bluuebunny/crossref_metadata_2025 huggingface dataset:
PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
Authors: Gessain Grégoire , Tsai Yu-Huan , Travier Laetitia , Bonazzi Matteo , Grayo Solène , Cossart Pascale , Charlier Caroline , Disson Olivier , Lecuit Marc
Published: January 2015

Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate.
PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness
Authors: Yang Meixiang , Li Dan , Chang Zai , Yang Zhongzhou , Tian Zhigang , Dong Zhongjun
Published: January 2015

E4BP4, a circadian protein, is indispensable for NK cell development. It remains largely unknown which signal is required to induce E4BP4 expression and what effects it has during NK cell differentiation. Here, we reveal that PDK1, a kinase upstream of mTOR, connects IL-15 signaling to E4BP4. Early deletion of PDK1 caused a severe loss of NK cells and compromised antitumor activity in vivo. PDK1-deficient NK cells displayed much weaker IL-15–induced mTOR activation and E4BP4 induction, as well as remarkable reduction in CD122, a receptor subunit specifying NK cell responsiveness to IL-15. The phenotypes were partially reversible by ectopic expression of E4BP4 or bypassed activation of mTOR. We also determined that PDK1-mediated metabolic signaling was dispensable for NK cell terminal maturation and survival. Thus, we identify a role for PDK1 signaling as a key mediator in regulating E4BP4 expression during early NK cell development. Our findings underscore the importance of IL-15 self-responsiveness through a positive feedback loop that involves PDK1–mTOR–E4BP4–CD122 signaling.
Quantitative visualization of alternative exon expression from RNA-seq data
Authors: Katz Yarden , Wang Eric T. , Silterra Jacob , Schwartz Schraga , Wong Bang , Thorvaldsdóttir Helga , Robinson James T. , Mesirov Jill P. , Airoldi Edoardo M. , Burge Christopher B.
Published: January 2015

Motivation: Analysis of RNA sequencing (RNA-Seq) data revealed that the vast majority of human genes express multiple mRNA isoforms, produced by alternative pre-mRNA splicing and other mechanisms, and that most alternative isoforms vary in expression between human tissues. As RNA-Seq datasets grow in size, it remains challenging to visualize isoform expression across multiple samples.

Results: To help address this problem, we present Sashimi plots, a quantitative visualization of aligned RNA-Seq reads that enables quantitative comparison of exon usage across samples or experimental conditions. Sashimi plots can be made using the Broad Integrated Genome Viewer or with a stand-alone command line program.

Availability and implementation: Software code and documentation freely available here: http://miso.readthedocs.org/en/fastmiso/sashimi.html

Contact:  mesirov@broadinstitute.org, airoldi@fas.harvard.edu or cburge@mit.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Whartonia (Fascutonia) natsumei (Acari: Trombiculidae): A New Bat Chigger Collected from Plecotus auritus (Chiroptera: Vespertilionidae) in Japan, with Host and Distribution Records of the Genus Whartonia
Authors: Takahashi Mamoru , Takahashi Hisae , Kikuchi Hirosato
Published: January 2015

We describe and illustrate a new bat chigger, Whartonia (Fascutonia) natsumei Takahashi, Takahashi & Kikuchi n. sp., ex. Plecotus auritus (Linnaeus, 1758), from Japan, and summarize the host and distribution records of the chiggers of the genus Whartonia . With the description of a new species here, the number of Whartonia species increases to 40 composed of 22 species from Asia, 14 from North and South America in addition to Central America, and four from Africa.
Effects of Larval Competitors and Predators on Oviposition Site Selection of Anopheles gambiae Sensu Stricto
Authors: Munga Stephen , Minakawa Noboru , Zhou Guofa , Barrack Okeyo-Owuor J. , Githeko Andrew K. , Yan Guiyun
Published: January 2015

We examined whether predators and competitors influence selection of oviposition sites by Anopheles gambiae Giles. Mosquitoes in cages laid significantly fewer eggs in rainwater conditioned with a predator (backswimmers, Notonecta sp.) than in unconditioned rainwater. Rainwater conditioned with a putative competitor (tadpoles, Xenopus sp.) also had fewer eggs than unconditioned rainwater. Similarly, mosquitoes laid significantly fewer eggs in rainwater conditioned with five and 50 An. gambiae larvae than in unconditioned rainwater. When larvae were present, significantly more eggs were laid in containers with five larvae than in containers with higher densities, but the differences in number of eggs laid were not significant among the densities of 40, 70, and 100 larvae. This study demonstrated that caged An. gambiae females avoid oviposition in habitats with supposed competitors and predators.
Occurrence of Serotonin Immunoreactivity in the Central Nervous System and Midgut of Adult Female Tabanus nigrovittatus (Diptera: Tabanidae)
Authors: Haselton Aaron T. , Yin Chih-Ming , Stoffolano John G.
Published: January 2015

Serotonin is an important neuromessenger used in a variety of signaling pathways throughout the animal kingdom. In insects, serotonin has been demonstrated to mediate feeding and feeding-related behaviors. In this study, serotonin antibody was localized in cells and processes throughout the central nervous system (CNS) and midgut of female horse fly Tabanus nigrovittatus Macquart. In the CNS, immunoreactivity was localized in cells and processes throughout the brain and ventral nerve cord. In the midgut, a fine network of immunoreactive processes was observed running along the outer surface of the midgut, with a decrease in innervation toward the posterior region of the midgut.
Evidence That Scabies Mites (Acari: Sarcoptidae) Influence Production of Interleukin-10 and the Function of T-Regulatory Cells (Tr1) in Humans
Authors: Arlian Larry G. , Morgan Marjorie S. , Paul Cassandra C.
Published: January 2015

We performed experiments to determine whether an extract of Sarcoptes scabiei (De Geer) influenced cytokine expression by human T-lymphocytes. Peripheral blood mononuclear cells from five sensitized donors and four donors without sensitization to scabies mites were challenged with a T-cell mitogen alone, with scabies extract (SS) alone, or with mitogen and SS together. Supernatants were analyzed for the cytokines interferon-γ (IFNγ), interleukin (IL)-2, IL-4, and IL-10. No IL-2 or IL-4 was produced in response to scabies extract. Cells from both naïve and sensitized donors produced large amounts of IFNγ and IL-10. The lack of IL-4 but high levels of IL-10 suggests that IL-10 was likely secreted by type 1 T-regulatory cells, which were activated by something in the scabies extract. IL-10 has anti-inflammatory and immune-suppressive effects. It may play a key role in depressing the inflammatory and immune responses in humans so that clinical symptoms are not seen until 4–6 wk after a person becomes infested with scabies mites.
Laboratory Transmission of Japanese Encephalitis and West Nile Viruses by Molestus Form of Culex pipiens (Diptera: Culicidae) Collected in Uzbekistan in 2004
Authors: Turell M. J. , Mores C. N. , Dohm D. J. , Komilov N. , Paragas J. , Lee J. S. , Shermuhemedova D. , Endy T. P. , Kodirov A. , Khodjaev S.
Published: January 2015

We evaluated the molestus form of Culex pipiens pipiens (L.) (hereafter referred to as "molestus") captured near Tashkent, Uzbekistan, for their ability to transmit Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV) and West Nile (family Flaviviridae, genus Flavivirus, WNV) viruses under laboratory conditions. These molestus were highly competent laboratory vectors of WNV, with infection and dissemination rates of 96 and 81%, respectively. Approximately 75% of female molestus that fed after development of a disseminated infection transmitted virus by bite. Therefore, ≈60% of those molestus taking a second bloodmeal between 16 and 25 d after an infectious bloodmeal would be expected to transmit WNV by bite. In contrast, these molestus were less efficient vectors of JEV, with infection and dissemination rates of 51 and 25%, respectively. In addition, only 33% of individuals with a disseminated infection transmitted JEV by bite, indicating a significant salivary gland barrier. Therefore, only ≈8% of orally exposed individuals would be expected to transmit JEV by bite if they took a second bloodmeal 16–25 d later. These data indicate that the molestus form of Cx. p. pipiens should be considered a potentially important vector of WNV in Uzbekistan and may become involved in the transmission of JEV, should this virus be introduced into Uzbekistan.
Characterizing Population Dynamics of Aedes sollicitans (Diptera: Culicidae) Using Meteorological Data
Authors: Shone Scott M. , Curriero Frank C. , Lesser Cyrus R. , Glass Gregory E.
Published: January 2015

Numerous studies have investigated the role of weather on insect species. For mosquitoes, these studies have yielded mixed results. Although it is clear that weather impacts mosquito population dynamics, these investigations have failed to accurately characterize their fluctuations. We use a novel graphical method to examine large numbers of meteorological aggregations of varying lengths and lags simultaneously to establish relationships between these summary variables and mosquito counts, to gain a better understanding of the weather effects. Poisson regression models were developed to characterize the population dynamics of Aedes sollicitans (Walker) by using meteorological data and a 34-yr set of daily mosquito count data. The models accurately characterize mosquito dynamics over time and space. The aggregated meteorological variables included in the model were lowest minimum tides between days 27 and 14 before trapping, total precipitation between days 22 and 9, total precipitation on day 1 and the day of trapping, cooling degree-days on day 0, average minimum relative humidity between days 28 and 9, lowest stream flow from day 11 to day 0, and lowest minimum temperature between days 28 and 13.
Investigation of Ground Level and Remote-Sensed Data for Habitat Classification and Prediction of Survival of Ixodes scapularis in Habitats of Southeastern Canada
Authors: Ogden N. H. , Barker I. K. , Beauchamp G. , Brazeau S. , Charron D. F. , Maarouf A. , Morshed M. G. , O’Callaghan C. J. , Thompson R. A. , Waltner-Toews D. , Waltner-Toews M. , Lindsay L. R.
Published: January 2015

In southeastern Canada, most populations of Ixodes scapularis Say, the Lyme disease vector, occur in Carolinian forests. Climate change projections suggest a northward range expansion of I. scapularis this century, but it is unclear whether more northerly habitats are suitable for I. scapularis survival. In this study, we assessed the suitability of woodlands of the Lower Great Lakes/St. Lawrence Plain region for I. scapularis by comparing tick egg survival in four different woodlands. Woodlands where I. scapularis are established, and sand dune where I. scapularis do not survive, served as positive and negative control sites, respectively. At two woodland sites, egg survival was the same as at the positive control site, but at two of the sites survival was significantly less than either the positive control site, or one of the other test sites. Egg survival in all woodland sites was significantly higher than in the sand dune site. Ground level habitat classification discriminated among woodlands in which tick survival differed. The likelihood that I. scapularis populations could persist in the different habitats, as deduced using a population model of I. scapularis, was significantly associated with variations in Landsat 7 ETM+ data (normalized difference vegetation index [NDVI] and Tasselled Cap indices). The NDVI index predicted habitat suitability at Long Point, Ontario, with high sensitivity but moderate specificity. Our study suggests that I. scapularis populations could establish in more northerly woodland types than those in which they currently exist. Suitable habitats may be detected by ground-level habitat classification, and remote-sensed data may assist this process.
Effects of Prior Infestation on Host Choice of Bat Flies (Diptera: Streblidae)
Authors: Dick Carl W. , Dick Sonya C.
Published: January 2015

Experimental approaches provide insight into the dynamics of species competition and coexistence, but studies of ectoparasitic arthropods are rare. Host choice experiments were undertaken in Amazonian Peru, by using obligate bat fly parasites of Seba’s short-tailed bat, Carollia perspicillata (L.). The fly species Trichobius joblingi Wenzel strongly preferred clean hosts to those previously infested with individuals of T. joblingi. Abundance thresholds may limit conspecific parasites on host individuals, and similar morphologies and habitat use may increase intraspecific competition among individuals of T. joblingi. T. joblingi did not distinguish between clean hosts and those previously infested with flies of another species, Speiseria ambigua Kessel. Results suggest that the presence of a morphologically dissimilar species does not preclude subsequent colonization. Differential microhabitat selection, aided by adaptive morphology, may facilitate species coexistence among ectoparasitic bat fly species.
Detection of Anaplasma phagocytophilum and Babesia odocoilei DNA in Ixodes scapularis (Acari: Ixodidae) Collected in Indiana
Authors: Steiner Fresia E. , Pinger Robert R. , Vann Carolyn N. , Abley Melanie J. , Sullivan Bridget , Grindle Nate , Clay Keith , Fuqua Clay
Published: January 2015

The blacklegged tick, Ixodes scapularis Say, first reported in Indiana in 1987, has now been detected in more than half of Indiana’s counties. The first case of human granulocytic ehrlichiosis (human anaplasmosis) in Indiana was reported in 2002. We now report the detection of Anaplasma phagocytophilum and Babesia odocoilei in I. scapularis ticks collected in northern Indiana. Using polymerase chain reaction analysis, 41 of 193 adult ticks (21.2%) collected from deer were positive for A. phagocytophylum, and 22 (11.4%) were positive for Babesia sp. Restriction fragment analysis of 12, and sequencing of another five of the amplified products identified these parasites as B. odocoilei. Five ticks (2.6%) were coinfected. Eight of 68 questing adult ticks (11.8%) were positive for A. phagocytophilum; seven (10.3%) were positive for Babesia sp. Six of the latter seven positive samples were determined to be B. odocoilei by restriction fragment analysis and sequencing of two samples. None of 39 pools of nymphs was positive for Babesia sp. Three of 15 ticks (20%) collected from a dog were positive for A. phagocytophilum and three ticks (20%) were positive for Babesia sp. One was confirmed as B. odocoilei. One tick was coinfected. This is the first report of the presence of these two agents in ticks in Indiana.
Genomic Characterization Reveals Insights Into Patulin Biosynthesis and Pathogenicity in Penicillium Species
Authors: Li Boqiang , Zong Yuanyuan , Du Zhenglin , Chen Yong , Zhang Zhanquan , Qin Guozheng , Zhao Wenming , Tian Shiping
Published: January 2015

Penicillium species are fungal pathogens that infect crop plants worldwide. P. expansum differs from P. italicum and P. digitatum, all major postharvest pathogens of pome and citrus, in that the former is able to produce the mycotoxin patulin and has a broader host range. The molecular basis of host-specificity of fungal pathogens has now become the focus of recent research. The present report provides the whole genome sequence of P. expansum (33.52 Mb) and P. italicum (28.99 Mb) and identifies differences in genome structure, important pathogenic characters, and secondary metabolite (SM) gene clusters in Penicillium species. We identified a total of 55 gene clusters potentially related to secondary metabolism, including a cluster of 15 genes (named PePatA to PePatO), that may be involved in patulin biosynthesis in P. expansum. Functional studies confirmed that PePatL and PePatK play crucial roles in the biosynthesis of patulin and that patulin production is not related to virulence of P. expansum. Collectively, P. expansum contains more pathogenic genes and SM gene clusters, in particular, an intact patulin cluster, than P. italicum or P. digitatum. These findings provide important information relevant to understanding the molecular network of patulin biosynthesis and mechanisms of host-specificity in Penicillium species.

Ballester et al. ( MPMI-09-14-0261-FI ) reported similar results and conclusions in MPMI's March 2015 Focus Issue.
Effect ofwaxy(Low Amylose) on Fungal Infection of Sorghum Grain
Authors: Funnell-Harris Deanna L. , Sattler Scott E. , O’Neill Patrick M. , Eskridge Kent M. , Pedersen Jeffrey F.
Published: January 2015

Loss of function mutations in waxy, encoding granule bound starch synthase (GBSS) that synthesizes amylose, results in starch granules containing mostly amylopectin. Low amylose grain with altered starch properties has increased usability for feed, food, and grain-based ethanol. In sorghum, two classes of waxy (wx) alleles had been characterized for absence or presence of GBSS: wxa(GBSS−) and wxb(GBSS+, with reduced activity). Field-grown grain of wild-type; waxy, GBSS−; and waxy, GBSS+plant introduction accessions were screened for fungal infection. Overall, results showed that waxy grains were not more susceptible than wild-type. GBSS−and wild-type grain had similar infection levels. However, height was a factor with waxy, GBSS+lines: short accessions (wxballele) were more susceptible than tall accessions (undescribed allele). In greenhouse experiments, grain from accessions and near-isogenic wxa, wxb, and wild-type lines were inoculated with Alternaria sp., Fusarium thapsinum, and Curvularia sorghina to analyze germination and seedling fitness. As a group, waxy lines were not more susceptible to these pathogens than wild-type, supporting field evaluations. After C. sorghina and F. thapsinum inoculations most waxy and wild-type lines had reduced emergence, survival, and seedling weights. These results are valuable for developing waxy hybrids with resistance to grain-infecting fungi.
Dynamics of Verticillium Species Microsclerotia in Field Soils in Response to Fumigation, Cropping Patterns, and Flooding
Authors: Short Dylan P. G. , Sandoya German , Vallad Gary E. , Koike Steven T. , Xiao Chang-Lin , Wu Bo-Ming , Gurung Suraj , Hayes Ryan J. , Subbarao Krishna V.
Published: January 2015

Verticillium dahliae is a soilborne, economically significant fungal plant pathogen that persists in the soil for up to 14 years as melanized microsclerotia (ms). Similarly, V. longisporum is a very significant production constraint on members of the family Brassicaceae. Management of Verticillium wilt has relied on methods that reduce ms below crop-specific thresholds at which little or no disease develops. Methyl bromide, a broad-spectrum biocide, has been used as a preplant soil fumigant for over 50 years to reduce V. dahliae ms. However, reductions in the number of ms in the vertical and horizontal soil profiles and the rate at which soil recolonization occurs has not been studied. The dynamics of ms in soil before and after methyl bromide + chloropicrin fumigation were followed over 3 years in six 8-by-8-m sites in two fields. In separate fields, the dynamics of ms in the 60-cm-deep vertical soil profile pre- and postfumigation with methyl bromide + chloropicrin followed by various cropping patterns were studied over 4 years. Finally, ms densities were assessed in six 8-by-8-m sites in a separate field prior to and following a natural 6-week flood. Methyl bromide + chloripicrin significantly reduced but did not eliminate V. dahliae ms in either the vertical or horizontal soil profiles. In field studies, increases in ms were highly dependent upon the crop rotation pattern followed postfumigation. In the vertical soil profile, densities of ms were highest in the top 5 to 20 cm of soil but were consistently detected at 60-cm depths. Six weeks of natural flooding significantly reduced (on average, approximately 65% in the total viable counts of ms) but did not eliminate viable ms of V. longisporum.
Ramularia collo-cygni—An Emerging Pathogen of Barley Crops
Authors: Havis Neil D. , Brown James K. M. , Clemente Gladys , Frei Peter , Jedryczka Malgorzata , Kaczmarek Joanna , Kaczmarek Maciej , Matusinsky Pavel , McGrann Graham R. D. , Pereyra Sylvia , Piotrowska Marta , Sghyer Hind , Tellier Aurelien , Hess Michael
Published: January 2015

Ramularia collo-cygni is the biotic factor responsible for the disease Ramularia leaf spot (RLS) of barley (Hordeum vulgare). Despite having been described over 100 years ago and being considered a minor disease in some countries, the fungus is attracting interest in the scientific community as a result of the increasing number of recorded economically damaging disease epidemics. New reports of disease spread and fungal identification using molecular diagnostics have helped redefine RLS as a global disease. This review describes recent developments in our understanding of the biology and epidemiology of the fungus, outlines advances made in the field of the genetics of both the fungus and host, and summarizes the control strategies currently available.
Using Cardiac Magnetic Resonance Imaging to Evaluate Cardiac Function and Predict Outcomes in Patients with Valvular Heart Disease
Authors: Emerson Dominic A. , Amdur Richard L. , Morrissette Jason R. , Mordini Federico E. , Nagy Christian D. , Greenberg Michael D. , Trachiotis Gregory D.
Published: January 2015

Objective

In valvular heart disease, elevated left atrial and pulmonary pressures contribute to right ventricular strain and, ultimately, right ventricle failure. Elevated pulmonary artery (PAP) and left ventricular end diastolic pressures are used as markers of right ventricle dysfunction and correlate with poor outcomes. Using cardiac magnetic resonance imaging (CMR), it is possible to directly quantify both left and right ventricular ejection function (LVEF and RVEF), and here, we compare CMR with traditional markers as outcome predictors.

Methods

A retrospective review of prospectively collected data was performed for patients from January 2004 to February 2008 at a single center (n = 103). Patients were divided into those receiving CMR (n = 56) and those receiving only catheterization (n = 47). Univariate and multivariate logistic regression models were applied to determine predictors of mortality. Finally, predictive models for mortality using PAP, mean PAP, and left ventricular end diastolic pressure were compared to models using LVEF and RVEF obtained from CMR.

Results

Preoperative average CMR LVEF and RVEF were 57% and 46%, respectively. Only age emerged as an isolated predictor of mortality ( P = 0.01) within the univariate models. Stepwise regression models were created using the catheterization or CMR data. When compared, the CMR model has a slightly better R2, c (prediction accuracy), and sensitivity/specificity (0.22 vs 0.28, 0.77 vs 0.82, and 0.63/0.62 vs 0.69/0.64, respectively).

Conclusions

Within our population, LVEF and RVEF predict mortality as least as well as traditional catheterization values. Additionally, CMR may identify of elevated PAPs caused by right ventricle dysfunction and those due to other causes, allowing these other causes to be addressed preoperatively.
A Geometric Model of the Normal Human Aortic Root and Design of a Fully Anatomic Aortic Root Graft
Authors: Crooke Philip S. , Beavan L. Alan , Griffin Charles D. , Mazzitelli Domenico , Rankin J. Scott
Published: January 2015

Objective

Available aortic root grafts generally flare outward in the sinus region, and this feature improves procedural ease. However, no current device is based on normal aortic root geometry, and a fully anatomic aortic root graft could further facilitate valve-sparing root operations.

Methods

To develop a model of the normal human aortic root, high-resolution computed tomographic angiogram images from 11 normal human aortas generated high-density x, y, z coordinates of valve and root structures in Mathematica. Three-dimensional least-squares regression analyses assessed geometry of the aortic valve and root. Shapes and dimensions were quantified, and minor variations in geometry were simplified during graft design.

Results

Normal aortic valve and root geometry was represented as three leaflet-sinus general ellipsoids nested within a cylindrical aorta. Sinotubular junction diameter was 5 mm larger than the valve base—with a slight funnel-shaped outward commissural flare but cylindrical geometry above the midvalve. The valve base was elliptical, but the midvalve and the sinotubular junction were circular above the midvalve level. Commissural locations on the base circumference were equidistant. On the basis of average three-dimensional geometry, a root graft was designed for root remodeling procedures—to be used with an internal geometric annuloplasty ring of the same design.

Conclusions

An aortic root graft was designed on the basis of mathematical analyses of computed tomographic angiogram images. The design incorporated three anatomic sinuses, commissural symmetry, and compatibility with geometric ring annuloplasty. The anatomic graft may prove useful for restoring aortic root geometry toward normal during aortic valve and root surgery.
Fatal Cardiac Arrest in 2 Children
Authors: Brenner Scott M. , Boucher Jenny
Published: January 2015

Introduction

Ondansetron is commonly used to treat vomiting in gastroenteritis, but has a United States Food and Drug Administration black box warning for risk of Q wave to T wave time interval (QT) prolongation. We report 2 pediatric cases of fatal refractory cardiac arrest after administration of ondansetron.

Cases

A 10-year-old previously healthy boy presented to the emergency room with gastroenteritis symptoms. After intravenous fluids, morphine, antibiotics, and 2 doses of ondansetron, the patient became unresponsive with agonal respirations and a wide complex tachycardia consistent with ventricular tachycardia. In a second case, an 86-day-old infant with previously unidentified congenital cardiomyopathy presented to our emergency department with gastroenteritis symptoms. The patient received ondansetron and subsequently experienced repeated bouts of supraventricular tachycardia which progressed to ventricular fibrillation. Resuscitation efforts failed in each case, and both patients expired.

Discussion

Ondansetron can cause dose-dependent QT prolongation effects, which are more clinically relevant when other proarrhythmic elements are present. There is very limited published experience on use of ondansetron in children younger than 2 years. Our 2 cases join 2 previous case reports of death after ondansetron administration for gastroenteritis. The pharmacology of ondansetron's cardiac effects and drug-induced QT prolongation is discussed.

Conclusions

Patients may have hidden risk factors that, together with ondansetron, could result in a proarrhythmic state that could lead to adverse effects, such as arrhythmias. Administration of ondansetron should be individualized and used cautiously in patients with risk factors for arrhythmia.
The contribution of Diamond Light Source to the study of strongly correlated electron systems and complex magnetic structures
Authors: Radaelli P. G. , Dhesi S. S.
Published: January 2015

We review some of the significant contributions to the field of strongly correlated materials and complex magnets, arising from experiments performed at the Diamond Light Source (Harwell Science and Innovation Campus, Didcot, UK) during the first few years of operation (2007–2014). We provide a comprehensive overview of Diamond research on topological insulators, multiferroics, complex oxides and magnetic nanostructures. Several experiments on ultrafast dynamics, magnetic imaging, photoemission electron microscopy, soft X-ray holography and resonant magnetic hard and soft X-ray scattering are described.
Catalysis seen in action
Authors: Tromp Moniek
Published: January 2015

Synchrotron radiation techniques are widely applied in materials research and heterogeneous catalysis. In homogeneous catalysis, its use so far is rather limited despite its high potential. Here, insights in the strengths and limitations of X-ray spectroscopy technique in the field of homogeneous catalysis are given, including new technique developments. A relevant homogeneous catalyst, used in the industrially important selective oligomerization of ethene, is taken as a worked-out example. Emphasis is placed on time-resolved operando X-ray absorption spectroscopy with outlooks to novel high energy resolution and emission techniques. All experiments described have been or can be done at the Diamond Light Source Ltd (Didcot, UK).
Diamond: shedding light on structure-based drug discovery
Authors: Brown David G. , Shotton Elizabeth J.
Published: January 2015

Structure-based drug design has become a key tool for the development of novel drugs. The process involves elucidating the three-dimensional structure of the potential drug molecule bound to the target protein that has been identified as playing a key role in the disease state. Using this three-dimensional information facilitates the process of making improvements to the potential drug molecule by highlighting existing and possible new interactions within the binding site. This knowledge is used to inform increases in potency and selectivity of the molecules as well as to help improve other drug-like properties. The speed and numbers of samples that can be studied, combined with the improved resolution of the structures that can be obtained using synchrotron radiation, have had a significant impact on the utilization of crystallography in the drug discovery process.
Live Imaging of Inorganic Phosphate in Plants with Cellular and Subcellular Resolution
Authors: Mukherjee Pallavi , Banerjee Swayoma , Wheeler Amanda , Ratliff Lyndsay A. , Irigoyen Sonia , Garcia L. Rene , Lockless Steve W. , Versaw Wayne K.
Published: January 2015

Despite variable and often scarce supplies of inorganic phosphate (Pi) from soils, plants must distribute appropriate amounts of Pi to each cell and subcellular compartment to sustain essential metabolic activities. The ability to monitor Pi dynamics with subcellular resolution in live plants is, therefore, critical for understanding how this essential nutrient is acquired, mobilized, recycled, and stored. Fluorescence indicator protein for inorganic phosphate (FLIPPi) sensors are genetically encoded fluorescence resonance energy transfer-based sensors that have been used to monitor Pi dynamics in cultured animal cells. Here, we present a series of Pi sensors optimized for use in plants. Substitution of the enhanced yellow fluorescent protein component of a FLIPPi sensor with a circularly permuted version of Venus enhanced sensor dynamic range nearly 2.5-fold. The resulting circularly permuted FLIPPi sensor was subjected to a high-efficiency mutagenesis strategy that relied on statistical coupling analysis to identify regions of the protein likely to influence Pi affinity. A series of affinity mutants was selected with dissociation constant values of 0.08 to 11 mm, which span the range for most plant cell compartments. The sensors were expressed in Arabidopsis (Arabidopsis thaliana), and ratiometric imaging was used to monitor cytosolic Pi dynamics in root cells in response to Pi deprivation and resupply. Moreover, plastid-targeted versions of the sensors expressed in the wild type and a mutant lacking the PHOSPHATE TRANSPORT4;2 plastidic Pi transporter confirmed a physiological role for this transporter in Pi export from root plastids. These circularly permuted FLIPPi sensors, therefore, enable detailed analysis of Pi dynamics with subcellular resolution in live plants.
A Maize Glutaredoxin Gene,Abphyl2,Regulates Shoot Meristem Size and Phyllotaxy
Authors: Yang Fang , Bui Huyen Thanh , Pautler Michael , Llaca Victor , Johnston Robyn , Lee Byeong-ha , Kolbe Allison , Sakai Hajime , Jackson David
Published: January 2015

Phyllotaxy describes the geometric arrangement of leaves and is important for plant productivity. Auxin is well known to regulate phyllotactic patterns via PIN1-dependent auxin polar transport, and studies of maize (Zea mays) aberrant phyllotaxy1 (abph1) mutants suggest the importance of auxin and cytokinin signaling for control of phyllotaxy. However, whether additional regulators control these patterns is poorly understood. Here, we report a new dominant maize mutant, Aberrant phyllotaxy2 (Abph2), in which the shoot meristems are enlarged and the phyllotactic pattern switches from alternate to decussate. Map-based cloning revealed that the Abph2 mutation was caused by transposition of a glutaredoxin gene, MALE STERILE CONVERTED ANTHER1 (MSCA1), which gained an altered expression pattern in Abph2 mutant embryos. msca1 loss-of-function mutants have reduced meristem size and revealed a novel function of glutaredoxins in meristem growth. In addition, MSCA1 interacts with a TGA transcription factor, FASCIATED EAR4, suggesting a novel regulatory module for regulating shoot meristem size.
Cytoplasmic Nucleation and Atypical Branching Nucleation Generate Endoplasmic Microtubules inPhyscomitrella patens
Authors: Nakaoka Yuki , Kimura Akatsuki , Tani Tomomi , Goshima Gohta
Published: January 2015

The mechanism underlying microtubule (MT) generation in plants has been primarily studied using the cortical MT array, in which fixed-angled branching nucleation and katanin-dependent MT severing predominate. However, little is known about MT generation in the endoplasm. Here, we explored the mechanism of endoplasmic MT generation in protonemal cells of Physcomitrella patens. We developed an assay that utilizes flow cell and oblique illumination fluorescence microscopy, which allowed visualization and quantification of individual MT dynamics. MT severing was infrequently observed, and disruption of katanin did not severely affect MT generation. Branching nucleation was observed, but it showed markedly variable branch angles and was occasionally accompanied by the transport of nucleated MTs. Cytoplasmic nucleation at seemingly random locations was most frequently observed and predominated when depolymerized MTs were regrown. The MT nucleator γ-tubulin was detected at the majority of the nucleation sites, at which a single MT was generated in random directions. When γ-tubulin was knocked down, MT generation was significantly delayed in the regrowth assay. However, nucleation occurred at a normal frequency in steady state, suggesting the presence of a γ-tubulin-independent backup mechanism. Thus, endoplasmic MTs in this cell type are generated in a less ordered manner, showing a broader spectrum of nucleation mechanisms in plants.
Expression, crystallization and preliminary crystallographic data analysis of VioD, a hydroxylase in the violacein-biosynthesis pathway
Authors: Ran Tingting , Gao Mengxiao , Wei Qiaoe , He Jianhua , Tang Lin , Wang Weiwu , Xu Dongqing
Published: January 2015

Violacein, a natural purple secondary metabolite, is sequentially biosynthesized by five enzymes in the following pathway: VioA–VioB–VioE–VioD–VioC. VioD, a flavin-dependent oxygenase, catalyzes the hydroxylation of the intermediate product prodeoxyviolaceinic acid (PVA) at the 5-position of one indole ring to yield proviolacein.In vitrobiochemical data have revealed this process, but the catalytic mechanism still remains largely unclear. Here, the cloning, expression, purification, crystallization and diffraction of VioD are reported. Crystals of VioD diffracted to 1.7 Å resolution and belonged to space groupP31, with unit-cell parametersa=b= 90.0,c= 94.5 Å, α = β = 90, γ = 120°. Solvent-content calculation and molecular-replacement results suggest the presence of two molecules of VioD in the asymmetric unit.
Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN
Authors: Takayanagi Hiroki , Yuzawa Satoru , Sumimoto Hideki
Published: January 2015

The adaptor protein LGN interactsviathe N-terminal domain comprising eight tetratricopeptide-repeat (TPR) motifs with its partner proteins mInsc, NuMA, Frmpd1 and Frmpd4 in a mutually exclusive manner. Here, the crystal structure of the LGN TPR domain in complex with human Frmpd4 is described at 1.5 Å resolution. In the complex, the LGN-binding region of Frmpd4 (amino-acid residues 990–1011) adopts an extended structure that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPR motifs. Comparison with the previously determined structures of the LGN–Frmpd1, LGN–mInsc and LGN–NuMA complexes reveals that these partner proteins interact with LGN TPR1–6viaa common core binding region with consensus sequence (E/Q)XEX4–5(E/D/Q)X1–2(K/R)X0–1(V/I). In contrast to Frmpd1, Frmpd4 makes additional contacts with LGNviaregions N- and C-terminal to the core sequence. The N-terminal extension is replaced by a specific α-helix in mInsc, which drastically increases the direct contacts with LGN TPR7/8, consistent with the higher affinity of mInsc for LGN. A crystal structure of Frmpd4-bound LGN in an oxidized form is also reported, although oxidation does not appear to strongly affect the interaction with Frmpd4.
Latest methods of fluorescence-based protein crystal identification
Authors: Meyer Arne , Betzel Christian , Pusey Marc
Published: January 2015

Successful protein crystallization screening experiments are dependent upon the experimenter being able to identify positive outcomes. The introduction of fluorescence techniques has brought a powerful and versatile tool to the aid of the crystal grower. Trace fluorescent labeling, in which a fluorescent probe is covalently bound to a subpopulation (<0.5%) of the protein, enables the use of visible fluorescence. Alternatively, one can avoid covalent modification and use UV fluorescence, exploiting the intrinsic fluorescent amino acids present in most proteins. By the use of these techniques, crystals that had previously been obscured in the crystallization drop can readily be identified and distinguished from amorphous precipitate or salt crystals. Additionally, lead conditions that may not have been obvious as such under white-light illumination can be identified. In all cases review of the screening plate is considerably accelerated, as the eye can quickly note objects of increased intensity.
Crystallization and preliminary X-ray crystallographic analysis of Z-ring-associated protein (ZapD) fromEscherichia coli
Authors: Son Sang Hyeon , Lee Hyung Ho
Published: January 2015

Bacterial cytokinesis is accomplished by the Z-ring, which is a polymeric structure that includes the tubulin homologue FtsZ at the division site. ZapD, a Z-ring-associated protein, directly binds to FtsZ and stabilizes the polymerization of FtsZ to form a stable Z-ring during cytokinesis. Structural analysis of ZapD fromEscherichia coliwas performed to investigate the mechanism of ZapD-mediated FtsZ stabilization and polymerization. ZapD was crystallized using a reservoir solution consisting of 1.5 Mlithium sulfate, 0.1 MHEPES pH 7.8, 2%(v/v) polyethylene glycol 400. X-ray diffraction data were collected to 2.95 Å resolution. The crystals belonged to the hexagonal space groupP64, with unit-cell parametersa=b= 109.5,c= 106.7 Å, γ = 120.0°. Two monomers were present in the asymmetric unit, resulting in a crystal volume per protein mass (VM) of 3.25 Å3Da−1and a solvent content of 62.17%.
The joint effects of personality and supervisory career mentoring in predicting occupational commitment
Authors: Arora Ridhi , Rangnekar Santosh
Published: January 2015

Purpose

– The purpose of this paper is to examine the joint effects of personality (agreeableness and conscientiousness) and perceived supervisory career mentoring (SCM) on occupational commitment (OC) in the Indian context. In addition, the role of SCM support as a predictor of OC was also analyzed.

Design/methodology/approach

– A cross-sectional survey-based research design was adopted using data from 121 employees of public and private sector organizations in North India.

Findings

– The results showed that the relationship between perceived SCM and OC was stronger for employees reporting high levels of agreeableness in contrast to low agreeableness. Further, perceived SCM support was observed as a significant predictor of OC in the Indian context.

Practical implications

– This study suggests that for fostering an occupationally committed workforce, it is critical for supervisory mentors to understand how to deal with employees of different personality traits. Further, supervisory mentors need to be trained and empowered to render vocational support to employees at all levels.

Originality/value

– The work advances the existing work on mentoring and vocational outcomes by demonstrating the crucial role of supervisory career support and personality interactions in predicting OC.
Post M&A ill-health
Authors: Makri Eleni , Ntalianis Filotheos
Published: January 2015

Purpose

– The current financial crisis in Greece has redefined the way organizations operate resulting in a dramatic increase in mergers and acquisitions (M&As). The purpose of this paper is twofold: first to explore, within the M&A context, the main effects of job-related stressors and perceived organizational support (POS) on merger survivors’ ill-health and second to examine the indirect links between these and commitment.

Design/methodology/approach

– Data were obtained from 140 employees of two merged financial institutions in Greece post-combination.

Findings

– The results indicated significant direct relationships between work-related stressors and POS and ill-health. As regards the indirect relationships, only the mediation link between organizational support, ill-health and commitment was supported.

Practical implications

– Implications, limitations and further research issues are discussed in light of the M&A context.

Originality/value

– The intention is to extend current stress and M&A literature findings (e.g. Cartwright and Cooper, 1993; Cartwrightet al., 2007), and further investigate the relationship between stressors and ill-health within a turbulent context, since little is known about the behavioral reactions arising as an outcome of M&As in a Greek setting. Thus, the unique contribution of this study is to examine this relationship in a double crisis context: the organizational crisis following the M&A and the financial crisis currently facing Greece, since the area of M&As in Greece has so far received little scholarly attention (Bellou, 2007, 2008).
Workplace fun matters … but what else?
Authors: Tews Michael J. , Michel John , Xu Shi , Drost Alex J.
Published: January 2015

Purpose

– The purpose of this paper is to extend research on fun in the workplace by focussing on its relationship with job embeddedness among Millennials. This research examined the influence of four dimensions of fun, including fun activities, manager support for fun, coworker socializing, and fun job responsibilities, on embeddedness. In addition, this research assessed the impact of fun relative to other aspects of the employment experience.

Design/methodology/approach

– Data were obtained from 234 full-time working Millennials via survey methodology.

Findings

– Fun job responsibilities were the most dominant predictor of embeddedness followed by perceived career opportunities and praise and rewards. The other dimensions of fun accounted for significant variance in embeddedness, yet their influence was more modest.

Research limitations/implications

– The research demonstrated that fun plays a role in enhancing Millennials’ embeddedness, accounting for significant additional variance beyond other important aspects of the employment experience. At the same time, some aspects of fun were more dominant predictors of embeddedness than others, and other aspects of the employment experience were more dominant predictors than certain aspects of fun. These findings should be interpreted in the context of the primary limitation that the data were cross-sectional.

Practical implications

– Workplace fun may play a role in enhancing embeddedness, but organizations should not lose sight of other human resource management practices.

Originality/value

– The present study examined the role of workplace fun in a more nuanced perspective by examining its relationship on embeddedness relative to other important constructs.
To what extent a “bad” job? Employee perceptions of job quality in community aged care
Authors: Clarke Marilyn
Published: January 2015

Purpose

– The purpose of this paper is to explore how community aged care workers evaluate job quality using a job quality framework.

Design/methodology/approach

– The study uses a qualitative approach. Data were collected using semi-structured interviews and focus groups from a large aged care organisation.

Findings

– Perceptions of job quality are influenced by individual motivations, match between life-stage and work flexibility, as well as broader community views of the value of this type of work. Intrinsic factors (e.g. autonomy, job content) moderate the impact of extrinsic factors such as pay and job security.

Research limitations/implications

– The sample is relatively small and the study is based on data from one aged care organisation which may not reflect employment conditions in other organisations.

Practical implications

– Attraction and retention of community care workers can be improved by addressing factors associated with remuneration (including employment contracts and hours of work) and career structures. Skill and experience-based career structures would help build organisational capacity as well as making these jobs more attractive.

Social implications

– The demand for community care will continue to increase. Attracting, retaining and managing this workforce will be critical to meeting society’s expectations regarding the future care needs of older people.

Originality/value

– This research explores an under-researched workforce group in a critical area of aged care management. It highlights two key areas with the potential to improve employee perceptions of job quality and therefore address issues related to attraction, retention, job satisfaction and ultimately organisational performance.