bluuebunny/crossref_metadata_2025 huggingface dataset:
Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke
Authors: Chen Zu-Lin , Yao Yao , Norris Erin H. , Kruyer Anna , Jno-Charles Odella , Akhmerov Akbarshakh , Strickland Sidney
Published: July 2013

Astrocytes express laminin and assemble basement membranes (BMs) at their endfeet, which ensheath the cerebrovasculature. The function of astrocytic laminin in cerebrovascular integrity is unknown. We show that ablation of astrocytic laminin by tissue-specific Cre-mediated recombination disrupted endfeet BMs and led to hemorrhage in deep brain regions of adult mice, resembling human hypertensive hemorrhage. The lack of astrocytic laminin led to impaired function of vascular smooth muscle cells (VSMCs), where astrocytes have a closer association with VSMCs in small arterioles, and was associated with hemorrhagic vessels, which exhibited VSMC fragmentation and vascular wall disassembly. Acute disruption of astrocytic laminin in the striatum of adult mice also impaired VSMC function, indicating that laminin is necessary for VSMC maintenance. In vitro, both astrocytes and astrocytic laminin promoted brain VSMC differentiation. These results show that astrocytes regulate VSMCs and vascular integrity in small vessels of deep brain regions. Therefore, astrocytes may be a possible target for hemorrhagic stroke prevention and therapy.
Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I
Authors: Davydenko Olga , Schultz Richard M. , Lampson Michael A.
Published: July 2013

Chromosome segregation during cell division depends on stable attachment of kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore–microtubule (K-MT) capture typically occur within minutes of nuclear envelope breakdown. In contrast, during meiosis I in mouse oocytes, formation of the acentrosomal bipolar spindle takes 3–4 h, and stabilization of K-MT attachments is delayed an additional 3–4 h. The mechanism responsible for this delay, which likely prevents stabilization of erroneous attachments during spindle formation, is unknown. Here we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I. Partial reduction of CDK1 activity delayed formation of stable attachments, whereas a premature increase in CDK1 activity led to precocious formation of stable attachments and eventually lagging chromosomes at anaphase I. These results indicate that the slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable K-MT attachments only after bipolar spindle formation, thus preventing attachment errors.
Syntaphilin puts the brakes on axonal mitochondria
Authors: Short Ben
Published: July 2013

Study reveals how an axonal mitochondrial protein arrests the organelles at active synapses.
Assessing association between protein truncating variants and quantitative traits
Authors: Rivas Manuel A. , Pirinen Matti , Neville Matthew J. , Gaulton Kyle J. , Moutsianas Loukas , Lindgren Cecilia M. , Karpe Fredrik , McCarthy Mark I. , Donnelly Peter
Published: July 2013

Motivation: In sequencing studies of common diseases and quantitative traits, power to test rare and low frequency variants individually is weak. To improve power, a common approach is to combine statistical evidence from several genetic variants in a region. Major challenges are how to do the combining and which statistical framework to use.

General approaches for testing association between rare variants and quantitative traits include aggregating genotypes and trait values, referred to as ‘collapsing’, or using a score-based variance component test. However, little attention has been paid to alternative models tailored for protein truncating variants. Recent studies have highlighted the important role that protein truncating variants, commonly referred to as ‘loss of function’ variants, may have on disease susceptibility and quantitative levels of biomarkers. We propose a Bayesian modelling framework for the analysis of protein truncating variants and quantitative traits.

Results: Our simulation results show that our models have an advantage over the commonly used methods. We apply our models to sequence and exome-array data and discover strong evidence of association between low plasma triglyceride levels and protein truncating variants at APOC3 (Apolipoprotein C3).

Availability: Software is available from http://www.well.ox.ac.uk/~rivas/mamba

Contact:  donnelly@well.ox.ac.uk
Identification of Species of Botryosphaeriaceae Causing Bot Gummosis in Citrus in California
Authors: Adesemoye A. O. , Mayorquin J. S. , Wang D. H. , Twizeyimana M. , Lynch S. C. , Eskalen A.
Published: July 2013

Members of the Botryosphaeriaceae family are known to cause Bot gummosis on many woody plants worldwide. To identify pathogens associated with Bot gummosis on citrus in California, scion and rootstock samples were collected in 2010 and 2011 from five citrus-growing counties in California. Symptoms observed on citrus included branch cankers, dieback, and gumming. Various fungal species were recovered from necrotic tissues of branch canker and rootstock samples. Species were identified morphologically and by phylogenetic comparison as ‘Eureka’ lemon, ‘Valencia’, ‘Washington Navel’, ‘Fukumoto’, grapefruit, ‘Satsuma’, and ‘Meyer’ lemon. Species were identified morphologically and by phylogenetic comparison of the complete sequence of the internal transcribed spacer regions, β-tubulin gene, and elongation factor α-1 genes with those of other species in GenBank. A consensus-unrooted most parsimonious tree resulting from multigene phylogenetic analysis showed the existence of three major clades in the Botryosphaeriaceae family. In total, 74 isolates were identified belonging to the Botryosphaeriaceae family, with Neofusicoccum spp., Dothiorella spp., Diplodia spp., (teleomorph Botryosphaeria), Lasiodiplodia spp., and Neoscytalidium dimidiatum (teleomorphs unknown) accounting for 39, 25, 23, 10, and 3% of the total, respectively. On inoculated Eureka lemon shoots, lesion length was significantly different (P < 0.05) among 14 isolates recovered from portions of cankered tissues of the original trees. Lesion lengths were significantly longer (P < 0.05) for shoots inoculated with isolates of Neofusicoccum luteum and shorter for shoots inoculated with isolates of Dothiorella viticola (P < 0.05) than those of other species. Identifying the distribution and occurrence of these fungal pathogens associated with Bot gummosis is useful for management applications during occasional outbreaks in California.
First Report of Iris yellow spot virus Infecting Green Onion in Indonesia
Authors: Pappu H. R. , Rauf A.
Published: July 2013

Green onion (Allium fistulosum L.) is an important vegetable crop for small-holder farmers for domestic consumption in Indonesia. Iris yellow spot virus (IYSV; family Bunyaviridae, genus Tospovirus) transmitted by Thrips tabaci is an economically important viral pathogen of bulb and seed onion crops in many onion-growing areas of the world (1,3). In Asia, IYSV has been reported in India and Sri Lanka (2,4). In April 2013, symptoms suspected to be caused by IYSV were observed on a 1-month-old green onion crop grown for their leaves in a farmer's field in Cipendawa, Pacet, Cianjur District, West Java. Symptoms consisted of elliptical to spindle-shaped, straw colored, irregular, chlorotic lesions with occasional green islands on the leaves. Approximately 25% of the field had plants with these symptoms. The presence of the virus was confirmed with an IYSV-specific Agdia Flash kit. IYSV infection was confirmed by RT-PCR with primers specific to the nucleoprotein (N) gene of IYSV. Primers 465c: 5′-AGCAAAGTGAGAGGACCACC-3′ and IYSV-239f: 5′ TGAGCCCCAATCAAGACG3′ (3) were used as forward and reverse primers, respectively, using total nucleic acids eluted from FTA cards that were previously coated with freshly prepared sap extracts from field samples. Amplicons of approximately 240 bp were obtained from four symptomatic plants tested but not from healthy and water controls. The amplicons were cloned and sequenced. Consensus sequence was derived from three clones. Comparison with IYSV N gene sequences available in GenBank showed sequence identity of 95 to 99% confirming the identity of the virus as IYSV. To our knowledge, this is the first report of IYSV infecting onion in Indonesia. The finding in Java underscores the need for conducting surveys in Java as well as other onion-growing regions of Indonesia to gain a better understanding of its incidence, distribution, and potential impact.

References: (1) D. H. Gent et al. Plant Dis. 88:446, 2004. (2) B. Mandal et al. Plant Dis. 96:468, 2012. (3) H. R. Pappu et al. Virus Res. 141:219, 2009. (4) K. S. Ravi et al. Plant Pathol. 55:288, 2006.
Infection of Sweetpotato by Fusarium solani and Macrophomina phaseolina Prior to Harvest
Authors: da Silva Washington L. , Clark Christopher A.
Published: July 2013

The end rot disease complex, caused mainly by Fusarium solani and Macrophomina phaseolina, can be an important postharvest problem in sweetpotato. The disease develops a few weeks after storage roots are harvested and stored. Isolations attempted after harvest showed that the pathogens can be present inside the storage roots before symptoms appear. To determine how and when end rot pathogens enter sweetpotato storage roots, two greenhouse experiments were designed using tissue culture-derived plants free of F. solani and M. phaseolina. In one experiment, plants were grown in autoclaved soil, and 1 month after transplanting, plants were inoculated at the soil line with either noninfested toothpicks or toothpicks infested with each fungus alone or combined. In the other experiment, plants were grown in noninfested soil or in soil infested with each fungus alone or combined. F. solani and M. phaseolina were isolated from roots, storage roots, and plant stems below the soil line, at the soil line, and 5 cm above the soil line in both experiments. This suggests these fungi are capable of invading sweetpotato plants and storage roots from infested soil, and can systemically colonize the plant from infected plant propagation material.
First Report of Fire Blight Caused by Erwinia amylovora on Pear in Tunisia
Authors: Rhouma A. , Helali F. , Chettaoui M. , Hajjouji M. , Hajlaoui M. R.
Published: July 2013

In the spring of 2012 and 2013, symptoms similar to those of fire blight were observed on pear trees (Pyrus communis cv. Alexandrine, Williams) in Tunisia at flowering stages. Disease symptoms appeared in 2012 in the region of Mornag and in the following year extended to the regions of Manouba and Tebourba. More recently, the disease was observed in the regions of Bizerte, Zaghouan, and Beja. The percentages of orchard areas that had infected plants varied from 10 to 40%. Some orchards in Mornag region exhibited more than 75% disease incidence. Symptoms were observed on flowers and young shoots. Blighted blossoms appeared wilted, shriveled, and brown, and dead flowers remained on the stems. Infected shoots wilted rapidly and often formed shepherd's crooks at their tips. Samples of diseased young shoots and flowers were subjected to pathogen isolation and identification. Bacteria were isolated from washed tissues on King's B medium (KB) (1). Colonies with morphology similar to that of Erwinia amylovora were purified by sub-culturing on KB. The strains were first characterized based on morphology and biochemical tests (1). Sixteen strains produced white colonies on KB, were gram-negative, did not produce a fluorescent pigment on KB, did not grow at 35°C, and induced a hypersensitive reaction when infiltrated into tobacco leaves (cv. Xanthi). These strains were identified as E. amylovora by double-antibody sandwich indirect-ELISA and immunofluorescene microscopy using a polyclonal antibody (2) and nested PCR targeting the pEA29 plasmid (3). Pathogenicity was tested using a detached-fruit assay (1). Each strain was inoculated onto three pear fruit (cv. Alexandrine) wounded with a scalpel dipped in a 109 CFU/ml bacterial suspension. The inoculated fruit were incubated at 25°C and 80% relative humidity in plates with sterile 1% agar. Negative controls consisted of fruit wounded with a scalpel dipped in sterile distilled water. Seven days after inoculation, symptoms of discoloration, browning, and production of bacterial ooze appeared at the inoculated points. No symptoms developed on negative controls. Reisolation of bacteria yielded colonies with characteristics of E. amylovora. Purified amplicons from nested PCR were sequenced (KF302525, KF302526) and a BLAST search of the GenBank database revealed 98% homology with E. amylovora strain HF560643.1.

References: (1) Anonymous. OEPP/EPPO Bull. 34:159, 2004. (2) M. T. Gorris et al. Acta Hortic. 411:41, 1996. (3) P. Llop et al. Appl. Environ. Microbiol. 66:2071, 2000.
Graduate Medical Education in Humanism and Professionalism
Authors: Garvey Katharine C. , Kesselheim Jennifer C. , Herrick Daniel B. , Woolf Alan D. , Leichtner Alan M.
Published: July 2013

The deterioration of humanism and professionalism during graduate medical training is an acknowledged concern, and programs are required to provide professionalism education for pediatric fellows. We conducted a needs assessment survey in a national sample of 138 first‐ and second‐year gastroenterology fellows (82% response rate). Most believed that present humanism and professionalism education met their needs, but this education was largely informal (eg, role modeling). Areas for formal education desired by >70% included competing demands of clinical practice versus research, difficult doctor–patient relationships, depression/burnout, angry parents, medical errors, work–life balance, and the patient illness experience. These results may guide curricula to formalize humanism and professionalism education in pediatric gastroenterology fellowships.
Androgenesis is a maternal trait in the invasive antWasmannia auropunctata
Authors: Rey Olivier , Facon Benoît , Foucaud Julien , Loiseau Anne , Estoup Arnaud
Published: July 2013

Androgenesis is the production of an offspring containing exclusively the nuclear genome of the fathering male via the maternal eggs. This unusual mating system is generally considered a male trait, giving to androgenetic males a substantial fitness advantage over their sexually reproducing relatives. We here provide the first empirical study of the evolutionary outcomes of androgenesis in a haplo-diploid organism: the invasive antWasmannia auropunctata. Some of the populations of this species have a classical haplo-diploid sexual mating system. In other populations, females and males are produced through parthenogenesis and androgenesis, respectively, whereas workers are produced sexually. We conducted laboratory reciprocal-cross experiments with reproductive individuals from both types of populations and analysed their progenies with genetic markers, to determine the respective contribution of males and females to the production of androgenetic males. We found that androgenesis was a parthenogenetic female trait. A population genetic study conductedin naturaconfirmed the parthenogenetic female origin of androgenesis, with the identification of introgression events of sexual male genotypes into androgenetic/parthenogenetic lineages. We argue that by producing males via androgenesis, parthenogenetic queen lineages may increase and/or maintain their adaptive potential, while maintaining the integrity of their own genome, by occasionally acquiring new male genetic material and avoiding inbreeding depression within the sexually produced worker cast.
Application of directed transfer function and network formalism for the assessment of functional connectivity in working memory task
Authors: Blinowska Katarzyna J. , Kamiński Maciej , Brzezicka Aneta , Kamiński Jan
Published: July 2013

The dynamic pattern of functional connectivity during a working memory task was investigated by means of the short-time directed transfer function. A clear-cut picture of transmissions was observed with the main centres of propagation located in the frontal and parietal regions, in agreement with imaging studies and neurophysiological hypotheses concerning the mechanisms of working memory. The study of the time evolution revealed that most of the time short-range interactions prevailed, whereas the communication between the main centres of activity occurred more sparsely and changed dynamically in time. The patterns of connectivity were quantified by means of a network formalism based on assortative mixing—an approach novel in the field of brain networks study. By means of application of the above method, we have demonstrated the existence of a modular structure of brain networks. The strength of interaction inside the modules was higher than between modules. The obtained results are compatible with theories concerning metabolic energy saving and efficient wiring in the brain, which showed that preferred organization includes modular structure with dense connectivity inside the modules and more sparse connections between the modules. The presented detailed temporal and spatial patterns of propagation are in line with the neurophysiological hypotheses concerning the role of gamma and theta activity in information processing during a working memory task.
Time-variant partial directed coherence for analysing connectivity: a methodological study
Authors: Leistritz L. , Pester B. , Doering A. , Schiecke K. , Babiloni F. , Astolfi L. , Witte H.
Published: July 2013

For the past decade, the detection and quantification of interactions within and between physiological networks has become a priority-in-common between the fields of biomedicine and computer science. Prominent examples are the interaction analysis of brain networks and of the cardiovascular–respiratory system. The aim of the study is to show how and to what extent results from time-variant partial directed coherence analysis are influenced by some basic estimator and data parameters. The impacts of the Kalman filter settings, the order of the autoregressive (AR) model, signal-to-noise ratios, filter procedures and volume conduction were investigated. These systematic investigations are based on data derived from simulated connectivity networks and were performed using a Kalman filter approach for the estimation of the time-variant multivariate AR model. Additionally, the influence of electrooculogram artefact rejection on the significance and dynamics of interactions in 29 channel electroencephalography recordings, derived from a photic driving experiment, is demonstrated. For artefact rejection, independent component analysis was used. The study provides rules to correctly apply particular methods that will aid users to achieve more reliable interpretations of the results.
Cardiovascular control and time domain Granger causality: insights from selective autonomic blockade
Authors: Porta Alberto , Castiglioni Paolo , Di Rienzo Marco , Bassani Tito , Bari Vlasta , Faes Luca , Nollo Giandomenico , Cividjan Andrei , Quintin Luc
Published: July 2013

We studied causal relations among heart period (HP), systolic arterial pressure (SAP) and respiration (R) according to the definition of Granger causality in the time domain. Autonomic pharmacological challenges were used to alter the complexity of cardiovascular control. Atropine (AT), propranolol and clonidine (CL) were administered to block muscarinic receptors, β-adrenergic receptors and centrally sympathetic outflow, respectively. We found that: (i) at baseline, HP and SAP interacted in a closed loop with a dominant causal direction from HP to SAP; (ii) pharmacological blockades did not alter the bidirectional closed-loop interactions between HP and SAP, but AT reduced the dominance of the causal direction from HP to SAP; (iii) at baseline, bidirectional interactions between HP and R were frequently found; (iv) the closed-loop relation between HP and R was unmodified by the administration of drugs; (v) at baseline, unidirectional interactions from R to SAP were often found; and (vi) while AT induced frequently an uncoupling between R and SAP, CL favoured bidirectional interactions. These results prove that time domain measures of Granger causality can contribute to the description of cardiovascular control by suggesting the temporal direction of the interactions and by separating different causality schemes (e.g. closed loop versus unidirectional relations).
Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins
Authors: Mesner Larry D. , Valsakumar Veena , Cieślik Marcin , Pickin Rebecca , Hamlin Joyce L. , Bekiranov Stefan
Published: July 2013

We have devised a method for isolating virtually pure and comprehensive libraries of restriction fragments that contained replication initiation sites (bubbles) in vivo. We have now sequenced and mapped the bubble-containing fragments from GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have compared origin distributions with a comprehensive replication timing study recently published for this cell line. We find that early-firing origins, which represent ∼32% of all origins, overwhelmingly represent zones, associate only marginally with active transcription units, are localized within large domains of open chromatin, and are significantly associated with DNase I hypersensitivity. Origin “density” falls from early- to mid-S-phase, but rises again in late S-phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin density calculated on the 1-Mb scale increases as a function of increasing chromatin compaction. Furthermore, the median efficiency of origins in late-replicating, heterochromatic domains is only 25% lower than in early-replicating euchromatic loci. Thus, the activation of early- and late-firing origins must be regulated by quintessentially different mechanisms. The aggregate data can be unified into a model in which initiation site selection is driven almost entirely by epigenetic factors that fashion both the long-range and local chromatin environments, with underlying DNA sequence and local transcriptional activity playing only minor roles. Importantly, the comprehensive origin map we have prepared for GM06990 overlaps moderately well with origin maps recently reported for the genomes of four different human cell lines based on the distributions of small nascent strands.
Spatio‐temporal dynamics in the response of woodland caribou and moose to the passage of grey wolf
Authors: Latombe Guillaume , Fortin Daniel , Parrott Lael
Published: July 2013

Predators impact prey populations not only by consuming individuals, but also by altering their behaviours. These nonlethal effects can influence food web properties as much as lethal effects. The mechanisms of nonlethal effects include chronic and temporary anti‐predator behaviours, the nature of which depends on the spatial dynamics of predators and the range over which prey perceive risk.

The relation between chronic and ephemeral responses to risk determines predator–prey interactions, with consequences that can ripple across the food web. Nonetheless, few studies have quantified the spatio‐temporal scales over which prey respond to predation threat, and how this response varies with habitat features.

We evaluated the reaction of radio‐collared caribou and moose to the passage of radio‐collared wolves, by considering changes in movement characteristics during winter and summer. We used an optimization algorithm to identify the rate at which the impact of prior passage of wolves decreases over time and with the predator's distance.

The spatial and temporal scales of anti‐predator responses varied with prey species and season. Caribou and moose displayed four types of behaviour following the passage of wolves: lack of response, increased selection of safe land cover types, decreased selection of risky cover types and increased selection of food‐rich forest stands. For example, moose increased their avoidance of open conifer stands with lichen in summer, which are selected by wolves in this season. Also in winter, caribou increased their selection of conifer stands with lichen for nearly 10 days following a wolf's passage. This stronger selection for food‐rich patches could indicate that the recent passage of wolves informs caribou on the current predator distribution and reveals the rate at which this information become less reliable over time.

Caribou and moose used anti‐predator responses that combine both long‐ and short‐term behavioural adjustments. The spatial game between wolves and their prey involves complex and nonlinear mechanisms that vary between species and seasons. A comprehensive assessment of risk effects on ecosystem dynamics thus requires the characterization of chronic and temporary anti‐predator behaviours.
The tail‐associated depolymerase of Erwinia amylovora phage L1 mediates host cell adsorption and enzymatic capsule removal, which can enhance infection by other phage
Authors: Born Yannick , Fieseler Lars , Klumpp Jochen , Eugster Marcel R. , Zurfluh Katrin , Duffy Brion , Loessner Martin J.
Published: July 2013

The depolymerase enzyme (DpoL1) encoded by the T7‐like phage L1 efficiently degrades amylovoran, an important virulence factor and major component of the extracellular polysaccharide (EPS) of its host, the plant pathogen Erwinia amylovora. Mass spectrometry analysis of hydrolysed EPS revealed that DpoL1 cleaves the galactose‐containing backbone of amylovoran. The enzyme is most active at pH 6 and 50°C, and features a modular architecture. Removal of 180 N‐terminal amino acids was shown not to affect enzyme activity. The C‐terminus harbours the hydrolase activity, while the N‐terminal domain links the enzyme to the phage particle. Electron microscopy demonstrated that DpoL1‐specific antibodies cross‐link phage particles at their tails, either lateral or frontal, and immunogold staining confirmed that DpoL1 is located at the tail spikes. Exposure of high‐level EPS‐producing Er. amylovora strain CFBP1430 to recombinant DpoL1 dramatically increased sensitivity to the Dpo‐negative phage Y2, which was not the case for EPS‐negative mutants or low‐level EPS‐producing Er. amylovora. Our findings indicate that enhanced phage susceptibility is based on enzymatic removal of the EPS capsule, normally a physical barrier to Y2 infection, and that use of DpoL1 together with the broad host range, virulent phage Y2 represents an attractive combination for biocontrol of fire blight.
A component analysis of a brief psycho‐educational couples' workshop: one‐year follow‐up results
Authors: Babcock Julia C. , Gottman John M. , Ryan Kimberly D. , Gottman Julie S.
Published: July 2013

This study tested moderators of treatment outcome of the ‘Art and Science of Love (ASL) Workshop’, a couples' group psycho‐educational intervention with 80 distressed married couples. Couples were randomly assigned to one of four conditions: (1) friendship enhancement alone, (2) conflict management alone, (3) combined friendship enhancement + conflict management or (4) bibliotherapy. Three outcomes were assessed: (1) relationship satisfaction, (2) friendship quality and (3) destructive conflict at pre‐, post‐ and one year following the intervention. All conditions led to increased marital satisfaction and decreased problems with friendship and destructive conflict at one‐year follow‐up. Examining exposure to the components of the ASL workshop in a 2×2 design – friendship enhancement (yes/no) vs. conflict management (yes/no) – revealed differential impact for men's and women's relationship outcomes over time. Results suggest that the combined condition produced the greatest changes in marital satisfaction and the greatest decreases in problems in friendship and conflict, particularly for men.

Practitioner points

A combination of friendship enhancement and conflict management is recommended to maximize outcomes.

Bibliotherapy alone may be effective for significantly distressed couples without co‐morbid problems.

Psycho‐education is recommended before a course of more intensive couple therapy.

Men and women have different needs and respond to particular aspects of the programme.

Women particularly value the component concerning how to deal with conflict constructively and require more than the friendship enhancement component of the programme.
The Impact of Fertility on Mothers' Labour Supply in Australia: Evidence from Exogenous Variation in Family Size
Authors: Moschion Julie
Published: July 2013

This paper estimates the impact of fertility on mothers' labour supply in Australia, using exogenous variation in family size generated by twin births and the gender mix of siblings. Results show that having more than one child decreases mothers' labour market participation by 12 percentage points and hours worked by around four hours per week. Having more than two children reduces labour market participation by 12 percentage points and hours worked by three hours a week. Compared with other countries, the effects for Australia are large.
State‐Level Unemployment and the Utilization of Preventive Medical Services
Authors: Tefft Nathan , Kageleiry Andrew
Published: July 2013

Objective

To study the association between macroeconomic conditions and preventive medical service utilization.

Data Sources/Study Setting

Secondary data collection of a survey of the civilian, non‐institutionalized population of adults (age 18 and older) in the United States between 1987 and 2010.

Study Design

Regression analyses that adjust for individual‐level demographic and socioeconomic determinants, state and time‐fixed effects, and state‐specific time trends.

Data Collection/Extraction Methods

State health departments, with technological and methodological assistance from the Centers for Disease Control and Prevention, conducted a cross‐sectional yearly telephone survey using a standardized questionnaire.

Principal Findings

The use of preventive medical services is procyclical: a 1 percentage point increase in the state‐level unemployment rate is associated with a 1.58 percent decrease in the quantity of distinct preventive care services utilized. Women and economically disadvantaged populations are shown to be especially sensitive to macroeconomic fluctuations.

Conclusions

Policy makers should be aware of cyclical changes in preventive care use, particularly among disadvantaged populations, when making challenging budgetary decisions during economic downturns. As physician recommendations can have a strong impact on patients' use, health care providers could increase efforts to persuade patients to seek screening exams and necessary vaccinations during periods of high unemployment.
Validation of Patient and Nurse Short Forms of the Readiness for Hospital Discharge Scale and Their Relationship to Return to the Hospital
Authors: Weiss Marianne E. , Costa Linda L. , Yakusheva Olga , Bobay Kathleen L.
Published: July 2013

Objective

To validate patient and nurse short forms for discharge readiness assessment and their associations with 30‐day readmissions and emergency department (ED) visits.

Data Sources/Study Setting

A total of 254 adult medical‐surgical patients and their discharging nurses from an Eastern US tertiary hospital between May and November, 2011.

Study Design

Prospective longitudinal design, multinomial logistic regression analysis.

Data Collection/Extraction Methods

Nurses and patients independently completed an eight‐item Readiness for Hospital Discharge Scale on the day of discharge. Patient characteristics, readmissions, and ED visits were electronically abstracted.

Principal Findings

Nurse assessment of low discharge readiness was associated with a six‐ to nine‐fold increase in readmission risk. Patient self‐assessment was not associated with readmission; neither was associated with ED visits.

Conclusions

Nurse discharge readiness assessment should be added to existing strategies for identifying readmission risk.
Adoption and Diffusion of Evidence‐Based Addiction Medications in Substance Abuse Treatment
Authors: Heinrich Carolyn J. , Cummings Grant R.
Published: July 2013

Objective

To examine the roles of facility‐ and state‐level factors in treatment facilities' adoption and diffusion of pharmaceutical agents used in addiction treatment.

Data Sources

Secondary data from the National Survey of Substance Abuse Treatment Services (N‐SSATS), Substance Abuse and Mental Health Services Administration (SAMHSA), Centers for Medicare and Medicaid Services, Alcohol Policy Information System, and Kaiser Family Foundation.

Study Design

We estimate ordered logit and multinomial logit models to examine the relationship of state and treatment facility characteristics to the adoption and diffusion of three pharmaceutical agents over 4 years when each was at a different stage of adoption or diffusion.

Data Collection

N‐SSATS data with facility codes, obtained directly from SAMHSA, were linked by state identifiers to the other publicly available, secondary data.

Principal Findings

The analysis confirms the importance of awareness and exposure to the adoption behavior of others, dissemination of information about the feasibility and effectiveness of innovations, geographical clustering, and licensing and accreditation in legitimizing facilities' adoption and continued use of pharmacotherapies in addiction treatment.

Conclusions

Policy and administrative levers exist to increase the availability of pharmaceutical technologies and their continued use by substance abuse treatment facilities.
Assessing Racial/Ethnic Disparities in Treatment across Episodes of Mental Health Care
Authors: Cook Benjamin Lê , Zuvekas Samuel H. , Carson Nicholas , Wayne Geoffrey Ferris , Vesper Andrew , McGuire Thomas G.
Published: July 2013

Objective

To investigate disparities in mental health care episodes, aligning our analyses with decisions to start or drop treatment, and choices made during treatment.

Study Design

We analyzed whites, blacks, and Latinos with probable mental illness from Panels 9–13 of the Medical Expenditure Panel Survey, assessing disparities at the beginning, middle, and end of episodes of care (initiation, adequate care, having an episode with only psychotropic drug fills, intensity of care, the mixture of primary care provider (PCP) and specialist visits, use of acute psychiatric care, and termination).

Findings

Compared with whites, blacks and Latinos had less initiation and adequacy of care. Black and Latino episodes were shorter and had fewer psychotropic drug fills. Black episodes had a greater proportion of specialist visits and Latino episodes had a greater proportion of PCP visits. Blacks were more likely to have an episode with acute psychiatric care.

Conclusions

Disparities in adequate care were driven by initiation disparities, reinforcing the need for policies that improve access. Many episodes were characterized only by psychotropic drug fills, suggesting inadequate medication guidance. Blacks' higher rate of specialist use contradicts previous studies and deserves future investigation. Blacks' greater acute mental health care use raises concerns over monitoring of their treatment.
Relative toxicity of different combinations of temephos and fenthion with Solanum xanthocarpum extract against anopheline larvae
Authors: Mohan Lalit , Sharma Preeti , Shrankhla  , Srivastava Chand Narayan
Published: July 2013

The relative toxicity of different concentrations of temephos and fenthion with petroleum ether root extract of Solanum xanthocarpum (Schrader) at 1 : 1, 1 : 2 and 1 : 4 ratios was evaluated against Anopheles stephensi (Liston) larvae. All combinations exhibited antagonism at concentrations lower than LC50 values and synergism at concentrations higher than their LC90 values. A 1 : 1 product ratio was the most effective.
Microsatellite variation in colonizing populations of yellow‐leggedAsian hornet,Vespa velutina nigrithorax, inSouthKorea
Authors: Choi Moon Bo , Lee Sihn‐Ae , Suk Ho Young , Lee Jong Wook
Published: July 2013

Introduction of exotic species poses a tremendous challenge to the preservation of original biodiversity and productivity in natural ecosystems. The yellow‐leggedAsian hornetVespa velutina nigrithorax, which is native to tropical/subtropical areas in Indo‐China, was identified in 2003 for the first time inSouthKorea and has established itself in a short period of time. Population genetic study of invasive species may provide exceptional opportunities to test evolutionary theory as well as patterns of colonization from the beginning of the process. Here, the genetic variability of this invasive hornet was examined using seven microsatellites to estimate the propagule pressure and to expect the spreading pathway of this invasive hornet across its range. Overall, there was a significant loss of genetic diversity in its invaded ranges compared to its native range, suggesting that this invasive hornet was introduced via a very small number of propagules. Our results also support that this invasive hornet has experienced a severe bottleneck, as a large reduction was mainly observed in the number of alleles but not in heterozygosity. No significant genetic structuring among populations was found. This study provides baseline information about the current demographic status of the invaded populations, which will help governing agencies prevent further invasions and manage native ecosystems.
Transcriptome sequencing of sea cucumber (Apostichopus japonicus) and the identification of gene‐associated markers
Authors: Zhou Z. C. , Dong Y. , Sun H. J. , Yang A. F. , Chen Z. , Gao S. , Jiang J. W. , Guan X. Y. , Jiang B. , Wang B.
Published: July 2013

Sea cucumber (Apostichopus japonicus) is an ecologically and economically important species in East and South‐East Asia. This project aimed to identify large numbers of gene‐associated markers and differentially expressed genes (DEGs) after lipopolysaccharides (LPS) challenge in A. japonicus using high‐throughput transcriptome sequencing. A total of 162 million high‐quality reads of 174 million raw reads were obtained by deep sequencing using Illumina HiSeq™ 2000 platform. Assembly of these reads generated 94 704 unigenes, with read length ranging from 200 to 16 153 bp (average length of 810 bp). A total of 36 005 were identified as coding sequences (CDSs), 32 479 of which were successfully annotated. Based on the assembly transcriptome, we identified 142 511 high‐quality single nucleotide polymorphisms (SNPs). Among them, 33 775, 63 120 and 45 616 were located in sequences without predicted CDS (non‐CDSs), CDSs and untranslated regions (UTRs), respectively. These putative SNPs included 82 664 transitions and 59 847 transversions. Totally, 89 375 (59.1%) were distributed in 15 473 known genes. A total of 6417 microsatellites were detected in 5970 unigenes, 3216 of which were annotated and 2481 were successfully subjected for primer design. The numbers of simple sequence repeats (SSRs) identified in non‐CDSs, CDSs and UTRs were 2367, 2316 and 1734. These potential SNPs and SSRs are expected to provide abundant resources for genetic, evolutionary and ecological studies in sea cucumber. Transcriptome comparison revealed 1330, 1347 and 1291 DEGs in the coelomocytes of A. japonicus at 4 h, 24 h and 72 h after LPS challenge, respectively. Approximately 58.4% (1802) of total DEGs have been successfully annotated.
Plant flavonoids target Pseudomonas syringae pv. tomato DC3000 flagella and type III secretion system
Authors: Vargas Paola , Farias Gabriela A. , Nogales Joaquina , Prada Harold , Carvajal Vivian , Barón Matilde , Rivilla Rafael , Martín Marta , Olmedilla Adela , Gallegos María‐Trinidad
Published: July 2013

Flavonoids are among the most abundant plant secondary metabolites involved in plant protection against pathogens, but micro‐organisms have developed resistance mechanisms to those compounds. We previously demonstrated that the MexAB‐OprM efflux pump mediates resistance of Pseudomonas syringae pv. tomato (Pto) DC3000 to flavonoids, facilitating its survival and the colonization of the host. Here, we have shown that tomato plants respond to Pto infection producing flavonoids and other phenolic compounds. The effects of flavonoids on key traits of this model plant‐pathogen bacterium have also been investigated observing that they reduce Pto swimming and swarming because of the loss of flagella, and also inhibited the expression and assembly of a functional type III secretion system. Those effects were more severe in a mutant lacking the MexAB‐OprM pump. Our results suggest that flavonoids inhibit the function of the GacS/GacA two‐component system, causing a depletion of rsmY RNA, therefore affecting the synthesis of two important virulence factors in Pto DC3000, flagella and the type III secretion system. These data provide new insights into the flavonoid role in the molecular dialog between host and pathogen.
The Future We Get Might Not Be the Future We Want: Analyzing the Rio+20 Outcomes
Authors: Pattberg Philipp , Mert Ayşem
Published: July 2013

The Rio+20 Summit resulted in a policy outcome that, according to most observers, did not meet the requirements for a deep transformation of the current unsustainable practices that contribute to global environmental change. In light of this assessment, scholars and practitioners have questioned the effectiveness of intergovernmental conferences to solve environmental problems and suggested alternatives, including voluntary commitments, public–private partnerships and bottom‐up approaches. This survey article analyzes the Rio+20 outcomes and argues that, while the overtly high expectations of the public, media, NGOs and scientists have not been met, the concrete results might include the seeds for a substantive transformation of current unsustainable practices. In this context, this article also urges leaders not to abandon international agreements for governing global change prematurely.
Institutional vertebratism hampers insect conservation generally; not just saproxylic beetle conservation
Authors: Leather S. R.
Published: July 2013

Read the Feature Paper: Protected areas and insect conservation: questioning the effectiveness of Natura 2000 network for saproxylic beetles in Italy

Other Commentaries on this paper: Knowledge gaps in protected area effectiveness

Response from the authors: Possible directions in the protection of the neglected invertebrate biodiversity
Role of the eIF4E binding protein 4E‐BP1 in regulation of the sensitivity of human pancreatic cancer cells to TRAIL and celastrol‐induced apoptosis
Authors: Chakravarthy Reka , Clemens Michael J. , Pirianov Grisha , Perdios Nectarios , Mudan Satvinder , Cartwright Judith E. , Elia Androulla
Published: July 2013

Background Information

Tumour cells can be induced to undergo apoptosis after treatment with the tumour necrosis factor α‐related death‐inducing ligand (TRAIL). Although human pancreatic cancer cells show varying degrees of response they can be sensitised to the pro‐apoptotic effects of TRAIL in the presence of celastrol, a natural compound extracted from the plant Tripterygium wilfordii Hook F. One important aspect of the cellular response to TRAIL is the control of protein synthesis, a key regulator of which is the eukaryotic initiation factor 4E‐binding protein, 4E‐BP1.

Results

We examined the effects of celastrol and TRAIL in several pancreatic cancer cell lines. In cells that are normally resistant to TRAIL, synergistic effects of TRAIL plus celastrol on commitment to apoptosis and inhibition of protein synthesis were observed. These were associated with a strong up‐regulation and dephosphorylation of 4E‐BP1. The enhancement of 4E‐BP1 expression, which correlated with a threefold increase in the level of the 4E‐BP1 transcript, was blocked by inhibitors of reactive oxygen species and the JNK protein kinase. When the expression of 4E‐BP1 was reduced by an inducible micro‐RNA, TRAIL‐mediated apoptosis was inhibited.

Conclusion

These results suggest that 4E‐BP1 plays a critical role in the mechanism by which TRAIL and celastrol together cause apoptotic cell death in human pancreatic tumour cells.
Origin and function of the major royal jelly proteins of the honeybee (Apis mellifera) as members of the yellow gene family
Authors: Buttstedt Anja , Moritz Robin F. A. , Erler Silvio
Published: July 2013

In the honeybee, Apis mellifera, the queen larvae are fed with a diet exclusively composed of royal jelly (RJ), a secretion of the hypopharyngeal gland of young worker bees that nurse the brood. Up to 15% of RJ is composed of proteins, the nine most abundant of which have been termed major royal jelly proteins (MRJPs). Although it is widely accepted that RJ somehow determines the fate of a female larva and in spite of considerable research efforts, there are surprisingly few studies that address the biochemical characterisation and functions of these MRJPs. Here we review the research on MRJPs not only in honeybees but in hymenopteran insects in general and provide metadata analyses on genome organisation of mrjp genes, corroborating previous reports that MRJPs have important functions for insect development and not just a nutritional value for developing honeybee larvae.
STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases
Authors: Camats Núria , Pandey Amit V. , Fernández‐Cancio Mónica , Fernández Juan M. , Ortega Ana M. , Udhane Sameer , Andaluz Pilar , Audí Laura , Flück Christa E.
Published: July 2013

Objective

The steroidogenic acute regulatory protein (StAR) transports cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY disorder of sex development (DSD) and failure of pubertal development. Partial loss of StAR activity may cause adrenal insufficiency only.

Patient

A newborn girl was admitted for mild dehydration, hyponatremia, hyperkalemia and hypoglycaemia and had normal external female genitalia without hyperpigmentation. Plasma cortisol, 17OH‐progesterone, DHEA‐S, androstendione and aldosterone were low, while ACTH and plasma renin activity were elevated, consistent with the diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and cytogenetics revealed a 46,XX karyotype. She was treated with fluids, hydrocortisone and fludrocortisone.

Design, Methods and Results

Genetic studies revealed a novel homozygous STAR mutation in the 3′ acceptor splice site of intron 4, c.466‐1G>A (IVS4‐1G>A). To test whether this mutation would affect splicing, we performed a minigene experiment with a plasmid construct containing wild‐type or mutant StAR gDNA of exons–introns 4–6 in COS‐1 cells. The splicing was assessed on total RNA using RT‐PCR for STAR cDNAs. The mutant STAR minigene skipped exon 5 completely and changed the reading frame. Thus, it is predicted to produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis revealed that this mutant protein lacks wild‐type exons 5–7 which are essential for StAR‐cholesterol interaction.

Conclusions

STAR c.466‐1A skips exon 5 and causes a dramatic change in the C‐terminal sequence of the protein, which is essential for StAR–cholesterol interaction. This splicing mutation is a loss‐of‐function mutation explaining the severe phenotype of our patient. Thus far, all reported splicing mutations of STAR cause a severe impairment of protein function and phenotype.