bluuebunny/crossref_metadata_2025 huggingface dataset:
Rodent blood-stagePlasmodiumsurvive in dendritic cells that infect naive mice
Authors: Wykes Michelle N. , Kay Jason G. , Manderson Anthony , Liu Xue Q. , Brown Darren L. , Richard Derek J. , Wipasa Jiraprapa , Jiang Suhua H. , Jones Malcolm K. , Janse Chris J. , Waters Andrew P. , Pierce Susan K. , Miller Louis H. , Stow Jennifer L. , Good Michael F.
Published: June 2011

Plasmodiumspp. parasites cause malaria in 300 to 500 million individuals each year. Disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. Infected individuals can also suffer relapses after several years, fromPlasmodium vivaxandPlasmodium ovalesurviving in hepatocytes.Plasmodium falciparumandPlasmodium malariaecan also persist after the original bout of infection has apparently cleared in the blood, suggesting that host cells other than erythrocytes (but not hepatocytes) may harbor these blood-stage parasites, thereby assisting their escape from host immunity. Using blood stage transgenicPlasmodium berghei-expressing GFP (PbGFP) to track parasites in host cells, we found that the parasite had a tropism for CD317+dendritic cells. Other studies using confocal microscopy, in vitro cultures, and cell transfer studies showed that blood-stage parasites could infect, survive, and replicate within CD317+dendritic cells, and that small numbers of these cells released parasites infectious for erythrocytes in vivo. These data have identified a unique survival strategy for blood-stagePlasmodium, which has significant implications for understanding the escape ofPlasmodiumspp. from immune-surveillance and for vaccine development.
Cdc42 and Tinman march to the same beat
Authors: Short Ben
Published: June 2011

Study describes a conserved genetic network that regulates heart function in flies and mammals.
Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii
Authors: Nair Sethu C. , Brooks Carrie F. , Goodman Christopher D. , Strurm Angelika , McFadden Geoffrey I. , Sundriyal Sandeep , Anglin Justin L. , Song Yongcheng , Moreno Silvia N.J. , Striepen Boris
Published: June 2011

Apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. Apicomplexan parasites contain a relict chloroplast, the apicoplast. The apicoplast is indispensable and an attractive drug target. The apicoplast is home to a 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway for the synthesis of isoprenoid precursors. This pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathway, is an effective antimalarial. Surprisingly, fosmidomycin has no effect on most other apicomplexans. Using Toxoplasma gondii, we establish that the pathway is essential in parasites that are highly fosmidomycin resistant. We define the molecular basis of resistance and susceptibility, experimentally testing various host and parasite contributions in T. gondii and Plasmodium. We demonstrate that in T. gondii the parasite plasma membrane is a critical barrier to drug uptake. In strong support of this hypothesis, we engineer de novo drug-sensitive T. gondii parasites by heterologous expression of a bacterial transporter protein. Mice infected with these transgenic parasites can now be cured from a lethal challenge with fosmidomycin. We propose that the varied extent of metabolite exchange between host and parasite is a crucial determinator of drug susceptibility and a predictor of future resistance.
Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas
Authors: Pilati Camilla , Amessou Mohamed , Bihl Michel P. , Balabaud Charles , Van Nhieu Jeanne Tran , Paradis Valérie , Nault Jean Charles , Izard Tina , Bioulac-Sage Paulette , Couchy Gabrielle , Poussin Karine , Zucman-Rossi Jessica
Published: June 2011

Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6–induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6–STAT3 pathway in benign hepatocellular tumorigenesis.
On the boundary of Kähler cones
Authors: Zhang Xiangwen
Published: June 2011

We study some geometric properties of a compact Kähler manifold

(

M
n

,
g
)

(M^n, g)

under a certain condition on the bisectional curvature. As an application, we give a new proof for an earlier result which asserts that any boundary class of the Kähler cone of

M
n

M^n

can be represented by a

C

∞

C^{\infty }

closed (1,1) form that is parallel and everywhere nonnegative.
Comparison principles for self-similar potential flow
Authors: Chen Gui-Qiang , Feldman Mikhail
Published: June 2011

We establish a strong comparison principle, as well as a weak comparison principle and a Hopf-type lemma, for elliptic solutions of the self-similar potential flow equation. A major difference from the steady case is that the coefficients of the equation depend on the potential function itself, as well as its gradient. We employ the divergence structure and other features of the equation to derive the results.
SpEED: fast computation of sensitive spaced seeds
Authors: Ilie Lucian , Ilie Silvana , Mansouri Bigvand Anahita
Published: June 2011

Summary: Multiple spaced seeds represent the current state-of-the-art for similarity search in bioinformatics, with applications in various areas such as sequence alignment, read mapping, oligonucleotide design, etc. We present SpEED, a software program that computes highly sensitive multiple spaced seeds. SpEED can be several orders of magnitude faster and computes better seeds than the existing leading software programs.

Availability: The source code of SpEED is freely available at www.csd.uwo.ca/~ilie/SpEED/

Contact:  ilie@csd.uwo.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Review Article: Patient Safety in Geriatrics: A Call for Action
Authors: Tsilimingras Dionyssios , Rosen Amy K. , Berlowitz Dan R.
Published: June 2011

Patient safety has become a major public health concern following the publication of the landmark report, To Err Is Human, by the Institute of Medicine in 1999. This report, along with a subsequent report, Crossing the Quality Chasm, recommended the design of a safer health care system by integrating well-established safety methods to avert medical errors. However, neither patient safety report specifically addressed the implications of safety for elderly patients. This article examines those implications by describing the association between aging and medical errors, identifying geriatric syndromes as medical errors, and focusing on six recommendations that will improve the safety of geriatric care. These six recommendations include the detection and reporting of geriatric syndromes, identifying system failures when geriatric syndromes occur, establishing dedicated geriatric units, improving the continuity of care, reducing adverse drug events, and improving geriatric training programs.
Chronic Exercise Improves Myocardial Inotropic Reserve Capacity Through α1-Adrenergic and Protein Kinase C-Dependent Effects in Senescent Rats
Authors: Korzick Donna H. , Hunter James C. , McDowell Mark K. , Delp Michael D. , Tickerhoof Marlena M. , Carson LaToya D.
Published: June 2011

We have previously demonstrated that α1-adrenergic (AR)-mediated contraction is diminished in the senescent rat heart, in part due to alterations in protein kinase C (PKC) signaling. Since chronic exercise training (EX) can exert independent effects on increasing α1-AR contraction in the adult rat heart, we sought to determine whether age-related defects in α1-AR contraction could be reversed by chronic EX. We further hypothesized that improved α1-AR contraction by EX may be PKC dependent. Adult (4 months; Y) and aged (24 months; O) male F344 rats were treadmill-trained (n = 12–13/group; TR) at ∼70% of VO2max for 12 weeks or remained sedentary (YSED, YTR, OSED, OTR). Training status was verified by plantaris citrate synthase activity and left ventricular (LV) contractile responses (dP/dt) to α1-AR stimulation were assessed in Langendorff-perfused hearts using the α1-AR agonist phenylephrine (PE; 10−5 M) with and without the PKC inhibitor chelerythrine (CE; 10−6 M). α1-AR stimulation elicited greater increases in LV dP/dt in hearts isolated from OTR (4525.4 ± 224.1 mmHg/s) versus OSED (3658.9 ± 291.0 mmHg/s), while CE abolished PE-induced effects (OTR, 4069.2 ± 341.2) versus (OSED, 3608.9 ± 321.2) (p <.01). Upon western blotting, phosphospecific antibodies directed at PKCε (pSer729) revealed greater levels in LV isolated from YTR versus YSED, and EX ameliorated aged-related reductions in OSED (p <.001). Basal PKCε mRNA levels were also greater in YTR and OTR versus YSED (p <.01). PE-induced increases in phosphor-PKCδ (pThr507) levels observed in OSED were attenuated in OTR (p <.03). Chronic EX was also associated with significant reductions in PKCα (pSer657) levels following PE in OTR (p <.002). The results indicate that age-related reductions in α1-AR contraction can be partially reversed by EX in the rat heart. These results further suggest that alterations in PKC levels underlie, at least in part, EX-induced improvements in α1-AR contraction.
The Effect of Age and Joint Angle on the Proportionality of Extensor and Flexor Strength at the Knee Joint
Authors: Savelberg Hans H. C. M. , Meijer Kenneth
Published: June 2011

Functional movements require concerted actions of monoarticular and biarticular agonists and antagonists. Understanding age-related changes of muscle function on performance requires insight in the contributions of different muscles to joint moments. Young and elderly participants performed isometric knee extensions and flexions at combinations of knee and hip joint angles. This approach allowed assessing changes in contribution of monoarticular and biarticular knee joint flexors and extensors. Reduced moments were found for elderly persons (flexors: −43%; extensors: −33%). In the flexor group, this reduction was mainly caused by retardation of the biarticular muscles; in the extensors, by reduced strength of the monoarticular muscles. This age-related reduction of joint moments occurred to be joint angle dependent for the extensors. In the flexor group, the reduction was almost invariant. Due to this difference in joint angle dependence, the proportionality between extensors and flexors varied over joint angles and differed with age. It has been discussed how this is related to changes in performances occurring with age.
Lifestyle, Nutritional Status, Health, and Mortality in Elderly People Across Europe: A Review of the Longitudinal Results of the SENECA Study
Authors: de Groot Lisette C. P. M. G. , Verheijden Marieke W. , de Henauw Stefaan , Schroll Marianne , van Staveren Wija A.
Published: June 2011

This article provides an overview of the longitudinal Survey in Europe on Nutrition and the Elderly: a Concerted Action (SENECA) study, which was designed to assess differences in dietary and lifestyle factors among elderly Europeans, and to identify the factors that contribute to healthy aging. Elderly people from Belgium, Denmark, France, Italy, Portugal, Spain, Switzerland, and The Netherlands participated in the SENECA study. Standardized measurements were conducted at baseline in 1988–1989 and were repeated in 1993 and 1999. Diet, physical activity, and smoking, as well as maintenance of health and survival, were assessed. At baseline, considerable differences in lifestyle factors existed among elderly people. Mealtime patterns as well as dietary intake varied across Europe, and geographical patterns were apparent. Similar results were found for engagement in sport or professional activities. The smoking prevalence among women was generally low. Distinct geographical differences were also observed in percentages of deaths during the SENECA study and in overall survival time. A healthy lifestyle was related to stable self-perceived health, a delay in functional dependence, and mortality. Inactivity and smoking, and to a lesser extent a low-quality diet, increased mortality risk. A combined effect of multiple unhealthy lifestyle factors was also observed. The SENECA study showed that a healthy lifestyle at older ages is related to a delay in the deterioration of health status and a reduced mortality risk. Improving and maintaining a healthy lifestyle in elderly people across Europe is a great challenge for the European Community.
An Immune Risk Phenotype, Cognitive Impairment, and Survival in Very Late Life: Impact of Allostatic Load in Swedish Octogenarian and Nonagenarian Humans
Authors: Wikby Anders , Ferguson Frederick , Forsey Rosalyn , Thompson Julie , Strindhall Jan , Löfgren Sture , Nilsson Bengt-Olof , Ernerudh Jan , Pawelec Graham , Johansson Boo
Published: June 2011

In the previous OCTO longitudinal study, we identified an immune risk phenotype (IRP) of high CD8 and low CD4 numbers and poor proliferative response. We also demonstrated that cognitive impairment constitutes a major predictor of nonsurvival. In the present NONA longitudinal study, we simultaneously examine in a model of allostatic load IRP and compromised cognition in 4-year survival in a population-based sample (n = 138, 86–94 years). Immune system measurements consisted of determinations of T-cell subsets, plasma interleukin 6 and cytomegalovirus and Epstein–Barr virus serology. Interleukin 2 responsiveness to concanavalin A, using data from the previous OCTO (octogenarians) immune study, hereafter OCTO immune, was also examined. Cognitive status was rated using a battery of neuropsychological tests. Logistic regression indicated that the IRP and cognitive impairment together predicted 58% of observed deaths. IRP was associated with late differentiated CD8+CD28−CD27− cells (p <.001), decreased interleukin 2 responsiveness (p <.05) and persistent viral infection (p <.01). Cognitive impairment was associated with increased plasma interleukin 6 (p <.001). IRP individuals with cognitive impairment were all deceased at the follow-up, indicating an allostatic overload.
Predictors of Physical Health: Toward an Integrated Model of Genetic and Environmental Antecedents
Authors: Johnson Wendy , Krueger Robert F.
Published: June 2011

People in higher-income groups tend to experience better physical health, yet this does not appear to be the direct result of access to medical care. This has prompted a search for psychological factors more likely to be present in high-income environments that might help to explain the relationship. Physical health has been associated with a number of such psychological measures including positive affect and well-being, negative affect and neuroticism, positive social relationships, and perceived control. Building from recent findings of moderation of genetic variance in physical health by income and perceived control, we explore the genetic and environmental relationships among all these variables in a nationwide U.S. twin sample. These relationships suggest possible mechanisms by which psychological characteristics, behaviors, physical health, and environmental circumstances could be influenced by common groups of genes with varying degrees of activity in different environments. We discuss the implications of such mechanisms for differential expression of genetic variation in the population and suggest ways in which consideration of such effects can inform gerontology research.
Social Context in Gene–Environment Interactions: Retrospect and Prospect
Authors: Shanahan Michael J. , Hofer Scott M.
Published: June 2011

While many behavioral scientists believe that gene–environment (GE) interactions play an important and perhaps pervasive role in human development and aging, little attention has been devoted to a fundamental conceptual issue: What is it about social context that could alter gene expression? We draw on existing examples of GE interactions to formulate a typology that identifies a set of generic mechanisms by which E moderates G. Empirical studies suggest four ideal types: Social context can trigger a genetic diathesis, compensate for a genetic diathesis, act as a control to prevent behaviors for which there is a genetic predisposition, and enhance adaptation through proximal processes. This typology highlights several problems, however, with prior empirical research, which may explain, in part, why so few GE interactions have actually been observed. These problems include inattention to the dynamic nature of social experience, the manifold, often-intercorrelated dimensions of social context (“EE interactions”), mediators that link social context and the genotype, and analytic models that examine GE interactions as processes that characterize individual development. In turn, these insights call for the integration of life course sociology and behavioral genetics to foster ways of studying genes, context, and aging.
Controlling Disease and Creating Disparities: A Fundamental Cause Perspective
Authors: Phelan Jo C. , Link Bruce G.
Published: June 2011

The United States and other developed countries experienced enormous improvements in population health during the 20th century. In the context of this dramatic positive change, health disparities by race and socioeconomic status emerged for several potent killers. Any explanation for current health disparities must take these changing patterns into account. Any explanation that ignores large improvements in population health and fails to account for the emergence of disparities for specific diseases is an inadequate explanation of current disparities. We argue that genetic explanations and some prominent social causation explanations are incompatible with these facts. We propose that the theory of “fundamental causes” can account for both vast improvements in population health and the creation of large socioeconomic and racial disparities in mortality for specific causes of death over time. Specifically, we argue that it is our enormously expanded capacity to control disease and death in combination with existing social and economic inequalities that create health disparities by race and socioeconomic status: When we develop the ability to control disease and death, the benefits of this new-found ability are distributed according to resources of knowledge, money, power, prestige, and beneficial social connections. We present data on changing mortality patterns by race and socioeconomic status for two types of diseases: those for which our capacity to prevent death has increased significantly and those for which we remain largely unable to prevent death. Time trends in mortality patterns are consistent with the fundamental cause explanation.
Rethinking Gender Differences in Health: Why We Need to Integrate Social and Biological Perspectives
Authors: Rieker Patricia P. , Bird Chloe E.
Published: June 2011

The complexity of gender differences in health (i.e., men's lower life expectancy and women's greater morbidity) extends beyond notions of either social or biological disadvantage. Gaps remain in understanding the antecedents of such differences and the issues this paradox raises regarding the connections between social and biological processes. Our goals in this analytic essay are to make the case that gender differences in health matter and that understanding these differences requires an explanation of why rational people are not effective in making health a priority in their everyday lives. We describe some salient gender health differences in cardiovascular disease, immune function and disorders, and depression and indicate why neither social nor biological perspectives alone are sufficient to account for them. We consider the limitations of current models of socioeconomic and racial/ethnic health disparities to explain the puzzling gender differences in health. Finally, we discuss constrained choice, a key issue that is missing in the current understanding of these gender differences, and call on the social science community to work with biomedical researchers on the interdisciplinary work required to address the paradoxical differences in men's and women's health.
A Life-Span Developmental Perspective on Social Status and Health
Authors: Alwin Duane F. , Wray Linda A.
Published: June 2011

This article presents a life-span developmental (LSD) perspective on the linkages between social status and health. The objective is to develop a conceptual framework that is useful in understanding why people are differentially exposed to risks of disease or protective factors and the social conditions that link the effects of risk and protective factors to the social environment over the life span. The discussion distinguishes between the complementary concepts of “life span,” “life cycle,” and “life course,” critical theoretical distinctions that may help refine hypotheses about the relationship between health and social status. We argue that life-cycle and life-course concepts can be viewed as embedded in a more general LSD perspective. Using the theoretical principles derived from this perspective, the review examines (a) gender differences, (b) race–ethnic experiences, (c) childhood experiences, (d) educational levels, (e) socioeconomic differences, and (f) age differences. The emphasis in the review is to highlight the value of a broader LSD perspective in the study of health inequalities. The article ends with a brief summary of where future research is headed and novel developments in the study of social status and health.
Hay Fever and Allergic Rhinitis
Authors: Smith Helen
Published: June 2011

Rhinitis is an inflammatory condition of the nasal mucosa which causes nasal discharge, itching, sneezing, nasal stuffiness, congestion and blockage. Rhinitis can be due to a variety of causes and is classified as allergic, nonallergic and infective. This article focuses on the diagnosis and management of rhinitis with an allergic aetiology.
Effects of Cultivar and Processing Condition on Physicochemical Properties and Starch Fractions in Parboiled Rice
Authors: Newton Jumaane , Wang Ya‐Jane , Mauromoustakos Andronikos
Published: June 2011

Starch can be classified into rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) according to its resistance to amylolytic enzymes. This study investigated the effects of cultivar and feedstock under varying parboiling conditions on the physicochemical properties and starch fractions of parboiled rice. Rice (rough or brown) was soaked, steamed under pressure, dried immediately or stored at room temperature for 24 hr prior to drying, and then treated with or without a repeated steam cycle prior to milling. The storage treatment significantly increased the retrograded amylopectin enthalpy and amylose‐lipid complex melting temperature of parboiled rice. Parboiled rice samples prepared from brown rice feedstock had higher peak melting temperatures but lower enthalpy values of retrograded amylopectin than samples prepared from rough rice after the storage treatment. The pasting viscosity of parboiled rice was most affected by the repeated autoclaving treatment and cultivar. Starch fractions in parboiled rice were significantly affected by cultivar and storage and by the interactions of cultivar and parboiling conditions. The storage treatment significantly increased SDS and generally decreased RDS in parboiled rice. Parboiled rice with different SDS and RS contents can be produced by varying rice cultivar and parboiling conditions.
Application of a Rank-Based Method for Improved Cultivar Selection in Soft Red Winter Wheat
Authors: Lackermann Karen V. , Esker Paul D.
Published: June 2011

Both grain yield and disease performance are important factors to consider for winter wheat (Triticum aestivum) cultivar selection. However, disease severity and yield data are often presented separately, making it difficult to compare values across multiple environments. The objective of this study was to use a rank-based method to compare cultivars based on yield and disease performance combined across multiple environments. Thirty-six wheat cultivars were planted at each of four Wisconsin locations (Arlington, Chilton, Janesville, and Lancaster) in 2009 and 2010. Plots were assessed four times during the growing season for powdery mildew, Septoria/Stagonospora leaf blotch, and leaf rust. Incidence and severity of Fusarium head blight were assessed at Zadoks growth stage 85 (soft dough). Within each location–year, cultivars were ranked for severity of each disease and for grain yield. One-way analysis of variance was performed to calculate an overall rank value that incorporated data for all four diseases and yield across the eight location–years. There was an effect of cultivar on overall rank (P < 0.0001). Powdery mildew rank was strongly correlated with overall rank (Spearman's rho = 0.485, P = 0.005), as was yield rank (Spearman's rho = 0.674, P < 0.0001). Cultivars described as “best” or “worst” cultivars were generally more consistent in their rankings across different measures. The use of a rank-based method provides an approach that will allow growers to base cultivar selection on multiple performance measures across multiple environments.
First Report of Strawberry necrotic shock virus in China
Authors: Li L. , Yang H.
Published: June 2011

Strawberry necrotic shock virus (SNSV) is an economically important viral pathogen that infects Fragaria and Rubus spp. SNSV was first identified in the 1950s and early studies indicated that SNSV was a strain of Tobacco streak virus (TSV). Recently, it was shown that SNSV was a distinct virus based on molecular characterization (2). Currently, SNSV is a tentative member of the Ilarvirus genus in the Bromoviridae family. In 2008, a small sampling survey for SNSV was done in Heilongjiang Province of China, and 15 strawberry samples were collected from symptomless strawberries in a home garden that had more than 5 years of strawberry cultivation history. Total nucleic acid was extracted from strawberry leaflets by modified cetyltrimethylammoniumbromide methods (3). Reverse transcription (RT)-PCR was operated with the published primer pair CPbeg F/CPend R (2). Amplified DNA fragments with the predicted size were obtained only in one strawberry sample, which was further cloned and sequenced. The sequence (GenBank Accession No. HQ830017) was closely related and highly homologous (89.7 to 98.5% identity) to that of viral isolates (GenBank Accession Nos. AY363228-AY363242) from Fragaria and Rubus spp. Phylogenetic analysis based on nucleotide sequence of the coat protein gene was done with the neighbor-joining method of MEGA 4.0 software. The result showed that all the isolates of SNSV fell into two distinct clades. The Chinese isolate formed one small clade with Japanese isolate 1291. The isolate was also transmitted to Chenopodium quinoa by mechanical inoculation in the greenhouse, and the symptom of chlorotic mottling could be found in C. quinoa and detected by RT-PCR. To determine whether the sample was infected by other strawberry viruses, RT-PCR assays with the published primer pairs SVBVdeta/SVBVdetb, SMoVdeta/SMoVdetb, and SMYEVdeta/SMYEVdetb were also performed for detection of Strawberry vein banding virus, Strawberry mottle virus, and Strawberry mild yellow edge virus using total nucleic acid extracted from the SNSV-positive sample as a template (1). The result indicated that it had been also infected by Strawberry mild yellow edge virus, although no visible symptoms were observed. To our knowledge, this is the first report of SNSV in strawberry in China. Additional work is needed to elucidate the biological characterization and significance of the finding.

References: (1) J. R. Thompson et al. J. Virol. Methods 111:85, 2003. (2) I. E. Tzanetakis et al. Arch. Virol. 149:2001, 2004. (3) H. Y. Yang et al. Acta Hortic. 764:127, 2007.
Wild Type Sensitivity and Mutation Analysis for Resistance Risk to Fluopicolide in Phytophthora capsici
Authors: Lu Xiao Hong , Hausbeck Mary K. , Liu Xi Li , Hao Jianjun J.
Published: June 2011

Crown, root, and fruit rot caused by Phytophthora capsici is an increasing problem for vegetable growers in Michigan and the United States. The newly registered fungicide fluopicolide is effective to limit crop loss but the potential for P. capsici to develop resistance is not well known. A laboratory study assessed the risk of P. capsici developing resistance to fluopicolide. Baseline sensitivity to fluopicolide was determined using 126 P. capsici Michigan isolates. Values of effective concentrations for 50% inhibition of mycelial growth ranged from 0.08 to 0.24 μg/ml and were distributed as a unimodal curve, indicating that all isolates were sensitive to fluopicolide. Mutants resistant to fluopicolide were obtained from five isolates by screening zoospores on fluopicolide-amended (5 μg/ml) media at a mutation frequency above 1.0 × 10–7. The mutant isolates were clustered with either intermediate (resistance factor [RF] = 3.53 to 77.91) or high (RF = 2481.40 to 7034.79) resistance. Resistance was stable through 10 mycelial transfers on fungicide-free medium. All resistant mutants showed similar fitness in zoospore production, cyst germination, and virulence compared with their sensitive parents, with few exceptions. No cross-resistance was detected between fluopicolide and five other fungicides. There could be a moderately high risk of field populations of P. capsici developing resistance to fluopicolide, and populations should be monitored.
First Report of Blue Mold Caused by Penicillium oxalicum in Tomato (Solanum lycopersicum) in Mexico
Authors: Picos-Munoz P. A. , Garcia-Estrada R. S. , Carrillo-Fasio J. A. , Leon-Felix J. , Allende-Molar R.
Published: June 2011

Tomato is the primary vegetable exported from Mexico to the United States. In June 2007, stem rots were observed in tomato cv. Imperial plants growing in a greenhouse in the Culiacan Valley. Disease symptoms included stem rot with a mycelial growth with a grayish blue sporulation. The disease was observed to be affecting 1% of the tomato plants growing in the greenhouse, and has been observed sporadically in greenhouses during subsequent agricultural cycles in other tomato-growing areas in Mexico. Affected stems showed initial symptoms of a dark brown necrotic area surrounding only the cut regions of pruned leaves and stems. As the infection continued on the tissues, the spot grew and then became covered with a grayish blue sporulation. Severe stem rot led to death of the plants. Rotted stems of tomato plants were collected and samples of the infected tissues were plated onto potato dextrose agar (PDA) to isolate the fungus. The preliminary identification of the pathogen was Penicillium oxalicum Currie & Thom on the basis of morphological criteria with ellipsoidal conidia approximately 4 × 3 μm borne in columns, conidiophores mostly biverticillate, and ampulliform phialides (2). The identification was confirmed by sequencing internal transcribed spacer 1 (ITS1), 5.8S, and ITS2 regions of the ribosomal DNA (GenBank Accession No. HM452308). The isolate was deposited in the Coleccion Nacional Microbiana y de Cultivos Celulares CINVESTAV-IPN, Mexico. Koch's postulates were fulfilled by reproducing stem rots on healthy inoculated tomato stems. Pathogenicity testing involved fungal growth on PDA for 5 days, after which a 4-mm disk of actively growing mycelia was transferred to wounds (4 × 4 mm) made with a scalpel in stems of 6-week-old tomato cv. Imperial plants. Inoculated plants were covered with plastic bags to maintain a high relative humidity for 24 h and were maintained in a greenhouse at 25 ± 2°C. Seven days after inoculation, all of the inoculated stems showed rot symptoms similar to those observed in the greenhouse. Stems that were inoculated only with an agar disk did not show any symptoms of the disease. The pathogen was reisolated from inoculated plants but not from noninoculated plants. Artificial inoculation was performed twice. Although P. oxalicum has been previously reported as a causal agent of cucumber (1) and tomato stem rots in Japan (3), to our knowledge, this is the first report of P. oxalicum causing stem rot in tomato plants in Mexico.

References: (1) T. M. O'Neill et al. Plant Pathol. 40:78, 1991. (2) J. I. Pitt. The Genus Penicillium and Its Teleomorphic States Eupenicillium and Talaromyces. Academic Press, London, UK, 1979. (3) S. Umemoto et al. J. Gen. Plant Pathol. 75:399, 2009.
Baseline Sensitivity of Natural Population and Resistance of Mutants in Phytophthora capsici to Zoxamide
Authors: Bi Yang , Cui Xiaolan , Lu Xiaohong , Cai Meng , Liu Xili , Hao Jianjun J.
Published: June 2011

Laboratory experiments were conducted to determine the baseline sensitivity of Phytophthora capsici and its risk for developing resistance to zoxamide. In total, 158 P. capsici isolates were collected from China. All 158 isolates were sensitive to zoxamide, with effective concentrations for 50% inhibition of mycelial growth of 0.023 to 0.383 μg/ml and a mean of 0.114 μg/ml, which showed a skewed unimodal distribution. Zoxamide-resistant mutants of P. capsici were obtained by either treating mycelial culture and zoospores with ultraviolet irradiation or adapting a culture on zoxamide-amended plates. The frequency of resistance selection averaged 1.8 × 10–7. Resistant isolates were also derived by selfing or crossing two sexually compatible isolates, resulting in a mean selection frequency of 0.47. The resistance factor (RF) for zoxamide was 25 to 100 in P. capsici mutants. Through 10 culture transfers, the mutants maintained high levels of RF (between 14 and 134) and had almost equal fitness as their wild-type parents in mycelial growth, sporulation, and virulence. There was no cross resistance between zoxamide and either flumorph, metalaxyl, azoxystrobin, or etridiazole. Based on the results above, P. capsici can develop resistance to zoxamide, and the risk is predicted to be moderate in nature.
Treatment of Infants and Toddlers With Cystic Fibrosis–related Pancreatic Insufficiency and Fat Malabsorption With Pancrelipase MT
Authors: Van de Vijver Els , Desager Kristine , Mulberg Andrew E , Staelens Sofie , Verkade Henkjan J , Bodewes Frank AJA , Malfroot Anne , Hauser Bruno , Sinaasappel Maarten , Van Biervliet Stefanie , Behm Martin , Pelckmans Paul , Callens Dirk , Veereman‐Wauters Gigi
Published: June 2011

Background:

Pancreatic enzyme replacement therapy (PERT) improves nutritional status and growth in patients with cystic fibrosis (CF) with pancreatic insufficiency (PI). The current recommendation for infants and young children, who are not able to swallow the whole capsule, is to open the capsule and mix the beads in a spoon with some applesauce; however, the efficacy and safety data of this approach are currently lacking. The aim of this study was to assess the efficacy, palatability (ease of swallowing), and safety of 4 dose levels of pancrelipase microtablets (Pancrease MT) in infants and young children with CF‐related PI.

Patients and Methods:

This study was a phase II randomized, investigator‐blinded, parallel‐group pilot study in DNA‐proven infants with CF and PI. The study design included a run‐in period (days 1–5) and an experimental period (days 6–11). Pancrelipase microtablets (2‐mm, enteric coated) were provided orally. Sixteen subjects, 6 to 30 months of age, were provided 500 U lipase/kg/meal for 5 days (baseline period). Subsequently, subjects were randomly assigned to 1 of 4 treatment groups (each n = 4), receiving 500, 1000, 1500, or 2000 U (Ph. EUR) of lipase/kg/meal, respectively, for 5 days (experimental period). The primary endpoint was medication efficacy assessed by the 72‐hour fecal fat excretion, expressed as coefficient of fecal fat absorption (CFA), and 13C mixed triglyceride breath test. Secondary endpoints were safety and palatability.

Results:

Overall compliance, defined as used study medication, was 89% to 99% for the entire study. None of the 4 dose regimens significantly influenced the CFA, relative to the baseline period (median range 83%–93%). During the run‐in period the median cumulative % 13C was 11 (range −8 to 59). After randomization the median cumulative % 13C was 18 (range 14–23) in the 500‐U, 14 (range −1 to 17) in the 1000‐U, 10 (range 10–27) in the 1500‐U, and 3 (range 1–49) in the 2000‐U groups. Palatability was scored fair to good by the parents in each of the treatment groups. Gastrointestinal symptoms were reported in some patients, including common adverse events reported in clinical trials involving pancreatic enzyme therapy. No serious or other adverse events were reported.

Conclusion:

Treatment with Pancrease MT at a dosage of 500 U lipase/kg/meal resulted in a CFA of approximately 89% in pediatric subjects ages 6 to 30 months with PI resulting from CF. Pancrease MT doses were well tolerated and mean palatability was scored as fair to good. Present results do not indicate that a dosage higher than 500 U (Ph. EUR) lipase/kg/meal increases the coefficient of fat absorption in a cohort of infants 6 to 30 months of age.
Immunophenotyping of Peripheral Eosinophils Demonstrates Activation in Eosinophilic Esophagitis
Authors: Nguyen Tammie , Gernez Yael , Fuentebella Judy , Patel Anup , Tirouvanziam Rabindra , Reshamwala Neha , Bass Dorsey , Berquist William E , Cox Kenneth L , Kerner John A , Nadeau Kari C
Published: June 2011

Background and Aim:

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by upper gastrointestinal symptoms and the presence of high numbers of eosinophils in the esophagus. Although eosinophils in the esophagus have been found to be activated in subjects with EoE, detailed studies of intracellular signaling pathways involved in the mechanism of activation of eosinophils in EoE have heretofore been limited. The aim of the study was to assess whether any surface molecules or transcription factors are activated in peripheral eosinophils in subjects with EoE.

Methods:

Eosinophils and CD3+ lymphocytes were identified directly from 50 μL of whole blood of EoE and control subjects. Using Hi‐FACS, levels of surface activation markers, including CD66b, and intracellular phosphoepitopes, including phosphorylated forms of signal transducer and activator of transcription (phospho‐STAT) 1 and 6, were measured within each cell subset.

Results:

Levels of surface CD66b as well as levels of intracellular phospho‐STAT1 and phospho‐STAT6 in peripheral blood eosinophils were significantly higher for untreated subjects with EoE vs healthy controls (P < 0.05). Levels of phospho‐STAT1 and phospho‐STAT6 in peripheral blood eosinophils were lower in subjects with EoE on therapy versus untreated subjects with EoE (P < 0.05).

Conclusions:

Levels of phospho‐STAT1 and phospho‐STAT6, transcription factors involved in inflammatory processes, were both significantly higher in peripheral eosinophils from untreated (ie, newly diagnosed) subjects with EoE versus subjects with EoE on therapy, healthy controls. Blood‐based measurements of CD66b and phospho‐STAT levels in peripheral eosinophils may be beneficial for identifying EoE.
Oral Choline Supplementation in Children With Intestinal Failure
Authors: Guerrerio Anthony L , Mattis Lynn , Conner Kim G , Hampsey Jenifer , Stasinopoulos D Mikis , DeJong Robert , Boctor Emad M , Sheth Shelia , Hamper Ulrike M , Scheimann Ann O
Published: June 2011

Choline deficiency leads to steatohepatitis, elevated transaminases, susceptibility to septic shock, and an increased risk of central catheter thrombosis. Children with intestinal failure (IF) are at risk for choline deficiency. In an unblinded, open‐label study, we studied 7 children with IF on parenteral nutrition, measured their plasma free choline level, and, if low, supplemented enterally with adequate intake (AI) doses of choline. Four to 6 weeks later we remeasured their plasma free choline. Unlike adults, infants did not respond to oral choline supplementation at AI doses. Additionally, we have calculated plasma free choline percentiles versus age for normal children.
Use of Deamidated Gliadin Peptide Antibodies to Monitor Diet Compliance in Childhood Celiac Disease
Authors: Monzani Alice , Rapa Anna , Fonio Paola , Tognato Eleonora , Panigati Laura , Oderda Giuseppina
Published: June 2011

Objective:

The aim of this study was to evaluate performance of serum antibodies against deamidated gliadin peptides (a‐DGPs) in detecting compliance with gluten‐free diet (GFD) in children with celiac disease (CD).

Patients and Methods:

Serum samples were collected the same day of endoscopy in 95 children with CD and 106 controls. We preliminarily calculated the cutoff of a‐DGP immunoglobulin A (IgA) and a‐DGP IgA+G in our population by receiver operating characteristic (ROC) curves. Of 95 children with CD, 28 were studied during the first year after GFD introduction, with interview and serum collection every 3 months. In addition, serum samples were collected in 106 children with CD on GFD for more than 1 year (range 1–14). In both groups of children with CD on GFD, we compared a‐DGP IgA and IgA+G performance in monitoring compliance with GFD with anti‐tissue transglutaminase antibodies (anti‐tTG) IgA and anti‐gliadin antibody (AGA) IgA.

Results:

The cutoff resulted in 13.1 arbitrary units (AU) for a‐DGP IgA (sensitivity 87.4, 95% confidence interval [CI] 79%–92%, specificity 97.2, 95% CI 92%–99%) and 16.5 for a‐DGP IgA+G (sensitivity 94.7, 95% CI 88%–98%, specificity 89.6, 95% CI 84%–95%). In the first year of GFD, at 6 to 8 months prevalence of positive a‐DGPs was significantly higher in partially versus strictly compliant children, and at 9 to 12 months only prevalence of positive a‐DGP IgA+G remained significantly higher. Moreover, at 9 to 12 months sensitivity to detect transgressions to GFD was 44% for a‐DGP IgA and 100% for a‐DGP IgA+G (P = 0.03). In the 106 children on GFD for more than 1 year, sensitivity to detect transgressions to GFD was 60% for a‐DGP IgA and 76% for a‐DGP IgA+G. Anti‐tTG IgA and AGA IgA sensitivity was much lower (24% and 4%, respectively). The 4 tests showed comparable high specificity.

Conclusions:

Both a‐DGPs showed higher sensitivity than anti‐tTG IgA and AGA IgA in monitoring compliance with GFD, but a‐DGP IgA+G seemed to perform better. a‐DGPs did not outperform anti‐tTG IgA for CD screening.
Vitamin D Supplementation and Status in Infants: A Prospective Cohort Observational Study
Authors: Pludowski Pawel , Socha Piotr , Karczmarewicz Elzbieta , Zagorecka Ewa , Lukaszkiewicz Jacek , Stolarczyk Anna , Piotrowska‐Jastrzebska Janina , Kryskiewicz Edyta , Lorenc Roman S , Socha Jerzy
Published: June 2011

Objective:

Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants.

Patients and Methods:

One hundred thirty‐four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25‐hydroxyvitamin D (25‐OHD) serum concentration at the 6th and 12th months were assessed.

Results:

Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25‐OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25‐OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25‐OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25‐OHD concentration change between the 6th and the 12th months negatively correlated with the 25‐OHD level assessed at the 6th month (r = −0.82; P < 0.0001).

Conclusions:

Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.
Skeletal Health of Children and Adolescents With Inflammatory Bowel Disease
Authors: Pappa Helen , Thayu Meena , Sylvester Francisco , Leonard Mary , Zemel Babette , Gordon Catherine
Published: June 2011

Current evidence points to suboptimal bone health in children and adolescents with inflammatory bowel disease (IBD) when compared with their healthy peers. This compromise is evident from diagnosis. The clinical consequences and long‐term outcome of this finding are still unknown. The mechanism of suboptimal bone health in children and adolescents with IBD lays mainly in reduced bone formation, but also reduced bone resorption, processes necessary for bone growth. Factors contributing to this derangement are inflammation, delayed growth and puberty, lean mass deficits, and use of glucocorticoids. We recognize that evidence is sparse on the topic of bone health in children and adolescents with IBD. In this clinical guideline, based on current evidence, we provide recommendations on screening and monitoring bone health in children and adolescents with IBD, including modalities to achieve this and their limitations; monitoring of parameters of growth, pubertal development, and reasons for concern; evaluation of vitamin D status and vitamin D and calcium intake; exercise; and nutritional support. We also report on the current evidence of the effect of biologics on bone health in children and adolescents with IBD, as well as the role of bone active medications such as bisphosphonates. Finally, we summarize the existing numerous gaps in knowledge and potential subjects for future research endeavors.
First spinosaurid dinosaur from Australia and the cosmopolitanism of Cretaceous dinosaur faunas
Authors: Barrett Paul M. , Benson Roger B. J. , Rich Thomas H. , Vickers-Rich Patricia
Published: June 2011

A cervical vertebra from the Early Cretaceous of Victoria represents the first Australian spinosaurid theropod dinosaur. This discovery significantly extends the geographical range of spinosaurids, suggesting that the clade obtained a near-global distribution before the onset of Pangaean fragmentation. The combined presence of spinosaurid, neovenatorid, tyrannosauroid and dromaeosaurid theropods in the Australian Cretaceous undermines previous suggestions that the dinosaur fauna of this region was either largely endemic or predominantly ‘Gondwanan’ in composition. Many lineages are well-represented in both Laurasia and Gondwana, and these observations suggest that Early–‘middle’ Cretaceous theropod clades possessed more cosmopolitan distributions than assumed previously, and that caution is necessary when attempting to establish palaeobiogeographic patterns on the basis of a patchily distributed fossil record.