bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenacibaculosis induction in the Senegalese sole (Solea senegalensis) and studies of Tenacibaculum maritimum survival against host mucus and plasma
Authors: Mabrok M , Machado M , Serra C R , Afonso A , Valente L M P , Costas B
Published: May 2016

Tenacibaculum maritimum, the aetiological agent for marine tenacibaculosis, is one of the most significant pathogens that threaten Senegalese sole, Solea senegalensis (Kaup), aquaculture. Because no immersion challenge with T. maritimum has been reported previously for this flatfish species, this study aimed to optimize bacterial yields as well as to establish a challenge model for tenacibaculosis induction. Several approaches were performed to optimize bacterial culture conditions, including treatment with non‐ionic surfactants, detergents, cellulase hydrolysis and strong shaking. A prolonged bath challenge was performed for 24 h under two different temperatures, 16 and 23 °C. Moreover, mucus and plasma bactericidal activities against T. maritimum were also assessed. Culturing bacteria with strong shaking and continuous shaking provided suitable culture conditions to obtain higher bacterial yields without aggregation and fluctuation, contrary to most other treatments that showed a huge amount of bacterial aggregates. A prolonged bath method for 24 h, without skin or gill scarification, was considered suitable for disease induction with high mortality rates. Moreover, data regarding mucus and plasma bactericidal activities suggested that there is a lack of host innate immune response against T. maritimum or that this particular pathogen presents evading strategies against Senegalese sole.
Nurses’ experiences of using a smart mobile device application to assist home care for patients with chronic disease: a qualitative study
Authors: Chiang Kuei‐Feng , Wang Hsiu‐Hung
Published: May 2016

Aims and objectives

To examine nurses’ experiences regarding the benefits and obstacles of using a smart mobile device application in home care.

Background

The popularity of mobile phones and Internet technology has established an opportunity for interaction between patients and health care professionals. Line is an application allowing instant communication that is available for free globally. However, the literature relating to use of Line in this area is limited.

Design

A qualitative study involving individual in‐depth interviews.

Methods

Participants included community nurses (N = 17) from six home care facilities in southern Taiwan who had used Line for home care of chronically ill patients for at least six months. The study was conducted using semi‐structured in‐depth interviews, which were recorded and converted into transcripts for content analysis.

Results

Seven themes emerged from data analysis: reduction in medical care consumption and costs, reduction in workload and stress, facilitating improvement in the quality of care, promotion of the nurse–patient relationship, perceived risk, lack of organisational incentives and operating procedures and disturbance to personal life.

Conclusions

Nurses considered Line valuable for use in home care. While this application has diverse functions, its video transfer function could in particular help nursing staff make prompt decisions about patients’ problems and promote nurse–patient relationships. However, there might be hidden risks including legal consequences, safety risks to patients, possible violations of professionalism and increased risk of nurse burnout. Increasing nursing staff awareness of using mobile messaging software applications is necessary.

Relevance to clinical practice

This study provides relevant information about the benefits, disadvantages, risks and limitations of nurses’ use of Line. The study also provides suggestions for software programmers and future organisational strategy and development.
Scale up of nutrition and health programs in Ethiopia and their overlap with reductions in child stunting
Authors: Wirth James P. , Matji Joan , Woodruff Bradley A. , Chamois Sylvie , Getahun Zewditu , White Jessica M. , Rohner Fabian
Published: May 2016

The prevalence of stunting in Sub‐Saharan Africa has changed little since 2000, and the number of stunted children has increased. In contrast, Ethiopia is an example where the national stunting prevalence and number of stunted children have decreased consistently. We compare regional differences and temporal patterns in stunting with large‐scale program coverage to identify where and when programs may have led to reductions in stunting. Data from three national demographic and health surveys and population statistics illustrate, at the regional level, where and when the prevalence and number of stunted children changed since 2000. Reports from large‐scale nutrition and health programs were used to identify ecologic associations between geographic program coverage and reductions in stunting. From 2000 to 2005, the decline in the national stunting prevalence was mainly a result of reductions in Oromiya, SNNP and Tigray. Few nutrition programs had high coverage during this time, and economic growth may have contributed to stunting reduction by increasing household wealth and investments in sanitation. From 2005 to 2011, declines in stunting prevalence in Amhara, SNNP, Somali and Oromiya were largely responsible for national reductions. Numerous programs were implemented at scale and could have plausibly improved stunting. While ecologic relationships suggest that economic growth and large‐scale programs may have contributed to the reduction in stunting in Ethiopia, stunting did not decrease in all regions despite increased program coverage expansion of the health system. Additional impact evaluations are needed identify the most effective programs to accelerate the reduction in the prevalence and number of stunted children. © 2016 John Wiley & Sons Ltd
Initial genetic diversity enhances population establishment and alters genetic structuring of a newly established Daphnia metapopulation
Authors: Holmes Christopher J. , Pantel Jelena H. , Schulz Kimberly L. , Cáceres Carla E.
Published: May 2016

When newly created habitats are initially colonized by genotypes with rapid population growth rates, later arriving colonists may be prevented from establishing. Although these priority effects have been documented in multiple systems, their duration may be influenced by the diversity of the founding population. We conducted a large‐scale field manipulation to investigate how initial clonal diversity influences temporal and landscape patterns of genetic structure in a developing metapopulation. Six genotypes of obligately asexual Daphnia pulex were stocked alone (no clonal diversity) or in combination (‘high’ clonal diversity) into newly created experimental woodland ponds. We also measured the population growth rate of all clones in the laboratory when raised on higher‐quality and lower‐quality resources. Our predictions were that in the 3 years following stocking, clonally diverse populations would be more likely to persist than nonclonally diverse populations and exhibit evidence for persistent founder effects. We expected that faster growing clones would be found in more pools and comprise a greater proportion of individuals genotyped from the landscape. Genetic composition, both locally and regionally, changed significantly following stocking. Six of 27 populations exhibited evidence for persistent founder effects, and populations stocked with ‘high’ clonal diversity were more likely to exhibit these effects than nonclonally diverse populations. Performance in the laboratory was not predictive of clonal persistence or overall dominance in the field. Hence, we conclude that although laboratory estimates of fitness did not fully explain metapopulation genetic structure, initial clonal diversity did enhance D. pulex population establishment and persistence in this system.
Inbreeding depression in a critically endangered carnivore
Authors: Norén Karin , Godoy Erika , Dalén Love , Meijer Tomas , Angerbjörn Anders
Published: May 2016

Harmful effects arising from matings between relatives (inbreeding) is a long‐standing observation that is well founded in theory. Empirical evidence for inbreeding depression in natural populations is however rare because of the challenges of assembling pedigrees supplemented with fitness traits. We examined the occurrence of inbreeding and subsequent inbreeding depression using a unique data set containing a genetically verified pedigree with individual fitness traits for a critically endangered arctic fox (Vulpes lagopus) population. The study covered nine years and was comprised of 33 litters with a total of 205 individuals. We recorded that the present population was founded by only five individuals. Over the study period, the population exhibited a tenfold increase in average inbreeding coefficient with a final level corresponding to half‐sib matings. Inbreeding mainly occurred between cousins, but we also observed two cases of full‐sib matings. The pedigree data demonstrated clear evidence of inbreeding depression on traditional fitness traits where inbred individuals displayed reduced survival and reproduction. Fitness traits were however differently affected by the fluctuating resource abundande. Inbred individuals born at low‐quality years displayed reduced first‐year survival, while inbred individuals born at high‐quality years were less likely to reproduce. The documentation of inbreeding depression in fundamental fitness traits suggests that inbreeding depression can limit population recovery. Introducing new genetic material to promote a genetic rescue effect may thus be necessary for population long‐term persistence.
Molecular mechanisms of postmating prezygotic reproductive isolation uncovered by transcriptome analysis
Authors: Pease James B. , Guerrero Rafael F. , Sherman Natasha A. , Hahn Matthew W. , Moyle Leonie C.
Published: May 2016

Little is known about the physiological responses and genetic mutations associated with reproductive isolation between species, especially for postmating prezygotic isolating barriers. Here, we examine changes in gene expression that accompany the expression of ‘unilateral incompatibility’ (UI)—a postmating prezygotic barrier in which fertilization is prevented by gamete rejection in the reproductive tract [in this case of pollen tubes (male gametophytes)] in one direction of a species cross, but is successful in the reciprocal crossing direction. We use whole‐transcriptome sequencing of multiple developmental stages of male and female tissues in two Solanum species that exhibit UI to: (i) identify transcript differences between UI‐competent and UI noncompetent tissues; (ii) characterize transcriptional changes specifically associated with the phenotypic expression of UI; and (iii) using these comparisons, evaluate the behaviour of a priori candidate loci for UI and identify new candidates for future manipulative work. In addition to describing transcriptome‐wide changes in gene expression that accompany this isolating barrier, we identify at least five strong candidates for involvement in postmating prezygotic incompatibility between species. These include three novel candidates and two candidates that are strongly supported by prior developmental, functional, and quantitative trait locus mapping studies. These latter genes are known molecular players in the intraspecific expression of mate choice via genetic self‐incompatibility, and our study supports prior evidence that these inter‐ and intraspecific postmating prezygotic reproductive behaviours share specific genetic and molecular mechanisms.
Genomic analysis reveals depression due to both individual and maternal inbreeding in a free‐living mammal population
Authors: Bérénos Camillo , Ellis Philip A. , Pilkington Jill G. , Pemberton Josephine M.
Published: May 2016

There is ample evidence for inbreeding depression manifested as a reduction in fitness or fitness‐related traits in the focal individual. In many organisms, fitness is not only affected by genes carried by the individual, but also by genes carried by their parents, for example if receiving parental care. While maternal effects have been described in many systems, the extent to which inbreeding affects fitness directly through the focal individual, or indirectly through the inbreeding coefficients of its parents, has rarely been examined jointly. The Soay sheep study population is an excellent system in which to test for both effects, as lambs receive extended maternal care. Here, we tested for both maternal and individual inbreeding depression in three fitness‐related traits (birthweight and weight and hindleg length at 4 months of age) and three fitness components (first‐year survival, adult annual survival and annual breeding success), using either pedigree‐derived inbreeding or genomic estimators calculated using ~37 000 SNP markers. We found evidence for inbreeding depression in 4‐month hindleg and weight, first‐year survival in males, and annual survival and breeding success in adults. Maternal inbreeding was found to depress both birthweight and 4‐month weight. We detected more instances of significant inbreeding depression using genomic estimators than the pedigree, which is partly explained through the increased sample sizes available. In conclusion, our results highlight that cross‐generational inbreeding effects warrant further exploration in species with parental care and that modern genomic tools can be used successfully instead of, or alongside, pedigrees in natural populations.
MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response
Authors: Zupin L. , Polesello V. , Alberi G. , Moratelli G. , Crocè S. L. , Masutti F. , Pozzato G. , Crovella S. , Segat L.
Published: May 2016

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose‐binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta‐analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.
Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus
Authors: Garabet L. , Gilboe I.‐M. , Mowinckel M.‐C. , Jacobsen A. F. , Mollnes T. E. , Sandset P. M. , Jacobsen E.‐M.
Published: May 2016

Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30‐40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003‐2009, and from 353 controls. All samples were analysed for anti‐β2 glycoprotein 1 (anti‐β2GP1) and anticardiolipin antibodies (aCL), C‐reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90 mg/l; P < 0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P = 0.665). Median C3 levels were similar in cases (1.03 g/l) and controls (1.00 g/l), whereas median C4 levels were 0.16 g/l in cases versus. 0.19 in controls (P < 0.0001). However, aPL‐positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07 g/l; P = 0.001) and C4 levels (0.11 versus 0.16 g/l; P < 0.0001) compared to aPL‐negative patients. Lower C3 and C4 values in aPL‐positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL‐positive SLE patients compared to SLE patients without aPL.
System level analysis of cacao seed ripening reveals a sequential interplay of primary and secondary metabolism leading to polyphenol accumulation and preparation of stress resistance
Authors: Wang Lei , Nägele Thomas , Doerfler Hannes , Fragner Lena , Chaturvedi Palak , Nukarinen Ella , Bellaire Anke , Huber Werner , Weiszmann Jakob , Engelmeier Doris , Ramsak Ziva , Gruden Kristina , Weckwerth Wolfram
Published: May 2016

Theobroma cacao and its popular product, chocolate, are attracting attention due to potential health benefits including antioxidative effects by polyphenols, anti‐depressant effects by high serotonin levels, inhibition of platelet aggregation and prevention of obesity‐dependent insulin resistance. The development of cacao seeds during fruit ripening is the most crucial process for the accumulation of these compounds. In this study, we analyzed the primary and the secondary metabolome as well as the proteome during Theobroma cacao cv. Forastero seed development by applying an integrative extraction protocol. The combination of multivariate statistics and mathematical modelling revealed a complex consecutive coordination of primary and secondary metabolism and corresponding pathways. Tricarboxylic acid (TCA) cycle and aromatic amino acid metabolism dominated during the early developmental stages (stages 1 and 2; cell division and expansion phase). This was accompanied with a significant shift of proteins from phenylpropanoid metabolism to flavonoid biosynthesis. At stage 3 (reserve accumulation phase), metabolism of sucrose switched from hydrolysis into raffinose synthesis. Lipids as well as proteins involved in lipid metabolism increased whereas amino acids and N‐phenylpropenoyl amino acids decreased. Purine alkaloids, polyphenols, and raffinose as well as proteins involved in abiotic and biotic stress accumulated at stage 4 (maturation phase) endowing cacao seeds the characteristic astringent taste and resistance to stress. In summary, metabolic key points of cacao seed development comprise the sequential coordination of primary metabolites, phenylpropanoid, N‐phenylpropenoyl amino acid, serotonin, lipid and polyphenol metabolism thereby covering the major compound classes involved in cacao aroma and health benefits.
Computationally Efficient Uncertainty Minimization in Wind Turbine Extreme Load Assessments
Authors: Choe Youngjun , Pan Qiyun , Byon Eunshin
Published: May 2016

To harvest more energy from wind, wind turbine size has rapidly increased, entailing the serious concern on the reliability of the wind turbine. Accordingly, the international standard requires turbine designers to estimate the extreme load that could be imposed on a turbine during normal operations. At the design stage, physics-based load simulations can be used for this purpose. However, simulating the extreme load associated with a small load exceedance probability is computationally prohibitive. In this study, we propose using importance sampling combined with order statistics to reduce the computational burden significantly while achieving much better estimation accuracy than existing methods.
The Reliability of Functional Movement Screen Scores Assigned by Athletic Trainers
Authors: Sorenson Eric A.
Published: May 2016

Context:

The Functional Movement Screen (FMS) consists of a battery of seven tests that are widely used to systematically evaluate movement.

Objective:

To evaluate the interrater agreement and intrarater reliability of FMS scores assigned by athletic trainers who reviewed video recordings of the movements.

Design:

Interrater agreement and test–retest intrarater reliability.

Setting:

Laboratory.

Subjects:

Eight athletic trainers rated the movements of 15 college-aged participants.

Measurements:

Component and composite FMS scores.

Results:

Median values for interrater agreement (0.90) and intrarater reliability (0.88) of the FMS composite score were acceptable. With the exception of the rotary stability test, all of the component scores demonstrated acceptable values for scoring consistency (> 0.80).

Conclusions:

Both component and composite FMS scores assigned by athletic trainers were highly consistent, both in terms of scores assigned by different raters and scores assigned by the same raters on two different occasions.
Lumbar- and Cervicothoracic-Spine Loading During a Fast-Bowling Spell
Authors: Greig Matt , Nagy Philip
Published: May 2016

Context:

Epidemiological studies highlight a prevalence of lumbar vertebrae injuries in cricket fast bowlers, with governing bodies implementing rules to reduce exposure. Analysis typically requires complex and laboratory-based biomechanical analyses, lacking ecological validity. Developments in GPS microtechnologies facilitate on-field measures of mechanical intensity, facilitating screening toward prevention and rehabilitation.

Objective:

To examine the efficacy of using GPS-mounted triaxial accelerometers to quantify accumulated body load and to investigate the effect of GPS-unit placement in relation to epidemiological observations.

Design:

Repeated measures, field-based.

Setting:

Regulation cricket pitch.

Participants:

10 male injury-free participants recruited from a cricket academy (18.1 ± 0.6 y).

Intervention:

Each participant was fitted with 2 GPS units placed at the cervicothoracic and lumbar spines to measure triaxial acceleration (100 Hz). Participants were instructed to deliver a 7-over spell of fast bowling, as dictated by governing-body guidelines.

Main Outcome Measures:

Triaxial total accumulated body and the relative uniaxial contributions were calculated for each over.

Results:

There was no significant main effect for overs bowled, in either total load or the triaxial contributions to total load. This finding suggests no cumulative fatigue effect across the 10-over spell. However, there was a significant main effect for GPS-unit location, with the lumbar unit exposed to significantly greater load than the cervicothoracic unit in each of the triaxial planes.

Conclusions:

There was no evidence to suggest that accumulated load significantly increased as a result of spell duration. In this respect the governing-body guidelines for this age group can be considered safe, or potentially even conservative. However, the observation of higher body load at the lumbar spine than at the cervicothoracic spine supports epidemiological observations of injury incidence. GPS microtechnologies might therefore be considered in screening and monitoring of players toward injury prevention and/or during rehabilitation.
Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in Trypanosoma cruzi
Authors: Shaw Aubie K. , Kalem Murat C. , Zimmer Sara L.
Published: May 2016

Chagas disease is caused by insect-transmitted
Trypanosoma cruzi
. Halting
T. cruzi
’s life cycle in one of its various human and insect life stages would effectively stop the parasite’s infection cycle.
T. cruzi
is exposed to a variety of environmental conditions in its different life stages, and gene expression must be remodeled to survive these changes. In this work, we look at the impact that one of these changes, nutrient depletion, has on the expression of the 20 gene products encoded in the mitochondrial genome that is neglected by whole-genome studies. We show increases in mitochondrial RNA abundances in starved insect-stage cells, under two conditions in which transition to the infectious stage occurs or does not. This report is the first to show that
T. cruzi
mitochondrial gene expression is sensitive to environmental perturbations, consistent with mitochondrial gene expression regulatory pathways being potential antiparasitic targets.
Performance, egg quality, and sensory analysis of the eggs of quails fed whole rice bran stabilized with organic acids and stored for different amounts of time
Authors: Gopinger E. , Bavaresco C. , Ziegler V. , Lemes J.S. , Lopes D.C.N. , Elias M.C. , Xavier E.G.
Published: May 2016

Whole rice bran (WRB) was added to Japanese quail feed, and the effects of stabilization of the WRB with organic acids and its storage for different amounts of time were evaluated with respect to performance and egg quality, centesimal composition, and sensory characteristics. We used 150 90-d-old Japanese quails. We had a 5 × 2 factorial scheme of five storage periods (0, 30, 60, 90, and 120 d), with and without organic acid treatment. To replace corn, 20% WRB was added to the diet. Feed consumption increased for up to 71 d of bran storage (P = 0.01) and then subsequently decreased. An increasing quadratic relationship was observed between egg mass and storage time for up to 71 d of storage (P = 0.03); egg mass then decreased thereafter. The specific gravity of the eggs produced by birds that received treated WRB at 0 d of storage was greater than those of eggs produced by birds that received treated WRB after 90 d of storage. In conclusion, the organic acid treatment maintained the quality of the WRB over up to 120 d of storage and could comprise 20% of the laying quails’ diet without affecting growth performance, egg quality, bromatological composition, or the sensory attributes of the eggs.
Does RAID Improve Lifetime of SSD Arrays?
Authors: Moon Sangwhan , Reddy A. L. Narasimha
Published: May 2016

Parity protection at the system level is typically employed to compose reliable storage systems. However, careful consideration is required when SSD-based systems employ parity protection. First, additional writes are required for parity updates. Second, parity consumes space on the device, which results in write amplification from less efficient garbage collection at higher space utilization.

This article analyzes the effectiveness of SSD-based RAID and discusses the potential benefits and drawbacks in terms of reliability. A Markov model is presented to estimate the lifetime of SSD-based RAID systems in different environments. In a small array, our results show that parity protection provides benefit only with considerably low space utilizations and low data access rates. However, in a large system, RAID improves data lifetime even when we take write amplification into account.
A Fast and Compact Language Model Implementation Using Double-Array Structures
Authors: Norimatsu Jun-Ya , Yasuhara Makoto , Tanaka Toru , Yamamoto Mikio
Published: May 2016

The language model is a widely used component in fields such as natural language processing, automatic speech recognition, and optical character recognition. In particular, statistical machine translation uses language models, and the translation speed and the amount of memory required are greatly affected by the performance of the language model implementation.

We propose a fast and compact implementation of
n
-gram language models that increases query speed and reduces memory usage by using a double-array structure, which is known to be a fast and compact trie data structure. We propose two types of implementation: one for backward suffix trees and the other for reverse tries. The data structure is optimized for space efficiency by embedding model parameters into otherwise unused spaces in the double-array structure.

We show that the reverse trie version of our method is among the smallest state-of-the-art implementations in terms of model size with almost the same speed as the implementation that performs fastest on perplexity calculation tasks. Similarly, we achieve faster decoding while keeping compact model sizes, and we confirm that our method can utilize the efficiency of the double-array structure to achieve a balance between speed and size on translation tasks.
The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin
Authors: Wang Yifan , Bernhardy Andrea J. , Cruz Cristina , Krais John J. , Nacson Joseph , Nicolas Emmanuelle , Peri Suraj , van der Gulden Hanneke , van der Heijden Ingrid , O'Brien Shane W. , Zhang Yong , Harrell Maribel I. , Johnson Shawn F. , Candido Dos Reis Francisco J. , Pharoah Paul D. P. , Karlan Beth , Gourley Charlie , Lambrechts Diether , Chenevix-Trench Georgia , Olsson Håkan , Benitez Javier J. , Greene Mark H. , Gore Martin , Nussbaum Robert , Sadetzki Siegal , Gayther Simon A. , Kjaer Susanne K. ,   kConFab Investigators, D'Andrea Alan D. , Shapiro Geoffrey I. , Wiest David L. , Connolly Denise C. , Daly Mary B. , Swisher Elizabeth M. , Bouwman Peter , Jonkers Jos , Balmaña Judith , Serra Violeta , Johnson Neil
Published: May 2016

Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo. Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778–90. ©2016 AACR.
PDT: What's Past Is Prologue
Authors: Cengel Keith A. , Simone Charles B. , Glatstein Eli
Published: May 2016

Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497–9. ©2016 AACR.

See related article by Dougherty et al., Cancer Res 1978;38:2628–35.

Visit the Cancer Research 75th Anniversary timeline.
Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials
Authors: Park Hee Chul , Yu Jeong Il , Cheng Jason Chia-Hsien , Zeng Zhao Chong , Hong Ji Hong , Wang Michael Lian Chek , Kim Mi Sook , Chi Kwan Hwa , Liang Po-Ching , Lee Rheun-Chuan , Lau Wan-Yee , Han Kwang Hyub , Chow Pierce Kah-Hoe , Seong Jinsil
Published: May 2016

A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended.
Effect of Lysosomotropic Polyamineoxidase Inhibitor MDL-72527 on Platelet Activation
Authors: Liu Guoxing , Cao Hang , Liu Guilai , Heinzmann David , Chen Hong , Umbach Anja T. , Gawaz Meinrad , Lang Florian
Published: May 2016

Background/Aims: The polyamine oxidase inhibitor MDL-72527 (N1,N4-bis(2,3-butadienyl)-1,4-butanediamine) were expected to increase the abundance of spermine, a powerful inhibitor of platelet activation. Nothing is known, however, on the sensitivity of platelet function and survival to MDL-72527 exposure. The present study thus explored whether MDL-72527 modifies function and survival of platelets without and with platelet activation by collagen related peptide (CRP). Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to MDL-72527 (100 µM) with or without subsequent activation with CRP (2-5 µg/ml). Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, generation of reactive oxygen species (ROS) from DCFDA fluorescence, phospholipid scrambling of the cell membrane from annexin-V-binding, platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: In the absence of CRP, exposure of platelets to MDL-72527 did not significantly modify [Ca2+]i, P-selectin abundance, αIIbβ3 integrin abundance, ROS, annexin-V-binding, and forward scatter. The addition of 2-5 µg/ml CRP was followed by significant increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activation, ROS abundance, annexin-V-binding, and aggregation as well as a significant decrease of forward scatter, all effects significantly blunted or virtually abolished in the presence of MDL-72527. Conclusions: MDL-72527 is a powerful inhibitor of platelet activation, apoptosis and aggregation.
Idiopathic Adulthood Ductopenia: 'It Is Out There'
Authors: Bilal Mohammad , Kazemi Ali , Babich Michael
Published: May 2016

Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic entity of unknown origin characterized by loss of inter-lobular bile ducts that was first described two decades ago. Although the diagnostic criteria have been described in detail, IAD continues to be a rare diagnosis. Our thorough literature search revealed less than a hundred cases of IAD reported. Here we present a 34-year-old female with no significant past history who was evaluated for persistent elevation of serum alkaline phosphate levels. Serology was negative for all viral hepatitides, and a chronic liver disease workup was unremarkable. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography did not reveal any abnormalities in the biliary tree. Finally, a liver biopsy demonstrated ductopenia involving greater than 50% of the portal triads, making a diagnosis of IAD. Since the disease can progress rapidly, close follow-up is warranted, so liver transplantation can be pursued if deemed necessary.
What Factors Influence Language Impairment Considering Resilience as well as Risk
Authors: Conti-Ramsden Gina , Durkin Kevin
Published: May 2016

The considerable variation observed in the profiles of children with language impairment (LI) raises challenges for the diagnosis, treatment and prevention of language difficulties, in particular since LI can present substantial issues calling for the investment of clinical, educational and public health resources. In this review paper, we examine biological, psychological and environmental factors that appear to influence the developmental course of LI. In this review paper we are interested not only in examining deficits and risk factors but also in identifying strengths of children with LI that can act as protective factors providing the child with a scaffold for more positive development and better outcomes.
In the Aftermath of Helicobacter pylori: Other Helicobacters Rising Up to Become the Next Gastric Epidemic?
Authors: Øverby Anders , Yamagata Murayama Somay , Matsui Hidenori , Nakamura Masahiko
Published: May 2016

Non-Helicobacter pylori-Helicobacters including H. suis, H. heilmanniisensu stricto and H. felis comprise a group of bacteria that may inhabit the stomach of humans and animals. Human gastric infection has been associated with gastritis, ulcer, MALT lymphoma and cancer. Although the fastidious nature of these organisms has hampered their research, recent advancements in in vitro cultivation and recent reports on in vivo models and prevalence studies in humans suggest this group of bacteria to be of more clinical significance than earlier believed. The present review discusses their history, microbiology and relevance to human health.
Vocabulários de compromissos e estatuto adamantinos: Ordem terceira de São Francisco (1778), Irmandade de Nossa Sra. do Amparo (1782), Irmandade do Santíssimo Sacramento (1785)
Authors: Duchowny Aléxia Teles , Figueiredo Bárbara Magalhães , Longo Daniela Santos , Coelho Sueli Maria
Published: May 2016

Esta obra é composta por três vocabulários de documentos das seguintes irmandades setecentistas, da cidade de Diamantina, Minas Gerais, Brasil: (i) o estatuto manuscrito da Ordem Terceira de São Francisco, datado de 1778, (ii) o livro de compromisso manuscrito da Irmandade de Nossa Senhora do Amparo, de 1782 e, finalmente, (iii) o compromisso, impresso em Lisboa, em 1785, da Irmandade do Santíssimo Sacramento. Foram coletadas, na sua totalidade, as palavras em língua portuguesa que constituem os três documentos, com a quantificação das variantes, a identificação de sua origem, na maioria das vezes latina, e uma classificação gramatical sucinta. Deseja-se, assim, trazer contribuições, principalmente, para a Etimologia e a Lexicologia, e também para as Ciências das humanidades de um modo geral, incluindo-se, aqui, entre outras, a Linguística.
Sobre os nomes populares dados aos felinos do gênero Leopardus (Mammalia, Carnivora, Felidae)
Authors: Papavero Nelson
Published: May 2016

São listados em ordem cronológica, com as respectivas referências bibiográficas, os nomes populares aplicados aos felinos do gênero Leopardus (Mammalia, Carnivora,Felidae) (L. pardalis (Linnaeus, 1758), L. colocolo (Molina, 1782), L. geoffroyi (d’Orbigny & Gervais, 1844), L. tigrinus (Schreber, 1775) e L. wiedii (Schinz, 1821). São acrescentados comentários sobre o nome ocelote, impropriamente atribuído a Leopardus tigrinus.
Um observatório de imprensa na Amazônia: o papel educativo do Lacrima
Authors: Souza Rafael Bellan Rodrigues de
Published: May 2016

O texto relata a experiência educativa do Laboratório de Crítica de Mídia do Amazonas (Lacrima), debatendo o papel dos observatórios de imprensa na formação da audiência ativa. Parte de uma aprendizagem não escolar, por meio dos observatórios críticos de mídia ventila-se uma superfície de comunicação unificada entre especialistas e não iniciados, em que são compartilhados saberes que podem ampliar a consciência sobre as relações entre mídia e poder. Iniciativa acadêmica associada ao curso de Jornalismo da UFAM, o observatório constituiu-se como uma mídia radical alternativa na cidade de Parintins (AM), objetivando não apenas o exercício do media watching, mas também o aprendizado do público no sentido da construção de uma contra-hegemonia comunicacional.
Ficção televisiva brasileira e fãs online: mapeamentos e investigações
Authors: Néia Lucas Martins
Published: May 2016

O presente texto apresenta uma síntese da obra Por uma teoria de fãs da ficção televisiva brasileira[1], resultado de dez pesquisas colaborativas desenvolvidas entre 2014 e 2015 pela equipe de investigadores da rede Obitel Brasil. Enfocam-se as diferentes abordagens dadas à questão do fã da ficção televisiva brasileira como sujeito ativo na produção cultural, inserido no contexto das tecnologias digitais. Ressalta-se, por fim, a importância destes estudos no atual panorama da Comunicação.[1] LOPES, Maria Immacolata Vassallo de (org.). Por uma teoria de fãs da ficção televisiva brasileira. Coleção Teledramaturgia, vol. 4. Porto Alegre: Sulina, 2015. O livro foi publicado com o apoio do Globo Universidade. Versão digital disponível para download no endereço: .
Que horas ela volta? Uma crônica cinematográfica
Authors: Magno Maria Ignes Carlos
Published: May 2016

O filme Que horas ela volta? (2015), de Anna Muylaert e o sucesso de crítica e de público, despertou o interesse em entender o porquê de uma história tão simples estar fazendo tanto sucesso. A proposta dessa resenha é a de pensar o filme sob a ótica da crônica. Uma crônica cinematográfica.
Editorial
Authors: Fígaro Roseli
Published: May 2016

Não se aplica
O Programa Mais Educação e a Crítica da Mídia: desafios e potencialidades
Authors: Lemes Eduarda Schneider , Fiegenbaum Ricardo
Published: May 2016

Este artigo é resultado de uma pesquisa sobre as oficinas de Jornal Escolar, do Programa Mais Educação do MEC, desenvolvidas na escola Dr. Augusto Simões Lopes, na cidade de Pelotas/RS. O programa oferece atividades em dez macrocampos, entre eles o de Comunicação e Uso de Mídias, no qual são desenvolvidos projetos de comunicação. O objetivo é estimular a leitura crítica dos meios pela apropriação, pelos alunos, das técnicas de produção, mobilizando o conceito de Educomunicação. Em nossa perspectiva, aquelas oficinas se configuram um sistema de interação social potencialmente crítico, recolocando o tema da crítica da mídia no âmbito da circulação numa sociedade em vias de midiatização, indo, assim, mais além da perspectiva da Leitura Crítica. A pesquisa buscou investigar esse processo e as potencialidades que dele emergem na relação entre Comunicação e Educação.
O mito do referencial
Authors: Popper Karl R.
Published: May 2016

Publicado originalmente com o título “The Myth of the Framework”. In: Joseph C. Pitt & Marcello Pera (Eds.) – Rational Changes in Science: Essays on Scientific Reasoning – Reidel, Dordrecht, 1976, p. 35-62. © Sir Karl Popper 1976.Tradução de Mário A. Eufrásio (Departamento de Sociologia – FFLCH-USP, Pesquisador do CNPq) e de Pedro Motta de Barros (doutorando em história da ciência, pesquisador do Centro de História da Ciência da Universidade de São Paulo-CHC/USP).
The Lulu Drawings
Authors: Kentridge William
Published: May 2016

The drawings, made with brush and ink on dictionary pages between 2011 and 2015, were created for use in the production of Alban Berg's opera Lulu. The physicality of ink—black ink, ink as blood, the harsh lines and clarity of images corresponding to the ruthless world—becomes an aesthetic equivalent of the instability of desire, a central construct in the opera. Lulu is both less and more than she wants to be, and more and less than her suitors imagine her to be. As such, she is often represented in a fractured formation in the drawings; constructed on multiple sheets; created to deconstruct and to fall apart. As femme fatale, she exists in many forms and there are myriad women representing her.
Accumulated Experience
Authors: Linsley Johanna
Published: May 2016

Martha Wilson, Mona/Marcel/Marge, P.P.O.W Gallery, New York, October 22–December 22, 2015. Rose English, A Premonition of the Act, Camden Arts Centre, London, December 12, 2015–March 6, 2016. Martha Wilson's playful and incisive self-portraiture practice, produced in a variety of guises, has been profoundly influential since the early 1970s and continues to be so today. Her recent solo exhibition at P.P.O.W Gallery, Mona/Marcel/Marge, was composed mostly of photographic works in which Wilson adopts a range of identities, from Vincent van Gogh to the mash-up that gives the show its title—Wilson as Mona Lisa, with the vertical blue hair of Marge Simpson and, when viewed from certain angles, a thin mustache à la Duchamp. Many of the works also deal with aging, particularly as a challenge to prescriptive standards of female beauty. Humor and lightness are characteristic of these challenges. For instance, Thin-skinned has Wilson in profile against a dark background, the image held in a baroque, gold frame, with Wilson shown peeling a layer of skin off her face. The formality of the portrait shades knowingly into kitsch while the word/image play with “thin skin” is gleeful, even breezy. Similarly, Makeover is a series of five photos in which Wilson's face gradually transforms, through the magic of Photoshop, into a young Catherine Deneuve. There is clearly a critique here about demands on women with regard to appearance, as well as a giddy playfulness that finds cracks in the surface of these demands.
Opera for the Domestic Apocalypse
Authors: Tanner-Kennedy Dana
Published: May 2016

“America's house of cards is crumbling,” sings one of the inhabitants of the homestead at the center of Dog Days, a new chamber opera featured at the 2016 Prototype Festival. “Well, you can only be on top for so long, I guess,” he shrugs. Set in the middle of a total war of unknown origins, Dog Days places a small cross-section of society under the microscope, and we watch as it dissolves before our eyes. A seemingly typical nuclear family, complete with mother, father, daughter, two sons, and a dog makes up the heart of the work. It is the kind of traditional middle-class family unit exemplary of what politicians refer to as the “real America,” save for the fact that the pet dog is actually a homeless man in a dog costume.