bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo
Biotinylation of the
Toxoplasma
Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis
Authors: Nadipuram Santhosh M. , Kim Elliot W. , Vashisht Ajay A. , Lin Andrew H. , Bell Hannah N. , Coppens Isabelle , Wohlschlegel James A. , Bradley Peter J. 
Published: August 2016

ABSTRACT

Toxoplasma gondii
is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the
Toxoplasma
life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δ
gra38
and Δ
gra40
parasites showed no altered phenotype, disruption of
GRA39
results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking
GRA39
showed dramatically reduced virulence and a lower tissue cyst burden
in vivo
. Together, the findings from this work reveal a partial vacuolar proteome of
T. gondii
and identify a novel GRA that plays a key role in parasite replication and pathogenesis.

IMPORTANCE
Most intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In
Toxoplasma
, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that
in vivo
biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease.
The Double-Stranded DNA Virosphere as a Modular Hierarchical Network of Gene Sharing
Authors: Iranzo Jaime , Krupovic Mart , Koonin Eugene V. 
Published: August 2016

ABSTRACT
Virus genomes are prone to extensive gene loss, gain, and exchange and share no universal genes. Therefore, in a broad-scale study of virus evolution, gene and genome network analyses can complement traditional phylogenetics. We performed an exhaustive comparative analysis of the genomes of double-stranded DNA (dsDNA) viruses by using the bipartite network approach and found a robust hierarchical modularity in the dsDNA virosphere. Bipartite networks consist of two classes of nodes, with nodes in one class, in this case genomes, being connected via nodes of the second class, in this case genes. Such a network can be partitioned into modules that combine nodes from both classes. The bipartite network of dsDNA viruses includes 19 modules that form 5 major and 3 minor supermodules. Of these modules, 11 include tailed bacteriophages, reflecting the diversity of this largest group of viruses. The module analysis quantitatively validates and refines previously proposed nontrivial evolutionary relationships. An expansive supermodule combines the large and giant viruses of the putative order “Megavirales” with diverse moderate-sized viruses and related mobile elements. All viruses in this supermodule share a distinct morphogenetic tool kit with a double jelly roll major capsid protein. Herpesviruses and tailed bacteriophages comprise another supermodule, held together by a distinct set of morphogenetic proteins centered on the HK97-like major capsid protein. Together, these two supermodules cover the great majority of currently known dsDNA viruses. We formally identify a set of 14 viral hallmark genes that comprise the hubs of the network and account for most of the intermodule connections.

IMPORTANCE
Viruses and related mobile genetic elements are the dominant biological entities on earth, but their evolution is not sufficiently understood and their classification is not adequately developed. The key reason is the characteristic high rate of virus evolution that involves not only sequence change but also extensive gene loss, gain, and exchange. Therefore, in the study of virus evolution on a large scale, traditional phylogenetic approaches have limited applicability and have to be complemented by gene and genome network analyses. We applied state-of-the art methods of such analysis to reveal robust hierarchical modularity in the genomes of double-stranded DNA viruses. Some of the identified modules combine highly diverse viruses infecting bacteria, archaea, and eukaryotes, in support of previous hypotheses on direct evolutionary relationships between viruses from the three domains of cellular life. We formally identify a set of 14 viral hallmark genes that hold together the genomic network.
Outcome of adenotonsillectomy in children with Down syndrome and obstructive sleep apnoea
Authors: Maris Mieke , Verhulst Stijn , Wojciechowski Marek , Van de Heyning Paul , Boudewyns An 
Published: August 2016

ObjectiveTo evaluate the outcome of adenotonsillectomy (AT) in a cohort of children with Down syndrome (DS) and obstructive sleep apnoea (OSA).DesignRetrospective, cross-sectional study.SettingTertiary care centre.PatientsChildren with DS and OSA, without previous upper airway (UA) surgery.InterventionsAT and full overnight polysomnography.Main outcome resultsA significant improvement of the obstructive apnoea-hypopnoea index (oAHI) after AT was obtained. No differences in sleep efficiency or sleep fragmentation were found postoperatively. Almost half of the children had persistent OSA (oAHI ≥5/hour).ResultsData are presented as median (lower–upper quartile). Thirty-four children were included, median age 4.0 years (2.7–5.8), body mass index (BMI) z-score 0.81 (−0.46–1.76), and oAHI 11.4/hour (6.5–22.7). The majority presented with severe OSA (58.9%). AT was performed in 22 children, tonsillectomy in 10 and adenoidectomy in two. Postoperatively, a significant improvement of the oAHI was measured from 11.4/hour (6.5–22.7) to 3.6/hour (2.1–9.5) (p=0.001), with a parallel increase of the minimum oxygen saturation (p=0.008). Children with initially more severe OSA had significantly more improvement after UA surgery (p=0.001). Persistent OSA was found in 47.1% of the children.ConclusionsAT results in a significant improvement of OSA in children with DS without a change in sleep efficiency or sleep stage distribution. Severe OSA was associated with a larger reduction of OSA severity. Almost half of the children had persistent OSA, which was not correlated to age, gender or BMI z-score.
Role of physician perception of patient smile on pretest probability assessment for acute pulmonary embolism
Authors: Kline Jeffrey A , Neumann Dawn , Hall Cassandra L , Capito Jacob 
Published: August 2016

BackgroundMany clinicians use a global visual interpretation of patient appearance to decide if a patient looks sick or not. For patients with suspected acute pulmonary embolism (PE), we tested the relationship between visual appearance of a happy patient facial affect and probability of PE+ on CT pulmonary angiography (CTPA).MethodsEligible patients were selected by usual care to undergo CTPA, the criterion standard for PE+ or PE−. Prior to CTPA result, trained study personnel obtained physician pretest probability using the gestalt method (visual analogue scale, 0%–100%), the Wells score (0–12) and physicians’ impression of whether the patient smiled during the initial examination (smile+). Patients' faces were also video recorded and analysed with an automated neural network-based algorithm (Noldus FaceReader) for happy affect.ResultsOf the 208 patients enrolled, 27 were PE+ and smile+ was more frequent in patients with PE+ than PE−, a finding confirmed by the Noldus. The diagnostic sensitivity and specificity of smile was low, and physicians overestimated presence of an alternative diagnosis more likely to PE with smile+ than smile− patients in patients with true PE. As a result, the area under the receiver operating characteristic curve (AUROC) was lower for the Wells score in smile+ patients. However, the physicians’ mean gestalt estimate of PE did not differ with smile status, nor did smile status affect the AUROC for gestalt.ConclusionsIn patients with suspected PE, physician recollection of patients’ smile+ was more common in PE+ patients, and was associated with a less accurate Wells score, primarily because physicians overestimated probability of alternative diagnosis. However, the overall diagnostic accuracy of physicians’ gestalt did not differ with perceived smile status. These data suggest that the patients’ smile had less effect on the numeric gestalt pretest probability assessment than on the binary decision about an alternative diagnosis.
Temperature–Salinity Structure of the North Atlantic Circulation and Associated Heat and Freshwater Transports
Authors: Xu Xiaobiao , Rhines Peter B. , Chassignet Eric P. 
Published: August 2016

Abstract
This study investigates the circulation structure and relative contribution of circulation components to the time-mean meridional heat and freshwater transports in the North Atlantic, using numerical results of a high-resolution ocean model that are shown to be in excellent agreement with the observations. The North Atlantic circulation can be separated into the large-scale Atlantic meridional overturning circulation (AMOC) that is diapycnal and the subtropical and subpolar gyres that largely flow along isopycnal surfaces but also include prominent gyre-scale diapycnal overturning in the Subtropical Mode Water and Labrador Sea Water. Integrals of the meridional volume transport as a function of potential temperature θ and salinity S yield streamfunctions with respect to θ and to S, and heat functions. These argue for a significant contribution to the heat transport by the southward circulation of North Atlantic Deep Water. At 26.5°N, the isopycnic component of the subtropical gyre is colder and fresher in the northward-flowing western boundary currents than the southward return flows, and it carries heat southward and freshwater northward, opposite of that of the diapycnal component. When combined, the subtropical gyre contributes virtually zero to the heat transport and the AMOC is responsible for all the heat transport across this latitude. The subtropical gyre however significantly contributes to the freshwater transport, reducing the 0.5-Sv (1 Sv ≡ 106 m3 s–1) southward AMOC freshwater transport by 0.13 Sv. In the subpolar North Atlantic near 58°N, the diapycnal component of the circulation, or the transformation of warm saline upper Atlantic water into colder fresher deep waters, is responsible for essentially all of the heat and freshwater transports.
Predicting Outcomes after Uvulopalatopharyngoplasty for Adult Obstructive Sleep Apnea
Authors: Choi Ji Ho , Cho Seok Hyun , Kim Soo‐Nyung , Suh Jeffrey D. , Cho Jae Hoon 
Published: August 2016

ObjectiveUvulopalatopharyngoplasty (UPPP) remains one of the most common surgical treatments for patients with obstructive sleep apnea. However, the results after UPPP are unpredictable. The purpose of this meta‐analysis is to identify predictors of success after UPPP.Data SourcesA literature search was performed utilizing PubMed, EMBASE, SCOPUS, and the Cochrane Library.Review MethodsThe keywords and medical subject heading terms used were uvulopalatopharyngoplasty and UPPP. Studies were included if UPPP was used as a single surgical procedure for the treatment of obstructive sleep apnea and results were presented separately as responder (surgical success) and nonresponder (surgical failure). Exclusion criteria included pediatric patients and other surgical procedures (eg, nasal and hypopharyngeal) performed at the same time as the UPPP. Age, body mass index, preoperative apnea‐hypopnea index, Friedman stage, and several cephalometric variables were compared between responders and nonresponders.ResultsA total of 1257 studies were screened, with 15 studies included in this meta‐analysis. Our results demonstrate that Friedman stage I is a strong predictor for success after UPPP, while Friedman stage III and low hyoid position are negative predictors. Age, body mass index, preoperative apnea‐hypopnea index, and other cephalometric measurements were not significant.ConclusionFriedman stage and hyoid position are important predictors for UPPP.
Geniculate Ganglion Tumors
Authors: Lahlou Ghizlene , Nguyen Yann , Russo Francesca Yoshie , Ferrary Evelyne , Sterkers Olivier , Bernardeschi Daniele 
Published: August 2016

ObjectiveFacial nerve tumors are rare lesions mostly located in the geniculate ganglion. This study aims to compare those tumors limited to the geniculate ganglion in terms of clinical features and postoperative outcomes.Study DesignCase series with chart review.SettingsUniversity tertiary reference center.Subjects and MethodsMedical charts were reviewed for 17 patients who had surgery for geniculate ganglion tumor removal (10 hemangiomas, 6 schwannomas, 1 meningioma). Hemangiomas and schwannomas were compared for preoperative facial nerve function, hearing, tumor size, and postoperative outcomes.ResultsFacial palsy was observed in all cases. Regarding the preoperative facial nerve function, severe facial palsy (House‐Brackmann grades V and VI) was present in 70% of cases for hemangiomas and for no case of schwannoma (P =. 01), although hemangiomas were significantly smaller tumors (P =. 01). Hearing loss was observed in 4 cases (23.5%) and was related to tumor volume (P <. 0001). A complete excision was achieved in all cases, and a facial nerve graft was performed immediately after interruption in 16 patients (94%). Postoperative facial nerve function was improved or stabilized in 94% of cases. A preoperative House‐Brackman grade VI was shown as a negative factor for postoperative facial nerve function.ConclusionsDifferences in clinical presentations could help in establishing the good therapeutic option depending on the tumor type. Surgery, when indicated, is safe and effective, and postoperative outcomes are not related to tumor type.
Legal Responses to Economic Liberalization: The Case of Unfair Trade Practices
Authors: Pathak Akhileshwar 
Published: August 2016

This paper traces the evolution of law and practices in the past 20 years focusing on one aspect of unfair trade practices — unfairness in holding of games, contests, lotteries, and similar schemes for promoting sales and services in the context of India transitioning from a state controlled to a liberalized economy. With competition in the economy, firms have got into aggressive and competitive trade practices to entice the customers. These practices raise questions about the truthfulness and fairness of representation of products, services, advertisements, and schemes and modalities for promotion of products and services. There is a need for adequate law against unfair trade practices and a justice delivery system to have some ‘rules of the game’ to compete among themselves. The Monopolies and Restrictive Trade Practices (MRTP) Act, 1969, was amended in 1984 to introduce a chapter on unfair trade practices. One of the provisions pertained to the holding of games and lotteries. It stated that ‘the conduct of any contest, lottery, game of chance or skill’ for promoting sales, services or business interest was an unfair trade practice and should, therefore, be disallowed. Following the provision, the MRTP Commission had stopped almost all promotion schemes which had an element of draw or lottery. For example, Whirlpool Ltd. had launched a ‘Scratch a Gift Scheme’ and Coca-Cola Ltd. had introduced a promotional scheme for Coke. Considering them to be lottery schemes, the Commission had restrained the companies. The judgement of the Supreme Court in the ‘Horlicks Hidden Wealth Prize Offer’ changed the entire scenario. The Commission considered this scheme to be a kind of lottery and, thus, an unfair trade practice. However, the Supreme Court, in its short judgement in 1998, commented that this was not a case of lottery as there was no draw of lots or that a price was charged for participation in the draw. The fact that some bottles of Horlicks contained a slip of paper which entitled the buyer to a prize is not a lottery in the ordinary sense of the word. Following the judgement, in all the pending cases before the Commission, the parties successfully argued that their schemes did not attract the provision of unfair trade practice as they had not charged extra for participation in the scheme. Ever since, there has been no restraint on holding of such promotion schemes. In this context, the firms would need to do the following: objectively examine if such schemes have any effect on the promotion of products demonstrate the genuineness of a scheme by disclosing vital information work towards formulating appropriate regulations.
Quality of Service of Primary Health Centres: Insights from a Field Study
Authors: Rameshan P , Singh Shailendra 
Published: August 2016

This paper provides an evaluation of the quality of services and customer orientation of Primary Health Centres (PHCs) against the backdrop of the changed environment in the country with customer focus and efficiency emerging as the cornerstones of economic transactions in private and public sectors alike. It focuses on ten selected PHCs of Uttar Pradesh and covers the following stakeholders: Customers including patients who use the health care facilities of PHCs as well as the relatives and their personal attendants. Community members covering the village public, local shopkeepers, local government functionaries, local intelligentsia such as teachers and others having an interest or stake in PHC activities. Doctors and staff of the PHCs. District Medical Officials responsible for controlling and monitoring the PHC activities. The paper draws, among others, the following conclusions: The customers and community members of the villages perceived the facilities and services of PHCs to be deficient in many respects. Neither doctors and PHC staff nor the district officials are able to refute adequately the issues raised by villagers about the quality of service of PHCs. While villagers do not like the panchayat (local government) coming into the picture for improving the services of PHCs, district officials totally discount privatization as a means for providing effective primary health care in rural areas. While it is not very easy to solve the primary health care problems of the Indian villagers, yet the policy-makers can take recourse to the following measures to improve the facilities and services of PHCs in future: Form village committees to monitor PHC facilities, resources, and services. Identify industry patrons/sponsors for each PHC for developing infrastructure, facilities, and logistics without straining the scarce government resources. Constitute district-level user committees to monitor not only the PHC activities of a district but also the activities of the District Medical Offices. Enable panchayat and district administration to perform monitoring and supporting functions to ensure multiple checks on activities of the PHCs and District Medical Offices.
Marketing Mix Elements Influencing Brand Equity and Brand Choice
Authors: Chattopadhyay Tanmay , Shivani Shraddha , Krishnan Mahesh 
Published: August 2016

This study develops and empirically tests a model for determining the determinants and effects of brand equity for the Indian passenger car market. Towards the same, the Brand Equity Creation Model developed by Yoo, Donthu and Lee (2000) was expanded and combined with the Brand Choice Model developed by Erdem, et al (1999). The dimensions of brand equity were thought to affect Overall Brand Equity, which in turn affected the final brand choice made by the consumers. The effect that ten selected marketing activities had on the dimensions of brand equity was examined. The passenger car market was differentiated on the basis of the price of car as premium, volume, and economy type and shopping centre intercept survey was conducted to collect respondent data across ten centres throughout the country. Multiple time passenger car buyers were considered as the respondent base for the study. A total of 1,932 consumers were contacted and 302 valid responses were received. Structural Equation Model was used as the tool for analysis. The results showed that: Of the ten marketing mix elements considered, some had a very strong impact on brand equity because they positively impacted both the dimensions considered for the study. However, contrary to what many previous studies reported, country of origin and price promotion did not impact the brand equity for such consumers. Advertising frequency is not a builder of brand equity; word-of-mouth is a better determinant of brand equity for repeat passenger car buyers. The different results obtained in this study vis- à- vis those from earlier studies suggest that the cultural differences between consumers of two countries mediates the effect of the marketing efforts on brand equity creation. Again since each of the dimensions of brand equity under this study was found to positively impact brand choice, it has been posited that the probability of the consumers choosing the final brand is increased with an increase in the equity of the brand. Geographical limitation of the sample and absence of interaction of marketing mix elements amongst themselves were identified as some of the key limitations of the study.
Applying Structural Systems Thinking to Frame Perspectives on Social Work Innovation
Authors: Stringfellow Erin J. 
Published: August 2016

Objective: Innovation will be key to the success of the Grand Challenges Initiative in social work. A structural systems framework based in system dynamics could be useful for considering how to advance innovation. Method: Diagrams using system dynamics conventions were developed to link common themes across concept papers written by social work faculty members and graduate students ( N = 19). Results: Transdisciplinary teams and ethical partnerships with communities and practitioners will be needed to responsibly develop high-quality innovative solutions. A useful next step would be to clarify to what extent factors that could “make or break” these partnerships arise from within versus outside of the field of social work and how this has changed over time. Conclusions: Advancing innovation in social work will mean making decisions in a complex, ever-changing system. Principles and tools from methods that account for complexity, such as system dynamics, can help improve this decision-making process.