta left-parenthesis StartAbsoluteValue u EndAbsoluteValue squared right-parenthesis u equals 0 comma left-parenthesis t comma x right-parenthesis element-of double-struck upper R times double-struck upper R comma">

i

u

t

−

h

0

u
+
β
(

|

u

|

2

)
u
=
0
,
(
t
,
x
)
∈

R

×

R

,

\begin{equation*} iu_{t} -h_{0}u + \beta ( |u|^{2} )u=0 , (t,x)\in \mathbb {R}\times \mathbb {R}, \end{equation*}

with

h

0

=
−

d

2

d

x

2

+
P
(
x
)

h_{0}= -\frac {d^{2}}{dx^{2}} +P(x)

a Schrödinger operator with finitely many spectral bands. We assume the existence of an orbitally stable family of ground states. Exploiting dispersive estimates in Cuccagna (2008), Cuccagna and Visciglia (2009), and following the argument in Cuccagna (to appear) we prove that under appropriate hypotheses the ground states are asymptotically stable.
A property of 𝐶_{𝑝}[0,1]
Authors: Levin Michael
Published: December 2010

We prove that for every finite-dimensional compact metric space

X
X

there is an open continuous linear surjection from

C
p

[
0
,
1
]

C_p[0,1]

onto

C
p

(
X
)

C_p(X)

. The proof makes use of embeddings introduced by Kolmogorov and Sternfeld in connection with Hilbert’s 13th problem.
Ruled Lagrangian submanifolds of the 6-sphere
Authors: Lotay Jason
Published: December 2010

This article sets out to serve a dual purpose. On the one hand, we give an explicit description of the Lagrangians in the nearly Kähler 6-sphereS6\mathcal {S}^6which areruledby circles of constant radius using ‘Weierstrass formulae’. On the other hand, we recognise all known examples of these Lagrangians as being ruled by such circles. Therefore, we describe all families of Lagrangians inS6\mathcal {S}^6whose second fundamental form satisfies natural pointwise conditions—the so-called ‘second order families’.
Lipschitz-Killing curvatures of self-similar random fractals
Authors: Zähle M.
Published: December 2010

For a large class of self-similar random sets

F
F

in

R

d

\mathbb {R}^d

, geometric parameters

C
k

(
F
)

C_k(F)

,

k
=
0
,
…
,
d

k=0,\ldots ,d

, are introduced. They arise as a.s. (average or essential) limits of the volume

C
d

(
F
(
ε
)
)

C_d(F(\varepsilon ))

, the surface area

C

d
−
1

(
F
(
ε
)
)

C_{d-1}(F(\varepsilon ))

and the integrals of general mean curvatures over the unit normal bundles

C
k

(
F
(
ε
)
)

C_k(F(\varepsilon ))

of the parallel sets

F
(
ε
)

F(\varepsilon )

of distance

ε
\varepsilon

rescaled by

ε

D
−
k

\varepsilon ^{D-k}

as

ε
→
0

\varepsilon \rightarrow 0

. Here

D
D

equals the a.s. Hausdorff dimension of

F
F

. The corresponding results for the expectations are also proved.
Linear inequalities for enumerating chains in partially ordered sets
Authors: Hsiao Samuel , Rose Lauren , Stahl Rachel , Winston Ezra
Published: December 2010

We characterize the linear inequalities satisfied by flag

f
f

-vectors of all finite bounded posets. We do the same for semipure posets. In particular, the closed convex cone generated by flag

f
f

-vectors of bounded posets of fixed rank is shown to be simplicial, and the closed cone generated by flag

f
f

-vectors of semipure posets of fixed rank is shown to be polyhedral. The extreme rays of both of these cones are described explicitly in terms of quasisymmetric functions. The extreme rays of the first cone are then used to define a new basis for the algebra of quasisymmetric functions. This basis has nonnegative structure constants, for which a combinatorial interpretation involving lattice paths is given.
Uniqueness of Ginzburg-Rallis models: The Archimedean case
Authors: Jiang Dihua , Sun Binyong , Zhu Chen-Bo
Published: December 2010

In this paper we prove the uniqueness of Ginzburg-Rallis models in the Archimedean case. As a key ingredient, we introduce a new descent argument based on two geometric notions attached to submanifolds, which we call metrical properness and unipotent

χ
\chi

-incompatibility.
Ralstonia solanacearum Virulence Increased Following Large Interstrain Gene Transfers by Natural Transformation
Authors: Coupat-Goutaland Bénédicte , Bernillon Dominique , Guidot Alice , Prior Philippe , Nesme Xavier , Bertolla Franck
Published: December 2010

Horizontal gene transfer (HGT) is a major driving force of evolution and is also likely to play an important role in the threatening emergence of novel pathogens, especially if it involves distantly related strains with substantially different pathogenicity. In this study, the impact of natural transformation on pathogenicity in six strains belonging to the four phylotypes of the plant-pathogenic bacterium Ralstonia solanacearum was investigated. The study focused on genomic regions that vary between donor and recipient strains and that carry genes involved in pathogenicity such as type III effectors. First, strains from R. solanacearum species complex were naturally transformed with heterologous genomic DNA. Transferred DNA regions were then determined by comparative genomic hybridization and polymerase chain reaction sequencing. We identified three transformant strains that acquired large DNA regions of up to 80 kb. In one case, strain Psi07 (phylotype IV tomato isolate) acquired 39.4 kb from GMI1000 (phylotype I tomato isolate). Investigations revealed that i) 24.4 kb of the acquired region contained 20 new genes, ii) an allelic exchange of 12 genes occurred, and iii) 27 genes (33.4 kb) formerly present in Psi07 were lost. Virulence tests with the three transformants revealed a significant increase in the aggressiveness of BCG20 over its Psi07 parent on tomato. These findings demonstrate the potential importance of HGT in the pathogenic evolution of R. solanacearum strains and open new avenues for studying pathogen emergence.
A Necrosis-Inducing Elicitor Domain Encoded by Both Symptomatic and AsymptomaticPlantago asiatica mosaic virusIsolates, Whose Expression Is Modulated by Virus Replication
Authors: Komatsu Ken , Hashimoto Masayoshi , Maejima Kensaku , Shiraishi Takuya , Neriya Yutaro , Miura Chihiro , Minato Nami , Okano Yukari , Sugawara Kyoko , Yamaji Yasuyuki , Namba Shigetou
Published: December 2010

Systemic necrosis is the most destructive symptom induced by plant pathogens. We previously identified amino acid 1154, in the polymerase domain (POL) of RNA-dependent RNA polymerase (RdRp) of Plantago asiatica mosaic virus (PlAMV), which affects PlAMV-induced systemic necrosis in Nicotiana benthamiana. By point-mutation analysis, we show that amino acid 1,154 alone is not sufficient for induction of necrotic symptoms. However, PlAMV replicons that can express only RdRp, derived from a necrosis-inducing PlAMV isolate, retain their ability to induce necrosis, and transient expression of PlAMV-encoded proteins indicated that the necrosis-eliciting activity resides in RdRp. Moreover, inducible-overexpression analysis demonstrated that the necrosis was induced in an RdRp dose-dependent manner. In addition, during PlAMV infection, necrotic symptoms are associated with high levels of RdRp accumulation. Surprisingly, necrosis-eliciting activity resides in the helicase domain (HEL), not in the amino acid 1,154-containing POL, of RdRp, and this activity was observed even in HELs of PlAMV isolates of which infection does not cause necrosis. Moreover, HEL-induced necrosis had characteristics similar to those induced by PlAMV infection. Overall, our data suggest that necrotic symptoms induced by PlAMV infection depend on the accumulation of a non–isolate specific elicitor HEL (even from nonnecrosis isolates), whose expression is indirectly regulated by amino acid 1,154 that controls replication.
Effect of Silicon Nutrition on Oxidative Stress Induced by Phytophthora melonis Infection in Cucumber
Authors: Mohaghegh P. , Khoshgoftarmanesh A. H. , Shirvani M. , Sharifnabi B. , Nili N.
Published: December 2010

The effect of silicon nutrition on root rot of cucumber caused by Phytophthora melonis was studied in a greenhouse experiment. Two cucumber cultivars (Cucumis sativus ‘Dominus’ and ‘Super Dominus’) fertilized with three concentrations of Si (0.0, 1.0, and 1.7 mM Si in the form of sodium silicate) were not inoculated or were inoculated with P. melonis. The P. melonis isolate significantly decreased root dry weights, although the magnitude of growth reduction varied with cultivar and Si concentration. Silicon nutrition at either concentration significantly reduced disease severity relative to the treatment that received no silicon. There was a significant negative correlation between the extent of root rot caused by P. melonis and the extent of electrolyte leakage of roots. Roots infected with P. melonis had greater root catalase (CAT) and ascorbate peroxidase (APX) activities. There was a positive correlation between silicon concentrations and CAT and APX activities in plants inoculated with P. melonis. Silicon improved activity of antioxidant enzymes, resulting in enhanced crop resistance to oxidative stress induced by P. melonis infection and improved cucumber growth.
First Report of Tomato yellow leaf curl virus Infecting Cowpea in China
Authors: Dai F. M. , Zeng R. , Chen W. J. , Lu J. P.
Published: December 2010

Tomato yellow leaf curl virus (TYLCV) is a devastating pathogen of tomato that causes significant yield losses in many tropical and subtropical regions (1). In China, this virus was first found in 2006 on tomato in Shanghai (2). In October 2008, chlorotic yellow leaves of cowpea (Vigna sinensis) were observed in Qingpu, Shanghai, China with 15 to 20% incidence in plants in high tunnels. Large populations of whiteflies were observed in association with the diseased cowpea. The disease agent was transmitted to cowpea (and tomato) by whiteflies, which resulted in chlorotic yellow leaves on cowpea (yellow leaf curl symptoms on tomato) that were identical to those observed in the field. On the basis of the suspected insect vector, symptomology, and severe epidemics of tomato yellow leaf curl disease (TYLCD) in Shanghai in recent years, Tomato yellow leaf curl virus was suspected as the causal agent. Total DNA was extracted from four symptomatic cowpea samples. PCR was performed with specific primers V416 (5′-CAAGGCACAAACAAGCGACG-3′) and C1287 (5′-CTCAACTTCCGAATTTGGACGAC-3′) to amplify a 872-bp DNA fragment of the viral coat protein (CP) gene and an amplicon of the expected size was obtained in all four samples but not from healthy leaf samples. The PCR products were sequenced and the sequences were identical among samples. Primers TYLCV-F (5′-CAGGAGGCAGCCAAGTATGAG-3′) and TYLCV-R (5′-ACTAATGCCTGTTCYTTCATTCC-3′) (Y = C or T/U) were designed on the basis of the sequence (Accession No. HM804856) and reported (Accession No. FM163463) CP gene to amplify the full-length viral DNA of cowpea isolate (CN:SH:Cowpea:08). The sequence was determined to be 2,781 nucleotides long (Accession No. GU434143). A comparison of the sequence with those in GenBank shows that the cowpea isolate has the highest nucleotide sequence identity (99%) with TYLCV isolate XH2 from tomato in Xinghua, Jiangsu, China (Accession No. GU111505). To our knowledge, this is the first report of TYLCV infecting cowpea in China and also the first report in the world.

References: (1) H. Czosnek and H. Laterrot. Arch. Virol. 142:1391, 1997. (2) J. B. Wu et al. Plant Dis. 90:1359, 2006.
The validity of DSM‐IV cannabis abuse and dependence criteria in adolescents and the value of additional cannabis use indicators
Authors: Piontek Daniela , Kraus Ludwig , Legleye Stéphane , Bühringer Gerhard
Published: December 2010

Aims  This study assessed the validity of DSM‐IV cannabis abuse and dependence criteria in an adolescent general population sample and evaluated the usefulness of additional cannabis use indicators.

Design and setting  Data came from the 2008 Survey on Health and Consumption during the Day of Defense Preparation (ESCAPAD), a cross‐sectional self‐administered survey conducted in France.

Participants  The analytical sample comprised 3641 adolescents aged 17–19 years who reported cannabis use in the past 12 months.

Measurements  To assess DSM‐IV criteria of cannabis abuse and dependence, the Munich Composite International Diagnostic Interview (M‐CIDI) was used. As additional cannabis use indicators, daily use, use when alone and use before midday were assessed. Confirmatory factor analyses and two‐parameter logistic item response theory (IRT) models were run. Differential item functioning was assessed using the IRT log‐likelihood ratio approach.

Results  A one‐factor model comprising both abuse and dependence criteria showed the best fit to the data. Abuse item legal problems showed the greatest severity, whereas dependence items larger/longer and tolerance were found least severe. Discriminatory power was lowest for impaired control and legal problems. Additional cannabis use indicators increased the precision of the overall DSM‐IV criterion set. Gender‐based differential item functioning was observed for items tolerance, withdrawal and use before midday.

Conclusion  The current DSM conceptualization with two distinct and graded diagnostic classes has limited validity among adolescents. In forthcoming revisions of the classification system, several existing criteria should be revised or dropped, new indicators of substance use disorders should be included and gender should be considered.
Review article: chronic hepatitis B – anti‐viral or immunomodulatory therapy?
Authors: Rijckborst V. , Sonneveld M. J. , Janssen H. L. A.
Published: December 2010

Aliment Pharmacol Ther 2011; 33: 501–513

Background  First‐line treatment options for chronic hepatitis B (CHB) consist of nucleos(t)ide analogues with a high barrier to resistance (entecavir and tenofovir) or the immunomodulatory agent peginterferon (PEG‐IFN). The optimal choice for individual patients remains controversial.

Aim  To review treatment options for CHB, with a focus on deciding between prolonged nucleos(t)ide analogue therapy or a finite course of PEG‐IFN.

Methods  A comprehensive literature search was undertaken.

Results  Long‐lasting, treatment‐maintained suppression of hepatitis B virus (HBV) DNA without resistance is achievable in most patients by entecavir or tenofovir. A sustained off‐treatment response is, however, unlikely and long‐term therapy must be anticipated. PEG‐IFN offers a higher rate of sustained response in a subgroup of patients, but is frequently complicated by side effects. Pre‐treatment predictors of response, including HBV genotype, alanine aminotransferase and HBV DNA levels, aid in selecting patients for PEG‐IFN therapy. Furthermore, on‐treatment markers such as quantitative hepatitis B surface antigen may be applied to identify nonresponders early during the PEG‐IFN treatment course, thereby preventing unnecessary treatment.

Conclusions  Both nucleos(t)ide analogues and PEG‐IFN can be prescribed as first‐line treatment options for CHB. However, PEG‐IFN should only be considered for patients with a high chance of response based on pre‐treatment and on‐treatment factors.
Systematic review: the diagnosis and staging of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis
Authors: Dowman J. K. , Tomlinson J. W. , Newsome P. N.
Published: December 2010

Aliment Pharmacol Ther2011;33:525–540

Background Non‐alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of non‐alcoholic steatohepatitis (NASH) and fibrosis identifies an at‐risk group with increased risk of cardiovascular and liver‐related deaths. The identification and management of this at‐risk group remains a clinical challenge.

Aim To perform a systematic review of the established and emerging strategies for the diagnosis and staging of NAFLD.

Methods Relevant research and review articles were identified by searching PubMed, MEDLINE and EMBASE.

Results There has been a substantial development of non‐invasive risk scores, biomarker panels and radiological modalities to identify at‐risk patients with NAFLD without recourse to liver biopsy on a routine basis. These modalities and algorithms have improved significantly in their diagnosis and staging of fibrosis and NASH in patients with NAFLD, and will likely impact on the number of patients undergoing liver biopsy.

Conclusions Staging for NAFLD can now be performed by a combination of radiological and laboratory techniques, greatly reducing the requirement for invasive liver biopsy.
Transforming growth factor‐β1 in asthmatic airway smooth muscle enlargement: is fibroblast growth factor‐2 required?
Authors: Bossé Y. , Stankova J. , Rola‐Pleszczynski M.
Published: December 2010

Enlargement of airway smooth muscle (ASM) tissue around the bronchi/bronchioles is a histopathological signature of asthmatic airway remodelling and has been suggested to play a critical role in the increased lung resistance and airway hyperresponsiveness seen in asthmatic patients. The pleiotropic cytokine, TGF‐β1, is believed to contribute to several aspects of asthmatic airway remodelling and is known to influence the growth of many cell types. Increased TGF‐β1 expression/signalling and ASM growth have been shown to occur concurrently in animal models of asthma. Abundant studies further substantiate this association by showing that therapeutic strategies that reduce or prevent TGF‐β1 overexpression/signalling lead to a parallel decrease or prevention of ASM enlargement. Finally, recent findings have supported a direct link of causality between TGF‐β1 overexpression/signalling and the overgrowth of ASM tissue. To follow‐up on thesein vivostudies, many investigators have pursued detailed investigation of ASM in cell culture conditions, assessing the direct role of TGF‐β1 on cellular proliferation and/or hypertrophy. Inconsistencies among thein vitrostudies suggest that the effect of TGF‐β1 on ASM cell proliferation/hypertrophy is contextual. A hypothesis focusing on fibroblast growth factor‐2 is presented at the end of this review, which could potentially reconcile the apparent discrepancy between the conflictingin vitrofindings with the consistentin vivofinding that TGF‐β1 is required for ASM enlargement in asthma.

Cite this as: Y. Bossé, J. Stankova and M. Rola‐Pleszczynski,Clinical & Experimental Allergy, 2010 (40) 710–724.
Purification and identification of an ACE inhibitory peptide from the peptic hydrolysate of Acetes chinensis and its antihypertensive effects in spontaneously hypertensive rats
Authors: Cao Wenhong , Zhang Chaohua , Hong Pengzhi , Ji Hongwu , Hao Jiming
Published: December 2010

Acetes chinensis is a marine shrimp found in the coastal waters of China. The shrimp was hydrolysed by pepsin to prepare hydrolysates with angiotensin I‐converting enzyme (ACE) inhibitory activity. The hydrolysate with the highest ACE inhibitory activity resulted from a 3–5 h incubation at 45 °C and pH 2.5 with pepsin. Gel filtration and RP‐HPLC were used to separate ACE inhibitory peptides from the hydrolysate. The gel filtration fraction of the hydrolysate with a molecular weight range from 1320 Da to 311 Da exerted the highest ACE inhibition activity. This fraction was separated by RP‐HPLC into fifteen fractions, of which fraction F9 showed 92.7% of the ACE inhibition activity. Its peptide sequence was determined to be Leu–His–Pro. It showed a potent antihypertensive activity in spontaneously hypertensive rats. The results suggested that this peptide may be a potent ACE inhibitor which might be developed into a healthy food to lower blood pressure.
A novel subcutaneous controlled‐release amoxicillin degradable implant for extended‐interval administration in veterinary medicine
Authors: HORWITZ E. , KAGAN L. , AVNI‐MAGEN N. , DARYI D. , GATI I. , HOFFMAN A. , FRIEDMAN M. , LAVY E.
Published: December 2010

Horwitz, E., Kagan, L., Avni‐Magen, N., Daryi, D., Gati, I., Hoffman, A., Friedman, M., Lavy, E. A novel subcutaneous controlled‐release amoxicillin degradable implant for extended‐interval administration in veterinary medicine. J. vet. Pharmacol. Therap.34, 494–498.

Dosage forms of antimicrobials play a critical role in facilitating the attainment of pharmacokinetic–pharmacodynamic (PK–PD) targets as well as adherence in both veterinary and human medicine. The purpose of this study was to develop and evaluate a controlled‐release subcutaneous amoxicillin implant for single‐dose therapy of large ruminants such as goats, sheep, and deer. The degradable implant, designed to attain PK–PD targets following single administration, was evaluated for amoxicillin release rate and time–concentration profile. In vitro release studies demonstrated constant‐rate release of approximately 40% of amoxicillin content within 96 h. In an in vivo study in goats, serving as a model for target animals, a serum concentration of approximately 0.4 mg/L was achieved within 8 h of implant insertion and maintained for >6 days. In comparison, in control goats given a standard single intramuscular amoxicillin dose of 15 mg/kg, amoxicillin peaked at 1.2 mg/L after 1 h, rapidly dropping to below detection level at 8 h. These results suggest that the proposed implant offers a unique modality for animal caregivers to conveniently administer a full antimicrobial course following a single dose of an efficient PK–PD‐optimized dosage form. Furthermore, modifications of implant composition may allow for tailoring of its characteristics to various PK, PD, microbiological, and clinical requirements.
Plasma pharmacokinetics of abamectin in fallow deer (Cervus dama dama) following subcutaneous administration
Authors: ŽELE D. , TAVČAR‐KALCHER G. , KOBAL S. , VENGUŠT G. , VENGUŠT A. , GRABNAR I.
Published: December 2010

Žele, D., Tavčar‐Kalcher, G., Kobal, S., Vengušt, G., Vengušt, A., Grabnar, I. Plasma pharmacokinetics of abamectin in fallow deer (Cervus dama dama) following subcutaneous administration. J. vet. Pharmacol. Therap.34, 455–459.

The pharmacokinetics of abamectin (ABM) following a single subcutaneous administration of 200 μg/kg was evaluated in adult fallow deer by following ABM concentration in blood plasma. A nonlinear mixed effects modelling procedure was used for pharmacokinetic analysis. The time course of ABM concentration was described by a two‐compartment model with first‐order absorption. Abamectin absorption in fallow deer was rapid with a peak plasma concentration of 120.7 ± 33.2 ng/mL observed at 19.1 ± 7.7 h (mean ± SD). Half‐lives of the distribution and terminal phase were 17.2 and 119.3 h, respectively. Typical apparent clearance of the bioavailable fraction (CL/F) was 0.795 L/h and was independent of animal weight. Considering the obtained pharmacokinetic parameters in our study, we may assume that effective parasite control in fallow deer is obtained using the usual recommended dose of 200 μg/kg.
Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands
Authors: de Vries Willemien , de Langen Zacharias J. , Aronson Daniel C. , Hulscher Jan B. F. , Peeters Paul M. J. G. , Jansen‐Kalma Pauline , Verkade Henkjan J. ,   also on behalf of NeSBAR
Published: December 2010

de Vries W, de Langen ZJ, Aronson DC, Hulscher JBF, Peeters PMJG, Jansen‐Kalma P, Verkade HJ also on behalf of NeSBAR. Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands. Pediatr Transplantation 2011: 15:176–183. © 2010 John Wiley & Sons A/S.

Abstract:  In order to further improve the outcome of BA, we characterized the mortality of BA patients who did not undergo OLT in the Netherlands, and compared our results with international data. For this purpose, we analyzed the causes of mortality of non‐transplanted BA patients before the age of five yr, using the NeSBAR database. To evaluate trends in mortality, we compared the cohort 1987–1996 (n = 99) with 1997–2008 (n = 111). We compared clinical condition at OLT assessment with available international data, using the PELD‐score. Mortality of non‐transplanted BA children was 26% (26/99) in 1987–1996 and 16% (18/111) in 1997–2008 (p = 0.09). Sepsis was the prevailing direct cause of death (30%; 13/44). PELD‐scores at the time of assessment were higher in non‐transplanted BA patients (median 20.5; range 13–40) compared with international data (mean/median between 11.7 and 13.3). Based on our national data, we conclude that pretransplant mortality of BA patients is still considerable, and that sepsis is a predominant contributor. Our results strongly indicate that the prognosis of patients with BA in the Netherlands can be improved by earlier listing of patients for OLT and by improving pretransplant care.
Effect of method and time of first colostrum feeding on serum immunoglobulin concentration, health status and body weight gain in mithun (Bos frontalis) calves
Authors: Mech A. , Dhali A. , Baruah K. K. , Singh R. K. , Mondal S. K. , Rajkhowa C.
Published: December 2010

The effect of method and time of first colostrum feeding on the concentration of serum immunoglobulin (Ig) was evaluated in mithun (Bos frontalis) calves. The hypotheses were that the variable method and time of first colostrum feeding might affect the level of serum Ig and in turn the growth performance and health status of the claves during the early age. The newborn calves were randomly allotted to one of the four experimental groups – G‐1: allowed to suckle the dam at own choice, G‐2: separated immediately after birth and allowed to suckle the dam first at 6 h and then at own choice, G‐3: bottle fed ad libitum colostrum of its own dam first at 6 h and then at 6‐h intervals until 24 h, G‐4: bottle fed ad libitum colostrum of its own dam within 1 h, at 6 h and then at 6‐h intervals until 24 h. The concentrations of IgG, IgM, and IgA were lowest (p < 0.01) at birth and increased following colostrum feeding irrespective of the experimental group. Highest concentrations of all the Ig classes were observed at 12–24 h after birth. The concentrations then transiently decreased from day 7 to 14, and then steadily increased after day 28. The concentrations of IgG (p < 0.01) and IgA (p < 0.05) were higher in G‐1 in relation to the other groups during the first week after birth. Similarly, higher concentration of IgA (p < 0.05) was found in G‐1 in relation to the other groups during the rest of the experimental period. The apparent absorption efficiency of colostral IgG was higher (p < 0.05) in G‐4 in relation to G‐3. Growth rate and health status were not influenced by the method and time of first colostrum feeding. In conclusion, a 6‐h delay in the first colostrum feeding reduced the level of serum Ig noticeably.
Fish meal – nutritive value
Authors: Cho J. H. , Kim I. H.
Published: December 2010

Understanding the interactions between nutrition and immune system is crucial for adjusting nutrient allowances in dietary formulations that optimize production efficiency. Among various animal proteins, fish meal (FM) is rich in protein (amino acids), readily available throughout most of the world, and competitively priced against other animal proteins (e.g. milk and blood). In addition, many researchers reported that FM is traditionally recognized as a high digestible protein with a high content of amino acids, vitamins and minerals for pigs. Supplementation of fatty acids by FM and fish oil (FO) is one strategy to modify an animal immune response. As a result of FM and FO effects, those supplementations can result in improved performance and immunity of young animals.
Severity of coronary atherosclerosis is an independent predictor of the left ventricular ejection fraction
Authors: Jia En‐Zhi , Xu Zhen‐Xia , Yang Zhi‐Jian , Zhu Tie‐Bing , Wang Lian‐Sheng , Cao Ke‐Jiang , Ma Wen‐Zhu
Published: December 2010

1. We studied the association between the level of the left ventricular ejection fraction and the severity of coronary atherosclerosis.

2. The study population consisted of 850 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis. Anthropometric measurements including the body mass index, blood pressure, blood lipids, blood glucose and leucocyte count were taken. The severity of coronary atherosclerosis was defined by the Gensini score.

3. When the level of the left ventricular ejection fraction was examined as a categorical variable classified by quartile values, subjects with a high left ventricular ejection fraction level had significantly lower Gensini scores than those with a low left ventricular ejection fraction level (P = 0.000). Spearman’s correlation analysis suggested that the left ventricular ejection fraction was significantly negatively associated with Gensini score (r = −0.213, P = 0.000). Multiple stepwise linear regression analysis showed that the Gensini score was significantly independently associated with the left ventricular ejection fraction level (β = −0.194, P = 0.000). Furthermore, multivariable stepwise logistic regression analysis showed that the Gensini score was the independent risk factor for dysfunction of left ventricular ejection (OR = 2.048, 95% CI = 1.517–2.763).

4. The severity of coronary atherosclerosis was defined by the Gensini score. This was a strong and statistically highly significant predictor of the left ventricular ejection fraction level and dysfunction of left ventricular ejection independent of other major risk factors including age, body mass index, blood pressure, fasting blood glucose, blood lipid and leucocyte count.
Rapid increases of gamma power in the auditory cortex following noise trauma in humans
Authors: Ortmann Magdalene , Müller Nadia , Schlee Winfried , Weisz Nathan
Published: December 2010

Tinnitus is an auditory perception in the absence of any external sound source. It has been suggested that tinnitus is related to enhanced synchronization of neuronal activity in the auditory cortex. Usually a hearing damage can be identified suggesting auditory deprivation to central auditory regions to be fundamental for neurophysiological processes related to tinnitus. Until now, human research has been conducted on patients with chronic tinnitus (> 6 months). However, neuronal activity accompanying auditory deprivation and putatively tinnitus may not remain constant over time, making it difficult to directly relate outcomes of current animal studies (acute tinnitus) to chronic tinnitus in humans, and vice versa. We investigated 14 amateur rock musicians who frequently reported a short‐term tinnitus immediately after band practice. Magnetoencephalographic resting‐state recordings, audiometry and tinnitus testing were performed at two separate occasions: with and without previous exposure to loud music. Analyses revealed that transient tinnitus was accompanied by temporary hearing loss in both ears and increased gamma activity in the right auditory cortex in 13 out of 14 cases. Additionally, tinnitus frequency was strongly correlated to hearing loss. Analogous to animal studies, our results show for the first time in humans that noise trauma leads rapidly to increased neuronal synchrony in the auditory cortex. Importantly, the strongly right‐lateralized effect implies that it does not reflect tinnitus percept per se. This could rather have been triggered by greater discontinuities of hearing loss at high frequencies that were particularly pronounced in the left ear.
Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus principal cells
Authors: Koehler Seth D. , Pradhan Shashwati , Manis Paul B. , Shore Susan E.
Published: December 2010

In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in the guinea pig receive and respond to somatosensory inputs and perform multisensory integration. DCN pyramidal cells respond to sounds with characteristic spike‐timing patterns that are partially controlled by rapidly inactivating potassium conductances. Deactivating these conductances can modify both spike rate and spike timing of responses to sound. Somatosensory pathways are known to modify response rates to subsequent acoustic stimuli, but their effect on spike timing is unknown. Here, we demonstrate that preceding tonal stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters the first spike latency, the first interspike interval and the average discharge regularity of firing evoked by the tone. These effects occur whether the neuron is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that multisensory integration in DCN alters spike‐timing representations of acoustic stimuli in pyramidal cells. These changes likely occur through synaptic modulation of intrinsic excitability or synaptic inhibition.
Probability of survival based on etiology of cardiopulmonary arrest in pediatric patients
Authors: Berens Richard J. , Cassidy Laura D. , Matchey Jennifer , Campbell Deborah , Colpaert Krista D. , Welch Tangela , Lawson Michelle , Peterson Cheryl , O’Flynn Justine , Dearth Mary , Tieves Kelly S.
Published: December 2010

Objective:  To aggregate data across institutions to identify, characterize, and differentiate potential survivors from nonsurvivors based on etiology of event.

Aim:  To evaluate the association of the cardiopulmonary resuscitation (CPR) duration and probability of survival (Ps), stratified by etiology of arrest.

Background:  In‐hospital cardiac arrests occur in 2–6% of pediatric patients with poor survival rates resulting in significant expenditures of time and resources.

Methods:  Retrospective data from six pediatric hospitals on patients suffering from pulseless cardiac arrests receiving CPR for over one minute were analyzed. Data included demographics, reason for code, precardiac arrest diagnosis, devices and treatment, management strategies during cardiac arrest, compression duration, outcome at hospital discharge, and neurologic outcome of survivors at hospital discharge. Results of logistic regression analysis generated predicated probabilities of survival for duration of compression. Patients were stratified by cardiac‐induced cardiac arrests (CICA) and respiratory‐induced cardiac arrest (RICA).

Results:  A total of 257 patients were included, and 27% of CICA and 35% of RICA patients survived to hospital discharge. Ps was initially lower for the CICA patients (Ps at 1 min = 29%) and remained constant (Ps at 60 min = 25%). RICA patients’Ps was higher initially (Ps at 1 min = 62%) but demonstrated a dramatic drop within the first 60 min of CPR (Ps at 60 min = 0.2%).

Conclusions:  Probability of survival curves based on duration of CPR was statistically significantly different for CICA patients compared to RICA patients.
Ketorolac tromethamine: stereo‐specific pharmacokinetics and single‐dose use in postoperative infants aged 2–6 months
Authors: Lynn Anne M. , Bradford Heidi , Kantor Eric D. , Andrew Marilee , Vicini Paolo , Anderson Gail D.
Published: December 2010

Objective:  We determined the postoperative pharmacokinetics (PK), safety, and analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single intravenous (IV) administration of racemic ketorolac or placebo.

Background:  Information on the PK of ketorolac in infants is limited. Unblinded studies suggest ketorolac may be useful in infants.

Methods:  This double‐blinded, placebo‐controlled study enrolled 14 infants (aged <6 months) postoperatively. At 6–18 h after surgery, infants were randomized to receive placebo, 0.5 mg·kg−1, or 1 mg·kg−1 ketorolac IV. All infants received morphine sulfate as needed for pain control. Blood was collected up to 12‐h postdosing. Analysis used noncompartmental and compartmental population modeling methods.

Results:  In addition to noncompartmental and empirical Bayes PK modeling, data were integrated with a previously studied data set comprising 25 infants and toddlers (aged 6–18 months). A two‐compartmental model described the comprehensive data set. The population estimates of the R (+) isomer were (%CV): central volume of distribution 1130 (10%) ml, peripheral volume of distribution 626 (25%) ml, and clearance from the central compartment 7.40 (8%) ml·min−1. Those of the S (−) isomer were 1930 (15%) ml, 319 (58%) ml, and 39.5 (13%) ml·min−1. Typical elimination half‐lives were 191 and 33 min, respectively. There was a trend for increased clearance and central volume with increasing age and weight. The base model suggested that clearance of the S (−) isomer was weakly related to age; however, when body size adjustment was added to the model, no covariates were significant. Safety assessment showed no changes in renal or hepatic function tests, surgical drain output, or continuous oximetry between groups. Cumulative morphine administration showed large inter‐patient variability and was not different between groups.

Conclusion:  Stereo‐isomer‐specific clearance of ketorolac in infants (aged 2–6 months) shows rapid elimination of the analgesic S (−) isomer as reported in infants aged 6–18 months. No adverse effects were seen after a single IV ketorolac dose.
ANALYTICAL MARXISM
Authors: Veneziani Roberto
Published: December 2010

Abstract This paper provides a comprehensive survey of the literature on Analytical Marxism (AM) and analyses its relevance for social theory. AM is precisely defined and distinguished from Rational Choice Marxism (RCM). The different substantive implications of the two approaches are discussed: according to RCM, the role of Marxism in the social sciences is exhausted, whereas AM has reconstructed a set of propositions that aim to provide the foundations of a distinctive approach in social theory. The methodological debate around and within AM is analysed and the shortcomings of methodological individualism and rational choice theory are stressed, raising doubts on the claim that RCM is the only scientific approach to Marx's theory. Yet, wholesale rejections on a priori methodological or exegetical grounds are questioned. A focused, immanent critique of RCM is developed, which emphasizes the lack of an adequate analysis of structural constraints and endogenous preferences in RCM models. It is argued that the analysis of endogenous preferences and structural constraints is consistent with an anti‐reductionist AM approach and it may provide the outline of a fertile, distinctive research programme in explanatory social theory that builds on the core of Marxism identified by AM.
Entrepreneurial Orientation: A Theoretical and Empirical Examination of the Consequences of Differing Construct Representations
Authors: George Bradley A.
Published: December 2010

abstract

There has been much debate in the literature over the nature of the entrepreneurial orientation (EO) construct regarding its dimensionality and whether or not the dimensions of the construct are independent. This paper examines two different measurement models of the EO construct that have been put forth in the literature and describes the implications of each model with regard to these issues as well as their broader theoretical and practical implications for studies regarding EO. Finally, a Monte Carlo simulation shows that misspecification of the construct can inflate structural parameter estimates by over 240 per cent and critical ratios by up to 68 per cent, illustrating the threat to the statistical conclusion validity studies and emphasizing the importance of congruence between the theoretical definition of the construct and its measurement.
HEALTH CARE SPECIAL REPORT: THE HEALTH CARE QUANDARY
Authors: Goldberg Beverly
Published: December 2010

Health care in the UK is under intense scrutiny as its government tries to balance rising demands and spiralling costs. Beverly Goldberg, after reviewing the state of health care in other developing nations, says that while the health care profession is fraught with many problems, there are numerous possible solutions.
MAKING BETTER RISK MANAGEMENT DECISIONS
Authors: Birkinshaw Julian , Jenkins Huw
Published: December 2010

During a three‐year research project on risk management in large organisations, Julian Birkinshaw and Huw Jenkins interviewed three dozen executives from a diverse array of business sectors. Their findings reveal that risk management must be personal to be successful.
EXECUTIVE SUMMARY: THE FASTEST WAY FROM KNOWING TO NETWORKING
Authors: Crainer Stuart
Published: December 2010

Louise Mors, ‘Innovation in a global consulting firm: When the problem is too much diversity’, Strategic Management Journal 31, no. 8, August 2010.
Low‐cumulative dose isotretinoin treatment in mild‐to‐moderate acne: efficacy in achieving stable remission
Authors: Borghi A. , Mantovani L. , Minghetti S. , Giari S. , Virgili A. , Bettoli V.
Published: December 2010

Background  Aimed at the reduction of post‐treatment relapse of severe acne, the cumulative dose of oral isotretinoin should be ≥120 mg/kg. However, data on the appropriate oral isotretinoin treatment regimen in mild and moderate acne are lacking.

Objective  The purpose of this study was to determine the efficacy of an isotretinoin‐sparing protocol in inducing permanent remission of mild and moderate acne.

Methods  In this open, prospective, non‐comparative study, 150 patients affected with mild‐to‐moderate acne were treated with isotretinoin until complete recovery and for a further month of treatment, independent of the total cumulative dose reached. Patients then underwent a 1‐year maintenance therapy with adapalene 0.1% cream. Patients were followed up for a further year, without any treatment.

Results  A total of 139 patients completed the study. Overall, patients received a mean of 80.92 mg/kg cumulative dose of isotretinoin. In the 2‐year follow‐up, relapse only appeared in 13 patients (9.35%).

Conclusion  Comparing our findings with published data, this isotretinoin‐sparing regimen was shown to be effective in inducing stable remission and preventing acne relapses in patients with mild‐to‐moderate acne. Low‐cumulative dose regimens may potentially lead to a lower incidence of side‐effects and to lower costs than higher doses.