bluuebunny/crossref_metadata_2025 huggingface dataset:
Release of bio‐active dentine extracellular matrix components by histone deacetylase inhibitors (HDACi)
Authors: Duncan H. F. , Smith A. J. , Fleming G. J. P. , Reid C. , Smith G. , Cooper P. R.
Published: November 2015

Aim

To characterize dentine matrix component (DMC) release and smear layer removal by histone deacetylase inhibitors (HDACis).

Methodology

DMCs were extracted from powdered human dentine over 14 days using three HDACis, valproic acid (VPA), trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) and compared with a control extractant, 10% (w/v) EDTA. Protein compositions of the resultant extracts were analysed by 1D‐polyacrylamide gel electrophoresis (1D‐PAGE), TGF‐β‐1 and MMP‐9 ELISAs and a high‐throughput growth factor antibody array. Dentine discs with a standardized smear layer were prepared from human molars and treated with EDTA (17% w/v), polyacrylic acid (PA) (20% v/v) and the experimental HDACis prior to analysis by scanning electron microscopy. Parametric ELISA data were analysed using one‐way anova and Tukey's post hoc test, whilst nonparametric smear layer data were analysed by Kruskal–Wallis test and Mann–Whitney U‐test (P < 0.05).

Results

HDACis did not remove smear layer in the presence or absence of PA pre‐treatment (P ≥ 0.478). 1D‐PAGE analysis demonstrated different protein profiles for EDTA and HDACi extracts. All HDACi solutions released TGF‐β‐1 although less effectively than EDTA (P < 0.001), whilst MMP‐9 was extracted in significantly higher concentration by EDTA and VPA compared with TSA (P < 0.012). Antibody array analysis demonstrated the ability of HDACis to extract a complex cocktail of established/novel growth factors from dentine, albeit significantly less efficiently than EDTA for certain cytokines (TGF‐β‐1, PDGF‐AA, VEGF‐A) and significantly more effectively for others (GDF‐15, IGF‐1, EGRF‐1, NGFR, BDNF, SCF‐R).

Conclusions

HDACi release a range of bioactive DMCs that could promote dentine repair processes in vivo; however, they are ineffective at removing smear layer.
Effects of electron beam irradiation on microbial inactivation and quality of kimchi paste during storage
Authors: Cheon Seon Hwa , Seo Hye Young , Chung Young Bae , Chun Ho Hyun
Published: November 2015

The effects of electron beam irradiation on microbial inactivation and quality of noninoculated and inoculated (Listeria monocytogenes) kimchi pastes were examined. Kimchi paste samples were irradiated at doses of 2, 4, 6, 8 and 10 kGy and stored for 21 days at 4 °C. Irradiation (10 kGy) reduced the populations of total aerobic bacteria, lactic acid bacteria, and yeast and moulds in the samples by 1.72, 2.24 and 0.86 log CFU g−1, respectively, compared to the control. In particular, coliforms were not detected at 8 and 10 kGy, and the population of L. monocytogenes in inoculated samples was significantly decreased by 2.67 log CFU g−1. Electron beam irradiation delayed the changes in O2 and CO2 concentrations, pH, acidity and reducing sugar content observed in kimchi paste during storage. These results suggest that electron beam irradiation can be used to improve the microbiological safety and shelf life of kimchi paste.
Birt–Hogg–Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome
Authors: Hasumi Hisashi , Baba Masaya , Hasumi Yukiko , Furuya Mitsuko , Yao Masahiro
Published: November 2015

Birt–Hogg–Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt–Hogg–Dubé syndrome‐associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron‐sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt–Hogg–Dubé syndrome patients. The folliculin gene (FLCN) that is responsible for Birt–Hogg–Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin‐interacting protein 1 (FNIP1) and folliculin‐interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP‐activated protein kinase‐mediated energy sensing, Ppargc1a‐driven mitochondrial oxidative phosphorylation and mTORC1‐dependent cell proliferation. Birt–Hogg–Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer.
Progreso social y producción mundializada. El caso del sector de los textiles y el vestido
Authors: GIMET Céline , GUILHON Bernard , ROUX Nathalie
Published: November 2015

La especialización vertical generada por la fragmentación de la producción en redes mundiales no solo está motivada por la ventaja comparativa, sino también por las estrategias de deslocalización de las empresas líderes, que determinan el papel y el poder negociador de los productores locales. Este estudio examina las consecuencias de tal especialización en los textiles y el vestido en 26 países con abundante mano de obra de 1990 a 2007. Las regresiones de efectos fijos con datos de panel revelan que el sector no siempre gana con la integración comercial internacional: se observa una correlación negativa entre la especialización vertical y los salarios reales relativos.
Fuera de las sombras: Clasificación de las economías por el grado y la intensidad de la informalización
Authors: WILLIAMS Colin C.
Published: November 2015

Dado el predominio de la informalidad en el mundo, el autor propone una clasificación de los países según el grado y la intensidad de la misma, y no por la composición de su economía formal. A partir de datos de la OIT de 36 países en desarrollo, muestra que existe una correlación significativa entre el grado y la intensidad de la informalización en los países e indicadores sociales y económicos como el PIB per cápita, la corrupción, la pobreza, los impuestos y las cotizaciones sociales. Concluye destacando las aportaciones teóricas y de políticas del estudio.
Presiones en contra y a favor de la formalización. Regulación y empleo informal en Mozambique
Authors: DIBBEN Pauline , WOOD Geoffrey , WILLIAMS Colin C.
Published: November 2015

La economía informal representa la mayor parte del empleo en muchas economías emergentes. Según la teoría de la regulación, toda actividad económica se regula por un complejo engranaje de mecanismos formales e informales. A partir del caso de Mozambique, este artículo explora las presiones a favor y en contra de la formalización y las formas que puede tomar la regulación, sobre la base de una investigación cualitativa consistente en entrevistas en profundidad a personal directivo y observaciones. Los resultados revelan la ambivalencia del Estado al respecto, con actuaciones «progresistas», centradas en la modernización de normativas e instituciones, y otras «conservadoras» que inhiben el proceso de formalización.
Incumplimiento de la Ley de fábricas de la India. Alcance y pautas
Authors: CHATTERJEE Urmila , KANBUR Ravi
Published: November 2015

Existen pocos datos sistemáticos sobre el alcance del incumplimiento de la legislación en los países en desarrollo, que se cree generalizado. Con datos de dos encuestas de empresas, los autores cuantifican el incumplimiento de la Ley de fábricas de la India y observan que las empresas infractoras doblan a las conformes y superan con mucho a las que eluden la ley mediante ciertos ajustes. Analizan las principales tendencias y pautas de incumplimiento y las ponen en relación con la ausencia de empresas de tamaño medio en la India y los debates sobre reglamentación. También destacan cuestiones para investigaciones futuras.
Modern Conservatism: Ideology, modernisation and Conservative strategies for success
Authors: Dommett Kate
Published: November 2015

The Conservative party has largely recovered from the travails of the late ‘80s and 1990s, says Kate Dommett, but David Cameron's modernisation agenda has been worn away as his party has gained power. With a leadership contest on the far horizon, what is the shape and substance of the modern Tory ideology?
Ahead of their time: From progressive rock to the progressive alliance
Authors: Robinson Emily
Published: November 2015

Emily Robinson traces the parallel paths of ‘progressiveness’ in rock music and politics – in both cases, she argues, to be progressive was at first something optimistic and forward‐looking but in the end came to be derided as ‘expertise at the expense of authenticity’.
Love and management: Reflections on the 2015 refugee crisis
Authors: Finch Tim
Published: November 2015

Tim Finch reflects on the ‘significant, perhaps seminal’ moment in which public attitudes to the refugee crisis changed. Given the scale of the challenge facing Europe, he says, it is vital that this ‘rediscovered humanity’ is paired with a new sense of order and fairness in how migration is managed.
Resurrected right, disorientated left: Pre‐crisis economics and post‐crisis emotions
Authors: Berry Craig
Published: November 2015

The Conservative party's ability to embrace popular concerns around value, place and equality has enabled it to resurrect the old pre‐crisis growth model, says Craig Berry, in a move which none of the post‐crisis narratives offered by the Labour party has yet been able to disrupt or overturn.
The future isn't working
Authors: Srnicek Nick , Williams Alex
Published: November 2015

Full employment is a tenet of classic social democracy – but what if that just isn't applicable anymore? Nick Srnicek and Alex Williams survey the state of the British labour market and ask how a modern Labour party might reframe the issue of work so that it is sustainable and sustaining in the face of technological change.
On Stalin's team: The years of living dangerously in Soviet politics
Authors: Fitzpatrick Sheila
Published: November 2015

Sheila Fitzpatrick offers a brief tour of her new book, which takes an insistently humanising view of Stalin and the group of men who supported his leadership and later succeeded him.
Impact of Implementing the 2013 ACC/AHA Cholesterol Guidelines on Vascular Events in a Statewide Community‐Based Practice Registry
Authors: Egan Brent M. , Li Jiexiang , Fleming Douglas O. , White Kellee , Connell Kenneth , Davis Robert A. , Sinopoli Angelo
Published: November 2015

Electronic health record data were analyzed to estimate the number of statin‐eligible adults with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines not taking statin therapy and the impact of recommended statin therapy on 10‐year atherosclerotic cardiovascular disease (ASCVD10) events. Adults aged 21 to 80 years in an outpatient network with ≥1 clinic visit(s) from January 2011 to June 2014 with data to calculate ASCVD10 were eligible. Moderate‐intensity statin therapy was assumed to lower low‐density lipoprotein cholesterol by 30% and high‐intensity therapy was assumed to reduce low‐density lipoprotein cholesterol by 50%. ASCVD events were assumed to decline 22% for each 39 mg/dL decline in low‐density lipoprotein cholesterol. Among 411,768 adults, 260,434 (63.2%) were not taking statins and 103,478 (39.7%) were eligible for a statin, including 79,069 (76.4%) patients with hypertension. Estimated ASCVD10 events were 18,781 without and 13,328 with statin therapy, a 29.0% relative and 5.3% absolute risk reduction with a number needed to treat of 19. The 2013 cholesterol guidelines are a relatively efficient approach to reducing ASCVD in untreated, statin‐eligible adults who often have concomitant hypertension.
β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a GLP‐1 receptor dependent and independent control
Authors: Gleizes Céline , Kreutter Guillaume , Abbas Malak , Kassem Mohamad , Constantinescu Andrei Alexandru , Boisramé‐Helms Julie , Yver Blandine , Toti Florence , Kessler Laurence
Published: November 2015

Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell‐derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon‐like peptide (GLP)‐1 analogue, is known to promote insulin secretion and β‐cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin‐m5f β‐cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross‐talk model. Methyl‐β‐cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N‐éthylmaleimide‐sensitive‐factor Attachment protein Receptor (SNARE)‐dependent exocytosis. Cytokines induced a two‐fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two‐fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD‐treated cells showed similar patterns. Cells pre‐treated by saturating concentration of the GLP‐1r antagonist exendin (9‐39), showed a partial abolishment of the liraglutide‐driven insulin secretion and liraglutide‐decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP‐1r‐dependent and ‐independent pathways. Our results confirm an integrative β‐cell response to GLP‐1 that targets receptor‐mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation‐driven procoagulant events.
Improving detection of familial hypercholesterolaemia in primary care using electronic audit and nurse‐led clinics
Authors: Green Peter , Neely Dermot , Humphries Steve E. ,   the Medway FH Audit Steering Committee, Saunders Tanya , Gray Val , Gordon Louise , Payne Jules , Carter Slade , Neuwirth Clare , Rees Alan , Gallagher Hazel
Published: November 2015

Rationale, aims and objectives

In the UK fewer than 15% of familial hypercholesterolemia (FH) cases are diagnosed, representing a major gap in coronary heart disease prevention. We wished to support primary care doctors within the Medway Clinical Commissioning Group (CCG) to implement NICE guidance (CG71) and consider the possibility of FH in adults who have raised total cholesterol concentrations, thereby improving the detection of people with FH.

Methods

Utilizing clinical decision support software (Audit+) we developed an FH Audit Tool and implemented a systematic audit of electronic medical records within GP practices, first identifying all patients diagnosed with FH or possible FH and next electronically flagging patients with a recorded total cholesterol of >7.5 mmol L−1 or LDL‐C > 4.9 mmol L−1 (in adults), for further assessment. After a 2‐year period, a nurse‐led clinic was introduced to screen more intensely for new FH index cases. We evaluated if these interventions increased the prevalence of FH closer to the expected prevalence from epidemiological studies.

Results

The baseline prevalence of FH within Medway CCG was 0.13% (1 in 750 persons). After 2 years, the recorded prevalence of diagnosed FH increased by 0.09% to 0.22% (1 in 450 persons). The nurse advisor programme ran for 9 months (October 2013–July 2014) and during this time, the recorded prevalence of patients diagnosed with FH increased to 0.28% (1 in 357 persons) and the prevalence of patients ‘at risk and unscreened’ reduced from 0.58% to 0.14%.

Conclusions

Our study shows that two simple interventions increased the detection of FH. This systematic yet simple electronic case‐finding programme with nurse‐led review allowed the identification of new index cases, more than doubling the recorded prevalence of detected disease to 1 in 357 (0.28%). This study shows that primary care has an important role in identifying patients with this condition.
Membrane‐bound tetramer and trimer Aβ oligomeric species correlate with toxicity towards cultured neurons
Authors: Jana Metta K. , Cappai Roberto , Pham Chi L. L. , Ciccotosto Giuseppe D.
Published: November 2015

Amyloid beta (Aβ) peptide is the major constituent of the extracellular amyloid plaques deposited in the brains of Alzheimer's disease patients and is central to the pathogenic pathway causing this disease. The identity of the neurotoxic Aβ species remains elusive. We previously reported that Aβ toxicity correlates strongly with its neuronal cell binding leading us to hypothesize that neuronal cell death is caused by the binding of a specific oligomeric Aβ species. To identify the specific oligomeric Aβ species that is associated with cell death, we treated mouse cortical neuronal cultures with synthetic Aβ40 and Aβ42 peptides and identified that the cellular Aβ binding and neurotoxicity were time and concentration dependent. We found a significant correlation between the amount of trimer and tetramer species bound to neurons with increasing neurotoxicity. We prepared Aβ40 oligomers (up to tetramers) using photo‐induced cross‐linking of unmodified peptides to confirm this oligomer‐specific neurotoxic activity. Our results identify the Aβ tetramer, followed by the trimer, as the most toxic low‐order oligomers Aβ species.

image

Our findings suggested that binding of amyloid‐β (Aβ) tetramer and trimer, not monomer or dimer, to neurons is critical to induce neuronal cell death associated with Alzheimer's Disease. We proposed that Aβ trimer and tetramer are the potential neurotoxic Aβ species. This would provide more specific therapeutic target for Alzheimer's Disease.

Read the Editorial Highlight for this article on page 437.
Sex‐Related Differences in Rat Choroid Plexus and Cerebrospinal Fluid: A cDNA Microarray and Proteomic Analysis
Authors: Quintela T. , Marcelino H. , Deery M. J. , Feret R. , Howard J. , Lilley K. S. , Albuquerque T. , Gonçalves I. , Duarte A. C. , Santos C. R. A.
Published: November 2015

The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood and the cerebrospinal fluid (CSF), which is mostly produced by the CP itself. Because the CP transcriptome is regulated by the sex hormone background, the present study compared gene/protein expression profiles in the CP and CSF from male and female rats aiming to better understand sex‐related differences in CP functions and brain physiology. We used data previously obtained by cDNA microarrays to compare the CP transcriptome between male and female rats, and complemented these data with the proteomic analysis of the CSF of castrated and sham‐operated males and females. Microarray analysis showed that 17 128 and 17 002 genes are expressed in the male and female CP, which allowed the functional annotation of 141 and 134 pathways, respectively. Among the most expressed genes, canonical pathways associated with mitochondrial dysfunctions and oxidative phosphorylation were the most prominent, whereas the most relevant molecular and cellular functions annotated were protein synthesis, cellular growth and proliferation, cell death and survival, molecular transport, and protein trafficking. No significant differences were found between males and females regarding these pathways. Seminal functions of the CP differentially regulated between sexes were circadian rhythm signalling, as well as several canonical pathways related to stem cell differentiation, metabolism and the barrier function of the CP. The proteomic analysis identified five down‐regulated proteins in the CSF samples from male rats compared to females and seven proteins exhibiting marked variation in the CSF of gonadectomised males compared to sham animals, whereas no differences were found between sham and ovariectomised females. These data clearly show sex‐related differences in CP gene expression and CSF protein composition that may impact upon neurological diseases.
A bibliometric study of scientific literature in Scopus on botanicals for treatment of androgenetic alopecia
Authors: Rondanelli Mariangela , Perna Simone , Peroni Gabriella , Guido Davide
Published: November 2015

Background

In androgenetic alopecia, a number of botanicals are available that can effectively slow or reduce hair loss and inflammation or stimulate partial hair regrowth. The aim of this study was to provide a descriptive overview of the impact and production of literature on botanicals used for androgenetic alopecia and to perform a citation analysis of the related research articles.

Methods

We searched for “alopecia” OR “androgenetic alopecia” OR “hair loss” AND “Camelia sinensis” OR (and other 15 botanicals) in ARTICLE (Title/Abstract/Keyword) in Scopus database.

Results

A total of 29 references, that is, research articles, were retrieved by SCOPUS search, and 93.1% had been published since 2000. The majority (48.3%) describe applications of hair grow stimulants, followed by inhibitors of 5‐alpha‐reductase applications (27.6%), and studies concerning inhibitors of inflammation (24.1%). The citation analysis revealed a growing interest for this topic and the papers on hair grow stimulants are most cited. Citation trend of inhibition of 5‐alpha‐reductase articles is growing in the last years.

Conclusions

This study has highlighted three important aspects: (1) growing interest for this topic; (2) evidences mainly in hair grow stimulants and recently in the inhibition of 5‐alpha‐reductase, as demonstrated by article and citation counts across years; (3) in addition, all major studies have been focused on green tea epigallocatechin‐3‐gallate, Serenoa repens, Citrullus colocynthis and Cuscuta reflexa.
Therapy service use in children and adolescents with cerebral palsy: An Australian perspective
Authors: Meehan Elaine , Harvey Adrienne , Reid Susan M , Reddihough Dinah S , Williams Katrina , Crompton Kylie E , Omar Suhaila , Scheinberg Adam
Published: November 2015

Aim

The aim of this study was to describe the patterns of therapy service use for a sample of children and adolescents with cerebral palsy over a 1 year period and to identify factors associated with frequency of therapy and parental satisfaction with therapy frequency.

Methods

Parents of 83 children completed a survey on their child's use of occupational therapy, physiotherapy and speech and language pathology services over the previous year. Participants were randomly selected from a sample stratified by age and Gross Motor Function Classification System (GMFCS) level.

Results

During the year prior to survey completion, 83% of children had received occupational therapy, 88% had received physiotherapy and 60% had received speech and language pathology services. Frequency of therapy was higher for younger children (P < 0.01), those classified at GMFCS levels IV–V (P < 0.05) and those attending schools specifically for children with disabilities.

Conclusions

Current structures for therapy service delivery for children with cerebral palsy are systems‐based, and age‐based funding systems and the organisation of services around the education system are preventing the delivery of needs‐based therapy. Paediatricians that care for children and young people with cerebral palsy need to pay particular attention to those that may miss out on therapy due to age or school type, and support these families in accessing appropriate therapy.
Impact of social media on the health of children and young people
Authors: Richards Deborah , Caldwell Patrina HY , Go Henry
Published: November 2015

This paper reviews the literature on the impact of social media on the health of children and young people. Relevant papers were identified from Medline, Embase and PsycINFO databases. The studies identified that the health impact of social media on children and young people was greatest on mental health and specifically in the areas of self‐esteem and well‐being, with related issues around cyberbullying and ‘Facebook Depression’, with an association between the use of social media and self‐esteem and body image. However, it is difficult to determine the cause and effect, which is likely to be related to the nature of the young person. There is little work on the impact of social media on younger children. More research is needed to identify those most at risk of harm from social media and risk mitigation strategies to assist health‐care professionals to provide essential education for parents and young people.
Hospitalisations up to adulthood for children born with orofacial clefts
Authors: Bell Jane , Nassar Natasha , Turner Robin , Bower Carol , Gillett David , McBain Wilma , Raynes‐Greenow Camille
Published: November 2015

Aim

The aim of this study was to compare hospital admissions from infancy to adulthood, between children born with orofacial clefts (OFC) and those withoutOFC.

Methods

The method used was a cohort study using record‐linked administrative datasets. Participants included all children liveborn inWesternAustralia (WA) between 1980 and 2010 diagnosed withOFC, who were frequency matched by year of birth to randomly selected liveborn children withoutOFC. We calculated rate ratios (RR) of hospital admission, number and reason of admissions, cumulative length of stay, for each cleft type (cleft lip only (CLO), cleft lip and palate (CL+P), cleft palate only (CPO), noOFC) and by age period (infancy, pre‐school, primary and high school ages, and early adulthood).

Results

Overall, 1396 children were diagnosed with anOFCand compared with 6566 children withoutOFC. Individuals born withOFCwere up to three times more likely to be admitted to hospital, had more admissions and longer cumulative length of stay in all age periods. Children withOFCwere also more likely to be admitted for ear and digestive system conditions (RRup to 30 and six times higher, respectively). Children withCL+PandCPOwere more likely to be admitted for respiratory conditions (RR1.3–2.0) and children withCPOwere six times more likely to be admitted for care for other congenital anomalies.

Conclusions

Throughout childhood, individuals born withOFCwere more likely to be admitted, and had more hospitalisations than those withoutOFC. Children born withCL+PorCPOhad a higher hospitalisation burden than children born withCLO.
Melatonin inhibits paraquat‐induced cell death in bovine preimplantation embryos
Authors: Pang Yun‐Wei , Sun Ye‐Qing , Sun Wei‐Jun , Du Wei‐Hua , Hao Hai‐Sheng , Zhao Shan‐Jiang , Zhu Hua‐Bin
Published: November 2015

Preimplantation embryos are sensitive to oxidative stress‐induced damage that can be caused by reactive oxygen species (ROS) originating from normal embryonic metabolism and/or the external surroundings. Paraquat (PQ), a commonly used pesticide and potent ROS generator, can induce embryotoxicity. The present study aimed to investigate the effects of melatonin on PQ‐induced damage during embryonic development in bovine preimplantation embryos. PQ treatment significantly reduced the ability of bovine embryos to develop to the blastocyst stage, and the addition of melatonin markedly reversed the developmental failure caused by PQ (20.9% versus 14.3%). Apoptotic assay showed that melatonin pretreatment did not change the total cell number in blastocysts, but the incidence of apoptotic nuclei and the release of cytochrome c were significantly decreased. Using real‐time quantitative polymerase chain reaction analysis, we found that melatonin pre‐incubation significantly altered the expression levels of genes associated with redox signaling, particularly by attenuating the transcript level of Txnip and reinforcing the expression of Trx. Furthermore, melatonin pretreatment significantly reduced the expression of the pro‐apoptotic caspase‐3 and Bax, while the expression of the anti‐apoptotic Bcl‐2 and XIAP was unaffected. Western blot analysis showed that melatonin protected bovine embryos from PQ‐induced damage in a p38‐dependent manner, but extracellular signal‐regulated kinase (ERK) and c‐JUN N‐terminal kinase (JNK) did not appear to be involved. Together, these results identify an underlying mechanism by which melatonin enhances the developmental potential of bovine preimplantation embryos under oxidative stress conditions.
Effect of arginine and threonine administered in ovo on digestive organ developments and subsequent growth performance of broiler chickens
Authors: Tahmasebi S. , Toghyani M.
Published: November 2015

This trial was conducted to investigate the effect of arginine (Arg), threonine (Thr) and Arg + Thr administered in ovo on growth performance, digestive organs and intestinal morphology in broiler chickens. On day 14 of incubation, 400 fertile eggs were randomly allotted to five experimental treatments through injection in the amniotic fluid including: (i) control (none injected), (ii) sham (0.5 ml of 0.5% saline), (iii) Arg (35 mg/egg), (iv) Thr (25 mg/egg) and (v) Arg + Thr (35 + 25 mg/egg). After hatching, chicks were given a commercial corn–soya bean diet up to 42 days of age. Daily feed intake (FI) and body weight (BW) of chicks were measured during different periods of the trial. Digestive organs were measured for their relative weight and intestinal length on days 11 and 42 of age. Intestinal morphometric traits were evaluated on day 11 of the experiment. Supplementing amino acids affected the performance of broiler chicks as Thr significantly increased FI and BW across starter, grower and finisher periods compared with sham and control (p < 0.05). Furthermore, Arg + Thr injection increased jejunal weight compared with control on day 42 (p < 0.05). Moreover, Arg inclusion led to the greatest villus height and crypt depth among treatments in duodenum (p > 0.05); however, amino acid supplemented groups had lower villus height than control in jejunum (p < 0.05). Negative correlations found between digestive organs related to day 11 of age containing pancreas (r = −0.484; p = 0.030), duodenal (r = −0.577; p = 0.007) as well as ileal lengths (r = −0.471; p = 0.035) and FI of entire period. Otherwise, positive relationships were observed between duodenum (r = 0.580; p = 0.007) and ileum (r = 0.582; p = 0.007) weights on day 42 and FI of chickens across the entire phase. In conclusion, Arg and particularly Thr injection into amnion can improve FI and post‐hatch growth performance of chickens which may be mediated by the development of digestive organs.
Sex in Its Daily Relational Context
Authors: Dewitte Marieke , Van Lankveld Jacques , Vandenberghe Sjouke , Loeys Tom
Published: November 2015

Introduction

The present study measured the daily correlates of sexual behavior in an ecologically valid context by relying on a daily diary approach.

Aim

Examining the dyadic and multicomponent nature of sexual behavior is essential to create valid models of sexual responding that are better aligned with the day-to-day context of having sex in a relationship.

Methods and Main Outcome Measures

During 3 weeks, heterosexual couples completed, two times a day, an electronic diary to report on mood, own and perceived partner behavior, relational feelings (in the evening), sexual activity, physical intimacy, and masturbation (in the morning). This design allowed testing bidirectional temporal associations between daily context and different types of sexual behavior.

Results

Positive mood, displays of positive partner behavior, perceived positive partner behavior, and positive relational feelings predicted more sexual activity and intimacy in men, which then further increased their positive mood, perceived positive partner behavior, and positive feelings about the relationship on the following day. Women showed a similar pattern of predictors regarding sexual activity as men, though the effect of sexual behavior on next-day feelings and behavior was more relationship-oriented rather than affecting personal mood. Intimacy was related to almost all daily variables in women, but related only to own and perceived positive partner behavior and positive relational feelings the next day. Several partner effects also reached significance, and these were more influential in predicting male than female intimacy. Solitary sexual activity showed a different pattern of results than dyadic sexual activity, with men experiencing masturbation as negatively in the context of their relationship.

Conclusion

These results confirm the regulatory function of sex and intimacy in maintaining a positive relational climate and indicate that the quality of the everyday relational context is important to get partners in the mood to act in a sexual way.
Appreciating the wrongfulness of criminal conduct: Implications for the age of criminal responsibility
Authors: Wagland Paul , Bussey Kay
Published: November 2015

Purpose

Although the ability to appreciate the wrongfulness of criminal conduct and to distinguish it from childish mischief forms the basis of Age of Criminal Responsibility (ACR) legislation in many countries, empirical research on the extent to which children possess this ability is limited. It was the aim of this study to investigate this issue.

Methods

A total of 132 males and females from four age groups (8, 12, and 16 years and adults) participated in the study. Participants listened to a series of vignettes which described a person committing a transgression. The seriousness of the transgressions varied across vignettes. Participants then provided ratings on the wrongfulness and outcome expectations associated with the conduct described in the vignette.

Results

Participants from all age groups evaluated criminal conduct more negatively than mischievous conduct. Participants from all age groups also anticipated more negative self‐reactions, more negative reactions from peers, and more severe legal sanctions for criminal conduct.

Conclusions

Eight‐year‐olds from the study sample demonstrated that they meet the current cognitive standard associated with achieving the ACR. These 8‐year‐olds also provided evidence that they were comparable to older children and adults in terms of their understanding of the wrongfulness of criminal behaviour and the ability to distinguish it from mischievous behaviour.
Looking into the past – the reaction of three grouse species to climate change over the last million years using whole genome sequences
Authors: Kozma Radoslav , Melsted Páll , Magnússon Kristinn P. , Höglund Jacob
Published: November 2015

Tracking past population fluctuations can give insight into current levels of genetic variation present within species. Analysing population dynamics over larger timescales can be aligned to known climatic changes to determine the response of species to varying environments. Here, we applied the Pairwise Sequentially Markovian Coalescent (psmc) model to infer past population dynamics of three widespread grouse species; black grouse, willow grouse and rock ptarmigan. This allowed the tracking of the effective population size (Ne) of all three species beyond 1 Mya, revealing that (i) early Pleistocene cooling (~2.5 Mya) caused an increase in the willow grouse and rock ptarmigan populations, (ii) the mid‐Brunhes event (~430 kya) and following climatic oscillations decreased the Ne of willow grouse and rock ptarmigan, but increased the Ne of black grouse and (iii) all three species reacted differently to the last glacial maximum (LGM) – black grouse increased prior to it, rock ptarmigan experienced a severe bottleneck and willow grouse was maintained at large population size. We postulate that the varying psmc signal throughout the LGM depicts only the local history of the species. Nevertheless, the large population fluctuations in willow grouse and rock ptarmigan indicate that both species are opportunistic breeders while black grouse tracks the climatic changes more slowly and is maintained at lower Ne. Our results highlight the usefulness of the psmc approach in investigating species’ reaction to climate change in the deep past, but also that caution should be taken in drawing general conclusions about the recent past.
The vascular plant‐pathogenic bacterium Ralstonia solanacearum produces biofilms required for its virulence on the surfaces of tomato cells adjacent to intercellular spaces
Authors: Mori Yuka , Inoue Kanako , Ikeda Kenichi , Nakayashiki Hitoshi , Higashimoto Chikaki , Ohnishi Kouhei , Kiba Akinori , Hikichi Yasufumi
Published: November 2015

The mechanism of colonization of intercellular spaces by the soil‐borne and vascular plant‐pathogenic bacterium Ralstonia solanacearum strain OE1‐1 after invasion into host plants remains unclear. To analyse the behaviour of OE1‐1 cells in intercellular spaces, tomato leaves with the lower epidermis layers excised after infiltration with OE1‐1 were observed under a scanning electron microscope. OE1‐1 cells formed microcolonies on the surfaces of tomato cells adjacent to intercellular spaces, and then aggregated surrounded by an extracellular matrix, forming mature biofilm structures. Furthermore, OE1‐1 cells produced mushroom‐type biofilms when incubated in fluids of apoplasts including intercellular spaces, but not xylem fluids from tomato plants. This is the first report of biofilm formation by R. solanacearum on host plant cells after invasion into intercellular spaces and mushroom‐type biofilms produced by R. solanacearum in vitro. Sugar application led to enhanced biofilm formation by OE1‐1. Mutation of lecM encoding a lectin, RS‐IIL, which reportedly exhibits affinity for these sugars, led to a significant decrease in biofilm formation. Colonization in intercellular spaces was significantly decreased in the lecM mutant, leading to a loss of virulence on tomato plants. Complementation of the lecM mutant with native lecM resulted in the recovery of mushroom‐type biofilms and virulence on tomato plants. Together, our findings indicate that OE1‐1 produces mature biofilms on the surfaces of tomato cells after invasion into intercellular spaces. RS‐IIL may contribute to biofilm formation by OE1‐1, which is required for OE1‐1 virulence.
Identification of pathogenicity‐related genes in Fusarium oxysporum f. sp. cepae
Authors: Taylor Andrew , Vágány Viktória , Jackson Alison C. , Harrison Richard J. , Rainoni Alessandro , Clarkson John P.
Published: November 2015

Pathogenic isolates of Fusarium oxysporum, distinguished as formae speciales (f. spp.) on the basis of their host specificity, cause crown rots, root rots and vascular wilts on many important crops worldwide. Fusarium oxysporum f. sp. cepae (FOC) is particularly problematic to onion growers worldwide and is increasing in prevalence in the UK. We characterized 31 F. oxysporum isolates collected from UK onions using pathogenicity tests, sequencing of housekeeping genes and identification of effectors. In onion seedling and bulb tests, 21 isolates were pathogenic and 10 were non‐pathogenic. The molecular characterization of these isolates, and 21 additional isolates comprising other f. spp. and different Fusarium species, was carried out by sequencing three housekeeping genes. A concatenated tree separated the F. oxysporum isolates into six clades, but did not distinguish between pathogenic and non‐pathogenic isolates. Ten putative effectors were identified within FOC, including seven Secreted In Xylem (SIX) genes first reported in F. oxysporum f. sp. lycopersici. Two highly homologous proteins with signal peptides and RxLR motifs (CRX1/CRX2) and a gene with no previously characterized domains (C5) were also identified. The presence/absence of nine of these genes was strongly related to pathogenicity against onion and all were shown to be expressed in planta. Different SIX gene complements were identified in other f. spp., but none were identified in three other Fusarium species from onion. Although the FOC SIX genes had a high level of homology with other f. spp., there were clear differences in sequences which were unique to FOC, whereas CRX1 and C5 genes appear to be largely FOC specific.
Influence and analysis of low‐dosage steroid therapy in severe aristolochic acid nephropathy patients
Authors: Ma Dong‐Hong , Zheng Fa‐Lei , Su Ying , Li Ming‐Xi , Guo Ming‐Hong
Published: November 2015

Aim

To investigate the effect of low‐dosage steroid therapy in patients with severe aristolochic acid nephropathy (AAN).

Methods

Forty‐three chronic AAN patients in the Peking Union Medical College Hospital and the First Affiliated Hospital of Xinxiang Medical College were included in this study from November 1998 to October 2013. According to the treatment method, the patients were divided into a steroid group (SG, n = 25) and a control group (CG, n = 18). The serum biochemical indicators at the basement in the two groups exhibited no obvious statistical differences. In comparison with the baseline data, the levels of serum creatinine at 3, 6, 9, and 12 months were analyzed. The blood pressure, haemoglobin, serum biochemical indicators, and the side‐effects of steroid application were also observed. Urinary macrophage chemoattractant protein‐1 (MCP‐1) and transforming growth factor‐1 (TGF‐1) amounts were measured as well.

Results

(i) The serum creatinine content in the CG group was significantly higher than the baseline level during the follow‐up(6, 9, and 12 months later), whereas in the SG group it decreased during the 3–6 month period and remained stable within 1 year. (ii) The biochemical indicators, blood pressure, and haemoglobin persisted stable. (iii) The side‐effects of low‐dosage steroid therapy were not severe and were tolerated by the AAN patients. (4) Urinary MCP‐1 and TGF‐1 concentrations were positively correlated with serum creatinine and decreased in the SG group.

Conclusion

Low‐dosage steroid therapy reversed or delayed the renal failure progression in severe chronic AAN patients, which may be associated with the suppression of MCP‐1 and TGF‐β1 activities.
Nucleostemin promotes the proliferation of human glioma via Wnt/β‐Catenin pathway
Authors: Bao Zhen , Wang Yunfeng , Yang Lixiang , Wang Lin , Zhu Lianxin , Ban Na , Fan Shaochen , Chen Wenjuan , Sun Jie , Shen Chaoyan , Cui Gang
Published: November 2015

Nucleostemin, nucleolar guanosine triphosphate (GTP)‐binding protein 3, is a member of the MMR1/HSR1 GTP‐binding protein family. The important roles of nucleostemin in self‐renewal, cell cycle regulation, apoptosis, and cell proliferation of various cancer types as been shown. Nevertheless, its expression and potential functions in human glioma is still unclear. In the present study, we demonstrated that up‐regulation of nucleostemin was tightly related to poor 5‐year‐survival ratios. In serum‐starved and re‐feeding models of U251 and U373MG, we observed the rising expression of nucleostemin and p‐β‐Catenin (p‐Tyr645) were accompanied with cell proliferation markers (cyclin D1 and proliferating cell nuclear antigen (PCNA)). Employing nucleostemin‐depletion models, we found down‐regulated nucleostemin and p‐β‐Catenin. The flow cytometry analysis proved the weakened cell proliferation. Moreover, we detected the translocation of β‐Catenin into the nucleus was impaired, meaning the inhibition of the Wnt/β‐Catenin pathway. Taken together, we identified a positive correlation between up‐regulation of nucleostemin and human glioma cell proliferation and that knocking‐down nucleostemin alleviated glioma proliferation by reducing β‐Catenin transportation into the nucleus. All results suggested that nucleostemin might accelerate human glioma proliferation via the Wnt/β‐Catenin pathway.
Uncoupling of sodium and chloride to assist breeding for salinity tolerance in crops
Authors: Genc Yusuf , Oldach Klaus , Taylor Julian , Lyons Graham H.
Published: November 2015

The separation of toxic effects of sodium (Na+) and chloride (Cl−) by the current methods of mixed salts and subsequent determination of their relevance to breeding has been problematic.

We report a novel method (Na+ humate) to study the ionic effects of Na+ toxicity without interference from Cl−, and ionic and osmotic effects when combined with salinity (NaCl). Three cereal species (Hordeum vulgare, Triticum aestivum and Triticum turgidum ssp. durum with and without the Na+ exclusion gene Nax2) differing in Na+ exclusion were grown in a potting mix under sodicity (Na+ humate) and salinity (NaCl), and water use, leaf nutrient profiles and yield were determined.

Under sodicity, Na+‐excluding bread wheat and durum wheat with the Nax2 gene had higher yield than Na+‐accumulating barley and durum wheat without the Nax2 gene. However, under salinity, despite a 100‐fold difference in leaf Na+, all species yielded similarly, indicating that osmotic stress negated the benefits of Na+ exclusion.

In conclusion, Na+ exclusion can be an effective mechanism for sodicity tolerance, while osmoregulation and tissue tolerance to Na+ and/or Cl− should be the main foci for further improvement of salinity tolerance in cereals. This represents a paradigm shift for breeding cereals with salinity tolerance.
Critical realism in nursing: an emerging approach
Authors: Schiller Catharine J.
Published: November 2015

Critical realism, a philosophical framework originally developed by Roy Bhaskar in the 1970s, represents a relatively new approach to research generally and to nursing research in particular. This article explores the ontological and epistemological tenets of critical realism and examines the application of critical realist principles to nursing research and practice through a review of the literature. It is evident that few published nursing research studies have, as of yet, utilized critical realism as their paradigm of choice. Both the strengths and limitations of the presentation and use of critical realism in these studies are discussed in this article. Given the varying degrees of success of the authors in explicating critical realism as a philosophical framework, the value of critical realism to the research study, and the ways in which usage of the critical realist framework influenced development of the study and interpretation of findings, it is evident that the quality of future publications espousing the use of critical realism must continue to be strengthened significantly.
Russellian Monism and Epiphenomenalism
Authors: Robinson William S.
Published: November 2015

Contemporaries often reject epiphenomenalism (EPI) out of hand, while Russellian Monism (RM) is regarded as worthy of further development. It is argued here that this difference of attitudes is indefensible, because the easy rejection of EPI is due to its violating a certain Causal Intuition, and RM implicitly violates that same intuition. An enriched version of RM mitigates the violation, but the same mitigation results if we make a parallel enrichment of EPI. If RM and EPI are approached on a level playing field, it is not obvious which will prove to be the better view.
Historical Moral Responsibility: Is the Infinite Regress Problem Fatal?
Authors: Barnes Eric Christian
Published: November 2015

Some compatibilists have responded to the manipulation argument for incompatibilism by proposing an historical theory of moral responsibility which, according to one version, requires that agents be morally responsible for having their pro‐attitudes if they are to be morally responsible for acting on them. This proposal, however, leads obviously to an infinite regress problem. I consider a proposal by Haji and Cuypers that addresses this problem and argue that it is unsatisfactory. I then go on to propose a new solution inspired by the libertarian theory of Robert Kane.