bluuebunny/crossref_metadata_2025 huggingface dataset:
First‐arrival traveltime sound speed inversion with a priori information
Authors: Hooi Fong Ming , Carson Paul L.
Published: July 2014

Purpose:

A first‐arrival travel‐time sound speed algorithm presented by Tarantola [Inverse Problem Theory and Methods for Model Parameter Estimation (SIAM, Philadelphia, PA, 2005)] is adapted to the medical ultrasonics setting. Through specification of a covariance matrix for the object model, the algorithm allows for natural inclusion of physical a priori information of the object. The algorithm's ability to accurately and robustly reconstruct a complex sound speed distribution is demonstrated on simulation and experimental data using a limited aperture.

Methods:

The algorithm is first demonstrated generally in simulation with a numerical breast phantom imaged in different geometries. As this work is motivated by the authors' limited aperture dual sided ultrasound breast imaging system, experimental data are acquired with a Verasonics system with dual, 128 element, linear L7‐4 arrays. The transducers are automatically calibrated for usage in the eikonal forward model.A priori information such as knowledge of correlated regions within the object is obtained via segmentation of B‐mode images generated from synthetic aperture imaging.

Results:

As one illustration of the algorithm's facility for inclusion ofa priori information, physically grounded regularization is demonstrated in simulation. The algorithm's practicality is then demonstrated through experimental realization in limited aperture cases. Reconstructions of sound speed distributions of various complexity are improved through inclusion of a priori information. The sound speed maps are generally reconstructed with accuracy within a few m/s.

Conclusions:

This paper demonstrates the ability to form sound speed images using two opposed commercial linear arrays to mimic ultrasound image acquisition in the compressed mammographic geometry. The ability to create reasonably good speed of sound images in the compressed mammographic geometry allows images to be readily coregistered to tomosynthesis image volumes for breast cancer detection and characterization studies.
Regulating gene drives
Authors: Oye Kenneth A. , Esvelt Kevin , Appleton Evan , Catteruccia Flaminia , Church George , Kuiken Todd , Lightfoot Shlomiya Bar-Yam , McNamara Julie , Smidler Andrea , Collins James P.
Published: July 2014

Regulatory gaps must be filled before gene drives could be used in the wild
Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming
Authors: Gonzalez-Muñoz Elena , Arboleda-Estudillo Yohanna , Otu Hasan H. , Cibelli Jose B.
Published: July 2014

Factor in oocyte assists reprogramming

Unfertilized eggs contain components that can dedifferentiate other cells that have gone down the path toward a specific cell fate. Gonzalez-Muñoz
et al.
show that the protein-folding factor ASF1A facilitates this reprogramming event and it acts at a particular phase of germ cell division termed metaphase II. ASF1A helps turn differentiated cells such as human adult dermal fibroblasts into undifferentiated pluripotent stem cells.

Science
, this issue p.
822
Genome Sequence of Lactobacillus delbrueckii subsp.
lactis
CNRZ327, a Dairy Bacterium with Anti-Inflammatory Properties
Authors: El Kafsi Hela , Binesse Johan , Loux Valentin , Buratti Julien , Boudebbouze Samira , Dervyn Rozenn , Hammani Amal , Maguin Emmanuelle , van de Guchte Maarten
Published: July 2014

Lactobacillus delbrueckii
subsp.
lactis
CNRZ327 is a dairy bacterium with anti-inflammatory properties both
in vitro
and
in vivo
. Here, we report the genome sequence of this bacterium, which appears to contain no less than 215 insertion sequence (IS) elements, an exceptionally high number regarding the small genome size of the strain.
Genome Sequences of the Oxytetracycline Production Strain Streptomyces rimosus R6-500 and Two Mutants with Chromosomal Rearrangements
Authors: Baranasic Damir , Zucko Jurica , Nair Mridul , Pain Arnab , Long Paul F. , Hranueli Daslav , Cullum John , Starcevic Antonio
Published: July 2014

The genome sequence of
Streptomyces rimosus
R6-500, an industrially improved strain which produces high titers of the important antibiotic oxytetracycline, is reported, as well as the genome sequences of two derivatives arising due to the genetic instability of the strain.
Curtobacterium
sp. Genome Sequencing Underlines Plant Growth Promotion-Related Traits
Authors: Bulgari Daniela , Minio Andrea , Casati Paola , Quaglino Fabio , Delledonne Massimo , Bianco Piero A.
Published: July 2014

Endophytic bacteria are microorganisms residing in plant tissues without causing disease symptoms. Here, we provide the high-quality genome sequence of
Curtobacterium
sp. strain S6, isolated from grapevine plant. The genome assembly contains 2,759,404 bp in 13 contigs and 2,456 predicted genes.
Characterization of a Genogroup I Sapovirus Isolated from Chimpanzees in the Republic of Congo
Authors: Mombo Illich M. , Berthet Nicolas , Bouchier Christiane , Fair Joseph N. , Schneider Bradley S. , Renaud François , Leroy Eric M. , Rougeron Virginie
Published: July 2014

Sapoviruses, which are members of the
Caliciviridae
family, are small nonenveloped viruses known to infect a large spectrum of mammalian hosts. We report here the first complete genome sequences of two genogroup I sapoviruses isolated from fecal samples from chimpanzees living in the Tchimpounga sanctuary, Republic of Congo.
Draft Genome Sequences of Respiratory and Urinary Tract Isolates of Acinetobacter baumannii from the Same Patient
Authors: Golemboski Daniel , Eardly Bertrand D.
Published: July 2014

Acinetobacter baumannii
is a frequent hospital-acquired human pathogen. This report describes the draft genome sequences of two distinct
A. baumannii
clinical isolates from the same patient. A comparison of the genomes revealed differences in antibiotic resistance and will enable the determination of genomic differences responsible for virulence at each body site.
Whole Genome Sequence of Polyresistant Mycobacterium tuberculosis CWCFVRF PRTB 19 Sputum Isolate from Chennai, India, Closely Clustering with East African Indian 5 Genogroup
Authors: Lakshmipathy Dhanurekha , Vetrivel Umashankar , Ramasubban Gayathri , Kulandai Lily Therese , Madhavan Hajib Narahari , Sridhar R. , Meenakshi N.
Published: July 2014

We announce the draft genome sequence of a polyresistant
Mycobacterium tuberculosis
strain (CWCFVRF PRTB 19) isolated from the sputum of a clinically suspected tuberculosis patient, and it closely clusters to the East African Indian 5 (EAI5) lineage.
Genome Sequence of “
Candidatus
Arthromitus” sp. Strain SFB-Mouse-NL, a Commensal Bacterium with a Key Role in Postnatal Maturation of Gut Immune Functions
Authors: Bolotin Alexander , de Wouters Tomas , Schnupf Pamela , Bouchier Christiane , Loux Valentin , Rhimi Moez , Jamet Alexandre , Dervyn Rozenn , Boudebbouze Samira , Blottière Hervé M. , Sorokin Alexei , Snel Johannes , Cerf-Bensussan Nadine , Gaboriau-Routhiau Valérie , van de Guchte Maarten , Maguin Emmanuelle
Published: July 2014

“
Candidatus
Arthromitus” sp. strain SFB-mouse-NL (SFB, segmented filamentous bacteria) is a commensal bacterium necessary for inducing the postnatal maturation of homeostatic innate and adaptive immune responses in the mouse gut. Here, we report the genome sequence of this bacterium, which sets it apart from earlier sequenced mouse SFB isolates.
Draft Genome Sequences of the Alga-Degrading Bacteria Aeromonas hydrophila Strain AD9 and Pseudomonas pseudoalcaligenes Strain AD6
Authors: Lenneman Eric M. , Barney Brett M.
Published: July 2014

Aeromonas hydrophila
AD9 and
Pseudomonas pseudoalcaligenes
AD6 have been linked to algal cell degradation. Here we report the draft genomes of
A. hydrophila
AD9 and
P. pseudoalcaligenes
AD6 for the investigation of causative agents for algal cell degradation.
Draft Genome Sequence of the Endosymbiont “
Candidatus
Ruthia magnifica” UCD-CM (Phylum
Proteobacteria
)
Authors: Lee Ruth D. , Jospin Guillaume , Coil David A. , Eisen Jonathan A.
Published: July 2014

Here, we present the draft genome of the endosymbiont “
Candidatus
Ruthia magnifica” UCD-CM, a member of the phylum
Proteobacteria
, found from the gills of a deep-sea giant clam,
Calyptogena magnifica
. The assembly consists of 1,160,249 bp contained in 18 contigs.
Role of psychotherapy in managing a case of generalised aggressive periodontitis
Authors: Priyadarshini D , Nadig Prasad , Deshpande Neeraj , Deshpande Anshula
Published: July 2014

Generalised aggressive periodontitis is characterised by “generalized interproximal attachment loss affecting atleast three permanent teeth other than first molars and incisors.” The management of generalised aggressive periodontitis is challenging as it involves an interdisciplinary approach. When the patient presents himself late to the clinician, the tooth and bone loss can be up to 60%. Natural teeth and alveolar bone contribute to the contour and aesthetics of the face. Loss of teeth in younger age may lead to attitude, behaviour changes and may cause psychological depression and withdrawal from society. The main distinguishing feature of this case report is the psychological counselling provided along with periodontal and prosthetic treatment.
Ortner’s syndrome: a case report and review of the literature
Authors: Hurtarte Sandoval A R , Carlos Zamora R , Gómez Carrasco J M , Jurado Ramos A
Published: July 2014

We present a case of a 67-year-old man who was an active smoker, with a clinical history of ischaemic cardiopathy, hypertension, who presented to the emergency room with hoarseness of voice of 2 weeks duration. No other neurological or cardiorespiratory symptoms were found. Physical examination revealed an aortic regurgitation murmur with radial pulse difference between the upper limbs and femoral pulse difference on lower limbs. Laryngoscopy examination revealed a left vocal cord paralysis in the paramedian position, without signs of malignancy. Thoracoabdominal CT angiography was performed to rule out an aortic dissection. CT revealed a dissection in the descending thoracic aortic arch and abdominal aorta. Cardiovascular surgery was consulted and decided to place endoprosthesis at the thoracic and abdominal aortic area. Hoarseness eventually resolved during the following weeks. Ortner’s syndrome is described as hoarseness of voice caused by compression of the left recurrent laryngeal nerve of cardiovascular origin.
Successful treatment of calciphylaxis by a multidisciplinary approach
Authors: Borges Lisa , Rosa Pedro , Dias Emanuel , Cássio Isabel
Published: July 2014

A 48-year-old woman performing peritoneal dialysis for end-stage renal disease presented with a painful leg ulcer. The investigation revealed an elevated parathyroid hormone level and the histological examination of the biopsy tissue from the ulcer revealed medial calcification of the arterioles, consistent with calciphylaxis. The patient developed additional ulcers in the lower limbs and treatment with antibiotics, cinacalcet, sevelamer, sodium thiosulfate, low calcium dialysate and hyperbaric oxygen therapy was instituted. The patient had a favourable outcome and after 9 months the ulcers had healed and the parathyroid hormone level reached the normal range. Calciphylaxis is a rare and life-threatening disorder associated with a mortality of 60-80%. Its pathogenesis is not fully understood hence there is no consensus in the treatment of this pathology.
Cytomegalovirus pouchitis in a patient with Crohn's disease
Authors: Mabvuure Nigel Tapiwa , Maclean Laura , Oien Karin , Gaya Daniel
Published: July 2014

Colectomy with ileoanal pouch formation is usually contraindicated in patients with Crohn's disease (CD) due to the risk of recurrent disease and pouch failure. We report the case of a patient, initially thought to have ulcerative colitis (UC), who underwent such surgery but subsequently developed perianal CD. She presented with diarrhoea and weight loss. Inflammatory markers were raised. Pouchoscopy revealed deep ulcers within the pouch. The main differential diagnoses were idiopathic pouchitis and recurrent CD. However, immunohistochemical staining demonstrated positivity for cytomegalovirus (CMV). Stool frequency, C reactive protein and albumin normalised within 48 h of starting oral valgancyclovir. At 15 weeks, pouch appearances were improved, no histological evidence of CMV was found and baseline pouch function had returned. This case highlights that CD can present many years after surgery for apparent UC. Also, CMV pouchitis should be considered as a differential cause of pouchitis especially as it is treatable with antiviral therapy.
ACE inhibitors: upper respiratory symptoms
Authors: Pinargote Paulette , Guillen Denisse , Guarderas Juan C
Published: July 2014

Cough and angioedema are well-known adverse reactions of ACE inhibitors. However, other adverse effects of upper airways such as postnasal drainage, rhinitis and nasal blockage, are less frequently recognised. These might share the same pathophysiological mechanism: bradykinin accumulation. We present two patients with ACE inhibitor-induced upper respiratory symptoms that improved after the discontinuation of ACE-inhibitors and substitution with angiotensin II receptor blockers. The incidence of these adverse events is not accurately known, since these are not required to be reported, but it is estimated to be low. This presents challenges to the physician and demonstrates the importance of keeping it as a differential diagnosis. Most physicians are aware of ACE inhibitor-induced cough but not of ACE inhibitor-induced nasal blockage, rhinitis or postnasal drainage. Identifying these can avoid unnecessary diagnostic tests and inappropriate treatment.
A randomised controlled trial to compare the clinical and cost-effectiveness of prism glasses, visual search training and standard care in patients with hemianopia following stroke: a protocol
Authors: Rowe F J , Barton P G , Bedson E , Breen R , Conroy E J , Cwiklinski E , Dodridge C , Drummond A , Garcia-Finana M , Howard C , Johnson S , MacIntosh C , Noonan C P , Pollock A , Rockliffe J , Sackley C , Shipman T ,   VISION (vision impairment in stroke: intervention or not)
Published: July 2014

Introduction

Homonymous hemianopia is a common and disabling visual problem after stroke. Currently, prism glasses and visual scanning training are proposed to improve it. The aim of this trial is to determine the effectiveness of these interventions compared to standard care.

Methods and analysis

The trial will be a multicentre three arm individually randomised controlled trial with independent assessment at 6 week, 12 week and 26 week post-randomisation. Recruitment will occur in hospital, outpatient and primary care settings in UK hospital trusts. A total of 105 patients with homonymous hemianopia and without ocular motility impairment, visual inattention or pre-existent visual field impairment will be randomised to one of three balanced groups. Randomisation lists will be stratified by site and hemianopia level (partial or complete) and created using simple block randomisation by an independent statistician. Allocations will be disclosed to patients by the treating clinician, maintaining blinding for outcome assessment. The primary outcome will be change in visual field assessment from baseline to 26 weeks. Secondary measures will include the Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual-5D and Short Form-12 questionnaires. Analysis will be by intention to treat.

Ethics and dissemination

This study has been developed and supported by the UK Stroke Research Network Clinical Studies Group working with service users. Multicentre ethical approval was obtained through the North West 6 Research ethics committee (Reference 10/H1003/119). The trial is funded by the UK Stroke Association. Trial Registration: Current Controlled TrialsISRCTN05956042. Dissemination will consider usual scholarly options of conference presentation and journal publication in addition to patient and public dissemination with lay summaries and articles.

Trial Registration

Current Controlled TrialsISRCTN05956042.
Contraception counselling of female soldiers in primary healthcare facilities
Authors: Crabb Sarah L
Published: July 2014

Background

Effectiveness of barrier and oral contraceptive pills is dependent on daily adherence and consistency that cannot always be guaranteed by military lifestyle. Long-acting reversible contraceptive (LARC) methods could provide a good alternative to guarantee effective contraception in unpredictable scenarios, and recent studies have suggested they could provide wider non-contraceptive benefits. LARC has been proven to be more cost effective than the combined oral contraceptive pill. The National Institute of Health and Care Excellence (NICE) has released guidelines on contraception provision to ensure all women receive the contraception method that is most appropriate to the individual.

Method

A retrospective audit of 105 sets of primary healthcare notes of serving female soldiers was assessed to establish contraceptive choices and whether appropriate information had been provided within the last year of their last consultation.

Results

100% had seen a healthcare provider capable of providing contraceptive advice in the last year. 69% documented as using some form of non-surgical contraception versus 58% quoted as national usage. 21% were using some form of LARC versus 8% national usage. 66% of eligible women had not had LARC discussed with them, and of these 50% did not have any contraceptive usage documented. Among other consultations, 41% had had a medical within the year period, of which over half had no documented contraceptive status.

Conclusions

As military healthcare providers, we have more exposure to our patients than NHS equivalents and this small study suggests there is an increased demand for contraception. Contraceptive choice counselling should be a mandatory part of routine initial medicals. If the situation demands a medical for any other reason, a documented contraception status should form an important part of the risk assessment process.
Properties of high-density matter in neutron stars
Authors: Weber Fridolin , Contrera Gustavo A. , Orsaria Milva G. , Spinella William , Zubairi Omair
Published: July 2014

This short review aims at giving a brief overview of various states of matter that have been suggested to exist in the ultra-dense centers of neutron stars. Particular emphasis is put on the role of quark deconfinement in neutron stars and on the possible existence of compact stars made of absolutely stable strange quark matter (strange stars). Astrophysical phenomena, which distinguish neutron stars from quark stars, are discussed and the question of whether or not quark deconfinement may occur in neutron stars is investigated. Combined with observed astrophysical data, such studies are invaluable to delineate the complex structure of compressed baryonic matter and to put firm constraints on the largely unknown equation of state of such matter.
Every finite group action on a compact 3-manifold preserves infinitely many hyperbolic spatial graphs
Authors: Ikeda Toru
Published: July 2014

We consider symmetries of spatial graphs in compact 3-manifolds described by smooth finite group actions. This paper provides a method for constructing an infinite family of hyperbolic spatial graphs with given symmetry by connecting spatial graph versions of hyperbolic tangles in 3-cells of polyhedral cell decompositions induced from triangulations of the 3-manifolds. This method is applicable also to the case of ideal triangulations.
SINGLE WALLED-BORON NITRIDE NANOTUBES BASED NANORESONATOR FOR SENSING OF ACETONE MOLECULES
Authors: TRIVEDI SANDESH , SHARMA SATISH C. , HARSHA SURAJ P.
Published: July 2014

Sensor application for detection of acetone molecule(s) present in human breath is developed for cantilevered single walled-boron nitride nanotube (SW-BNNT) and analyzed in the present work. The same can be used for continuous monitoring of diabetes. Biocompatibility nature of BNNTs justify their use in biomedical applications. The possible use of the BNNT as nanomechanical resonators is explored in the present study. An atomistic three dimensional (3D) space frame model of fixed-free SW-BNNT-based nanoresonator is developed. The proposed model investigates the feasibility of SW-BNNT for sensing acetone molecules present in human breath for detecting diabetes. Dynamic analysis of fixed-free SW-BNNT for variable aspect ratios of nanotubes is carried out. Presence of acetone molecule(s) causes a shift in the resonant frequency of SW-BNNT. It is observed that this frequency shift is quite significant with presence of more acetone molecules and shows mass sensitivity of SW-BNNT toward acetone molecules. Continuum mechanics-based analytical approach has been used to validate the newly developed sensor equations as the results are found to be in close proximity. The result thus paves new path for the application of SW-BNNTs as biosensor for detection of acetone molecule(s) present in human breath.
Thinking platforms for smarter urban water systems: fusing technical and socio-economic models and tools
Authors: Makropoulos Christos
Published: July 2014

Engineering is currently expanding its conceptual boundaries by accepting the challenge of interdisciplinarity, while often adopting social and biological concepts in developing tools (e.g. evolutionary optimization or interactive autonomous agents) or even world views (e.g. co-evolution, resilience, adaptation). The emerging socio-technical knowledge domain is still very much restricted by partial knowledge associated with the lack of long-term transdisciplinary research effort and the unavailability of robust, integrated tools able to cover both the technical and the socio-economic domains and to act as ‘thinking platforms’ for long-term scenario planning and strategic decision making under (high-order) uncertainties. Here we present an example of a toolkit that attempts to bridge this gap focusing on urban water (UW) systems and their management. The toolkit consists of three tools: the UW Optioneering Tool (UWOT); the UW Agent Based Modelling Platform (UWABM); and the UW System Dynamic Environment (UWSDE). The tools are briefly presented and discussed, focusing on interactions and data flows between them and their typical results are illustrated through a case study example. A further tool (a Cellular Automata Based Urban Growth Model) is currently under development and an early coupling with the other tools is also discussed. It is argued that this type of extended model fusion, beyond what has traditionally been thought of as ‘integrated modelling’ in the engineering domain is a new frontier in the understanding of environmental systems and presents a promising, emerging field in modelling interactions between our societies and cities, and our environment.
Anthropology, China, and the Chinese Century
Authors: Pieke Frank N.
Published: July 2014

If the twenty-first century will be a Chinese one, what will its anthropology bring? The new realities of life in China have fundamentally reshaped the anthropology of modern China. With the disappearance of the planned economy, a whole range of structures, networks, organizations, and practices has emerged at the interface of state and society. Moreover, Chinese society is shaped by globalization, transnationalism, and cosmopolitanism to a degree never seen before. What happens under the impact of these changes is new and unique for the People's Republic of China, both recognizably Chinese and generically modern. Anthropological research on these changes will impact the discipline of anthropology as a whole, just as China's rise will change the world order.
Cadherin Adhesion and Mechanotransduction
Authors: Leckband D.E. , de Rooij J.
Published: July 2014

Cadherins are the principal adhesion proteins at intercellular junctions and function as the biochemical Velcro that binds cells together. Besides this mechanical function, cadherin complexes are also mechanotransducers that sense changes in tension and trigger adaptive reinforcement of intercellular junctions. The assembly and regulation of cadherin adhesions are central to their mechanical functions, and new evidence is presented for a comprehensive model of cadherin adhesion, which is surprisingly more complex than previously appreciated. Recent findings also shed new light on mechanisms that regulate cadherin junction assembly, adhesion, and mechanotransduction. We further describe recent evidence for cadherin-based mechanotransduction, and the rudiments of the molecular mechanism, which involves α-catenin and vinculin as key elements. Potential roles of a broader cast of possible force-sensitive partners are considered, as well as known and speculative biological consequences of adhesion and force transduction at cadherin-mediated junctions.
Cytoplasmic Polyadenylation Element Binding Proteins in Development, Health, and Disease
Authors: Ivshina Maria , Lasko Paul , Richter Joel D.
Published: July 2014

The cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific mRNA binding proteins that control translation in development, health, and disease. CPEB1, the founding member of this family, has become an important model for illustrating general principles of translational control by cytoplasmic polyadenylation in gametogenesis, cancer etiology, synaptic plasticity, learning, and memory. Although the biological functions of the other members of this protein family in vertebrates are just beginning to emerge, it is already evident that they, too, mediate important processes, such as cancer etiology and higher cognitive function. In Drosophila, the CPEB proteins Orb and Orb2 play key roles in oogenesis and in neuronal function, as do related proteins in Caenorhabditis elegans and Aplysia. We review the biochemical features of the CPEB proteins, discuss their activities in several biological systems, and illustrate how understanding CPEB activity in model organisms has an important impact on neurological disease.
Weak Polarized Electron Scattering
Authors: Erler Jens , Horowitz Charles J. , Mantry Sonny , Souder Paul A.
Published: July 2014

Scattering polarized electrons provides an important probe of the weak interactions. Precisely measuring the parity-violating left–right cross-section asymmetry (ALR) is the goal of a number of experiments that have recently been completed or are in progress. The experiments are challenging, given that ALR is small, typically between 10−4 and 10−8. By carefully choosing appropriate targets and kinematics, one can isolate various pieces of the weak Lagrangian, providing a search for physics beyond the Standard Model. For other choices, unique features of the strong interaction are being studied, including the radius of the neutron density in heavy nuclei, charge symmetry violation, and higher-twist terms. This article reviews the theory behind the experiments, as well as the general techniques used in the experimental program.
The Power of Information: The ICT Revolution in Agricultural Development
Authors: Nakasone Eduardo , Torero Maximo , Minten Bart
Published: July 2014

We review the state of information and communication technologies (ICTs) and their impact on agricultural development in developing countries, documenting the rapid changes that have taken place over the past decade. Although there remains a wide gap in access between rural and urban areas, the spread of mobile phones in rural areas has led to important changes in the agricultural sector. We find that access to mobile phones has generally improved agricultural market performance at the macro level; however, impacts at the micro level are mixed. Evidence regarding the impact of market information systems (MIS) delivered through mobile phones on farm prices and income is limited, but the evidence points to strong, heterogeneous impacts. Similarly, the rollout of extension programs though ICTs is still in an early stage, and little research is available regarding such programs’ impacts.
The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology
Authors: Greco Todd M. , Diner Benjamin A. , Cristea Ileana M.
Published: July 2014

In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes. Alterations in protein abundances, interactions, posttranslational modifications, subcellular localizations, and secretion are temporally regulated during the progression of an infection. Consequently, understanding viral infection at the molecular level requires versatile approaches that afford both breadth and depth of analysis. Mass spectrometry is uniquely positioned to bridge this experimental dichotomy. Its application to both unbiased systems analyses and targeted, hypothesis-driven studies has accelerated discoveries in viral pathogenesis and host defense. Here, we review the contributions of mass spectrometry–based proteomic approaches to understanding viral morphogenesis, replication, and assembly and to characterizing host responses to infection.
Viruses and the DNA Damage Response: Activation and Antagonism
Authors: Luftig Micah A.
Published: July 2014

Viruses must interact with their hosts in order to replicate; these interactions often provoke the evolutionarily conserved response to DNA damage, known as the DNA damage response (DDR). The DDR can be activated by incoming viral DNA, during the integration of retroviruses, or in response to the aberrant DNA structures generated upon replication of DNA viruses. Furthermore, DNA and RNA viral proteins can induce the DDR by promoting inappropriate S phase entry, by modifying cellular DDR factors directly, or by unintentionally targeting host DNA. The DDR may be antiviral, although viruses often require proximal DDR activation of repair and recombination factors to facilitate replication as well as downstream DDR signaling suppression to ensure cell survival. An unintended consequence of DDR attenuation during infection is the long-term survival and proliferation of precancerous cells. Therefore, the molecular basis for DDR activation and attenuation by viruses remains an important area of study that will likely provide key insights into how viruses have evolved with their hosts.
Acinar cell-specific knockout of the PTHrP gene decreases the proinflammatory and profibrotic responses in pancreatitis
Authors: Bhatia Vandanajay , Rastellini Cristiana , Han Song , Aronson Judith F. , Greeley George H. , Falzon Miriam
Published: July 2014

Pancreatitis is a necroinflammatory disease with acute and chronic manifestations. Accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic pancreatitis (CP). Pancreatic parathyroid hormone-related protein (PTHrP) levels are elevated in a mouse model of cerulein-induced AP. Here, we show elevated PTHrP levels in mouse models of pancreatitis induced by chronic cerulein administration and pancreatic duct ligation. Because acinar cells play a major role in the pathophysiology of pancreatitis, mice with acinar cell-specific targeted disruption of the Pthrp gene ( PTHrP Δacinar) were generated to assess the role of acinar cell-secreted PTHrP in pancreatitis. These mice were generated using Cre-LoxP technology and the acinar cell-specific elastase promoter. PTHrP Δacinar exerted protective effects in cerulein and pancreatic duct ligation models, evident as decreased edema, histological damage, amylase secretion, pancreatic stellate cell (PSC) activation, and extracellular matrix deposition. Treating acinar cells in vitro with cerulein increased IL-6 expression and NF-κB activity; these effects were attenuated in PTHrP Δacinar cells, as were the cerulein- and carbachol-induced elevations in amylase secretion. The cerulein-induced upregulation of procollagen I expression was lost in PSCs from PTHrP Δacinar mice. PTHrP immunostaining was elevated in human CP sections. The cerulein-induced upregulation of IL-6 and ICAM-1 (human acinar cells) and procollagen I (human PSCs) was suppressed by pretreatment with the PTH1R antagonist, PTHrP ( 7 – 34 ). These findings establish PTHrP as a novel mediator of inflammation and fibrosis associated with CP. Acinar cell-secreted PTHrP modulates acinar cell function via its effects on proinflammatory cytokine release and functions via a paracrine pathway to activate PSCs.
Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis
Authors: Liu Yannan , Yuan Jingzhen , Tan Tanya , Jia Wenzhuo , Lugea Aurelia , Mareninova Olga , Waldron Richard T. , Pandol Stephen J.
Published: July 2014

Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase Cε (PKCε) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCε in pancreatic acinar cells and that PKCε mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCε in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCε resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCε protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCε knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCε, suggesting that PKCε regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCε deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCε activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCε is a potential target for prevention and/or treatment of acute pancreatitis.
Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation
Authors: Hooijman Pleuni E. , Paul Marinus A. , Stienen Ger J. M. , Beishuizen Albertus , Van Hees Hieronymus W. H. , Singhal Sunil , Bashir Muhammad , Budak Murat T. , Morgen Jacqueline , Barsotti Robert J. , Levine Sanford , Ottenheijm Coen A. C.
Published: July 2014

Several studies have indicated that diaphragm dysfunction develops in patients on mechanical ventilation (MV). Here, we tested the hypothesis that the contractility of sarcomeres, i.e., the smallest contractile unit in muscle, is affected in humans on MV. To this end, we compared diaphragm muscle fibers of nine brain-dead organ donors (cases) that had been on MV for 26 ± 5 h with diaphragm muscle fibers from nine patients (controls) undergoing surgery for lung cancer that had been on MV for less than 2 h. In each diaphragm specimen we determined 1) muscle fiber cross-sectional area in cryosections by immunohistochemical methods and 2) the contractile performance of permeabilized single muscle fibers by means of maximum specific force, kinetics of cross-bridge cycling by rate of tension redevelopment, myosin heavy chain content and concentration, and calcium sensitivity of force of slow-twitch and fast-twitch muscle fibers. In case subjects, we noted no statistically significant decrease in outcomes compared with controls in slow-twitch or fast-twitch muscle fibers. These observations indicate that 26 h of MV of humans is not invariably associated with changes in the contractile performance of sarcomeres in the diaphragm.
Osteopontin Shapes Immunosuppression in the Metastatic Niche
Authors: Sangaletti Sabina , Tripodo Claudio , Sandri Sara , Torselli Ilaria , Vitali Caterina , Ratti Chiara , Botti Laura , Burocchi Alessia , Porcasi Rossana , Tomirotti Andrea , Colombo Mario P. , Chiodoni Claudia
Published: July 2014

The matricellular protein osteopontin (OPN, Spp-1) is widely associated with cancer aggressiveness when produced by tumor cells, but its impact is uncertain when produced by leukocytes in the context of the tumor stroma. In a broad study using Spp1−/− mice along with gene silencing in tumor cells, we obtained evidence of distinct and common activities of OPN when produced by tumor or host cells in a spontaneously metastatic model of breast cancer. Different cellular localization of OPN is associated with its distinct activities, being mainly secreted in tumor cells while intracellular in myeloid cells. OPN produced by tumor cells supported their survival in the blood stream, whereas both tumor- and host-derived OPN, particularly from myeloid cells, rendered the metastatic site more immunosuppressive. Myeloid-derived suppressor cells (MDSC) expanded with tumor progression at both primary and lung metastatic sites. Of the expanded monocytic and granulocytic cell populations of MDSCs, the monocytic subset was the predominant source of OPN. In Spp1−/− mice, the inhibition of lung metastases correlated with the expansion of granulocyte-oriented MDSCs. Notably, monocytic MDSCs in Spp1−/− mice were less suppressive than their wild-type counterparts due to lower expression of arginase-1, IL6, and phospho-Stat3. Moreover, fewer regulatory T cells accumulated at the metastatic site in Spp1−/− mice. Our data find correlation with lung metastases of human mammary carcinomas that are associated with myeloid cells expressing OPN. Overall, our results unveiled novel functions for OPN in shaping local immunosuppression in the lung metastatic niche. Cancer Res; 74(17); 4706–19. ©2014 AACR.
Mutant IDH1-Driven Cellular Transformation Increases RAD51-Mediated Homologous Recombination and Temozolomide Resistance
Authors: Ohba Shigeo , Mukherjee Joydeep , See Wendy L. , Pieper Russell O.
Published: July 2014

Isocitrate dehydrogenase 1 (IDH1) mutations occur in most lower grade glioma and not only drive gliomagenesis but are also associated with longer patient survival and improved response to temozolomide. To investigate the possible causative relationship between these events, we introduced wild-type (WT) or mutant IDH1 into immortalized, untransformed human astrocytes, then monitored transformation status and temozolomide response. Temozolomide-sensitive parental cells exhibited DNA damage (γ-H2AX foci) and a prolonged G2 cell-cycle arrest beginning three days after temozolomide (100 μmol/L, 3 hours) exposure and persisting for more than four days. The same cells transformed by expression of mutant IDH1 exhibited a comparable degree of DNA damage and cell-cycle arrest, but both events resolved significantly faster in association with increased, rather than decreased, clonogenic survival. The increases in DNA damage processing, cell-cycle progression, and clonogenicity were unique to cells transformed by mutant IDH1, and were not noted in cells transformed by WT IDH1 or an oncogenic form (V12H) of Ras. Similarly, these effects were not noted following introduction of mutant IDH1 into Ras-transformed cells or established glioma cells. They were, however, associated with increased homologous recombination (HR) and could be reversed by the genetic or pharmacologic suppression of the HR DNA repair protein RAD51. These results show that mutant IDH1 drives a unique set of transformative events that indirectly enhance HR and facilitate repair of temozolomide-induced DNA damage and temozolomide resistance. The results also suggest that inhibitors of HR may be a viable means to enhance temozolomide response in IDH1-mutant glioma. Cancer Res; 74(17); 4836–44. ©2014 AACR.
Bioactive Lipids, LPC and LPA, Are Novel Prometastatic Factors and Their Tissue Levels Increase in Response to Radio/Chemotherapy
Authors: Schneider Gabriela , Sellers Zachariah Payne , Abdel-Latif Ahmed , Morris Andrew J. , Ratajczak Mariusz Z.
Published: July 2014

Bioactive lipids are fundamental mediators of a number of critical biologic processes such as inflammation, proliferation, and apoptosis. Rhabdomyosarcoma (RMS) is common in adolescence with histologic subtypes that favor metastasis. However, the factors that influence metastasis are not well appreciated. Here, it is shown that lysophosphatidylcholine (LPC) and its derivative, lysophosphatidic acid (LPA), strongly enhance motility and adhesion of human RMS cells. Importantly, these metastatic-associated phenotypes were observed at physiologic concentrations of these lipids, which naturally occur in biologic fluids. Moreover, the effects of these bioactive lipids were much stronger as compared with known peptide-based prometastatic factors in RMS, such as stromal-derived factor-1 or hepatocyte growth factor/scatter factor. Finally, both LPC and LPA levels were increased in several organs after γ-irradiation or chemotherapy, supporting the hypothesis that radio/chemotherapy induces an unwanted prometastatic environment in these organs.

Implications: LPC and LPA play a previously underappreciated role in dissemination of RMS and suggest that antimetastatic treatment with specific molecules blocking LPC/LPA activity should be part of standard radio/chemotherapy arsenal. Mol Cancer Res; 12(11); 1560–73. ©2014 AACR.
O ensino de arte na educação brasileira
Authors: Iavelberg Rosa
Published: July 2014

O presente artigo discorre sobre o ensino de arte na educação brasileira, explicitando relações entre as leis e os documentos de âmbito federal que dão as diretrizes para a educação em arte nas escolas de educação básica. Abordamos o recorte do 1º ao 9º ano do Ensino Fundamental, a formação de professores de arte, as mudanças teóricas e práticas no tempo e a escrita curricular em diferentes contextos educativos.
Sobre a educação básica no Brasil
Authors: Souza Paulo Nathanael Pereira de
Published: July 2014

Analisamos a extensão e a gravidade da crise de pertinência e de qualidade que avassala na atualidade a educação brasileira em todos os graus de escolaridade, com ênfase no ensino básico, por ser ele estruturante na formação das novas gerações e obrigatório por lei a todos os brasileiros, da pré-escola ao ensino médio. Buscamos discutir as facetas mais destacadas da crise e encerramos com recomendações sobre possíveis ações de emergência que os governos poderiam implementar, no curto e no médio prazo, a fim de modificar para melhor esse quadro inaceitável de resultados obtidos pelos alunos de todos os níveis e modalidades de educação no Brasil, evitando-se perder tempo com novas reformas radicais, que, como demonstra a história, custam a ser aprovadas pelo Congresso Nacional e pouco chegam à sala de aula das escolas.
Epidemiology and Public Health Policy of Tobacco Use and Cardiovascular Disorders in Low- and Middle-Income Countries
Authors: Saleheen Danish , Zhao Wei , Rasheed Asif
Published: July 2014

All forms of tobacco lead to an increased risk of cardiovascular disorders. During the past few decades, the number of people who consume tobacco has increased worldwide because of an overall increase in the global population. It is estimated that close to 80% of the >1.3 billion people who smoke tobacco in the world are in low- and middle-income countries. Smokeless forms of tobacco are also widely consumed in low- and middle-income countries, including chewable and snuffed forms. Lack of targeted and effective strategies to control tobacco consumption contributes to a large burden of cardiovascular disorders in low- and middle-income countries, where cardiovascular disorders have become the leading cause of morbidity and mortality. In this review, we evaluate the epidemiology of tobacco use in low- and middle-income countries and assess the public health policies needed to control tobacco use in such regions for the prevention of cardiovascular disorders and other tobacco-related morbidities and mortality.
Evidence for Stroke Family Caregiver and Dyad Interventions
Authors: Bakas Tamilyn , Clark Patricia C. , Kelly-Hayes Margaret , King Rosemarie B. , Lutz Barbara J. , Miller Elaine L.
Published: July 2014

Stroke is a leading cause of severe, long-term disability. Most stroke survivors are cared for in the home by a family caregiver. Caregiver stress is a leading cause of stroke survivor institutionalization, which results in significant costs to the healthcare system. Stroke family caregiver and dyad intervention studies have reported a variety of outcomes. A critical analysis of 17 caregiver intervention studies and 15 caregiver/stroke survivor dyad intervention studies was conducted to provide evidence-based recommendations for the implementation and future design of stroke family caregiver and dyad interventions.
Abuse and Subclinical Cardiovascular Disease Among Midlife Women
Authors: Thurston Rebecca C. , Chang Yuefang , Derby Carol A. , Bromberger Joyce T. , Harlow Sioban D. , Janssen Imke , Matthews Karen A.
Published: July 2014

Background and Purpose—

Some evidence suggests that abuse may be related to cardiovascular disease (CVD) risk among women. However, this relation has largely been addressed using self-reported measures of CVD. We tested whether a history of abuse was related to subclinical CVD among midlife women without clinical CVD.

Methods—

The Study of Women’s Health Across the Nation (SWAN) is a longitudinal cohort study of women transitioning through the menopause. One thousand four hundred two white, black, Hispanic, and Chinese SWAN participants completed measures of childhood and adult physical and sexual abuse, underwent a blood draw, completed physical measures, and underwent a carotid artery ultrasound at SWAN study visit 12. Associations between abuse and intima media thickness and plaque were tested in linear and multinomial logistic regression models controlling for age, site, race/ethnicity, financial strain, education, body mass index, lipids, blood pressure, measures of insulin resistance, smoking, alcohol use, physical activity, and medication use.

Results—

Findings indicated that a history of childhood sexual abuse was associated with higher intima media thickness controlling for standard CVD risk factors and other confounders (β=0.022; SE=0.010;
P
<0.05; adjusted mean childhood sexual abuse: 0.800 mm versus no childhood sexual abuse: 0.782 mm).

Conclusions—

Childhood sexual abuse was associated with higher intima media thickness controlling for CVD risk factors and other confounders. These findings indicate the importance of considering the potential impact of early-life stressors on women’s later cardiovascular health.