bluuebunny/crossref_metadata_2025 huggingface dataset:
TEMPORARY RIVERS: LINKING ECOHYDROLOGY, ECOLOGICAL QUALITY AND RECONCILIATION ECOLOGY
Authors: Arthington A. H. , Bernardo J. M. , Ilhéu M.
Published: August 2014

Temporary streams and rivers, also referred to as intermittent, are defined as waterways that cease to flow at some points in space and time along their course. They are shaped by alternating wet and dry periods over annual and inter‐annual cycles, making them one of the most dynamic freshwater ecosystems. These distinctive systems represent a substantial proportion of the total number, length and discharge of the global river network and are expected to become more widespread and face increasing pressures in many regions as a result of human activities and climate change. This collection of papers arose from the Conference on ‘Ecohydrology and Ecological Quality in Temporary Rivers’ held at the University of Evora, Portugal, 12–14 September 2012. The primary objectives of the meeting were to bring together researchers and expertise from a range of temporary ecosystems, from small temporary Mediterranean and Californian streams to intermittent rivers from semi‐arid and arid zones. A common thread through the discussions was the assessment of ecological conditions within these dynamic ecosystems. To undertake a ’condition assessment’ is challenging because of the need to differentiate between biotic responses to anthropogenic pressures and natural variability associated with the hydro‐climatology and disturbance regime typical of these systems, that is, drought, drying and flooding. The management of degraded intermittent streams and rivers presents many new challenges, not least how to reconcile ecological and societal goals for emerging ‘novel’ ecosystems. Reconciliation ecology presents a realistic way of managing novel ecosystems given their value and desirable ecological services to society, rather than trying to restore to an original ecological state that may not be sustainable or economically possible. Copyright © 2014 John Wiley & Sons, Ltd.
A General Approach to Predicting Ecological Responses to Environmental Flows: Making Best Use of the Literature, Expert Knowledge, and Monitoring Data
Authors: Webb J. A. , de Little S. C. , Miller K. A. , Stewardson M. J. , Rutherfurd I. D. , Sharpe A. K. , Patulny L. , Poff N. L.
Published: August 2014

Around the world, governments are making huge investments in environmental flows. However, much of the rationale for these releases is based on expert opinion and is thus open to challenge. Empirical studies that relate ecological responses to flow restoration are mostly case studies of limited generality. Radically, different approaches are required to inform the development of general models that will allow us to predict the effects of environmental flows. Here, we describe the modelling framework being used in a major study of environmental flows in the Australian state of Victoria. The framework attempts to make best use of all the information available from the literature, experts, and monitoring data, to inform the development of general quantitative response models. It uses systematic review of the literature to develop evidence‐based conceptual models, formal expert elicitation to provide an initial quantification of model links, and data derived from purpose‐designed monitoring programs over large spatial scales. These elements come together in a Bayesian hierarchical model that quantifies the relationship between flow variation and ecological response and hence can be used to predict ecological responses to flow restoration. We illustrate the framework using the example of terrestrial vegetation encroachment into regulated river channels. Our modelling framework aims to develop general flow‐response models and can immediately be used to demonstrate the ecological return on investment from environmental flow programs. However, the framework also has the potential to be incorporated into planning and decision‐making processes, helping to drive a transformation in evidence‐based practice for environmental flow management. © 2014 The Authors. River Research and Applications published by John Wiley & Sons, Ltd.
Fate, Transport and Effects of Pollutants Originating from Acid Mine Drainage in the Olifants River, South Africa
Authors: Dabrowski J. M. , Dabrowski J. , Hill L. , MacMillan P. , Oberholster P. J.
Published: August 2014

Concentrations of pollutants were measured in water, sediment and algal samples collected along a longitudinal gradient from a stretch of the Olifants River, South Africa, that receives acid mine drainage (AMD) from the Klipspruit River. The effects of AMD were determined through macroinvertebrate biotic indices (SASS5) and multivariate analysis of macroinvertebrate communities. The acidic Klipspruit River caused increased concentrations of total Al, Fe and Mn in the Olifants River. Upon mixing of the Klipspruit with that from the alkaline Olifants River, Al and Fe precipitate rapidly, leading to lower concentrations in the dissolved phase and higher concentrations in the suspended phase and in sediment at sites in close proximity to the confluence. Similarly, filamentous algae accumulated high concentrations of Al, Fe and Zn immediately after the confluence. Mn remains in the dissolved phase, and sediment and algal concentrations increase with increasing distance downstream. Metal speciation analysis indicate that Al is rapidly converted from more toxic forms (e.g. Al3+ and Al(OH)2+) to less toxic forms (e.g. Al(OH)3(aq) and Al(OH)4−). In contrast, Mn remains in the soluble Mn2+ form. Macroinvertebrate metrics and community structure showed clear signs of deterioration in water quality in the Olifants River downstream of the point of AMD input. While total TDS concentrations at all sites fall within ranges likely to affect macroinvertebrates, the relative composition of major ions changes as a result of AMD input, which may also account for the observed changes in macroinvertebrate communities. Further downstream, the Wilge River discharges into the Olifants River and significantly improves water quality downstream of the confluence. Future mining and development activities in the Wilge catchment should be carefully managed and monitored so as to ensure sufficient flows of acceptable quality to prevent further deterioration of water quality in the Olifants River and downstream reservoirs. Copyright © 2014 John Wiley & Sons, Ltd.
Life‐History Plasticity of Riparian Annual Plants Adapted to Extreme Variations in Water Level: Mesocosm Experiments
Authors: Song Y. , Ke X. , Liu W. , Davy A. J. , Liu G.
Published: August 2014

The riparian zones of reservoirs associated with regulated rivers in China experience annual fluctuations in water level of up to 30 m that may vary in timing from year to year. Few plant species can tolerate such hydrological perturbation, but short‐lived riparian annuals might be evolutionarily pre‐adapted to such conditions. This study investigated plasticity of life history in four annual species: one typically associated with free‐flowing rivers (Panicum bisulcatum) and three that colonize reservoir margins (Cyperus michelianus, Fimbristylis miliacea and Eclipta prostrata). We found that all four species produced non‐dormant seeds that survived prolonged submergence; germination percentage was independent of the time of exposure by receding waters. Although growth was reduced as a result of shorter growing seasons, all four species completed their life cycles and produced seeds before winter. In addition, P. bisulcatum and C. michelianus allocated biomass to seed production, at the expense of roots and stems, in response to later establishment. All species responded to later establishment with a reduced vegetative growth period before seed production. C. michelianus, F. miliacea and E. prostrate could also delay the onset of flowering time by up to 2 months. P. bisulcatum, a plant that can flower only after exposure to short days, consequently had a fixed flowering time and could accommodate delayed establishment only with a progressively shorter period of vegetative growth. This lower flexibility might explain its absence from reservoir margins. The conceptual framework presented here offers a tool to predict the establishment of vegetation under hydrological disturbance in riparian environments and thereby provides insights into improved restoration practice. Copyright © 2014 John Wiley & Sons, Ltd.
Beyond Fun and Games
Authors: Wood Summer , Jocius Robin
Published: August 2014

It is no secret that technology is ever evolving and impacting the ways in which we engage in society. This reality is also true when considering how young children express knowledge. In this article we discuss the ways in which three iPad applications were used for critical responses to children's literature. We highlight the ways in which two elementary Black male students used these digital tools to respond critically to issues of power and equity presented in the children's literature used in the tutoring program in which they were taking part.
Fungi associated with drug recalls and rare disease outbreaks
Authors: Ahearn Donald G , Doyle Stulting R
Published: August 2014

Fungi rarely cause disease outbreaks associated with use of microbe-contaminated drugs. These rare episodes typically involve a restricted spectrum of common environmental species with relatively low virulence, rather than classical pathogens. Review of data involving over-the-counter contact lens solutions and prescription drug-related recalls revealed six episodes during the past decade with significant adverse health and financial impact (including loss of vision and death). Contaminations involved fungi mostly identified with the genera Aspergillus, Exserohilum, Fusarium, Paecilomyces, and Rhizopus. These organisms are noted for their capacity to produce resistant morphotypes (chlamydoconidia, ascospores) under various adverse conditions, generally with temperature survival/tolerances markedly in excess of maximal growth temperatures. High constituent levels of melanin, trehalose and heat-shock proteins facilitate differential survival of morphotypes following exposures to toxic chemicals and temperatures above 80 °C. Adverse environmental factors that induce resistant morphotypes are suggested to occur more readily in situ than during in vitro testing. Rare unexplained, sporadic drug contamination episodes with select thermotolerant fungi may relate, in part, to resistant dormant stages.
Fatty Acid Profiles of Virgin Olive Oils from the Five Olive‐Growing Zones of Extremadura (Spain)
Authors: Martínez Manuel , Fuentes Manuel , Franco Nieves , Sánchez Jacinto , de Miguel Concepción
Published: August 2014

In this study, 278 samples of virgin olive oil from 40 mills belonging to five olive‐growing zones of Extremadura were evaluated according to their fatty acid composition. An analysis of variance of the fatty acid contents, and their principal group subtotals and ratios revealed significant differences at the 95 % confidence level between zones. Means were compared using Tukey's HSD test (p < 0.05). A discriminant analysis, taking the zone as the grouping variable and the different fatty acids and their ratios as independent variables, explained nearly 90 % of the variance with the first two functions. The model correctly classified 88.8 % of the analysed samples into their proper olive‐growing zone. Validation against an extra test set of 30 samples resulted in 90 % being correctly classified; the results of the discriminant analysis were therefore considered to be validated. A two‐dimensional graphical representation of the different groups studied using the first two resulting canonical discriminant functions clearly showed the Sierra Norte of Cáceres and Vegas del Guadiana each to be clearly separated from the rest and from each other, while the other three zones—Siberia, Serena and Tierra de Barros—overlapped considerably.
ROS‐dependent prostate apoptosis response‐4 (Par‐4) up‐regulation and ceramide generation are the prime signaling events associated with curcumin‐induced autophagic cell death in human malignant glioma
Authors: Thayyullathil Faisal , Rahman Anees , Pallichankandy Siraj , Patel Mahendra , Galadari Sehamuddin
Published: August 2014

Malignant gliomas are extremely resistant to therapies that induce apoptosis, but are less resistant to therapies that induce autophagy. Therefore, drugs targeting autophagy are promising in the management of malignant gliomas. In this study, we investigated the anti‐glioma potential of curcumin in vitro, and further examined the molecular mechanisms of curcumin‐induced cell death in human malignant glioma. Here, we provide evidence that curcumin is cytotoxic against human malignant glioma cell lines, and the mechanism of cell death caused by curcumin is associated with features of autophagy. Curcumin suppresses the growth of human malignant glioma cells via ROS‐dependent prostate apoptosis response‐4 (Par‐4) induction and ceramide generation. Extracellular supplementation of antioxidants such as glutathione and N‐acetylcysteine to glioma cells abrogated the Par‐4 induction, ceramide generation, and in turn, prevented curcumin‐induced autophagic cell death. Moreover, tumor cells transfected with Par‐4 gene sensitized the curcumin‐induced autophagic cell death. Overall, this study describes a novel signaling pathway by which curcumin induces ROS‐dependent Par‐4 activation and ceramide generation, leading to autophagic cell death in human malignant glioma cells.
Early life arsenic exposure and brain dopaminergic alterations in rats
Authors: Chandravanshi Lalit P. , Shukla Rajendra K. , Sultana Sarwat , Pant Aditya B. , Khanna Vinay K.
Published: August 2014

Recently, we found that early life exposure to arsenic at low doses resulted to cause brain cholinergic deficits and exhibited a trend of recovery on withdrawal of arsenic exposure. In continuation to this, the present study has been carried out to assess the impact of low level arsenic exposure on brain dopaminergic system and associated behavior in developing rats and investigate if neurobehavioral changes are recovered or persistent. Early life exposure (PD22–PD59) to arsenic (2 or 4 mg/kg body weight, p.o.) in rats resulted to increase the motor activity on PD60, compared to controls. The hyperactivity in arsenic exposed rats was found to be linked with increase in the binding of DA‐D2 receptors (38%, 56%), mRNA expression of DAR‐D2 receptor gene (68%, 97%) and expression of tyrosine hydroxylase protein (1.93, 2.73‐fold) in the corpus striatum as compared to controls on PD60. Exposure to arsenic enhanced generation of ROS (47%, 84%) and was associated with decrease in the mitochondrial membrane potential (13.3%, 15.33%), activity of mitochondrial complexes and increased oxidative stress. Disruption in the expression of pro‐apoptotic, anti‐apoptotic and stress marker proteins was also distinct in the corpus striatum of arsenic exposed rats. The severity of changes in the behavioral and neurochemical endpoints were found to persist in rats exposed to arsenic at high dose and exhibited a trend of recovery at low dose on withdrawal of arsenic exposure on PD90. Early life arsenic exposure appears to be critical and vulnerable as development of dopamine receptors continues during this period.
Hurdles on the road to personalized medicine
Authors: Tursz Thomas , Bernards Rene
Published: August 2014

Cancer treatment is slowly shifting from an approach in which the tissue of origin and the histology were the guiding principles for the choice of chemotherapy towards a genotype‐centric approach in which the changes in the cancer genome are used to select patients for treatment with highly selective and targeted drugs. This transition has all the hallmarks of a disruptive innovation and requires major adjustments in the way that cancer is diagnosed and treated. We discuss here the hurdles on the road ahead to a more personalized treatment of cancer.
Reliability of Magnetic Resonance Imaging Assessment of Rotator Cuff: The ROW Study
Authors: Jain Nitin B. , Collins Jamie , Newman Joel S. , Katz Jeffrey N. , Losina Elena , Higgins Laurence D.
Published: August 2014

Background

Physiatrists encounter patients with rotator cuff disorders, and imaging is frequently an important component of their diagnostic assessment. However, there is a paucity of literature on the reliability of magnetic resonance imaging (MRI) assessment between shoulder specialists and musculoskeletal radiologists.

Objective

We assessed inter‐ and intrarater reliability of MRI characteristics of the rotator cuff.

Design

Cross‐sectional secondary analyses in a prospective cohort study.

Setting

Academic tertiary care centers.

Patients

Subjects with shoulder pain were recruited from orthopedic and physiatry clinics.

Methods

Two shoulder‐fellowship–trained physicians (a physiatrist and a shoulder surgeon) jointly performed a blinded composite MRI review by consensus of 31 subjects with shoulder pain. Subsequently, MRI was reviewed by one fellowship‐trained musculoskeletal radiologist.

Main Outcome Measurements

We calculated the Cohen kappa coefficients and percentage agreement among the 2 reviews (composite review of 2 shoulder specialists versus that of the musculoskeletal radiologist). Intrarater reliability was assessed among the shoulder specialists by performing a repeated blinded composite MRI review. In addition to this repeated composite review, only one of the physiatry shoulder specialists performed an additional review.

Results

Interrater reliability (shoulder specialists versus musculoskeletal radiologist) was substantial for the presence or absence of tear (kappa 0.90 [95% confidence interval {CI}, 0.72‐1.00]), tear thickness (kappa 0.84 [95% CI, 0.70‐0.99]), longitudinal size of tear (kappa 0.75 [95% CI, 0.44‐1.00]), fatty infiltration (kappa 0.62 [95% CI, 0.45‐0.79]), and muscle atrophy (kappa 0.68 [95% CI, 0.50‐0.86]). There was only fair interrater reliability of the transverse size of tear (kappa 0.20 [95% CI, 0.00‐0.51]). The kappa for intrarater reliability was high for tear thickness (0.88 [95% CI, 0.72‐1.00]), longitudinal tear size (0.61 [95% CI, 0.22‐0.99]), fatty infiltration (0.89 [95% CI, 0.80,‐0.98]), and muscle atrophy (0.87 [95% CI, 0.76‐0.98]). Intrarater reliability for the individual shoulder specialist was similar to that of the composite reviews.

Conclusions

There was high interrater and intrarater reliability for most findings on shoulder MRI. Analysis of our data supports the reliability of MRI assessment by shoulder specialists for rotator cuff disorders.
Modified midfacial translocation for access to ventral skull base tumours
Authors: Hussain A , Shakeel M , Vallamkondu V , Kamel M
Published: August 2014

Objective:

To describe our technical modifications of midfacial translocation for access to the nasopharynx, and anterior, central and lateral skull base.

Design:

Retrospective chart review of a prospective case series.

Setting:

Department of Otolaryngology-Head and Neck Surgery, Aberdeen Royal Infirmary, Scotland, UK.

Methods:

Along with demographics, other parameters studied were adequacy of exposure, completeness of resection, aesthetic outcome and complications. Our main outcome measures included adequacy of exposure, partial or total resection of tumour, aesthetic outcome, and complications related to surgical technique.

Results:

A total of 48 patients underwent modified midfacial translocation at our institution for nasopharyngeal, parapharyngeal, and anterior, central and lateral skull base tumours. In all cases, the exposure was deemed to be adequate. Two patients developed wound dehiscence in previously irradiated fields. Other incisions healed very well and the aesthetic outcome was regarded as satisfactory.

Conclusion:

Modified midfacial translocation is based on the principle of temporary craniofacial disassembly for access to the skull base. Our modifications offer adequate access and a better aesthetic outcome. All incisions are placed through the aesthetic sub units of the nose with preservation of the lip. Preservation of the bony piriform aperture prevents airway compromise.
Thoracic Spondylodiscitis Caused by Methicillin-resistant Staphylococcus aureus as a Superinfection of Pulmonary Tuberculous Granuloma in an Immunocompetent Patient: A Case Report
Authors: Donnarumma Pasquale , Tarantino Roberto , Palmarini Valeria , De Giacomo Tiziano , Delfini Roberto
Published: August 2014

Study Design

Case report.

Objective

To describe a very rare case of an immunocompetent man who underwent surgery for thoracic spondylodiscitis caused by methicillin-resistant Staphylococcus aureus (MRSA) that developed as a superinfection of a pulmonary tuberculous granuloma.

Methods

Posterior decompression and pedicle screw vertebral fixation were followed by T5–T6 anterior somatotomy with implant of an expandable mesh and lateral plating as symptoms worsened. During the anterior approach, an atypical resection of the left lower lobe was also performed.

Results

A tuberculous granuloma was detected on histology. Ziehl-Neelsen stain confirmed the diagnosis. Culture also detected MRSA.

Conclusions

Early medical management is the first choice for spondylodiscitis to eradicate the infection and alleviate pain. Immobilization of the affected spine segments can protect the patient from vertebral collapse and from the appearance of neurologic deficits. Surgery is suggested if there are compressive effects on the spinal cord, spinal epidural abscess, vertebral collapse, and deformity. We decided to remove the abscess and to restore the anterior column using an anterior approach. Moreover, in this case, an anterior approach allowed us to identify the etiology of the lesion and to determine the best chemotherapy regimen.
TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival
Authors: Raphaël Maylis , Lehen’kyi V’yacheslav , Vandenberghe Matthieu , Beck Benjamin , Khalimonchyk Sergiy , Vanden Abeele Fabien , Farsetti Leonardo , Germain Emmanuelle , Bokhobza Alexandre , Mihalache Adriana , Gosset Pierre , Romanin Christoph , Clézardin Philippe , Skryma Roman , Prevarskaya Natalia
Published: August 2014

Significance

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective Ca
2+
channel that exercises its normal physiological function via Ca
2+
absorption in the intestine and kidney. Intriguingly, we show that the TRPV6 channel may switch from its well-known constitutive activity to the store operated due to the remodeling mechanism involving STIM1/Orai1/TRPC1-induced activation of TRPV6 channel translocation to the plasma membrane via the Ca
2+
/Annexin I/S100A11 pathway. Moreover, we demonstrate that the discovered mechanism is used by prostate cancer cells. This channel is absent in healthy prostate and is expressed de novo in prostate cancer cells, where it changes the role by supplying Ca
2+
, which is used in cancer to increase cell survival.
Theaflavins enhance intestinal barrier of Caco-2 Cell monolayers through the expression of AMP-activated protein kinase-mediated Occludin, Claudin-1, and ZO-1
Authors: Park Ha-Young , Kunitake Yuri , Hirasaki Naoto , Tanaka Mitsuru , Matsui Toshiro
Published: August 2014

We investigated the effect of theaflavins (TFs) on membrane barrier of Caco-2 cells. For fluorescein-transport experiments, the apparent permeability (Papp) of fluorescein in Caco-2 cells pretreated with 20 μM TFs were significantly decreased compared with that in untreated cells. Although the respective monomeric catechins did not show any Papp reduction, purpurogallin pretreatment resulted in a significant Papp reduction similar to that of TF-3′-O-gallate (TF3′G) pretreatment. This indicates that the benzotropolone moiety may play a crucial role in the Papp reduction or tight junction (TJ)-closing effect induced by TFs. In TF-3′-O-gallate-pretreated Caco-2 cells, fluorescein transport was completely restored by compound C (AMPK inhibitor). In addition, TF3′G significantly increased both the mRNA and protein expression of TJ-related proteins (occludin, claudin-1, and ZO-1) as well as the phosphorylation of AMPK. It was, thus, concluded that TFs could enhance intestinal barrier function by increasing the expression of TJ-related proteins through the activation of AMPK in Caco-2 cells.
A motor isolation effect: When object manipulability modulates recall performance
Authors: Guérard Katherine , Lagacé Sébastien
Published: August 2014

Previous studies suggested that the language production architecture is recruited during verbal retention, and others proposed that spatial memory relies on the oculomotor system. The objective of the present study was to investigate the role of the motor system in object memory, by examining the effect of objects’ affordances on retention. In a serial recall task, we manipulated the manipulability of objects to retain in memory. We used an isolation paradigm where we isolated the manipulability level of one object from the list. We showed that recall performance improved for the isolated object (Experiment 1) and that this advantage was abolished when participants were required to perform motor suppression during the task (Experiment 2). In Experiment 3, we showed that the abolition of the motor isolation effect in Experiment 2 was not due to an effect of distraction since motor suppression was shown not to interfere with a semantic isolation effect. It is argued that motor affordances play a role in object memory, but only when the motor characteristics of an object allow discriminating it from the other objects in the list.
The interaction of visual and linguistic saliency during syntactic ambiguity resolution
Authors: Coco Moreno I. , Keller Frank
Published: August 2014

Psycholinguistic research using the visual world paradigm has shown that the processing of sentences is constrained by the visual context in which they occur. Recently, there has been growing interest in the interactions observed when both language and vision provide relevant information during sentence processing. In three visual world experiments on syntactic ambiguity resolution, we investigate how visual and linguistic information influence the interpretation of ambiguous sentences. We hypothesize that (1) visual and linguistic information both constrain which interpretation is pursued by the sentence processor, and (2) the two types of information act upon the interpretation of the sentence at different points during processing. In Experiment 1, we show that visual saliency is utilized to anticipate the upcoming arguments of a verb. In Experiment 2, we operationalize linguistic saliency using intonational breaks and demonstrate that these give prominence to linguistic referents. These results confirm prediction (1). In Experiment 3, we manipulate visual and linguistic saliency together and find that both types of information are used, but at different points in the sentence, to incrementally update its current interpretation. This finding is consistent with prediction (2). Overall, our results suggest an adaptive processing architecture in which different types of information are used when they become available, optimizing different aspects of situated language processing.
Orienting of Attention: Then and Now
Authors: Posner Michael I.
Published: August 2014

It is nearly 35 years since I gave the 7th Sir Frederick Bartlett lecture at Oxford University. This was published as a paper entitled “Orienting of attention in the quarterly journal”. The topic was then primarily in psychology, but now equally often in neuroscience. This paper summarizes the background of the reaction time methods used in the original paper and findings that emerged later on the sensory consequences of orienting, mainly in the visual system. It then discusses the brain network that is the source of the sensory amplification and other brain networks that are involved in attention. Next, it reviews studies of the development of attentional networks in early life. Finally, it indicates how the new tools available to explore the human brain can lead to further progress.
Frameshift alignment: statistics and post-genomic applications
Authors: Sheetlin Sergey L. , Park Yonil , Frith Martin C. , Spouge John L.
Published: August 2014

Motivation: The alignment of DNA sequences to proteins, allowing for frameshifts, is a classic method in sequence analysis. It can help identify pseudogenes (which accumulate mutations), analyze raw DNA and RNA sequence data (which may have frameshift sequencing errors), investigate ribosomal frameshifts, etc. Often, however, only ad hoc approximations or simulations are available to provide the statistical significance of a frameshift alignment score.

Results: We describe a method to estimate statistical significance of frameshift alignments, similar to classic BLAST statistics. (BLAST presently does not permit its alignments to include frameshifts.) We also illustrate the continuing usefulness of frameshift alignment with two ‘post-genomic’ applications: (i) when finding pseudogenes within the human genome, frameshift alignments show that most anciently conserved non-coding human elements are recent pseudogenes with conserved ancestral genes; and (ii) when analyzing metagenomic DNA reads from polluted soil, frameshift alignments show that most alignable metagenomic reads contain frameshifts, suggesting that metagenomic analysis needs to use frameshift alignment to derive accurate results.

Availability and implementation: The statistical calculation is available in FALP ( http://www.ncbi.nlm.nih.gov/CBBresearch/Spouge/html_ncbi/html/index/software.html ), and giga-scale frameshift alignment is available in LAST ( http://last.cbrc.jp/falp ).

Contact:  spouge@ncbi.nlm.nih.gov or martin@cbrc.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations
Authors: Keane Michael , Craig Thomas , Alföldi Jessica , Berlin Aaron M. , Johnson Jeremy , Seluanov Andrei , Gorbunova Vera , Di Palma Federica , Lindblad-Toh Kerstin , Church George M. , de Magalhães João Pedro
Published: August 2014

Motivation: The naked mole rat ( Heterocephalus glaber ) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs.

Results: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat’s extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource ( http://www.naked-mole-rat.org ), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species.

Availability and implementation: The Naked Mole Rat Genome Resource is freely available online at http://www.naked-mole-rat.org . This resource is open source and the source code is available at https://github.com/maglab/naked-mole-rat-portal .

Contact:  jp@senescence.info
Protein–protein binding affinity prediction from amino acid sequence
Authors: Yugandhar K. , Gromiha M. Michael
Published: August 2014

Motivation: Protein–protein interactions play crucial roles in many biological processes and are responsible for smooth functioning of the machinery in living organisms. Predicting the binding affinity of protein–protein complexes provides deep insights to understand the recognition mechanism and identify the strong binding partners in protein–protein interaction networks.

Results: In this work, we have collected the experimental binding affinity data for a set of 135 protein–protein complexes and analyzed the relationship between binding affinity and 642 properties obtained from amino acid sequence. We noticed that the overall correlation is poor, and the factors influencing affinity depends on the type of the complex based on their function, molecular weight and binding site residues. Based on the results, we have developed a novel methodology for predicting the binding affinity of protein–protein complexes using sequence-based features by classifying the complexes with respect to their function and predicted percentage of binding site residues. We have developed regression models for the complexes belonging to different classes with three to five properties, which showed a correlation in the range of 0.739–0.992 using jack-knife test. We suggest that our approach adds a new aspect of biological significance in terms of classifying the protein–protein complexes for affinity prediction.

Availability and implementation: Freely available on the Web at http://www.iitm.ac.in/bioinfo/PPA_Pred/

Contact:  gromiha@iitm.ac.in

Supplementary information:  Supplementary data are available at Bioinformatics online.
Human structural proteome-wide characterization of Cyclosporine A targets
Authors: Hu Gang , Wang Kui , Groenendyk Jody , Barakat Khaled , Mizianty Marcin J. , Ruan Jishou , Michalak Marek , Kurgan Lukasz
Published: August 2014

Motivation: Off-target interactions of a popular immunosuppressant Cyclosporine A (CSA) with several proteins besides its molecular target, cyclophilin A, are implicated in the activation of signaling pathways that lead to numerous side effects of this drug.

Results: Using structural human proteome and a novel algorithm for inverse ligand binding prediction, ILbind, we determined a comprehensive set of 100+ putative partners of CSA. We empirically show that predictive quality of ILbind is better compared with other available predictors for this compound. We linked the putative target proteins, which include many new partners of CSA, with cellular functions, canonical pathways and toxicities that are typical for patients who take this drug. We used complementary approaches (molecular docking, molecular dynamics, surface plasmon resonance binding analysis and enzymatic assays) to validate and characterize three novel CSA targets: calpain 2, caspase 3 and p38 MAP kinase 14. The three targets are involved in the apoptotic pathways, are interconnected and are implicated in nephrotoxicity.

Contact:  lkurgan@ece.ualberta.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Merging of multi-string BWTs with applications
Authors: Holt James , McMillan Leonard
Published: August 2014

Motivation : The throughput of genomic sequencing has increased to the point that is overrunning the rate of downstream analysis. This, along with the desire to revisit old data, has led to a situation where large quantities of raw, and nearly impenetrable, sequence data are rapidly filling the hard drives of modern biology labs. These datasets can be compressed via a multi-string variant of the Burrows–Wheeler Transform (BWT), which provides the side benefit of searches for arbitrary k -mers within the raw data as well as the ability to reconstitute arbitrary reads as needed. We propose a method for merging such datasets for both increased compression and downstream analysis.

Results : We present a novel algorithm that merges multi-string BWTs in O(LCS×N) time where LCS is the length of their longest common substring between any of the inputs, and N is the total length of all inputs combined (number of symbols) using O(N×log2(F)) bits where F is the number of multi-string BWTs merged. This merged multi-string BWT is also shown to have a higher compressibility compared with the input multi-string BWTs separately. Additionally, we explore some uses of a merged multi-string BWT for bioinformatics applications.

Availability and implementation : The MSBWT package is available through PyPI with source code located at https://code.google.com/p/msbwt/ .

Contact : holtjma@cs.unc.edu
Personality Disorders
Authors: Caligor Eve , Yeomans Frank , Levin Ze’ev
Published: August 2014

This chapter discusses the personality disorders. Patients with personality disorders exhibit enduring patterns of behavior that are maladaptive, inflexible, and pervasive. These patients experience difficulty in three core domains of personality functioning: sense of self, interpersonal relationships, and affect regulation. Patients with the cluster A personality disorders (paranoid, schizoid, and schizotypal) tend to suffer profound compromise of functioning. Features that are shared by many patients with the cluster B disorders (borderline, narcissistic, antisocial, and histrionic) include emotional reactivity, poor impulse control, and an unclear sense of identity. Patients with borderline, narcissistic, and antisocial personality disorders are also often characterized by high levels of aggression, whereas patients with histrionic personality disorder share a more favorable prognosis with the cluster C personality disorders (avoidant, dependent, and obsessive-compulsive). Psychotherapy is the backbone of treatment for the personality disorders.
Oxford Handbook for the Foundation Programme
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

The Oxford Handbook for the Foundation Programme returns for a new edition with clear and thorough clinical guidance and honest advice to help you excel in your first two years as a doctor. This new online edition has been fully updated in line with the latest guidelines from NICE, Resuscitation Council UK, and the British Thoracic Society among others. It gives you practical, step-by-step guidance on everything from neurological to gastroenterological presentations. Emergency presentations are highlighted in red and indexed to give you fast access to the information you need. This edition also includes a fully revised chapter on pharmacopeia with references to the British National Formulary, as well as chapters on practical procedures and interpreting results. It’s also a unique resource for things they don't teach you at medical school about being a doctor and life on the wards. The authors have drawn on their own experiences and careful research to help you understand issues ranging from your pay and pension, stress and workplace relations, paperwork, and career development.
Being a doctor
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

The Foundation Programme

The Foundation
Programme

Applying to the
Foundation Programme

The FP curriculum and
assessment

Starting as an F1

Before you start

Your first day

Occupational
health

What to carry

How to be an F1

Getting organised

Being efficient

Communication

Patient-centred
care

Communication and
conduct...
Life on the wards
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

The medical team

The multidisciplinary
team

Daily ward duties

Ward rounds

Being on-call

Night shifts

Writing in the
notes

Common symbols in the
notes

Anatomical terms and
planes

Forms

Discharge summaries
(TTOs/TTAs)

Fitness to work
notes

Referrals

Referral letters

Investigation
requests

Radiology

Common ward dilemmas...
Resuscitation
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

Early warning scores

Peri-arrest

In-hospital
resuscitation

Advanced Life Support
(ALS)

Arrest equipment and
tests

Advanced Trauma Life Support
(ATLS)

Paediatric Basic Life
Support

Newborn Life Support
(NLS)

Obstetric arrest

of the ‘unwell’ patient has repeatedly been shown to improve outcome. Identification
of such patients allows suitable changes in management, including early involvement of
critical care teams or transfer to critical care areas (HDU/ICU) where necessary....
Endocrinology
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

Hypoglycaemia
emergency

Hypoglycaemia

Hyperglycaemia
emergency

Hyperglycaemia

Sliding scales

Diabetes mellitus

Pituitary axis

Adrenal disease

Thyroid disease

Call for senior help early
if patient deteriorating.

• Blood glucose is normally >3.5mmol/l

• Poorly controlled diabetics can have symptoms of
hypoglycaemia with a glucose >3.5mmol/l.

• Protect airway...
Procedures
Authors: Raine Tim , Dawson James , Sanders Stephan , Eccles Simon
Published: August 2014

Practical procedures

Laboratories

Achievement of Core
Foundation Skills

Blood and injections

Taking blood
(venepuncture)

Femoral stab

Blood tubes

IV cannulation

Taking blood in
children

Arterial blood gas
(ABG)

SC/IM injections

IV injections

Cardiology

ECGs and cardiac
monitors

Exercise tolerance
test

Chemical cardioversion
(adenosine)

Cardioversion and
defibrillation...
Bacillus invictae sp. nov., isolated from a health product
Authors: Branquinho Raquel , Sousa Clara , Osório Hugo , Meirinhos-Soares Luís , Lopes João , Carriço João A. , Busse Hans-Jürgen , Abdulmawjood Amir , Klein Günter , Kämpfer Peter , Pintado Manuela E. , Peixe Luísa V.
Published: August 2014

A Gram-positive, rod-shaped, endospore-forming

Bacillus

isolate, Bi.FFUP1
T, recovered in Portugal from a health product was subjected to a polyphasic study and compared with the type strains of

Bacillus pumilus

,

Bacillus safensis

,

Bacillus altitudinis

and

Bacillus xiamenensis

, the phenotypically and genotypically most closely related species. Acid production from cellobiose, d-glucose and d-mannose and absence of acid production from d-arabinose, erythritol, inositol, maltose, mannitol, raffinose, rhamnose, sorbitol, starch and l-tryptophan discriminated this new isolate from the type strains of the most closely related species. Additionally, a significant different protein and carbohydrate signature was evidenced by spectroscopic techniques, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Fourier transform IR spectroscopy with attenuated total reflectance. Using a chemometric approach, the score plot generated by principal component analysis clearly delineated the isolate as a separate cluster. The quinone system for strain Bi.FFUP1
T comprised predominantly menaquinone MK-7 and major polar lipids were diphosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. Strain Bi.FFUP1
T showed ≥99 % 16S rRNA gene sequence similarity to

B. safensis

FO-036bT,

B. pumilus

(7061T and SAFR-032),

B. altitudinis

41KF2bT and

B. xiamenensis

HYC-10T. Differences in strain Bi.FFUP1
T
gyrB and rpoB sequences in comparison with the most closely related species and DNA–DNA hybridization experiments with Bi.FFUP1
T and

B. pumilus

ATCC 7061T,

B. safensis

FO-036bT,

B. altitudinis

41KF2bT and

B. xiamenensis

HYC-10T gave relatedness values of 39.6 % (reciprocal 38.0 %), 49.9 % (reciprocal 42.9 %), 61.9 % (reciprocal 52.2 %) and 61.7 % (reciprocal 49.2 %), respectively, supported the delineation of strain Bi.FFUP1
T as a representative of a novel species of the genus

Bacillus

, for which the name

Bacillus

invictae sp. nov. is proposed, with strain Bi.FFUP1
T ( = DSM 26896T = CCUG 64113T) as the type strain.
Local Fields of the Hippocampus: More than Meets the Eye
Authors: Agarwal Gautam
Published: August 2014

A standard methodology in systems neuroscience is to establish correlations between the brain and the world. These correlations have been robustly observed when probing the activity of single neurons. For example, there are cells that activate vigorously when subjects are presented with images of certain celebrities (e.g. the “Jennifer Aniston” neuron, Quiroga et al., 2005). While single neuron measurements provide remarkable insights into the functional specificity of different brain areas, it remains unclear how single cell activity arises from, and contributes to, the collective activity of brain networks. New technologies allow for the simultaneous recording of spikes from hundreds of cells, yet we are still far from observing entire neuronal circuits in action.

An alternative approach in monitoring neuronal populations is to measure local field potentials (LFPs). These potentials arise from the coordinated activity of thousands of nearby neurons. LFPs often exhibit oscillations of various frequencies, which correlate with different states of awareness, such as alertness, relaxation, or drowsiness. However, establishing correlations between LFPs and specific behavioral events can be challenging, because the contributions of different neurons to the LFP usually cannot be distinguished. In this chapter, we examine LFPs recorded from the rat hippocampus. At first glance, these LFPs appear to bear little relation to the subject’s changing environment. However, through appropriate signal processing, we find that carried in the structure of the LFP is a remarkably precise stream of information (Agarwal et al., 2014).
Neuronal control of locomotor handedness in Drosophila
Authors: Buchanan Sean M. , Kain Jamey S. , de Bivort Benjamin L.
Published: August 2014

Handedness in humans – better performance using either the left or right hand – is personally familiar, moderately heritable1, and regulated by many genes2, including those involved in general body symmetry3. But behavioral handedness, i.e. lateralization, is a multifaceted phenomenon. For example, people display clockwise or counter-clockwise biases in their walking behavior that is uncorrelated to their hand dominance4,5, and lateralized behavioral biases have been shown in species as disparate as mice (paw usage6), octopi (eye usage7), and tortoises (side rolled on during righting8). However, the mechanisms by which asymmetries are instilled in behavior are unknown, and a system for studying behavioral handedness in a genetically tractable model system is needed. Here we show thatDrosophila melanogasterflies exhibit striking variability in their left-right choice behavior during locomotion. Very strongly biased "left-handed" and "right-handed" individuals are common in every line assayed. The handedness of an individual persists for its lifetime, but is not passed on to progeny, suggesting that mechanisms other than genetics determine individual handedness. We use theDrosophilatransgenic toolkit to map a specific set of neurons within the central complex that regulates the strength of behavioral handedness within a line. These findings give insights into choice behaviors and laterality in a simple model organism, and demonstrate that individuals from isogenic populations reared under experimentally identical conditions nevertheless display idiosyncratic behaviors.
An analytical approach to bistable biological circuit discrimination using real algebraic geometry
Authors: Siegal-Gaskins Dan , Franco Elisa , Zhou Tiffany , Murray Richard M
Published: August 2014

Biomolecular circuits with two distinct and stable steady states have been identified as essential components in a wide range of biological networks, with a variety of mechanisms and topologies giving rise to their important bistable property. Understanding the differences between circuit implementations is an important question, particularly for the synthetic biologist faced with determining which bistable circuit design out of many is best for their specific application. In this work we explore the applicability of Sturm?s theorem--a tool from 19th-century real algebraic geometry--to comparing ?functionally equivalent? bistable circuits without the need for numerical simulation. We first consider two genetic toggle variants and two different positive feedback circuits, and show how specific topological properties present in each type of circuit can serve to increase the size of the regions of parameter space in which they function as switches. We then demonstrate that a single competitive monomeric activator added to a purely-monomeric (and otherwise monostable) mutual repressor circuit is sufficient for bistability. Finally, we compare our approach with the Routh-Hurwitz method and derive consistent, yet more powerful, parametric conditions. The predictive power and ease of use of Sturm?s theorem demonstrated in this work suggests that algebraic geometric techniques may be underutilized in biomolecular circuit analysis.