bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Who Shot J. R. Matters: Dallas as the Pinnacle of Human Evolutionary Television
Authors: Fisher Maryanne L.
Published: June 2012

The TV series Dallas remains one of the most popular shows to ever have been broadcast on American TV. It was a serialized prime-time soap opera with weekly 45 minute episodes that ran from 1978 until 1991. This long-running show is one of the few to have been entirely released in DVD format; all 14 seasons are available as of 2011, and reruns are still aired internationally. Hundreds of thousands of visitors still tour the Southfork Ranch used for filming, outside Dallas, Texas. I will argue that the reason for this show's success is because it routinely depicted themes that align with our evolved psychology. Using arguments that have been created to discuss literary Darwinism and gossip, I propose that this show depicted topics that have adaptive value; Dallas both exploits our evolved interests but also may act as a learning device for solving adaptive problems. Over the course of human evolution, it may have increased individual fitness to know who is wealthy or owns plentiful resources, has power and status, cheats on or poaches mates, engages in sibling rivalry, enhances their attractiveness, and so on. Dallas depicts these topics, and others, and thus, it is sensible that it would have been so successful among international audiences, and across decades.
Mutual synergistic protein folding in split intein
Authors: Zheng Yuchuan , Wu Qin , Wang Chunyu , Xu Min-qun , Liu Yangzhong
Published: June 2012

Inteins are intervening protein sequences that undergo self-excision from a precursor protein with the concomitant ligation of the flanking polypeptides. Split inteins are expressed in two separated halves, and the recognition and association of two halves are the first crucial step for initiating trans-splicing. In the present study, we carried out the structural and thermodynamic analysis on the interaction of two halves of DnaE split intein from Synechocystis sp. PCC6803. Both isolated halves (IN and IC) are disordered and undergo conformational transition from disorder to order upon association. ITC (isothermal titration calorimetry) reveals that the highly favourable enthalpy change drives the association of the two halves, overcoming the unfavourable entropy change. The high flexibility of two fragments and the marked thermodynamic preference provide a robust association for the formation of the well-folded IN/IC complex, which is the basis for reconstituting the trans-splicing activity of DnaE split intein.
Evidence of Local Adaptation in Westslope Cutthroat Trout
Authors: Drinan Daniel P. , Zale Alexander V. , Webb Molly A. H. , Taper Mark L. , Shepard Bradley B. , Kalinowski Steven T.
Published: June 2012

An understanding of the process of local adaptation would allow managers to better protect and conserve species. Many salmonids are in need of such efforts, and because they often persist in differing, isolated environments, they are useful organisms for studying local adaptation. In addition, the temperature sensitivity of salmonids provides a likely target for natural selection. We studied thermal adaptation in four wild populations and one hatchery stock of westslope cutthroat trout Oncorhynchus clarkii lewisi. The mean summer temperatures of source streams ranged from 6.7°C to 11.2°C. Embryos were collected from the wild, and embryonic development, embryonic survival, and juvenile growth were determined. A significant relationship between median embryonic survival and source stream temperature was detected. Based on a rank test, populations from colder streams had a greater decline in median embryonic survival at warm temperatures than populations from warmer streams. Embryonic development and juvenile growth did not appear to be influenced by source. These findings suggest that populations are thermally adapted to their source streams and this should be considered by managers. However, further study is necessary to sort out the potential confounding factors, whether genetic or epigenetic.
Nucleostemin maintains self-renewal of embryonic stem cells and promotes reprogramming of somatic cells to pluripotency
Authors: Qu Jian , Bishop J. Michael
Published: June 2012

Nucleostemin (NS) is a nucleolar GTP-binding protein that was first identified in neural stem cells, the functions of which remain poorly understood. Here, we report that NS is required for mouse embryogenesis to reach blastulation, maintenance of embryonic stem cell (ESC) self-renewal, and mammary epithelial cell (MEC) reprogramming to induced pluripotent stem (iPS) cells. Ectopic NS also cooperates with OCT4 and SOX2 to reprogram MECs and mouse embryonic fibroblasts to iPS cells. NS promotes ESC self-renewal by sustaining rapid transit through the G1 phase of the cell cycle. Depletion of NS in ESCs retards transit through G1 and induces gene expression changes and morphological differentiation through a mechanism that involves the MEK/ERK protein kinases and that is active only during a protracted G1. Suppression of cell cycle inhibitors mitigates these effects. Our results implicate NS in the maintenance of ESC self-renewal, demonstrate the importance of rapid transit through G1 for this process, and expand the known classes of reprogramming factors.
Lineage-based identification of cellular states and expression programs
Authors: Hashimoto Tatsunori , Jaakkola Tommi , Sherwood Richard , Mazzoni Esteban O. , Wichterle Hynek , Gifford David
Published: June 2012

Summary: We present a method, LineageProgram, that uses the developmental lineage relationship of observed gene expression measurements to improve the learning of developmentally relevant cellular states and expression programs. We find that incorporating lineage information allows us to significantly improve both the predictive power and interpretability of expression programs that are derived from expression measurements from in vitro differentiation experiments. The lineage tree of a differentiation experiment is a tree graph whose nodes describe all of the unique expression states in the input expression measurements, and edges describe the experimental perturbations applied to cells. Our method, LineageProgram, is based on a log-linear model with parameters that reflect changes along the lineage tree. Regularization with L1 that based methods controls the parameters in three distinct ways: the number of genes change between two cellular states, the number of unique cellular states, and the number of underlying factors responsible for changes in cell state. The model is estimated with proximal operators to quickly discover a small number of key cell states and gene sets. Comparisons with existing factorization, techniques, such as singular value decomposition and non-negative matrix factorization show that our method provides higher predictive power in held, out tests while inducing sparse and biologically relevant gene sets.

Contact:  gifford@mit.edu
Fast alignment of fragmentation trees
Authors: Hufsky Franziska , Dührkop Kai , Rasche Florian , Chimani Markus , Böcker Sebastian
Published: June 2012

Motivation: Mass spectrometry allows sensitive, automated and high-throughput analysis of small molecules such as metabolites. One major bottleneck in metabolomics is the identification of ‘unknown’ small molecules not in any database. Recently, fragmentation tree alignments have been introduced for the automated comparison of the fragmentation patterns of small molecules. Fragmentation pattern similarities are strongly correlated with the chemical similarity of the molecules, and allow us to cluster compounds based solely on their fragmentation patterns.

Results: Aligning fragmentation trees is computationally hard. Nevertheless, we present three exact algorithms for the problem: a dynamic programming (DP) algorithm, a sparse variant of the DP, and an Integer Linear Program (ILP). Evaluation of our methods on three different datasets showed that thousands of alignments can be computed in a matter of minutes using DP, even for ‘challenging’ instances. Running times of the sparse DP were an order of magnitude better than for the classical DP. The ILP was clearly outperformed by both DP approaches. We also found that for both DP algorithms, computing the 1% slowest alignments required as much time as computing the 99% fastest.

Contact:  sebastian.boecker@uni-jena.de
Dissect: detection and characterization of novel structural alterations in transcribed sequences
Authors: Yorukoglu Deniz , Hach Faraz , Swanson Lucas , Collins Colin C. , Birol Inanc , Sahinalp S. Cenk
Published: June 2012

Motivation: Computational identification of genomic structural variants via high-throughput sequencing is an important problem for which a number of highly sophisticated solutions have been recently developed. With the advent of high-throughput transcriptome sequencing (RNA-Seq), the problem of identifying structural alterations in the transcriptome is now attracting significant attention.

In this article, we introduce two novel algorithmic formulations for identifying transcriptomic structural variants through aligning transcripts to the reference genome under the consideration of such variation. The first formulation is based on a nucleotide-level alignment model; a second, potentially faster formulation is based on chaining fragments shared between each transcript and the reference genome. Based on these formulations, we introduce a novel transcriptome-to-genome alignment tool, Dissect (DIScovery of Structural Alteration Event Containing Transcripts), which can identify and characterize transcriptomic events such as duplications, inversions, rearrangements and fusions. Dissect is suitable for whole transcriptome structural variation discovery problems involving sufficiently long reads or accurately assembled contigs.

Results: We tested Dissect on simulated transcripts altered via structural events, as well as assembled RNA-Seq contigs from human prostate cancer cell line C4-2. Our results indicate that Dissect has high sensitivity and specificity in identifying structural alteration events in simulated transcripts as well as uncovering novel structural alterations in cancer transcriptomes.

Availability: Dissect is available for public use at: http://dissect-trans.sourceforge.net

Contact:  denizy@mit.edu; fhach@cs.sfu.ca; cenk@cs.sfu.ca
DACTAL: divide-and-conquer trees (almost) without alignments
Authors: Nelesen Serita , Liu Kevin , Wang Li-San , Linder C. Randal , Warnow Tandy
Published: June 2012

Motivation: While phylogenetic analyses of datasets containing 1000–5000 sequences are challenging for existing methods, the estimation of substantially larger phylogenies poses a problem of much greater complexity and scale.

Methods: We present DACTAL, a method for phylogeny estimation that produces trees from unaligned sequence datasets without ever needing to estimate an alignment on the entire dataset. DACTAL combines iteration with a novel divide-and-conquer approach, so that each iteration begins with a tree produced in the prior iteration, decomposes the taxon set into overlapping subsets, estimates trees on each subset, and then combines the smaller trees into a tree on the full taxon set using a new supertree method. We prove that DACTAL is guaranteed to produce the true tree under certain conditions. We compare DACTAL to SATé and maximum likelihood trees on estimated alignments using simulated and real datasets with 1000–27 643 taxa.

Results: Our studies show that on average DACTAL yields more accurate trees than the two-phase methods we studied on very large datasets that are difficult to align, and has approximately the same accuracy on the easier datasets. The comparison to SATé shows that both have the same accuracy, but that DACTAL achieves this accuracy in a fraction of the time. Furthermore, DACTAL can analyze larger datasets than SATé, including a dataset with almost 28 000 sequences.

Availability: DACTAL source code and results of dataset analyses are available at www.cs.utexas.edu/users/phylo/software/dactal.

Contact:  tandy@cs.utexas.edu
Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks
Authors: Penfold Christopher A. , Buchanan-Wollaston Vicky , Denby Katherine J. , Wild David L.
Published: June 2012

Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.

Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.

Availability: The methods outlined in this article have been implemented in Matlab and are available on request.

Contact:  d.l.wild@warwick.ac.uk

Supplementary Information:  Supplementary data is available for this article.
GraphClust: alignment-free structural clustering of local RNA secondary structures
Authors: Heyne Steffen , Costa Fabrizio , Rose Dominic , Backofen Rolf
Published: June 2012

Motivation: Clustering according to sequence–structure similarity has now become a generally accepted scheme for ncRNA annotation. Its application to complete genomic sequences as well as whole transcriptomes is therefore desirable but hindered by extremely high computational costs.

Results: We present a novel linear-time, alignment-free method for comparing and clustering RNAs according to sequence and structure. The approach scales to datasets of hundreds of thousands of sequences. The quality of the retrieved clusters has been benchmarked against known ncRNA datasets and is comparable to state-of-the-art sequence–structure methods although achieving speedups of several orders of magnitude. A selection of applications aiming at the detection of novel structural ncRNAs are presented. Exemplarily, we predicted local structural elements specific to lincRNAs likely functionally associating involved transcripts to vital processes of the human nervous system. In total, we predicted 349 local structural RNA elements.

Availability: The GraphClust pipeline is available on request.

Contact:  backofen@informatik.uni-freiburg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Ranking models of transmembrane β-barrel proteins using Z-coordinate predictions
Authors: Hayat Sikander , Elofsson Arne
Published: June 2012

Motivation: Transmembrane β-barrels exist in the outer membrane of gram-negative bacteria as well as in chloroplast and mitochondria. They are often involved in transport processes and are promising antimicrobial drug targets. Structures of only a few β-barrel protein families are known. Therefore, a method that could automatically generate such models would be valuable. The symmetrical arrangement of the barrels suggests that an approach based on idealized geometries may be successful.

Results: Here, we present tobmodel; a method for generating 3D models of β-barrel transmembrane proteins. First, alternative topologies are obtained from the BOCTOPUS topology predictor. Thereafter, several 3D models are constructed by using different angles of the β-sheets. Finally, the best model is selected based on agreement with a novel predictor, ZPRED3, which predicts the distance from the center of the membrane for each residue, i.e. the Z-coordinate. The Z-coordinate prediction has an average error of 1.61 Å. Tobmodel predicts the correct topology for 75% of the proteins in the dataset which is a slight improvement over BOCTOPUS alone. More importantly, however, tobmodel provides a Cα template with an average RMSD of 7.24 Å from the native structure.

Availability: Tobmodel is freely available as a web server at: http://tobmodel.cbr.su.se/. The datasets used for training and evaluations are also available from this site.

Contact:  arne@bioinfo.se
A rostro-caudal gradient of structured sequence processing in the left inferior frontal gyrus
Authors: Uddén Julia , Bahlmann Jörg
Published: June 2012

In this paper, we present two novel perspectives on the function of the left inferior frontal gyrus (LIFG). First, a structured sequence processing perspective facilitates the search for functional segregation within the LIFG and provides a way to express common aspects across cognitive domains including language, music and action. Converging evidence from functional magnetic resonance imaging and transcranial magnetic stimulation studies suggests that the LIFG is engaged in sequential processing in artificial grammar learning, independently of particular stimulus features of the elements (whether letters, syllables or shapes are used to build up sequences). The LIFG has been repeatedly linked to processing of artificial grammars across all different grammars tested, whether they include non-adjacent dependencies or mere adjacent dependencies. Second, we apply the sequence processing perspective to understand how the functional segregation of semantics, syntax and phonology in the LIFG can be integrated in the general organization of the lateral prefrontal cortex (PFC). Recently, it was proposed that the functional organization of the lateral PFC follows a rostro-caudal gradient, such that more abstract processing in cognitive control is subserved by more rostral regions of the lateral PFC. We explore the literature from the viewpoint that functional segregation within the LIFG can be embedded in a general rostro-caudal abstraction gradient in the lateral PFC. If the lateral PFC follows a rostro-caudal abstraction gradient, then this predicts that the LIFG follows the same principles, but this prediction has not yet been tested or explored in the LIFG literature. Integration might provide further insights into the functional architecture of the LIFG and the lateral PFC.
Visual artificial grammar learning: comparative research on humans, kea (
Nestor notabilis
) and pigeons (
Columba livia
)
Authors: Stobbe Nina , Westphal-Fitch Gesche , Aust Ulrike , Fitch W. Tecumseh
Published: June 2012

Artificial grammar learning (AGL) provides a useful tool for exploring rule learning strategies linked to general purpose pattern perception. To be able to directly compare performance of humans with other species with different memory capacities, we developed an AGL task in the visual domain. Presenting entire visual patterns simultaneously instead of sequentially minimizes the amount of required working memory. This approach allowed us to evaluate performance levels of two bird species, kea (
Nestor notabilis
) and pigeons (
Columba livia
), in direct comparison to human participants. After being trained to discriminate between two types of visual patterns generated by rules at different levels of computational complexity and presented on a computer screen, birds and humans received further training with a series of novel stimuli that followed the same rules, but differed in various visual features from the training stimuli. Most avian and all human subjects continued to perform well above chance during this initial generalization phase, suggesting that they were able to generalize learned rules to novel stimuli. However, detailed testing with stimuli that violated the intended rules regarding the exact number of stimulus elements indicates that neither bird species was able to successfully acquire the intended pattern rule. Our data suggest that, in contrast to humans, these birds were unable to master a simple rule above the finite-state level, even with simultaneous item presentation and despite intensive training.
The neurobiology of syntax: beyond string sets
Authors: Petersson Karl Magnus , Hagoort Peter
Published: June 2012

The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty.
Physiological mechanisms of imprinting and homing migration in Pacific salmon Oncorhynchus spp.
Authors: Ueda H.
Published: June 2012

After several years of feeding at sea, salmonids have an amazing ability to migrate long distances from the open ocean to their natal stream to spawn. Three different research approaches from behavioural to molecular biological studies have been used to elucidate the physiological mechanisms underpinning salmonid imprinting and homing migration. The study was based on four anadromous Pacific salmon Oncorhynchus spp., pink salmon Oncorhynchus gorbuscha, chum salmon Oncorhynchus keta, sockeye salmon Oncorhynchus nerka and masu salmon Oncorhynchus masou, migrating from the North Pacific Ocean to the coast of Hokkaido, Japan, as well as lacustrine O. nerka and O. masou in Lake Toya, Hokkaido, where the lake serves as the model oceanic system. Behavioural studies using biotelemetry techniques showed swimming profiles from the Bering Sea to the coast of Hokkaido in O. keta as well as homing behaviours of lacustrine O. nerka and O. masou in Lake Toya. Endocrinological studies on hormone profiles in the brain–pituitary–gonad axis of O. keta, and lacustrine O. nerka identified the hormonal changes during homing migration. Neurophysiological studies revealed crucial roles of olfactory functions on imprinting and homing during downstream and upstream migration, respectively. These findings are discussed in relation to the physiological mechanisms of imprinting and homing migration in anadromous and lacustrine salmonids.
Neoproterozoic–Devonian stratigraphic evolution of the eastern Murzuq Basin, Libya: a tale of tilting in the central Sahara
Authors: Le Heron Daniel Paul , Meinhold Guido , Bergig Khalid A.
Published: June 2012

The Murzuq Basin is one of the most petroliferous basins of North Africa. Its remote eastern flank has been largely ignored since early reconnaissance work in the 1950s and 1960s. This article presents new stratigraphic and sedimentological data on the Neoproterozoic through Devonian succession from the Mourizidie and Dor el Gussa regions. The Neoproterozoic to Cambrian Mourizidie and Hasawnah formations in the eastern part of the Mourizidie region dip to the east and north‐east, resting directly on late Precambrian metasediments and granitoids. These strata record the initial progradation of sand‐dominated braidplain systems upon peneplained Precambrian basement. Rhyolite clasts in the Hasawnah Formation may record tectonically driven uplift and unroofing in the southern Tibesti Massif or tectonomagmatic rejuvenation to the south of this massif. In the western part of the Mourizidie region, Late Ordovician through Silurian strata (Mamuniyat and Tanezzuft–Akakus formations) directly overlie late Precambrian metasediments and granitoids, and dip at a low angle towards the west into the Murzuq Basin. Elsewhere at the eastern Murzuq Basin flank, in Dor el Gussa, Late Ordovician glaciogenic sediments rest with angular unconformity upon shallow marine sandstones of Cambrian–Ordovician age. This angular unconformity may also occur in the Mourizidie region and indicates widespread tectonism, either as a result of a Middle–Late Ordovician orogenic event, far‐field tectonism related to the opening of the Rheic Ocean along the northern margin of Gondwana or alternatively crustal depression associated with the growth of Late Ordovician ice sheets. Unconformity development was also probably associated with glacial incision. Following ice sheet retreat, isostatic rebound during deglaciation resulted in uplift of tens to hundreds of metres, locally removing all Cambrian and Ordovician formations. Rising sea levels in the Silurian led to deposition of the Tanezzuft Formation on Precambrian basement in the northwestern Mourizidie region.
Pilot study of rosiglitazone as an in vivo probe of paclitaxel exposure
Authors: Hertz Daniel L. , Walko Christine M. , Bridges Arlene S. , Hull J. Heyward , Herendeen Jill , Rollins Kristan , Watkins Paul B. , Dees E. Claire
Published: June 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Paclitaxel and rosiglitazone are primarily metabolized by CYP2C8 and their in vitro metabolism by human liver microsomes is correlated. Probe assays that quantify the in vivo activity of CYP enzymes which are important in drug metabolism have been developed for use in clinical pharmacology research. A probe of CYP2C8 that is easy to administer and interpret may be valuable for individualized dosing of paclitaxel.

WHAT THIS STUDY ADDS

• This pilot study demonstrates for the first time that there is an in vivo correlation between paclitaxel and rosiglitazone exposure. The finding, that a single rosiglitazone plasma concentration after oral dosing may explain significant variance in paclitaxel exposure, suggests that rosiglitazone may satisfy the requirements of a clinically useful in vivo probe. However, it is acknowledged that there is a need for further studies evaluating the use of rosiglitazone as a CYP2C8 probe and quantifying the relationship, in order to guide dosing of narrow therapeutic index drugs metabolized primarily by CYP2C8, such as paclitaxel.

AIMS To evaluate the use of rosiglitazone and the erythromycin breath test (ERMBT), as probes of CYP2C8 and CYP3A4, respectively, to explain inter‐individual variability in paclitaxel exposure.

METHODS The concentration of rosiglitazone at 3 h and ERMBT results were included in a regression model to explain the variability in paclitaxel exposure in 14 subjects.

RESULTS Rosiglitazone concentration was significantly correlated with paclitaxel exposure (P= 0.018) while ERMBT had no predictive value (P= 0.47).

CONCLUSIONS The correlation between the exposure of rosiglitazone and paclitaxel likely reflects mutual dependence on the activity of CYP2C8. Rosiglitazone or similar agents may have value as in vivo probes of CYP2C8 activity.
Peripheral quantitative computed tomography (pQCT) reveals alterations in the three‐dimensional bone structure in children with haemophilia
Authors: Ranta S. , Viljakainen H. , Mäkipernaa A. , Mäkitie O.
Published: June 2012

Children with haemophilia are at risk of suboptimal bone mass accrual and low bone mineral density (BMD). We recently demonstrated that although BMD in Finnish children with haemophilia was within the normal range, their whole body BMD was significantly lower and hypercalciuria more prevalent than in controls. This study sought to determine the bone structure and strength in physically active children with haemophilia. To investigate the underlying mechanisms in this group, we conducted a case–control study to assess bone structure and strength by peripheral quantitative computed tomography (pQCT) at the radius. The study group comprised 29 patients (mean age 12.2 years) and 46 age‐matched controls. Children with haemophilia had decreased total BMD Z‐score at the distal radius (P ≤ 0.001), but increased cortical bone density at the proximal radius (P ≤ 0.001). Total bone area at the proximal radius was significantly lower in children with haemophilia (P = 0.002), whereas there were no differences in cortical bone area or in polar Strength‐Strain Index, a parameter of bone strength, between the patients and controls. Patients with mild to moderate haemophilia and on‐demand treatment had inferior bone strength compared to those with moderate to severe haemophilia and prophylaxis. Our findings suggest altered skeletal development in patients with haemophilia in the radius, resulting in smaller bone size and higher cortical bone density. Importantly, bone strength at the radius appears equal to healthy children. Prophylactic treatment seems to have a beneficial effect on bone health.
The development of a patient partnership programme and its impact on quality improvements in a comprehensive haemophilia care service
Authors: Grogan A. , Coughlan M. , O' Mahony B. , McKee G.
Published: June 2012

It has long been advocated that patient input in service quality development is essential. We have developed a model of quality evaluation and improvement within a comprehensive haemophilia service, and describe the issues and improvements that resulted from the process. The project utilized an action research methodology. Seven patients were recruited from the haemophilia service for the initial focus groups. The main themes initially explored were as follows: patient experience of the outpatient, inpatient and weekend services and provision of information. The focus group data were analysed using basic content analysis. The main themes the initial focus group identified were the need to optimize the annual review, emergency care and inpatient facilities. Following this, the haemophilia care team worked on improving these issues. At the second focus group the patients contributed at a higher level – patient participation. Patients assisted in addressing outstanding issues such as ID alert card content and the algorithm of care for emergency services. Finally, a patient panel was developed and the relationship became one of direct negotiation and partnership with the haemophilia team to address issues within the service. The expectations and needs of patients attending the haemophilia comprehensive care service are complex. The process of including patients as partners at the highest level of patient involvement evolved and proved an effective method of service evaluation and development, facilitating lateral decision‐making, not only improving care directly, but also improving the user experience.
SMARCB1/INI1 inactivation in renal medullary carcinoma
Authors: Calderaro Julien , Moroch Julien , Pierron Gaelle , Pedeutour Florence , Grison Camille , Maillé Pascale , Soyeux Pascale , de la Taille Alexandre , Couturier Jérome , Vieillefond Annick , Rousselet Marie Christine , Delattre Olivier , Allory Yves
Published: June 2012

Calderaro J, Moroch J, Pierron G, Pedeutour F, Grison C, Maillé P, Soyeux P, de la Taille A, Couturier J, Vieillefond A, Rousselet M C, Delattre O & Allory Y  (2012) Histopathology 61, 428–435

SMARCB1/INI1 inactivation in renal medullary carcinoma

Aims:  Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle‐cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied.

Methods and results:  Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription.

Conclusions:  The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities.
Image and statistical analysis of melanocytic histology
Authors: Miedema Jayson , Marron James Stephen , Niethammer Marc , Borland David , Woosley John , Coposky Jason , Wei Susan , Reisner Howard , Thomas Nancy E
Published: June 2012

Miedema J, Marron J S, Niethammer M, Borland D, Woosley J, Coposky J, Wei S, Reisner H & Thomas N E  (2012) Histopathology 61, 436–444

Image and statistical analysis of melanocytic histology

Aims:  We applied digital image analysis techniques to study selected types of melanocytic lesions.

Methods and results:  We used advanced digital image analysis to compare melanocytic lesions as follows: (i) melanoma to nevi, (ii) melanoma subtypes to nevi, (iii) severely dysplastic nevi to other nevi and (iv) melanoma to severely dysplastic nevi. We were successful in differentiating melanoma from nevi [receiver operating characteristic area (ROC) 0.95] using image‐derived features, among which those related to nuclear size and shape and distance between nuclei were most important. Dividing melanoma into subtypes, even greater separation was obtained (ROC area 0.98 for superficial spreading melanoma; 0.95 for lentigo maligna melanoma; and 0.99 for unclassified). Severely dysplastic nevi were best differentiated from conventional and mildly dysplastic nevi by differences in cellular staining qualities (ROC area 0.84). We found that melanomas were separated from severely dysplastic nevi by features related to shape and staining qualities (ROC area 0.95). All comparisons were statistically significant (P < 0.0001).

Conclusions:  We offer a unique perspective into the evaluation of melanocytic lesions and demonstrate a technological application with increasing prevalence, and with potential use as an adjunct to traditional diagnosis in the future.
LPS induces IL‐8 expression through TLR4, MyD88, NF‐kappaB and MAPK pathways in human dental pulp stem cells
Authors: He W. , Qu T. , Yu Q. , Wang Z. , Lv H. , Zhang J. , Zhao X. , Wang P.
Published: June 2012

Aim

To evaluate the effects of lipopolysaccharide (LPS) on interleukin‐8 (IL‐8) and related intracellular signalling pathways in human dental pulp stem cells (hDPSCs).

Methodology

Human pulp tissues were isolated from human impacted third molars, and the hDPSCs were cultured and characterized. The effects of LPS on IL‐8 and Toll‐like receptor 4 (TLR4) gene expression in hDPSCs were investigated using real‐time quantitative RT‐PCR and ELISA. Whether TLR4/MyD88/NF‐кB was involved in the LPS‐induced up‐regulation of IL‐8 in hDPSCs was determined using transient transfection, luciferase assay and ELISA. The involvement of MAPKs in the LPS‐induced up‐regulation of IL‐8 in hDPSCs was investigated via transient transfection, luciferase assay, ELISA and western blot. The data were statistically analysed using Student's t‐test or one‐way anova followed by the Student–Neumann–Keuls test.

Results

Cells exposed to LPS not only displayed an enhanced expression of TLR4 but also showed an elevated IL‐8 gene expression; exposure to LPS also resulted in the induction of IL‐8 gene transcription via promoter activation. The LPS‐induced IL‐8 promoter activation was inhibited through dominant‐negative mutations in TLR4 and MyD88, but not in TLR2. The LPS‐induced IL‐8 protein release was attenuated through the administration of TLR4‐neutralizing antibody or MyD88 inhibitory peptide and a dominant‐negative mutation in IκBα. In contrast, IL‐8 protein release was enhanced through the expression of NF‐κB p65. Treatment with PDTC, TPCK or Bay117082 effectively antagonized LPS‐induced IL‐8 protein release. Moreover, both the promoter activity and the LPS‐induced release of IL‐8 were diminished upon the administration of U0126 and SB203580, but not SP600125. Moreover, the exposure to LPS activated ERK1/2 and p38 MAPK phosphorylation in cells.

Conclusions

This study reports the LPS‐mediated transcriptional and post‐translational up‐regulation of IL‐8, which is a process that also involves TLR4, MyD88, NF‐κB and MAPK.
Functional, biochemical and pasting properties of extruded bean (Phaseolus vulgaris) cotyledons
Authors: Lopes Lilian Cristian Mattos , de Aleluia Batista Karla , Fernandes Kátia Flávia , de Andrade Cardoso Santiago Raquel
Published: June 2012

Response surface methodology was used to investigate the effects of extrusion conditions – namely moisture content (12.3–23.7 g 100 g−1) and temperature (150–178 °C) – on physicochemical, antinutritional compounds, functional and pasting properties of extruded bean cotyledons. Results indicated that extrusion cooking did not change the chemical composition of bean flours, but completely eliminated the activity of the trypsin and α‐amylase inhibitors and haemagglutinins. The extrusion significantly improved starch and protein digestibility, water solubility and absorption of bean cotyledon. In addition, extrusion conditions significantly affected pasting properties, resulting in extrudate flours with different peaks and final viscosity values. From the results obtained in this work, it is possible to design a product with specific physicochemical, functional and nutritional properties using the appropriate moisture and temperature during extrusion.
Purification and characterisation of two acidic peroxidase isoforms from the sheaths of bamboo shoots
Authors: Hsu Shou‐Kuo , Chung Yun‐Chin , Chang Chen‐Tien , Sung Hsien‐Yi
Published: June 2012

Three isoforms of peroxidase (POD) were isolated from the sheaths of bamboo shoots by chromatofocusing on Polybuffer exchanger PBE 94. POD‐A was partially purified, and POD‐B and POD‐C were purified and characterised. POD‐A was a basic peroxidase, whereas POD‐B and POD‐C were acidic peroxidases with different isoelectric points. Using o‐phenylenediamine (OPD) as a hydrogen‐donor, the optimum temperatures for function of POD‐B and POD‐C were 55 and 45–55 °C, respectively, while both had the same optimum pH of 4.5. Both isoforms were stable between 30 and 60 °C and between pH 4.5 and 10. The activities of the POD isoforms towards hydrogen‐donors were both pH and concentration dependent. Under optimal conditions, POD‐B and POD‐C catalysed the oxidation of catechol, pyrogallol, and OPD at higher rates than guaiacol, o‐dianisidine and 2, 2’‐azino‐bis‐ (3‐ethylbenzothiazoline‐6‐sulphonic acid). Both isoforms were almost completely inhibited by chemical modification reagent diethyl pyrocarbonate (4.5 mM).
Nursing student attitudes towards older people: validity and reliability of the Italian version of the Kogan Attitudes towards Older People scale
Authors: Matarese Maria , Lommi Marzia , Pedone Claudio , Alvaro Rosaria , De Marinis Maria Grazia
Published: June 2012

Aim.  This paper reports a study testing the validity and reliability of the Italian version of the Kogan Attitude towards Older People scale.

Background.  Nursing students’ attitudes towards older people can affect their preference for working with them. One of the most common instruments used to assess these attitudes is the Kogan Attitude towards Older People scale. Previous validation studies performed on college students internationally have demonstrated good reliability and validity. The psychometric properties of the Italian version have not yet been tested.

Design.  A cross‐sectional, descriptive study.

Method.  The study was conducted from March–June 2010 with a convenience sample of nursing students attending two Italian universities. Reliability was evaluated using internal consistency and item‐to‐total correlation. Content and construct validity were evaluated using a content validity index and principal factor analysis.

Results.  A total of 1637 nursing students participated in the study. Two factors were extracted from the factor analysis: prejudice describing a negative disposition and appreciation indicating a favourable feeling and opinion towards older people.

Conclusion.  The Kogan Attitude towards Older People scale applied to Italian nursing students exhibited good internal consistency. The two‐dimensional construct of the scale was congruent with some, but not all, results of previous studies due to methodological differences among the studies. Based on the study findings, the scale can be recommended for future research studies in Italy including use as pre/post‐test measurement associated with nursing education programmes.
Enabling overweight children to improve their food and exercise habits – school nurses’ counselling in multilingual settings
Authors: Magnusson Maria B , Kjellgren Karin I , Winkvist Anna
Published: June 2012

Aims and objectives.  The study aimed at analysing school nurses’ counselling of overweight and obese children in settings with many immigrants, focusing on content concerning food and physical activity and how this was communicated.

Background.  For people with a predisposition for overweight, the weight control process requires cognitive skills. School nurses’ counselling of overweight children has the potential to support this process by enabling personal resources in the children and their families. However, there is uncertainty among nurses about how to conduct supportive counselling.

Design.  An explorative design was used when collecting and analysing data.

Method.  Twenty‐two counselling sessions between eight school nurses and 20 overweight children were audio‐recorded and analysed using qualitative content analysis. Most of the participating schools represented areas with low socioeconomic status and a high proportion of immigrants and refugees.

Results.  Less adequate skills in enabling resources in the children and their parents were observed. Concurrently, school nurses provided inadequate explanations about food and physical activity. Topics related to general nutrition models were frequently communicated as general advice instead of individually tailored counselling. Counselling families with other languages and food cultures than the traditional Swedish created additional difficulties.

Conclusions.  Improved nutritional knowledge for nurses may enhance their skills in enabling children’s and families’ resources. School nurses should be provided with opportunities to cooperate with other professions in counteracting overweight.

Relevance to clinical practice.  Our findings demonstrate a relationship between content skills and person‐centeredness in the counselling. This highlights the importance of inter‐professional collaboration to ensure a high quality of lifestyle counselling. School health authorities should give high priority to facilitating school nurses’ evidence‐based continuing education.
Prioritization of a plant polysaccharide over a mucus carbohydrate is enforced by a Bacteroides hybrid two‐component system
Authors: Lynch Jonathan B. , Sonnenburg Justin L.
Published: June 2012

Bacteroides is a dominant genus within the intestinal microbiota of healthy humans. Key adaptations of the Bacteroides to the dynamic intestinal ecosystem include a diverse repertoire of genes involved in sensing and processing numerous diet‐ and host‐derived polysaccharides. One such adaptation is the carbohydrate‐sensing hybrid two‐component system (HTCS) family of signalling sensors, which has been widely expanded within the Bacteroides. Using Bacteroides thetaiotaomicron as a model, we have created a chimeric HTCS consisting of the well‐characterized sensing domain of one HTCS, BT1754, and the regulatory domain of another HTCS, BT0366, to explore the regulatory capabilities of these molecules. We found that the BT0366 regulatory region directly binds to and mediates induction of the adjacent polysaccharide utilization locus (PUL) using whole‐genome transcriptional profiling after inducing signalling through our chimeric protein. We also found that BT0366 activation simultaneously leads to repression of distal PULs involved in mucus carbohydrate consumption. These results suggest a novel mechanism by which an HTCS enforces a nutrient hierarchy within the Bacteroides via induction and repression of multiple PULs. Thus, hybrid two‐component systems provide a mechanism for prioritizing consumption of carbohydrates through simultaneous binding and regulation of multiple polysaccharide utilization loci.
Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor‐alpha in diverticular disease of the colon: a case–control study
Authors: Tursi A. , Elisei W. , Brandimarte G. , Giorgetti G. M. , Inchingolo C. D. , Nenna R. , Picchio M. , Giorgio F. , Ierardi E.
Published: June 2012

Background  Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF‐α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD).

Methods  Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups.

Key Results  The expression of bFGF, SD1, and TNF‐α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF‐α expression dropped significantly.

Conclusions & Inferences  Mucosal TNF‐α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF‐α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD.