bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxoplasma gondiisalvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole
Authors: Romano Julia D. , Sonda Sabrina , Bergbower Emily , Smith Maria Elisa , Coppens Isabelle
Published: April 2013

The obligate intracellular protozoan Toxoplasma gondii actively invades mammalian cells and, upon entry, forms its own membrane-bound compartment, named the parasitophorous vacuole (PV). Within the PV, the parasite replicates and scavenges nutrients, including lipids, from host organelles. Although T. gondii can synthesize sphingolipids de novo, it also scavenges these lipids from the host Golgi. How the parasite obtains sphingolipids from the Golgi remains unclear, as the PV avoids fusion with host organelles. In this study, we explore the host Golgi–PV interaction and evaluate the importance of host-derived sphingolipids for parasite growth. We demonstrate that the PV preferentially localizes near the host Golgi early during infection and remains closely associated with this organelle throughout infection. The parasite subverts the structure of the host Golgi, resulting in its fragmentation into numerous ministacks, which surround the PV, and hijacks host Golgi–derived vesicles within the PV. These vesicles, marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. Scavenged sphingolipids contribute to parasite replication since alterations in host sphingolipid metabolism are detrimental for the parasite's growth. Thus our results reveal that T. gondii relies on host-derived sphingolipids for its development and scavenges these lipids via Golgi-derived vesicles.
Nebulin binding impedes mutant desmin filament assembly
Authors: Baker Laura K. , Gillis David C. , Sharma Sarika , Ambrus Andy , Herrmann Harald , Conover Gloria M.
Published: April 2013

Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I). These mutants were chosen because the mutated residues are located within the nebulin-binding regions of desmin. We discovered that, although nebulin M160–164 bound to both desmin tetrameric complexes and mature filaments, all three mutants exhibited significantly delayed filament assembly kinetics when bound to nebulin. Correspondingly, all three mutants displayed enhanced binding affinities and capacities for nebulin relative to wild-type desmin. Electron micrographs showed that nebulin associates with elongated normal and mutant DIFs assembled in vitro. Moreover, we measured significantly delayed dynamics for the mutant desmin E245D relative to wild-type desmin in fluorescence recovery after photobleaching in live-cell imaging experiments. We propose a mechanism by which mutant desmin slows desmin remodeling in myocytes by retaining nebulin near the Z-discs. On the basis of these data, we suggest that for some filament-forming desmin mutants, the molecular etiology of desminopathy results from subtle deficiencies in their association with nebulin, a major actin-binding filament protein of striated muscle.
Polo-like kinase phosphorylation of bilobe-resident TbCentrin2 facilitates flagellar inheritance inTrypanosoma brucei
Authors: de Graffenried Christopher L. , Anrather Dorothea , Von Raußendorf Freia , Warren Graham
Published: April 2013

In the protist parasite Trypanosoma brucei, the single Polo-like kinase (TbPLK) controls the inheritance of a suite of organelles that help position the parasite's single flagellum. These include the basal bodies, the bilobe, and the flagellar attachment zone (FAZ). TbCentrin2 was previously shown to be a target for TbPLK in vitro, and this is extended in this study to in vivo studies, highlighting a crucial role for serine 54 in the N-terminal domain. Duplication of the bilobe correlates with the presence of TbPLK and phospho-TbCentrin2, identified using phosphospecific antiserum. Mutation of S54 leads to slow growth (S54A) or no growth (S54D), the latter suggesting that dephosphorylation is needed to complete bilobe duplication and subsequent downstream events necessary for flagellum inheritance.
MAP65/Ase1 promote microtubule flexibility
Authors: Portran D. , Zoccoler M. , Gaillard J. , Stoppin-Mellet V. , Neumann E. , Arnal I. , Martiel J. L. , Vantard M.
Published: April 2013

Microtubules (MTs) are dynamic cytoskeletal elements involved in numerous cellular processes. Although they are highly rigid polymers with a persistence length of 1–8 mm, they may exhibit a curved shape at a scale of few micrometers within cells, depending on their biological functions. However, how MT flexural rigidity in cells is regulated remains poorly understood. Here we ask whether MT-associated proteins (MAPs) could locally control the mechanical properties of MTs. We show that two major cross-linkers of the conserved MAP65/PRC1/Ase1 family drastically decrease MT rigidity. Their MT-binding domain mediates this effect. Remarkably, the softening effect of MAP65 observed on single MTs is maintained when MTs are cross-linked. By reconstituting physical collisions between growing MTs/MT bundles, we further show that the decrease in MT stiffness induced by MAP65 proteins is responsible for the sharp bending deformations observed in cells when they coalign at a steep angle to create bundles. Taken together, these data provide new insights into how MAP65, by modifying MT mechanical properties, may regulate the formation of complex MT arrays.
Primary proteasome inhibition results in cardiac dysfunction
Authors: Herrmann Joerg , Wohlert Christine , Saguner Ardan M. , Flores Ana , Nesbitt Lisa L. , Chade Alejandro , Lerman Lilach O. , Lerman Amir
Published: April 2013

Aims

The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart.

Methods and results

Female domestic pigs were randomized to a normal diet without (N) or with twice‐weekly subcutaneous injections of the proteasome inhibitor MLN‐273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P < 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P < 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P < 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI.

Conclusion

The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic–restrictive cardiomyopathy phenotype.
First Report of Blueberry scorch virus in Elderberry in Poland
Authors: Kalinowska E. , Paduch-Cichal E. , Chodorska M.
Published: April 2013

Blueberry scorch virus (BlScV) is a member of the genus Carlavirus and one of the most widespread pathogens of highbush blueberry (Vaccinium corymbosum L.). The virus was first reported in the United States and has been reported in several countries in Europe, including Italy, Germany, the Netherlands, and Poland. Symptoms of scorch disease in highbush blueberry include necrosis of flower blossoms and leaves, shoot blight, and chlorosis. Sometimes BlScV infection is symptomless or limited to single blossoms and shoots, but all highbush blueberry cultivars are susceptible to virus infection. Cranberry (V. macrocarpon L.) and wild black huckleberry (V. membranaceum L.) are known as natural and symptomless hosts of BlScV (1). In June 2012, during the research concerning the occurrence of BlScV in plants outside Vaccinium sp., 15 leaf samples from five elderberry bushes (Sambucus nigra L., family Adoxaceae) were randomly collected from the Lodzkie region in Central Poland and three were positive in double antibody sandwich (DAS)-ELISA using specific antiserum (Agdia Inc., Elkhart, IN). To confirm the presence of the virus, total nucleic acid was extracted from ELISA-positive elderberry samples according to established protocol (T. Malinowski. Proc. 4th Int. EFPP Symposium, 445, 1996) and used in one step reverse transcription PCR. Primers were developed against the published NJ-2, BC-1, and BC-2 sequences of BlScV (GenBank Accession Nos. NC_003499, AY941198, and AY941199, respectively). The forward primer, RDP_1 (5′-ATGGCACTCACATACAGAAGTCC-3′), and the reverse primer, RDP_2 (5′-TGCCTCTTCAATGCACGATGTTC-3′), were used to amplify a 420-bp fragment of the RNA-dependent RNA polymerase gene of the virus. Amplicons of expected size were obtained from three DAS-ELISA-positive samples, while no products were observed for the negative control (DAS-ELISA-negative elderberry tissues). Sequence of one selected PCR product revealed 100, 88, and 87% nucleotide sequence identity and 100, 96, and 96% amino acid sequence identity with BC-2, NJ-2, and BC-1, respectively. BlScV-infected elderberry bushes were asymptomatic. As BlScV is transmitted by aphids in a non-persistent manner, infected elderberry bushes near highbush blueberry plantings may play an important role in virus spread. The potential for BlScV infection of plants outside family Ericaceae should be investigated. To the best of our knowledge, this is the first report of BlScV infecting elderberry.

Reference: (1) R. R. Martin et al. Viruses 4:2831, 2012.
First Report of Pepper vein yellows virus Infecting Sweet Pepper in Spain
Authors: Villanueva F. , Castillo P. , Font M. I. , Alfaro-Fernández A. , Moriones E. , Navas-Castillo J.
Published: April 2013

In November 2012, unusual symptoms were observed in plants of sweet pepper (Capsicum annuum L.) grown in commercial greenhouses of Almería Province, southeastern Spain. Symptoms included interveinal yellowing, upward leaf curling, and internode shortening, and were more evident in the upper part of the plant. Abnormal ripening of fruits was observed in symptomatic plants, with fruits remaining orange in the red varieties and yellow in the orange varieties, thus reducing their marketability. During December 2012 and January 2013, severe outbreaks of this disease syndrome occurred, with many greenhouses exhibiting almost 100% incidence. The symptoms observed were similar to those reported for isolates of Pepper vein yellows virus (PeVYV, genus Polerovirus, family Luteoviridae) (previously also named Pepper yellow leaf curl virus [PYLCV] and Pepper yellows virus [PYV]) (2,4). Twenty five symptomatic leaf and/or fruit samples (some of them supplied by Zeraim Ibérica, S.A.), each from a different greenhouse, were analyzed and all reacted positively in double-antibody sandwich-ELISA with an antiserum against the polerovirus Cucurbit aphid-borne yellows virus (CABYV) (Sediag, Longvic, France), known to cross-react with PeVYV (2). Total RNA was extracted by TRIsure reagent (Bioline, London, United Kingdom) from symptomatic leaves and analyzed by reverse transcription (RT)-PCR with primers Pol-G-F (5′-GAYTGCTCYGGYTTYGACTGGAG-3′) and Pol-G-R (5′-GATYTTATAYTCATGGTAGGCCTTGAG-3′) designed for universal detection of poleroviruses by amplifying the RNA-dependent RNA polymerase (RdRp) and coat protein (CP) partial genes (3). DNA fragments of the expected size (1.1 kbp) were amplified supporting a polerovirus infection in all the analyzed samples. The PCR product obtained from one sample (Almería-1) was extracted from agarose gel with a QIAquick gel extraction kit (Qiagen, Hilden, Germany), cloned in pGEM-T Easy vector (Promega, Madison, WI), and one clone was sequenced (Macrogen Inc., Seoul, South Korea). The PCR products amplified from three other samples (2-13, 7-13, and 8-13) were directly sequenced. The nucleotide identity between the amplified fragments (GenBank Accession Nos. KC769487, KC839992 to 94), calculated after alignment with ClustalW, was 99.7 to 100%. The highest nucleotide identity of the Spanish sequences was with a PeVYV isolate from Turkey (FN600344, named as PYV) (98.5 to 98.7%). The spread of PeVYV in Spain is additional evidence of the emergence of this virus as a global threat for pepper crops after its first detection in Japan in 1995 and recent reports from the Mediterranean Basin (1,2).

References: (1) N. Buzkan et al. Arch. Virol. 158:881, 2013. (2) A. Dombrovsky et al. Phytoparasitica 38:477, 2010. (3) D. Knierim et al. Plant Pathol. 59:991, 2010. (4) R. Murakami et al. Arch. Virol. 156:921, 2011.
QoI Resistance in Fusicladium carpophilum Populations from Almond in California and Evaluation of Molecular Resistance Mechanisms
Authors: Luo Y. , Hou L. , Förster H. , Adaskaveg J. E.
Published: April 2013

Disease management failures have been reported in California for almond scab caused by Fusicladium carpophilum following quinone outside inhibitor (QoI) applications. Resistance in the pathogen populations was found to be common and at high incidence in the major almond-growing regions beginning in 2003, 4 years after registration of azoxystrobin on this crop. Two levels of azoxystrobin resistance, moderate and high, were identified with 50% effective concentration (EC50) values between 0.15 and 10 μg/ml or >40 μg/ml, respectively. Reference isolates collected before resistance was detected had EC50 values <0.05 μg/ml. High-resistance was associated with a G143A mutation in the mitochondrial cytochrome b gene. For the less commonly found moderately resistant isolates, no mutations in the gene were detected between codons 122 and 212. Using primers targeting the G143A mutation or the cytochrome b gene of all F. carpophilum isolates in quantitative polymerase chain reaction (qPCR) analyses, the frequency of highly resistant isolates was accurately determined in mixtures of conidia with selected ratios of sensitive and resistant isolates. The frequency of high resistance in bulked samples of scab lesions, however, was generally underestimated compared with in vitro testing of fungicide sensitivity of fungal isolates from the same lesions. Competition experiments using conidial suspensions demonstrated stability of the highly resistant genotype in the presence of different amounts of sensitive and moderately resistant genotypes. Analysis of covariance of linear regressions of cycle threshold values on DNA concentrations derived from qPCR amplifications using two primer pairs for cytochrome b alleles with and without the G143 mutation showed that several isolates differed in their slopes and midpoints. Thus, heteroplasmy of mitochondrial-inherited QoI resistance is suggested as a likely cause for incongruence in estimating resistance frequencies using the two methods.
Fate of Artificial MicroRNA-Mediated Resistance to Plant Viruses in Mixed Infections
Authors: Martínez Fernando , Elena Santiago F. , Daròs José-Antonio
Published: April 2013

Artificial microRNAs (amiRNAs) are the expression products of engineered microRNA (miRNA) genes that efficiently and specifically downregulate RNAs that contain complementary sequences. Transgenic plants expressing high levels of one or more amiRNAs targeting particular sequences in the genomes of some RNA viruses have shown specific resistance to the corresponding virus. This is the case of the Arabidopsis thaliana transgenic line 12-4 expressing a high level of the amiR159-HC-Pro targeting 21 nucleotides in the Turnip mosaic virus (TuMV) (family Potyviridae) cistron coding for the viral RNA-silencing suppressor HC-Pro that is highly resistant to TuMV infection. In this study, we explored the fate of this resistance when the A. thaliana 12-4 plants are challenged with a second virus in addition to TuMV. The A. thaliana 12-4 plants maintained the resistance to TuMV when this virus was co-inoculated with Tobacco mosaic virus, Tobacco rattle virus (TRV), Cucumber mosaic virus (CMV), Turnip yellow mosaic virus, Cauliflower mosaic virus (CaMV), Lettuce mosaic virus, or Plum pox virus. However, when the plants were preinfected with these viruses, TuMV was able to co-infect 12-4 plants preinfected with TRV, CaMV, and, particularly, CMV. Therefore, preinfection by another virus jeopardizes the amiRNA-mediated resistance to TuMV.
A Faster and a Stronger Defense Response: One of the Key Elements in Grapevine Explaining Its Lower Level of Susceptibility to Esca?
Authors: Lambert Carole , Khiook Ian Li Kim , Lucas Sylvia , Télef-Micouleau Nadège , Mérillon Jean-Michel , Cluzet Stéphanie
Published: April 2013

Wood diseases like Esca are among the most damaging afflictions in grapevine. The defense mechanisms in this plant–pathogen interaction are not well understood. As some grapevine cultivars have been observed to be less susceptible to Esca than others, understanding the factors involved in this potentially stronger defense response can be of great interest. To lift part of this veil, we elicited Vitis vinifera plants of two cultivars less susceptible to Esca (‘Merlot’ and ‘Carignan’) and of one susceptible cultivar (‘Cabernet Sauvignon’), and monitored their defense responses at the leaf level. Our model of elicitation consisted in grapevine cuttings absorbing a culture filtrate of one causal agent of Esca, Phaemoniella chlamydospora. This model might reflect the early events occurring in Esca-affected grapevines. The two least susceptible cultivars showed an earlier and stronger defense response than the susceptible one, particularly with regard to induction of the PAL and STS genes, and a higher accumulation of stilbene compounds and some pathogenesis-related proteins.
Developmental Effects of Neonatal Isoflurane and Sevoflurane Exposure in Rats
Authors: Seubert Christoph N. , Zhu Wanting , Pavlinec Christopher , Gravenstein Nikolaus , Martynyuk Anatoly E.
Published: April 2013

Background:

The general anesthetics, isoflurane and sevoflurane, cause developmental abnormalities in neonatal animal models via incompletely understood mechanisms. Despite many common molecular targets, isoflurane and sevoflurane exhibit substantial differences in their actions. The authors sought to determine whether these differences can also be detected at the level of neurodevelopmental effects.

Methods:

Postnatal rats, 4–6 days old, were exposed to 1.2% isoflurane or 2.1% sevoflurane for 1–6 h and studied for immediate and delayed effects.

Results:

Isoflurane exposure was associated with weaker seizure-like electroencephalogram patterns than sevoflurane exposure. Confronted with a new environment at a juvenile age, the sevoflurane-exposed rats spent significantly more time in an “immobile” state than unexposed rats. Electroencephalographic (mean ± SE, 55.5 ± 12.80 s vs. 14.86 ± 7.03 s; P = 0.014; n = 6–7) and spontaneous behavior (F
(2,39) = 4.43; P = 0.018) effects of sevoflurane were significantly diminished by pretreatment with the Na+–K+–2Cl– cotransporter inhibitor bumetanide, whereas those of isoflurane were not. Pretreatment with bumetanide, however, diminished isoflurane-induced activation of caspase-3 in the cerebral cortex (F(2,8) = 22.869; P = 0.002) and prevented impairment in sensorimotor gating function (F
(2,36) = 5.978; P = 0.006).

Conclusions:

These findings in combination with results previously reported by the authors suggest that isoflurane and sevoflurane produce developmental effects acting via similar mechanisms that involve an anesthetic-induced increase in neuronal activity. At the same time, differences in their effects suggest differences in the mediating mechanisms and in their relative safety profile for neonatal anesthesia.
Prospective Randomized Crossover Study of a New Closed-loop Control System versus Pressure Support during Weaning from Mechanical Ventilation
Authors: Clavieras Noémie , Wysocki Marc , Coisel Yannael , Galia Fabrice , Conseil Matthieu , Chanques Gerald , Jung Boris , Arnal Jean-Michel , Matecki Stefan , Molinari Nicolas , Jaber Samir
Published: April 2013

Background:

Intellivent is a new full closed-loop controlled ventilation that automatically adjusts both ventilation and oxygenation parameters. The authors compared gas exchange and breathing pattern variability of Intellivent and pressure support ventilation (PSV).

Methods:

In a prospective, randomized, single-blind design crossover study, 14 patients were ventilated during the weaning phase, with Intellivent or PSV, for two periods of 24 h in a randomized order. Arterial blood gases were obtained after 1, 8, 16, and 24 h with each mode. Ventilatory parameters were recorded continuously in a breath-by-breath basis during the two study periods. The primary endpoint was oxygenation, estimated by the calculation of the difference between the Pao
2/Fio2
ratio obtained after 24 h of ventilation and the Pao
2/Fio2
ratio obtained at baseline in each mode. The variability in the ventilatory parameters was also evaluated by the coefficient of variation (SD to mean ratio).

Results:

There were no adverse events or safety issues requiring premature interruption of both modes. The Pao
2/Fio2
(mean ± SD) ratio improved significantly from 245 ± 75 at baseline to 294 ± 123 (P = 0.03) after 24 h of Intellivent. The coefficient of variation of inspiratory pressure and positive end-expiratory pressure (median [interquartile range]) were significantly higher with Intellivent, 16 [11–21] and 15 [7–23]%, compared with 6 [5–7] and 7 [5–10]% in PSV. Inspiratory pressure, positive end-expiratory pressure, and Fio2
changes were adjusted significantly more often with Intellivent compared with PSV.

Conclusions:

Compared with PSV, Intellivent during a 24-h period improved the Pao
2/Fio2
ratio in parallel with more variability in the ventilatory support and more changes in ventilation settings.
Effects of Volatile Anesthetic Choice on Hospital Length-of-stay
Authors: Kopyeva Tatyana , Sessler Daniel I. , Weiss Stephanie , Dalton Jarrod E. , Mascha Edward J. , Lee Jae H. , Kiran Ravi P. , Udeh Belinda , Kurz Andrea
Published: April 2013

Background:

Volatile anesthetic prices differ substantially. But differences in drug-acquisition cost would be inconsequential if hospitalization were prolonged by more soluble anesthetics. The authors tested the hypothesis that the duration of hospitalization is prolonged with isoflurane anesthesia.

Methods:

Initially, the authors queried their electronic records and used propensity matching to generate homogeneous sets of adults having inpatient noncardiac surgery who were given desflurane, sevoflurane, and isoflurane. The authors then conducted a prospective alternating intervention trial in which adults (mostly having colorectal surgery) were assigned to isoflurane or sevoflurane, based on protocol.

Results:

In the retrospective analysis, 2,898 matched triplets were identified among 43,352 adults, each containing one patient receiving isoflurane, desflurane, and sevoflurane, respectively. The adjusted geometric mean (95% CI) hospital length-of-stay for the isoflurane cases was 2.85 days (2.78–2.93); this was longer than that observed for both desflurane (2.64 [2.57–2.72]; P < 0.001) and sevoflurane (2.55 [2.48–2.62]; P < 0.001). In the prospective trial (N = 1,584 operations), no difference was found; the adjusted ratio of means (95% CI) of hospital length-of-stay in patients receiving isoflurane versus sevoflurane was 0.98 (0.88–1.10), P = 0.77, with adjusted geometric means (95% CI) estimated at 4.1 (3.8–4.4) and 4.2 days (3.8–4.5), respectively.

Conclusions:

Results of the propensity-matched retrospective analysis suggested that avoiding isoflurane significantly reduced the duration of hospitalization. In contrast, length-of-stay was comparable in our prospective trial. Volatile anesthetic choice should not be based on concerns about the duration of hospitalization. These studies illustrate the importance of following even the best retrospective analysis with a prospective trial.
FLECKED RETINA, CHOROIDOPATHY, AND RETINAL PIGMENT EPITHELIAL TEAR IN FAMILIAL PULMONARY ARTERIAL HYPERTENSION
Authors: Torfs Sara , Leys Anita M.
Published: April 2013

Background:

Thanks to advancement in treatment modalities, the medial survival rate of patients with familial pulmonary arterial hypertension (FPAH) has been improved. Unfortunately, ocular complications because of the chronically elevated systemic venous pressure become more frequent.

Methods:

The authors report new FPAH-associated fundus changes in a 50-year-old male patient treated with sildenafil. The anomalies were studied with autofluorescence, fluorescein and indocyanine green angiography, and spectral optical coherence tomography including enhanced depth imaging.

Results:

Loss of vision and cystoid macular edema were associated with a flecked retina, a thick choroid, central serous choroidopathy-like changes in both eyes and with retinal pigment epithelium detachments and a retinal pigment epithelium tear in the right eye.

Conclusion:

Treatment of ocular findings associated with FPAH mainly involves optimal control of pulmonary arterial hypertension and ophthalmic supportive treatment toward preventing acute ocular complications. The ocular complications occur as a result of enhanced pressure in the superior vena cava and in the ophthalmic veins, resulting in dilation of the ocular veins and congestion of the choroid. Sildenafil treatment in FPAH may enhance the congestion of the choroid and can induce central serous choroidopathy-like changes. A flecked retina, central serous choroidopathy-like changes, and retinal pigment epithelium tear are rare complications of FPAH.
Ultrasensitive response motifs: basic amplifiers in molecular signalling networks
Authors: Zhang Qiang , Bhattacharya Sudin , Andersen Melvin E.
Published: April 2013

Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm.
A new role for
muscle segment homeobox
genes in mammalian embryonic diapause
Authors: Cha Jeeyeon , Sun Xiaofei , Bartos Amanda , Fenelon Jane , Lefèvre Pavine , Daikoku Takiko , Shaw Geoff , Maxson Robert , Murphy Bruce D. , Renfree Marilyn B. , Dey Sudhansu K.
Published: April 2013

Mammalian embryonic diapause is a phenomenon defined by the temporary arrest in blastocyst growth and metabolic activity within the uterus which synchronously becomes quiescent to blastocyst activation and implantation. This reproductive strategy temporally uncouples conception from parturition until environmental or maternal conditions are favourable for the survival of the mother and newborn. The underlying molecular mechanism by which the uterus and embryo temporarily achieve quiescence, maintain blastocyst survival and then resume blastocyst activation with subsequent implantation remains unknown. Here, we show that uterine expression of
Msx1
or
Msx2
, members of an ancient, highly conserved homeobox gene family, persists in three unrelated mammalian species during diapause, followed by rapid downregulation with blastocyst activation and implantation. Mice with uterine inactivation of
Msx1
and
Msx2
fail to achieve diapause and reactivation. Remarkably, the North American mink and Australian tammar wallaby share similar expression patterns of
MSX1
or
MSX2
as in mice
—
it persists during diapause and is rapidly downregulated upon blastocyst activation and implantation. Evidence from mouse studies suggests that the effects of
Msx
genes in diapause are mediated through Wnt5a, a known transcriptional target of uterine
Msx
. These studies provide strong evidence that the
Msx
gene family constitutes a common conserved molecular mediator in the uterus during embryonic diapause to improve female reproductive fitness.
EBE, an AP2/ERF Transcription Factor Highly Expressed in Proliferating Cells, Affects Shoot Architecture in Arabidopsis
Authors: Mehrnia Mohammad , Balazadeh Salma , Zanor María-Inés , Mueller-Roeber Bernd
Published: April 2013

We report about ERF BUD ENHANCER (EBE; At5g61890), a transcription factor that affects cell proliferation as well as axillary bud outgrowth and shoot branching in Arabidopsis (Arabidopsis thaliana). EBE encodes a member of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor superfamily; the gene is strongly expressed in proliferating cells and is rapidly and transiently up-regulated in axillary meristems upon main stem decapitation. Overexpression of EBE promotes cell proliferation in growing calli, while the opposite is observed in EBE-RNAi lines. EBE overexpression also stimulates axillary bud formation and outgrowth, while repressing it results in inhibition of bud growth. Global transcriptome analysis of estradiol-inducible EBE overexpression lines revealed 48 EBE early-responsive genes, of which 14 were up-regulated and 34 were down-regulated. EBE activates several genes involved in cell cycle regulation and dormancy breaking, including D-type cyclin CYCD3;3, transcription regulator DPa, and BRCA1-ASSOCIATED RING DOMAIN1. Among the down-regulated genes were DORMANCY-ASSOCIATED PROTEIN1 (AtDRM1), AtDRM1 homolog, MEDIATOR OF ABA-REGULATED DORMANCY1, and ZINC FINGER HOMEODOMAIN5. Our data indicate that the effect of EBE on shoot branching likely results from an activation of genes involved in cell cycle regulation and dormancy breaking.
Awareness and use of e‐journals by IIT Delhi and Delhi University library users
Authors: Nisha Faizul , Ali Naushad
Published: April 2013

Purpose

The purpose of this paper is to examine the use of e‐journals by the users of IIT Delhi and Delhi University.

Design/methodology/approach

Survey research was conducted to access e‐journal use among IIT Delhi and Delhi University users. A stratified random sample method was used for selection of respondents. The survey was conducted through a structured questionnaire taking a random sample of 300 users (PG and PhD) from different disciplines of IIT Delhi and Delhi University libraries and the response rate was 66.66 per cent. The questionnaires were administered personally among the users of IIT Delhi and Delhi University during the survey period (March‐May 2011).

Findings

From this survey it was found that most of the users are aware of e‐journals and they are not only using them for building and updating their knowledge but also for collecting relevant material for their study and research purposes as information can be acquired expeditiously through e‐journals. The main aim of consulting these journals is for retrieving information regarding research, publishing research papers and manuscripts, assignments, presentations, seminars, and largely to update their own knowledge. However, this study also reveals several inherent problems especially with the use of e‐journals e.g. slow downloading as revealed by maximum IIT Delhi and Delhi University users. Other mechanical deficits like non‐availability of a particular issue, lack of training and limited access to terminals are also present while using e‐journals.

Research limitations/implications

The present study consists only of e‐journal users of IIT Delhi and Delhi University. The geographical coverage is restricted to Delhi. The responses have been taken from users and the data have been collected during the months of March‐May 2011 only.

Practical implications

The problem is selected by the investigator to understand the use of e‐journals by IIT Delhi and Delhi University users so that libraries can make further improvement in their e‐journal services depending upon the results and suggestions.

Originality/value

The paper provides suggestions derived from the analysis of data which in turn will help to enhance the use of e‐journal services and fulfill the needs and requirements of users in the libraries of IIT Delhi and Delhi University.
Dimensions of hospital service quality: a critical review
Authors: P. Pai Yogesh , T. Chary Satyanarayana
Published: April 2013

Purpose

– The purpose of this paper is to review the service quality dimensions established in various studies conducted across the world specifically applied to health care.

Design/methodology/approach

– Studies conducted on quality of care selected from literature databases – Ebsco, Emerald Insight, ABI/Inform – was subjected to a comprehensive in-depth content analysis.

Findings

– Service quality has been extensively studied with considerable efforts taken to develop survey instruments for measuring purposes. The number of dimensional structure varies across the studies. Self-administered questionnaire dominates in terms of mode of administration adopted in the studies, with respondents ranging from 18 to 85 years. Target sample size ranged from 84-2,000 respondents in self-administered questionnaires and for mail administration ranged from 300-2,600 respondents. Studies vary in terms of the scores used ranging from four to ten-point scale. A total of 27 of the studies have used EFA, 11 studies have used structural equation modelling and eight studies used gap scores. Cronbach
'
s alpha is the most commonly used measure of scale reliability. There is variation in terms of measuring the content, criteria and construct validation among the studies.

Practical implications

– The literature offers dimensions used in assessing patient perceived service quality. The review reveals diversity and a plethora of dimensions and methodology to develop the construct discussed.

Originality/value

– The reported study describes and contrasts a large number of service-quality measurement constructs and highlights the usage of dimensions. The findings are valuable to academics in terms of dimensions and methodology used, approach for analysis; whereas findings are of value to practitioners in terms of the dimensions found in the research and to identify the gap in their setting.
An evidence based approach to creating an age‐friendly culture
Authors: Broughan Christine
Published: April 2013

Purpose

Recent changes in demographics make older workers a key issue for HR practices, policy and procedure. There exists a clear business case for valuing older workers but organizations are often unclear as to how this should be achieved. The aim of this paper is to show how an evidence‐based approach using a tool from Coventry University and ACAS can help in creating an age‐friendly culture.

Design/methodology/approach

Coventry University and ACAS have developed an age audit tool (AAT) that enables organizations to examine various areas of the business. The results of the AAT allow organizations to develop targeted action orientated strategies that are pertinent to their situation.

Findings

Pilot results suggest that the AAT is relevant to different types and size of organization. However, like any change management approach, moving towards an age friendly policy will require careful planning, top level buy‐in and ownership. It will also need to be evidence based and aligned to other HR policies, procedures and government legislation.

Originality/value

As more organizations use the AAT we will be able to build a picture of the issues facing organizations and provide focused workshops, conferences and consultancy. The anonymous data gathered will also allow companies to benchmark against similar organizations in their sector.
Why do Italian households prefer adjustable rate mortgages?
Authors: Zocchi Paola
Published: April 2013

Purpose

In Italy three quarters of the stock of households' mortgage debt is exposed to interest rate risk. The aim of this paper is to explain why the majority of mortgage holders in the Italian residential mortgage market have chosen a mortgage with a variable interest rate.

Design/methodology/approach

The empirical analysis has been carried out on a sample of 959 Italian households on the basis of data from the Survey on Household Income and Wealth by the Bank of Italy and covers the period between 1997 and 2006.

Findings

The outcomes raise some doubts about the efficiency of the Italian mortgage market in terms of risk allocation between banks and householders. Fixed rate mortgage (FRM) versus adjustable rate mortgage (ARM) choice appears to be guided by a short‐term outlook informed by the need to maximize a household's immediate utility. Furthermore, households seem to embrace a myopic perspective, since the preference for ARMs increases with the lengthening of the maturity of the mortgage and with any increase in the size of the principal amount. Also, lending policies appear to have a considerable influence on a household's FRM‐ARM choice.

Practical implications

It seems that the Italian mortgage market requires adequate initiatives to improve households' financial literacy. Some measures to mitigate the assumption of the interest rate risk by households would be also welcomed.

Originality/value

This study represents the first investigation into the relationship between lending policies of banks and householders' mortgage choice from the perspective of a country distinguished by a high and persistent preference for the adjustable rate mortgages.
Can plant–microbe–insect interactions enhance or inhibit the spread of invasive species?
Authors: Bennett Alison E.
Published: April 2013

Invasive species are one of the great challenges facing the world leading to great economic losses. Increasing numbers of species introductions are also increasing the likelihood of new species interactions – particularly between plants, microbes and insects.

Frequently discovered interactions between plants, microbes and insects are giving rise to a new field: plant–microbe–insect (PMI) interactions. This paper focuses on novel PMI interactions created from the introduction of new plant, insect and microbe species. In particular, this paper asks: Do novel PMI interactions promote or inhibit invasive plants, microbes and insects? And can we predict whether novel PMI interactions are likely to become invasive?

While we might predict that novel PMI interactions are likely to be simple additive interactions due to their relatively short period of interaction, instead this review demonstrates that most novel PMI interactions are actually nonadditive. This manuscript shows that there are a great number of instances where invasive species are promoted by novel PMI interactions. By contrast, the studied cases where PMI interactions limit invasive species are predominantly biocontrol PMI interactions.

Future research on novel PMI interactions should focus on predicting future novel PMI interactions that promote invasive species. Given that many novel PMI interactions involve plant pathogens and their insect vectors, this novel PMI interaction deserves more focus. New research should also focus on non‐novel PMI interactions that could be manipulated to hinder the spread of invasive plant, microbe and insect species.
Tyrosine metabolic enzymes from insects and mammals: A comparative perspective
Authors: Vavricka Christopher John , Han Qian , Mehere Prajwalini , Ding Haizhen , Christensen Bruce M. , Li Jianyong
Published: April 2013

Differences in the metabolism of tyrosine between insects and mammals present an interesting example of molecular evolution. Both insects and mammals possess fine‐tuned systems of enzymes to meet their specific demands for tyrosine metabolites; however, more homologous enzymes involved in tyrosine metabolism have emerged in many insect species. Without knowledge of modern genomics, one might suppose that mammals, which are generally more complex than insects and require tyrosine as a precursor for important catecholamine neurotransmitters and for melanin, should possess more enzymes to control tyrosine metabolism. Therefore, the question of why insects actually possess more tyrosine metabolic enzymes is quite interesting. It has long been known that insects rely heavily on tyrosine metabolism for cuticle hardening and for innate immune responses, and these evolutionary constraints are likely the key answers to this question. In terms of melanogenesis, mammals also possess a high level of regulation; yet mammalian systems possess more mechanisms for detoxification whereas insects accelerate pathways like melanogenesis and therefore must bear increased oxidative pressure. Our research group has had the opportunity to characterize the structure and function of many key proteins involved in tyrosine metabolism from both insects and mammals. In this mini review we will give a brief overview of our research on tyrosine metabolic enzymes in the scope of an evolutionary perspective of mammals in comparison to insects.
Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti‐epidermal growth factor receptor monoclonal antibodies: A meta‐analysis
Authors: Xu Qi , Xu An Tao , Zhu Ming Ming , Tong Jin Lu , Xu Xi Tao , Ran Zhi Hua
Published: April 2013

Objective

This study aimed to evaluate the predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer (mCRC) treated with anti‐epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs).

Methods

Computer searches of the literature on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti‐EGFR MoAbs and/or overall survival (OS) and progression‐free survival (PFS) with different BRAF gene expression in mCRC patients were eligible.

Results

A total of 19 studies including 2875 patients was enrolled in the meta‐analysis. BRAF mutation was detected in 246 patients. The ORR was 18.4% (40/217) in mutant BRAF group and 41.7% (831/1993) in the wild‐type BRAF group. The overall risk ratio (RR) for the ORR of BRAF mutation patients compared with wild‐type BRAF patients was 0.58 (95% confidence intervals [CI] 0.35–0.94, P = 0.027). The median PFS of patients with BRAF mutation was significantly shorter than that of patients with wild‐type BRAF (hazard ratio [HR] 2.98, 95% CI 2.07–4.27, P < 0.001) and the median OS of patients with BRAF mutation was also significantly shorter than that of those with wild‐type BRAF (HR 2.85, 95% CI 2.31–3.52, P < 0.001).

Conclusion

BRAF mutation is associated with poor response to anti‐EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with mCRC.
Value of 18F‐FDG‐PET/CT in the detection of recurrent hepatocellular carcinoma after hepatectomy or radiofrequency ablation: A comparative study with contrast‐enhanced ultrasound
Authors: Wang Xiao Yan , Chen Dong , Zhang Xiang Song , Chen Zhi Feng , Hu An Bin
Published: April 2013

Objective

To evaluate the role of positron emission tomography/computer tomography with fluorine‐18 fluorodeoxyglucose (18F‐FDG‐PET/CT) in detecting hepatocellular carcinoma (HCC) recurrence after hepatectomy and/or radiofrequency ablation (RFA) and to compare its efficacy with contrast‐enhanced ultrasound (CEUS).

Methods

A total of 36 HCC patients were included in this study. All patients underwent both 18F‐FDG‐PET/CT and CEUS at least once for the diagnosis of HCC recurrence. The time interval between PET/CT and CEUS was 14 ± 3 days. All patients were followed up for at least 24 months.

Results

In all, 32 patients were confirmed to have HCC recurrence by pathology and clinical follow‐up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F‐FDG‐PET/CT for intrahepatic HCC recurrence were 96.7%, 83.3%, 96.7%, 83.3% and 94.4%, respectively. The corresponding values of CEUS were 56.7%, 100%, 100%, 31.6% and 63.9%, respectively. The sensitivity and accuracy of 18F‐FDG‐PET/CT for the diagnosis of HCC recurrence were significantly higher than those of CEUS (P < 0.01, respectively).

Conclusions

Compared with CEUS, 18F‐FDG‐PET/CT has higher sensitivity and accuracy in detecting the local recurrence of HCC after hepatectomy and/or RFA. It can be used to detect recurrent extrahepatic lesions of HCC effectively.
Regional Tectonic Transformation in East Kunlun Orogenic Belt in Early Paleozoic: Constraints from the Geochronology and Geochemistry of Helegangnaren Alkali‐feldspar Granite
Authors: Ruibao LI , Xianzhi PEI , Zhuochen LI , Yu SUN , Lei PEI , Guochao CHEN , Youxin CHEN , Chengjun LIU , Fanghui WEI
Published: April 2013

The Helegangnaren feldspar granite exposed in the eastern part of East Kunlun, is characterized by high concentrations of SiO2 and alkaline, low abundances of Fe, Mg and Ca, metaluminous‐weak peraluminous. Trace elements analysis shows that the granite is depleted extremely in Ba, Sr and Eu, and rich in some large‐ion lithophile elements and high field strength elements. Besides, the granite has high Ga contents, the values of 104(Ga/Al) vary from 2.50 to 2.77, which is mainly greater than the lower limit of A‐type granites (2.6), and is higher than the I‐ and S‐type granites’ average (2.1 and 2.28, respectively). Rare earth element (REE) is characterized by relatively high fractionations of light REE (LREE) and heavy REE (HREE) (LREE/HREE=9.3–13.60, (La/Yb)N=10.92–18.02), pronounced negative Eu anomalies (δEu=0.08–0.13), and exhibits right‐dipping gull pattern. Major elements, rare elements and trace elements features show the granite is ascribed to A‐type granite and A2 subtype in tectonic genetic type. They are plotted into post‐collision or within‐plate area in a variety of tectonic discriminations. Geological and geochemical data comprehensively suggest that the granite is formed in a post‐collision extensive tectonic setting. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) zircon U‐Pb dating yields a weighted mean age of 425 Ma, belonging to Middle Silurian, which is similar to the age of the post‐collision geological events in the region. The differences of magmatic rocks in formation age, rocks assemblage and rocks series systematically indicate that the regional tectonic stress regime in the East Kunlun orogenic belt experienced a major transformation from compress to extension in Middle Silurianin, and the Helegangnaren feldspar granite intruded in the early stage of tectonic transformation.