bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Kineret® on ovarian ischemia reperfusion injury in a rat model
Authors: Nayki Umit Arslan , Nayki Cenk , Cetin Nihal , Cimen Ferda Keskin , Coban Abdulkadir , Mammadov Renad , Tas Ismail Hakkı , Malkoc Ismail
Published: August 2016

Aim

To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries.

Methods

Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR‐50); 100 mg/kg Kineret® + ovarian IR (KIR‐100); and sham operation (SOC). KIR‐50 (n = 10) and KIR‐100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups.

Results

In rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL‐1β) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret® at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL‐1β and a decrease in tGSH caused by IR more significantly than administration of Kineret® at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret® significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret® at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret.

Conclusion

Our findings indicate that Kineret® might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion.
Perinatal outcome of monochorionic diamniotic twin pregnancies complicated with isolated amniotic fluid volume abnormality of one twin less than 26 weeks of gestation
Authors: Kawamura Hiroshi , Ishii Keisuke , Mabuchi Aki , Yamamoto Ryo , Hayashi Shusaku , Mitsuda Nobuaki
Published: August 2016

Aim

To evaluate the incidence of twin‐twin transfusion syndrome (TTTS) and the perinatal outcome at 28 days of age in monochorionic diamniotic (MCDA) pregnancies complicated with isolated polyhydramnios (I‐Poly) and isolated oligohydramnios (I‐Oligo) diagnosed < 26 weeks of gestation.

Methods

This was a retrospective study of women with MCDA pregnancies diagnosed with I‐Poly or I‐Oligo before 26 weeks of gestation over a period of six years. The incidence of subsequent TTTS and neonatal outcome in terms of intact survival (IS) at 28 days of age were evaluated. Intact survival was defined as being alive without any neurological complications at 28 days of age.

Results

There were 30 cases of I‐Poly and 53 of I‐Oligo that were eligible as per the inclusion criteria. Subsequent TTTS were complicated in six (20.0%) of the I‐Poly and 26 (49.0%) of the I‐Oligo cases. Among subjects with I‐Poly, 17 had spontaneously normalized amniotic fluid volume. Prolonged oligohydramnios until intrauterine death, delivery or the onset of emerging TTTS was noted in 16 cases of I‐Oligo. Both the twins exhibited IS in 26 (86.7%) cases of I‐Poly and 31 (58.4%) cases of I‐Oligo.

Conclusion

One‐fifth of I‐Poly and half of I‐Oligo MCDA twins at < 26 weeks of gestation potentially develop TTTS. I‐Oligo in particular should be regarded as a high‐risk condition as neonatal IS is less than 60%.
The role of hypoxia in oral cancer and potentially malignant disorders: a review
Authors: Kujan Omar , Shearston Kate , Farah Camile S.
Published: August 2016

Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated ‘potentially malignant disorders’. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia‐induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena.
Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis
Authors: Hov Johannes R. , Boberg Kirsten M. , Taraldsrud Eli , Vesterhus Mette , Boyadzhieva Maria , Solberg Inger Camilla , Schrumpf Erik , Vatn Morten H. , Lie Benedicte A. , Molberg Øyvind , Karlsen Tom H.
Published: August 2016

Background & Aims

The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC.

Methods

Antineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA‐B and HLA‐DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA‐DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease.

Results

Antineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA‐positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA‐B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA‐positive than ‐negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA‐positive patients. In UC patients without liver disease, HLA‐DRB1*03 was more prevalent in pANCA‐positive compared with ‐negative patients (P=.03).

Conclusions

Antineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC‐UC disease spectrum.
“Blue” Morality and the Legitimacy of the State—Ed Rubin's Soul, Self, and Society: The New Morality and the Modern State
Authors: Carbone June
Published: August 2016

Ed Rubin's provocative new book, Soul, Self, and Society: The New Morality & the Modern State (2015), attempts to capture the relationship between morality and the state. It maintains that that there are three comprehensive moral systems: the morality of honor that characterized feudal relationships and survives today in failed states and urban gangs, the morality of higher purposes that linked individual self-worth and state legitimacy to a shared belief system, and the morality of self-fulfillment that entrusts development of a moral code to each individual and sees the role of the state as creating the conditions for individual flourishing. This review essay argues that Rubin's work is critically important in explaining that the idea of self-fulfillment combines public tolerance with private discipline, and rests on obligation as well as freedom. It suggests, however, that if the new morality were to truly take hold, it would weaken the links between citizen and state that make the system possible.
Activist Lawyers in Post-Tiananmen China
Authors: Stern Rachel E.
Published: August 2016

What do the activities of twenty-first-century Chinese lawyers tell us about the origins and prospects of legal activism under authoritarianism? This essay fits China's Human Rights Lawyers (2014) into an emerging literature on authoritarian legality. The book offers an insider view of a circle of lawyers interested in using China's newly accessible courts as a platform for social activism. It highlights the difficulty of rights lawyers' day-to-day work against the backdrop of the Chinese state's long-term experiment in how to harness the power of law without ceding political control.
The Performance Pay Premium and Wage Dispersion in Britain
Authors: Bryson Alex , Forth John , Stokes Lucy
Published: August 2016

Estimates of the performance pay (PP) premium using household survey data are upwardly biased due to the use of PP contracts in higher paying workplaces. Using nationally representative linked employer‐employee data we estimate the PP premium at the mean and across the wage distribution, after accounting for workplace heterogeneity. We then present the effects of PP on the wage distribution. Failure to account for the use of PP in high paying workplaces overstates the PP premium by one‐third. The premium rises as one moves up the wage distribution, but the effect is more modest after having accounted for workplace heterogeneity.
Differentially regulated high‐affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces marneffei
Authors: Pasricha Shivani , Schafferer Lukas , Lindner Herbert , Joanne Boyce Kylie , Haas Hubertus , Andrianopoulos Alex
Published: August 2016

Iron is a key trace element important for many biochemical processes and its availability varies with the environment. For human pathogenic fungi iron acquisition can be particularly problematical because host cells sequester free iron as part of the acute‐phase response to infection. Fungi rely on high‐affinity iron uptake systems, such as reductive iron assimilation (RIA) and siderophore‐mediated iron uptake (non‐RIA). These have been extensively studied in pathogenic fungi that exist outside of host cells, but much less is known for intracellular fungal pathogens. Talaromyces marneffei is a dimorphic fungal pathogen endemic to Southeast Asia. In the host T. marneffei resides within macrophages where it grows as a fission yeast. T. marneffei has genes of both iron assimilation systems as well as a paralogue of the siderophore biosynthetic gene sidA, designated sidX. Unlike other fungi, deletion of sidA or sidX resulted in cell type‐specific effects. Mutant analysis showed that T. marneffei yeast cells also employ RIA for iron acquisition, providing an additional system in this cell type that differs substantially from hyphal cells. These data illustrate the specialized iron acquisition systems used by the different cell types of a dimorphic fungal pathogen and highlight the complexity in siderophore‐biosynthetic pathways amongst fungi.
Aspidistra obtusata sp. nov. (Asparagaceae) from Vietnam
Authors: Vislobokov Nikolay A.
Published: August 2016

Aspidistra obtusata is described and illustrated as a new species from southern Vietnam. The new species resembles A. truongii, but differs in smaller diameter of perigone (12.6–14.9 mm vs 25–35 mm), shape of tepals (elliptic, obtuse vs triangular‐ovate) and pistil (widely obconic vs mushroom‐shaped). A molecular characterization of the new species (based on data of plastid psbA‐trnH and nuclear 5S‐NTS regions) is also given, and compared with the most similar congeners.
A grapevine cytochrome P450 generates the precursor of wine lactone, a key odorant in wine
Authors: Ilc Tina , Halter David , Miesch Laurence , Lauvoisard Florian , Kriegshauser Lucie , Ilg Andrea , Baltenweck Raymonde , Hugueney Philippe , Werck‐Reichhart Danièle , Duchêne Eric , Navrot Nicolas
Published: August 2016

Monoterpenes are important constituents of the aromas of food and beverages, including wine. Among monoterpenes in wines, wine lactone has the most potent odor. It was proposed to form via acid‐catalyzed cyclization of (E)‐8‐carboxylinalool during wine maturation. It only reaches very low concentrations in wine but its extremely low odor detection threshold makes it an important aroma compound.

Using LC‐MS/MS, we show here that the (E)‐8‐carboxylinalool content in wines correlates with their wine lactone content and estimate the kinetic constant for the very slow formation of wine lactone from (E)‐8‐carboxylinalool. We show that (E)‐8‐carboxylinalool is accumulated as a glycoside in grape (Vitis vinifera) berries and that one of the cytochrome P450 enzymes most highly expressed in maturing berries, CYP76F14, efficiently oxidizes linalool to (E)‐8‐carboxylinalool.

Our analysis of (E)‐8‐carboxylinalool in Riesling × Gewurztraminer grapevine progeny established that the CYP76F14 gene co‐locates with a quantitative trait locus for (E)‐8‐carboxylinalool content in grape berries.

Our data support the role of CYP76F14 as the major (E)‐8‐carboxylinalool synthase in grape berries and the role of (E)‐8‐carboxylinalool as a precursor to wine lactone in wine, providing new insights into wine and grape aroma metabolism, and new methods for food and aroma research and production.
Frequency and occurrence of the carrot pathogen ‘Candidatus Liberibacter solanacearum’ haplotype C in Finland
Authors: Haapalainen M. , Kivimäki P. , Latvala S. , Rastas M. , Hannukkala A. , Jauhiainen L. , Lemmetty A. , Pirhonen M. , Virtanen A. , Nissinen A. I.
Published: August 2016

Occurrence of ‘Candidatus Liberibacter solanacearum’ (CLso) was studied in field‐grown carrots (Daucus carota) in different regions of Finland. In addition, the frequency of CLso in carrots and in field populations of its vector, the carrot psyllid (Trioza apicalis), was studied in southwestern Finland. CLso was detected in six of the seven regions where the main carrot cultivation areas are located. The highest disease incidence was found in southwestern Finland, in the area where this carrot pathogen was originally found. In the Tavastia Proper and Southwest Finland regions, CLso was detected in 26 out of 30 randomly chosen fields inspected in 2013 and 2014, and in a third of those fields more than 10% of plants showed symptoms. Of those carrots showing both psyllid feeding‐associated leaf curling and CLso infection‐associated leaf discolouration symptoms, 77% were CLso positive in the PCR test. Some symptomless carrots from the affected fields also tested positive. Of the carrot psyllid individuals collected from the same area, 60% were CLso positive. Elsewhere, disease incidence was variable in South Ostrobothnia in western Finland and low but established in South Savonia in eastern Finland. CLso was not detected in the North Ostrobothnia region. Sequencing of the amplified DNA fragments confirmed that the bacteria in the carrot samples from different areas within Finland all represented CLso haplotype C. The frequent occurrence and wide distribution of this pathogen, transmitted by a psyllid that does not migrate over long distances, suggest that it is persistent in Finland.
Development of the cardiorespiratory system in dogs from days 16 to 46 of pregnancy
Authors: Martins AA , Favaron PO , de Jesus Oliveira L , Schäfer BT , Oliveira FD , Miglino MA
Published: August 2016

Contents

Dogs have been studied for several reasons, such as the genetic improvement, their use as experimental models, in zoonotic research, cell therapy and as a model for human diseases. However, many features relating to the embryonic development of dogs remain unknown because of the absence of embryological studies. Considering the importance of the cardiorespiratory system in the development of embryos, the aim of this study was to investigate the development of the main cardiorespiratory organs of dog embryos and foetuses with estimated gestational ages from 16 to 46 days using macro‐ and microscopic descriptions. On day 16 of development, the neural tube and crest were formed, the anterior and posterior neuropore closure had begun and the somites had developed. Between days 22 and 27 of gestation, the lung buds and the initial formation of the primary bronchi and heart chambers were observed. The heart chambers exhibited the endo‐, myo‐ and epicardial layers but did not have obvious differences in thickness among each other. Between days 41 and 46 of gestation, the nasal conchae and septa and trachea were formed, which exhibited characteristic epithelia. The lung formation and lobation were complete. The heart and major vessels exhibited mature histological architecture when their anatomical development was complete. The results of this study contribute to a more accurate definition of the embryonic and foetal developmental stages in dogs.
Malignant pleural fluid from mesothelioma has potent biological activities
Authors: Cheah Hui Min , Lansley Sally M. , Varano della Vergiliana Julius F. , Tan Ai Ling , Thomas Rajesh , Leong Su Lyn , Creaney Jenette , Lee Yun Chor Gary
Published: August 2016

ABSTRACT

Background and objective

Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo‐resistance of mesothelioma.

Methods

Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed.

Results

Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan‐blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23‐fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13‐fold in six mesothelioma cell lines using scratch‐wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm2 vs 28.0 cm2 at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed‐induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs.

Conclusion

This ‘proof‐of‐concept’ study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology.
Early Jurassic North Atlantic sea‐surface temperatures from TEX86 palaeothermometry
Authors: Robinson Stuart A. , Ruhl Micha , Astley David Lee , Naafs B. David A. , Farnsworth Alexander J. , Bown Paul R. , Jenkyns Hugh C. , Lunt Daniel J. , O'Brien Charlotte , Pancost Richard D. , Markwick Paul J.
Published: August 2016

Early Jurassic marine palaeotemperatures have been typically quantified by oxygen‐isotope palaeothermometry of benthic and nektonic carbonate and phosphatic macrofossils. However, records of Early Jurassic sea‐surface temperatures that can be directly compared with general circulation model simulations of past climates are currently unavailable. The TEX86 sea‐surface temperature proxy is based upon the relative abundance of glycerol dialkyl glycerol tetraethers preserved in organic‐carbon‐bearing sediments. This proxy has been used extensively on Cretaceous and Cenozoic materials and, in one study, on Middle and Upper Jurassic sediments. Here, TEX86 is applied, for the first time, to Lower Jurassic (Sinemurian–Pliensbachian) sediments cored at Deep Sea Drilling Project Site 547 in the North Atlantic. The abundance of glycerol dialkyl glycerol tetraethers in these sediments is very low, despite biomarker and Rock‐Eval data suggesting that thermal maturity is, generally, low. Sea floor oxygenation and a high input of reworked terrestrially sourced organic matter may explain the low concentrations. For samples from which it was possible to quantify the relative abundance of glycerol dialkyl glycerol tetraethers, TEX86 values range from 0·78 to 0·88, equating to sea‐surface temperatures in excess of >28°C. These temperatures are broadly comparable with new general circulation model simulations of the Sinemurian and Pliensbachian stages and support the general view of a predominantly warm climate. The new proxy data suggest that, under favourable geological conditions, it is possible to extend the record of TEX86‐based sea‐surface temperatures back into the Early Jurassic.
Nutrient availability and corn growth in a poultry litter biochar‐amended loam soil in a greenhouse experiment
Authors: Brantley K. E. , Savin M. C. , Brye K. R. , Longer D. E.
Published: August 2016

Nutrient‐rich biochar produced from animal wastes, such as poultry litter, may increase plant growth and nutrient uptake although the role of direct and indirect mechanisms, such as stimulation of the activity of mycorrhizal fungi and plant infection, remains unclear. The effects of poultry litter biochar in combination with fertilizer on mycorrhizal infection, soil nutrient availability and corn (Zea mays L.) growth were investigated by growing corn in a loam soil in a greenhouse with biochar (0, 5 and 10 Mg/ha) and nitrogen (N) and phosphorus (P) fertilizer (0, half and full rates). Biochar did not affect microbial biomass C or N, mycorrhizal infection, or alkaline phosphomonoesterase activities, but acid phosphomonoesterase activities, water‐soluble P, Mehlich‐3 Mg, plant height, aboveground and root biomass, and root diameter were greater with 10 Mg/ha than with no biochar. Root length, volume, root tips and surface area were greatest in the fully fertilized soil receiving 10 Mg/ha biochar compared to all other treatments. The 10 Mg/ha biochar application may have improved plant access to soil nutrients by promoting plant growth and root structural features, rather than by enhancing mycorrhizal infection rates.
HLA class I variation in Iranian Lur and Kurd populations: high haplotype and allotype diversity with an abundance of KIR ligands
Authors: Ashouri E. , Norman P. J. , Guethlein L. A. , Han A. S. , Nemat‐Gorgani N. , Norberg S. J. , Ghaderi A. , Parham P.
Published: August 2016

HLA‐A, ‐B and ‐C alleles of 285 individuals, representing three Iranian Lur populations and one Iranian Kurd population were sequenced completely, yielding human leukocyte antigen (HLA) class I genotypes at high resolution and filling four fields of the official HLA nomenclature. Each population has 87–99 alleles, evenly distributed between the three HLA class I genes, 145 alleles being identified in total. These alleles were already known, named and deposited in the HLA database. The alleles form 316 different HLA A‐B‐C haplotypes, with each population having between 80 and 112 haplotypes. The four Iranian populations form a related group that is distinguished from other populations, including other Iranians. All four KIR ligands – the A3/11, Bw4, C1 and C2 epitopes – are well represented, particularly Bw4, which is carried by three high‐frequency allotypes: HLA‐A*24:02, HLA‐A*32:01 and HLA‐B*51:01. In the Lur and Kurd populations, between 82% and 94% of individuals have the Bw4 epitope, the ligand for KIR3DL1. HLA‐B*51:01 is likely of Neandertal origin and associated with Behcet's disease, also known as the Silk Road disease. The Lordegan Lur have the highest frequency of HLA‐B*51:01 in the world. This allele is present on 46 Lur and Kurd haplotypes. Present at lower frequency is HLA‐B*51:08, which is also associated with Behcet's disease. In the four Iranian populations, 31 haplotypes encode both Bw4+HLA‐A and Bw4+HLA‐B, a dual combination of Bw4 epitopes that is relatively rare in other populations, worldwide. This study both demonstrates and emphasizes the value of studying HLA class I polymorphism at highest resolution in anthropologically well‐defined populations.
A multiplex allele‐specific real‐time polymerase chain reaction assay for HLA‐B*13:01 genotyping in four Chinese populations
Authors: Liu Z. , Chen G. , Kang X. , Han M. , Chen R. , Chen C. , Wang H.
Published: August 2016

Human leukocyte antigen HLA‐B*13:01 is identified currently as a marker of individual susceptibility to drug‐induced hypersensitivity reaction, such as dapsone‐induced hypersensitivity reactions (DIHRs) and trichloroethylene‐induced dermatitis. Therefore, screening for the HLA‐B*13:01 allele can assist clinics in identifying patients at risk of developing DIHRs. By combining the allele‐specific primers with TaqMan probes, we established a single tube, triplex real‐time PCR to detect HLA‐B*13:01. The reliability of this assay was validated by the comparison of genotyping results with those by sequence‐based typing (SBT). With this assay, the distribution of HLA‐B*13:01 in a total of 350 blood samples from four ethnic groups: Han, Tibetan, Uighur, and Buyei were determined. A 100% concordance was observed between the results with the established real‐time PCR and SBT in 100 samples. The detection limit of this assay was 0.016 ng genomic DNA. The prevalence of HLA‐B*13:01 carriers were 11%, 8%, 1%, and 2% in the Buyei (n = 100), Northern Han (n = 100), Tibetan (n = 100), and Uighur (n = 50) populations, respectively. The multiplex real‐time PCR assay provided a fast and reliable method for accurate detection of HLA‐B*13:01 allele prior to dapsone administration in clinical practice and onset of the reaction after exposure to trichloroethylene.
Against Deductive Closure
Authors: Thorn Paul D.
Published: August 2016

The present article illustrates a conflict between the claim that rational belief sets are closed under deductive consequences, and a very inclusive claim about the factors that are sufficient to determine whether it is rational to believe respective propositions. Inasmuch as it is implausible to hold that the factors listed here are insufficient to determine whether it is rational to believe respective propositions, we have good reason to deny that rational belief sets are closed under deductive consequences.
Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone
Authors: Tan H. Y. , Steyn F. J. , Huang L. , Cowley M. , Veldhuis J. D. , Chen C.
Published: August 2016

Key points

Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth.

Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth.

We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone–insulin‐like growth factor‐1 (GH–IGF‐1) axis.

We propose that hyperinsulinaemia promotes growth while suppressing the GH–IGF‐1 axis.

It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth.

Defects in melanocortin‐4‐receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH)‐mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin‐like growth factor‐1 (IGF‐1) production and/or release relative to pubertal growth. We demonstrate early‐onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH–IGF‐1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia‐associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild‐type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair‐fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a consequence of hyperphagia‐associated hyperinsulinaemia. It is proposed that physiological responses essential to maintain energy flux (hyperinsulinaemia and the suppression of GH release) override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Implications of these findings are likely to extend beyond individuals with defects in MC4R signalling, encompassing physiological changes central to mechanisms of growth and energy homeostasis universal to hyperphagia‐associated childhood‐onset obesity.
Nuclear Heat Supply Fluctuation Tests by Non-Nuclear Heating With HTTR
Authors: Inaba Yoshitomo , Sekita Kenji , Nemoto Takahiro , Honda Yuki , Tochio Daisuke , Sato Hiroyuki , Nakagawa Shigeaki , Takada Shoji , Sawa Kazuhiro
Published: August 2016

The nuclear heat utilization systems connected to high-temperature gas-cooled reactors (HTGRs) will be designed on the basis of non-nuclear-grade standards in terms of easier entry for the chemical plant companies and the construction economics of the systems. Therefore, it is necessary that the reactor operations can be continued even if abnormal events occur in the systems. The Japan Atomic Energy Agency has developed a calculation code to evaluate the absorption of thermal-load fluctuations by the reactors when the reactor operations are continued after such events, and has improved the code based on the high-temperature engineering test reactor (HTTR) operating data. However, there were insufficient data on the transient temperature behavior of the metallic components and the graphite core support structures corresponding to the fluctuation of the reactor inlet coolant temperature for further improvement of the code. Thus, nuclear heat supply fluctuation tests with the HTTR were carried out in non-nuclear heating operation to focus on the thermal effect. In the tests, the coolant helium gas temperature was heated to 120°C by the compression heat of the gas circulators in the HTTR, and a sufficiently large fluctuation of 17°C for the reactor inlet coolant was achieved by devising a new test procedure under the ideal condition without the effect of the nuclear power. Then, the temperature responses of the metallic components and the graphite core support structures were investigated. The test results adequately showed as predicted that the temperature responses of the metallic components are faster than those of the graphite blocks, and the mechanism of the thermal-load fluctuation absorption by the metallic components was clarified.
Development and Test of Oxide/Oxide Ceramic Matrix Composites Combustor Liner Demonstrators for Aero-engines
Authors: Behrendt Thomas , Hackemann Stefan , Mechnich Peter , Shi Yuan , Hönig Sandrine , Hofmann Severin , Koch Dietmar
Published: August 2016

Ceramic matrix composites (CMC) offer the potential of increased service temperatures and are thus an interesting alternative to conventional combustor alloys. Tubular combustor liner demonstrators made of an oxide/oxide CMC were developed for a lean combustor in a future aero-engine in the medium thrust range and tested at engine conditions. During the design, various aspects like protective coating, thermomechanical design, and development of a failure model for the CMC as well as design and test of an attachment system were taken into account. The tests of the two liners were conducted at conditions up to 80% take-off. A new protective coating was tested successfully with a coating thickness of up to t = 1 mm. Different inspection criteria were derived in order to detect crack initiation at an early stage for a validation of the failure model. With the help of detailed pre- and post-test computer tomography (CT) scans to account for the microstructure of the CMC, the findings of the failure model were in reasonable agreement with the test results.
Numbering-Up of Microscale Devices for Megawatt-Scale Supercritical Carbon Dioxide Concentrating Solar Power Receivers
Authors: Zada Kyle R. , Hyder Matthew B. , Kevin Drost M. , Fronk Brian M.
Published: August 2016

Concentrated solar power (CSP) plants have the potential to reduce the consumption of nonrenewable resources and greenhouse gas emissions in electricity production. In CSP systems, a field of heliostats focuses solar radiation on a central receiver, and energy is then transferred to a thermal power plant at high temperature. However, maximum receiver surface fluxes are low (30–100 W cm−2) with high thermal losses, which has contributed to the limited market penetration of CSP systems. Recently, small (∼4 cm2), laminated micro pin-fin devices have shown potential to achieve concentrated surface fluxes over 100 W cm−2 using supercritical CO2 as the working fluid. The present study explores the feasibility of using these microscale unit cells as building blocks for a megawatt-scale (250 MW thermal) open solar receiver through a numbering-up approach, where multiple microscale unit cell devices are connected in parallel. A multiscale model of the full-scale central receiver is developed. The model consists of interconnected unit cell and module level (i.e., multiple unit cells in parallel) submodels which predict local performance of the central receiver. Each full-scale receiver consists of 3000 micro pin-fin unit cells divided into 250 modules. The performance of three different full-scale receivers is simulated under representative operating conditions. The results show that the microscale unit cells have the potential to be numbered up to megawatt applications while providing high heat flux and thermal efficiency. At the design incident flux and surface emissivity, a global receiver efficiency of approximately 90% when heating sCO2 from 550 °C to 650 °C at an average incident flux of 110 W cm−2 can be achieved.
Experimental Characterization of Rotor Convective Heat Transfer Coefficients in the Vicinity of a Leaf Seal
Authors: Pelegrin-Garcia Juan-Diego , Gillespie David R. H. , Pekris Michael J. , Franceschini Gervas , Ganin Leonid
Published: August 2016

Leaf seals are filament seals for use at static to rotating interfaces in the engine secondary air system. They offer reduced leakage rates and better off-design performance over conventional labyrinth seals. If compared with advanced brush seals, leaf seals are more compliant due to their lower stiffness and can withstand higher axial pressure differences. Although leaf seals can exhibit hydrodynamic air-riding, this is not always the case and seal–rotor contact can occur. As a result, friction between the leaf tips and the rotor causes heat generation and wear. To predict the diameter of the rotating shaft and the seal life, the shaft and seal interface temperature needs to be estimated. In the steady state, this is determined by the ratio of convective heat transfer through the seal to that through the shaft. To that end, the convective heat transfer characteristics of the flow over the shaft around the seal are required to build accurate thermal models. In this paper, the convective heat transfer coefficient (HTC) distribution in the close vicinity of a typical leaf seal is investigated in a new test facility. The experimental setup and test method are described in detail, and accuracy considerations are included. The methodology employed to derive HTC is explained with reference to an analogous computational fluid dynamics (CFD) model. The importance of the choice of an appropriate driving gas temperature is demonstrated. Experimental HTC maps are presented for a blow-down seal geometry operating over a range of engine representative pressure ratios. Insight is gained into the flow field characteristics and heat transfer around the seal.
Device characteristics and performance estimation of nearly lattice-matched InAlN/AlGaN heterostructure field-effect transistors
Authors: Miyoshi Makoto , Tsutsumi Tatsuya , Nishino Gosuke , Miyachi Yuta , Okada Mayuko , Freedsman Joseph J. , Egawa Takashi
Published: August 2016

A nearly lattice-matched In0.12Al0.88N/Al0.21Ga0.79N heterostructure field-effect transistor (HFET) was fabricated and its device characteristics were evaluated. The fabricated device showed good pinch-off characteristics with a high breakdown field of 118 V/μm. A simple device calculation based on the experimental results showed the possibility that a low specific on-resistance below those of conventional AlGaN-channel HFETs can be achieved for InAlN/AlGaN HFETs in the case where a specific contact resistivity is less than 1 × 10−5 Ω cm2.
Quantitative classification of harbor seal breeding calls in Georgia Strait, Canada
Authors: Nikolich Katrina , Frouin-Mouy Héloïse , Acevedo-Gutiérrez Alejandro
Published: August 2016

During breeding season, male harbor seals (Phoca vitulina) produce underwater calls used in sexual competition and advertisement. Call characteristics vary among populations, and within-population differences are thought to represent individual variation. However, vocalizations have not been described for several populations of this widely-distributed and genetically diverse species. This study describes the vocal repertoire of harbor seals from British Columbia, Canada. Underwater recordings were made near Hornby Island during the summer of 2014 using a single hydrophone. A wide variability was detected in breeding vocalizations within this single breeding site. Four candidate call types were identified, containing six subtypes. Linear discriminant analysis showed 88% agreement with subjective classification of call types, and 74% agreement for call subtypes. Classification tree analysis gave a 92% agreement with candidate call types, with all splits made on the basis of call duration. Differences in duration may have reflected individual differences among seals. This study suggests that the vocal repertoire of harbor seals in this area comprises a vocal continuum rather than discrete call types. Further work with the ability to localize calls may help to determine whether this complexity represents variability due to propagation conditions, animal orientation, or differences among individual seals.
Amplitude-dependent Lamb wave dispersion in nonlinear plates
Authors: Packo Pawel , Uhl Tadeusz , Staszewski Wieslaw J. , Leamy Michael J.
Published: August 2016

The paper presents a perturbation approach for calculating amplitude-dependent Lamb wave dispersion in nonlinear plates. Nonlinear dispersion relationships are derived in closed form using a hyperelastic stress-strain constitutive relationship, the Green-Lagrange strain measure, and the partial wave technique integrated with a Lindstedt-Poincaré perturbation approach. Solvability conditions are derived using an operator formalism with inner product projections applied against solutions to the adjoint problem. When applied to the first- and second-order problems, these solvability conditions lead to amplitude-dependent, nonlinear dispersion corrections for frequency as a function of wavenumber. Numerical simulations verify the predicted dispersion shifts for an example nonlinear plate. The analysis and identification of amplitude-dependent, nonlinear Lamb wave dispersion complements recent research focusing on higher harmonic generation and internally resonant waves, which require precise dispersion relationships for frequency-wavenumber matching.
NASA flies into Namibia's cloud laboratory
Authors: Hand Eric
Published: August 2016

Commingling smoke and fog pose thorny climate puzzles
Research watchdog's new leader faces staff revolt
Authors: Kaiser Jocelyn
Published: August 2016

ORI head tries to chart future course, but staff warn of “tensions and conflict” in letters to her superiors
The exoplanet next door
Authors: Clery Daniel
Published: August 2016

Earth-like planet found 4 light-years away around Proxima Centauri, the closest star
The carbon accountant
Authors: Starr Douglas
Published: August 2016

Richard Heede pins much of the responsibility for climate change on just 90 companies. Others say that's a cop-out
Building devices from colloidal quantum dots
Authors: Kagan Cherie R. , Lifshitz Efrat , Sargent Edward H. , Talapin Dmitri V.
Published: August 2016

From quantum dot to quantum dot

A wide range of materials can now be synthesized into semiconducting quantum dots. Because these materials grow from solutions, there is scope to combine quantum dots into devices by using simple, low-cost manufacturing processes. Kagan
et al.
review recent progress in tailoring and combining quantum dots to build electronic and optoelectronic devices. Because it is possible to tune the size, shape, and connectivity of each of the quantum dots, there is potential for fabricating electronic materials with properties that are not available in traditional bulk semiconductors.

Science
, this issue p.
885
pVHL suppresses kinase activity of Akt in a proline-hydroxylation–dependent manner
Authors: Guo Jianping , Chakraborty Abhishek A. , Liu Pengda , Gan Wenjian , Zheng Xingnan , Inuzuka Hiroyuki , Wang Bin , Zhang Jinfang , Zhang Linli , Yuan Min , Novak Jesse , Cheng Jin Q. , Toker Alex , Signoretti Sabina , Zhang Qing , Asara John M. , Kaelin William G. , Wei Wenyi
Published: August 2016

Activation of the serine-threonine kinase Akt promotes the survival and proliferation of various cancers. Hypoxia promotes the resistance of tumor cells to specific therapies. We therefore explored a possible link between hypoxia and Akt activity. We found that Akt was prolyl-hydroxylated by the oxygen-dependent hydroxylase EglN1. The von Hippel–Lindau protein (pVHL) bound directly to hydroxylated Akt and inhibited Akt activity. In cells lacking oxygen or functional pVHL, Akt was activated to promote cell survival and tumorigenesis. We also identified cancer-associated Akt mutations that impair Akt hydroxylation and subsequent recognition by pVHL, thus leading to Akt hyperactivation. Our results show that microenvironmental changes, such as hypoxia, can affect tumor behaviors by altering Akt activation, which has a critical role in tumor growth and therapeutic resistance.
Characterization of berkelium(III) dipicolinate and borate compounds in solution and the solid state
Authors: Silver Mark A. , Cary Samantha K. , Johnson Jason A. , Baumbach Ryan E. , Arico Alexandra A. , Luckey Morgan , Urban Matthew , Wang Jamie C. , Polinski Matthew J. , Chemey Alexander , Liu Guokui , Chen Kuan-Wen , Van Cleve Shelley M. , Marsh Matthew L. , Eaton Teresa M. , van de Burgt Lambertus J. , Gray Ashley L. , Hobart David E. , Hanson Kenneth , Maron Laurent , Gendron Frédéric , Autschbach Jochen , Speldrich Manfred , Kögerler Paul , Yang Ping , Braley Jenifer , Albrecht-Schmitt Thomas E.
Published: August 2016

Bonding to berkelium

A geographical theme prevailed in the recent naming of the heaviest chemical elements. The choices brought to mind berkelium (Bk) and californium (Cf), the names chosen for elements 97 and 98 over half a century ago. Silver
et al.
now revisit the chemistry of Bk, which has proven fiercely challenging to study over the years on account of its vigorous radioactive decay. Synthetic crystallized Bk borate and dipicolinate compounds structurally resembled Cf analogs in the solid state but manifested distinct electronic and magnetic characteristics stemming from spin-orbit coupling effects.

Science
, this issue p.
888
Do you speak lion?
Authors: Adams W. M.
Published: August 2016

To be effective, conservation decisions must be transparent and based on diverse views
Proline hydroxylation linked to Akt activation
Authors: Voulgarelis Michael , Tsichlis Philip N.
Published: August 2016

Oxygen-sensing enzymes regulate the Akt kinase
Building Star Trek
Building Star Trek
Mick Grogan
Yap Films for Smithsonian Channel and Discovery Canada, 2016 Premieres on Sunday, 4 September at 8:00 pm ET/PT
Authors: Jasny Barbara
Published: August 2016

September 8, 2016, will mark the 50th anniversary of the first show of the television series Star Trek. To commemorate this, the Smithsonian Air and Space Museum is hosting the show’s restored 11-foot USS Enterprise, and the Experience Music Project Museum in Seattle has built a re-creation of the ship’s flight deck. In honor of these events, the Smithsonian channel will be airing a 2-hour special that describes the exhibits and looks at the effect Star Trek has had on science and technology.
A path toward understanding neurodegeneration
Authors: Kosik K. S. , Sejnowski T. J. , Raichle M. E. , Ciechanover A. , Baltimore D.
Published: August 2016

A focus on cell biology may accelerate progress in disease prevention and cures
Accurate Detection of Avian Respiratory Viruses by Use of Multiplex PCR-Based Luminex Suspension Microarray Assay
Authors: Laamiri Nacira , Fällgren Pia , Zohari Siamak , Ben Ali Jaouher , Ghram Abdeljelil , Leijon Mikael , Hmila Issam
Published: August 2016

A novel oligonucleotide suspension microarray (Luminex microsphere system) was developed for the rapid detection of avian respiratory viruses of major clinical importance. This test was optimized and validated with 70 clinical samples. The developed tool was accurate for high-throughput detection and differentiation of the most important avian respiratory viruses: avian influenza virus (AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and infectious laryngotracheitis virus (ILTV) in single- and mixed-virus infections. A multiplex reverse transcriptase PCR (RT-PCR), followed by a monoplex or a multiplex Luminex assays, were realized using a Luminex 200 analyzer instrument. The sensitivity, specificity, and reproducibility of the multiplex DNA suspension microarray system were evaluated. The results showed no significant differences in the median fluorescence intensity (MFI) value in monoplex and multiplex Luminex assays. The sensitivity and specificity proved to be completely concordant with monoplex real-time RT-PCR. We demonstrated that the multiplex DNA suspension microarray system is an accurate, high-throughput, and relatively simple method for the rapid detection of the main respiratory viruses of poultry.
Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection
Authors: Stevenson Emma C. , Major Giles A. , Spiller Robin C. , Kuehne Sarah A. , Minton Nigel P.
Published: August 2016

Clostridium difficile
(
Peptoclostridium difficile
) is a common health care-associated infection with a disproportionately high incidence in elderly patients. Disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. Around 20% of patients may suffer recurrent disease, which often requires rehospitalization of patients.
C. difficile
was isolated from stool samples from a patient with two recurrent
C. difficile
infections. PCR ribotyping, whole-genome sequencing, and phenotypic assays were used to characterize these isolates. Genotypic and phenotypic screening of
C. difficile
isolates revealed multiple PCR ribotypes present and the emergence of rifamycin resistance during the infection cycle. Understanding both the clinical and bacterial factors that contribute to the course of recurrent infection could inform strategies to reduce recurrence. (This study has been registered at ClinicalTrials.gov under registration no. NCT01670149.)