bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles
Authors: Li Long , Zhang Yudie , Wang Jizeng
Published: June 2017

Biophysical-factor-dependent cellular uptake of nanoparticles (NPs) through receptor-diffusion-mediated endocytosis bears significance in pathology, cellular immunity and drug-delivery systems. Advanced nanotechnology of NP synthesis provides methods for modifying NP surface with different ligand distributions. However, no report discusses effects of ligand distribution on NP surface on receptor-diffusion-mediated cellular uptake. In this article, we used a statistical dynamics model of receptor-diffusion-mediated endocytosis to examine ligand-distribution-dependent cellular uptake dynamics by considering that ligand–receptor complexes drive engulfing to overcome resistance to membrane deformation and changes in configuration entropy of receptors. Results showed that cellular internalization of NPs strongly depended on ligand distribution and that cellular-uptake efficiency of NPs was high when ligand distribution was within a range around uniform distribution. This feature of endocytosis ensures robust infection ability of viruses to enter host cells. Interestingly, results also indicated that optimal ligand distribution associated with highest cellular-uptake efficiency slightly depends on distribution pattern of ligands and density of receptors, and the optimal distribution becomes uniform when receptor density is sufficiently large. Position of initial contact point is also a factor affecting dynamic wrapping. This study explains why most enveloped viruses present almost homogeneous ligand distribution and is useful in designing controlled-release drug-delivery systems.
Whole genome sequences of Malawi cichlids reveal multiple radiations interconnected by gene flow
Authors: Malinsky Milan , Svardal Hannes , Tyers Alexandra M. , Miska Eric A. , Genner Martin J. , Turner George F. , Durbin Richard
Published: June 2017

The hundreds of cichlid fish species in Lake Malawi constitute the most extensive recent vertebrate adaptive radiation. Here we characterize its genomic diversity by sequencing 134 individuals covering 73 species across all major lineages. Average sequence divergence between species pairs is only 0.1-0.25%. These divergence values overlap diversity within species, with 82% of heterozygosity shared between species. Phylogenetic analyses suggest that diversification initially proceeded by serial branching from a generalistAstatotilapia-likeancestor. However, no single species tree adequately represents all species relationships, with evidence for substantial gene flow at multiple times. Common signatures of selection on visual and oxygen transport genes shared by distantly related deep water species point to both adaptive introgression and independent selection. These findings enhance our understanding of genomic processes underlying rapid species diversification, and provide a platform for future genetic analysis of the Malawi radiation.

One Sentence Summary: The genomes of 73 cichlid fish species from Lake Malawi uncover evolutionary processes underlying a large adaptive evolutionary radiation.
On the use of the experimentally determined enzyme inhibition constant as a measure of absolute binding affinity
Authors: Darras Fouad H. , Pang Yuan-Ping
Published: June 2017

Defined as a state function representing an inhibitor’s absolute affinity for its target enzyme, the experimentally determined enzyme inhibition constant (Ki) is widely used to rank order binding affinities of different inhibitors for a common enzyme or different enzymes for a common inhibitor and to benchmark computational approaches to predicting binding affinity. Herein, we report that adsorption of bis(7)-tacrine to the glass container surface increased itsKiagainstElectrophorus electricusacetylcholinesterase (eeAChE) to 3.2 ± 0.1 nM (n = 5) compared to 2.9 ± 0.4 pM (n = 5) that was determined using plastic containers with other assay conditions kept the same. We also report that, due to binding or “adsorption” of bis(7)-tacrine to the inactiveeeAChE, the bis(7)-tacrineKiincreased from 2.9 ± 0.4 pM (n = 5) to 734 ± 70 pM (n = 5) as the specificeeAChE activity decreased from 342 U/mg to 26 U/mg while other assay conditions were kept the same. These results caution against usingKis to rank order binding potencies, define selectivity, or benchmark computational methods without knowing detailed assay conditions.

Abbreviations

Ki

enzyme inhibition constant

AChE

acetylcholinesterase

eeAChE

Electrophorus electricusAChE

ATCh

acetylthiocholine chloride

bis(7)-tacrine

1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydro-acridinium dihydrochloride

DTNB

5,5’-dithiobis(2-nitrobenzoic acid)

SEA

specific enzyme activity

tacrine

9-amino-1,2,3,4-tetrahydroacridinium monohydrochloride.
Compositional Canonical Correlation Analysis
Authors: Graffelman Jan , Pawlowsky-Glahn Vera , Egozcue Juan José , Buccianti Antonella
Published: June 2017

The study of the relationships between two compositions by means of canonical correlation analysis is addressed A coimnositional version of canonical correlation analysis is developed. and called CODA-CCO. We consider two approaches, using the centred log-ratio transformation and the calculation of all possible pairwise log-ratios within sets. The relationships between both approaches are pointed out, and their merits are discussed. The related covariance matrices are structurally singular, and this is efficiently dealt with by using generalized inverses. We develop compositional canonical biplots and detail their properties. The canonical biplots are shown to be powerful tools for discovering the most salient relationships between two compositions. Some guidelines for compositional canonical biplots construction are discussed. A geological data set with X-ray fluorescence spectrometry measurements on major oxides and trace elements is used to illustrate the proposed method. The relationships between an analysis based on centred log-ratios and on isometric log-ratios are also shown.
Theta phase synchronization between the human hippocampus and the prefrontal cortex supports learning of unexpected information
Authors: Gruber Matthias J. , Hsieh Liang-Tien , Staresina Bernhard P. , Elger Christian E. , Fell Juergen , Axmacher Nikolai , Ranganath Charan
Published: June 2017

Events that violate predictions are thought to not only modulate activity within the hippocampus and prefrontal cortex, but also to enhance communication between the two regions. Several studies in rodents have shown that synchronized theta oscillations facilitate communication between the prefrontal cortex and hippocampus during salient events, but it remains unclear whether similar oscillatory mechanisms support interactions between the two regions in humans. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and prefrontal cortex from two patients undergoing presurgical evaluation for pharmaco-resistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal-prefrontal theta phase synchronization was significantly higher during encoding of unexpected study items, compared to contextually expected study items. In contrast, we did not find increased theta synchronization between the prefrontal cortex and rhinal cortex. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and prefrontal cortex during the processing of contextually salient information.
Morphological and transcriptomic evidence for ammonium induction of sexual reproduction inThalassiosira pseudonanaand other centric diatoms
Authors: Moore Eric R. , Bullington Briana S. , Weisberg Alexandra J. , Jiang Yuan , Chang Jeff , Halsey Kimberly H.
Published: June 2017

The reproductive strategy of diatoms includes asexual and sexual phases, but in many species, including the model centric diatomThalassiosira pseudonana, sexual reproduction has never been observed. Furthermore, the environmental factors that trigger sexual reproduction in diatoms are not understood. Although genome sequences of a few diatoms are available, little is known about the molecular basis for sexual reproduction. Here we show that ammonium reliably induces the key sexual morphologies, including oogonia, auxospores, and spermatogonia, in two strains ofT. pseudonana,T. weissflogii, andCyclotella cryptica. RNA sequencing revealed 1,274 genes whose expression patterns changed whenT. pseudonanawas induced into sexual reproduction by ammonium. Some of the induced genes are linked to meiosis or encode flagellar structures of heterokont and cryptophyte algae. The identification of ammonium as an environmental trigger suggests an unexpected link between diatom bloom dynamics and strategies for enhancing population genetic diversity.
Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy
Authors: Lacey Cameron J. , Doudney Kit , Bridgman Paul G. , George Peter M. , Mulder Roger T. , Zarifeh Julie J. , Kimber Bridget , Cadzow Murray J. , Black Michael A. , Merriman Tony R. , Lehnert Klaus , Bickley Vivienne M , Pearson John F. , Cameron Vicky A. , Kennedy Martin A.
Published: June 2017

The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, Cardio-MetaboChip genotyping array analysis and array comparative genomic hybridization on these subjects. The most striking finding from these analyses was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs clearly impacted on genes of cardiac relevance includingRBFOX1, GPC5, KCNRG, CHODL, andGPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not fall into a clear pathophysiological pathway. However, the recognition that SCM cases display a high rate of unusual CNV, and that SCM predisposition may therefore be associated with these CNVs, offers a novel perspective and a new approach by which to understand this enigmatic condition.
Cutting Thick Sections Using a Vibratome
Authors: Iulianella Angelo
Published: June 2017

Sectioning with a vibrating microtome (vibratome) is a valuable procedure for generating thick sections that can be used for immunohistochemistry and in situ hybridization. It is particularly useful for revealing histological and 3D detail in tissues and embryos that have been subjected to various whole-mount histological procedures such as β-galactosidase and alkaline phosphatase staining, and fluorescent and DAB (diaminobenzidine) immunostaining. Vibratome sectioning does not involve any harsh organic solvents and is therefore suited for processing specimens stained with fluorescent antibodies or dyes. In addition, live tissue can be sectioned for subsequent culture, manipulation, and live imaging. Very few materials are required for vibratome sectioning, and it is a relatively straightforward procedure that is quickly mastered. This protocol describes basic vibratome sectioning that can be used for any staining procedure typically used in histology.
Direct protein crystallization on ultrathin membranes for diffraction measurements at X-ray free-electron lasers
Authors: Opara Nadia , Martiel Isabelle , Arnold Stefan A. , Braun Thomas , Stahlberg Henning , Makita Mikako , David Christian , Padeste Celestino
Published: June 2017

A new era of protein crystallography started when X-ray free-electron lasers (XFELs) came into operation, as these provide an intense source of X-rays that facilitates data collection in the `diffract-before-destroy' regime. In typical experiments, crystals sequentially delivered to the beam are exposed to X-rays and destroyed. Therefore, the novel approach of serial crystallography requires thousands of nearly identical samples. Currently applied sample-delivery methods, in particular liquid jets or drop-on-demand systems, suffer from significant sample consumption of the precious crystalline material. Direct protein microcrystal growth by the vapour diffusion technique inside arrays of nanolitre-sized wells is a method specifically tailored to crystallography at XFELs. The wells, with X-ray transparent Si3N4windows as bottoms, are fabricated in silicon chips. Their reduced dimensions can significantly decrease protein specimen consumption. Arrays provide crystalline samples positioned in an ordered way without the need to handle fragile crystals. The nucleation process inside these microfabricated cavities was optimized to provide high membrane coverage and a quasi-random crystal distribution. Tight sealing of the chips and protection of the crystals from dehydration were achieved, as confirmed by diffraction experiments at a protein crystallography beamline. Finally, the test samples were shown to be suitable for time-resolved measurements at an XFEL at femtosecond resolution.
The impact of anion ordering on octahedra distortion and phase transitions in SrTaO2N and BaTaO2N
Authors: Wang Chun-Hai , Kennedy Brendan J. , Menezes de Oliveira André L. , Polt Julia , Knight Kevin Steven
Published: June 2017

In this work we synthesized BaTaO2N and SrTaO2N using a two-step high-temperature solid-state reaction method and analysed the structural distortions, relative to the ideal cubic perovskite structure, according to group theory. From a complete distortion analysis/refinement using high-resolution neutron diffraction data in the temperature range 8 to 613 K, we identified tetragonal structures for BaTaO2N [P4/mmm(No. 123)] and SrTaO2N [I4/mcm(No. 140)]. In contrast to an anion-disordered cubic perovskite (Pm \overline{3}m No. 221) with Ta at the cell center, both systems show a site preference for oxygen anions in the two opposite corners (along thecaxis) of the Ta–O/N octahedra rather than the four square corners in theabplane (Γ3+occupancy distortion), which induces a tetragonal elongation of the unit cell with thecaxis being longer than theaaxis. A further Ta–O/N octahedra displacement [R5−(a,0,0), rotation about thecaxis] distortion was observed in SrTaO2N. This distortion mode is accompanied by an increased unit-cell distortion that decreases as the temperature increases. Ultimately a second-order phase transition caused by the loss of theR5−(a,0,0) mode was observed at 400–450 K.
Formation and distortion of iodidoantimonates(III): the first isolated [SbI6]3−octahedron
Authors: Bujak Maciej
Published: June 2017

The ability to intentionally construct, through different types of interactions, inorganic–organic hybrid materials with desired properties is the main goal of inorganic crystal engineering. The primary deformation, related to intrinsic interactions within inorganic substructure, and the secondary deformation, mainly caused by the hydrogen bond interactions, are both responsible for polyhedral distortions of halogenidoantimonates(III) with organic cations. The evolution of structural parameters, in particular the Sb—I secondary- and O/N/C—H...I hydrogen bonds, as a function of temperature assists in understanding the contribution of those two distortion factors to the irregularity of [SbI6]3−polyhedra. In tris(piperazine-1,4-diium) bis[hexaiodidoantimonate(III)] pentahydrate, (C4H12N2)3[SbI6]2·5H2O (TPBHP), where the isolated [SbI6]3–units were found, distortion is governed only by O/N/C—H...I hydrogen bonds, whereas in piperazine-1,4-diium bis[tetraiodidoantimonate(III)] tetrahydrate, (C4H12N2)[SbI4]2·4H2O (PBTT), both primary and O—H...I secondary factors cause the deformation of one-dimensional [{SbI4}n]n−chains. The larger in spatial dimensions piperazine-1,4-diium cations, in contrast to the smaller water of crystallization molecules, do not significantly contribute to the octahedral distortion, especially in PBTT. The formation of isolated [SbI6]3−ions in TPBHP is the result of specific second coordination sphere hydrogen bond interactions that stabilize the hybrid structure and simultaneously effectively separate and prevent [SbI6]3−units from mutual interactions. The temperature-induced changes, further supported by the analysis of data retrieved from the Cambridge Structural Database, illustrate the significance of both primary and secondary distortion factors on the deformation of octahedra. Also, a comparison of packing features in the studied hybrids with those in the non-metal containing piperazine-1,4-diium diiodide diiodine (C4H12N2)I2·I2(PDD) confirms the importance and hierarchy of different types of interactions.
An ordering phase transition, short hydrogen bonds and highZ′ in the structure of Ni(Hpydc)2·3H2O
Authors: Derikvand Zohreh , Powers Xian B. , Olmstead Marilyn M.
Published: June 2017

The structure of Ni(Hpydc)2·3H2O (H2pydc = pyridine-2,6-dicarboxylic acid, also known as dipicolinic acid) has been reinvestigated at variable temperatures. At room temperature, it matches the known structure in the space groupP21/c, but at 180 K it undergoes a phase transformation to a twinned structure inCc. By 120 K, the structure is ordered and twinned withZ′ = 4, and shows interesting short hydrogen-bonding interactions that include the formation of hydroxonium species.
Chiral and achiral crystals, charge-assisted hydrogen-bond patterns and self-organization of selected solid diaminium thiosulfates
Authors: Brozdowska Agnieszka , Chojnacki Jarosław
Published: June 2017

A series of diaminium thiosulfates, derivatives of diamines: NH2CH2CH(CH3)NH2(1) and NH2(CH2)nNH2,n= 3–6 [(2)–(5)] and thiosulfuric acid were prepared and their structures determined by single-crystal X-ray diffraction analysis. Compounds (1), (2) and (4) turned out to be hydrates. The crystal structure of 1,2-propylenediaminium thiosulfate is chiral and exhibits spontaneous resolution. Crystals for both enantiomers [(1a) and (1b)] were obtained with high enantiometric excess and examined. An extended network of strong, charge-assisted hydrogen bonding of the+N—H...O−type (also O—H...O and O—H...S for hydrates) is most likely the main factor defining crystal packing and the variable conformation of the cations. The formation of chiral hydrogen-bond motifs – distorted cubans – seems to induce the formation of chiral solid-state structure from achiral components in the case of (4). Diaminium thiosulfates with an odd number of C atoms in the alkyl chain [compounds (1), (2) and (4)] form three-dimensional supramolecular networks, while in the case of diaminium salts with an even number of C atoms [(3) and (5)], two-dimensional layers of hydrogen-bond domains are observed. The aminium thiosulfates were also characterized by elemental analysis, NMR and Fourier transform (FT)–IR spectroscopy. The conformations of α,ω-alkyldiaminium cations in the solid state are discussed and rationalized by DFT calculations.
Recent developments in theCCP-EMsoftware suite
Authors: Burnley Tom , Palmer Colin M. , Winn Martyn
Published: June 2017

As part of its remit to provide computational support to the cryo-EM community, the Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) has produced a software framework which enables easy access to a range of programs and utilities. The resulting software suite incorporates contributions from different collaborators by encapsulating them in Python task wrappers, which are then made accessibleviaa user-friendly graphical user interface as well as a command-line interface suitable for scripting. The framework includes tools for project and data management. An overview of the design of the framework is given, together with a survey of the functionality at different levels. The currentCCP-EMsuite has particular strength in the building and refinement of atomic models into cryo-EM reconstructions, which is described in detail.
Numerical study of turbulent cavitating flows in thermal regime
Authors: Goncalves Eric , Zeidan Dia
Published: June 2017

Purpose

The aim of this work is to quantify the relative importance of the turbulence modelling for cavitating flows in thermal regime. A comparison of various transport-equation turbulence models and a study of the influence of the turbulent Prandtl number appearing in the formulation of the turbulent heat flux are proposed. Numerical simulations are performed on a cavitating Venturi flow for which the running fluid is freon R-114 and results are compared with experimental data.

Design/methodology/approach

A compressible, two-phase, one-fluid Navier–Stokes solver has been developed to investigate the behaviour of cavitation models including thermodynamic effects. The code is composed by three conservation laws for mixture variables (mass, momentum and total energy) and a supplementary transport equation for the volume fraction of gas. The mass transfer between phases is closed assuming its proportionality to the mixture velocity divergence.

Findings

The influence of turbulence model as regard to the cooling effect due to the vaporization is weak. Only the k – ε Jones–Launder model under-estimates the temperature drop. The amplitude of the wall temperature drop near the Venturi throat increases with the augmentation of the turbulent Prandtl number.

Originality/value

The interaction between Reynolds-averaged Navier–Stokes turbulence closure and non-isothermal phase transition is rarely studied. It is the first time such a study on the turbulent Prandtl number effect is reported in cavitating flows.
International business in an era of anti-globalization
Authors: Meyer Klaus E.
Published: June 2017

Purpose

The apparent onset of an era of anti-globalization creates significant challenges for international business (IB) practice, research and education. This paper aims to discuss the implication of these challenges for IB scholarship.

Design/methodology/approach

This essay assesses the needs for research in IB in view of the challenges posed by the anti-globalization movement.

Findings

The author identifies and analyzes two sets of concerns of the anti-globalization movement: the unequal distribution of the benefits of globalization and emergent constraints on national sovereignty. On that basis, he offers suggestions on how international business scholars may contribute to addressing these challenges through research, teaching and public engagement.

Practical implications

Businesses need to understand the economic and institutional arguments motivating the anti-globalization movement and to address them within their scope of activity.

Social implications

Globalization benefits societies, in general, but some groups do not benefit unless specific remedial action is taken. If these groups are not supported, they can cause political disruption to IB and, hence, economic prosperity.

Originality/value

This paper offers a pathway for IB scholars to contribute to discourses on globalization and anti-globalization.
On the optimal size of bilateral investment treaty network in foreign direct investment flows
Authors: Oh Chang Hoon , Fratianni Michele
Published: June 2017

Purpose

The aim of this paper first is to go beyond the static effects of bilateral investment treaties (BITs) and empirically estimate the marginal effects of the stock of BITs on foreign direct investment flows.

Design/methodology/approach

These statistical models use a gravity equation.

Findings

This paper finds that BITs is subject to diminishing returns measured in terms of FDI flows. Diminishing returns are more pronounced among country-pairs that have not signed BITs but have their own BIT network than among country-pairs with their own BITs.

Research limitations/implications

The subsidiary finding is that a measure of a country’s BIT network characteristic, capturing conditions favorable for a mix of horizontally and vertically integrated activities, may be the limiting force underlying the diminishing returns of the stock of BITs.

Originality/value

For a given country’s BIT network, a multinational enterprise finds more value in investing where a bilateral treaty is in place. This suggests either stronger property-rights protection or greater latitude to use the host country as an export platform.
The chances that an emergency physician will demonstrate three abdominal aortic aneurysms by ultrasound in the emergency department for credentialing: A statistician's view
Authors: Chu Kevin H , Pelecanos Anita , Brown Nathan J , Brown Anthony FT
Published: June 2017

The Australasian College for Emergency Medicine requires 15 proctored examinations of the aorta for credentialing in ultrasonography for abdominal aortic aneurysm (AAA). Furthermore, at least three examinations need to be positive for an aneurysm. In the ED where AAA presentations are sporadic, what are the chances that an emergency physician (EP) will have the opportunity to demonstrate three AAAs in the next 12 months? The probability of an event occurring within a given time‐frame can be modelled by the Poisson distribution. Central to the Poisson distribution is the infrequency of the event such as encountering an AAA in the ED. An EP working 30 clinical hours/week in our tertiary‐referral hospital ED can be expected to encounter 15.6 (3.6 symptomatic + 12 asymptomatic) AAA in the next 12 months. The probability of seeing three or more cases during this time is 99.9%. Assuming a proctor can be found for half the cases, the probability of an EP performing proctored ultrasound examinations in at least three AAAs is 98%. This probability drops to 89% if a proctor can be found for only one‐third of cases. For an EP to be almost 100% certain of meeting the credentialing requirements, he/she would need almost 10 proctored ultrasound cases of AAA to be available within his/her shifts during the year. The Poisson distribution has enabled us to model the probability of encountering a given number of AAA in the ED. Analysis such as this may help rationalise the numbers needed for credentialing.
Visualising emergency department capacity in an ‘Emergency Department Capacity Clock’: A novel tool to assess and communicate overcrowding and access block
Authors: Dar Ohad , Loubser Jacques
Published: June 2017

Hospital‐wide engagement is required to alleviate the problem of ED crowding and its associated adverse effects. To this end, the article describes a novel visualisation termed ‘the ED Capacity Clock’, which can be formatted using business intelligence software. This radial diagram represents ED capacity and its consumption in a format that can be understood intuitively and at a glance. The ED Capacity Clock is designed to promote common understanding and discussion between relevant hospital services and also acts as an auditing tool to monitor processes implemented to alleviate ED crowding.
A Hostile Takeover of Nature? Placing Value in Conservation Finance
Authors: Kay Kelly
Published: June 2017

Conservation finance is a nascent field that claims to “deliver maximum conservation impacts, while, at the same time, generating returns for investors” (Credit Suisse/WWF). While geographers have questioned the ability of conservation finance to play a significant role in international biodiversity conservation, an emerging cohort of boutique private equity firms are actively generating returns on North American conservation projects. This raises the question: how are these firms generating profits, and in turn, returns for their shareholders? Drawing from a Marxian understanding of finance as redistributive, I argue that these firms are generating profits through a process similar to a corporate hostile takeover. Using the examples of ranchland and timberland investment in the United States, I show that (1) the materialities and historical geographies of these landscapes play a crucial role their monetization, and (2) shareholder returns are generated through a combination of traditional real estate sales and revaluations, public monies, and commodity production.
Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries
Authors: Makubi Abel , Roberts David J.
Published: June 2017

Frank iron deficiency has been associated with a wide range of cardiac and pulmonary abnormalities including non‐ischaemic cardiomyopathy. Iron deficiency anaemia and isolated iron deficiency are well‐defined adverse prognostic factors in non‐ischaemic cardiac failure. Furthermore, iron‐deficient patients in chronic heart failure with a serum ferritin of <100 μg/l or <300 μg/l with reduced transferrin saturation of <20%, who were given intravenous iron showed improved clinical outcomes. Iron deficiency with or without anaemia affects over a quarter of the world's population, but the impact of iron deficiency in heart failure and the effective management of iron deficiency in heart failure in Lower and Middle Income Countries (LMICs) is not well described. Heart failure in African cohorts occurs at a younger age than in North America and Europe and is more likely to be due to hypertension. Recent studies suggest that iron deficiency anaemia, which is very common in heart failure patients in Africa, and iron deficiency are independently associated with a poor prognosis in heart failure. Preliminary data suggest that iron deficiency in patients with heart failure can be treated with oral iron, with significant beneficial effects on haematological and physiological variables. Cost may prohibit the use of intravenous iron on a large scale in LMICs and optimal regimes to treat iron deficiency in heart failure patients with oral iron therapy remain to be defined.
ZP1609/danegaptide and mitochondrial connexin hemichannels: a harbinger for peptide drug design
Authors: DeLalio Leon J , Isakson Brant E
Published: June 2017

Linked Articles

This article is a Commentary on Boengler K, Bulic M, Schreckenberg R, Schlüter K‐D, Schulz R (2017). The gap junction modifier ZP1609 decreases cardiomyocyte hypercontracture following ischaemia/reperfusion independent from mitochondrial connexin 43. Br J Pharmacol 174: 2060–2073. https://doi.org/10.1111/bph.13804
COX‐2‐selective inhibitors celecoxib and deracoxib modulate transient receptor potential vanilloid 3 channels
Authors: Spyra Stefan , Meisner Anne , Schaefer Michael , Hill Kerstin
Published: June 2017

Background and Purpose

The transient receptor potential vanilloid 3 (TRPV3) channel is a heat‐sensitive ion channel, which is predominantly expressed in keratinocytes. TRPV3 channels are involved in numerous physiological and pathophysiological processes within the skin, including cutaneous nociception, temperature sensation and development of itch. The role of TRPV3 channels in such processes is poorly understood; therefore, the establishment of selective modulators of TRPV3 channels is highly desirable.

Experimental Approach

Novel TRPV3‐modulating compounds were identified using fluorometric intracellular Ca2+ assays and further evaluated with electrophysiological techniques.

Key Results

TRPV3 activity, elicited by 2‐aminoethoxydiphenyl borate (2‐APB), was efficaciously enhanced by deracoxib and celecoxib, two COX‐2‐selective inhibitors. They exerted their potentiating effect via a direct interaction with TRPV3 as evident from excised inside‐out recordings. Structurally‐related COX‐2 inhibitors affected TRPV3 channel gating to a much lesser degree. Similar results were obtained in HEK293 cells stably expressing cyan fluorescent protein‐tagged mouse TRPV3 channels and in a mouse keratinocyte cell line, endogenously expressing TRPV3. The effects of celecoxib and deracoxib on TRPV3 were dependent on the stimulus used to activate TRPV3. While 2‐APB and heat‐activated TRPV3 channels were potentiated by celecoxib, carvacrol‐activated channels were inhibited by celecoxib.

Conclusions and Implications

We identified a new class of drugs that modulate TRPV3 channels. The most potent compound celecoxib is an approved analgesic and anti‐inflammatory drug, which is currently being investigated for its topical application in the treatment of skin cancer. As TRPV3 is highly expressed in skin, celecoxib might affect TRPV3 activity in vivo when used at high local concentrations.
Completion in vocational and academic upper secondary school: The importance of school motivation, self‐efficacy, and individual characteristics
Authors: Dæhlen Marianne
Published: June 2017

A vast amount of research is devoted to identifying factors that predict early school leaving. However, there is no simple explanation because the results show that young people leave education prematurely for various reasons, such as their level of school involvement, their background characteristics and different school systems. This article investigates the importance of school motivation, self‐efficacy and the characteristics of students and their families for completing school and examines students in the vocational and academic tracks separately. With a focus on school completion, this study is guided by the following research question: Do students who obtain an upper secondary diploma have greater motivation and stronger beliefs about their abilities than those who choose to leave early? When adjusting for background characteristics, the results indicated no, or a relatively low, relationship between school motivation/self‐efficacy and completion. The most predictable variable is prior school performances, particularly for students in the vocational track.
Synthesis and oxidation resistance of V2AlC powders by molten salt method
Authors: Wang Bingxin , Zhou Aiguo , Hu Qianku , Wang Libo
Published: June 2017

Herein, ternary carbide V2AlC was synthesized by molten salt method from elemental powders with molar ratio of V:Al:C=2:1.2:1 and same mass of NaCl. According to thermal analysis of the starting mixture, at 800°C, NaCl melts to form ionic liquid environment for the formation reaction of V2AlC, which starts at the temperature above 1050°C. The existence of NaCl in starting mixture results in the synthesis of V2AlC at 1050°C. And following annealing at 1400°C can remove the impurities of Al23V4 and C to synthesize pure V2AlC. Without NaCl, V2AlC cannot be synthesized at 1050°C and V2AlC synthesized at 1400°C is not pure. For the purpose to measure oxidation resistance of V2AlC samples, as‐synthesized V2AlC powders were pressed to cylinder shape (Φ10 mm×2 mm) and the cylinders (relative density of 82.7%) were heated in air. At temperature below 400°C, the oxidation was not obvious. At 650°C, a rough film composed of V2O5 and Al2O3 was formed and cover the surface of V2AlC. The film resulted in good oxidation resistance of V2AlC. At 800°C, the rough film transformed to needle‐like crystals, which were mainly composed of V2O5. The oxidation resistance became very bad. V2AlC can be completely oxidized to form V2O5 and Al2O3.
Patient‐reported outcomes (PROs) in chronic urticaria
Authors: Moestrup Kristian , Ghazanfar Misbah N. , Thomsen Simon F.
Published: June 2017

Chronic urticaria is an itching skin disease which persists for more than 6 weeks. Chronic urticaria has great impact on the daily life of the patient, and the fluctuating nature of the symptoms complicates the monitoring and treatment of the disease. Currently, there are no reliable biomarkers to identify and measure disease activity in chronic spontaneous urticaria. Consequently, use of patient‐reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview of seven different PROs used in chronic urticaria and highlight their strengths, limitations, and use in clinical practice and research.
Role of poly(ADP‐ribose) polymerase activation in the pathogenesis of periodontitis in diabetes
Authors: Adachi Kei , Miyajima Shin‐ichi , Nakamura Nobuhisa , Miyabe Megumi , Kobayashi Yasuko , Nishikawa Toru , Suzuki Yuki , Kikuchi Takeshi , Kobayashi Shuichiro , Saiki Tomokazu , Mizutani Makoto , Ohno Norikazu , Noguchi Toshihide , Mitani Akio , Matsubara Tatsuaki , Naruse Keiko
Published: June 2017

Aim

The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP‐ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor.

Materials and Methods

Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5‐isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP‐ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro‐CT analyses.

Results

Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine‐positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor.

Conclusions

These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.
Anxiety disorders, gender nonconformity, bullying and self‐esteem in sexual minority adolescents: prospective birth cohort study
Authors: Jones Abbeygail , Robinson Emily , Oginni Olakunle , Rahman Qazi , Rimes Katharine A.
Published: June 2017

Background

Sexual minority adolescents (i.e. youth not exclusively heterosexual) report more anxiety than heterosexual youth on symptom questionnaires but no research has used standardised diagnostic tools to investigate anxiety disorder risk. This study uses a UK birth cohort to investigate the risk of anxiety disorders in sexual minority and heterosexual youth using a computerised structured clinical interview and explores the influence of gender nonconformity, bullying and self‐esteem.

Methods

Participants were 4,564 adolescents (2,567 girls and 1,996 boys) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Logistic regression analyses were performed to investigate the association between sexual orientation at 15.5 years and the presence of an anxiety disorder at 17.5 years. Covariates including maternal occupation, ethnicity, mother‐reported childhood gender nonconformity at 30, 42 and 57 months, child‐reported gender nonconformity at 8 years, child‐reported bullying between 12 and 16 years and self‐esteem at 17.5 years were added sequentially to regression models.

Results

Sexual minority adolescents (i.e. those not exclusively heterosexual) had higher early childhood gender nonconformity (CGN), lower self‐esteem and reported more bullying than adolescents identifying as 100% heterosexual. Minority sexual orientation at 15.5 years was associated with increased risk of an anxiety disorder at 17.5 years for girls (OR 2.55, CI 1.85–3.52) and boys (OR 2.48, CI 1.40–4.39). Adjusting for ethnicity, maternal occupation, mother‐reported and child‐reported CGN had minimal impact on this association. Adjusting for bullying between 12 and 16 years and self‐esteem at 17.5 years reduced the strength of the associations, although the overall association remained significant for both sexes (girls OR 2.14 and boys OR 1.93).

Conclusions

Sexual minority youth are at increased risk of anxiety disorders relative to heterosexual youth at 17.5 years. Bullying between 12–16 years and lower self‐esteem may contribute to this risk.
Dream emotions: a comparison of home dream reports with laboratory early and late REM dream reports
Authors: Sikka Pilleriin , Revonsuo Antti , Sandman Nils , Tuominen Jarno , Valli Katja
Published: June 2017

The aim of this study was to compare the emotional content of dream reports collected at home upon morning awakenings with those collected in the laboratory upon early and late rapid eye movement (REM) sleep awakenings. Eighteen adults (11 women, seven men; mean age = 25.89 ± 4.85) wrote down their home dreams every morning immediately upon awakening during a 7‐day period. Participants also spent two non‐consecutive nights in the sleep laboratory where they were awoken 5 min into each continuous REM sleep stage, upon which they gave a verbal dream report. The content of a total of 151 home and 120 laboratory dream reports was analysed by two blind judges using the modified Differential Emotions Scale. It was found that: (1) home dream reports were more emotional than laboratory early REM dream reports, but not more emotional than laboratory late REM dream reports; (2) home dream reports contained a higher density of emotions than laboratory (early or late REM) dream reports; and (3) home dream reports were more negative than laboratory dream reports, but differences between home and early REM reports were larger than those between home and late REM reports. The results suggest that differences between home and laboratory dream reports in overall emotionality may be due to the time of night effect. Whether differences in the density of emotions and negative emotionality are due to sleep environment or due to different reporting procedures and time spent in a sleep stage, respectively, remains to be determined in future studies.
Risk factors for vertical transmission of hepatitis E virus infection
Authors: Sharma S. , Kumar A. , Kar P. , Agarwal S. , Ramji S. , Husain S. A. , Prasad S. , Sharma S.
Published: June 2017

Hepatitis E virus (HEV) infection can be vertically transmitted, but the factors that transmit the disease to foetuses are still unclear. We studied a total of 144 pregnant women with HEV infection. Cord blood and newborn samples were taken for analysis. Nutritional factors were evaluated on the basis of anthropometric parameters and biochemical factors, and HEV viral load was quantified by real‐time PCR. Sequencing of HEV‐positive samples was performed. Approximately 14.63% (6/41) of pregnant patients with acute liver failure (ALF) died before delivery. Vertical transmission was observed in 46.09% (59/128) of HEV‐IgM‐positive mothers. Approximately 23.80% (10/42) of newborns in the acute viral hepatitis group and 29.41% (5/17) in the ALF group were positive for HEV‐RNA. No significant difference was observed in the occurrence of vertical transmission in HEV groups. Viral load was found to be a significant predictor for vertical transmission of HEV infection adjusted with haemoglobin and folate in derivation cohort group. Incorporating these variables, a new score predicting vertical transmission of HEV was derived. Using these significant predictors, the probability for vertical transmission of HEV was well stratified in the validation group (P>.05). In conclusion, viral load was associated with vertical transmission of HEV infection. A valid prediction score model was generated that was verified in a validation cohort group.
Local governance of Gunao Lake, Tikub Lake and Dagatan Lake: Small lakes of the Mount Banahaw–San Cristobal–Malepunyo Corridor, Philippines
Authors: Brillo B. B. C.
Published: June 2017

Although many lakes in the Philippines are threatened, the effectiveness of their governance has not received sufficient attention to date. This predicament is most severe in regard to small lakes as their localized governance has least been given consideration over the years. Predicated on this observation, this study explores the local governance of three small lakes (Gunao Lake; Tikub Lake; Dagatan Lake) situated between the Mount Banahaw–San Cristobal and Mount Malepunyo area. Specifically, it analyses the role of local governments in managing and developing the small lakes. Using data from interviews, observations and the few existing documents on these lakes, this study contends that the main feature of governance regarding the three lakes is the Municipal Governments’ commitment and determination, which is consequential in their development over time. For Gunao Lake, the failure of the Municipal Government of Dolores to link the development of the lake with the tourism agenda in the Mount Banahaw area has resulted in its lack of tourism development. For Tikub Lake, the consistent push of the Municipal Government of Tiaong for its tourism agenda is key in the incremental improvement and preservation of the lake. For Dagatan Lake, the persistence of the Municipal Government of San Antonio in pursuing the restoration project and searching for a patron to finance the endeavour is crucial in the revival of the lake. Overall, this study highlights the distinct praxis of local governance regarding each of these small lakes, extends scholarship in regard to lake governance and offers a broad template for managing the many existing small lakes in the country.
Divergent taxonomic and functional responses of microbial communities to field simulation of aeolian soil erosion and deposition
Authors: Ma Xingyu , Zhao Cancan , Gao Ying , Liu Bin , Wang Tengxu , Yuan Tong , Hale Lauren , Nostrand Joy D. Van , Wan Shiqiang , Zhou Jizhong , Yang Yunfeng
Published: June 2017

Aeolian soil erosion and deposition have worldwide impacts on agriculture, air quality and public health. However, ecosystem responses to soil erosion and deposition remain largely unclear in regard to microorganisms, which are the crucial drivers of biogeochemical cycles. Using integrated metagenomics technologies, we analysed microbial communities subjected to simulated soil erosion and deposition in a semiarid grassland of Inner Mongolia, China. As expected, soil total organic carbon and plant coverage were decreased by soil erosion, and soil dissolved organic carbon (DOC) was increased by soil deposition, demonstrating that field simulation was reliable. Soil microbial communities were altered (p < .039) by both soil erosion and deposition, with dramatic increase in Cyanobacteria related to increased stability in soil aggregates. amyA genes encoding α‐amylases were specifically increased (p = .01) by soil deposition and positively correlated (p = .02) to DOC, which likely explained changes in DOC. Surprisingly, most of microbial functional genes associated with carbon, nitrogen, phosphorus and potassium cycling were decreased or unaltered by both erosion and deposition, probably arising from acceleration of organic matter mineralization. These divergent responses support the necessity to include microbial components in evaluating ecological consequences. Furthermore, Mantel tests showed strong, significant correlations between soil nutrients and functional structure but not taxonomic structure, demonstrating close relevance of microbial function traits to nutrient cycling.