bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life and Quality of Support for People with Severe Intellectual Disability and Complex Needs
Authors: Beadle‐Brown J. , Leigh J. , Whelton B. , Richardson L. , Beecham J. , Baumker T. , Bradshaw J.
Published: May 2015

Background

People with severe and profound intellectual disabilities often spend substantial time isolated and disengaged. The nature and quality of the support appears to be important in determining quality of life.

Methods

Structured observations and staff questionnaires were used to explore the quality of life and quality of support for 110 people with severe and profound disabilities and complex needs.

Results

On average, people spent approximately 40% of their time engaged in meaningful activities, received contact from staff 25% of the time (6% in the form of assistance to be engaged). Just over one‐third received consistently good active support, which was associated with other measures of quality of support and emerged as the strongest predictor of outcomes.

Conclusions

Quality of life and quality of support were relatively poor, although with about one‐third of people receiving skilled support. Consistently good active support was the best predictor of outcome and proposed as a good indicator of skilled support.
Sexual antagonism in the pistil varies among populations of a hermaphroditic mixed‐mating plant
Authors: Hersh E. , Madjidian J. A. , Andersson S. , Strandh M. , Armbruster W. S. , Lankinen Å.
Published: May 2015

Sexual conflicts and their evolutionary outcomes may be influenced by population‐specific features such as mating system and ecological context; however, very few studies have investigated the link between sexual conflict and mating system. The self‐compatible, mixed‐mating hermaphrodite Collinsia heterophylla (Plantaginaceae) is thought to exhibit a sexual conflict over timing of stigma receptivity. This conflict involves (i) delayed stigma receptivity, which intensifies pollen competition, and (ii) early fertilization forced by pollen, which reduces seed set. We investigated the potential for the conflict to occur under field conditions and performed glasshouse crosses within eight populations to assess its consistency across populations. Flowers were visited, and produced seeds after pollination, at all developmental stages, suggesting that the conflict can be of significance under natural conditions. In the glasshouse, early pollination imposed costs in all populations. Overall, the timing of first seed set was most strongly affected by the maternal parent, denoting stronger female than male ability to influence the onset of stigma receptivity. Crosses also revealed a negative relationship between donor‐ and recipient‐related onset of receptivity within individuals, a novel result hinting at trade‐offs in sex allocation or a history of antagonistic selection. Neither timing of stigma receptivity, timing of first seed set, nor pollen competitive ability covaried with population outcrossing rate. In conclusion, these results indicate that sexually antagonistic selection may be present in varying degrees in different populations of C. heterophylla, but this variation does not appear to be directly related to mating system variation.
Social monogamy vs. polyandry: ecological factors associated with sex roles in two closely related birds within the same habitat
Authors: Goymann W. , Makomba M. , Urasa F. , Schwabl I.
Published: May 2015

Why mainly males compete and females take a larger share in parental care remains an exciting question in evolutionary biology. Role‐reversed species are of particular interest, because such ‘exceptions’ help to test the rule. Using mating systems theory as a framework, we compared the reproductive ecology of the two most contrasting coucals with regard to sexual dimorphism and parental care: the black coucal with male‐only care and the biparental white‐browed coucal. Both species occur in the same lush habitat and face similar ecological conditions, but drastically differ in mating system and sexual dimorphism. Black coucals were migratory and occurred at high breeding densities. With females being obligatory polyandrous and almost twice as heavy as males, black coucals belong to the most extreme vertebrates with reversed sexual dimorphism. Higher variance in reproductive success in fiercely competing females suggests that sexual selection is stronger in females than in males. In contrast, resident white‐browed coucals bred at low densities and invariably in pairs. They were almost monomorphic and the variance in reproductive success was similar between the sexes. Black coucals were more likely to lose nests than white‐browed coucals, probably facilitating female emancipation of parental care in black coucals. We propose that a combination of high food abundance, high population density, high degree of nest loss and male bias in the adult sex ratio represent ecological conditions that facilitate role reversal and polyandry in coucals and terrestrial vertebrates in general.
Volatile organic compounds released by Rumex confertus following Hypera rumicis herbivory and weevil responses to volatiles
Authors: Piesik D. , Wenda‐Piesik A. , Krasińska A. , Wrzesińska D. , Delaney K. J.
Published: May 2015

We report in this study large induction of volatile organic compounds (VOCs) from a single inflorescence of mossy sorrel (Rumex confertus Willd., Polygonaceae), by herbivory of the weevil (Hypera rumicis L., Coleoptera: Curculionidae). VOCs blend induced by the weevil herbivory included 1 green leaf volatiles (GLVs) ((Z)‐3‐hexen‐1‐yl acetate), five terpenes ((Z)‐β‐ocimene, linalool, geranyl acetate, β‐caryophyllene and (E)‐β‐farnesene), three esters (benzyl acetate, methyl salicylate and methyl anthranilate) and one aromatic heterocyclic organic compound (indole). Uninjured plants produced only detectable amounts of VOCs. A Y‐tube experiment revealed that both females and males of H. rumicis were not attracted to any of tested concentrations (1, 5, 25, 125 ng/min). Also both females and males were significantly repelled by the highest concentrations (25 and 125 ng/min). Additionally, concentration of 5 ng/min proved to be repellent for females of H. rumicis.
Examination criteria and calibration procedures for prevention trials of the Early Childhood Caries Collaborating Centers
Authors: Warren John J. , Weber‐Gasparoni Karin , Tinanoff Norman , Batliner Terence S. , Jue Bonnie , Santo William , Garcia Raul I. , Gansky Stuart A. ,   Early Childhood Caries Collaborating Centers
Published: May 2015

Objectives

To summarize diagnostic criteria and examiner training and calibration of the National Institute of Dental and Craniofacial Research‐funded Early Childhood Caries Collaborating Centers (EC4) and report examiner calibration results from 2010 to 2014. The EC4 at Boston University, University of Colorado, and University of California San Francisco are performing randomized controlled early childhood caries (ECC) prevention trials with caries as the main outcome measure.

Methods

The EC4 with University of Iowa consultants developed standardized tooth and tooth surface status examination criteria for use in field conditions, examiner training materials, and examiner calibration and re‐calibration methodologies. Calibration and re‐calibration were performed with 1‐ to 5‐year‐old children in the San Francisco Mission District in which assessments from each examiner to be calibrated were compared with those from a single gold standard examiner from 2010 to 2014. Cohen's kappa statistic was used to determine inter‐examiner agreement.

Results

A total of seven examiners were successfully (re)calibrated during that period, examining a total of 231 children. Overall unweighted Cohen's kappas for 10 surface conditions exceeded the criterion of 0.70. However, separate agreement for assessment of noncavitated lesions, as in other studies, was lower.

Conclusions

An experienced multidisciplinary and multi‐institutional team was able to develop criteria and training materials to anticipate situations and field conditions the main trials would encounter. Examiners were successfully trained and (re)calibrated.
Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs
Authors: Yata M. , McLachlan A. J. , Foster D. J. R. , Page S. W. , Beijerink N. J.
Published: May 2015

Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single‐dose, operator‐blinded, parallel‐dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24‐h period following dosing. Pimobendan and its active metabolite were quantified using an ultra‐high‐performance liquid chromatography–mass spectrometer (UHPLC‐MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (Tmax) 1.1 h] and readily converted to the active metabolite (metabolite Tmax 1.3 h). The elimination half‐life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2–4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.
Neuropeptide Y restores non‐receptor‐mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension
Authors: Hartl Johannes , Dietrich Peter , Moleda Lukas , Müller‐Schilling Martina , Wiest Reiner
Published: May 2015

Background & Aims

Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY‐effects in portal hypertension, we investigated its role for non‐receptor‐mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham‐operated rats.

Methods

Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non‐receptor‐mediated vasoconstriction. Dose–response curves to KCl (30–300 mM) were used to bypass G protein‐coupled receptor mechanisms. Potential involvement of the cyclooxygenase‐pathway was tested by non‐selective cyclooxygenase‐inhibition using indomethacin.

Results

KCl‐induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl‐evoked vascular sensitivity being not different between study groups. However, KCl‐induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY‐induced enhancement of vasoconstriction.

Conclusions

Receptor‐independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non‐receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.
Factors affecting redox potential and differential sensitivity ofSoxRto redox‐active compounds
Authors: Lee Kang‐Lok , Singh Atul K. , Heo Lim , Seok Chaok , Roe Jung‐Hye
Published: May 2015

SoxRis a [2Fe‐2S]‐containing sensor‐regulator, which is activated through oxidation by redox‐active compounds (RACs).SoxRs show differential sensitivity toRACs, partly due to different redox potentials, such thatEscherichia coli(Ec)SoxRwith lower potential respond to broader range ofRACsthanStreptomyces coelicolor(Sc)SoxR.InS. coelicolor, theRACsthat do not activate ScSoxRdid not inhibit growth, suggesting that ScSoxRis tuned to respond to growth‐inhibitoryRACs. Based on sequence comparison and mutation studies, two critical amino acids around the [2Fe‐2S] binding site were proposed as key determinants of sensitivity. ScSoxR‐like mutation (R127L/P131V) in EcSoxRchanged its sensitivity profile as ScSoxR, whereas EcSoxR‐like mutation (L126R/V130P) in ScSoxRcaused relaxed response. In accordance, the redox potentials of EcSoxRR127L/P131Vand ScSoxRL126R/V130Pwere estimated to be −192 ± 8 mV and −273 ± 10 mV, respectively, approaching that of ScSoxR(−185 mV) and EcSoxR(−290 mV). Molecular dynamics simulations revealed that theR127LandP131Vsubstitutions in EcSoxRcaused more electropositive environment around [2Fe‐2S], making it harder to get oxidized. This reveals a mechanism to modulate redox‐potential in [Fe‐S]‐containing sensors by point mutations and to evolve a sensor with differential sensitivity to achieve optimal cellular physiology.
Does elevation of serum creatinine in patients with chronic hepatitis C under therapy of telaprevir mean renal impairment?
Authors: Matsui Katsuomi , Kamijo‐Ikemori Atsuko , Sugaya Takeshi , Ikeda Hiroki , Okuse Chiaki , Shibagaki Yugo , Yasuda Takashi , Kimura Kenjiro
Published: May 2015

Aim

Treatment with telaprevir (TVR) entails adverse side‐effects including anaemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C.

Methods

Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (i) patients with an increase in SCr during the treatment (n = 8), and (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were evaluated.

Results

Although there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase‐in‐SCr group during the triple therapy. The SCr level returned to the pre‐treatment level after cessation of TVR. There were no differences in urinary L‐FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre‐treatment tended to be higher in the increase‐in‐SCr group. Urinary L‐FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR.

Conclusion

Elevation of SCr levels with TVR therapy may not suggest renal impairment.
A member of the Phosphate transporter 1 (Pht1) family from the arsenic‐hyperaccumulating fern Pteris vittata is a high‐affinity arsenate transporter
Authors: DiTusa Sandra Feuer , Fontenot Elena B. , Wallace Robert W. , Silvers Molly A. , Steele Thomas N. , Elnagar Alia H. , Dearman Kelsey M. , Smith Aaron P.
Published: May 2015

Pteris vittata exhibits enhanced arsenic uptake, but the corresponding mechanisms are not well known. The prevalent form of arsenic in most soils is arsenate, which is a phosphate analog and a substrate for Phosphate transporter 1 (Pht1) transporters. Herein we identify and characterize three P. vittata Pht1 transporters.

Pteris vittata Pht1 cDNAs were isolated and characterized via heterologous expression in Saccharomyces cerevisiae (yeast) and Nicotiana benthamiana leaves. Expression of the PvPht1 loci in P. vittata gametophytes was also examined in response to phosphate deficiency and arsenate exposure.

Expression of each of the PvPht1 cDNAs complemented the phosphate uptake defect of a yeast mutant. Compared with yeast cells expressing Arabidopsis thaliana Pht1;5, cells expressing PvPht1;3 were more sensitive to arsenate, and accumulated more arsenic. Uptake assays with yeast cells and radiolabeled 32P revealed that PvPht1;3 and AtPht1;5 have similar affinities for phosphate, but the affinity of PvPht1;3 for arsenate is much greater. In P. vittata gametophytes, PvPht1;3 transcript levels increased in response to phosphate (Pi) deficiency and arsenate exposure.

PvPht1;3 is induced by Pi deficiency and arsenate, and encodes a phosphate transporter that has a high affinity for arsenate. PvPht1;3 probably contributes to the enhanced arsenate uptake capacity and affinity exhibited by P. vittata.
The AC5 protein encoded by Mungbean yellow mosaic India virus is a pathogenicity determinant that suppresses RNA silencing‐based antiviral defenses
Authors: Li Fangfang , Xu Xiongbiao , Huang Changjun , Gu Zhouhang , Cao Linge , Hu Tao , Ding Ming , Li Zhenghe , Zhou Xueping
Published: May 2015

It is generally accepted that begomoviruses in the family Geminiviridae encode four proteins (from AC1/C1 to AC4/C4) using the complementary‐sense DNA as template. Although AC5/C5 coding sequences are increasingly annotated in databases for many begomoviruses, the evolutionary relationships and functions of this putative protein in viral infection are obscure.

Here, we demonstrate several important functions of the AC5 protein of a bipartite begomovirus, Mungbean yellow mosaic India virus (MYMIV). Mutational analyses and transgenic expression showed that AC5 plays a critical role in MYMIV infection. Ectopic expression of AC5 from a Potato virus X (PVX) vector resulted in severe mosaic symptoms followed by a hypersensitive‐like response in Nicotiana benthamiana.

Furthermore, MYMIV AC5 effectively suppressed post‐transcriptional gene silencing induced by single‐stranded but not double‐stranded RNA. AC5 was also able to reverse transcriptional gene silencing of a green fluorescent protein transgene by reducing methylation of promoter sequences, probably through repressing expression of a CHH cytosine methyltransferase (DOMAINS REARRANGED METHYLTRANSFERASE2) in N. benthamiana.

Our results demonstrate that MYMIV AC5 is a pathogenicity determinant and a potent RNA silencing suppressor that employs novel mechanisms to suppress antiviral defenses, and suggest that the AC5 function may be conserved among many begomoviruses.
Does allergy begin in utero?
Authors: Lockett Gabrielle A. , Huoman Johanna , Holloway John W.
Published: May 2015

It has been recognized for centuries that allergic disease runs in families, implying a role for genetic factors in determining individual susceptibility. More recently, a range of evidence shows that many of these genetic factors, together with in utero environmental exposures, lead to the development of allergic disease through altered immune and organ development. Environmental exposures during pregnancy including diet, nutrient intake and toxin exposures can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming. Understanding of these factors will be essential in identifying at‐risk individuals and possible development of therapeutic interventions for the primary prevention of allergic disease. In this review, we summarize the evidence that suggests allergic disease begins in utero, together with possible mechanisms for the effect of environmental exposures during pregnancy on allergic disease risk, including epigenetics.
Vitamin D levels and vitamin D receptor gene polymorphisms in asthmatic children: a case–control study
Authors: Einisman Helly , Reyes María Loreto , Angulo Jenniffer , Cerda Jaime , López‐Lastra Marcelo , Castro‐Rodriguez Jose A.
Published: May 2015

Background

Vitamin D deficiency and single nucleotide polymorphisms (SNP) in the gene encoding vitamin D receptor (VDR) have been associated with asthma.

Objective

To compare 25‐hydroxyvitamin D (25OHD) levels and the frequency of 3 SNPs in the VDR gene between asthmatic and healthy children.

Methods

In persistent asthmatic and healthy control children, the 25OHD levels were measured using radioimmunoassay and SNPs (FokI, ApaI, and TaqI) were analyzed by a PCR‐RFLP assay. Relevant medical history was collected.

Results

About 75 asthmatic (median age: 9.1 years) and 227 healthy children (10.3 years) were studied. In the whole population, the proportion of sufficient, insufficient, and deficient levels of 25OHD were 14.9%, 44%, and 41.1%, respectively. 25OHD sufficiency status was similar in asthmatic and healthy children (p = 0.57). However, the proportion of 25OHD sufficient levels among asthmatics according to the Global Initiative for Asthma treatment steps 2, 3, and 4 was significantly different (8.6%, 16.6%, and 43.7%, respectively, p = 0.046). All patients on step 4 of the treatment (16/16) were heterozygous for the C allele (FokI VDR SNP). There was a lower presence of the C allele among asthmatics in step 2 (30/33), step 3 (16/24), and controls (45/50), p = 0.007, but this significance did not persist after logistic regression. No significant differences in ApaI and TaqI were found.

Conclusions

We found a possible association of vitamin D sufficiency status and FokI C allele with higher requirement of therapy to reach asthma control, suggesting that it may be involved in treatment response. Variations in VDR might also play a role in the 25OHD levels.
Down‐regulation of crambe fatty acid desaturase and elongase in Arabidopsis and crambe resulted in significantly increased oleic acid content in seed oil
Authors: Li Xueyuan , Mei Desheng , Liu Qing , Fan Jing , Singh Surinder , Green Allan , Zhou Xue‐Rong , Zhu Li‐Hua
Published: May 2015

High oleic oil is an important industrial feedstock that has been one of the main targets for oil improvement in a number of oil crops. Crambe (Crambe abyssinica) is a dedicated oilseed crop, suitable for industrial oil production. In this study, we down‐regulated the crambe fatty acid desaturase (FAD) and fatty acid elongase (FAE) genes for creating high oleic seed oil. We first cloned the crambe CaFAD2, CaFAD3 and CaFAE1 genes. Multiple copies of each of these genes were isolated, and the highly homologous sequences were used to make RNAi constructs. These constructs were first tested in Arabidopsis, which led to the elevated oleic or linoleic levels depending on the genes targeted, indicating that the RNAi constructs were effective in regulating the expression of the target genes in nonidentical but closely related species. Furthermore, down‐regulation of CaFAD2 and CaFAE1 in crambe with the FAD2–FAE1 RNAi vector resulted in even more significant increase in oleic acid level in the seed oil with up to 80% compared to 13% for wild type. The high oleic trait has been stable in subsequent five generations and the GM line grew normally in greenhouse. This work has demonstrated the great potential of producing high oleic oil in crambe, thus contributing to its development into an oil crop platform for industrial oil production.
Small RNA and degradome sequencing reveals important microRNA function in Astragalus chrysochlorus response to selenium stimuli
Authors: Cakir Ozgur , Candar‐Cakir Bilgin , Zhang Baohong
Published: May 2015

Selenium (Se), an essential element, plays important roles in human health as well as environmental sustainability. Se hyperaccumulating plants are thought as an alternative selenium resource, recently. Astragalus species are known as hyperaccumulator of Se by converting it to nonaminoacid compounds. However, Se‐metabolism‐related hyperaccumulation is not elucidated in plants yet. MicroRNAs (miRNAs) are key molecules in many biological and metabolic processes via targeting mRNAs, which may also play an important role in Se accumulation in plants. In this study, we identified 418 known miRNAs, belonging to 380 families, and 151 novel miRNAs induced by Se exposure in Astragalus chyrsochlorus callus. Among known miRNAs, the expression of 287 families was common in both libraries, besides 71 families were expressed only in Se‐treated sample, whereas 60 conserved families were expressed in control tissue. miR1507a, miR1869 and miR2867‐3p were mostly up‐regulated, whereas miR1507‐5p and miR8781b were significantly down‐regulated by Se exposure. Computational analysis shows that the targets of miRNAs are involved in different types of biological mechanisms including 47 types of cellular component, 103 types of molecular function and 144 types of biological process. Degradome analysis shows that 1256 mRNAs were targeted by 499 miRNAs. We conclude that some known and novel miRNAs such as miR167a, miR319, miR1507a, miR4346, miR7767‐3p, miR7800, miR9748 and miR‐n93 target transcription factors, disease resistance proteins and some specific genes like cysteine synthase and might be related to plant hormone signal transduction, plant–pathogen interaction and sulphur metabolism pathways.
Venobiliary fistula related to umbilical venous catheter in a newborn
Authors: Türk Erdal , Soylar Ramazan , Akca Tulay , Serter Selim , Karaca İrfan
Published: May 2015

We present a case of venobiliary fistula due to umbilical venous catheter (UVC). UVC was inserted the day before surgery in a newborn who was scheduled for type IIIB jejunal atresia surgery. The UVC was superimposed on the liver. It was noted that the gastric drainage became chylous and increased to 790 and then 1977 mL daily. I.v. contrast tomography with 650 mL contrast showed that the opaque substance was dispersed around the catheter and a venobiliary fistula formed, with the administered fluid accumulating in the duodenum. Rapid improvement was seen in the clinical picture after the UVC was removed. Venobiliary fistula may develop in patients with UVC that is not placed appropriately, and can direct the fluid administered from the UVC to the gastrointestinal system through the choledochal duct. The importance of contrast computed tomography in the diagnosis of venobiliary fistula in the newborn is also emphasized.
Association of TNFSF15 polymorphisms in Korean children with Crohn's disease
Authors: Lee Yeoun Joo , Kim Kyung Mo , Jang Joo Young , Song Kyuyoung
Published: May 2015

Background

Genome‐wide association studies have identified tumor necrosis factor superfamily member 15 (TNFSF15) as a Crohn's disease (CD)‐related gene. The aim of this study was to evaluate the association between five TNFSF15 polymorphisms and CD in Korean children and analyze their genotypes in relation to phenotype.

Methods

Five single‐nucleotide polymorphisms of TNFSF15 (rs3810936, rs6478108, rs6478109, rs7848647, rs7865494) were genotyped in 108 CD patients and in 599 healthy controls. Risk allele, genotype, and haplotype were analyzed in CD patients and controls, and genotype–phenotype relationships were studied.

Results

There were significant associations of rs3810936, rs6478108, rs6478109, rs7848647 with CD in Korean pediatric patients (P = 6.5×10‐8, P = 1.3×10‐8, P = 3.7×10‐8, P = 2.9×10‐8, respectively). The adjusted OR (aOR) for the homozygous risk allele genotype was significantly higher than that for the homozygous genotype for the opposite allele: rs3810936, aOR, 5.36 (95%CI: 2.61–10.98, P = 4.6×10‐6); rs6478108, aOR, 6.62 (95%CI: 3.03–14.46, P = 2.2×10‐6); rs6478109, aOR, 6.24 (95%CI: 2.85–13.66, P = 4.6×10‐6); rs7848647, aOR, 6.32 (95%CI: 2.89–13.81, P = 3.8×10‐6). The risk allele of rs3810936 was associated with later symptom onset, later diagnosis, and the presence of perianal lesion (P = 0.013, P = 0.016 and P = 0.029).

Conclusion

There was a significant association of TNFSF15 with pediatric CD in Korean patients.
Oxidant and antioxidant status in neonatal proven and clinical sepsis according to selenium status
Authors: Asci Ali , Surmeli‐Onay Ozge , Erkekoglu Pinar , Yigit Sule , Yurdakok Murat , Kocer‐Gumusel Belma
Published: May 2015

Background

Selenium is a trace element required for the functioning of the immune system. Neonatal sepsis is a serious condition leading to morbidity and mortality in neonates worldwide. The purpose of this study was to measure selenium and plasma selenoprotein P (SePP), selenoenzyme activity, and alterations in oxidant/antioxidant status with immune biomarkers in neonates with clinical (n = 27) and proven neonatal sepsis (n = 25).

Methods

Erythrocyte selenium and SePP; plasma lipid peroxidation (LP), protein oxidation and total antioxidant capacity and erythrocyte total glutathione (GSH) concentration; erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase (CAT) and total superoxide dismutase (SOD) activity were measured spectrophotometrically/spectrofluorometrically. Plasma interleukin 2 and 6 were also measured.

Results

Erythrocyte selenium and SePP were markedly lower both in the clinical and proven sepsis groups versus control. Erythrocyte GPx activity was higher only in the clinical sepsis group. TrxR activity was markedly lower in proven sepsis. SOD activity and GSH were markedly higher both in clinical sepsis and in proven sepsis. CAT activity was significantly higher both in clinical sepsis and in proven sepsis. LP and protein oxidation were significantly higher in both of the sepsis groups.

Conclusions

Both selenium‐dependent and selenium‐independent blood redox systems were altered in sepsis, suggesting that sepsis causes an imbalance between cellular antioxidant and oxidant states.
The Homophobic Sexual Harassment Claim and Sexuality Discrimination
Authors: Rocha James
Published: May 2015

In sexual harassment law scholarship, it is often argued that the reasonable person standard should give way to a reasonable victim (woman) standard. Yet, this latter standard may unintentionally invite homophobic employees to attempt to use a reasonable homophobe standard to charge gay supervisors with harassment merely for being openly gay at work. In response, I argue that we currently act on an unjustifiable distinction whereby we treat sexuality behavior (behavior that indicates one's sexuality) as necessarily sexualized only for GLBTQ behavior. By disallowing this discriminatory treatment, we can preserve the reasonable victim standard and undermine the homophobe's warrantless charges.
Niccolò Machiavelli: Father of Modern Constitutionalism
Authors: Sellers Mortimer N. S.
Published: May 2015

Niccolò Machiavelli is the father of modern constitutionalism. Constitutionalism began anew in the modern world with the study of the ancient republics and it was Machiavelli who inaugurated this revived science of politics. Five hundred years after the composition of Il Principe and the Discorsi we are still working out the implications of applying reason to the structures of law and government in pursuit of justice and the common good. Modern constitutionalism and ancient republicanism share three central beliefs: first, that government should serve justice and the common good; second, that government should do so through known and stable laws; third, that these will best be secured through the checks and balances of a well‐designed constitution. Machiavelli took the theories and experiences of republican Rome and applied them to his own era. This application of reason to constitutional design transformed the politics of emergent modernity and reconfigured government throughout the world.
Machiavelli and the Problem of Dictatorship
Authors: Geuna Marco
Published: May 2015

Machiavelli is the first modern political thinker who pays great attention to the magistracy of dictatorship. “Dictatorial authority,” as he puts it, is fundamental to the survival and prosperity of republics: It is the magistracy, the “ordinary mode,” to which they turn to deal with “extraordinary accidents,” political and military emergencies. Machiavelli's gaze is cast both on the Ancient and the Modern world: Although he concentrates on the Roman magistracy, he also pays attention to magistracies of the modern world that were in some way similar, such as the Council of the Ten in the Republic of Venice. In my paper, I will attempt to reconstruct the essential points of Machiavelli's discussion on dictatorship; in the concluding remarks, I will briefly tackle the more general question of the relationship between politics and law in his work as a whole.
Machiavelli at 500: From Cynic to Vigilant Supporter of International Law
Authors: Follesdal Andreas
Published: May 2015

Machiavelli's 500‐year‐old treatiseThe Princeoutlined the central features of the realist tradition in international relations. His premises led him to question the likelihood of efficacious and stable international law and international courts, a skepticism that has present‐day proponents.Machiavelli's reluctance was due to a combination of features ofhuman natureand a focus on anarchic features of therelations among states. This article challenges these assumptions and implications: Other interpretations of human nature are closer toMachiavelli's text, and current relations among states are significantly different. The revised assumptions should makeMachiavelli's followers more optimistic about international law and international courts.
Machiavelli, Guicciardini and the “Governo Largo”
Authors: Pinelli Cesare
Published: May 2015

Niccolò Machiavelli's support for what he calls governo largo, or popular government, is usually contrasted with the diffidence towards it of Francesco Guicciardini, the Florentine aristocrat. The article argues that both these authors grounded their vision on Polybius' theory of “mixed government,” though adapting it in different directions. In examining this difference, the article reaches the conclusion that it concerns far less the degree of popular participation in political decision‐making and government than the value that Machiavelli and Guicciardini respectively ascribe to it in comparison with that of safety‐liberty (or legal certainty). In this respect, their theories may be viewed as anticipating the tensions between democracy and the rule of law, the co‐presence of which provides the essential foundation of the structure of present‐day constitutional democracies.
Histopathology of the idiopathic interstitial pneumonias (IIP): A review
Authors: Tabaj Gabriela C. , Fernandez Cristina F. , Sabbagh Eduardo , Leslie Kevin O.
Published: May 2015

The 2013 American Thoracic Society/European Respiratory Society consensus classification update of the idiopathic interstitial pneumonias (IIP) included several important modifications to the organization and spectrum of the diseases that were proposed in an earlier multidisciplinary consensus document in 2002. The histopathology of the now ‘major’ and ‘rare’ IIP is presented here with exposition of the newly included entity of a distinctive upper lobe fibrotic lung disease referred to as idiopathic pleuroparenchymal fibroelastosis. The ‘rare histological patterns’ of acute fibrinous and organizing pneumonia and bronchiolocentric patterns of interstitial pneumonia are illustrated and discussed.
Accuracy of PaO2/FiO2 calculated from SpO2 for severity assessment in ED patients with pneumonia
Authors: Sanz Francisco , Dean Nathan , Dickerson Justin , Jones Barbara , Knox Daniel , Fernández‐Fabrellas Estrella , Chiner Eusebi , Briones María Luisa , Cervera Ángela , Aguar María Carmen , Blanquer José
Published: May 2015

Background and objective

Assessment of oxygenation in patients with community‐acquired pneumonia is critical for treatment. The accuracy of percutaneous oxygen saturation (SpO2) determined by pulse oximetry is uncertain, and it has limited value in patients receiving supplemental oxygen. We hypothesized that calculation of partial arterial oxygen concentration/inspired oxygen faction (PaO2/FiO2) from SpO2 by the Ellis or Rice equations might adequately correlate with PaO2/FiO2 measured by arterial blood gases.

Methods

We studied 1004 patients with pneumonia in the emergency department with simultaneous measurement of SpO2 and PaO2 from two cohorts from Valencia, Spain and Utah, USA. We compared SpO2 with measured SaO2, compared the equations' accuracy in calculating PaO2/FiO2 and determined how often patients would be misclassified at clinically important thresholds. We compared estimated PaO2/FiO2 to measured PaO2/FiO2 using the Spearman correlation.

Results

Pairwise correlation of SpO2 with SaO2 was moderate (rho = 0.66; P < 0.01). Both equations performed similarly among patients with lower PaO2/FiO2 ratios. The Ellis equation estimated PaO2/FiO2 from SpO2 more accurately than the Rice equation in patients with PaO2/FiO2 ≥200. Simple agreement between calculated and measured P/F was 91% and 92%, respectively.

Conclusions

The Ellis equation was more accurate than the Rice equation for estimating PaO2/FiO2, especially at higher levels of P/F ratio. Estimation of PaO2/FiO2 from SpO2 is accurate enough for initial oxygenation assessment. Ellis and Rice equations could misclassify 20% and 30% of patients, respectively, at higher levels of PaO2/FiO2. For patients with abnormal oxygenation falling near thresholds for clinical decision making, arterial blood gas measurement preferably on room air is more accurate.
Interleukin‐33 Triggers B1 Cell Expansion and Its Release of Monocyte/Macrophage Chemoattractants and Growth Factors
Authors: Ahmed Ammad , Koma Mousa Komai
Published: May 2015

B1 B lymphocytes are natural IgM‐producing cells primarily found in peritoneum and mucosal sites. They perform vital functions during the early defence against viral and bacterial infections. Murine B1 cells express IL‐33 receptor complex on activation. IL‐33 is a new addition to the IL‐1 family with a strong role in Th2 immunity. B1 cells have been recognized to exacerbate contact sensitivity by producing IgM and IL‐5 in response to interleukin‐33. However, the exact response of IL‐33/ST2 signalling in B1 cells is not completely understood. In this study, we report that murine B1 cells respond directly to IL‐33 in a ST2‐dependent manner. This interaction instigates B1b cell proliferation in a time‐dependent manner in vivo. Furthermore, it also mediates monocyte/macrophage and granulocyte recruitment via B1 cell release of chemokines (MCP‐1 and MIP‐1 alpha). It was noted that upon stimulation, B1b cells additionally release an angiogenic inducer vascular endothelial growth factor and granulocyte–monocyte colony‐stimulating factor (GM‐CSF). Our findings suggest that these IL‐33‐mediated B1 cells might be able to play a vital role in the recruitment and growth of monocytes and granulocytes.
A Conversation with Cohn on the Activation of CD4 T Cells
Authors: Bretscher P. A.
Published: May 2015

Despite an agreement on most issues surrounding models for how lymphocytes are activated and inactivated, and arising out of the 1970 Two Signal Model of lymphocyte activation, Cohn and I have different perspectives on two critical issues concerning the activation of CD4 T cells. One issue is the origin of the first effector T helper (eTh) cells, postulated by both of us to be required to optimally activate precursor Th (pTh), that is naïve CD4 T cells, to further generate eTh cells. The second issue arises from our agreement that the antigen‐dependent CD4 T cell cooperation, that we both postulate is required to activate naïve CD4 T (pTh) cells, most likely is mediated by the operational recognition of linked epitopes. Although agreeing on the centrality of this operational mechanism, we disagree about how it might be realized at the molecular/cellular level. I respond here to issues raised by Cohn concerning these two mechanistic questions, in his response to my recent article on the activation and inactivation of mature CD4 T cells.
Environment, livelihood and household: The ethno‐history of Rana Tharus Badaghar households
Authors: Lam Lai Ming
Published: May 2015

This paper focuses on the changes occurring in households in the indigenous Rana Tharus community. I discuss the household not in terms of physical structure but instead on the social aspects: how people relate to each other through the lens of the household context. I argue that the fluid nature of households makes its flexible to different ecological environments and socio‐economic scenarios. My ethnography of Rana households clearly illustrated that the formation, structure and management of Rana households was fundamentally linked to people's livelihoods. Before 1950s, abundant land resources allowed Ranas to live in joint‐type households. This particular household arrangement not only fulfilled labour needs but also secured the mutual security for every household member. Gradually, undivided and big households (known in Rana as Badaghar) became the ideal model for Ranas as soon as such establishments did not become divided or separated. This household structure also served as an important safety net for most Ranas and fundamental to other social relationships especially Mukhiya (household head system) and Kurmaa (patrilineal kin). However, since the 1950s, new socio‐economic landscapes have significantly challenged the maintenance of traditional Rana households. Within the lifetime of most Ranas, they first experienced household fission and the disappearance of the Mukhiya system. The dynamic relationships between Rana household and new ecological, social and economic landscapes are explored here. It is concluded that the household is a critical institution allowing anthropologists to better understand the long‐term social impacts caused by state policies and ecological changes. This is because people often practice their new household relations in their everyday life as a response to environmental and livelihood changes.
GSK‐3β Phosphorylation of Cytoplasmic Dynein Reduces Ndel1 Binding to Intermediate Chains and Alters Dynein Motility
Authors: Gao Feng J. , Hebbar Sachin , Gao Xu A. , Alexander Michael , Pandey Jai P. , Walla Michael D. , Cotham William E. , King Stephen J. , Smith Deanna S.
Published: May 2015

Glycogen synthase kinase 3 (GSK‐3) has been linked to regulation of kinesin‐dependent axonal transport in squid and flies, and to indirect regulation of cytoplasmic dynein. We have now found evidence for direct regulation of dynein by mammalian GSK‐3β in both neurons and non‐neuronal cells. GSK‐3β coprecipitates with and phosphorylates mammalian dynein. Phosphorylation of dynein intermediate chain (IC) reduces its interaction with Ndel1, a protein that contributes to dynein force generation. Two conserved residues, S87/T88 in IC‐1B and S88/T89 in IC‐2C, have been identified as GSK‐3 targets by both mass spectrometry and site‐directed mutagenesis. These sites are within an Ndel1‐binding domain, and mutation of both sites alters the interaction of IC's with Ndel1. Dynein motility is stimulated by (i) pharmacological and genetic inhibition of GSK‐3β, (ii) an insulin‐sensitizing agent (rosiglitazone) and (iii) manipulating an insulin response pathway that leads to GSK‐3β inactivation. Thus, our study connects a well‐characterized insulin‐signaling pathway directly to dynein stimulation via GSK‐3 inhibition.
Ex Vivo Evaluation of Skin Staples for Typhlotomy Closure in Cattle
Authors: Caramello Vittorio , Comino Francesco , Giusto Gessica , Gandini Marco
Published: May 2015

Objective

To compare 2 sutured techniques with a skin stapled technique for typhlotomy closure in bovines.

Study Design

Ex‐vivo study.

Sample Population

Bovine fresh cadaveric ceca (n = 27).

Methods

Typhlotomies (4 cm in length) were made on the cecal apex and closed with 1 of the following techniques: hand‐sewn, 2‐layer suture consisting of a continuous, full‐thickness layer oversewn with a Cushing layer (Group FC); hand‐sewn, double inverting suture consisting of a 1st Cushing layer oversewn with an additional Cushing layer (Group CC); skin staples (Group S). Closure time, bursting pressure, and related costs of each technique were calculated and compared.

Results

Median (range) construction time for group S was 1.12 (0.49–1.3) min and was significantly shorter than for group FC 5.14 min (3.45–7.44), and for group CC 4.26 min (2.3–5.52) (95% CI 3.342–4.851), (P = .007). There was no significant difference between bursting pressures of group S (91.67 ± 15.41 mmHg, 95% CI 79.82–103.5) compared with group FC (119.4 ± 40.03 mmHg, 95% CI 88.67–150.2) (P = .160) and compared with group CC (103.3 ± 32.31 mmHg, 95% CI 78.5–128.2) (P = .707)

Conclusion

Hand‐sewn techniques are effective but fairly demanding in terms of time. Skin staples are less time‐consuming, and resist pressures comparable to those resisted by handsewn techniques. For this reason, an SKS technique may be a valid option for typhlotomy closure in cattle.
High Emitter Light Duty Vehicle Contributions to On-road Mobile Emissions in 2018 and 2030
Authors: Collet Susan , Kidokoro Toru , Kinugasa Yukio , Karamchandani Prakash , DenBleyker Allison
Published: May 2015

Quantifying the proportion of normal- and high-emitting vehicles and their emissions is vital for creating an air quality improvement strategy for emission reduction policies. This paper includes the California LEV III and United States Environmental Protection Agency Tier 3 vehicle regulations in this projection of high emitter quantification for 2018 and 2030. Results show high emitting vehicles account for up to 6% of vehicle population and vehicle miles traveled. Yet, they will contribute to over 75% of exhaust and 66% of evaporative emissions. As these high emitting vehicles are gradually retired from service and are removed from the roads, the overall effect on air quality from vehicle emissions will be reduced.
Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination
Authors: Ono Taisuke , Takada Shingo , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: May 2015

New Findings

What is the central question of this study?

We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress.

What is the main finding and its importance?

We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin‐induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus.

Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti‐inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin‐induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg−1
i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg−1 day−1) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross‐sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle‐specific ubiquitin E3 ligase atrogin‐1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor‐κB activation, concentrations of the inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β and oxidative stress were increased in the skeletal muscle from DM mice and inhibited in DM+Curcumin mice. Curcumin ameliorated skeletal muscle atrophy in DM mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 DM.