bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular principles of human virus protein–protein interactions
Authors: Halehalli Rachita Ramachandra , Nagarajaram Hampapathalu Adimurthy
Published: November 2014

Motivation: Viruses, from the human protein–protein interaction network perspective, target hubs, bottlenecks and interconnected nodes enriched in certain biological pathways. However, not much is known about the general characteristic features of the human proteins interacting with viral proteins (referred to as hVIPs) as well as the motifs and domains utilized by human-virus protein–protein interactions (referred to as Hu-Vir PPIs).

Results: Our study has revealed that hVIPs are mostly disordered proteins, whereas viral proteins are mostly ordered proteins. Protein disorder in viral proteins and hVIPs varies from one subcellular location to another. In any given viral-human PPI pair, at least one of the two proteins is structurally disordered suggesting that disorder associated conformational flexibility as one of the characteristic features of virus–host interaction. Further analyses reveal that hVIPs are (i) slowly evolving proteins, (ii) associated with high centrality scores in human-PPI network, (iii) involved in multiple pathways, (iv) enriched in eukaryotic linear motifs (ELMs) associated with protein modification, degradation and regulatory processes, (v) associated with high number of splice variants and (vi) expressed abundantly across multiple tissues. These aforementioned findings suggest that conformational flexibility, spatial diversity, abundance and slow evolution are the characteristic features of the human proteins targeted by viral proteins. Hu-Vir PPIs are mostly mediated via domain–motif interactions (DMIs) where viral proteins employ motifs that mimic host ELMs to bind to domains in human proteins. DMIs are shared among viruses belonging to different families indicating a possible convergent evolution of these motifs to help viruses to adopt common strategies to subvert host cellular pathways.

Availability and implementation: Hu-Vir PPI data, DDI and DMI data for human–virus PPI can be downloaded from http://cdfd.org.in/labpages/computational_biology_datasets.html.

Contact: han@cdfd.org.in

Supplementary information:  Supplementary data are available at Bioinformatics online.
NucleusJ: an ImageJ plugin for quantifying 3D images of interphase nuclei
Authors: Poulet Axel , Arganda-Carreras Ignacio , Legland David , Probst Aline V. , Andrey Philippe , Tatout Christophe
Published: November 2014

Summary:  NucleusJ is a simple and user-friendly ImageJ plugin dedicated to the characterization of nuclear morphology and chromatin organization in 3D. Starting from image stacks, the nuclear boundary is delimited by combining the Otsu segmentation method with optimization of nuclear sphericity. Chromatin domains are segmented by partitioning the nucleus using a 3D watershed algorithm and by thresholding a contrast measure over the resulting regions. As output, NucleusJ quantifies 15 parameters including shape and size of nuclei as well as intra-nuclear objects and their position within the nucleus. A step-by-step documentation is available for self-training, together with data sets of nuclei with different nuclear organization.

Availability and implementation: Dataset of nuclei is available at https://www.gred-clermont.fr/media/WorkDirectory.zip. NucleusJ is available at http://imagejdocu.tudor.lu/doku.php?id=plugin:stacks:nuclear_analysis_plugin:start.

Contact:  philippe.andrey@versailles.inra.fr and christophe.tatout@univ-bpclermont.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Single-cell transcriptional analysis to uncover regulatory circuits driving cell fate decisions in early mouse development
Authors: Chen Haifen , Guo Jing , Mishra Shital K. , Robson Paul , Niranjan Mahesan , Zheng Jie
Published: November 2014

Motivation: Transcriptional regulatory networks controlling cell fate decisions in mammalian embryonic development remain elusive despite a long time of research. The recent emergence of single-cell RNA profiling technology raises hope for new discovery. Although experimental works have obtained intriguing insights into the mouse early development, a holistic and systematic view is still missing. Mathematical models of cell fates tend to be concept-based, not designed to learn from real data. To elucidate the regulatory mechanisms behind cell fate decisions, it is highly desirable to synthesize the data-driven and knowledge-driven modeling approaches.

Results: We propose a novel method that integrates the structure of a cell lineage tree with transcriptional patterns from single-cell data. This method adopts probabilistic Boolean network (PBN) for network modeling, and genetic algorithm as search strategy. Guided by the ‘directionality’ of cell development along branches of the cell lineage tree, our method is able to accurately infer the regulatory circuits from single-cell gene expression data, in a holistic way. Applied on the single-cell transcriptional data of mouse preimplantation development, our algorithm outperforms conventional methods of network inference. Given the network topology, our method can also identify the operational interactions in the gene regulatory network (GRN), corresponding to specific cell fate determination. This is one of the first attempts to infer GRNs from single-cell transcriptional data, incorporating dynamics of cell development along a cell lineage tree.

Availability and implementation: Implementation of our algorithm is available from the authors upon request.

Contact:  zhengjie@ntu.edu.sg

Supplementary information:  Supplementary data are available at Bioinformatics online.
Multilevel regularized regression for simultaneous taxa selection and network construction with metagenomic count data
Authors: Liu Zhenqiu , Sun Fengzhu , Braun Jonathan , McGovern Dermot P.B. , Piantadosi Steven
Published: November 2014

Motivation: Identifying disease associated taxa and constructing networks for bacteria interactions are two important tasks usually studied separately. In reality, differentiation of disease associated taxa and correlation among taxa may affect each other. One genus can be differentiated because it is highly correlated with another highly differentiated one. In addition, network structures may vary under different clinical conditions. Permutation tests are commonly used to detect differences between networks in distinct phenotypes, and they are time-consuming.

Results: In this manuscript, we propose a multilevel regularized regression method to simultaneously identify taxa and construct networks. We also extend the framework to allow construction of a common network and differentiated network together. An efficient algorithm with dual formulation is developed to deal with the large-scale n ≪ m problem with a large number of taxa (m) and a small number of samples (n) efficiently. The proposed method is regularized with a general Lp (p∈[0,2]) penalty and models the effects of taxa abundance differentiation and correlation jointly. We demonstrate that it can identify both true and biologically significant genera and network structures.

Availability and implementation: Software MLRR in MATLAB is available at http://biostatistics.csmc.edu/mlrr/.

Contact:  liuzx@cshs.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Reconceptualizing Successful Aging Among Black Women and the Relevance of the Strong Black Woman Archetype
Authors: Baker Tamara A. , Buchanan NiCole T. , Mingo Chivon A. , Roker Rosalyn , Brown Candace S.
Published: November 2014

Although there are multiple pathways to successful aging, little is known of what it means to age successfully among black women. There is a growing body of literature suggesting that black women experience a number of social challenges (sexism and racism) that may present as barriers to aging successfully. Applying aspects of the Strong Black Women ideal, into theoretical concepts of successful aging, may be particularly relevant in understanding which factors impair or promote the ability of black women to age successfully. The Strong Black Women archetype is a culturally salient ideal prescribing that black women render a guise of self-reliance, selflessness, and psychological, emotional, and physical strength. Although this ideal has received considerable attention in the behavioral sciences, it has been largely absent within the gerontology field. Nevertheless, understanding the dynamics of this cultural ideal may enhance our knowledge while developing an appreciation of the black woman’s ability to age successfully. Rather than summarize the social, physical, and mental health literature focusing on health outcomes of black women, this conceptual review examines the Strong Black Women archetype and its application to the lived experiences of black women and contributions to current theories of successful aging. Focusing on successful aging exclusively among black women enhances our understanding of this group by considering their identity as women of color while recognizing factors that dictate their ability to age successfully.
Modelling the spread and connectivity of waterborne marine pathogens: the case of PaV1 in the Caribbean
Authors: Kough Andrew S. , Paris Claire B. , Behringer Donald C. , Butler Mark J.
Published: November 2014

The PaV1 virus infects spiny lobsters (Panulirus argus) throughout most of the Caribbean, where its prevalence in adult lobsters can reach 17% and where it poses a significant risk of mortality for juveniles. Recent studies indicate that vertical transmission of the virus is unlikely and PaV1 has not been identified in the phyllosoma larval stages. Yet, the pathogen appears subclinically in post-larvae collected near the coast, suggesting that lobster post-larvae may harbour the virus and perhaps have aided in the dispersal of the pathogen. Laboratory and field experiments also confirm the waterborne transmission of the virus to post-larval and early benthic juvenile stages, but its viability in the water column may be limited to a few days. Here, we coupled Lagrangian modelling with a flexible matrix model of waterborne and post-larval-based pathogen dispersal in the Caribbean to investigate how a large area with complex hydrology influences the theoretical spread of disease. Our results indicate that if the virus is waterborne and only viable for a few days, then it is unlikely to impact both the Eastern and Northwestern Caribbean, which are separated by dispersal barriers. However, if PaV1 can be transported between locations by infected post-larvae, then the entire Caribbean becomes linked by pathogen dispersal with higher viral prevalence in the North. We identify possible regions from which pathogens are most likely to spread, and highlight Caribbean locations that function as dispersal “gateways” that could facilitate the rapid spread of pathogens into otherwise isolated areas.
Distribution and habitat preferences of five species of wrasse (Family Labridae) in a Norwegian fjord
Authors: Skiftesvik Anne Berit , Durif Caroline M. F. , Bjelland Reidun M. , Browman Howard I.
Published: November 2014

Wrasse (Labridae) are used widely as cleaner fish to control sea lice infestation in commercial farming of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) in Norway. As a result, there is an intense fishery for wrasse along the Norwegian coast. Little is known of the population ecology of wrasse and, therefore, an evaluation of their distribution, demographics, and habitat preferences was required as a baseline from which to assess the impact of the fishery. We analysed experimental catch data from a 3-year survey carried out in 1997–1999 (before the fishery began) during and after the wrasse spawning season in a Norwegian fjord. Corkwing wrasse (Symphodus melops) was always the most abundant species, ranging from 52 to 68% of the catches. Goldsinny (Ctenolabrus rupestris) and rock cook (Centrolabrus exoletus) were the second most abundant species (up to 30%). Ballan (Labrus bergylta) and cuckoo (Labrus mixtus) wrasse represented <2% of the catches. Rock cook was relatively more abundant at more exposed stations, while corkwing wrasse was characteristic of more sheltered stations. Goldsinny and ballan wrasse both occupied mainly intermediate stations in the more protected areas. Smaller fish were found at the most protected areas, while larger fish were found at the more exposed stations. Sex ratio in goldsinny and rock cook varied significantly from year to year. In corkwing, the sex ratio remained the same each year, and females were always in larger proportion (61–66%). Spawning occurred mainly in June for goldsinny, rock cook, and corkwing wrasse. The fact that species composition and/or size distributions vary considerably over very small distances must be considered in monitoring programmes. Erroneous conclusions about shifts in species composition can easily be made simply because sampling gear are set in slightly different areas.
Endometriotic mesenchymal stem cells exhibit a distinct immune phenotype
Authors: Koippallil Gopalakrishnan Nair Aghila Rani , Pandit Hrishikesh , Warty Neeta , Madan Taruna
Published: November 2014

Endometriosis is a significant debilitating gynecological problem affecting women of the reproductive age group and post-menopause. Recent reports suggest a role for endometriotic mesenchymal stem cells (ectopic MSCs) in the pathogenesis of endometriosis. To investigate the plausible mechanisms leading to the pathogenic behavior of ectopic MSCs, we compared the immunomodulatory properties of eutopic (healthy) and ectopic MSCs. We analyzed MSC phenotypes, differentiation potential, differential gene expression for an array of pattern recognition receptors (PRRs) and pro-inflammatory cytokine release along with markers of migration and angiogenesis among eutopic and ectopic MSCs. Further, alterations in immunosuppressive functions of eutopic and ectopic MSCs were examined by co-culturing them with mitogen-activated allogeneic PBMCs. Transcripts of PRRs such as all Toll-like receptors (TLR1–10), except TLR8, collectins (CL-L1, CL-P1 and CL-K1), NOD-1 and NOD-2 receptors and secreted pro-inflammatory cytokines like IL-6, IFN-γ, vascular endothelial growth factor (VEGF), epidermal growth factor and MCP-1 were significantly up-regulated in ectopic MSCs. The anti-inflammatory cytokine transforming growth factor-β showed significant down-regulation, while IL-10 showed a significant increase in ectopic MSCs. Further, ectopic MSCs showed up-regulated expression for markers of migration and angiogenesis such as matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 and VEGF, respectively. We report here that proliferation of PBMCs was less inhibited upon co-culture with ectopic MSCs compared with eutopic MSCs. The findings suggest that ectopic MSCs with increased levels of TLRs, collectins, pro-inflammatory cytokines and markers of migration and angiogenesis exhibit a distinct immune phenotype compared to eutopic MSCs. This distinct phenotype may be responsible for the reduced immunosuppressive property of ectopic MSCs and may be associated with the pathogenesis of endometriosis.
AKARI infrared camera observations of the 3.3 μm PAH feature in Swift/BAT AGNs
Authors: Castro Angel , Miyaji Takamitsu , Shirahata Mai , Ichikawa Kohei , Oyabu Shinki , Clark David M. , Imanishi Masatoshi , Nakagawa Takao , Ueda Yoshihiro
Published: November 2014

We explore the relationships between the 3.3 μm polycyclic aromatic hydrocarbon (PAH) feature and active galactic nucleus (AGN) properties of a sample of 54 hard X-ray selected bright AGNs, including both Seyfert 1 and Seyfert 2 type objects, using the InfraRed Camera (IRC) on board the infrared astronomical satellite AKARI. The sample is selected from the nine-month Swift/BAT survey in the 14–195 keV band and all of them have measured X-ray spectra at E ≲ 10 keV. These X-ray spectra provide measurements of the neutral hydrogen column density (NH) towards the AGNs. We use the 3.3 μm PAH luminosity (L3.3μm) as a proxy for star-formation activity and hard X-ray luminosity (L14–195 keV) as an indicator of the AGN activity. We search for possible differences in star-formation activity between type 1 (unabsorbed) and type 2 (absorbed) AGNs. We have made several statistical analyses taking the upper limits of the PAH lines into account utilizing survival analysis methods. The results of our log (L14–195 keV) versus log  (L3.3 μm) regression show a positive correlation and the slope for the type 1/unobscured AGNs is steeper than that of type 2/obscured AGNs at a 3 σ level. Our analysis also shows that the circumnuclear star formation is more enhanced in type 2/absorbed AGNs than type 1/unabsorbed AGNs for low X-ray luminosity/low Eddington ratio AGNs, while there is no significant dependence of star-formation activities on the AGN type in the high X-ray luminosities/Eddington ratios.
Dwarf nova EZ Lyncis second visit to instability strip
Authors: Pavlenko Elena P. , Kato Taichi , Sosnovskij Aleksei A. , Andreev Maksim V. , Ohshima Tomohito , Sklyanov Aleksander S. , Bikmaev Ilfan F. , Galeev Almaz I.
Published: November 2014

The analysis of 14 periodograms of EZ Lyn for data spaced over 565 d in 2012–2014 (2–3.5 yr after the 2010 outburst) yielded the existence of a stable signal around 100 cycles/day (c/d) and three signals around 310 c/d, 338 c/d, and 368 c/d (the corresponding periods are 864 s, 279 s, 256 s, and 235 s). We interpret them as independent nonradial pulsations of the white dwarf in EZ Lyn, but the possibility that a linear combination of a frequency of 100 c/d and a harmonic of the orbital period might produce a frequency of 368 c/d also cannot be excluded. The signal at 100 c/d was detected as a transient during the first stay in the instability strip. The period at 338 c/d has been a known nonradial pulsation since EZ Lyn entered the instability strip after the 2010 outburst. We detected the signals around 310 c/d and 368 c/d for the first time. We applied the two-dimensional least absolute shrinkage and selection operator (Lasso) analysis for the first time to explore the behavior of these signals on a time scale of hours in nightly runs of observations having a duration of 6–12 hr. The Lasso analysis revealed the simultaneous existence of all three frequencies (310 c/d, 338 c/d, and 368 c/d) on a majority of nights of observations, but with variable amplitudes and variable drifts of frequencies by 2%–6% on a time scale of ∼ 5–7 hr. The largest drift we detected corresponded to 17.5 s in period in ∼ 5 hr.
Patents and Cumulative Innovation: Causal Evidence from the Courts
*
Authors: Galasso Alberto , Schankerman Mark
Published: November 2014

Cumulative innovation is central to economic growth. Do patent rights facilitate or impede follow-on innovation? We study the causal effect of removing patent rights by court invalidation on subsequent research related to the focal patent, as measured by later citations. We exploit random allocation of judges at the U.S. Court of Appeals for the Federal Circuit to control for endogeneity of patent invalidation. Patent invalidation leads to a 50% increase in citations to the focal patent, on average, but the impact is heterogeneous and depends on characteristics of the bargaining environment. Patent rights block downstream innovation in computers, electronics, and medical instruments, but not in drugs, chemicals, or mechanical technologies. Moreover, the effect is entirely driven by invalidation of patents owned by large patentees that triggers more follow-on innovation by small firms.
Ileal Neobladder With Mucous Plugs as a Cause of Obstructive Acute Kidney Injury Requiring Emergent Hemodialysis
Authors: Singla Montish , Shikha Deep , Lee Sunggeun , Baumstein Donald , Chaudhari Ashok , Carbajal Roger
Published: November 2014

Ileal neobladder is the preferred technique in the management of urinary diversion postradical cystectomy for bladder malignancy. The common complications associated with this procedure are atrophied kidney, chronic pyelonephritis, decreased renal function, ureteroileal or urethral anastomotic site stricture, urinary tract stones, incontinence, and hyperchloremic metabolic acidosis. Mucous plugs are also seen in 2%–3% patients. We present a rare presentation of a patient who required hemodialysis for severe hyperkalemia and acute kidney injury caused by mucous plugging of ileal neobladder.
Implementation of Crew Resource Management: A Qualitative Study in 3 Intensive Care Units
Authors: Kemper Peter F. , van Dyck Cathy , Wagner Cordula , de Bruijne Martine
Published: November 2014

Objectives

Classroom-based crew resource management (CRM) training has been increasingly applied in health care to improve safe patient care. Crew resource management aims to increase participants' understanding of how certain threats can develop as well as provides tools and skills to respond to such threats. Existing literature shows promising but inconclusive results that might be explained by the quality of the implementation. The present research systematically describes the implementation from the perspective of 3 trained intensive care units (ICUs).

Methods

The design of the study was built around 3 stages of implementation: (1) the preparation, (2) the actions after the CRM training, and (3) the plans for the future. To assess all stages in 3 Dutch ICUs, 12 semistructured interviews with implementation leaders were conducted, the End-of-Course Critique questionnaire was administered, and objective measurements consisting of the number and types of plans of action were reported.

Results

The results categorize initiatives that all 3 ICUs successfully launched, including the development of checklists, each using a different implementation strategy. All ICUs have taken several steps to sustain their approach for the foreseeable future. Three similarities between the units were seen at the start of the implementation: (1) acknowledgment of a performance gap in communication, (2) structural time allocated for CRM, and (3) a clear vision on how to implement CRM.

Conclusions

This study shows that CRM requires preparation and implementation, both of which require time and dedication. It is promising to note that all 3 ICUs have developed multiple quality improvement initiatives and aim to continue doing so.
Tissue-specific evolution of protein coding genes in human and mouse
Authors: Kryuchkova-Mostacci Nadezda , Robinson-Rechavi Marc
Published: November 2014

Protein-coding genes evolve at different rates, and the influence of different parameters, from gene size to expression level, has been extensively studied. While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals. Here we investigate these relations further, especially taking in account gene expression in different organs as well as indirect correlations between parameters. We used RNA-seq data from two large datasets, covering 22 mouse tissues and 27 human tissues. Over all tissues, evolutionary rate only correlates weakly with levels and breadth of expression. The strongest explanatory factors of strong purifying selection are GC content, expression in many developmental stages, and expression in brain tissues. While the main component of evolutionary rate is purifying selection, we also find tissue-specific patterns for sites under neutral evolution and for positive selection. We observe fast evolution of genes expressed in testis, but also in other tissues, notably liver, which are explained by weak purifying selection rather than by positive selection.
The Arabidopsis Vacuolar Sorting Receptor1 Is Required for Osmotic Stress-Induced Abscisic Acid Biosynthesis
Authors: Wang Zhen-Yu , Gehring Chris , Zhu Jianhua , Li Feng-Min , Zhu Jian-Kang , Xiong Liming
Published: November 2014

Osmotic stress activates the biosynthesis of the phytohormone abscisic acid (ABA) through a pathway that is rate limited by the carotenoid cleavage enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). To understand the signal transduction mechanism underlying the activation of ABA biosynthesis, we performed a forward genetic screen to isolate mutants defective in osmotic stress regulation of the NCED3 gene. Here, we identified the Arabidopsis (Arabidopsis thaliana) Vacuolar Sorting Receptor1 (VSR1) as a unique regulator of ABA biosynthesis. The vsr1 mutant not only shows increased sensitivity to osmotic stress, but also is defective in the feedback regulation of ABA biosynthesis by ABA. Further analysis revealed that vacuolar trafficking mediated by VSR1 is required for osmotic stress-responsive ABA biosynthesis and osmotic stress tolerance. Moreover, under osmotic stress conditions, the membrane potential, calcium flux, and vacuolar pH changes in the vsr1 mutant differ from those in the wild type. Given that manipulation of the intracellular pH is sufficient to modulate the expression of ABA biosynthesis genes, including NCED3, and ABA accumulation, we propose that intracellular pH changes caused by osmotic stress may play a signaling role in regulating ABA biosynthesis and that this regulation is dependent on functional VSR1.
ABCG26-Mediated Polyketide Trafficking and Hydroxycinnamoyl Spermidines Contribute to Pollen Wall Exine Formation in Arabidopsis
Authors: Quilichini Teagen D. , Samuels A. Lacey , Douglas Carl J.
Published: November 2014

Pollen grains are encased by a multilayered, multifunctional wall. The sporopollenin and pollen coat constituents of the outer pollen wall (exine) are contributed by surrounding sporophytic tapetal cells. Because the biosynthesis and development of the exine occurs in the innermost cell layers of the anther, direct observations of this process are difficult. The objective of this study was to investigate the transport and assembly of exine components from tapetal cells to microspores in the intact anthers of Arabidopsis thaliana. Intrinsically fluorescent components of developing tapetum and microspores were imaged in intact, live anthers using two-photon microscopy. Mutants of ABCG26, which encodes an ATP binding cassette transporter required for exine formation, accumulated large fluorescent vacuoles in tapetal cells, with corresponding loss of fluorescence on microspores. These vacuolar inclusions were not observed in tapetal cells of double mutants of abcg26 and genes encoding the proposed sporopollenin polyketide biosynthetic metabolon (ACYL COENZYME A SYNTHETASE5, POLYKETIDE SYNTHASE A [PKSA], PKSB, and TETRAKETIDE α-PYRONE REDUCTASE1), providing a genetic link between transport by ABCG26 and polyketide biosynthesis. Genetic analysis also showed that hydroxycinnamoyl spermidines, known components of the pollen coat, were exported from tapeta prior to programmed cell death in the absence of polyketides, raising the possibility that they are incorporated into the exine prior to pollen coat deposition. We propose a model where ABCG26-exported polyketides traffic from tapetal cells to form the sporopollenin backbone, in coordination with the trafficking of additional constituents, prior to tapetum programmed cell death.
BRASSINOSTEROID INSENSITIVE2 Interacts with ABSCISIC ACID INSENSITIVE5 to Mediate the Antagonism of Brassinosteroids to Abscisic Acid during Seed Germination inArabidopsis
Authors: Hu Yanru , Yu Diqiu
Published: November 2014

Seed germination and postgerminative growth are regulated by a delicate hormonal balance. Abscisic acid (ABA) represses Arabidopsis thaliana seed germination and postgerminative growth, while brassinosteroids (BRs) antagonize ABA-mediated inhibition and promote these processes. However, the molecular mechanism underlying BR-repressed ABA signaling remains largely unknown. Here, we show that the Glycogen Synthase Kinase 3-like kinase BRASSINOSTEROID INSENSITIVE2 (BIN2), a critical repressor of BR signaling, positively regulates ABA responses during seed germination and postgerminative growth. Mechanistic investigation revealed that BIN2 physically interacts with ABSCISIC ACID INSENSITIVE5 (ABI5), a bZIP transcription factor. Further genetic analysis demonstrated that the ABA-hypersensitive phenotype of BIN2-overexpressing plants requires ABI5. BIN2 was found to phosphorylate and stabilize ABI5 in the presence of ABA, while application of epibrassinolide (the active form of BRs) inhibited the regulation of ABI5 by BIN2. Consistently, the ABA-induced accumulation of ABI5 was affected in BIN2-related mutants. Moreover, mutations of the BIN2 phosphorylation sites on ABI5 made the mutant protein respond to ABA improperly. Additionally, the expression of several ABI5 regulons was positively modulated by BIN2. These results provide evidence that BIN2 phosphorylates and stabilizes ABI5 to mediate ABA response during seed germination, while BRs repress the BIN2-ABI5 cascade to antagonize ABA-mediated inhibition.
Helping Hands for Budding Prospects: ENTH/ANTH/VHS Accessory Proteins in Endocytosis, Vacuolar Transport, and Secretion
Authors: Zouhar Jan , Sauer Michael
Published: November 2014

Coated vesicles provide a major mechanism for the transport of proteins through the endomembrane system of plants. Transport between the endoplasmic reticulum and the Golgi involves vesicles with COPI and COPII coats, whereas clathrin is the predominant coat in endocytosis and post-Golgi trafficking. Sorting of cargo, coat assembly, budding, and fission are all complex and tightly regulated processes that involve many proteins. The mechanisms and responsible factors are largely conserved in eukaryotes, and increasing organismal complexity tends to be associated with a greater numbers of individual family members. Among the key factors is the class of ENTH/ANTH/VHS domain-containing proteins, which link membrane subdomains, clathrin, and other adapter proteins involved in early steps of clathrin coated vesicle formation. More than 30 Arabidopsis thaliana proteins contain this domain, but their generally low sequence conservation has made functional classification difficult. Reports from the last two years have greatly expanded our knowledge of these proteins and suggest that ENTH/ANTH/VHS domain proteins are involved in various instances of clathrin-related endomembrane trafficking in plants. This review aims to summarize these new findings and discuss the broader context of clathrin-dependent plant vesicular transport.
Remodeling American Sentencing: A Ten‐Step Blueprint for Moving Past Mass Incarceration
Authors: Tonry Michael
Published: November 2014

When and if the will to roll back mass incarceration and to create just, fair, and effective sentencing systems becomes manifest, the way forward is clear.

First, three‐strikes, mandatory minimum sentence, and comparable laws should be repealed.

Second, any three‐strikes, mandatory minimum sentence, and comparable laws that are not repealed should be substantially narrowed in scope and severity.

Third, any three‐strikes, mandatory minimum sentence, and comparable laws that are not repealed should be amended to include provisions authorizing judges to impose some other sentence “in the interest of justice.”

Fourth, life‐without‐possibility‐of‐parole laws should be repealed or substantially narrowed.

Fifth, truth‐in‐sentencing laws should be repealed.

Sixth, criminal codes should be amended to set substantially lower maximum sentences scaled to the seriousness of crimes.

Seventh, every state that does not already have one should establish a sentencing commission and promulgate presumptive sentencing guidelines.

Eighth, every state that does not already have one should establish a parole board and every state should establish a parole guidelines system.

Ninth, every state and the federal government should reduce its combined rate of jail and prison confinement to half its 2014 level by 2020.

Tenth, every state should enact legislation making all prisoners serving fixed terms longer than 5 years, or indeterminate terms, eligible for consideration for release at the expiration of 5 years, and making all prisoners 35 years of age or older eligible for consideration for release after serving 3 years.

These proposals are evidence‐based and mostly technocratic. Those calling for prison population targets and reducing the lengths of sentences being served may seem bold to some. Relative to the problems they address, they are modest and partial. Decreasing rates of imprisonment by half in the United States, a country with comparatively low crime rates, to a level that will remain 3 to 3.5 times those of other developed Western countries, can hardly be considered overly ambitious.
Barcoding Neotropical birds: assessing the impact of nonmonophyly in a highly diverse group
Authors: Chaves Bárbara R. N. , Chaves Anderson V. , Nascimento Augusto C. A. , Chevitarese Juliana , Vasconcelos Marcelo F. , Santos Fabrício R.
Published: November 2014

In this study, we verified the power of DNA barcodes to discriminate Neotropical birds using Bayesian tree reconstructions of a total of 7404 COI sequences from 1521 species, including 55 Brazilian species with no previous barcode data. We found that 10.4% of species were nonmonophyletic, most likely due to inaccurate taxonomy, incomplete lineage sorting or hybridization. At least 0.5% of the sequences (2.5% of the sampled species) retrieved from GenBank were associated with database errors (poor‐quality sequences, NuMTs, misidentification or unnoticed hybridization). Paraphyletic species (5.8% of the total) can be related to rapid speciation events leading to nonreciprocal monophyly between recently diverged sister species, or to absence of synapomorphies in the small COI region analysed. We also performed two series of genetic distance calculations under the K2P model for intraspecific and interspecific comparisons: the first included all COI sequences, and the second included only monophyletic taxa observed in the Bayesian trees. As expected, the mean and median pairwise distances were smaller for intraspecific than for interspecific comparisons. However, there was no precise ‘barcode gap’, which was shown to be larger in the monophyletic taxon data set than for the data from all species, as expected. Our results indicated that although database errors may explain some of the difficulties in the species discrimination of Neotropical birds, distance‐based barcode assignment may also be compromised because of the high diversity of bird species and more complex speciation events in the Neotropics.
Modelling animal movement using the Argos satellite telemetry location error ellipse
Authors: McClintock Brett T. , London Joshua M. , Cameron Michael F. , Boveng Peter L.
Published: November 2014

The Argos satellite telemetry system is popular for studying the movement and space use of marine animals. The life histories of marine mammals, in particular, result in a relatively large proportion of inaccurate locations, thus making analysis methods that do not account for location measurement error inappropriate for these data. Using a new Kalman filtering algorithm, Argos now provides locations and estimated error ellipses associated with each satellite fix, but to our knowledge, the location error ellipse has yet to be incorporated into analyses of animal movement or space use.

We first present an observation model utilizing the Argos error ellipse and then demonstrate how this observation model can be combined with a simple three‐dimensional movement model in a state‐space formulation to infer activity budgets and movement characteristics from location and dive data of two species of seal, the bearded seal (Erignathus barbatus) and the Hawaiian monk seal (Monachus schauinslandi). These example data sets are of variable quality and represent species that differ in both space use and latitudinal range relative to the polar orbits of Argos satellites. We also compare the results from our error ellipse model with those from an approximate (isotropic) error circle model.

We found the error circle to be a crude approximation of the actual anisotropic error ellipse for the higher quality bearded seal data, but inferences from the lower quality Hawaiian monk seal data were more robust to the choice of observation model. In both examples, we found the theoretical bivariate normal distribution corresponding to the error ellipse often failed to adequately explain the most extreme location outliers.

In practice, we suspect the inferential consequences of using traditional isotropic location quality classes or other crude approximations in lieu of the error ellipse will be largely case‐dependent. We support the Argos recommendation that practitioners wishing to more properly account for location measurement error utilize the error ellipse in analyses. However, the continued presence of outliers using the new algorithm suggests practitioners should consider using a fat‐tailed distribution derived from the error ellipse (e.g. bivariate t‐distribution) or filtering extreme outliers during data pre‐processing.
Big answers from small worlds: a user's guide for protist microcosms as a model system in ecology and evolution
Authors: Altermatt Florian , Fronhofer Emanuel A. , Garnier Aurélie , Giometto Andrea , Hammes Frederik , Klecka Jan , Legrand Delphine , Mächler Elvira , Massie Thomas M. , Pennekamp Frank , Plebani Marco , Pontarp Mikael , Schtickzelle Nicolas , Thuillier Virginie , Petchey Owen L.
Published: November 2014

Laboratory microcosm experiments using protists as model organisms have a long tradition and are widely used to investigate general concepts in population biology, community ecology and evolutionary biology. Many variables of interest are measured in order to study processes and patterns at different spatiotemporal scales and across all levels of biological organization. This includes measurements of body size, mobility or abundance, in order to understand population dynamics, dispersal behaviour and ecosystem processes. Also, a variety of manipulations are employed, such as temperature changes or varying connectivity in spatial microcosm networks.

Past studies, however, have used varying methods for maintenance, measurement, and manipulation, which hinders across‐study comparisons and meta‐analyses, and the added value they bring. Furthermore, application of techniques such as flow cytometry, image and video analyses, andin situenvironmental probes provide novel and improved opportunities to quantify variables of interest at unprecedented precision and temporal resolution.

Here, we take the first step towards a standardization of well‐established and novel methods and techniques within the field of protist microcosm experiments. We provide a comprehensive overview of maintenance, measurement and manipulation methods. An extensive supplement contains detailed protocols of all methods, and these protocols also exist in a community updateable online repository.

We envision that such a synthesis and standardization of methods will overcome shortcomings and challenges faced by past studies and also promote activities such as meta‐analyses and distributed experiments conducted simultaneously across many different laboratories at a global scale.
Impact of corneal cross‐linking on topical drug penetration in humans
Authors: Tappeiner Christoph , Tschopp Markus , Schuerch Kaspar , Frueh Beatrice E.
Published: November 2014

Purpose

To analyse the influence of corneal cross‐linking (CXL) with ultraviolet‐A (UV‐A) and riboflavin on drug permeability in human subjects.

Methods

Keratoconus patients (n = 23; mean age 26.9 ± 5.8 years) undergoing a standard CXL procedure with UV‐A (5.4 J/cm2, 30 min) and riboflavin in one eye were included in the study. The pupillary diameter, measured before and every 3 min for 30 min after the topical application of one drop of 2% pilocarpine, was used as an indirect measure of the corneal permeability. The pupillary diameter was measured with an infrared pupillometer device before (baseline) and 4 months after CXL.

Results

Prior to pilocarpine application, no significant difference in the pupillary diameter was detected before CXL and 4 months later. The mean decrease in the pupillary diameter after the application of pilocarpine was similar at baseline and the 4‐month follow‐up visit: mean decreases of 3.9 and 3.7 mm were observed 30 min after pilocarpine application, respectively (p > 0.05).

Conclusions

No significant influence of CXL on the corneal penetration of topically applied pilocarpine was observed in this clinical study.
High expression of metadherin correlates with malignant pathological features and poor prognostic significance in papillary thyroid carcinoma
Authors: Li Wen‐Fang , Wang Gen , Zhao Zong‐Bin , Liu Chang‐An
Published: November 2014

Background

Metadherin (MTDH) protein, also called astrocyte elevated gene‐1 (AEG‐1) is over expressed in a variety of malignant tumours, and is closely related to tumour invasion and the poor prognosis.

Objective

This study tries to explore the clinical pathological significance of MTDH expression in a large cohort of patients with PTC.

Design and patients

Immunohistochemistry was used to detect MTDH expression in 156 cases of PTC, 6 cases of anaplastic thyroid carcinoma (ATC), 10 cases of multinodular goitre (MNG) and 10 cases of thyroid adenoma tissues who received a thyroid operation between June 2003 and July 2008.

Measurements

Clinical pathological data of 156 cases of PTC were analysed according to MTDH expression. The Kaplan–Meier method was used to plot survival curves and log‐rank test to compare the postoperative survival results. The prognostic meaning of MTDH expression in PTC was evaluated by Cox regression analysis.

Results

The positive expression rates of MTDH in PTC and ATC tissues were 37·2% (58/156) and 50% (3/6), respectively, and MTDH positive expression rates were both 10% (1/10) in MNG and thyroid adenoma tissues. High MTDH expression in PTC was associated with larger tumour size (P = 0·030), high rates of lymph node (P = 0·041) and distant metastasis (P = 0·028), but no relation with the patient age, gender, tumour multicenter, extrathyroid invasion and tumour grade. High MTDH expression was associated with recurrence‐free survival (RFS) and disease‐specific survival rate (DSS) (P = 0·014, P = 0·001, respectively). Cox regression analysis showed that high MTDH expression was independent prognostic indicators for RFS and DSS in patients with PTC (P = 0·023 and P = 0·035, respectively).

Conclusion

High MTDH expression in PTC might play an important role in tumour growth and metastasis, and targeting MTDH treatment might have potential therapeutic value for patients with PTC.
Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy
Authors: Vieira Neto Leonardo , Wildemberg Luiz Eduardo , Moraes Aline B. , Colli Leandro M. , Kasuki Leandro , Marques Nelma Verônica , Gasparetto Emerson L. , de Castro Margaret , Takiya Christina Maeda , Gadelha Mônica R.
Published: November 2014

Objectives

To determine the dopamine receptor subtype 2 (DR2) mRNA levels and protein expression and to evaluate the effect of adjuvant cabergoline therapy on tumour volume (TV) in patients with postoperative residual nonfunctioning pituitary adenoma (NFPA).

Methods

The mRNA expression was quantified by real‐time RT‐PCR (TaqMan®), and protein expression was evaluated by immunohistochemistry. Tumours were classified according to the percentage of immunostained cells for DR2 as scores 1 (<50% of stained cells) or 2 (≥50%). Cabergoline was started at least 6 months after surgery in nine patients with residual tumours (3 mg/week). The cabergoline effect was prospectively evaluated by magnetic resonance imaging using three‐dimensional volume calculation. TV reduction >25% was considered significant.

Results

The DR2 mRNA expression was variable but was observed in 100% of the samples (N = 20). DR2 protein expression was also observed in all the tumours (N = 34). Twenty‐nine tumours (85%) were classified as score 2. The median DR2 mRNA expression was higher in the tumours classified as score 2 compared with score 1 (P = 0·007). TV reduction with cabergoline therapy was observed in 67% of the patients (6/9). The median TV before and after 6 months of treatment was 1·90 cm3 (0·61–8·74) and 1·69 cm3 (0·36–4·20) [P = 0·02], respectively.

Conclusion

In conclusion, DR2 is expressed in all adenomas and the majority of the patients in this study displayed tumour shrinkage on cabergoline (CAB) therapy. Thus, CAB might be useful in adjuvant therapy in NFPA patients with residual tumours after surgery.
Bone resorption in different parts of the mandible in patients restored with an implant overdenture. A retrospective radiographic analysis
Authors: Kremer Urs , Schindler Sven , Enkling Norbert , Worni Andreas , Katsoulis Joannis , Mericske‐Stern Regina
Published: November 2014

Aim

This study investigated the pattern of resorption of the mandibular ridge under implant‐supported overdentures.

Material and methods

Files of 60 patients were available for analysis (45 women and 15 men, mean age at the time of the follow‐up 76.5 ± 8.5 years, 54 patients restored with bars, 6 with ball anchors). A baseline was defined by different stable landmarks and quartered. Linear measurements from this baseline at different clinical relevant sites approximately at: (i) the area close to the mental foramen/close to the implant, (ii) the chewing center, and (iii) the distal edge of the denture flange were carried out on rotational tomograms (OPTs). The OPTs were taken after prosthetic restoration and at an individual follow‐up time (mean 11 ± 4.75 years). The known implant length served to scale each measurement to avoid any distortion errors.

Results

The resorption rate showed a high individual variation, but among the three sites, the difference was highly significant. Median values of site (i) left = −0.07 mm/right = +0.05 mm, site (ii) left = −0.60 mm/right = −0.55 mm, and site (iii) left = −1.58 mm/right = −2.01 mm.

Conclusions

The load of the distal flange of a mandibular implant overdenture increases bone resorption as a local factor, whereas implants may help to prevent resorption in the neighboring bone. An individual‐adapted follow‐up protocol should be established for each patient restored with an implant overdenture.
Activating Cannabinoid Receptor 2 Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis Via Activation of Autophagy and Inhibiting NLRP3 Inflammasome
Authors: Shao Bo‐Zong , Wei Wei , Ke Ping , Xu Zhe‐Qi , Zhou Jv‐Xiang , Liu Chong
Published: November 2014

Aims

Activation of cannabinoid receptor 2 (CB2R) has been reported to ameliorate the pathogenesis of experimental autoimmune encephalomyelitis (EAE). In this study, we examined whether autophagy is involved in the beneficial effect of CB2R on EAE and explored the mechanism with a focus on inflammasome activation.

Methods

EAE severity was analyzed with clinical score and histological score stained by hematoxylin and eosin or luxol fast blue in spinal cord. Immunoblot analysis was conducted to detect proteins of NOD‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome‐related caspase‐1 (Casp‐1) and the maturation of interleukin (IL)‐1β as well as autophagy‐related light chain 3 (LC3), and Beciln 1 both in vivo and in vitro. Reverse transcription and real‐time PCR were used to detect mRNA of NLRP3, IL‐1β and Casp‐1. Autophagy‐related gene 5 (ATG5)‐specific siRNA was transiently transfected in BV2 microglia, and immunofluorescence staining was carried out to detect the expression of NLRP3, caspase recruitment domain (ASC), and pro‐caspase‐1.

Results

The current data indicated that deleting CB2R decreased the expression of LC3‐II/LC3‐I ratio, Beclin 1 and increased caspase‐1 activation and IL‐1β production in the spinal cord of EAE mice, whereas activation of CB2R with a specific agonist HU‐308 induced inverse effects. Further study indicated that HU‐308 could promote autophagy and inhibit expression and activation of NLRP3 inflammasome in BV2 microglia. Blocking autophagy by ATG5‐specific siRNA dismissed the effort of CB2R in mediating NLRP3 inflammasome in vitro.

Conclusion

Collectively, our results demonstrated for the first time that CB2R plays a protective role in EAE through promoting autophagy and inhibiting NLRP3 inflammasome activation.