bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspidiotus rigidus Reyne (Hemiptera: Diaspididae): a devastating pest of coconut in the Philippines
Authors: Watson Gillian W. , Adalla Candida B. , Shepard B. Merle , Carner Gerald R.
Published: July 2014

The Philippines is the second largest producer of coconut products and, in some areas, coconut farming is the main source of livelihood.

A damaging armoured scale insect (Hemiptera: Diaspididae) infesting coconut palms was first found in the Philippines on Luzon Island (Batangas province) in 2009, and is now affecting most of the provinces of southern Luzon.

The scale pest is still spreading in the Visayan Islands and Mindanao.

Infestation stops photosynthesis; the leaves yellow and dry; fruits form less nutmeat and the coconut‐water is sour; weak new leaflets bend over or break off; and the tree dies in 6 months or less.

The scale pest is identified in the present study as Aspidiotus rigidus Reyne; it presents a significant quarantine threat to coconut‐producing countries worldwide.

Characters enabling the identification of A. rigidus, its host range and distribution are given.

Some literature on the natural enemies and control of A. rigidus is reviewed briefly.
Latent TGF‐β1 is Compartmentalized Between Blood and Seminal Plasma of HIV‐Positive Men and Its Activation in Semen is Negatively Correlated with Viral Load and Immune Activation
Authors: Kafka Jessica K. , Osborne Brendan J.W. , Sheth Prameet M. , Nazli Aisha , Dizzell Sara , Huibner Sanja , Kovacs Colin , Verschoor Chris P. , Bowdish Dawn M. , Kaul Rupert , Kaushic Charu
Published: July 2014

Problem

Semen is the primary medium for sexual transmission of HIV‐1 and contains high concentrations of TGF‐β1, but its role in regulating HIV‐mediated immune activation is unclear.

Method of Study

TGF‐β1 and sCD14 were compared in blood plasma (BP) and seminal plasma (SP) from HIV‐uninfected and infected, antiretroviral therapy (ART)‐naive and ART‐treated men and in THP‐1 cells following exposure to HIV‐1. The relationship between TGF‐β1 and sCD14 was determined by Spearman correlation.

Results

Active and latent forms of TGF‐β1 were compartmentalized between BP and SP. Highest active TGF‐β1 levels were present in SP of ART‐naïve chronic‐infected men and decreased following ART treatment. Latent TGF‐β1 was upregulated in BP following HIV infection, and highest levels were observed in BP of acute‐infected men. Similar expression trends were observed between latent TGF‐β1 and sCD14 in BP. A significant negative correlation was observed between active TGF‐β1, sCD14, and semen viral load in ART‐naive men.

Conclusion

TGF‐β1 is compartmentalized between blood and semen, possibly co‐expressed with sCD14 by activated monocytes/macrophages in BP as a result of HIV infection. Conversion of latent TGF‐β1 into its active form could contribute to regulation of viral load and immune activation in the male genital tract, but depends on the stage of infection.
Fetal growth and cardio‐metabolic risk factors in the 20‐year‐old offspring
Authors: Rytter Dorte , Bech Bodil H. , Frydenberg Morten , Henriksen Tine B. , Olsen Sjurdur F.
Published: July 2014

Objective

To investigate the association between prenatal growth patterns as estimated by biparietal diameter and cardio‐metabolic risk at 20 years.

Design

Follow‐up study.

Setting

Denmark 1988–2009.

Population

Two cohorts of children born between 1988 and 1990 (n = 707) and followed up in 2008–2009 (n = 333–509).

Methods

We have access to biparietal diameter from early ultrasound scan and birthweight. For each gender, biparietal diameter and birthweight, gestational age‐specific growth‐z‐scores were calculated. A change in growth trajectory was depicted as a shift in z‐score for the two growth measures. Multiple linear regression modeling was used to estimate associations between biparietal diameter and birthweight z‐scores and later cardio‐metabolic risk factors as well as estimating whether changing growth trajectory was associated with later cardio‐metabolic risk.

Main outcome measures

Self‐reported anthropometrics and clinically measured blood pressure, heart rate and biochemical measures associated with cardio‐metabolic health.

Results

After adjustments, biparietal diameter was not associated with any of the outcomes. Birthweight was positively associated with both adult height and weight and inversely associated with insulin, triglyceride and insulin resistance. Also, the data indicated a U‐shaped association between growth in the second half of pregnancy and adult body mass index among individuals with a low biparietal diameter in mid‐pregnancy.

Conclusion

Different patterns of intrauterine growth may be associated with later risk of cardio‐metabolic disease.
Subchronic Stimulation Performance of Transverse Intrafascicular Multichannel Electrodes in the Median Nerve of the Göttingen Minipig
Authors: Harreby Kristian R. , Kundu Aritra , Yoshida Ken , Boretius Tim , Stieglitz Thomas , Jensen Winnie
Published: July 2014

This work evaluated the subchronic stimulation performance of an intraneural multichannel electrode (transverse intrafascicular multichannel electrode, TIME) in a large human‐sized nerve. One or two TIMEs were implanted in the right median nerve above the elbow joint in four pigs for a period of 32 to 37 days (six TIMEs in total). The ability of the contact sites to recruit five muscles in the forelimb was assessed via their evoked electromyographic responses. Based on these responses, a selectivity index was defined. Four TIMEs were able to selectively recruit a subset of muscles throughout the implantation period. The required recruitment current significantly increased, while there was a tendency for the recruitment selectivity to decrease over time. Histological assessment showed that all TIMEs remained inside the nerve and that they were located between fascicles. The average thickness of the encapsulation of the electrode was estimated to be 115.4 ± 51.5 μm (mean ± SD). This study demonstrates the feasibility of keeping the TIME electrodes fixed and functional inside a large polyfascicular human‐sized nerve in a subchronic setting.
Population pharmacokinetics of deferiprone in healthy subjects
Authors: Bellanti Francesco , Danhof Meindert , Della Pasqua Oscar
Published: July 2014

Aims

To characterize the pharmacokinetics of deferiprone in healthy subjects using a model‐based approach and to assess the effect of demographic and physiological factors on drug exposure.

Methods

Data from 55 adult healthy subjects receiving deferiprone (solution 100 mg ml−1) were used for model building purposes. A population pharmacokinetic analysis was performed using nonmem v.7.2. The contribution of gender, age, weight and creatinine clearance (CLcr) on drug disposition was evaluated according to standard forward inclusion, backward deletion procedures. Model selection criteria were based on graphical and statistical summaries.

Results

A one compartment model with first order oral absorption was found to describe best the pharmacokinetics of deferiprone. Simulated exposure values were comparable with previously published data. Mean AUC estimates were 45.8 and 137.4 mg l−1 h, whereas Cmax increased from 17.6 to 26.5 mg l−1 after administration of 25 and 75 mg kg−1 doses, respectively. Gender differences in the apparent volume of distribution (20%) have been identified, which are unlikely to be of clinical relevance. Furthermore, simulation scenarios reveal that dose adjustment is required for patients with reduced CLcr. Doses of 60, 40 and 25 mg kg−1 for patients showing mild, moderate and severe renal impairment are proposed based on CLcr values of 60–89, 30–59 and 15–29 ml min−1, respectively.

Conclusions

Our analysis has enabled the assessment of the impact of gender and CLcr on the pharmacokinetics of deferiprone. Moreover, it provides the basis for dosing recommendations in renal impairment. The implication of these covariates on systemic exposure is currently not available in the prescribing information of deferiprone.
Human RAD23 homolog A is required for the nuclear translocation of apoptosis‐inducing factor during induction of cell death
Authors: Sudhakar Janaki N. , Chow Kuan‐Chih
Published: July 2014

Background Information

During the initiation of cell death, mitochondrial protein, apoptosis‐inducing factor (AIF), is transported to the nucleus. The mechanism of AIF nuclear translocation, however, is not clear. After protein synthesis, the AIF is originally targetted to the mitochondria, and the nuclear targetting is a secondary event. Therefore, we hypothesised that the nuclear translocation of AIF could be achieved by a novel pathway.

Results

By using yeast two‐hybrid assay, we identified the human UV excision repair protein RAD23 homolog A (hHR23A) interacts with AIF and their interaction was confirmed by co‐immunoprecipitation and fluorescence resonance energy transfer microscopy. Silencing the RAD23A gene expression inhibits the nuclear transportation of AIF and increases cisplatin resistance. Silencing the karyopherin alpha 2 (KPNA2) gene expression, however, did not affect the nuclear import of AIF. Moreover, 2,4‐dinitrophenol inhibits staurosporine‐induced nuclear translocation of AIF and increases cisplatin resistance.

Conclusions

These results suggest that hHR23A is required for the nuclear translocation of AIF during induction of cell death, and this process is energy dependent, but independent of karyopherins.
Detection of the secondary, low‐affinity β1‐adrenoceptor site in living cells using the fluorescent CGP 12177 derivative BODIPY‐TMR‐CGP
Authors: Gherbi K , Briddon S J , Hill S J
Published: July 2014

Background and Purpose

CGP 12177 not only inhibits agonist effects mediated through the catecholamine site of the β1‐adrenoceptor with high affinity, but also exhibits agonist effects of its own at higher concentrations through a secondary, low‐affinity β1‐adrenoceptor site or conformation. β‐blocker affinities for this ‘CGP 12177’ site of the human β1‐adrenoceptor have thus far only been characterized in functional studies. Here, we used the fluorescent CGP 12177 analogue BODIPY‐TMR‐CGP to directly investigate receptor–ligand interactions at the secondary binding site of the β1‐adrenoceptor.

Experimental Approach

The human β1‐adrenoceptor was stably expressed in CHO cells containing a cAMP response element (CRE)‐secreted placental alkaline phosphatase (SPAP) reporter gene construct. Functional responses of BODIPY‐TMR‐CGP were determined in the CRE‐SPAP reporter gene assay, and manual and automated confocal microscopy platforms used to investigate the binding properties of BODIPY‐TMR‐CGP.

Key Results

BODIPY‐TMR‐CGP displayed a pharmacological profile similar to that of CGP 12177, retaining agonist activity at the secondary β1‐adrenoceptor site. In confocal microscopy studies, specific BODIPY‐TMR‐CGP binding allowed clear visualization of β1‐adrenoceptors in live cells. Using a wider concentration range of labelled ligand in a high‐content fluorescence‐based binding assay than is possible in radioligand binding assays, two‐site inhibition binding curves of β‐adrenoceptor antagonists were revealed in CHO cells expressing the human β1‐adrenoceptor, but not the β2‐adrenoceptor.

Conclusions and Implications

The fluorescent CGP 12177 analogue allowed the detection of the β1‐adrenoceptor secondary site in both functional and binding studies. This suggests that BODIPY‐TMR‐CGP presents an important and novel fluorescent tool to investigate the nature of the secondary β1‐adrenoceptor site.
Molecular Modeling, Synthesis and Biological Evaluation of N‐Heteroaryl Compounds as Reverse Transcriptase Inhibitors Against HIV‐1
Authors: Singh Anuradha , Yadav Dipti , Yadav Madhu , Dhamanage Ashwini , Kulkarni Smita , Singh Ramendra K.
Published: July 2014

Different N‐heteroaryl compounds bearing pyrimidine and benzimidazole moieties have been designed in silico using Discovery studio 2.5 software, synthesized and evaluated for their inhibitory activity as reverse transcriptase inhibitors against HIV‐1 replication using laboratory adapted strains HIV‐1IIIB (X4, subtype B) and HIV‐1Ada5 (R5, subtype B), and the primary isolates HIV‐1UG070 (X4, subtype D) and HIV‐1VB59 (R5, subtype C). Cell‐based assay showed that compounds were active at 1.394 μm concentrations (Selectivity Index: 1.29–38.39). The studies on structure–activity relationship clearly suggested anti‐HIV activity of pyrimidine and benzimidazole derivatives and these findings were consistent with the in vitro cell‐based experimental data. The results of molecular modeling and docking confirmed that all compounds assumed a butterfly‐like conformation and showed H‐bond, ‘π–π’ and ‘π–+’ and hydrophobic interactions within flexible non‐nucleoside inhibitor binding pocket of HIV‐1 reverse transcriptase, similar to known non‐nucleoside reverse transcriptase inhibitors, such as nevirapine. In view of the results obtained, it can be said that the chemical skeletons of N, N′‐bis‐(pyridin‐2‐yl)‐succinamide (14 and 15) and 1, 4‐bis‐benzoimidazol‐1‐yl‐butane‐1, 4‐dione (16 and 17) may be used for developing potent inhibitors of HIV‐1 replication, with suitable structure/pharmacophore modifications.
Vitamin D supplementation could limit T helper‐17 response in multiple sclerosis
Authors: Najafipoor Adeleh , Roghanian Rasoul , Rahimi Maryam , Zarkesh‐Esfahani Sayyed Hamid , Shayegannejad Vahid
Published: July 2014

Objectives

Low vitamin D and high response of T helper‐17 (Th17) are two main risk factors in multiple sclerosis (MS). The purpose of the present study was to investigate whether vitamin D supplementation can reduce Th17 responses and interleukin‐17A (IL‐17A) production.

Methods

Serum samples of 17 relapsing–remitting MS patients were collected at onset of disease. They were supplemented with 50 000 IU/week vitamin D3 for 6 months. After 6 months, sampling was repeated from the patients. The serum level of 25‐hydroxyvitamin D and IL‐17A were measured at baseline, and after 6 months using commercially available enzyme‐linked immunosorbent assay. Statistical analyses were carried out by Wilcoxon test and Spearman's rho correlation coefficient.

Results

The levels of 25‐hydroxyvitamin D were generally deficient (29.4%) and insufficient (47%) in the patients at baseline. The initial IL‐17A levels (mean 3.9, standard error 0.28) were significantly decreased after vitamin D supplementation (mean 2.2, standard error 0.18, P < 0.0001). Furthermore, a positive correlation was seen between pre‐supplementation IL‐17A levels and reduction after supplementation (Spearman's rho = 0.61, P = 0.008).

Conclusion

In the present study, it was shown that vitamin D supplementation could reduce the level of IL‐17A in MS patients, and there was an association between these two risk factors in MS disease.
Gay Neighborhoods and the Rights of the Vicarious Citizen
Authors: Greene Theodore
Published: July 2014

Drawing on a combination of qualitative methods using data collected from gay neighborhoods in Chicago and Washington, DC, this article develops the notion of vicarious citizenship—the exercise of rights and claims–making by nonresidential stakeholders who personally identify politically, economically, or socio–culturally with a local community. Vicarious citizens include a diversity of self–identified community members, some of whom were former or displaced residents of the neighborhood, who draw on a variety of socio–territorial practices to mobilize against perceived normative and political threats to their visions of authentic community. At times, vicarious citizens may hold differing and even conflicting perspectives on the functions of community, challenging the claims of local residents and those with more material stakes in the local area. I argue the notion of vicarious citizenship can expand our understanding of how gay neighborhoods remain relevant among certain LGBT populations who, for a variety of reasons, select into neighborhoods outside established gay areas. Vicarious citizenship can also be found in other nonresident communities.
The Urban Ethnic Community and Collective Action: Politics, Protest, and Civic Engagement by Hmong Americans in Minneapolis–St. Paul
Authors: Hein Jeremy
Published: July 2014

This paper replicates and extends Sampson et al.'s (2005) collective efficacy explanation of civic action events to ethnic communities formed through international migration. It examines political, social movement, and civic collective action of Hmong Americans in Minneapolis–St. Paul through a content analysis of events reported in one of the community's ethnic newspapers from 2002 to 2011 (N = 541). Initially a dispersed group of refugees from Laos, by the early 2000s, 25 percent of all Hmong Americans lived in the Minneapolis–St. Paul metropolitan area. Most (68 percent) of their collective action is for civic engagement, not politics or protest. This civic engagement is mostly for socioeconomic improvement (53 percent) but also social solidarity (47 percent). As Sampson et al. found in Chicago, the spatial distribution of Hmong collective action is shaped more by the location of ethnic and public institutions than by ethnic residential concentration. The paper concludes that the analysis of collective action events in ethnic communities should combine social ecology, institutional, and interactional models.
A Neighborhood Shopping Street and the Making of Urban Cultures and Economies in Germany
Authors: Kuppinger Petra
Published: July 2014

This paper examines the cultural, social, and economic contributions of multi–ethnic neighborhood businesses to the transformation of German cityscapes. The diversity on N–Street in Stuttgart has been at the forefront of urban transformations and cultural production. I show that neighborhood stores and shopping streets are sites of urban experiments and cultural beginnings which produce new authenticities in the face of rapid urban homogenization. Combining theoretical debates about urban “authenticities,” the creative potential of immigrant neighborhoods, and ethnic/cross–cultural economies, I analyze transformations of N–Street and the surrounding neighborhood. I argue that neighborhood shopping streets are relevant nodes and agents in urban transformations and the production of urban futures. Based on ethnographic fieldwork, I introduce N–Street's history, its current configuration of genuinely local urban cultures and economies, and its cultural complexity and cultural and economic innovation.
Mapping Change in Human Pressure Globally on Land and within Protected Areas
Authors: GELDMANN JONAS , JOPPA LUCAS N. , BURGESS NEIL D.
Published: July 2014

It is widely accepted that the main driver of the observed decline in biological diversity is increasing human pressure on Earth's ecosystems. However, the spatial patterns of change in human pressure and their relation to conservation efforts are less well known. We developed a spatially and temporally explicit map of global change in human pressure over 2 decades between 1990 and 2010 at a resolution of 10 km2. We evaluated 22 spatial data sets representing different components of human pressure and used them to compile a temporal human pressure index (THPI) based on 3 data sets: human population density, land transformation, and electrical power infrastructure. We investigated how the THPI within protected areas was correlated to International Union for Conservation of Nature (IUCN) management categories and the human development index (HDI) and how the THPI was correlated to cumulative pressure on the basis of the original human footprint index. Since the early 1990s, human pressure increased 64% of the terrestrial areas; the largest increases were in Southeast Asia. Protected areas also exhibited overall increases in human pressure, the degree of which varied with location and IUCN management category. Only wilderness areas and natural monuments (management categories Ib and III) exhibited decreases in pressure. Protected areas not assigned any category exhibited the greatest increases. High HDI values correlated with greater reductions in pressure across protected areas, while increasing age of the protected area correlated with increases in pressure. Our analysis is an initial step toward mapping changes in human pressure on the natural world over time. That only 3 data sets could be included in our spatio‐temporal global pressure map highlights the challenge to measuring pressure changes over time.

Mapeo del Cambio en la Presión Humana Global en Tierra y Dentro de Áreas Protegidas
Connectivity of wood thrush breeding, wintering, and migration sites based on range‐wide tracking
Authors: Stanley Calandra Q. , McKinnon Emily A. , Fraser Kevin C. , Macpherson Maggie P. , Casbourn Garth , Friesen Lyle , Marra Peter P. , Studds Colin , Ryder T. Brandt , Diggs Nora E. , Stutchbury Bridget J. M.
Published: July 2014

Many migratory animals are experiencing rapid population declines, but migration data with the geographic scope and resolution to quantify the complex network of movements between breeding and nonbreeding regions are often lacking. Determining the most frequently used migration routes and nonbreeding regions for a species is critical for understanding population dynamics and making effective conservation decisions. We tracked the migration of individual Wood Thrushes (Hylocichla mustelina) (n = 102) from across their range with light‐level geolocators and, for the first time, quantified migration routes and wintering regions for distinct breeding populations. We identified regional and species‐level migratory connectivity networks for this declining songbird by combining our tracking results with range‐wide breeding abundance estimates and forest cover data. More than 50% of the species occupied the eastern wintering range (Honduras to Costa Rica), a region that includes only one‐third of all wintering habitat and that is undergoing intensive deforestation. We estimated that half of all Wood Thrushes in North America migrate south through Florida in fall, whereas in spring approximately 73% funnel northward through a narrow span along the central U.S. Gulf Coast (88–93°W). Identifying migratory networks is a critical step for conservation of songbirds and we demonstrated with Wood Thrushes how it can highlight conservation hotspots for regional populations and species as a whole.

Conectividad de Sitios de Reproducción, Invierno y Migración del Zorzal con Base en Rastreo de Cobertura Amplia
A Model for Developing, Evaluating, and Disseminating Best Practices in Education and Training
Authors: Weinberger Morris , Pusek Susan N. , Esserman Denise A. , Loehr Laura A. , Miller William C. , Orringer Eugene P. , Weaver Mark A.
Published: July 2014

With the shift toward team‐based translational science came recognition that existing strategies for training individual investigators and retaining them in the biomedical workforce would be inadequate. To support this shift, it is important to: develop innovative strategies to educate and train diverse members of research teams; evaluate those programs; and disseminate best practices broadly. We have developed a four‐phase model to facilitate the development, evaluation, and widespread dissemination of innovative strategies to train the biomedical research workforce. Phase I (Innovate) involves small scale trials of programs to address perceived training needs or new methods of delivery. Phase II (Incubate) refines and evaluates promising Phase I activities on a larger scale. Phase III (Translate) seeks to replicate initial successes either locally (Phase IIIa) or with other interested institutions (Phase IIIb). Phase IV (Disseminate) assesses whether identified local best practices can have success on a broader scale. We present specific examples from our own experience that demonstrate the utility of this model, and then conclude with opportunities and challenges related to the education and training of this workforce.
Postural control at 4 years in very preterm children compared with term‐born peers
Authors: Lorefice Lucy E , Galea Mary P , Clark Ross A , Doyle Lex W , Anderson Peter J , Spittle Alicia J
Published: July 2014

Aim

To compare postural control at 4 years' corrected age in very preterm children (VPT; <30wks gestational age) with term‐born (>37wks gestational age) comparison participants.

Method

Ninety VPT children (45 males, 45 females; mean age at assessment 4y 1mo; mean birthweight 1022g; mean gestational age 27.3wks) and 36 term comparison participants (17 males, 19 females; mean age at assessment 4y; mean birthweight 3507g; mean gestational age 39.4wks) were assessed for postural stability with a portable force plate, the Wii Balance Board. Tasks included static two‐limbed standing with eyes open, eyes closed, eyes open on a foam mat, eyes closed on a foam mat, a cognitive dual task, and single leg standing on each limb. The cognitive dual task involved showing the participants a series of pictures that appeared on screen at 2‐second intervals. Impaired postural control was defined as increased postural sway measured by centre of pressure path‐length velocity. Functional performance was assessed during dynamic jumping and hopping tasks using the outcome measure flight time, with shorter time indicating worse performance.

Results

VPT children had impaired static and dynamic balance, with increased postural sway under all conditions, and reduced flight times compared with children born at term. When results were adjusted for body weight, the only group differences in postural control were in the cognitive dual task (cm/s; mean difference 0.6; 95% confidence interval [CI] 0.02, 1.2; p=0.04) and flight times (ms; jumping; mean difference −26.0; 95% CI −47.1, −5.0; p=0.02; left leg hopping; mean difference −30.1; 95% CI −48.5, −11.8; p=0.002).

Interpretation

VPT children demonstrated reduced postural control at 4 years of age compared with term‐born children when presented with a cognitive dual task. They also performed worse during jumping and hopping tasks.
Ecological biogeography of Mexican bats: the relative contributions of habitat heterogeneity, beta diversity, and environmental gradients to species richness and composition patterns
Authors: López‐González Celia , Presley Steven J. , Lozano Abraham , Stevens Richard D. , Higgins Christopher L.
Published: July 2014

Mexico has higher mammalian diversity than expected for its size and geographic position. High environmental hetero geneity throughout Mexico is hypothesized to promote high turnover rates (β‐diversity), thus contributing more to observed species richness and composition than within‐habitat (α) diversity. This is true if species are strongly associated with their environments, such that changes in environmental attributes will result in changes in species composition. Also, greater heterogeneity in an area will result in greater species richness. This hypothesis has been deemed false for bats, as their ability to fly would reduce opportunities for habitat specialization. If so, we would expect no significant relationships between 1) species composition and environmental variables, 2) species richness and environmental heterogeneity, 3) β‐diversity and environmental heterogeneity. We tested these predictions using 31 bat assemblages distributed across Mexico. Using variance partitioning we evaluated the relative contribution of vegetation, climate, elevation, horizontal heterogeneity (a variate including vegetation, climate, and elevational heterogeneity), spatial variation (lat‐long), and vertical hetero geneity (of vegetation strata) to variation in bat species composition and richness. Variation in vegetation explained 92% of the variation in species composition and was correlated with all other variables examined, indicating that bats respond directly to habitat composition and structure. Beta‐diversity and vegetational heterogeneity were significantly correlated. Bat species richness was significantly correlated with vertical, but not horizontal, heterogeneity. Nonetheless, neither horizontal nor vertical heterogeneity were random; both were related to latitude and to elevation. Variation in bat community composition and richness in Mexico were primarily explained by local landscape heterogeneity and environmental factors. Significant relationships between β‐diversity and environmental variation reveal differences in habitat specialization by bats, and explain their high diversity in Mexico. Understanding mechanisms acting along environmental or geographic gradients is as important for understanding spatial variation in community composition as studying mechanisms that operate at local scales.
Serum cystatin C and serum and urine NGAL in the kidney function assessment of patients with MGUS
Authors: Stelmach‐Goldys Agnieszka , Czarkowska‐Paczek Bozena , Wyczalkowska‐Tomasik Aleksandra , Paczek Leszek
Published: July 2014

Objectives

Monoclonal gammopathy of undetermined significance (MGUS) occurs without other symptoms, although monoclonal proteins can cause kidney injuries. Here, we assessed kidney function and identified the best follow‐up parameters in patients with MGUS without kidney damage symptoms.

Methodology

Forty‐six patients with MGUS were included in the study group. The control group (CRT, n = 23) consisted of healthy subjects matched for age and sex. Serum cystatin C was determined using an immunonephelometric method, serum and urine neutrophil gelatinase‐associated lipocalin (NGAL) was measured with an immunoenzymatic method, and cathepsin B activity was determined fluorometrically.

Results

Serum cystatin C and urine NGAL were higher, and serum NGAL was lower in MGUS patients compared with CRT. Neither serum cystatin C, nor serum or urine NGAL, correlated with the biomarkers of MGUS. The serum activity of cathepsin B did not differ between groups and did not correlate with serum cystatin C. Serum cystatin C correlated with serum creatinine, while serum NGAL did not correlate with serum creatinine or cystatin C. The estimated glomerular filtration rates (eGFRs) in MGUS were within normal range and correlated with serum cystatin C. The strongest correlation was observed for CKD‐EPI. Seven patients presented with albuminuria >30 mg/day. There was a correlation between albuminuria in this group and λ free light chains.

Conclusions

The kidney function in MGUS patients is impaired, although there are no clinical and standard laboratory test manifestations. Cystatin C and urine, but not serum, NGAL should be considered markers for kidney injury. CKD‐EPI is recommended for eGFR assessment.
The measurement and importance of non‐motor symptoms in Parkinson disease
Authors: Schapira A. H. V.
Published: July 2014

Click here to view the accompanying paper in this issue.
Macrophage migration inhibitory factor (MIF) in the stratum corneum: a marker of the local severity of atopic dermatitis
Authors: Yasuda Chie , Enomoto Akiko , Ishiwatari Shioji , Mori Naoya , Kagoyama Ko , Matsunaga Kenji , Yoshihisa Yoko , Matsukuma Shoko , Shimizu Tadamichi
Published: July 2014

Different biomarkers are used to evaluate the severity of atopic dermatitis (AD); however, it remains difficult to determine the severity of localized skin lesions. MIF plays an essential role in the pathophysiology of skin inflammation. To establish whether the MIF level in the stratum corneum (SC) serves as a marker of the severity of AD lesions, we examined the SC MIF (scMIF) levels in AD patients. The SC of the cheek, neck and upper arm skin was collected using tape stripping, and the scMIF levels were measured. Consequently, the scMIF levels were found to be significantly higher in the involved skin lesions than the uninvolved areas within the same patient. Moreover, the scMIF levels were significantly correlated with the severity of local skin lesions. These findings suggest that the scMIF level can be used as an effective marker for evaluating the local severity of AD.
Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis of zebrafish embryos
Authors: Lee Hung‐Chieh , Lin Yi‐Zhen , Lai Yen‐Ting , Huang Wei‐Jhen , Hu Jia‐Rung , Tsai Jen‐Ning , Tsai Huai‐Jen
Published: July 2014

Glycogen synthase kinase 3 beta (Gsk3b) acts as a negative modulator in endothelial cells through the Wnt/β–catenin/PI3K/AKT/Gsk3b axis in cancer‐induced angiogenesis. However, the function of Gsk3b during embryonic angiogenesis remains unclear. Here, either gsk3b knockdown by morpholino or Gsk3b loss of activity by LiCl treatment had serious phenotypic consequences, such as defects in the positioning and patterning of intersegmental blood vessels and reduction of vegfaa121 and vegfaa165 transcripts. In embryos treated with the phosphatidylinositol 3‐kinase inhibitor, angiogenesis was severely inhibited, along with reduced Wnt, phosphorylated AKT and phosphorylated Gsk3b, suggesting that the remaining Gsk3b in somites could still degrade β–catenin, resulting in decreased vascular endothelial growth factor Aa(VegfAa) expression. However, in gsk3b‐mRNA‐overexpressed embryos, intersegmental vessels ectopically sprouted by the increase in phosphorylated‐Gsk3b which prevented the degradation of β–catenin and promoted the increase in phosphorylated AKT activity, thus increasing VegfAa expression in somites. Interestingly, the Gsk3b‐dependent cross‐talk between PI3K/AKT and Wnt/β–catenin suggests that Wnt/β–catenin and PI3K/AKT interaction controls embryonic angiogenesis by a positive feedback loop rather than a hierarchical framework such as that found in cancer‐induced angiogenesis. Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/β–catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos.
Intermittent hemodialysis treatment in cefepime‐induced neurotoxicity: Case report, pharmacokinetic modeling, and review of the literature
Authors: Mani Laila‐Yasmin , Kissling Sébastien , Viceic Dragana , Vogt Bruno , Burnier Michel , Buclin Thierry , Renard Delphine
Published: July 2014

Cefepime is a broad‐spectrum cephalosporin indicated for in‐hospital treatment of severe infections. Acute neurotoxicity, an increasingly recognized adverse effect of this drug in an overdose, predominantly affects patients with reduced renal function. Although dialytic approaches have been advocated to treat this condition, their role in this indication remains unclear. We report the case of an 88‐year‐old female patient with impaired renal function who developed life‐threatening neurologic symptoms during cefepime therapy. She was treated with two intermittent 3‐hour high‐flux, high‐efficiency hemodialysis sessions. Serial pre‐, post‐, and peridialytic (pre‐ and postfilter) serum cefepime concentrations were measured. Pharmacokinetic modeling showed that this dialytic strategy allowed for serum cefepime concentrations to return to the estimated nontoxic range 15 hours earlier than would have been the case without an intervention. The patient made a full clinical recovery over the next 48 hours. We conclude that at least 1 session of intermittent hemodialysis may shorten the time to return to the nontoxic range in severe clinically patent intoxication. It should be considered early in its clinical course pending chemical confirmation, even in frail elderly patients. Careful dosage adjustment and a high index of suspicion are essential in this population.
Helicobacter pylori Induces Cell Migration and Invasion Through Casein Kinase 2 in Gastric Epithelial Cells
Authors: Lee Yeo Song , Lee Do Yeon , Yu Da Yeon , Kim Shin , Lee Yong Chan
Published: July 2014

Background

Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA‐dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2‐mediated migration and invasion in gastric epithelial cells.

Materials and Methods

AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA+) and Hp8822 (CagA−) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E‐cadherin complex. We also examined β‐catenin transactivation through promoter assay and MMP7 expression by real‐time PCR and ELISA.

Results

H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori‐infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α‐catenin depletion through dissociation of the α‐/β‐catenin complex in H. pylori‐infected cells. We also found that H. pylori induces β‐catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2.

Conclusions

We show for the first time that CagA+ H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA+ H. pylori in the gastric cancer invasion and metastasis.
Role of 3‐D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
Authors: Fujino Hatsue , Kimura Tomoki , Aikata Hiroshi , Miyaki Daisuke , Kawaoka Tomokazu , Kan Hiromi , Fukuhara Takayuki , Kobayashi Tomoki , Naeshiro Noriaki , Honda Yohji , Tsuge Masataka , Hiramatsu Akira , Imamura Michio , Kawakami Yoshiiku , Hyogo Hideyuki , Takahashi Shoichi , Yoshimatsu Rika , Yamagami Takuji , Kenjo Masahiro , Nagata Yasushi , Awai Kazuo , Chayama Kazuaki
Published: July 2014

Aim

To evaluate the response, survival and safety on 3‐D conformal radiotherapy (3D‐CRT) for major portal vein tumor thrombosis (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC).

Methods

In this retrospective study, 83 advanced HCC patients treated with HAIC who met the following criteria were enrolled: (i) PVTT of the main trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii) Child–Pugh score of 5–7; (iv) performance status of 0 or 1; and (v) no history of sorafenib treatment. The response, overall survival (OS), time to treatment failure (TTF), post‐progression survival (PPS) and safety were compared between HAIC combined with 3D‐CRT for PVTT (RT group, n = 41) and HAIC alone (non‐RT group, n = 42).

Results

The objective response of PVTT was significantly higher in the RT group (56.1%) than in the non‐RT group (33.3%), while that of intrahepatic tumor and OS were not significantly different between groups. Median OS, TTF and PPS were significantly longer in the RT group than in the non‐RT group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months, respectively) among intrahepatic tumor non‐responders to HAIC, whereas those were not significantly different between groups among intrahepatic tumor responders to HAIC. By multivariate analysis, the combination of 3D‐CRT with HAIC was an independent contributing factor for OS (hazard ratio, 3.2; 95% confidence interval, 1.692–6.021; P < 0.001) among intrahepatic HCC non‐responders to HAIC.

Conclusion

3D‐CRT for PVTT combined with HAIC could provide survival benefit to non‐responder to HAIC.
Suppression of hepatocellular carcinoma development in hepatitis C patients given interferon‐based antiviral therapy
Authors: Hiramatsu Naoki , Oze Tsugiko , Takehara Tetsuo
Published: July 2014

The advance of antiviral treatment for chronic hepatitis C has brought a high sustained virological response (SVR) rate. In this review article, the suppressive effect of interferon (IFN)‐based therapy on the development of hepatocellular carcinoma (HCC), risk factors for developing HCC and the characteristics of HCC development after SVR among chronic hepatitis C patients given IFN‐based therapy were studied. The HCC incidence has been revealed to decrease with IFN‐based antiviral therapy, especially in SVR, and the risk factors for developing HCC were older age, advanced liver fibrosis and male sex. α‐Fetoprotein levels at 24 weeks after the end of IFN‐based treatment was associated strongly with HCC incidence irrespective of virological response. In patients with SVR, other risk factors were glucose metabolism disorders, lipid metabolism disorders and alcohol intake. Extra attention to the possibility of HCC incidence should be required for these SVR patients. Antiviral therapy with a combination of HCV‐specific direct‐acting antivirals (DAA) is expected to be utilized in the future. However, it is not known whether DAA‐based treatment can suppress HCC to the level of IFN‐based treatment. Further research is required to clarify this.
Collaborative Doctoral Programmes: Employer Engagement, Knowledge Mediation and Skills for Innovation
Authors: Kitagawa Fumi
Published: July 2014

This paper investigates forms of collaborative doctoral programmes that enable employer engagement in innovation and skills development. Collaborative doctoral programmes exist in different national contexts for the development of the science and technology human capital. Such programmes are also seen as policy tools that enhance relationships between academia and industry. Illustrative cases of collaborative doctoral programmes in theUnitedKingdom highlight the co‐existence and co‐evolution of several models of collaborative doctoral programmes. Collaborative doctoral programmes, both centre format and non‐centre format, provide an institutional space where doctoral students as social actors can build their professional identities as the nascent bridging scientists. For the university, both internal and external management and governance of such hybrid space for knowledge production and mediation is of critical importance for the long‐term impact.
European Mobility of United Kingdom Educated Graduates. Who Stays, Who Goes?
Authors: Behle Heike
Published: July 2014

Official figures from the Home Office show an increase in mobility of the highly‐skilled from the United Kingdom (UK) to other European countries. This paper analyses the social composition of intra‐European mobile graduates from the UK in the context of recent political developments (Bologna‐Process, European Higher Education Area). Using quantitative and qualitative data from a longitudinal study of students and its follow‐up study, the paper compares the social composition and current activity of intra‐European mobile graduates with those remaining in the UK. Personal and higher education‐related variables together with the current type of employment were significant for the distinction between intra‐European mobile graduates and ‘UK stayers’. UK‐educated mobile graduates were identified as ‘Eurostars’, who come from high social classes or studied at high tariff higher education institutions. Mobility was identified as one way for UK‐educated graduates to avoid employment in non‐graduate jobs and add further value to their undergraduate degrees.
No evidence of sex‐biased dispersal in an island population of Common Blackbirds Turdus merula
Authors: Engler Jan O. , Sacher Thomas , Elle Ortwin , Coppack Timothy , Bairlein Franz
Published: July 2014

Natal dispersal has major consequences for the dynamics and genetic structure of populations. Female‐biased natal dispersal, otherwise the norm in birds, is overridden when the place to move is limited, as on isolated islands. This effect was confirmed for the fist time in a European study system, the Common Blackbird breeding on Heligoland Island. Spatially restricted and sexually uniform natal dispersal may be a prerequisite for successful establishment of populations on remote islands or isolated habitat fragments, and this could play a major role in speciation processes.
Intercultural strategies to co‐construct and interpret humor
Authors: Moalla Asma
Published: July 2014

This paper investigates the way humor is co‐constructed and negotiated in talk‐in interaction among speakers of American English and Tunisian learners of English. Participants' audio‐recorded data of natural conversations, and in‐depth and playback interviews revealed that interactional difficulties in interdiscourse humor did exist. Those difficulties, however, did not lead to communication breakdowns and conflicts as much as they contributed to strengthening relationships and developing relational identities through the accommodation strategies participants made to their speech and to their interpretation of meaning. Accommodation strategies were found to be jointly used to facilitate and attenuate communication and to overcome differences and avoid misunderstandings.
Major histocompatibility complex class II polymorphisms in forest musk deer (Moschus berezovskii) and their probable association with purulent disease
Authors: Li L. , Wang B. B. , Ge Y. F. , Wan Q. H.
Published: July 2014

Genes of the major histocompatibility complex (MHC) family are crucial in immune responses because they present pathogenic peptides to T cells. In this study, we analysed the genetic variation in forest musk deer (Moschus berezovskii)MHCII genes and its potential association with musk deer purulent disease. In total, 53 purulent disease‐susceptible and 46 purulent disease‐resistant individuals were selected forMHCII exon 2 fragment analysis. Among them, 16DQalleles and four additionalDRalleles were identified, withDQexon 2 fragments displaying a low level of polymorphism. The nonsynonymous substitutions exceeded the synonymous substitutions in the peptide‐binding sites ofDQA2,DQB1 andDQB2. Then, 28MHCII alleles were used to analyse the distribution patterns of purulent disease between the susceptible and resistant groups. Among them, three alleles (DQA1*01,DQA1*02 andDQA2*04) were found to be resistant, and five alleles (DRB3*07,DQA1*03,DQA1*04,DQA2*05 andDQA2*06) were found to increase susceptibility. Additionally, three haplotypes were found to be putatively associated with musk deer purulent disease. However, these three haplotypes were only found in the resistant or susceptible group, and their frequencies were low. The results from our study support a contributory role ofMHCII polymorphisms in the development of purulent disease in forest musk deer.
Consensus recommendations for using the Multiplate® for platelet function monitoring before cardiac surgery
Authors: Kong R. , Trimmings A. , Hutchinson N. , Gill R. , Agarwal S. , Davidson S. , Arcari M.
Published: July 2014

Patients requiring urgent cardiac surgery are usually already taking antiplatelet drugs including aspirin and a P2Y12 ADP receptor antagonist (e.g., clopidogrel, prasugrel or ticagrelor). This presents clinicians with the challenge of balancing the risk of thrombotic complications, if antiplatelet drugs are stopped before surgery, with the problems of excessive bleeding when surgery is performed in the absence of adequate platelet function. Preoperative platelet function monitoring is able to identify when patients have recovered platelet function. The Multiplate® (multiple electrode impedance platelet aggregometer) is a point of care device that enables monitoring of platelet function. The authors offer recommendations based on real‐world, collective experience in the use of platelet function monitoring. These cover the use of the Multiplate® analyser to predict the need for platelet transfusion in the perioperative period and the individualized waiting period after cessation of P2Y12 ADP receptor antagonists before cardiac surgery.