bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximal Roux‐en‐Y Gastric Bypass Alters Drug Absorption Pattern But Not Systemic Exposure of CYP3A4 and P‐glycoprotein Substrates
Authors: Chan Lingtak‐Neander , Lin Yvonne S. , Tay‐Sontheimer Jessica C. , Trawick Dorothy , Oelschlager Brant K. , Flum David R. , Patton Kristen K. , Shen Danny D. , Horn John R.
Published: March 2015

Study Objectives

To evaluate the effect of Roux‐en‐Y gastric bypass surgery (RYGB) on the pharmacokinetics of midazolam (a CYP3A4 substrate) and digoxin (a P‐glycoprotein substrate).

Design

Prospective, nonblinded, longitudinal, single‐dose pharmacokinetic study in three phases: presurgery baseline and postoperative assessments at 3 and 12 months.

Patients

Twelve obese patients meeting current standards for bariatric surgery.

Measurements and Main Results

At each study visit, patients received a single dose of oral digoxin and midazolam at 8 a.m. Blood samples were collected at regular intervals for 24 hours after dosing. Continuous 12‐lead electrocardiogram (EKG), heart rate, blood pressure, and respiratory rate were monitored, and pharmacokinetic parameters from the three visits were compared. The peak plasma concentration (Cmax) of midazolam increased by 66% and 71% at 3‐ and 12‐month post‐RYGB (p=0.017 and p=0.001, respectively), whereas the median time to peak concentration (Tmax) was reduced by 50%. The mean Cmax for 1′‐hydroxymidazolam increased by 87% and 80% at 3 and 12 months (p=0.001 and p<0.001, respectively). However, neither the area under the concentration‐time curve (AUC) for midazolam nor the metabolite‐to‐parent AUC ratio changed significantly over time. For digoxin, the median Tmax decreased from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months, respectively. The mean AUC for digoxin, heart rate, and EKG patterns were similar across the three study phases.

Conclusion

Contemporary proximal RYGB increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin. The Cmax of a CYP3A4 substrate with a high extraction ratio was substantially increased after RYGB.
Peptides from the inside of the antibodies are active against infectious agents and tumours
Authors: Ciociola Tecla , Giovati Laura , Sperindè Martina , Magliani Walter , Santinoli Claudia , Conti Giorgio , Conti Stefania , Polonelli Luciano
Published: March 2015

Synthetic peptides, representative of sequences related to the complementarity determining regions and constant region of antibodies, proved to exert in vitro, ex vivo and/or in vivo antimicrobial, antiviral, anti‐tumour and/or immunomodulatory activities, conceivably mediated by different mechanisms of action and regardless of the specificity and isotype of the belonging immunoglobulin. Antibody‐derived peptides can show intrinsic properties of self‐aggregation in β structures, able to assemble on molecular targets and dissociate spontaneously, leading to the formation of hydrogels. Whilst the self‐assembled state may provide protection against proteases and the slow kinetic of dissociation assures a release of the active form over time, the receptor affinity is responsible for targeted delivery. Peptides derived from single amino acid substitution of bioactive antibody fragments, adopted as surrogates of natural point mutations, displayed further differential biological activities. Overall, these observations allow to envisage that antibodies could represent an unlimited source of new anti‐infective and anti‐tumour peptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Agenesis of right upper lobe of lung
Authors: Kuo Chiu‐Ping , Lu Yen‐Ta , Lin Rong‐Luh
Published: March 2015

Agenesis of the right upper lobe of the lung is a very uncommon congenital anomaly and may be referred to chest clinics in adulthood for an incidental finding of abnormal chest radiograph. The presentations of chest radiograph may imitate many common situations such as right upper lobe collapse presenting as an ipsilateral shifting of the mediastinum or elevation of the right hemidiaphragm due to eventration or subdiaphragmatic lesions. A chest computed tomography is considered the most conclusive examination used to diagnose lung agenesis. Three‐dimensional reconstructed images can be particularly helpful in delineating abnormalities of the bronchi and associated arterial and venous structures. We describe here a young woman with allergic rhinitis and bronchial asthma since her early childhood. She was referred to our clinic for an incidental finding of abnormal chest radiograph after a school health checkup. Right upper lobe atelectasis or intra‐abdominal lesions were initially suspected. After a thorough image study, she was diagnosed as a case of agenesis of the right upper lobe. Our report emphasizes the importance that a high index of suspicion and adequate image investigation are necessary to diagnose congenital lung anomalies.
1‐Aza‐15‐Crown‐5 Functionalized Graphene Oxide for 2D Graphene‐Based Li+‐ion Conductor
Authors: Banerjee Moutusi , Gupta Abhisek , Saha Shyamal K. , Chakravorty Dipankar
Published: March 2015

Attachment of Li+ ion on graphene surface to realize Li+‐ion conductor is a real challenge because of the weak interaction between the ions and the functional groups of graphene oxide; although, a large number of theoretical results are already available in the literature. To overcome this problem, graphene oxide is functionalized by 1‐aza‐15‐crown‐5, the cage‐like structure containing four oxygens that can bind Li+ ion through electrostatic interaction. Li+ migration on graphene surface has been investigated using ac relaxation mechanism. Perfect Debye‐type relaxation behavior with β (relaxation exponent) value ≈1 resulting from single ion is observed. The activation energy of Li+ migration arising due to cation‐π interaction is found to be 0.37 eV, which agrees well with recently reported theoretical value. It is believed that this study will help to design isolated ion conductors for Li+‐ion battery.
Obstacles to wastewater reuse: an overview
Authors: Duong Kimberly , Saphores Jean‐Daniel M.
Published: March 2015

With growing water scarcity worldwide, reclaimed wastewater is an increasingly attractive option for meeting household water demand, especially in urban areas. However, reluctance by households to use treated wastewater persists. In this article, we discuss the ‘yuck factor,’ health risk concerns, and cost considerations, which are key obstacles to wastewater reuse by households. We then summarize successful and unsuccessful case studies of wastewater reuse around the world. Reasons for the success (or failure) of each case study draws upon unique contextual, historical, and cultural circumstances. Direct potable reuse—where purified wastewater is added to the potable water supply directly—is rare; most successful projects are nonpotable wastewater reuse schemes—where purified water is placed into an environmental buffer before entering a drinking water distribution system. Our review of experiences around the world suggests approaches for improving public acceptability of wastewater reuse schemes. The literature also suggests that there is an urgent need to collect more wastewater treatment and reuse data, to research ways of better assessing and reducing health risk associated with emerging pollutants in reclaimed wastewater, and to better price both drinking water and recycled wastewater. WIREs Water 2015, 2:199–214. doi: 10.1002/wat2.1074

This article is categorized under:

Engineering Water > Planning Water

Engineering Water > Sustainable Engineering of Water

Human Water > Water as Imagined and Represented
The Impact of In‐situ Fabric Surface Energy on Dehydration of Fabrics
Authors: Chen Tao , Liu Xiaoyun , You Qiushi , Yu Danni , Wang Jiping
Published: March 2015

Reducing liquid surface tension is widely used to increase the efficiency of the centrifugal dehydration in textile wet processing. However, increasing the dehydration efficiency by decreasing fabric surface energy is seldom studied. In this work, the impact of in situ fabric surface energy on residual moisture content (RMC) of fabrics in the dehydration processes was investigated. Different types of fluorocarbon surfactants including cationic, anionic, nonionic and amphoteric were adopted as additives in this study. The liquid surface tension and RMC were efficiently decreased when fluorocarbon surfactants were used. Notably, a cationic fluorocarbon surfactant displays similar surface tension but distinct dehydration efficiency. The in situ fabric surface energy was evaluated by measuring the n‐octane contact angle on the cotton fabric surface under the surfactant solution using the captive bubble method. It was found that the cationic fluorocarbon surfactant system gave the lowest fabric surface energy, which was probably because cationic fluorocarbon surfactants are easier to adsorb onto the surface of cotton fabric to form a fluorocarbon layer. The chemical composition (19F, 12C and 16O) analysis of the cotton fabric surface by X‐ray photoelectron spectroscopy confirms the hypothesis.
Synthesis, Characterization, and Performance of a Novel Polymeric Cationic Surfactant Based on Low Molecular Weight Chitosan and 3‐Chloro‐2‐Hydroxypropyl Dimethyl Dehydroabietyl Ammonium Chloride (CHPDMDHA)
Authors: Qi Fan , Cai Zhao‐sheng , Zhu Xue‐mei , Shang Shi‐bing , Pei Li‐jun
Published: March 2015

A series of novel polymeric cationic surfactants based on low molecular weight chitosan (LWCS) and 3‐chloro‐2‐hydroxypropyl dimethyl dehydroabietyl ammonium chloride (CHPDMDHA), LWCS‐g‐CHPDMDHA, were obtained by the grafting modification of LWCS with CHPDMDHA as grafting agent. The structure of LWCS‐g‐CHPDMDHA was confirmed by FT‐IR and 1H NMR, and the degree of quaternizing substitution (DS) of LWCS‐g‐CHPDMDHA was determined according to the results of elemental analysis. The aggregation behavior and surface activities of LWCS‐g‐CHPDMDHA in aqueous solution were investigated by transmission electron microscopy (TEM) and determination of surface tension, respectively. The experimental results showed that the DS and molecular weight (Mw) of LWCS have significant influence on the critical micelle concentrations (CMC) and the surface tensions at the CMC (γcmc). The shape of aggregates changed with the variation of concentration of LWCS‐g‐CHPDMDHA in aqueous solution. When the LWCS‐g‐CHPDMDHA was utilized as an emulsifier, the increase of DS of LWCS‐g‐CHPDMDHA and Mw of LWCS were favorable for improving the stability of emulsions composed of water and benzene.
Synthesis, Characterization and Cytotoxicity Evaluation of an Oleic Acid Derived Novel Bicephalous Dianionic Surfactant
Authors: Kalhapure Rahul S. , Akamanchi Krishnacharya G.
Published: March 2015

A novel oleic acid derived bicephalous dianionic surfactant disodium (Z) 3,3′‐(oleoylazanediyl)dipropanoate containing one hydrophobic carbon chain and two hydrophilic head groups was synthesized, characterized and evaluated for cytotoxicity for the purpose of introducing a new biocompatible surfactant. The head group 3,3′‐azanediyldipropanoate was synthesized through Michael addition of methyl acrylate to benzylamine and subsequent reductive debenzylation with Pd/C, H2 and was condensed with an oleic acid moiety via amide bond formation. Ester groups at the periphery were hydrolyzed using acetyl chloride‐water and the diacid formed was neutralized with sodium bicarbonate to obtain the desired surfactant. The CMC was determined by conductometry, log Poctanol/water by ChemSW software and the hydrophilic‐lipophilic balance (HLB) by the Davies method and ChemSW. In vitro cytotoxicity study was performed using sulforhodamine B assay and the in vivo skin irritation study was performed on male New Zealand white rabbits as per OECD guideline 404. The CMC was found to be 1.9 mm/l which was almost half of the CMC of sodium oleate. The Log Poctanol/water value of −3.87 and the HLB values of 35.22 and 34.46 by the Davies method and ChemSW software respectively revealed the hydrophilic nature of the surfactant. The surfactant did not exhibit any cytotoxicity at any of the concentrations tested and was found to be non‐irritating by in vivo skin irritation studies. The findings of the present work suggest that the synthesized novel bicephalous dianionic surfactant is a safe and biocompatible excipient. It has the potential to be an attractive alternative to linear and gemini surfactants for applications in biological studies and pharmaceutical drug delivery systems.
Insertion of sequences at the original provirus integration site of mouseROSA26 locus using the CRISPR/Cas9 system
Authors: Quadros Rolen M. , Harms Donald W. , Ohtsuka Masato , Gurumurthy Channabasavaiah B.
Published: March 2015

Targeted transgenic mouse models, where an exogenous gene is inserted into a specified genomic locus to achieve its stable and reliable expression, have been widely used in biomedical research. However, the available methodologies for targeted insertion of sequences require many laborious steps that involve the use of embryonic stem (ES) cells. We recently developed Pronuclear Injection‐based Targeted Transgenesis (PITT), a method that uses a recombinase‐mediated cassette exchange (RMCE) to enable insertion of sequences at a predetermined genomic locus, such asROSA26. The PITT technique uses fertilized eggs (instead of ES cells) collected from ‘seed mice’ that contain the RMCE landing pad. The PITT method can rapidly generate reliable targeted transgenic mice; it requires a seed mouse, which in our previous study was generated using ES cell targeting approaches. Here, we demonstrate that seed mice containing the RMCE landing pad can be developed rapidly by using the CRISPR/Cas9 system. One of the CRISPR targets tested in this study enabled the insertion of sequences precisely at the originalROSA26 provirus integration site. We anticipate that using a similar approach, PITT landing pad sequences can be rapidly and precisely inserted at other genomic loci to develop an array of PITT tools. This two‐step strategy combines the best features of the two newer technologies—rapid creation of PITT landing pads using the CRISPR/Cas9 system and efficient and precise insertion of larger cassettes at the landing pads using PITT. This study also revealed that anomalous and mosaic sequence insertions can occur with the CRISPR/Cas9 system.
Ocular metastasis of colorectal cancer
Authors: Khawaja Muhammad Rizwan , Minturn John T , Spittler A John , Chiorean E Gabriela
Published: March 2015

Approximately 20% of patients with colorectal cancer have metastatic disease at time of diagnosis, and another 25-35% develop metastases during the course of their disease. Liver, peritoneum, and lungs are the most common sites of metastases. We report the case of a 60-year-old female who presented with ocular metastasis 4 years after her initial curative-intent treatment for T3N1M0 rectal adenocarcinoma. After local eye radiation therapy, she received palliative systemic chemotherapy and enjoyed a good quality of life for 32 months before succumbing to progressive disease. Ocular metastasis of colorectal cancer is rare. When present, it usually occurs in the setting of diffuse hematogenous spread. In addition to local therapy, systemic chemotherapy should also be considered.
Pregnancy outcome according to pre‐pregnancy body mass index and gestational weight gain
Authors: Gesche Joanna , Nilas Lisbeth
Published: March 2015

Objective

To assess birth weight in relation to gestational weight gain (GWG) among women who were and were not obese before pregnancy.

Methods

For a retrospective cohort study, data were obtained for women with a pre‐pregnancy body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) of at least 30 who had a singleton delivery at a center in Denmark in 2010–2011. Data were also obtained for 455 non‐obese women (BMI 20.0–24.9). GWG was expressed in absolute terms and relative to published recommendations (11–16 kg in non‐obese women; 5–9 kg in obese women).

Results

A total of 231 obese women were included in analyses. In non‐obese and obese women, fetal weight was highest when GWG was above the recommended amount. Among women who had a GWG in line with the recommendations, mean birth weight was higher among those with a pre‐pregnancy BMI of 35.0–39.9 (3758 ± 410 g) or at least 40 (3671 ± 374 g) than among non‐obese women (3394 ± 453 g; P = 0.0058).

Conclusion

Birth weight is related to both maternal BMI and GWG. In obese women, adherence to GWG recommendations does not seem to prevent increased birth weights.
Meta‐analysis of Foley catheter plus misoprostol versus misoprostol alone for cervical ripening
Authors: Chen Wenhang , Xue Jing , Gaudet Laura , Walker Mark , Wen Shi Wu
Published: March 2015

Background

The effectiveness of Foley catheter plus misoprostol for cervical ripening has not been convincingly shown in trials.

Objectives

To summarize the evidence comparing Foley catheter plus misoprostol versus misoprostol alone for cervical ripening.

Search strategy

Embase, Medline, and Cochrane Collaboration databases were searched with the terms “Foley catheter,” “misoprostol,” “cervical ripening,” and “labor induction.”

Selection criteria

Randomized controlled trials comparing the methods of cervical ripening for delivery of a viable fetus were included.

Data collection and analysis

Study characteristics, quality, and outcomes were recorded. Random‐effects models were used to combine data.

Main results

Eight trials were included, with 1153 patients overall. In a pooled analysis of seven high‐quality studies, the combination group had a decreased time to delivery (mean difference –2.36 hours, 95% confidence interval [CI] –4.07 to –0.66; P = 0.007). Risk of chorioamnionitis was significantly increased in the combination group (risk ratio [RR] 2.07, 95% CI 1.04–4.13; P = 0.04), and that of tachysystole with fetal heart rate changes was decreased (RR 0.58, 95% CI 0.38–0.91; P = 0.02). Frequency of cesarean did not differ (P = 0.77).

Conclusions

The combined use of Foley catheter and misoprostol results in a reduced time to delivery, a reduced frequency tachysystole with fetal heart rate changes, and an increased incidence of chorioamnionitis.
What adult electrocardiogram (ECG) diagnoses and/or findings do residents in emergency medicine need to know?
Authors: Patocka Catherine , Turner Joel , Wiseman Jeffrey
Published: March 2015

Objective

There is no evidence-based description of electrocardiogram (ECG) interpretation competencies for emergency medicine (EM) trainees. The first step in defining these competencies is to develop a prioritized list of adult ECG findings relevant to EM contexts. The purpose of this study was to categorize the importance of various adult ECG diagnoses and/or findings for the EM trainee.

Methods

We developed a list of potentially important adult ECG diagnoses/findings and conducted a Delphi opinion-soliciting process. Participants used a 4-point Likert scale to rate the importance of each diagnosis for EM trainees. Consensus was defined as a minimum of 75% agreement at the second round or later. In the absence of consensus, stability was defined as a shift of 20% or less after successive rounds.

Results

A purposive sampling of 22 emergency physicians participated in the Delphi process, and 16 (72%) completed the process. Of those, 15 were from 11 different EM training programs across Canada and one was an expert in EM electrocardiography. Overall, 78 diagnoses reached consensus, 42 achieved stability and one diagnosis achieved neither consensus nor stability. Out of 121 potentially important adult ECG diagnoses, 53 (44%) were considered “must know” diagnoses, 61 (50%) “should know” diagnoses, and 7 (6%) “nice to know” diagnoses.

Conclusion

We have categorized adult ECG diagnoses within an EM training context, knowledge of which may allow clinical EM teachers to establish educational priorities. This categorization will also facilitate the development of an educational framework to establish EM trainee competency in ECG interpretation.
Regimes during liquid drop impact on a liquid pool
Authors: Ray Bahni , Biswas Gautam , Sharma Ashutosh
Published: March 2015

Water drops falling on a deep pool can either coalesce to form a vortex ring or splash, depending on the impact conditions. The transition between coalescence and splashing proceeds via a number of intermediate steps, such as thick and thin jet formation and gas-bubble entrapment. We perform simulations to determine the conditions under which bubble entrapment and jet formation occur. A regime map is established for Weber numbers ranging from 50 to 300 and Froude numbers from 25 to 600. Vortex ring formation is seen for all of the regimes; it is greater for the coalescence regime and less in the case of the thin jet regime.
A hybrid molecular–continuum method for unsteady compressible multiscale flows
Authors: Borg Matthew K. , Lockerby Duncan A. , Reese Jason M.
Published: March 2015

We present an internal-flow multiscale method (‘unsteady-IMM’) for compressible, time-varying/unsteady flow problems in nano-confined high-aspect-ratio geometries. The IMM is a hybrid molecular–continuum method that provides accurate flow predictions at macroscopic scales because local microscopic corrections to the continuum-fluid formulation are generated by spatially and temporally distributed molecular simulations. Exploiting separation in both time and length scales enables orders of magnitude computational savings, far greater than seen in other hybrid methods. We apply the unsteady-IMM to a converging–diverging channel flow problem with various time- and length-scale separations. Comparisons are made with a full molecular simulation wherever possible; the level of accuracy of the hybrid solution is excellent in most cases. We demonstrate that the sensitivity of the accuracy of a solution to the macro–micro time-stepping, as well as the computational speed-up over a full molecular simulation, is dependent on the degree of scale separation that exists in a problem. For the largest channel lengths considered in this paper, a speed-up of six orders of magnitude has been obtained, compared with a notional full molecular simulation.
Network-theoretic approach to sparsified discrete vortex dynamics
Authors: Nair Aditya G. , Taira Kunihiko
Published: March 2015

We examine discrete vortex dynamics in two-dimensional flow through a network-theoretic approach. The interaction of the vortices is represented with a graph, which allows the use of network-theoretic approaches to identify key vortex-to-vortex interactions. We employ sparsification techniques on these graph representations based on spectral theory to construct sparsified models and evaluate the dynamics of vortices in the sparsified set-up. Identification of vortex structures based on graph sparsification and sparse vortex dynamics is illustrated through an example of point-vortex clusters interacting amongst themselves. We also evaluate the performance of sparsification with increasing number of point vortices. The sparsified-dynamics model developed with spectral graph theory requires a reduced number of vortex-to-vortex interactions but agrees well with the full nonlinear dynamics. Furthermore, the sparsified model derived from the sparse graphs conserves the invariants of discrete vortex dynamics. We highlight the similarities and differences between the present sparsified-dynamics model and reduced-order models.
Resilience of plant-insect interactions in an oak lineage through Quaternary climate change
Authors: Su Tao , Adams Jonathan M. , Wappler Torsten , Huang Yong-Jiang , Jacques Frédéric M. B. , Liu Yu-Sheng (Christopher) , Zhou Zhe-Kun
Published: March 2015

Plant-insect interactions are vital for structuring terrestrial ecosystems. It is still unclear how climate change in geological time might have shaped plant-insect interactions leading to modern ecosystems. We investigated the effect of Quaternary climate change on plant-insect interactions by observing insect herbivory on leaves of an evergreen sclerophyllous oak lineage (QuercussectionHeterobalanus, HET) from a late Pliocene flora and eight living forests in southwestern China. Among the modern HET populations investigated, the damage diversity tends to be higher in warmer and wetter climates. Even though the climate of the fossil flora was warmer and wetter than modern sample sites, the damage diversity is lower in the fossil flora than in modern HET populations. Eleven out of 18 damage types in modern HET populations are observed in the fossil flora. All damage types in the fossil flora, except for one distinctive gall type, are found in modern HET populations. These results indicate that Quaternary climate change did not cause extensive extinction of insect herbivores in HET forests. The accumulation of a more diverse herbivore fauna over time supports the view of plant species as evolutionary “islands” for colonization and turnover of insect species.
Was the Ediacaran–Cambrian radiation a unique evolutionary event?
Authors: Erwin Douglas H.
Published: March 2015

The extent of morphologic innovation during the Ediacaran–Cambrian diversification of animals was unique in the history of metazoan life. This episode was also associated with extensive changes in the redox state of the oceans, in the structure of benthic and pelagic marine ecosystems, in the nature of marine sediments, and in the complexity of developmental interactions in Eumetazoa. But did the phylogenetic and morphologic breadth of this episode simply reflect the unusual outcome of recurrent evolutionary processes, or was it the unique result of circumstances, whether in the physical environment, in developmental mechanisms, or in ecological interactions? To better characterize the uniqueness of the events, I distinguish among these components on the basis of the extent of sensitivity to initial conditions and unpredictability, which generates a matrix of possibilities from fully contingent to fully deterministic. Discriminating between these differences is important for informing debates over determinism versus the contingency in the history of life, for understanding the nature of evolutionary theory, and for interpreting historically unique events.
Taphonomic biases in the insect fossil record: shifts in articulation over geologic time
Authors: Karr Jered A. , Clapham Matthew E.
Published: March 2015

Insect taphonomy is a topic that has drawn interest because of its potential biases on diversity patterns and the ecological information recorded by ancient insect faunas. Other than the onset of common amber fossilization in the Cretaceous, very little is known about long-term trends in the nature and quality of insect preservation and, as a result, the effects of taphonomic biases are poorly constrained. We assembled a database of nearly 7000 Carboniferous–Pliocene insect adpression (compression and impression) species from the primary literature to assess changes in insect taphonomy over time and test biotic and environmental controls on preservation. We grouped the fossils into 10-Myr bins and scored preservation of holotype specimens as either articulated bodies or isolated wings; articulated specimens with a body implied a generally higher quality of preservation. Paleozoic and Triassic insect holotypes are known overwhelmingly from isolated wings (only 12% articulated bodies), but our database shows a significant increase in the percentage preserved as articulated bodies, to more than 70%, beginning about 160 Myr ago in the Late Jurassic. This transition could reflect variations in the robustness of different insect orders and shifts in the taxonomic composition of insect faunas, but all the major orders in the database exhibit significant increases in articulation. Instead, a shift to increased preservation in lacustrine paleoenvironments, which contain a greater proportion of articulated body fossils, explains most of the trend. The pronounced Late Jurassic increase in articulation has implications for evolutionary and ecological reconstructions, for example, suggesting that preserved insect diversity may be biased downward in the earlier part of their history when articulation was poor.
A morphospace of planktonic marine diatoms. II. Sampling standardization and spatial disparity partitioning
Authors: Kotrc Benjamin , Knoll Andrew H.
Published: March 2015

Morphospace occupation through time provides a view of diversification distinct from the more familiar taxonomic tabulations. However, this view is subject to the same geological biases long recognized in studies of taxonomic diversification, where techniques for correcting secular bias in sampling have become standard practice. In this study, we apply sampling standardization techniques to a morphospace investigation to test whether observed stratigraphic trends in morphospace occupation are artifacts of trends in sampling. When sampling bias is corrected by randomized subsampling, all disparity metrics show stationary patterns, or at most directional changes of small magnitude. Metrics describing the average dispersion of taxa in morphospace are less subject to sampling bias than those describing the total extent of morphospace occupied. We also investigate a measure of disparity that is insensitive to sampling intensity, introducing a geographic component of morphological disparity. By analogy to α and β components of taxonomic diversity, we suggest the notions of α and β disparity, and find that α disparity remains roughly constant through time. Our analysis also allows us to present the first taxonomic diversity curve of diatoms under shareholder quorum subsampling (SQS), showing similar results to previously published subsampling methods: a roughly twofold rise over the Cenozoic, with peak diversity around the Eocene/Oligocene boundary. Tests for methodological bias from choices in ordination method and data culling during morphospace construction indicate that our results are relatively insensitive to both factors: Cenozoic occupation of planktonic diatom morphospace is largely unchanging. We find a similarly stationary pattern when we directly analyze the morphological data, seeing no change in the prevalence of taxa with different sets of morphological characters. More broadly, our results make clear that a complete view of morphological disparity must consider sampling biases, which can be addressed with wellestablished, quantitative methods in morphospaces populated using occurrence-level data.
Testing for escalation in Lower Mississippian camerate crinoids
Authors: Thompson Jeffrey R. , Ausich William I.
Published: March 2015

Crinoids were relatively unaffected by the end-Devonian Hangenberg mass extinction event. Major clades of Devonian durophagous fishes suffered significant extinctions, however, and the dominant surviving clades were biting or nipping predators. In part as a response to the Hangenberg event, early Mississippian crinoids underwent an adaptive radiation, while fish clades with a shell-crushing durophagous strategy diversified. Durophagous predators are inferred to have been more effective predators on camerate crinoids; and it is hypothesized, following the predictions of escalation, that through the early Mississippian, camerate crinoids evolved more effective anti-predatory strategies in response. We test this hypothesis of escalation by examining the changes in spinosity and plate convexity among camerate crinoids throughout this interval. A new method was formulated to test for an increase in convexity of the tegmen plates. Traits inAgaricocrinus,Aorocrinus, andDorycrinus(Family Coelocrinidae) were tested for congruence to the escalation hypothesis, and results were mixed. Convexity of tegmen plates inAgaricocrinus, spine length/calyx diameter inAorocrinus, calyx size inAorocrinus, central spine length inDorycrinus, and spine width inDorycrinusdid not have size increase trends supporting escalation. Rather than an increase in convexity, the variance of convexity inAgaricocrinustegmen plates narrowed, which could reflect an optimum. Alternatively, morphological change consistent with the escalation hypothesis occurred in calyx size ofAgaricocrinusand in lateral spine length and calyx size inDorycrinus. Furthermore, central and lateral spine length, parameters of the spine width, and size trends support escalation whenAorocrinusandDorycrinusare treated as a lineage. Thus, inferred escalation acted on traits differently within a single lineage and was relevant for both speciation and the diversification of a new genus.
Geographic variation of parasitic and predatory traces on mollusks in the northern Adriatic Sea, Italy: implications for the stratigraphic paleobiology of biotic interactions
Authors: Warren Huntley John , Scarponi Daniele
Published: March 2015

Parasitic trematode worms leave characteristic pits in their bivalve mollusk hosts and represent an ideal system for analyzing parasite-host interactions through space and time with statistically meaningful sample sizes. Previous work in Late Pleistocene–Holocene sequences from the Po plain revealed significant long-term fluctuations in trematode prevalence values: higher prevalence in retrogradational environments (TST) and negligible prevalence in progradational environments (HST). Here we expand upon this work by investigating traces of parasitism, kleptoparasitism, and predation on mollusk death assemblages from two domains along the northern Adriatic coastline. The domain north of the Po delta (TST-like) and the southern domain (including the Po delta; HST-like) comprise environments comparable to those recovered in late Holocene (<6 Kyr) subsurface progradational deposits. We collected 17,299 specimens representing 111 species from 11 locations on the northern Adriatic coast of Italy. Our results reveal high predation pressure, a high diversity of host taxa, and widespread presence of trematode infestation in starved, oligotrophic, environmentally more stable (i.e., TST-like) settings north of the Po delta. Immediately south of the Po delta, in settings with strong and variable sedimentary input, almost no infestation is recorded. The reappearance of infestation is evident in the southern portion of the study area (i.e., Cattolica-Montemarciano), relatively far from the highly stressed environments south of the Po River. There is no significant difference in trematode prevalence values between fossil and modern samples. The distribution of spionid traces (an indicator of stressed environments) was nearly the opposite of that displayed by trematodes. Drilling frequency is highest in TST-like environments and is not correlated with diversity indices. These results suggest that temporal trends of trematode prevalence (and possibly also other biotic interactions) in sedimentary successions are controlled by environmental changes driven by glacio-eustatic dynamics, and reaffirm the importance of interpreting temporal trends in the context of spatial variation.
Robust Focus Measure Operator Using Adaptive Log-Polar Mapping for Three-Dimensional Shape Recovery
Authors: Lee Ik-Hyun , Mahmood Muhammad Tariq , Choi Tae-Sun
Published: March 2015

Shape from focus (SFF) is a passive optical technique that reconstructs object shape from a sequence of image taken at different focus levels. In SFF techniques, computing focus measurement for each pixel in the image sequence, through a focus measure operator, is the fundamental step. Commonly used focus measure operators compute focus quality in Cartesian space and suffer from erroneous focus quality and lack in robustness. Thus, they provide erroneous depth maps. In this paper, we introduce a new focus measure operator that computes focus quality in log-polar transform (LPT) Properties of LPT, such as biological inspiration, data selection, and edge invariance, enable computation of better focus quality in the presence of noise. Moreover, instead of using a fixed patch of the image, we suggest the use of an adaptive window. The focus quality is assessed by computing variation in LPT. The effectiveness of the proposed technique is evaluated by conducting experiments using image sequences of different simulated and real objects. The comparative analysis shows that the proposed method is robust and effective in the presence of various types of noise.
Dawn Spacecraft Enters into Orbit Around Dwarf Planet Ceres
Authors: Showstack Randy
Published: March 2015

A 16-month investigation of the dwarf planet Ceres could reveal a lot about the most massive body in the asteroid belt and could advance our understanding of the formation of terrestrial planets.
GM‐CSF and uPA are required for Porphyromonas gingivalis‐induced alveolar bone loss in a mouse periodontitis model
Authors: Lam Roselind S , O'Brien‐Simpson Neil M , Hamilton John A , Lenzo Jason C , Holden James A , Brammar Gail C , Orth Rebecca K , Tan Yan , Walsh Katrina A , Fleetwood Andrew J , Reynolds Eric C
Published: March 2015

Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and urokinase‐type plasminogen activator (uPA) can contribute to the progression of chronic inflammatory diseases with possible involvement of macrophages. In this study, we investigated the role of both GM‐CSF and uPA in Porphyromonas gingivalis‐induced experimental periodontitis using GM‐CSF−/− and uPA−/− mice. Intra‐oral inoculation of wild‐type (WT) C57BL/6 mice with P. gingivalis resulted in establishment of the pathogen in plaque and a significant increase in alveolar bone resorption. The infected mice also exhibited a CD11b+ CD86+ macrophage infiltrate into the gingival tissue, as well as P. gingivalis‐specific pro‐inflammatory cytokine and predominantly IgG2b antibody responses. In comparison, intra‐oral inoculation of P. gingivalis did not induce bone resorption and there was significantly less P. gingivalis recovered from plaque in GM‐CSF−/− and uPA−/− mice. Furthermore, P. gingivalis did not induce a macrophage gingival infiltrate or activate isolated peritoneal macrophages from the gene‐deficient mice. Pro‐inflammatory P. gingivalis‐specific T‐cell cytokine responses and serum interferon‐gamma (IFN‐γ) and IgG2b concentrations were significantly lower in GM‐CSF−/− mice. In uPA−/− mice, T‐cell responses were lower but serum IFN‐γ and IgG2b levels were comparable with WT mice levels. These results suggest that GM‐CSF and uPA are both involved in the progression of experimental periodontitis, possibly via a macrophage‐dependent mechanism(s).
p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration
Authors: Turvey Michelle E , Klingler‐Hoffmann Manuela , Hoffmann Peter , McColl Shaun R
Published: March 2015

Phosphoinositide 3‐kinase γ (PI3Kγ) consists of the catalytic subunit p110γ that forms a mutually exclusive heterodimer with one of the two adaptor subunits, p101 or p84. Although activation of PI3Kγ is necessary for cell migration downstream of G‐protein‐coupled receptor engagement, particularly within the immune system, aberrant PI3Kγ signalling has been associated with transformation, increased migration and the progression of multiple cancer types. Regulation of PI3Kγ signal activation and duration is critical to controlling and maintaining coordinated cellular migration; however, the mechanistic basis for this is not well understood. We have recently demonstrated that, in contrast to the tumour‐promoting potential of p110γ and p101, p84 possesses tumour‐suppressor activity, suggesting a negative regulatory role within PI3Kγ signalling. The present study investigated the role of p84 phosphorylation in the context of PI3Kγ signalling, cell migration and p84‐mediated tumour suppression. Two putative phosphorylation sites were characterised within p84, Ser358 and Thr607. Expression of wild‐type p84 reduced the oncogenic potential of MDA.MB.231 cells and inhibited metastatic lung colonisation in vivo, effects that were dependent on Thr607. Furthermore, loss of Thr607 enhanced migration of MDA.MB.231 cells in vitro and prevented the induction of p84/p110γ dimers. The dimerisation of wild‐type p84 with p110γ was not detected at the plasma membrane, indicating an inhibitory interaction preventing PI3Kγ lipid‐kinase activity. In contrast, Ser358 phosphorylation was not determined to be critical for p84 activity in the context of migration. Our findings suggest that p84 binding to p110γ may represent a novel negative feedback signal that terminates PI3Kγ activity.
Genomic and phenotypic differentiation among Methanosarcina mazei populations from Columbia River sediment
Authors: Youngblut Nicholas D , Wirth Joseph S , Henriksen James R , Smith Maria , Simon Holly , Metcalf William W , Whitaker Rachel J
Published: March 2015

Methanogenic archaea are genotypically and phenotypically diverse organisms that are integral to carbon cycling in anaerobic environments. Owing to their genetic tractability and ability to be readily cultivated, Methanosarcina spp. have become a powerful model system for understanding methanogen biology at the cellular systems level. However, relatively little is known of how genotypic and phenotypic variation is partitioned in Methanosarcina populations inhabiting natural environments and the possible ecological and evolutionary implications of such variation. Here, we have identified how genomic and phenotypic diversity is partitioned within and between Methanosarcina mazei populations obtained from two different sediment environments in the Columbia River Estuary (Oregon, USA). Population genomic analysis of 56 M. mazei isolates averaging <1% nucleotide divergence revealed two distinct clades, which we refer to as ‘mazei-T’ and ‘mazei-WC’. Genomic analyses showed that these clades differed in gene content and fixation of allelic variants, which point to potential differences in primary metabolism and also interactions with foreign genetic elements. This hypothesis of niche partitioning was supported by laboratory growth experiments that revealed significant differences in trimethylamine utilization. These findings improve our understanding of the ecologically relevant scales of genomic variation in natural systems and demonstrate interactions between genetic and ecological diversity in these easily cultivable and genetically tractable model methanogens.
Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development
Authors: Berbée Jimmy F. P. , Boon Mariëtte R , Khedoe P. Padmini S. J. , Bartelt Alexander , Schlein Christian , Worthmann Anna , Kooijman Sander , Hoeke Geerte , Mol Isabel M. , John Clara , Jung Caroline , Vazirpanah Nadia , Brouwers Linda P.J. , Gordts Philip L.S.M. , Esko Jeffrey D. , Hiemstra Pieter S. , Havekes Louis M. , Scheja Ludger , Heeren Joerg , Rensen Patrick C.N.
Published: March 2015

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.
Cenpj/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1
Authors: Garcez Patricia P. , Diaz-Alonso Javier , Crespo-Enriquez Ivan , Castro Diogo , Bell Donald , Guillemot François
Published: March 2015

The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that Cenpj, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of Cenpj during cortical development by in utero electroporation knockdown and found that silencing Cenpj in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of Cenpj in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that Cenpj mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in Cenpj.
Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy
Authors: Madhusudhan Thati , Wang Hongjie , Dong Wei , Ghosh Sanchita , Bock Fabian , Thangapandi Veera Raghavan , Ranjan Satish , Wolter Juliane , Kohli Shrey , Shahzad Khurrum , Heidel Florian , Krueger Martin , Schwenger Vedat , Moeller Marcus J. , Kalinski Thomas , Reiser Jochen , Chavakis Triantafyllos , Isermann Berend
Published: March 2015

Endoplasmic reticulum (ER) stress is associated with diabetic nephropathy (DN), but its pathophysiological relevance and the mechanisms that compromise adaptive ER signalling in podocytes remain unknown. Here we show that nuclear translocation of the transcription factor spliced X-box binding protein-1 (sXBP1) is selectively impaired in DN, inducing activating transcription factor-6 (ATF6) and C/EBP homology protein (CHOP). Podocyte-specific genetic ablation of XBP1 or inducible expression of ATF6 in mice aggravates DN. sXBP1 lies downstream of insulin signalling and attenuating podocyte insulin signalling by genetic ablation of the insulin receptor or the regulatory subunits phosphatidylinositol 3-kinase (PI3K) p85α or p85β impairs sXBP1 nuclear translocation and exacerbates DN. Corroborating our findings from murine DN, the interaction of sXBP1 with p85α and p85β is markedly impaired in the glomerular compartment of human DN. Thus, signalling via the insulin receptor, p85, and XBP1 maintains podocyte homeostasis, while disruption of this pathway impairs podocyte function in DN.
Comparison between single-molecule and X-ray crystallography data on yeast F1-ATPase
Authors: Steel Bradley C. , Nord Ashley L. , Wang Yamin , Pagadala Vijayakanth , Mueller David M. , Berry Richard M.
Published: March 2015

Single molecule studies in recent decades have elucidated the full chemo-mechanical cycle of F1-ATPase, mostly based on F1 from thermophilic bacteria. In contrast, high-resolution crystal structures are only available for mitochondrial F1. Here we present high resolution single molecule rotational data on F1 from Saccharomyces cerevisiae, obtained using new high throughput detection and analysis tools. Rotational data are presented for the wild type mitochondrial enzyme, a “liver” isoform and six mutant forms of yeast F1 that have previously been demonstrated to be less efficient or partially uncoupled. The wild-type and “liver” isoforms show the same qualitative features as F1 from Escherichia coli and thermophilic bacteria. The analysis of the mutant forms revealed a delay at the catalytic dwell and associated decrease in Vmax, with magnitudes consistent with the level of disruption seen in the crystal structures. At least one of the mutant forms shows a previously un-observed dwell at the ATP binding angle, potentially attributable to slowed release of ADP. We discuss the correlation between crystal structures and single molecule results.