bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel model of predator–prey interactions reveals the sensitivity of forage fish: piscivore fishery trade-offs to ecological conditions
Authors: Essington Timothy E. , Baskett Marissa L. , Sanchirico James N. , Walters Carl
Published: December 2014

Ecosystem-based fisheries management seeks to consider trade-offs among management objectives for interacting species, such as those that arise through predator–prey linkages. In particular, fisheries-targeting forage fish (small and abundant pelagic fish) might have a detrimental effect on fisheries-targeting predators that consume them. However, complexities in ecological interactions might dampen, negate, or even reverse this trade-off, because small pelagic fish can be important predators on egg stages of piscivorous fish. Further, the strength of this trade-off might depend on the extent to which piscivorous fish targeted by fisheries regulate forage species productivity. Here, we developed a novel delay-differential bioeconomic model of predator–prey and fishing dynamics to quantify how much egg predation or weak top-town control affects the strength of trade-off between forage and piscivore fisheries, and to measure how ecological interactions dictate policies that maximize steady-state profits. We parameterized the model based on ecological and economic data from the North Sea Atlantic cod (Gadus morhua) and Atlantic herring (Clupea harengus). The optimal policy was very sensitive to the ecological interactions (either egg predation or weak top-down control of forage by predators) at relatively low forage prices but was less sensitive at high forage fish prices. However, the optimal equilibrium harvest rates on forage and piscivores were not substantially different from what might be derived through analyses that did not consider species interactions. Applying the optimal multispecies policy would produce substantial losses (>25%) in profits in the piscivore fishery, and the extent of loss was sensitive to ecological scenarios. While our equilibrium analysis is informative, a dynamic analysis under similar ecological scenarios is necessary to reveal the full economic and ecological benefits of applying ecosystem-based fishery management policies to predator–prey fishery systems.
Testis-expressed cluster of microRNAs 959-964 controls spermatid differentiation inDrosophila
Authors: Ryazansky Sergei , Mikhaleva Elena , Akulenko Natalia , Olenkina Oxana
Published: December 2014

MicroRNAs are a wide class of ∼22 nt non-coding RNAs of metazoans capable of inhibiting target mRNAs translation by binding to partially complementary sites in their 3’UTRs. Due to their regulatory potential, miRNAs are implicated in functioning of a broad range of biological pathways and processes. Here we investigate the functions of the miR-959-964 cluster expressed predominantly in testes ofDrosophila melanogaster. The deletion of miR-959-964 resulted in male sterility due to the disturbance of the spermatid individualization process. Analysis of the transcriptome by microarray followed by luciferase reporter assay revealeddidum, for, fdland CG10512 as the targets of miR-959-964. Moreover, the deletion of miR-959-964 is accompanied by a decreased the expression of genes responsible for microtubule-based movement and spermatid differentiation. Thus, we suggest that miR-959-964 can control the process of spermatid individualization by direct and indirect modulating the expression of different components of the individualization process. In addition, we have shown that in comparison to other miRNAs, the rate of evolution of the testis-specific miR-959-964 cluster is unusually high, indicating its possible involvement in speciation via reproductive isolation.
Genome-engineering with CRISPR-Cas9 in the mosquitoAedes aegypti
Authors: Kistler Kathryn E. , Vosshall Leslie B. , Matthews Benjamin J.
Published: December 2014

The mosquitoAedes aegyptiis a potent vector of the Chikungunya, yellow fever, and Dengue viruses, which result in hundreds of millions of infections and over 50,000 human deaths per year. Loss-of-function mutagenesis inAe. aegyptihas been established with TALENs, ZFNs, and homing endonucleases, which require the engineering of DNA-binding protein domains to generate target specificity for a particular stretch of genomic DNA. Here, we describe the first use of the CRISPR-Cas9 system to generate targeted, site-specific mutations inAe. aegypti. CRISPR-Cas9 relies on RNA-DNA base-pairing to generate targeting specificity, resulting in cheaper, faster, and more flexible genome-editing reagents. We investigate the efficiency of reagent concentrations and compositions, demonstrate the ability of CRISPR-Cas9 to generate several different types of mutations via disparate repair mechanisms, and show that stable germ-line mutations can be readily generated at the vast majority of genomic loci tested. This work offers a detailed exploration into the optimal use of CRISPR-Cas9 inAe. aegyptithat should be applicable to non-model organisms previously out of reach of genetic modification.
A FISH-based chromosome map for the European corn borers yields insights into ancient chromosomal fusions in the silkworm
Authors: Yasukochi Yuji , Ohno Mizuki , Shibata Fukashi , Jouraku Akiya , Nakano Ryo , Ishikawa Yukio , Sahara Ken
Published: December 2014

A significant feature of the genomes of Lepidoptera, butterflies and moths, is the high conservation of chromosome organization. Recent remarkable progress in genome sequencing of Lepidoptera has revealed that syntenic gene order is extensively conserved across phylogenetically distant species. The ancestral karyotype of Lepidoptera is thought to ben= 31; however, that of the most well studied moth,Bombyx mori, isn= 28, suggesting that three chromosomal fusion events occurred in this lineage. To identify the boundaries between predicted ancient fusions involvingB. morichromosomes 11, 23 and 24, we constructed FISELbased chromosome maps of the European corn borer,Ostrinia nubilalis(n= 31). We first determined 511 Mb genomic sequence of the Asian corn borer,Ostrinia furnacalis, a congener ofO. nubilalis, and isolated BAC and fosmid clones that were expected to localize in candidate regions for the boundaries using these sequences. Combined with FISH and genetic analysis, we narrowed down the candidate regions to 40kb – 1.5Mb, in strong agreement with a previous estimate based on the genome of a butterfly,Melitaea cinxia. The significant difference in the lengths of the candidate regions where no functional genes were observed may reflect the evolutionary time after fusion events.
High-pressure crystallography of periodic and aperiodic crystals
Authors: Hejny Clivia , Minkov Vasily S.
Published: January 2015

More than five decades have passed since the first single-crystal X-ray diffraction experiments at high pressure were performed. These studies were applied historically to geochemical processes occurring in the Earth and other planets, but high-pressure crystallography has spread across different fields of science including chemistry, physics, biology, materials science and pharmacy. With each passing year, high-pressure studies have become more precise and comprehensive because of the development of instrumentation and software, and the systems investigated have also become more complicated. Starting with crystals of simple minerals and inorganic compounds, the interests of researchers have shifted to complicated metal–organic frameworks, aperiodic crystals and quasicrystals, molecular crystals, and even proteins and viruses. Inspired by contributions to the microsymposium `High-Pressure Crystallography of Periodic and Aperiodic Crystals' presented at the 23rd IUCr Congress and General Assembly, the authors have tried to summarize certain recent results of single-crystal studies of molecular and aperiodic structures under high pressure. While the selected contributions do not cover the whole spectrum of high-pressure research, they demonstrate the broad diversity of novel and fascinating results and may awaken the reader's interest in this topic.
Crystal structure of tetraaquabis(thiocyanato-κN)nickel(II)–2,5-dimethylpyrazine (1/4)
Authors: Suckert Stefan , Wriedt Mario , Jess Inke , Näther Christian
Published: January 2015

In the crystal structure of the title compound, [Ni(NCS)2(H2O)4]·4C6H8N2, the NiIIcations are coordinated by four water ligands and twotrans-coordinated terminallyN-bonded thiocyanate anions in a slightly distorted octahedral geometry. The asymmetric unit consists of a Ni2+cation located on a centre of inversion, two water molecules and one thiocyanate ligand, as well as two uncoordinated 2,5-dimethylpyrazine ligands in general positions. In the crystal, discrete complex molecules are linked into a three-dimensional network by O—H...N hydrogen bonding between the water H atoms and the 2,5-dimethylpyrazine N atoms.
Crystal structure of bis(9H-6-aminopurin-1-ium) hexafluoridosilicate(IV) dihydrate
Authors: Belhouas Ratiba , Bouacida Sofiane , Boudaren Chaouki , Daran Jean-Claude , Chtoun El Hossain
Published: January 2015

The asymmetric unit of the title compound, 2C5H6N5+·SiF62−·2H2O, contains one adeninium cation, half of a hexafluoridosilicate anion located on an inversion centre and one lattice water molecule. The adeninium cations are connected through N—H...N hydrogen bonds involving one H atom of the –NH2group and the H atom of the protonated N atom of the adenine ring system, forming centrosymmetric ring motifs of the typeR22(10) andR22(8), respectively. The overall connection of the cation leads to the formation of planar ribbons parallel to (122). In the ribbons, slipped π–π stacking interactions, with a centroid-to-centroid distance of 3.6938 (9) Å, an interplanar distance of 3.455 Å and a slippage of 1.306 Å is observed. The hexafluoridosilicate anion and the water molecule are linked through O—H...F hydrogen bonds [ring motifR44(12)] into chains parallel to [100]. The cationic ribbons and anionic chains are finally connected through additional N—H...O, N—H...F and O—H...F hydrogen bonds into a three-dimensional network in which layers of adeninium cations and fluoridosilicate anions alternate parallel to (001).
Crystal structure of 4-[1-(2-hydroxypropyl)-4,5-diphenyl-1H-imidazol-2-yl]benzoic acid
Authors: Jasinski Jerry P. , Mohamed Shaaban K. , Akkurt Mehmet , Abdelhamid Antar A. , Albayati Mustafa R.
Published: January 2015

In the title compound, C25H22N2O3, the central imidazole ring makes dihedral angles of 48.43 (10), 20.23 (10) and 75.38 (11)° with the benzene ring and the two phenyl rings, respectively. The phenyl ring adjacent to the N-bonded 2-hydroxypropyl group shows the greatest twist, presumably to minimize steric interactions. In the crystal, molecules are linked by O—H...N, O—H...O and C—H...O hydrogen bonds, forming a three-dimensional network. In addition, C—H...π interactions are also observed.
Crystal structure of 2-(4-methylphenyl)-4H-1,3-benzothiazine
Authors: Sandhya N. C. , Chandra  , Suresha G. P. , Lokanath N. K. , Mahendra M.
Published: January 2015

In the title compound, C15H13NS, the thiazine ring adopts a boat conformation. The dihedral angle between the planes of the benzene ring of the benzothiazine unit and the tolyl ring is 19.52 (9)°. In the crystal, molecules are linked by weak C—H...π interactions into a tape structure along theb-axis direction.
Crystal structure of chlorido{1-(2,3-dimethyl-5-oxido-1-phenyl-1H-pyrazol-2-ium-4-yl-κO)-2-[3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-ylidene-κO]hydrazin-1-ido-κN1}copper(II) from laboratory X-ray powder data
Authors: Kovalchukova Olga , Nguen Van , Strashnova Svetlana , Kuznetsov Dmitry , Berikashvili Teimuraz
Published: January 2015

In the title compound, [Cu(C21H19N6O2)Cl], the CuIIatom is in a slightly distorted square-planar coordination involving two O atoms from the pyrazolone rings [Cu—O = 2.088 (10) and 1.975 (10) Å], an N atom of the azo group [Cu—N = 2.048 (13) Å] and a chloride anion [Cu—Cl = 2.183 (5) Å]. The organic anions act as tridentate chelating ligands. The molecules stack in columns along thecaxis.
Crystal structure and thermal behaviour of pyridinium styphnate
Authors: Muthulakshmi Selvarasu , Kalaivani Doraisamyraja
Published: January 2015

In the crystal structure of the title molecular salt, C5H6N+·C6H2N3O8−(systematic name: pyridinium 3-hydroxy-2,4,6-trinitrophenolate), the pyridinium cation and the 3-hydroxy-2,4,6-trinitrophenolate anion are linked through bifurcated N—H...(O,O) hydrogen bonds, forming anR12(6) ring motif. The nitro groupparawith respect to phenolate ion forms an intramolecular hydrogen bond with the adjacent phenolic –OH group, which results in anS(6) ring motif. The nitro group flanked by the phenolate ion and the phenolic –OH group deviates noticeably from the benzene ring, subtending a dihedral angle of 89.2 (4)°. The other two nitro groups deviate only slightly from the plane of the benzene ring, making dihedral angles of 2.8 (4) and 3.4 (3)°. In the crystal, the 3-hydroxy-2,4,6-trinitrophenolate anions are linked through O—H...O hydrogen bonds, forming chains along [100]. These anionic chains, to which the cations are attached, are linkedviaC—H...O hydrogen bonds, forming a three-dimensional structure. Impact friction sensitivity tests and TGA/DTA studies on the title molecular salt imply that it is an insensitive high-energy-density material.
Crystal structure ofcis-tetraaquadichloridocobalt(II) sulfolane disolvate
Authors: Boudraa Mhamed , Bouacida Sofiane , Bouchareb Hasna , Merazig Hocine , Chtoun El Hossain
Published: January 2015

In the title compound, [CoCl2(H2O)4]·2C4H8SO2, the CoIIcation is located on the twofold rotation axis and is coordinated by four water molecules and two adjacent chloride ligands in a slightly distorted octahedral coordination environment. Thecisoidangles are in the range 83.27 (5)–99.66 (2)°. The threetransoidangles deviate significantly from the ideal linear angle. The crystal packing can be described as a linear arrangement of complex units alongcformed by bifurcated O—H...Cl hydrogen bonds between two water molecules from one complex unit towards one chloride ligand of the neighbouring complex. Two solvent molecules per complex are attached to this infinite chainviaO—H...O hydrogen bonds in which water molecules act as the hydrogen-bond donor and sulfolane O atoms as the hydrogen-bond acceptor sites.
Crystal structure of 4-{(E)-[2-(pyridin-4-ylcarbonyl)hydrazin-1-ylidene]methyl}phenyl acetate monohydrate
Authors: Datta Riya , Ramya V. , Sithambaresan M. , Kurup M. R. Prathapachandra
Published: January 2015

The asymmetric unit of the title compound, C15H13N3O3·H2O, comprises a 4-{(E)-[2-(pyridin-4-ylcarbonyl)hydrazinylidene]methyl}phenyl acetate molecule and a solvent water molecule linked by O—H...O and O—H...N hydrogen bonds from the water molecule and a C—H...O contact from the organic molecule. The compound adopts anEconformation with respect to the azomethine bond and the dihedral angle between the pyridine and benzene rings is 21.90 (7)°. The azomethine bond [1.275 (2) Å] distance is very close to the formal C=N bond length, which confirms the azomethine bond formation. An extensive set of O—H...O, O—H...N, N—H...O and C—H...O hydrogen bonds builds a two-dimensional network progressing along thecaxis.
Crystal structures of 2,6-bis[(1H-1,2,4-triazol-1-yl)methyl]pyridine and 1,1-[pyridine-2,6-diylbis(methylene)]bis(4-methyl-1H-1,2,4-triazol-4-ium) iodide triiodide
Authors: Guino-o Marites A. , Folstad Matthew J. , Janzen Daron E.
Published: January 2015

In the structures of the 2,6-bis(1,2,4-triazoly-3-yl)methyl-substituted pyridine compound, C11H11N7, (I) and the iodide triiodide salt, C13H17N72+·I−·I3−, (II), the dihedral angles between the two triazole rings and the pyridine ring are 66.4 (1) and 74.6 (1)° in (I), and 68.4 (2)° in (II), in which the dication lies across a crystallographic mirror plane. The overall packing structure for (I) is two-dimensional with the layers lying parallel to the (001) plane. In (II), the triiodide anion lies within the mirror plane, occupying the space between the two triazole substituent groups and was found to have minor disorder [occupancy ratio 0.9761 (9):0.0239 (9)]. The overall packing of structure (II) can be described as two-dimensional with the layers stacking parallel to the (001) plane. In the crystal, the predominant intermolecular interactions in (I) and (II) involve the acidic hydrogen atom in the third position of the triazole ring, with either the triazole N-atom acceptor in weak C—H...N hydrogen bonds in (I), or with halide counter-ions through C—H...I interactions, in (II).
Crystal structure ofN,N′-bis(4-methylphenyl)dithiooxamide
Authors: Giannetto Antonino , Lanza Santo , Bruno Giuseppe , Nicoló Francesco , Amiri Rudbari Hadi
Published: January 2015

Two half molecules of the title compound, C16H16N2S2, are present in the asymmetric unit and both molecules are completed by crystallographic inversion centers at the mid-points of the central C—C bonds: the lengths of these bonds [1.538 (5) and 1.533 (5) Å] indicate negligible electronic delocalization. Thetrans-dithiooxamide fragment in each molecule is characterized by a pair of intramolecular N—H...S hydrogen bonds. In the crystal, molecules are linked by weak C—H..π interactions, generating a three-dimensional network.
Getting a low-paid job in French and UK supermarkets: from walk-in to online application?
Authors: Rieucau Geraldine
Published: January 2015

Purpose

– The purpose of this paper is to compare the recruitment practices of the French and UK retail industry. It analyses the influence of specific business constraints, labour market institutions and employment patterns on recruitment practices. It devotes attention to incidences of the shift from classic to web-based hiring methods.

Design/methodology/approach

– The cases of two leading food retail chains are explored. This research draws on a mixed approach using semi-structured interviews, the analysis of online job-advertisement content and web sites.

Findings

– According to the literature, local and informal hiring channels (walk-in application, word-of-mouth, in-store adverts) are mainly used to fill low-paid vacancies in food retail chains. They are congruent with the key screening criteria as they allow face-to-face selection and provide candidates from the surrounding area. However, the food retail chains in this research have implemented a centralised and at-a-distance process which contrasts with the classic methods. Based on an “Internet-only scheme” and online testing, it is especially selective in the UK.

Research limitations/implications

– The number of semi-structured interviews is limited. Additional investigations are needed to evaluate whether the at-a-distance processes are isolated or whether they reflect growing practices.

Practical implications

– Retail food employers have to maintain a diversity of local hiring channels and not to indiscriminately embrace the at-a-distance scheme, which is not adapted to evaluate the key requirements.

Social implications

– A centralised and at-a-distance recruitment process decreases unfair face-to-face discrimination in selection but at the same time introduces indirect discrimination. This process may be interpreted as a way to target students; there is a risk that it exacerbates inequalities in low-wage labour markets.

Originality/value

– The topic is poorly explored. There is a need to understand web-based recruitment.
Effects of starvation and hormones on DNA synthesis in silk gland cells of the silkworm, Bombyx mori
Authors: Li Yao‐Feng , Chen Xiang‐Yun , Zhang Chun‐Dong , Tang Xiao‐Fang , Wang La , Liu Tai‐Hang , Pan Min‐Hui , Lu Cheng
Published: January 2015

Silk gland cells of silkworm larvae undergo multiple cycles of endomitosis for the synthesis of silk proteins during the spinning phase. In this paper, we analyzed the endomitotic DNA synthesis of silk gland cells during larval development, and found that it was a periodic fluctuation, increasing during the vigorous feeding phase and being gradually inhibited in the next molting phase. That means it might be activated by a self‐regulating process after molting. The expression levels of cyclin E, cdt1 and pcna were consistent with these developmental changes. Moreover, we further examined whether these changes in endomitotic DNA synthesis resulted from feeding or hormonal stimulation. The results showed that DNA synthesis could be inhibited by starvation and re‐activated by re‐feeding, and therefore appears to be dependent on nutrition. DNA synthesis was suppressed by in vivo treatment with 20‐hydroxyecdysone (20E). However, there was no effect on DNA synthesis by in vitro 20E treatment or by either in vivo or in vitro juvenile hormone treatment. The levels of Akt and 4E‐BP phosphorylation in the silk glands were also reduced by starvation and in vivo treatment with 20E. These results indicate that the activation of endomitotic DNA synthesis during the intermolt stages is related to feeding and DNA synthesis is inhibited indirectly by 20E.
Anthropology and the Making of Billy Graham: Evangelicalism and Anthropology in the 20th‐Century United States
Authors: Howell Brian M.
Published: January 2015

In theorizing the relationship between Christianity (or religion) and anthropology, scholars have often emphasized the “incommensurability,” tension, or distance between two seemingly opposed epistemological frameworks. In this article, I take the case of Billy Graham, one of the most famous Christian leaders of the 20th century, as well as an undergraduate anthropology major, to illustrate how anthropology was imagined to serve Christian purposes, defined by the theological categories of religion. In the modernist Christianity of Graham's 20th‐century evangelicalism, anthropology could be comfortably subsumed under Christian categories. Rather than seeing anthropology, or any science, as being a product of, or coterminous with, secularism, Graham, and his college professors before him, understood anthropology to be fully amenable to Christian uses, so long as secular or atheistic influences were expunged. [Christianity, evangelicalism, secularism, science, race]
Resistin‐like molecule‐β (RELM‐β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man
Authors: Fang C. L. , Yin L. J. , Sharma S. , Kierstein S. , Wu H. F. , Eid G. , Haczku A. , Corrigan C. J. , Ying S.
Published: December 2014

Background

RELM‐β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM‐β plays a role in extracellular matrix deposition in asthmatic airways.

Methods

The effects of RELM‐β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM‐β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM‐β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro.

Results

Sensitisation and challenge of wild‐type mice with Af‐induced release of RELM‐β with a time course coincident with that of procollagen in the airways. Af‐induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM‐β−/− mice. RELM‐β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α‐smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM‐β in the submucosa. Exposure to RELM‐β increased TGF‐β1, TGF‐β2, collagen I, fibronectin, smooth muscle α‐actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells.

Conclusion

The data are consistent with the hypothesis that elevated RELM‐β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins.
Vitamin D supplementation and testosterone concentrations in male human subjects
Authors: Heijboer Annemieke C. , Oosterwerff Mirjam , Schroten Nicolas F. , Eekhoff Elisabeth M.W. , Chel Victor G.M. , de Boer Rudolf A. , Blankenstein Marinus A. , Lips Paul
Published: January 2015

Objective

A possible association between serum 25‐hydroxyvitamin D and testosterone levels has been reported; however, contradictory results have emerged.

Design

To investigate a causal link between vitamin D and testosterone status, we studied the effect of vitamin D supplementation on serum testosterone concentrations in three independent intervention studies including male patients with heart failure (study 1), male nursing home residents (study 2) and male non‐Western immigrants in the Netherlands (study 3).

Methods

In study 1, 92 subjects were randomized to either vitamin D (2000 IU cholecalciferol daily) or control. Blood was drawn at baseline, after 3 and 6 weeks. In study 2, 49 vitamin D deficient subjects received either vitamin D (600 IU daily) or placebo. Blood was drawn at baseline, after 8 and 16 weeks. In study 3, 43 vitamin D deficient subjects received either vitamin D (1200 IU daily) or placebo. Blood was drawn at baseline, after 8 and 16 weeks. Serum 25‐hydroxyvitamin D levels were measured using LC‐MS/MS or radioimmunoassay. Testosterone levels were measured using a 2nd generation immunoassay.

Results

Serum 25‐hydroxyvitamin D levels significantly increased in all treatment groups (median increase of 27, 30 and 36 nmol/l in studies 1, 2 3, respectively) but not in the control groups. The documented increase in 25‐hydroxyvitamin D levels, however, did not affect mean testosterone concentrations at the end of the study (median increase of 0, 0·5 and 0 nmol/l in studies 1, 2 and 3, respectively).

Conclusions

In this post hoc analysis of three small clinical trials of limited duration in men with normal baseline testosterone concentrations, vitamin D supplementation was not associated with an increase in circulating testosterone concentrations.
Time course of clinical and neuroradiological effects of delayed‐release dimethyl fumarate in multiple sclerosis
Authors: Kappos L. , Giovannoni G. , Gold R. , Phillips J. T. , Arnold D. L. , Hotermans C. , Zhang A. , Viglietta V. , Fox R. J. ,   the DEFINE and CONFIRM study investigators
Published: January 2015

Background and purpose

Delayed‐release dimethyl fumarate (DMF, also known as gastro‐resistant DMF), demonstrated efficacy and safety in relapsing−remitting multiple sclerosis in the 2‐year, randomized, placebo‐controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF.

Methods

Eligible patients were randomized to receive placebo, DMF 240 mg twice (BID) or three times (TID) daily or glatiramer acetate (GA; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis.

Results

A total of 2301 patients were randomized and received treatment with placebo (n = 771) or DMF BID (n = 769) or TID (n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0–12 (BID, P = 0.0159; TID, P = 0.0314); the proportion of patients relapsed beginning at week 10 (BID, P = 0.0427) and week 12 (TID, P = 0.0451); and the proportion of patients with 12‐week confirmed disability progression beginning at week 62 (BID, P = 0.0454) and week 72 (TID, P = 0.0399), compared with placebo. These effects were sustained throughout the 2‐year study period. DMF significantly reduced the odds of having a higher number of gadolinium‐enhancing lesions by 88% (BID) and 75% (TID) and the mean number of new or enlarging T2 lesions by 72% (BID) and 67% (TID), from the first post‐baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo).

Conclusions

In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing−remitting multiple sclerosis.
Pacific herring (Clupea pallasii) consumption by marine birds during winter in Prince William Sound, Alaska
Authors: Bishop Mary Anne , Watson Jordan T. , Kuletz Kathy , Morgan Tawna
Published: January 2015

Following the 1989 MV Exxon Valdez oil spill (EVOS) and subsequent herring population collapse in Alaska's Prince William Sound (PWS), the Pacific herring (Clupea pallasii) fishery was closed. In the 25 yr since EVOS, herring and several herring‐dependent marine bird species have failed to reach pre‐spill population levels. One hypothesis is that intense predation pressure may be inhibiting herring recovery. To inform herring modeling efforts, this study estimated marine bird consumption of juvenile and adult herring in PWS for 10 winters over an 18‐yr period (1989–90 through 2006–2007). Total estimated herring consumption by wintering marine birds averaged 2409 ± 950 t, indicating that avian consumption represents a substantial and inter‐annually variable source of herring mortality. Common murre (Uria aalge) consumed the greatest portion (16–80%) of herring in all years among marine bird species. Juvenile herring biomass consumed annually by common murre was greater than murre consumption of adult herring biomass. Time lag analyses showed that marine bird consumption of adult herring is negatively correlated with the amount of herring spawn observed in subsequent years, but such effects were not observed more than 2 yr. Our models indicate that during years in which herring recruitment is low or bird populations are particularly large, marine birds can consume up to 10% of the annual adult herring biomass. Our results highlight the importance of herring to wintering PWS birds. We propose that future management of herring stocks seeks to reduce negative impacts on marine birds that prey on herring.
Flow‐Through Stream Modeling with MODFLOW and MT3D: Certainties and Limitations
Authors: Ben Simon Rose , Bernard Stéphane , Meurville Charles , Rebour Vincent
Published: January 2015

This paper aims to assess MODFLOW and MT3D capabilities for simulating the spread of contaminants from a river exhibiting an unusual relationship with an alluvial aquifer, with the groundwater head higher than the river head on one side and lower on the other (flow‐through stream). A series of simulation tests is conducted using a simple hypothetical model so as to characterize and quantify these limitations. Simulation results show that the expected contaminant spread could be achieved with a specific configuration composed of two sets of parameters: (1) modeled object parameters (hydraulic groundwater gradient, hydraulic conductivity values of aquifer and streambed), and (2) modeling parameters (vertical discretization of aquifer, horizontal refinement of stream modeled with River [RIV] package). The influence of these various parameters on simulation results is investigated, and potential complications and errors are identified. Contaminant spread from stream to aquifer is not always reproduced by MT3D due to the RIV package's inability to simulate lateral exchange fluxes between stream and aquifer. This paper identifies the need for a MODFLOW streamflow package allowing lateral stream‐aquifer interactions and streamflow routine calculations. Such developments could be of particular interest for modeling contaminated flow‐through streams.
Thermal Influence of an Alpine Deep Hydrothermal Fault on the Surrounding Rocks
Authors: Dzikowski Marc , Josnin Jean Yves , Roche Nicolas
Published: January 2015

Major fault zones in mountain areas are often associated with cold‐water circulations and hydrothermal pathways. Compared with the massif as a whole, the deep groundwater flows in these high hydraulic‐conductivity zones modify the thermal state of the surrounding rock. This paper examines the thermal effects of groundwater flow in the area around the steeply dipping La Léchère deep fault zone (LFZ, French Alps) and associated shallow decompressed zone. We used a 3D numerical model drawn up from groundwater circulation data to investigate the La Léchère hydrothermal system and the thermal state of the rock in the valley sides. Hydrothermal simulations showed that convective flow into the LFZ cools the valley sides and creates a thermal upwelling under the valley floor. An unsteady thermal regime that continues for about 10,000 years is also needed to obtain the temperatures currently found under the valley floor in the LFZ. Temperature‐depth profiles around the LFZ show disturbances in the thermal gradients in the valley sides and the valley floor. Convective heat transfer into the LFZ and the decompressed zone, and conductive heat transfer in the surrounding rocks produce an unsteady, asymmetric thermal state in the rock on both sides of the LFZ.
New insights into the lymphovascular microanatomy of the colon and the risk of metastases in pT1 colorectal cancer obtained with quantitative methods and three‐dimensional digital reconstruction
Authors: Brown Peter J , Toh Eu‐Wing , Smith Katherine J E , Jones Pamela , Treanor Darren , Magee Derek , Burke Dermot , Quirke Phil
Published: January 2015

Aims

UK faecal occult blood test screening has tripled the proportion of pT1 colorectal cancers. The risk of metastasis is predicted by depth of invasion, suggesting that access to deep lymphovascular vessels is important. The aim of this study was to quantify the distribution and size of the submucosal vasculature, and generate a novel three‐dimensional (3D) model to validate the findings.

Methods and results

Thirty samples of normal large bowel wall were immunostained with CD31, a vascular endothelium marker, to identify blood vessels, which were quantified and digitally analysed for their number, circumference, area and diameter in the deep mucosa and submucosa (Sm1, Sm2, and Sm3). The model required serial sections, a double immunostain (using CD31 and D2‐40), and 3D reconstruction. Significant differences were shown between submucosal layers in the number, circumference and area of vessels (P < 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm2) but smaller [median area of 247 μm2, interquartile range (IQR) 162–373 μm2] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm2) but considerably larger (2086 μm2, IQR 1007–4784 μm2). The 3D model generated novel observations on lymphovascular structures.

Conclusions

The number and size of blood vessels do not increase with depth of submucosa, as hypothesized. The distribution of vessels suggests that we should investigate the area or volume of submucosal invasion rather than the depth.
Epstein–Barr virus‐positive plasmacytoma in immunocompetent patients
Authors: Loghavi Sanam , Khoury Joseph D , Medeiros L Jeffrey
Published: January 2015

Aims

Extramedullary plasmacytomas are often localized, clinically indolent neoplasms, and affected patients usually respond to radiation therapy or limited cycles of chemotherapy. In contrast, plasmablastic lymphomas are clinically aggressive neoplasms composed of immunoblastic or plasmablastic cells and associated with more mature plasma cells in some cases. Patients with plasmablastic lymphoma usually have a poor prognosis despite aggressive chemotherapy. Evidence of Epstein–Barr virus (EBV) infection is uncommon in plasmacytoma, but common in plasmablastic lymphoma, and is therefore helpful in differential diagnosis. The aim of this study is to describe four cases of plasmacytoma arising in immunocompetent individuals that were diffusely positive for Epstein–Barr virus‐encoded small RNA as shown by in‐situ hybridization.

Methods and results

We describe the clinicopathological and immunophenotypic findings of four EBV‐positive plasmacytomas arising in immunocompetent patients. These tumours were characterized by diffuse proliferation of mature‐appearing plasma cells intermixed with a briskly reactive, CD8‐positive, TIA‐1‐positive cytotoxic T‐cell infiltrate. Long‐term follow‐up was available for all patients, and all were alive and free of disease at last follow‐up (median 43.4 months).

Conclusions

We suggest the term EBV‐positive plasmacytoma in immunocompetent patients for these lesions. It is essential to distinguish these tumours from plasmablastic lymphoma, as the latter diagnosis is associated with a much poorer prog‐nosis, and patients require much more aggressive therapy.
Decreased expression of thymus‐specific proteasome subunit β5t in Down syndrome patients
Authors: Tomaru Utano , Tsuji Takahiro , Kiuchi Shizuka , Ishizu Akihiro , Suzuki Akira , Otsuka Noriyuki , Ito Tomoki , Ikeda Hitoshi , Fukasawa Yuichiro , Kasahara Masanori
Published: January 2015

Aims

The majority of patients with Down syndrome (DS), trisomy 21, have morphologically abnormal thymuses and present with intrinsic immunological abnormalities affecting mainly the cellular immune response. The aim of this study was to examine whether the expression of functionally important molecules is altered in thymic stromal cells in patients with DS.

Methods and results

We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as β5t, a thymoproteasome subunit, and cathepsins L and S. In patients with trisomy 13 and trisomy 18, the thymus was morphologically normal or showed only mild depletion of cortical thymocytes. In contrast, the thymus showed variable histological changes in patients with trisomy 21; six of 13 cases showed severe depletion of thymocytes accompanied by the disappearance of thymic lobular architecture. In such thymuses, spindle‐shaped keratin‐positive cells were densely distributed, and expression of β5t, but not of cathepsin L, was markedly decreased.

Conclusions

The present study suggests that abnormal thymic architecture and decreased expression of functionally important molecules in thymic stromal cells may be involved in immunological abnormalities in DS patients.
Tumour‐to‐tumour metastasis from papillary thyroid carcinoma with BRAF mutation to lung adenocarcinoma with EGFR mutation: the utility of mutation‐specific antibodies
Authors: Katsuya Yuki , Yoshida Akihiko , Watanabe Shun‐ichi , Tsuta Koji
Published: January 2015

Aims

Tumour‐to‐tumour metastasis is a rare event. The aim of this study is to demonstrate the utility of mutation‐specific antibodies to prove the occurrence of metastatic papillary thyroid cancer donor into lung adenocarcinoma recipient.

Methods and results

We report the case of an 80‐year‐old woman who had a papillary thyroid carcinoma with a v‐raf murine sarcoma viral oncogene homologue B1 mutation that metastasized into a lung adenocarcinoma with an epidermal growth factor receptor mutation. Immunohistochemical analysis with mutation‐specific antibodies not only clearly revealed two components, but also revealed their gene mutation statuses.

Conclusions

As a component of multimodal diagnostic tools, immunohistochemistry can avoid some pitfalls involved in the molecular diagnosis of complicated cases (such as our own) and can help to ensure that patients receive optimal treatments.
Abundance and abundance change in the world's parrots
Authors: Marsden Stuart J. , Royle Kay
Published: January 2015

Estimates of population density and abundance change (differences in density or encounter rates across land uses or time periods) form the cornerstone of much of our knowledge of species' responses to environmental conditions, extinction risks and potential conservation actions. Gathering baseline data on abundance of the world's c. 10 000 bird species and monitoring trends in the light of rapidly changing environmental and harvest pressures is a daunting prospect. With this in mind, we review literature on population densities and abundance changes across habitats in one of the world's largest and most threatened bird families, the parrots (Psittaciformes), to identify gaps in knowledge, model phylogenetic and other influences on abundance, and seek patterns that might guide thinking for data‐deficient taxa and situations. Density estimates were found for only 25% of 356 parrot species. Abundance change data were similarly limited and most came from logged forest, with very few comparisons across different anthropogenic habitats. Threatened species were no more likely to have a density estimate than non‐threatened species, and were less likely to have estimates of abundance change. Exploratory generalized linear mixed models indicated that densities are most influenced by genus, and are generally higher within protected areas than outside. It is unclear whether the latter effect stems from habitat protection, a reduction in poaching or both, but protected areas appear to be beneficial for parrots. Individual members of the ‘parakeet’ genera (e.g. Pyrrhura and Eos) were predictably abundant, whereas within larger‐bodied genera such as Ara (macaws), species were predictably uncommon (< 10 individuals per km2) and there was a long tail of extreme rarity. Responses of parrots to habitat change were highly variable, with natural variation in parrot abundance across different primary forests as great as that between primary forest and human‐altered forests. The speed at which environmental change is affecting the world's parrots far outstrips that of our current capacity to track their abundance and we assess the likely scale of data deficiency in this and other bird groups. Developments in survey and analysis methods such as variants of distance sampling and the integration of niche modelling with point density estimation may increase our effectiveness in monitoring parrots and other important and threatened bird groups.
Widespread supplementary feeding in domestic gardens explains the return of reintroduced Red KitesMilvus milvusto an urban area
Authors: Orros Melanie E. , Fellowes Mark D. E.
Published: January 2015

Reintroductions are commonly used to mitigate biodiversity loss. One prominent example is that of the Red KiteMilvus milvus, a charismatic raptor of conservation concern. This species has been reintroduced across theUKover the last 25 years following its near extinction after centuries of persecution. The species was not expected to recolonize urban areas; its historical association with human settlements is attributed to scavenging on human waste and refuse, a resource now greatly reduced on the streets of modern European cities. However, the species has become a common daytime visitor to a large conurbation centred on the town of Reading, southern England, approximately 20 km from the first English reintroduction site. Given a near‐absence of breeding and roost sites, we investigated foraging opportunities and habitat associations that might explain use by Red Kites of this urban area. Surveys of discarded human foods and road‐kill suggested that these could support at most 13–29 Kites per day. Face‐to‐face surveys of a cross‐section of residents revealed that 4.5% (equivalent to 4349 households) provided supplementary food for Red Kites in their gardens. Using estimates of per‐household resource provision from another study, we calculated that this is potentially sufficient to feed 142–320 Kites, a substantial proportion of the total estimated to visit the conurbation each day (between 140 and 440). Road transects found positive associations between Red Kites and residential areas. We suggest that the decision made by thousands of householders to provide supplementary food for Red Kites in their gardens is the primary factor explaining their daytime abundance in this urban area.
Al‐doped Ni/YSZ Anode Material with Improved Electrical Conductivity for MS‐SOFC Fabrication by Cosintering
Authors: Satardekar Pradnyesh , Sglavo Vincenzo M. , Montinaro Dario
Published: December 2014

The effect of Al doping on Ni‐YSZ anode sintering in metal‐supported solid oxide fuel cell (MS‐SOFC) was studied in the current work.The electrical conductivity of the Al‐doped anode was found to increase considerably. Such result may be attributed to the inhibited sintering of insulating YSZ caused by the segragation of Al2O3 at grain boundaries. It was found that the addition of Al to the anode accounts for a finer grained YSZ matrix, thus coating the conducting Ni grains to a lesser extent. 5 wt% Al‐doped NiO used for Ni‐YSZ anode material gave the finest microstucture and the highest electrical conductivity at room temperature although it showed the lowest bulk density. Overall, Al‐doped Ni‐YSZ anode material was found to be a suitable material for the anode in MS‐SOFC produced by cosintering.
Fleeing to Babylon: How the Erie Canal, Diffusion, and Social Structure Forever Changed American Calvinism
Authors: Rowe Justin
Published: January 2015

The following focuses on the Presbyterian Church in the early 19th century United States and suggests that by historically examining its structural dynamics, historians and social scientists alike can better understand not only American religious history but also the diffusion process of intellectual innovation.
Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors‐based therapy
Authors: Sultanik Philippe , Mallet Vincent , Lagaye Sylvie , Casrouge Armanda , Dorival Céline , Barthe Yoann , Fontaine Hélène , Hézode Christophe , Mottez Estelle , Bronowicki Jean‐Pierre , Carrat Fabrice , Theodorou Ioannis , Abel Laurent , Gayat Etienne , Fontanet Arnaud , Pol Stanislas , Albert Matthew L. ,   ANRS CO20‐CUPIC
Published: January 2015

Background & Aims

Chronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated‐interferon/ribavirin (PR) and HCV non‐structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment‐experienced cirrhotic patients from the ANRS CUPIC cohort.

Methods

We analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results.

Results

We identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC = 0.77, Se = 66%, Sp = 72%, NRI = 39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication.

Conclusion

These data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection.