bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain: biomedical knowledge manipulation
Authors: Croset Samuel , Overington John P. , Rebholz-Schuhmann Dietrich
Published: March 2013

Summary: Brain is a Java software library facilitating the manipulation and creation of ontologies and knowledge bases represented with the Web Ontology Language (OWL).

Availability and implementation: The Java source code and the library are freely available at https://github.com/loopasam/Brain and on the Maven Central repository (GroupId: uk.ac.ebi.brain). The documentation is available at https://github.com/loopasam/Brain/wiki.

Contact:  croset@ebi.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
HAL: a hierarchical format for storing and analyzing multiple genome alignments
Authors: Hickey Glenn , Paten Benedict , Earl Dent , Zerbino Daniel , Haussler David
Published: March 2013

Motivation: Large multiple genome alignments and inferred ancestral genomes are ideal resources for comparative studies of molecular evolution, and advances in sequencing and computing technology are making them increasingly obtainable. These structures can provide a rich understanding of the genetic relationships between all subsets of species they contain. Current formats for storing genomic alignments, such as XMFA and MAF, are all indexed or ordered using a single reference genome, however, which limits the information that can be queried with respect to other species and clades. This loss of information grows with the number of species under comparison, as well as their phylogenetic distance.

Results: We present HAL, a compressed, graph-based hierarchical alignment format for storing multiple genome alignments and ancestral reconstructions. HAL graphs are indexed on all genomes they contain. Furthermore, they are organized phylogenetically, which allows for modular and parallel access to arbitrary subclades without fragmentation because of rearrangements that have occurred in other lineages. HAL graphs can be created or read with a comprehensive C++ API. A set of tools is also provided to perform basic operations, such as importing and exporting data, identifying mutations and coordinate mapping (liftover).

Availability: All documentation and source code for the HAL API and tools are freely available at http://github.com/glennhickey/hal.

Contact:  hickey@soe.ucsc.edu or haussler@soe.ucsc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
pfsearchV3: a code acceleration and heuristic to search PROSITE profiles
Authors: Schuepbach Thierry , Pagni Marco , Bridge Alan , Bougueleret Lydie , Xenarios Ioannis , Cerutti Lorenzo
Published: March 2013

Summary: The PROSITE resource provides a rich and well annotated source of signatures in the form of generalized profiles that allow protein domain detection and functional annotation. One of the major limiting factors in the application of PROSITE in genome and metagenome annotation pipelines is the time required to search protein sequence databases for putative matches. We describe an improved and optimized implementation of the PROSITE search tool pfsearch that, combined with a newly developed heuristic, addresses this limitation. On a modern x86_64 hyper-threaded quad-core desktop computer, the new pfsearchV3 is two orders of magnitude faster than the original algorithm.

Availability and implementation: Source code and binaries of pfsearchV3 are freely available for download at http://web.expasy.org/pftools/#pfsearchV3, implemented in C and supported on Linux. PROSITE generalized profiles including the heuristic cut-off scores are available at the same address.

Contact:  pftools@isb-sib.ch
Identification of cancer fusion drivers using network fusion centrality
Authors: Wu Chia-Chin , Kannan Kalpana , Lin Steven , Yen Laising , Milosavljevic Aleksandar
Published: March 2013

Summary: Gene fusions are being discovered at an increasing rate using massively parallel sequencing technologies. Prioritization of cancer fusion drivers for validation cannot be performed using traditional single-gene based methods because fusions involve portions of two partner genes. To address this problem, we propose a novel network analysis method called fusion centrality that is specifically tailored for prioritizing gene fusions. We first propose a domain-based fusion model built on the theory of exon/domain shuffling. The model leads to a hypothesis that a fusion is more likely to be an oncogenic driver if its partner genes act like hubs in a network because the fusion mutation can deregulate normal functions of many other genes and their pathways. The hypothesis is supported by the observation that for most known cancer fusion genes, at least one of the fusion partners appears to be a hub in a network, and even for many fusions both partners appear to be hubs. Based on this model, we construct fusion centrality, a multi-gene-based network metric, and use it to score fusion drivers. We show that the fusion centrality outperforms other single gene-based methods. Specifically, the method successfully predicts most of 38 newly discovered fusions that had validated oncogenic importance. To our best knowledge, this is the first network-based approach for identifying fusion drivers.

Availability: Matlab code implementing the fusion centrality method is available upon request from the corresponding authors.

Contact:  perwu777@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells
Authors: Hald Bjørn Olav , Garkier Hendriksen Morten , Sørensen Preben Graae
Published: March 2013

Motivation: Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem—particularly for phase coherence in oscillating systems.

Results: The present article presents a novel strategy for construction of large-scale simulation programs of heterogeneous biological entities. The strategy is designed to be tractable, to handle heterogeneity and to handle computational cost issues simultaneously, primarily by writing a generator of the ‘model to be simulated’. We apply the strategy to model glycolytic oscillations among thousands of yeast cells coupled through the extracellular medium. The usefulness is illustrated through (i) benchmarking, showing an almost linear relationship between model size and run time, and (ii) analysis of the resulting simulations, showing that contrary to the experimental situation, synchronous oscillations are surprisingly hard to achieve, underpinning the need for tools to study heterogeneity. Thus, we present an efficient strategy to model the biological heterogeneity, neglected by ordinary mean-field models. This tool is well posed to facilitate the elucidation of the physiologically vital problem of synchronization.

Availability: The complete python code is available as Supplementary Information.

Contact:  bjornhald@gmail.com or pgs@kiku.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Workplace Heterogeneity and the Rise of West German Wage Inequality*
Authors: Card David , Heining Jörg , Kline Patrick
Published: March 2013

We study the role of establishment-specific wage premiums in generating recent increases in West German wage inequality. Models with additive fixed effects for workers and establishments are fit into four subintervals spanning the period from 1985 to 2009. We show that these models provide a good approximation to the wage structure and can explain nearly all of the dramatic rise in West German wage inequality. Our estimates suggest that the increasing dispersion of West German wages has arisen from a combination of rising heterogeneity between workers, rising dispersion in the wage premiums at different establishments, and increasing assortativeness in the assignment of workers to plants. In contrast, the idiosyncratic job-match component of wage variation is small and stable over time. Decomposing changes in mean wages between different education groups, occupations, and industries, we find that increasing plant-level heterogeneity and rising assortativeness in the assignment of workers to establishments explain a large share of the rise in inequality along all three dimensions.
Calcium flux and calpain-mediated activation of the apoptosis-inducing factor contribute to enterovirus 71-induced apoptosis
Authors: Lu Jia-Rong , Lu Wen-Wen , Lai Jian-Zhong , Tsai Fu-Lian , Wu Szu-Hsien , Lin Cheng-Wen , Kung Szu-Hao
Published: March 2013

Enterovirus 71 (EV71) is a causative agent of an array of childhood diseases with severe neurological manifestations implicated. EV71 infection is known to induce caspase-dependent apoptosis in cell cultures and animal models. However, whether an alternative apoptotic pathway independent of caspase activation can be triggered by EV71 infection has not been explored. In this study, we showed that calcium (Ca2+)-activated calpains are capable of mediating caspase-independent pathway activation during EV71-induced apoptosis in HeLa cells. Results from subcellular fractionation analysis and confocal imaging indicated that during EV71 infection, apoptosis-inducing factor (AIF), a primary mediator of the caspase-independent pathway, became truncated and translocated from the mitochondrion to nucleus. This was accompanied by the release of cytochrome c, and sharply decreased mitochondrial membrane potential. AIF knockdown data indicated significant protection against apoptotic cell death, with greater protection provided by the addition of a pan-caspase inhibitor. The Ca2+-dependent, calpain isoforms 1 and 2, but not cathepsins, were proven crucial for the altered AIF behaviour as studied by the pharmacological inhibitor and the knockdown approaches. We then analysed Ca2+ dynamics in the infected cells and found elevated levels of mitochondrial Ca2+. Treatment with ruthenium red, a mitochondrial Ca2+ influx inhibitor, significantly blocked calpain activations and AIF cleavage. Our conclusion was that calpain activation via Ca2+ flux plays an essential role in eliciting an AIF-mediated, caspase-independent apoptotic pathway in EV71-infected cells. These findings should be useful for understanding the virus-induced cytopathology and the impact of Ca2+ homeostasis on EV71 infection.
Using the structure of B+‐trees for enhancing logging mechanisms of databases
Authors: Kieseberg Peter , Schrittwieser Sebastian , Morgan Lorcan , Mulazzani Martin , Huber Markus , Weippl Edgar
Published: March 2013

Purpose

Today's database management systems implement sophisticated access control mechanisms to prevent unauthorized access and modifications. For instance, this is an important basic requirement for SOX (Sarbanes‐Oxley Act) compliance, whereby every past transaction has to be traceable at any time. However, malicious database administrators may still be able to bypass the security mechanisms in order to make hidden modifications to the database. This paper aims to address these issues.

Design/methodology/approach

In this paper the authors define a novel signature of a B+‐tree, a widely‐used storage structure in database management systems, and propose its utilization for supporting the logging in databases. This additional logging mechanism is especially useful in conjunction with forensic techniques that directly target the underlying tree‐structure of an index. Several techniques for applying this signature in the context of digital forensics on B+‐trees are proposed in the course of this paper. Furthermore, the authors' signature can be used to generate exact copies of an index for backup purposes, thereby enabling the owner to completely restore data, even on the structural level.

Findings

For database systems in enterprise environments, compliance to regulatory standards such as SOX (Sarbanes‐Oxley Act), whereby every past transaction has to be traceable at any time, is a fundamental requirement. Today's database management systems usually implement sophisticated access control mechanisms to prevent unauthorized access and modifications. Nonetheless malicious database administrators would be able to bypass the security mechanisms in order to make modifications to the database, while covering their tracks.

Originality/value

In this paper, the authors demonstrate how the tree structure of the underlying store engine can be used to enhance forensic logging mechanisms of the database. They define a novel signature for B+‐trees, which are used by the InnoDB storage engine. This signature stores the structure of database storage files and can help in reconstructing previous versions of the file for forensic purposes. Furthermore, the authors' signature can be used to generate exact copies of an index for backup purposes, thus enabling the owner to completely restore data, even on the structural level. The authors applied their concept to four real‐life scenarios in order to evaluate its effectiveness.
Disability and adult life: dependence on social security among former students with special educational needs in their late twenties
Authors: Myklebust Jon Olav
Published: March 2013

This article, by Jon Olav Myklebust from Volda University, Norway, presents analyses of social security dependence among students with special educational needs in Norway who at the start of upper secondary school had various disabilities – of a somatic, psychological and/or social nature. They were all educated in ordinary schools, in special or regular classes. These young people have been followed prospectively from their first years in upper secondary school and into their late twenties. The analyses indicate which circumstances contribute to social security dependence, with an emphasis on how the independent variables differently influence social security dependence among men and women.
Blame, guilt and the need for ‘labels’; insights from parents of children with special educational needs and educational practitioners
Authors: Broomhead Karen
Published: March 2013

Previous research on home–school relationships and blame has concentrated on the experiences of parents with children with behavioural, emotional and social difficulties (BESD). This has led to the voices of educational practitioners, as well as parents of children with other special educational needs, being neglected. This article, by Karen Broomhead of Lancaster University, details part of a larger study examining socio‐emotional aspects of home–school relationships between parents of children with special educational needs and educational practitioners. The study reported in this article explored perceptions of blame via semi‐structured interviews with 15 educational professionals and 22 parents of children with various special educational needs. The findings reveal that parental experiences of blame and guilt were influenced by the nature of their children's special educational needs, which consequently influenced parental focus on obtaining ‘labels’ of special educational needs for their children. The implications of these findings for educational practitioners are discussed.
DNA barcoding at riverscape scales: assessing biodiversity among fishes of the genus Cottus (Teleostei) in northern Rocky Mountain streams
Authors: Young Michael K. , McKelvey Kevin S. , Pilgrim Kristine L. , Schwartz Michael K.
Published: March 2013

There is growing interest in broad‐scale biodiversity assessments that can serve as benchmarks for identifying ecological change. Genetic tools have been used for such assessments for decades, but spatial sampling considerations have largely been ignored. Here, we demonstrate how intensive sampling efforts across a large geographical scale can influence identification of taxonomic units. We used sequences of mtDNA cytochrome c oxidase subunit 1 and cytochrome b, analysed with maximum parsimony networks, maximum‐likelihood trees and genetic distance thresholds, as indicators of biodiversity and species identity among the taxonomically challenging fishes of the genus Cottus in the northern Rocky Mountains, USA. Analyses of concatenated sequences from fish collected in all major watersheds of this area revealed eight groups with species‐level differences that were also geographically circumscribed. Only two of these groups, however, were assigned to recognized species, and these two assignments resulted in intraspecific genetic variation (>2.0%) regarded as atypical for individual species. An incomplete inventory of individuals from throughout the geographical ranges of many species represented in public databases, as well as sample misidentification and a poorly developed taxonomy, may have hampered species assignment and discovery. We suspect that genetic assessments based on spatially robust sampling designs will reveal previously unrecognized biodiversity in many other taxa.
Transcriptome sequencing and microarray development for the woodrat (Neotoma spp.): custom genetic tools for exploring herbivore ecology
Authors: Malenke J. R. , Milash B. , Miller A. W. , Dearing M. D.
Published: March 2013

Massively parallel sequencing has enabled the creation of novel, in‐depth genetic tools for nonmodel, ecologically important organisms. We present the de novo transcriptome sequencing, analysis and microarray development for a vertebrate herbivore, the woodrat (Neotoma spp.). This genus is of ecological and evolutionary interest, especially with respect to ingestion and hepatic metabolism of potentially toxic plant secondary compounds. We generated a liver transcriptome of the desert woodrat (Neotoma lepida) using the Roche 454 platform. The assembled contigs were well annotated using rodent references (99.7% annotation), and biotransformation function was reflected in the gene ontology. The transcriptome was used to develop a custom microarray (eArray, Agilent). We tested the microarray with three experiments: one across species with similar habitat (thus, dietary) niches, one across species with different habitat niches and one across populations within a species. The resulting one‐colour arrays had high technical and biological quality. Probes designed from the woodrat transcriptome performed significantly better than functionally similar probes from the Norway rat (Rattus norvegicus). There were a multitude of expression differences across the woodrat treatments, many of which related to biotransformation processes and activities. The pattern and function of the differences indicate shared ecological pressures, and not merely phylogenetic distance, play an important role in shaping gene expression profiles of woodrat species and populations. The quality and functionality of the woodrat transcriptome and custom microarray suggest these tools will be valuable for expanding the scope of herbivore biology, as well as the exploration of conceptual topics in ecology.
Extreme rainfall events predict irruptions of rat plagues in central Australia
Authors: Greenville Aaron C. , Wardle Glenda M. , Dickman Chris R.
Published: March 2013

A general understanding of the factors that regulate populations remains a central goal for ecologists, and species that increase rapidly to plague numbers followed by equally sudden crashes in abundance are particularly intriguing. Throughout central Australia, the long‐haired rat, Rattus villosissimus, is largely absent in dry times, but can irrupt into plague numbers after heavy rains. Using historical data we first relate the occurrence of plagues to exceptionally high rainfalls, and using live‐trapping records from rat irruptions in 1991 and 2011 in the eastern Simpson Desert, we then investigate the population structure at the plague front. In doing so, we ask if long‐haired rat plagues irrupt from multiple refugia, if young males are first to disperse and whether the rate of dispersal is rapid. Annual rainfall in the year preceding a plague successfully predicted the probability of an outbreak, with an 80% chance of a plague occurring after an annual rainfall of 750 mm. Trapping grids closest to drainage lines to the south of the study area had greater captures of long‐haired rats. Enhanced rat numbers in proximity to drainage areas suggested that the irruptive process unfolded from the south and demonstrated the existence of multiple refugia. In contrast to the resident fitness hypothesis, there was no difference in captures between the sexes or age‐classes of long‐haired rats. Heavier animals were caught at the invasion front, presumably because they could travel larger distances than smaller individuals, suggesting that larger individuals were maximizing their fitness by dispersing first to new resources. Captures of long‐haired rats were highest at the beginning of the irruption in both 1991 and 2011, suggesting rapid colonization. Although rare in occurrence, rodent population irruptions and the resulting dispersal across large areas, which may persist for a few years, can thus extend the domain of influence of exceptional rain years well into the future.
Genotoxicity and Carcinogenicity Studies of Bronchodilators and AntiAsthma Drugs
Authors: Brambilla Giovanni , Mattioli Francesca , Robbiano Luigi , Martelli Antonietta
Published: March 2013

This survey is a compendium of genotoxicity and carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long‐term carcinogenesis assays, 15 drugs had both genotoxicity and carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non‐carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.
Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi‐Automatic Methods Using Anti‐TNF Therapy as Model
Authors: Cars Thomas , Wettermark Björn , Malmström Rickard E. , Ekeving Gunnar , Vikström Bo , Bergman Ulf , Neovius Martin , Ringertz Bo , Gustafsson Lars L.
Published: March 2013

There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi‐automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi‐automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD‐10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi‐automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.
Involvement of Large‐Conductance Ca2+‐Activated K+ Channels in both Nitric Oxide and Endothelium‐Derived Hyperpolarization‐Type Relaxation in Human Penile Small Arteries
Authors: Király István , Pataricza János , Bajory Zoltán , Simonsen Ulf , Varro András , Papp Julius Gy. , Pajor Lászlo , Kun Attila
Published: March 2013

Large‐conductance Ca2+‐activated K+ channels (BKCa), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BKCa channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of BKCa channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BKCa channels in endothelium‐dependent and endothelium‐independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium‐dependent [nitric oxide (NO) and endothelium‐derived hyperpolarization (EDH)‐type] and endothelium‐independent (NO‐donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO‐ and EDH‐type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of BKCa channels. Iberiotoxin also inhibited relaxations induced by a NO‐donor, sodium nitroprusside. NS11021, a selective opener of BKCa channels, evoked pronounced relaxations that were inhibited in the presence of IbTX. NS13558, a BKCa‐inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BKCa channels are involved in both NO‐ and EDH‐type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of BKCa channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium‐dependent relaxation often associated with erectile dysfunction.
Purinoceptor‐mediated, Capsaicin‐resistant Excitatory Effect of Allyl Isothiocyanate on Neurons of the Guinea‐Pig Small Intestine
Authors: Bartho Lorand , Nordtveit Elin , Szombati Veronika , Benko Rita
Published: March 2013

Allyl isothiocyanate (AITC; 200 μM) caused atropine‐ and tetrodotoxin‐sensitive longitudinal muscle contraction on the guinea‐pig small intestine. The response was not influenced by hexamethonium, a functional blockade of capsaicin‐sensitive neurons or by antagonists acting at TRPV1 or TRPA1, but was abolished by the P2 purinoceptor antagonist PPADS (50 μM). It is concluded that cholinergic motoneurons are activated by a purinergic mechanism in the course of the AITC response, independently of capsaicin‐sensitive processes or even TRPA1.
Strike‐slip tectonics and basin inversion in the Western Mediterranean: the Post‐Messinian evolution of the Alboran Sea
Authors: Martínez‐García P. , Comas M. , Soto J. I. , Lonergan L. , Watts A. B.
Published: March 2013

A comprehensive interpretation of single and multichannel seismic reflection profiles integrated with biostratigraphical data and log information from nearby DSDP and ODP wells has been used to constrain the late Messinian to Quaternary basin evolution of the central part of the Alboran Sea Basin. We found that deformation is heterogeneously distributed in space and time and that three major shortening phases have affected the basin as a result of convergence between the Eurasian and African plates. During the Messinian salinity crisis, significant erosion and local subsidence resulted in the formation of small, isolated, basins with shallow marine and lacustrine sedimentation. The first shortening event occurred during the Early Pliocene (ca. 5.33–4.57 Ma) along the Alboran Ridge. This was followed by a major transgression that widened the basin and was accompanied by increased sediment accumulation rates. The second, and main, phase of shortening on the Alboran Ridge took place during the Late Pliocene (ca. 3.28–2.59 Ma) as a result of thrusting and folding which was accompanied by a change in the Eurasian/African plate convergence vector from NW‐SE to WNW‐ESE. This phase also caused uplift of the southern basins and right‐lateral transtension along the WNW‐ENE Yusuf fault zone. Deformation along the Yusuf and Alboran ridges continued during the early Pleistocene (ca. 1.81–1.19 Ma) and appears to continue at the present day together with the active NNE‐SSW trending Al‐Idrisi strike‐slip fault. The Alboran Sea Basin is a region of complex interplay between sediment supply from the surrounding Betic and Rif mountains and tectonics in a zone of transpression between the converging African and European plates. The partitioning of the deformation since the Pliocene, and the resulting subsidence and uplift in the basin was partially controlled by the inherited pre‐Messinian basin geometry.
The link between infection and cancer: Tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect
Authors: Maeda Hiroshi
Published: March 2013

This review focuses primarily on my own research, including pathogenic mechanisms of microbial infection, vascular permeability in infection and tumors, and effects of nitric oxide (NO), superoxide anion radical (), and 8‐nitroguanosine in the enhanced permeability and retention (EPR) effect for the tumor‐selective delivery of macromolecular agents (nanomedicines). Infection‐induced vascular permeability is mediated by activation of the kinin‐generating protease cascade (kallikrein–kinin) triggered by exogenous microbial proteases. A similar mechanism operates in cancer tissues and in carcinomatosis of the pleural and peritoneal cavities. Infection also stimulates generation via activation of xanthine oxidase while generating NO by inducing NO synthase. These chemicals function in mutation and carcinogenesis and promote inflammation, in which peroxynitrite (a product of and NO) activates MMP, damages DNA and RNA, and regenerates 8‐nitroguanosine and 8‐oxoguanosine. We showed vascular permeability by using macromolecular drugs, which are not simply extravasated through the vascular wall into the tumor interstitium but remain there for prolonged periods. We thus discovered the EPR effect, which led to the rational development of tumor‐selective delivery of polymer conjugates, micellar and liposomal drugs, and genes. Our styrene–maleic acid copolymer conjugated with neocarzinostatin was the first agent of its kind used to treat hepatoma. The EPR effect occurs not only because of defective vascular architecture but also through the generation of various vascular mediators such as kinin, NO, and vascular endothelial growth factor. Although most solid tumors, including human tumors, show the EPR effect, heterogeneity of tumor tissue may impede drug delivery. This review describes the barriers and countermeasures for improved drug delivery to tumors by using nanomedicines.
Synthesis and Antimalarial Bioassay of Quinine – Peptide Conjugates
Authors: Panda Siva S. , Ibrahim Mohamed A. , Küçükbay Hasan , Meyers Marvin J. , Sverdrup Francis M. , El‐Feky Said A. , Katritzky Alan R.
Published: March 2013

Amino acid and peptide conjugates of quinine were synthesized using microwave irradiation in 52–95% yields using benzotriazole methodology. The majority of these conjugates retain in vitro antimalarial activity with IC50 values below 100 nm, similar to quinine.
The effects of equine peripheral blood stem cells on cutaneous wound healing: a clinical evaluation in four horses
Authors: Spaas J. H. , Broeckx S. , Van de Walle G. R. , Polettini M.
Published: March 2013

Stem-cell therapy represents a promising strategy for the treatment of challenging pathologies, such as large, infected wounds that are unresponsive to conventional therapies. The present study describes the clinical application of peripheral blood stem cells (PBSCs) for the treatment of four adult Warmblood horses with naturally occurring wounds, which were unresponsive to conventional therapies for at least 3 months. A visual assessment was performed, and a number of wound-healing parameters (granulation tissue, crust formation and scar formation) were evaluated. In all cases, tissue overgrowth was visible within 4 weeks after PBSC injection, followed by the formation of crusts and small scars in the centre of the wound, with hair regeneration at the edges. In conclusion, this is the first report of PBSC therapy of skin wounds in horses, and it produced a positive visual and clinical outcome.
Antigen identification using skin deficient in basement-membrane protein: a novel tool for the diagnosis of subepidermal immunobullous diseases
Authors: Rao R. , Bhogal B. , Groves R.
Published: March 2013

Common unifying features of the subepidermal blistering diseases are the presence of tense blisters clinically and demonstration by immunofluorescence of linear deposition of immunoreactants along the dermoepidermal junction. Further characterization of subtype is possible by identification of the target antigen by immunoblotting. However, immunoblotting is time-consuming and may not be practical for routine use in the laboratory. In this report, we describe a simple technique to identify the target antigen by indirect immunofluorescence, using epidermolysis bullosa skin as substrate.
Association between copy-number variations of the human histamine H4 receptor gene and atopic dermatitis in a Chinese population
Authors: Chen B. , Ye T. , Shao Y. , Zhang J. , Zhong Q. , Hu X. , Zhang W. , Yu B.
Published: March 2013

Background

Atopic dermatitis (AD) is a chronic, relapsing allergic skin disease. The histamine H4 receptor (HRH4) has been shown to be associated with a number of autoimmune disorders, including AD.

Aim

To explore a possible association between copy-number variations (CNVs) of the HRH4 gene and the risk of AD in a Chinese population.

Methods

Genomic DNA and RNA were collected from 541 patients with AD and 613 healthy controls, and the CNVs and mRNA levels of HRH4 were examined. ELISA was used to measure the levels of IgE in all participants.

Results

Amplifications of HRH4 copy numbers were associated with the risk of developing AD (P < 0.05, OR = 1.85, 95% CI 1.30–2.63), whereas deletions of HRH4 copy numbers were not associated with disease risk for AD (P = 0.30, OR = 0.82, 95% CI 0.57–1.19). HRH4 mRNA levels were much higher in samples with HRH4 copy-number amplifications than in those without such amplifications (P < 0.05). IgE levels were associated with amplifications (P < 0.05, OR = 1.96, 95% CI 1.19–3.25), but not with deletions (P = 0.63, OR = 0.87, 95% CI 0.49–1.54) of HRH4 copy numbers.

Conclusions

CNVs of the HRH4 gene are associated with AD in a Chinese population.
Can Vitamin D Supplementation Improve the Severity of Congestive Heart Failure?
Authors: Amin Ahmad , Minaee Shima , Chitsazan Mitra , Naderi Nassim , Taghavi Sepideh , Ardeshiri Maryam
Published: March 2013

The aim of the present study was to investigate whether vitamin D supplementation could improve biochemical findings and functional capacity of patients with heart failure (HF). One hundred patients with New York Heart Association (NYHA) class I through III HF were included in this prospective study and their 25‐hydroxyvitamin D levels were evaluated. Only 6% of the participants had a sufficient serum concentration of 25(OH) D >30 nmol/L. Patients with insufficient or deficient serum levels of 25(OH) D (<30 ng/mL and <20 ng/mL, respectively) received oral vitamin D3 (cholecalciferol) for a total period of 4 months. Vitamin D supplementation increased mean serum concentration of 25(OH) D from 12.63±7.60 nmol/L to 54.49±18.01 nmol/L (P<.001). After vitamin D supplementation, the serum level of pro‐brain natriuretic peptide markedly decreased (P<.001). Cholecalciferol significantly decreased high‐sensitivity C‐reactive protein level (P<.001). Restoration of serum 25(OH) D level was also associated with substantial improvement in NYHA class (P<.001) and 6‐minute walk distance (P<.001).
Removal of aromatic amines and decolourisation of azo dye baths by electrochemical treatment
Authors: López‐Grimau Victor , Riera‐Torres Miquel , López‐Mesas Montserrat , Gutiérrez‐Bouzán Carmen
Published: March 2013

The presence of aromatic amines in effluent from dyeing processes of the textile industry is an added problem to the high coloration typical of this type of effluent. The main objective of the present work was to eliminate these two problems simultaneously by electrochemical treatment using bath solutions containing three azo dyes. For the analysis of amines, a liquid–liquid extraction method was developed as an easier and faster alternative to the method described in the standards and widely used in analytical laboratories. Four amines (aniline, o‐toluidine, 4‐chloroaniline and 4‐aminobiphenyl) were detected by GC‐MS in the residual azo dye baths. A total amine concentration of between 2.5 and 1 ppm was detected, 4‐aminobiphenyl being the main compound. Both residual colour and amines were removed by electrochemical treatment carried out at three current densities (3, 24 and 40 mA/cm2). At 24 mA/cm2, more than 90% of colour removal was achieved, and the total amine concentration was reduced to below 0.15 ppm.
Pretreating poly(p‐phenylene benzobisoxazole) fibre with polyphosphoric acid and dyeing with disperse dyes
Authors: Guan Yu , Mao Ya‐hong , Kong Qin‐ming , Zeng Xiao‐feng , Zhu Pu‐xin
Published: March 2013

In recent years, many advanced composite materials based on poly(p‐phenylene‐2,6‐benzobisoxazole) fibres have become prominent in applications requiring high‐strength and flame‐retardance such as body armour, industrial reinforcement materials and military camouflage. However, the application of these fibres used as protective clothing is limited due to difficulties in dyeing and printing. In the present work, a process for pretreating poly(p‐phenylene benzobisoxazole) fibre with polyphosphoric acid was applied, and the pretreated fibre was then dyed with disperse dyes via dip dyeing. Effects of pretreatment temperature and time on structure and properties were investigated. Surface morphology, crystallinity, chemical structure and degree of orientation of fibres were characterised. The results indicated that the supramolecular structure of the fibre was relaxed or swelled by polyphosphoric acid in the pretreatment process, so that the dyeability of poly(p‐phenylene benzobisoxazole) fibre was improved, with satisfactory dye exhaustion, K/S values and dyeing fastness. Also, with the appropriate pretreatment process, the swelling effect of polyphosphoric acid on the structure of poly(p‐phenylene benzobisoxazole) fibre was limited, so as to control the decrease in tensile strength and limiting oxygen index of the dyed fibre.
Use of β‐cyclodextrin in an antimigration coating for polyester fabric
Authors: Park Jong S , Kim Ik‐Soo
Published: March 2013

When β‐cyclodextrin was adopted as a dye catcher, the degree of dye migration onto adjacent fabrics as well as onto the coated surface was greatly reduced, while other physical properties, such as waterproofness and breathability, remained unaffected. When acetylation of β‐cyclodextrin was carried out, its solubility in an organic solvent, including methyl ethyl ketone and toluene, was greatly improved. Hence, it provided a smoother coated surface and an excellent antimigration effect in a direct‐coating system. These results confirm that β‐cyclodextrin is an effective dye catcher in a polyurethane‐based coating system, in which it prevents the migration of the dyes from coated polyester fabrics onto adjacent surfaces. The solubility of cyclodextrin can be optimised by a chemical modification of its cyclodextrin‐hydroxyl groups. Hence, this host–guest interaction demonstrates a universal and effective platform for antimigration coating systems.
Adefovir treatment for chronic hepatitis B in heart transplant recipients
Authors: Durante‐Mangoni Emanuele , Iossa Domenico , Pinto Daniela , Molaro Rosa , Agrusta Federica , Amarelli Cristiano , Ragone Enrico , Grimaldi Maria , Maiello Ciro , Utili Riccardo
Published: March 2013

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice‐monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV‐DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild‐to‐moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV‐DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV‐DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine‐resistant chronic hepatitis B.
From exploitation to conservation: habitat models using whaling data predict distribution patterns and threat exposure of an endangered whale
Authors: Torres Leigh G. , Smith Tim D. , Sutton Phil , MacDiarmid Alison , Bannister John , Miyashita Tomio
Published: March 2013

Aim

Sufficient data to describe spatial distributions of rare and threatened populations are typically difficult to obtain. For example, there are minimal modern offshore sightings of the endangered southern right whale, limiting our knowledge of foraging grounds and habitat use patterns. Using historical exploitation data of southern right whales (SRW), we aim to better understand their seasonal offshore distribution patterns in relation to broad‐scale oceanography, and to predict their exposure to shipping traffic and response to global climate change.

Location

Australasian region between 130° W and 100° E, and 30° S and 55° S.

Methods

We model 19th century whaling data with boosted regression trees to determine functional responses of whale distribution relative to environmental factors. Habitat suitability maps are generated and we validate these predictions with independent historical and recent sightings. We identify areas of increased risk of ship‐strike by integrating predicted whale distribution maps with shipping traffic patterns. We implement predicted ocean temperatures for the 2090–2100 decade in our models to predict changes in whale distribution due to climate change.

Results

Temperature in the upper 200 m, distance from the subtropical front, mixed layer depth, chlorophyll concentration and distance from ridges are the most consistent and influential predictors of whale distribution. Validation tests of predicted distributions determined generally high predictive capacity. We identify two areas of increased risk of vessel strikes and predict substantial shifts in habitat suitability and availability due to climate change.

Main conclusions

Our results represent the first quantitative description of the offshore foraging habitat of SRW. Conservation applications include identifying areas and causes of threats to SRW, generating effective mitigation strategies, and directing population monitoring and research efforts. Our study demonstrates the benefits of incorporating unconventional datasets such as historical exploitation data into species distribution models to inform management and help combat biodiversity loss.
Online solutions and the ‘Wallacean shortfall’: what does GBIF contribute to our knowledge of species' ranges?
Authors: Beck Jan , Ballesteros‐Mejia Liliana , Nagel Peter , Kitching Ian J.
Published: March 2013

Aim

To investigate the contribution to range filling, range extent and climatic niche space of species of information contained in the largest databank of digitized biodiversity data: the global biodiversity information facility (GBIF). We compared such information with a compilation of independent distributional data from natural history collections and other sources.

Location

Europe.

Methods

We used data for the hawkmoths (Lepidoptera, family Sphingidae) to assess three aspects of range information: (1) observed range filling in 100 km × 100 km grid cell squares, (2) observed European range extent and (3) observed climatic niche. Range extents were calculated as products of latitudinal and longitudinal extents. Areas derived from minimum convex polygons drawn onto a 2‐dimensional niche space representing the two main axes of a principal component analysis (PCA) were used to calculate climatic niche space. Additionally, record‐based permutation tests for niche differences were carried out.

Results

We found that GBIF provided many more distribution records than independent compilation efforts, but contributed less information on range filling, range extent and climatic niches of species.

Main conclusions

Although GBIF contributed relevant additional information, it is not yet an effective alternative to manual compilation and databasing of distributional records from collections and literature sources, at least in lesser‐known taxa such as invertebrates. We discuss possible reasons for our findings, which may help shape GBIF strategies for providing more informative data.