bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevation of hepatic sulphotransferase activities in mice with resistance to cystic fibrosis
Authors: FALANY Josie L. , GREER Heather , KOVACS Timea , SORSCHER Eric J. , FALANY Charles N.
Published: August 2015

The severity of intestinal disease in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) (-/−) mice has been reported to co-segregate with gene loci which contain the genes for hydroxysteroid sulphotransferase (SULT). Because of the potential involvement of steroid hormones in CF, we investigated levels of steroid SULT activity in the livers of CFTR mice to determine whether the levels of SULT activity correlate with the occurrence or severity of CF. To elucidate the possible role of SULT activity in ameliorating the deleterious effects of CF in CFTR (-/−) mice, we determined the levels of phenol SULT (PST), hydroxysteroid SULT [dehydroepiandrosterone (DHEA)-ST] and oestrogen SULT (EST) activity in control CFTR (+/+), heterozygous CFTR (+/−) and homozygous CFTR (-/−) mice, which survive to adulthood. The level of PST activity was not significantly different between any of the groups of mice, regardless of sex or genotype. Although DHEA-ST activity was significantly higher in female mice than in male mice, there was no difference in DHEA-ST activity that could be correlated with genotype. In contrast with PST and DHEA-ST activities, we found that some male and all female adult CFTR (-/−) mice had elevated, dramatically different levels of EST from both CFTR (+/+) and CFTR (+/−) mice. Results from these SULT activity experiments were confirmed by Northern-blot analysis of mouse-liver RNA. Subsequent studies with preweanling mice revealed no differences in the levels of EST that could be correlated with genotype. Thus this study indicates that EST is elevated significantly in CFTR (-/−) mice which survive to adulthood and provides important biochemical information that EST levels may be protective in CF.
Diacylglycerol activates the influx of extracellular cations in T-lymphocytes independently of intracellular calcium-store depletion and possibly involving endogenous TRP6 gene products
Authors: GAMBERUCCI Alessandra , GIURISATO Emanuele , PIZZO Paola , TASSI Maristella , GIUNTI Roberta , McINTOSH Deirdre Patricia , BENEDETTI Angelo
Published: August 2015

In Jurkat and human peripheral blood T-lymphocytes, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeant analogue of diacylglycerol, activated the influx of Ca2+, Ba2+ and Sr2+. OAG also caused plasma-membrane depolarization in Ca2+-free media that was recovered by the addition of bivalent cation, indicating the activation of Na+ influx. OAG-induced cation influx was (i) mimicked by the natural dacylglycerol 1-stearoyl-2-arachidonyl-sn-glycerol, (ii) not blocked by inhibiting protein kinase C or in the absence of phopholipase C activity and (iii) blocked by La3+ and Gd3+. Differently from OAG, both thapsigargin and phytohaemagglutinin activated a potent influx of Ca2+, but little influx of Ba2+ and Sr2+. Moreover, the influx of Ca2+ activated by thapsigargin and that activated by OAG were additive. Furthermore, several drugs (i.e. econazole, SKF96365, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2-aminoethoxy diphenylborate and calyculin-A), while inhibiting the influx of Ca2+ induced by both thapsigargin and phytohaemagglutinin, did not affect OAG-stimulated cation influx. Transient receptor potential (TRP) 3 and TRP6 proteins have been shown previously to be activated by diacylglycerol when expressed heterologously in animal cells [Hofmann, Obukhov, Schaefer, Harteneck, Gudermann and Schultz (1999) Nature (London) 397, 259–263]. In both Jurkat and peripheral blood T-lymphocytes, mRNA encoding TRP proteins 1, 3, 4 and 6 was detected by reverse transcriptase PCR, and the TRP6 protein was detected by Western blotting in a purified plasma-membrane fraction. We conclude that T-cells express a diacylglycerol-activated cation channel, unrelated to the channel involved in capacitative Ca2+ entry, and associated with the expression of TRP6 protein.
High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate
Authors: ZHANG Yuesheng , CALLAWAY Eileen C.
Published: August 2015

Sulphoraphane (SF), a naturally occurring isothiocyanate, is a potent anticarcinogen in animal experiments. The mechanism of action of sulphoraphane includes induction of Phase 2 detoxification enzymes, inhibition of carcinogen-activating Phase 1 enzymes, induction of apoptosis and cell cycle arrest, and anti-inflammation. We have recently found that it was accumulated in mammalian cells by up to several hundred-fold over the extracellular concentration, primarily by conjugation with intracellular GSH. The intracellular accumulation levels of SF can reach millimolar concentrations. The anticarcinogenic activity of SF is at least partly dependent on its accumulation levels in cells. Here we show, however, that the accumulated SF was rapidly exported mainly in the form of GSH conjugate (GS—SF) in cultured human cells. It appeared that to sustain the intracellular accumulation levels required a continuous uptake of SF to offset the rapid export of SF/GS—SF. These findings may have important implications for the development of an effective dosing regimen for SF. Moreover, the export was temperature-sensitive and was inhibited by known inhibitors of membrane pumps, suggesting the involvement of such a pump in exporting accumulated SF/GS—SF. Indeed, studies with human leukemia cells (HL60) with or without overexpression of multidrug resistance associated protein-1(MRP-1) and human myeloma cells (8226) with or without overexpression of P-glycoprotein-1 (Pgp-1) indicated that both MRP-1 and Pgp-1 are involved in the export of intracellular SF/GS—SF.
Matrix metalloproteinases in cancer
Authors: Itoh Yoshifumi , Nagase Hideaki
Published: August 2015

The extracellular matrix (ECM) holds cells together and maintains the three-dimensional structure of the body. It also plays critical roles in cell growth, differentiation, survival and motility. For a tumour cell to metastasize from the primary tumour to other organs, it must locally degrade ECM components that are the physical barriers for cell migration. The key enzymes responsible for ECM breakdown are matrix metalloproteinases (MMPs). To date, 23 MMP genes have been identified in humans and many are implicated in cancer. ECM degradation by MMPs not only enhances tumour invasion, but also affects tumour cell behaviour and leads to cancer progression. This review highlights recent developments with regard to the cellular and molecular mechanisms of MMPs that influence tumour cell growth, invasion and metastasis.
DNA recognition by nuclear receptors
Authors: Claessens Frank , Gewirth Daniel T
Published: August 2015

The nuclear receptors constitute a large family of ligand-inducible transcription factors. The control of many genetic pathways requires the assembly of these nuclear receptors in defined transcription-activating complexes within control regions of ligand-responsive genes. An essential step is the interaction of the receptors with specific DNA sequences, called hormone-response elements (HREs). These response elements position the receptors, and the complexes recruited by them, close to the genes of which transcription is affected. HREs are bipartite elements that are composed of two hexameric core half-site motifs. The identity of the response elements resides in three features: the nucleotide sequence of the two core motif half-sites, the number of base pairs separating them and the relative orientation of the motifs. The DNA-binding domains of nuclear receptors consist of two zinc-nucleated modules and a C-terminal extension. Residues in the first module determine the specificity of the DNA recognition, while residues in the second module are involved in dimerization. Indeed, nuclear receptors bind to their HREs as either homodimers or heterodimers. Depending on the type of receptor, the C-terminal extension plays a role in sequence recognition, dimerization, or both. The DNA-binding domain is furthermore involved in several other functions including nuclear localization, and interaction with transcription factors and co-activators. It is also the target of post-translational modifications. The DNA-binding domain therefore plays a central role, not only in the correct binding of the receptors to the target genes, but also in the control of other steps of the action mechanism of nuclear receptors.
Plant carotenoids and related molecules: important dietary antioxidants
Authors: Krinsky Norman I.
Published: August 2015

The antioxidant effects of dietary carotenoids such as ϐ-carotene have been well documented in various systems in vitro, using either organic solvents or membrane systems. However, the biologically relevant studies of the effects of ϐ-carotene on low-density lipoprotein (LDL) oxidation are still controversial, as are those studies using LDL from individuals supplemented with large amounts of ϐ-carotene. These findings do not agree with the epidemiological evidence which suggests that individuals who consume fruits and vegetables rich in carotenoids, or who have relatively high serum carotenoid levels, are at a lower risk of developing coronary heart disease. What is apparent is that studies that have looked at antioxidant protection in the whole organism have demonstrated a decrease in markers of lipid peroxidation after ϐ-carotene supplementation. Maybe those studies trying to pin-point the antioxidant site of carotenoids in vivo have been looking at the wrong tissue.
Oxidative damage by ozone and nitrogen dioxide: synergistic toxicity in vivo but no evidence of synergistic oxidative damage in an extracellular fluid
Authors: O'Neill Charles A. , van der Vliet Albert , Eiserich Jason P. , Last Jerold A. , Halliwell Barry , Cross Carroll E.
Published: August 2015

Inhalation of ozone (O3) and/or nitrogen dioxide (.NO2) is associated with the development of inflammation in the respiratory tract and various alterations in pulmonary functions. Respiratory tract lining fluids (RTLFs) represent the first biological fluids coming into contact with these inhaled toxicants. Using plasma as a surrogate for RTLFs, we have previously shown that O3 [Cross, Motchnik, Bruener, Jones, Kaur, Ames and Halliwell (1992) FEBS Lett. 298, 269-272] and .NO2 [Halliwell, Hu, Louie, Duvall, Tarkington, Motchnik and Cross (1992) FEBS Lett. 313, 62-66] are both capable of depleting antioxidants and damaging proteins and lipids. O3 particularly damages proteins, whereas .NO2 induces the peroxidation of lipids and nitrates aromatic amino acids. It has been reported that O3 and .NO2 cause synergistic toxicity in rodents [Gielzleichter, Witschi and Last (1992) Tox. Appl. Pharmacol. 116, 1-9]. In the present chapter, we review evidence showing that combined exposure of these two oxidant gases to human plasma fails to exert synergistic oxidative damage to plasma constituents, and in fact, O3 and .NO2 antagonize each other's actions. We conclude that the potentiating effect of these two gases on morbidity and mortality in rodents represents a complex interactive biological effect rather than a simple synergistic oxidative effect in extracellular fluids.
Side-effects of drugs used in the treatment of rheumatoid arthritis
Authors: Evans P.J. , Halliwell B.
Published: August 2015

A number of anti-inflammatory and other drugs used in the treatment of rheumatoid arthritis have been screened for their ability to cause oxidative damage to lipids and proteins in vitro. Although many drugs exhibited an antioxidant profile, a few drugs tested were pro-oxidant, increasing peroxidation of arachidonic acid by mixtures of haem proteins and H2O2. This system may be an appropriate model to use in the inflammatory situation, since microbleeding to release haemoglobin occurs in the inflamed rheumatoid joint, where H2O2 is produced by invading neutrophils. The damaging effects of the pro-oxidant drugs phenylbutazone, meclofenamic acid and flufenamic acid were investigated in some detail using this system. Arachidonic acid peroxidation was accentuated in a dose-dependent manner and in the presence of haem proteins and H2O2, phenylbutazone also causes inactivation of α1-antiproteinase, a major serine proteinase inhibitor in biological fluids. The above drugs may interact with ferryl haemoglobin, produced by the reaction of H2O2 with haemoglobin, to generate drug-derived radicals causing oxidative damage in these systems. If such reactions occur in vivo, they could contribute to the side-effects induced by these drugs on administration to certain rheumatoid arthritis patients.
Guidelines for the assembly of novel coiled-coil structures: α-sheets and α-cylinders
Authors: Walshaw John , Shipway Jennifer M. , Woolfson Derek N.
Published: August 2015

The coiled coil is a ubiquitous motif that guides many different protein-protein interactions. The accepted hallmark of coiled coils is a seven-residue (heptad) sequence repeat. The positions of this repeat are labelled a-b-c-d-e-f-g, with residues at a and d tending to be hydrophobic. Such sequences form amphipathic α-helices, which assemble into helical bundles via knobs-into-holes interdigitation of residues from neighbouring helices. We wrote an algorithm, SOCKET, to identify this packing in protein structures, and used this to gather a database of coiled-coil structures from the Protein Data Bank. Surprisingly, in addition to commonly accepted structures with a single, contiguous heptad repeat, we identified sequences with multiple, offset heptad repeats. These 'new' sequence patterns help to explain oligomer-state specification in coiled coils. Here we focus on the structural consequences for sequences with two heptad repeats offset by two residues, i.e. a/f′-b/g′-c/a′-d/b′-e/c′-f/d′-g/e′. This sets up two hydrophobic seams on opposite sides of the helix formed. We describe how such helices may combine to bury these hydrophobic surfaces in two different ways and form two distinct structures: open 'α-sheets' and closed 'α-cylinders'. We highlight these with descriptions of natural structures and outline possibilities for protein design.
Functional post-translational proteomics approach to study the role of N-glycans in the development of Caenorhabditis elegans
Authors: Schachter Harry , Chen Shihao , Zhang Wenli , Spence Andrew M. , Zhu Shaoxian , Callahan John W. , Mahuran Don J. , Fan Xiaolian , Bagshaw Rick D. , She Yi-Min , Rosa J Cesar , Reinhold Vernon N.
Published: August 2015

Glycosylation is one of the most common post-translational protein modifications. Carbohydrate-mediated interactions between cells and their environment are important in differentiation, embryogenesis, inflammation, cancer and metastasis and other processes. Humans and mice with mutations that prevent normal N-glycosylation show multi-systemic defects in embryogenesis, thereby proving that these molecules are essential for normal development; however, a large number of proteins undergo defective glycosylation in these human and mouse mutants, and it is therefore difficult to determine the precise molecular roles of specific N-glycans on individual proteins. We describe here a 'functional post-translational proteomics' approach that is designed to determine the role of N-glycans on individual glycoproteins in the development of Caenorhabditis elegans.
Glycosyltransferases and glycan structures contributing to the adhesive activities of L-, E- and P-selectin counter-receptors
Authors: Lowe John B.
Published: August 2015

In mammals, leucocytes of the adaptive and innate immune systems must move from their sites of origin to sites of maturation, or to where they are deployed against the invasion of pathogens. The vascular tree serves as the primary throughfare by which leucocytes move to these various destinations. Adhesion must be established between the leucocyte and the endothelial cells that line the vascular tree to enable leucocytes to escape the vascular compartment and then contribute to extravascular immune processes. A major fraction of these leucocyte endothelial-cell adhesive events initiate with, and require interactions between, the selectin family of cell adhesion molecules and their glycoconjugate counter-receptors. This article will review the structures of the glycan components of these counter-receptors, and the glycosyltransferases that control their expression.
The glycomes of Caenorhabditis elegans and other model organisms
Authors: Haslam Stuart M. , Gems David , Morris Howard R. , Dell Anne
Published: August 2015

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.
Use of anti-neoepitope antibodies for the analysis of degradative events in cartilage and the molecular basis for neoepitope specificity
Authors: Mort John S. , Flannery Carl R. , Makkerh Joe , Krupa Joanne C. , Lee Eunice R.
Published: August 2015

Degradation of the cartilage proteoglycan, aggrecan, is an essential aspect of normal growth and development, and of joint pathology. The roles of different proteolytic enzymes in this process can be determined from the sites of cleavage in the aggrecan core protein, which generates novel termini (neoepitopes). Antibodies specific for the different neoepitopes generated by such cleavage events provide powerful tools with which to analyse these processes. The same approach can be used to differentiate the processed, active forms of proteases from their inactive pro-forms. Since the proteolytic processing of these enzymes requires the removal of the inhibitory pro-region, it also results in the generation of N-terminal neoepitopes. Using the newborn rat long bone as a model system, it was shown that the active form of ADAMTS-4 [ADAM (a disintegrin and metalloproteinase) with thrombospondin motifs-4], but not ADAMTS-5, co-localizes with the aggrecan cleavage neoepitopes known to be produced by this metalloproteinase. Thus, in long bone growth, aggrecan turnover seems to be dependent on ADAMTS-4 activity. To demonstrate the molecular basis of the specificity of anti-neoepitope antibodies, the Fv region of a monoclonal antibody specific for a neoepitope generated by the ADAMTS-4-mediated cleavage of aggrecan has been modelled and the binding of the peptide epitope simulated. In the docked structure, the N-terminus of the peptide antigen is clearly buried in the binding-site cavity. The absence of an open cleft makes it impossible for the intact substrate to pass through the binding site, providing a rationale for the specificity of this class of antibodies.
Cofactor processing in galactose oxidase
Authors: Firbank Susan , Rogers Melanie , Guerrero Ramon Hurtado , Dooley David M. , Halcrow Malcolm A. , Phillips Simon E. V. , Knowles Peter F. , McPherson Michael J.
Published: August 2015

GO (galactose oxidase; E.C. 1.1.3.9) is a monomeric 68 kDa enzyme that contains a single copper ion and an amino acid-derived cofactor. The enzyme is produced by the filamentous fungus Fusarium graminearum as an extracellular enzyme. The enzyme has been extensively studied by structural, spectroscopic, kinetic and mutational approaches that have provided insight into the catalytic mechanism of this radical enzyme. One of the most intriguing features of the enzyme is the post-translational generation of an organic cofactor from active-site amino acid residues. Biogenesis of this cofactor involves the autocatalytic formation of a thioether bond between Cys-228 and Tyr-272, the latter being one of the copper ligands. Formation of this active-site feature is closely linked to the loss of an N-terminal 17 amino acid prosequence. When copper and oxygen are added to this pro-form of GO (pro GO), purified in copper-free conditions from the heterologous host Aspergillus nidulans, mature GO is formed by an autocatalytic process. Structural comparison of pro GO with mature GO reveals overall structural similarity, but with some regions showing significant local differences in main-chain position. Some side chains of the active-site residues differ significantly from their positions in the mature enzyme. These structural effects of the prosequence suggest that it may act as an intramolecular chaperone to provide an open active-site structure conducive to copper binding and chemistry associated with cofactor formation. The prosequence is not mandatory for processing, as a recombinant form of GO lacking this region and purified under copper-free conditions can also be processed in an autocatalytic copper- and oxygen-dependent manner.
Guanylyl cyclase: NO hits its target
Authors: Russwurm Michael , Koesling Doris
Published: August 2015

The NO receptor, NO-sensitive guanylyl cyclase, plays a key role in the NO/cGMP signal-transduction cascade. Two isoforms of the enzyme are currently known, the widely distributed vascular α1ϐ1 isoform and the neuronal α2ϐ1 isoform predominantly expressed in brain. Interaction with the PSD-95 (postsynaptic density protein-95) family of scaffolding proteins targets the neuronal α2ϐ1 isoform to synaptic membranes. The NO sensor of the guanylyl cyclase is formed by the prosthetic haem group, where NO binding takes place and induces the up to 200-fold activation of the enzyme. The haem group allows tight regulation of enzymic activity by NO and represents the most striking feature of the enzyme, as it differs in many aspects from the well-characterized haem groups of other haemoproteins. The new NO sensitizers such as YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole] affect activation by NO and CO by mechanisms that are currently subject to intense research.
How transcriptional and epigenetic programmes are played out on an individual mammalian gene cluster during lineage commitment and differentiation
Authors: Higgs Douglas R. , Vernimmen Douglas , De Gobbi Marco , Anguita Eduardo , Hughes Jim , Buckle Veronica , Iborra Franciso , Garrick David , Wood William G.
Published: August 2015

In the post-genomic era, a great deal of work has focused on understanding how DNA sequence is used to programme complex nuclear, cellular and tissue functions throughout differentiation and development. There are many approaches to these issues, but we have concentrated on understanding how a single mammalian gene cluster is activated or silenced as stem cells undergo lineage commitment, differentiation and maturation. In particular we have analysed the α globin cluster, which is expressed in a cell-type- and developmental stage-specific manner in the haemopoietic system. Our studies include analysis of the transcriptional programme that accompanies globin gene activation, focusing on the expression of relevant transcription factors and cofactors. Binding of these factors to the chromosomal domain containing the α globin cluster has been characterized by ChIP (chromatin immunoprecipitation). In addition, we have monitored the epigenetic modifications (e.g. nuclear position, timing of replication, chromatin modification, DNA methylation) that occur as the genes are activated (in erythroid cells) or silenced (e.g. in granulocytes) as haemopoiesis proceeds. Together, these observations provide a uniquely well-characterized model illustrating the mechanisms that regulate and memorize patterns of mammalian gene expression as stem cells undergo lineage specification, differentiation and terminal maturation.
A role for upstream binding factor in organizing ribosomal gene chromatin
Authors: Wright Jane E. , Mais Christine , Prieto José-Luis , McStay Brian
Published: August 2015

Human ribosomal genes are located in NORs (nucleolar organizer regions) on the short arms of acrocentric chromosomes. During metaphase, previously active NORs appear as prominent chromosomal features termed secondary constrictions, which are achromatic in chromosome banding and positive in silver staining. The architectural RNA polymerase I transcription factor UBF (upstream binding factor) binds extensively across the ribosomal gene repeat throughout the cell cycle. Evidence that UBF underpins NOR structure is provided by an examination of cell lines in which large arrays of a heterologous UBF binding sequences are integrated at ectopic sites on human chromosomes. These arrays efficiently recruit UBF even to sites outside the nucleolus, and during metaphase form novel silver-stainable secondary constrictions, termed pseudo-NORs, that are morphologically similar to NORs.
Modern Concepts in Biochemistry (Second Edition)
Authors: TURNBULL J.
Published: August 2015

Modern Concepts in Biochemistry (Second Edition)
Credential and Skill Mismatches Among Tertiary Graduates: The effect of labour market institutions on the differences between fields of study in 18 countries
Authors: Assirelli Giulia
Published: August 2015

This study provides new empirical evidence about tertiary graduates’ overeducation, by analysing the influence of labour market institutions on the incidence and distribution of the phenomenon across fields of study. In particular, the analyses focus on the level of employment protection, the regulation of access to the so-called liberal professions, and the propensity of welfare states to hire skilled workers. Data from two comparative surveys – REFLEX and HEGESCO – are used, and a wide set of information is employed to split overeducation in two forms of suboptimal allocation of individuals in the labour market: credential and skill mismatches. The first term refers to the mismatch between formal educational credentials and job requirements, whereas the second term refers to the mismatch between the skills acquired through education and those needed to perform a job. Results suggest that field of study differentials vary by country and that welfare and labour market institutions illuminate these cross-national variations. Moreover, the results support the claim that it is necessary to distinguish between credential and skill mismatches, showing that these institutional factors do not always affect them similarly.
Conflict and cooperation over sex: the consequences of social and genetic polyandry for reproductive success in dunnocks
Authors: Santos Eduardo S. A. , Santos Luana L. S. , Lagisz Malgorzata , Nakagawa Shinichi
Published: August 2015

Conflict and cooperation within and between the sexes are among the driving forces that lead to the evolution of mating systems. Among mating strategies, female genetic polyandry and male reproductive cooperation pose challenging evolutionary questions regarding the maintenance of systems where one sex suffers from reduced fitness.

Here, we investigate the consequences of social and genetic polyandry for reproductive success of females and males in a population of the dunnock,Prunella modularis.

We show that female multiple mating ameliorates the negative effects of inbreeding. We, however, found little evidence that females engage in extra‐group (pair) mating with less related or more heterozygous males.

Breeding in socially polyandrous groups reduced the amount of paternity lost to extra‐group males, such that, on average, cobreeding and monogamous males fledged a similar number of young. Importantly,c. 30% of cobreeding male dyads were related, suggesting they could gain indirect fitness benefits. Taken together, cobreeding males achieve equivalent reproductive success to monogamous counterparts under most circumstances.

Our study has revealed unexpected complexities in the variable mating system of dunnocks in New Zealand. Our results differ from the well‐known Cambridge dunnock study and can help our understanding of the evolution and maintenance of various breeding systems in the animal kingdom.
Priority threat management of non‐native plants to maintain ecosystem integrity across heterogeneous landscapes
Authors: Firn Jennifer , Martin Tara G. , Chadès Iadine , Walters Belinda , Hayes John , Nicol Sam , Carwardine Josie
Published: August 2015

Invasive non‐native plants have negatively impacted on biodiversity and ecosystem functions world‐wide. Because of the large number of species, their wide distributions and varying degrees of impact, we need a more effective method for prioritizing control strategies for cost‐effective investment across heterogeneous landscapes.

Here, we develop a prioritization framework that synthesizes scientific data, elicits knowledge from experts and stakeholders to identify control strategies, and appraises the cost‐effectiveness of strategies. Our objective was to identify the most cost‐effective strategies for reducing the total area dominated by high‐impact non‐native plants in the Lake Eyre Basin (LEB).

We use a case study of the ˜120 million ha Lake Eyre Basin that comprises some of the most distinctive Australian landscapes, including Uluru‐Kata Tjuta National Park. More than 240 non‐native plant species are recorded in the Lake Eyre Basin, with many predicted to spread, but there are insufficient resources to control all species.

Lake Eyre Basin experts identified 12 strategies to control, contain or eradicate non‐native species over the next 50 years. The total cost of the proposed Lake Eyre Basin strategies was estimated at AU$1·7 billion, an average of AU$34 million annually. Implementation of these strategies is estimated to reduce non‐native plant dominance by 17 million ha – there would be a 32% reduction in the likely area dominated by non‐native plants within 50 years if these strategies were implemented.

The three most cost‐effective strategies were controlling Parkinsonia aculeata, Ziziphus mauritiana and Prosopis spp. These three strategies combined were estimated to cost only 0·01% of total cost of all the strategies, but would provide 20% of the total benefits. Over 50 years, cost‐effective spending of AU$2·3 million could eradicate all non‐native plant species from the only threatened ecological community within the Lake Eyre Basin, the Great Artesian Basin discharge springs.

Synthesis and applications. Our framework, based on a case study of the ˜120 million ha Lake Eyre Basin in Australia, provides a rationale for financially efficient investment in non‐native plant management and reveals combinations of strategies that are optimal for different budgets. It also highlights knowledge gaps and incidental findings that could improve effective management of non‐native plants, for example addressing the reliability of species distribution data and prevalence of information sharing across states and regions.
Microscopic Pattern of Bone Fractures as an Indicator of Blast Trauma: A Pilot Study
Authors: Pechníková Marketa , Mazzarelli Debora , Poppa Pasquale , Gibelli Daniele , Scossa Baggi Emilio , Cattaneo Cristina
Published: August 2015

The assessment of fractures is a key issue in forensic anthropology; however, very few studies deal with the features of fractures due to explosion in comparison with other traumatic injuries. This study focuses on fractures resulting from blast trauma and two types of blunt force trauma (manual compression and running over), applied to corpses of pigs; 163 osteons were examined within forty fractures by the transmission light microscopy. Blast lesions showed a higher percentage of fracture lines through the Haversian canal, whereas in other types of trauma, the fractures went across the inner lamellae. Significant differences between samples hit by blast energy and those runover or manually compressed were observed (p < 0.05). The frequency of pattern A is significantly higher in exploded bones than in runover and compressed. Microscopic analysis of the fracture line may provide information about the type of trauma, especially for what concerns blast trauma.
Musculoskeletal disorders of the hand in type 2 diabetes mellitus: prevalence and its associated factors
Authors: Mustafa Khader N. , Khader Yousef S. , Bsoul Amal K. , Ajlouni Kamel
Published: August 2015

Aim

To assess the prevalence of musculoskeletal disorders of the hand among adult patients with type 2 diabetes mellitus (T2DM) and their relation to disease duration, glycemic control and microvascular complications.

Methods

A cross‐sectional study was conducted at the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan.

Results

One thousand patients with T2DM were included in this study (mean age 57.8 ± 9.5 years, 52.2% females and 47.8% males). Hand disorders were seen in 69.5% of patients, limited joint mobility (LJM) was the most prevalent (63.1%) condition followed by Dupuytren's contracture (DC) (18.6%). Trigger finger, thick skin and carpal tunnel syndrome (CTS) were found in 7.2%, 6.2% and 5.5% of patients, respectively. One disorder was seen in 45.4% of patients, two in18.2%, three in 4.9%, four in 0.9%, while only 0.1% of patients had all disorders. Female gender, age over 60 years and long duration of diabetes were associated with hand abnormalities. Hypertension was significantly associated with DC while retinopathy was associated with increased odds of thick skin, DC and CTS with P‐values 0.037, < 0.005 and 0.002, respectively.

Conclusion

Hand disorders are very common in T2DM. Female gender, old age, duration of diabetes, retinopathy and hypertension were significantly associated with hand disorders in T2DM.
Joint attention, shared goals, and social bonding
Authors: Wolf Wouter , Launay Jacques , Dunbar Robin I. M.
Published: August 2015

There has recently been interest in the ways in which coordinated movements encourage coactors to feel socially closer to one another, but this has generally overlooked the importance of necessary precursors to this joint action. Here we target two low‐level behaviours involved in social coordination that may mediate a relationship between joint actions and social bonding, namely joint attention and shared goals. Participants engaged in a simple reaction time task while sitting next to a partner performing the same task. In a joint attention condition, both participants attended to stimuli presented on the same half of a computer screen, while in a control condition, they attended to opposite sides of the computer screen. Shared goals were manipulated by giving participants the instruction to keep below a threshold score for both individual response times and accuracy (individual goal), or their joint mean response time and accuracy (i.e., averaging their mean response time and accuracy with that of their partner: shared goal). Attending to the same side of the screen led to higher ratings on a composite social bonding index directed towards a partner, while shared goals did not cause any effects on partner ratings. Joint attention was sufficient to encourage social closeness with an interaction partner, which suggests that any activities which encourage attending to the same point in space could have some influence on how connected coactors feel about one another.
The impact of effective paediatric adherence promotion interventions: systematic review and meta‐analysis
Authors: McGrady M. E. , Ryan J. L. , Gutiérrez‐Colina A. M. , Fredericks E. M. , Towner E. K. , Pai A. L. H.
Published: August 2015

Background

Understanding the impact of effective paediatric adherence promotion interventions on patients, families and the healthcare system is necessary to inform efforts to improve healthcare quality and control costs. Building on previous research suggesting that improving adherence may have far‐reaching benefits, the objective of this study was to quantify the impact of effective adherence promotion interventions for children and adolescents with a chronic medical condition on patients, families and the healthcare system.

Methods

Authors systematically reviewed articles indexed in PubMed, PsycINFO and CINAHL to identify randomized controlled trials of paediatric adherence promotion interventions. Interventions that improved paediatric adherence and examined patient‐level, family‐level or healthcare system‐level outcomes in children and adolescents (M age ≤ 18 years) with a chronic medical condition were included. Two authors independently extracted and classified outcome variables as patient‐level (quality of life and disease‐related activity restrictions), micro‐level (family functioning, family conflict, caregiver quality of life, caregiver sleep interruption, caregiver days away from work and patient missed school days) or macro‐level variables (emergency department visits, hospitalizations, outpatient visits and urgent care visits). Outcome variables detailed in previously published reviews (i.e. disease severity) were excluded.

Results

Twenty studies representing 19 unique samples met inclusion criteria. An additional eight articles representing trials that did not significantly improve adherence were included in post hoc analyses. Compared with control interventions, effective paediatric adherence promotion interventions improved patient quality of life and family‐level outcomes and decreased healthcare utilization among children and adolescents with a chronic medical condition.

Conclusions

Interdisciplinary efforts to improve healthcare quality and reduce spending among children and adolescents with a chronic medical condition may be enhanced by incorporating effective paediatric adherence promotion interventions. As relatively few chronic medical conditions were represented in included studies, future research should examine the impact of paediatric adherence promotion interventions in other populations.
Robust Articulated‐ICP for Real‐Time Hand Tracking
Authors: Tagliasacchi Andrea , Schröder Matthias , Tkach Anastasia , Bouaziz Sofien , Botsch Mario , Pauly Mark
Published: August 2015

We present a robust method for capturing articulated hand motions in realtime using a single depth camera. Our system is based on a realtime registration process that accurately reconstructs hand poses by fitting a 3D articulated hand model to depth images. We register the hand model using depth, silhouette, and temporal information. To effectively map low‐quality depth maps to realistic hand poses, we regularize the registration with kinematic and temporal priors, as well as a data‐driven prior built from a database of realistic hand poses. We present a principled way of integrating such priors into our registration optimization to enable robust tracking without severely restricting the freedom of motion. A core technical contribution is a new method for computing tracking correspondences that directly models occlusions typical of single‐camera setups. To ensure reproducibility of our results and facilitate future research, we fully disclose the source code of our implementation.
Homotopic Morphing of Planar Curves
Authors: Dym N. , Shtengel A. , Lipman Y.
Published: August 2015

This paper presents an algorithm for morphing between closed, planar piecewise‐C1 curves. The morph is guaranteed to be a regular homotopy, meaning that pinching will not occur in the intermediate curves.

The algorithm is based on a novel convex characterization of the space of regular closed curves and a suitable symmetric length‐deviation energy. The intermediate curves constructed by the morphing algorithm are guaranteed to be regular due to the convexity and feasibility of the problem.

We show that our method compares favorably with standard curve morphing techniques, and that these methods sometimes fail to produce a regular homotopy, and as a result produce an undesirable morph.

We explore several applications and extensions of our approach, including morphing networks of curves with simple connectivity, morphing of curves with different turning numbers with minimal pinching, convex combination of several curves, and homotopic morphing of b‐spline curves via their control polygon.
Fluticasone propionate in clinically suspected asthma patients with negative methacholine challenge test
Authors: Peiman Soheil , Abtahi Hamidreza , Akhondzadeh Shahin , Safavi Enayat , Moin Mostafa , Rahimi Foroushani Abbas
Published: August 2015

Introduction

Despite reports of response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/MCT−), treatment in these patients has not been prospectively studied.

Objective

We studied the role of a 12 week high dose inhaled fluticasone trial in CSA/MCT− patients.

Methods

After a 2 week run‐in period, CSA/MCT−patients were treated with 12 weeks of Fluticasone propionate 1000 µg/day. The Asthma Control Test (ACT), numeric cough score (NCS) and bronchodilator use were compared with their pretreatment values.

Results

Thirty‐four of 42 CSA/MCT−patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (14.7 ± 3.37 to 20.9 ± 3.1, P < 0.001). Posttreatment values of daytime (1.0 ± 1.0) and night‐time (0.6 ± 0.9) NCS decreased compared to their pretreatment values (2.8 ± 1.1 and 1.9 ± 1.3, respectively; P < 0.001). ACT score change (ΔACT) were significantly greater in those with pACT < 15 than in those ≥15 (P < 0.001) . Fifteen of 21 patients with ΔACT > 5 did not need to use bronchodilator for their symptom relief. Wheeze disappeared in all six patients with ΔACT > 5 after the trial. Six months after the study, steroid inhaler continued to be used by 72.2% of patients.

Conclusion

A significant portion of CSA/MCT− (especially those with pretreatment ACT score <15) respond to high dose fluticasone inhaler in terms of symptoms relief, disappearance of wheeze and need to bronchodilator use. ΔACT could not be predicted with any individual symptoms or signs before MCT, % FEV1 decline or symptoms during MCT and exhaled nitric oxide.
Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis
Authors: An Jian , Yang Hua‐Ping , Hu Cheng‐Ping , Cao Li‐Ming , Zhou Ya‐Fang , Xiao Qi‐Ming , Pan Pin‐Hua , Luo Bai‐Ling , Meng Jie , Zheng Zhi‐Yuan , Su Xiao‐Li , Li Yuan‐Yuan
Published: August 2015

Background and Aims

Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear.

Objectives

The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases.

Methods

Eighty‐seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist.

Results

In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason.

Conclusion

The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.
Electrophysiological evidence of phonetic normalization across coarticulation in infants
Authors: Mersad Karima , Dehaene‐Lambertz Ghislaine
Published: August 2015

The auditory neural representations of infants can easily be studied with electroencephalography using mismatch experimental designs. We recorded high‐density event‐related potentials while 3‐month‐old infants were listening to trials consisting of CV syllables produced with different vowels (/bX/ or /gX/). The consonant remained the same for the first three syllables, followed (or not) by a change in the fourth position. A consonant change evoked a significant difference around the second auditory peak (400–600 ms) relative to control trials. This mismatch response demonstrates that the infants robustly categorized the consonant despite coarticulation that blurs the phonetic cues, and at an age at which they do not produce these consonants themselves. This response was obtained even when infants had no visual articulatory information to help them to track the consonant repetition. In combination with previous studies establishing categorical perception and normalization across speakers, this result demonstrates that preverbal infants already have abstract phonetic representation integrating over acoustical features in the first months of life.
Mellow Parenting: systematic review and meta‐analysis of an intervention to promote sensitive parenting
Authors: MacBeth Angus , Law James , McGowan Iain , Norrie John , Thompson Lucy , Wilson Philip
Published: August 2015

Aim

To review and meta‐analyse Mellow Parenting interventions for parent–child dyads at high risk of adverse developmental outcomes.

Method

Using Preferred Reporting Items of Systematic reviews and Meta‐Analyses (PRISMA) guidelines, we extracted all published evaluations of Mellow Parenting and Mellow Babies programmes. We identified published studies with randomized controlled trials, quasi‐experimental or within‐subject pre–post designs. We incorporated ‘grey literature’ for unpublished publicly available evaluations. Effect sizes were calculated for impact of Mellow Parenting on parental mental health and child behaviour. Data were extracted on demographics, age of participants, country, and potential sources of bias.

Results

We identified eight papers, representing nine data sets, from five of which we calculated effect sizes. There was evidence of a medium treatment effect of Mellow Parenting compared with comparison groups on maternal well‐being and child problems. Drop‐out from treatment was variable. However, data were heterogeneous and there was evidence of methodological bias.

Interpretation

Our data give some support to claims for effectiveness of Mellow Parenting as a group intervention for families with multiple indices of developmental adversity. Given the methodological weaknesses of literature in the area, novel approaches are needed in future trials of low‐budget complex interventions in non‐commercial settings.