bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Glycerol‐3‐Phosphate Acyltransferase TbGAT is Dispensable for Viability and the Synthesis of Glycerolipids in Trypanosoma brucei
Authors: Patel Nipul , Pirani Karim A. , Zhu Tongtong , Cheung‐See‐Kit Melanie , Lee Sungsu , Chen Daniel G. , Zufferey Rachel 
Published: February 2016

AbstractGlycerolipids are the main constituents of biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans. Importantly, they occur as a structural component of the glycosylphosphatidylinositol lipid anchor of the abundant cell surface glycoproteins procyclin in procyclic forms and variant surface glycoprotein in bloodstream form, that play crucial roles for the development of the parasite in the insect vector and the mammalian host, respectively. The present work reports the characterization of the glycerol‐3‐phosphate acyltransferase TbGAT that initiates the biosynthesis of ester glycerolipids. TbGAT restored glycerol‐3‐phosphate acyltransferase activity when expressed in a Leishmania major deletion strain lacking this activity and exhibited preference for medium length, unsaturated fatty acyl‐CoAs. TbGAT localized to the endoplasmic reticulum membrane with its N‐terminal domain facing the cytosol. Despite that a TbGAT null mutant in T. brucei procyclic forms lacked glycerol‐3‐phosphate acyltransferase activity, it remained viable and exhibited similar growth rate as the wild type. TbGAT was dispensable for the biosynthesis of phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and GPI‐anchored protein procyclin. However, the null mutant exhibited a slight decrease in phosphatidylethanolamine biosynthesis that was compensated with a modest increase in production of ether phosphatidylcholine. Our data suggest that an alternative initial acyltransferase takes over TbGAT's function in its absence.
A radiological study on intra‐ and extra‐cranial calcifications in adults with X‐linked hypophosphatemia and associations with other mineralizing enthesopathies and childhood medical treatment
Authors: Gjørup H. , Kjaer I. , Beck‐Nielsen S. S. , Poulsen M. R. , Haubek D. 
Published: February 2016

Structured AbstractObjectives1) The objective of this study was to explore radiological signs of intracranial and nuchal ligament calcifications in adult patients with X‐linked hypophosphatemia (XLH) compared with controls and 2) to correlate signs of cranial calcifications in XLH patients with the presence of other extra‐cranial enthesopathies, with the severity of skeletal XLH impact and with medical treatment during childhood.Setting and Sample PopulationLateral and postero‐anterior cephalograms from 36 adult XLH patients and 49 adult controls and X‐rays from spine, pelvis, knees and ankles from 31 of the 36 XLH patients.MethodsRadiological signs of intracranial and nuchal ligament calcifications in XLH patients were compared with controls by Fischer's exact test. In XLH patients, the presence of cranial calcifications was correlated with the presence of other enthesopathies, with the severity of skeletal XLH impact and with medical treatment by Fischer's exact or chi‐squared test.ResultsSix (17%) XLH patients revealed major signs of intracranial calcifications. Nuchal ligament calcifications were common in XLH patients compared with controls (p = 0.018). Enthesopathy was present at 0–24 sites per XLH patient (median 2). Intracranial calcifications trended to correlate positively with vertebral enthesopathies (p = 0.059). Nuchal calcifications correlated positively with the severity of skeletal XLH impact (p = 0.040). Vertebral enthesopathies correlated negatively with medical treatment (p = 0.008).ConclusionMore XLH patients than controls showed nuchal ligament calcifications, and some XLH patients showed intracranial calcifications. Severely affected XLH patients often had nuchal ligament calcifications. Medically treated XLH patients had few vertebral enthesopathies.
Characterization of Electrical Reconnection Following Pulmonary Vein Isolation Using First‐ and Second‐Generation Cryoballoon
Authors: KOEKTUERK BUELENT , YORGUN HIKMET , KOEKTUERK OEZLEM , TURAN CEM H. , KESKIN KERIM , SCHOETT MORITZ , TURAN RAMAZAN G. , GORR EDUARD , HOPPE CHRISTIAN , HORLITZ MARC 
Published: February 2016

BackgroundSecond‐generation cryoballoon (CB‐2) is associated with improved outcomes for pulmonary vein isolation (PVI) compared to first generation (CB‐1). However, data regarding the predictors of pulmonary vein (PV) electrical reconnection are limited. In this study, we aimed to characterize the predilection sites and predictors of reconnection in patients with recurrent atrial tachyarrhythmia (ATa) after PVI using CB‐1 and CB‐2.MethodsA total of 59 patients (mean age: 62 ± 11 years and 66% male) with recurrent ATa after previous CB‐PVI, using either a 28‐mm CB‐1 or CB‐2, underwent repeat ablation. PV reisolation was performed by irrigated radiofrequency ablation using three‐dimensional electroanatomical mapping systems.ResultsElectrical PV reconnection was detected in 10 of 11 (91%) of CB‐1 patients compared to 41 of 48 (85%) of CB‐2 patients. Time to redo procedure after index CB‐1 was 8.9 ± 10.2 months and 11.2 ± 7.0 months in CB‐2. Bonus freeze was applied in all patients with CB‐1 and 41% of the patients with CB‐2. Superior quadrants of both superior PVs and inferior quadrants of the both inferior PVs exhibited higher predilection for conduction compared to other quadrants (P < 0.001). Multivariate binary logistic analysis revealed that right inferior PV (RIPV; odds ratio [OR]: 1.52, 95% confidence interval [CI]: 1.09–2.13, P = 0.014) and minimum temperature (OR: 1.09, 95% CI: 1.03–1.15, P = 0.004) were the independent predictors of electrical reconnection after CB‐2 ablation.ConclusionConduction gaps after CB‐1 and CB‐2 were higher in inferior PVs compared to superior PVs. The RIPV and minimum CB temperature were independent predictors of PV electrical reconnection after CB‐2.
Neck Pain and Cervical Dystonia: Treatment Outcomes from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy)
Authors: Charles P. David , Manack Adams Aubrey , Davis Thomas , Bradley Kathryn , Schwartz Marc , Brin Mitchell F. , Patel Atul T. 
Published: February 2016

AbstractBackgroundPain is a prevailing feature of cervical dystonia (CD), the most common form of focal dystonia. This analysis examined pain relief after onabotulinumtoxinA treatment in CD subjects with moderate/severe pain from the Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE).MethodsCD PROBE was a prospective, multicenter, observational registry of CD subjects who were naïve to botulinum toxin (BoNT), new to physician, or had not received BoNT within ≥ 16 weeks if in a clinical trial. Subjects were eligible for 3 treatments, with variable session intervals. Descriptive and inferential statistics were utilized to evaluate the change in pain scores in the population with moderate/severe neck pain at baseline (Pain Numeric Rating Scale [PNRS] score 4 to 10).ResultsOf 1046 enrolled, 733 (70.7%) had moderate/severe neck pain at baseline. Postinjection pain questionnaire responses 4 to 6 weeks after each of the 3 treatments revealed that a majority of subjects (67.1%, 72.4%, and 76.4%) reported pain relief; mean time to pain relief was 7.1, 7.4, and 7.6 days. All pain scales showed significant improvements from baseline to final visit (all P < 0.0001): PNRS, mean 6.6 to 3.8; CD Impact Profile‐58 Pain and Discomfort subscale, mean 78.7 to 56.5; and Toronto Western Spasmodic Torticollis Rating Scale Pain subscale, mean 12.6 to 8.5. Multivariable regression models showed that initial pain score significantly contributed to the final pain score for all scales.ConclusionResults from this real‐world clinical registry indicate that a majority of CD subjects with moderate/severe neck pain experience significant relief following onabotulinumtoxinA treatment.
Continuity and Change in Social Policy
Authors: Béland Daniel , Powell Martin 
Published: February 2016

AbstractWhile much has been written over the last two decades about social policy continuity and change, the literature is often fragmentary and imprecise, with little material exploring it in a systematic and rigorous manner. The objective of this article is to provide a critical reading of the recent literature, discussing concepts and issues such as paradigm shift, path dependence, punctuated equilibrium, ideational analysis and cumulative change (including conversion, layering and policy drift). It examines the degree and type of change, and explanations for change: the ‘how much, what type and why of change’. The article concludes with an overview of the contributions of this special issue of Social Policy & Administration devoted to the issues of policy continuity and change.
Policy Continuity and Change in Greek Social Policy in the Aftermath of the Sovereign Debt Crisis
Authors: Angelaki Marina 
Published: February 2016

AbstractThe extensive and radical reforms introduced in Greece's pension and health systems following the recent economic crisis provide a compelling case for the study of continuity and change in social policy. The article argues that a simple focus on retrenchment – as observed in pension and health in Greece in the aftermath of the crisis – provides only a partial understanding of the transformations taking place in the two sectors under study and their implications for the future structure of the two systems. While retrenchment has been the dominant feature associated with the fiscal consolidation effort undertaken in the context of the bailout agreements, other transformative processes have also taken place. In the case of pensions, a shift towards a more unified structure is observed, accompanied by a hesitant shift to a multi‐pillar system characterized by a reduction in public provision which is nonetheless not compensated by a strengthening of the second pillar. In the case of health, recent reforms attest to the gradual withering away of the public system through its shift to residualism. These changes have been made possible through the changes observed in the policy‐making process characterized by an unprecedented increase of the EU intrusiveness and the parallel decrease of the role and influence of social partners.
Photon counting x‐ray imaging with K‐edge filtered x‐rays: A simulation study
Authors: Atak Haluk , Shikhaliev Polad M. 
Published: February 2016

Purpose:In photon counting (PC) x‐ray imaging and computed tomography (CT), the broad x‐ray spectrum can be split into two parts using an x‐ray filter with appropriate K‐edge energy, which can improve material decomposition. Recent experimental study has demonstrated substantial improvement in material decomposition with PC CT when K‐edge filtered x‐rays were used. The purpose of the current work was to conduct further investigations of the K‐edge filtration method using comprehensive simulation studies.Methods:The study was performed in the following aspects: (1) optimization of the K‐edge filter for a particular imaging configuration, (2) effects of the K‐edge filter parameters on material decomposition, (3) trade‐off between the energy bin separation, tube load, and beam quality with K‐edge filter, (4) image quality of general (unsubtracted) images when a K‐edge filter is used to improve dual energy (DE) subtracted images, and (5) improvements with K‐edge filtered x‐rays when PC detector has limited energy resolution. The PC x‐ray images of soft tissue phantoms with 15 and 30 cm thicknesses including iodine, CaCO3, and soft tissue contrast materials, were simulated. The signal to noise ratio (SNR) of the contrast elements was determined in general and material‐decomposed images using K‐edge filters with different atomic numbers and thicknesses. The effect of the filter atomic number and filter thickness on energy separation factor and SNR was determined. The boundary conditions for the tube load and halfvalue layer were determined when the K‐edge filters are used. The material‐decomposed images were also simulated using PC detector with limited energy resolution, and improvements with K‐edge filtered x‐rays were quantified.Results:The K‐edge filters with atomic numbers from 56 to 71 and K‐edge energies 37.4–63.4 keV, respectively, can be used for tube voltages from 60 to 150 kVp, respectively. For a particular tube voltage of 120 kVp, the Gd and Ho were the optimal filter materials to achieve highest SNR. For a particular K‐edge filter of Gd and tube voltage of 120 kVp, the filter thickness 0.6 mm provided maximum SNR for considered imaging applications. While K‐edge filtration improved SNR of CaCO3 and iodine by 41% and 36%, respectively, in DE subtracted images, it did not deteriorate SNR in general images. For x‐ray imaging with nonideal PC detector, the positive effect of the K‐edge filter was increased when FWHM energy resolution was degraded, and maximum improvement was at 60% FWHM.Conclusions:This study has shown that K‐edge filtered x‐rays can provide substantial improvements of material selective PC x‐ray and CT imaging for nearly all imaging applications using 60–150 kVp tube voltages. Potential limitations such as tube load, beam hardening, and availability of filter material were shown to not be critical.
Technical Note: FreeCT_wFBP: A robust, efficient, open‐source implementation of weighted filtered backprojection for helical, fan‐beam CT
Authors: Hoffman John , Young Stefano , Noo Frédéric , McNitt‐Gray Michael 
Published: February 2016

Purpose:With growing interest in quantitative imaging, radiomics, and CAD using CT imaging, the need to explore the impacts of acquisition and reconstruction parameters has grown. This usually requires extensive access to the scanner on which the data were acquired and its workflow is not designed for large‐scale reconstruction projects. Therefore, the authors have developed a freely available, open‐source software package implementing a common reconstruction method, weighted filtered backprojection (wFBP), for helical fan‐beam CT applications.Methods:FreeCT_wFBP is a low‐dependency, GPU‐based reconstruction program utilizing c for the host code and Nvidia CUDA C for GPU code. The software is capable of reconstructing helical scans acquired with arbitrary pitch‐values, and sampling techniques such as flying focal spots and a quarter‐detector offset. In this work, the software has been described and evaluated for reconstruction speed, image quality, and accuracy. Speed was evaluated based on acquisitions of the ACR CT accreditation phantom under four different flying focal spot configurations. Image quality was assessed using the same phantom by evaluating CT number accuracy, uniformity, and contrast to noise ratio (CNR). Finally, reconstructed mass‐attenuation coefficient accuracy was evaluated using a simulated scan of a FORBILD thorax phantom and comparing reconstructed values to the known phantom values.Results:The average reconstruction time evaluated under all flying focal spot configurations was found to be 17.4 ± 1.0 s for a 512 row × 512 column × 32 slice volume. Reconstructions of the ACR phantom were found to meet all CT Accreditation Program criteria including CT number, CNR, and uniformity tests. Finally, reconstructed mass‐attenuation coefficient values of water within the FORBILD thorax phantom agreed with original phantom values to within 0.0001 mm2/g (0.01%).Conclusions:FreeCT_wFBP is a fast, highly configurable reconstruction package for third‐generation CT available under the GNU GPL. It shows good performance with both clinical and simulated data.
Role of Clinicogenomics in Infectious Disease Diagnostics and Public Health Microbiology
Authors: Westblade Lars F. , van Belkum Alex , Grundhoff Adam , Weinstock George M. , Pamer Eric G. , Pallen Mark J. , Dunne W. Michael 
Published: February 2016

ABSTRACT
Clinicogenomics is the exploitation of genome sequence data for diagnostic, therapeutic, and public health purposes. Central to this field is the high-throughput DNA sequencing of genomes and metagenomes. The role of clinicogenomics in infectious disease diagnostics and public health microbiology was the topic of discussion during a recent symposium (session 161) presented at the 115th general meeting of the American Society for Microbiology that was held in New Orleans, LA. What follows is a collection of the most salient and promising aspects from each presentation at the symposium.
Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence
Authors: McAuley Alexander J. , Torres Maricela , Plante Jessica A. , Huang Claire Y.-H. , Bente Dennis A. , Beasley David W. C. 
Published: February 2016

ABSTRACT

Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras
in vitro
and
in vivo
revealed differences in growth and virulence between the viruses, with
in vivo
pathogenesis often not being correlated with
in vitro
growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence.

IMPORTANCE
The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric viruses indicate a significant role for this sequence in determining the pathogenesis of the virus within the mammalian host. Our studies demonstrate that these chimeras are viable and suggest that such recombinant viruses may be useful for investigation of domain-specific antibody responses and the more extensive definition of the contributions of EIII to the tropism and pathogenesis of WNV or other flaviviruses.
Nucleic Acid Binding by Mason-Pfizer Monkey Virus CA Promotes Virus Assembly and Genome Packaging
Authors: Füzik Tibor , Píchalová Růžena , Schur Florian K. M. , Strohalmová Karolína , Křížová Ivana , Hadravová Romana , Rumlová Michaela , Briggs John A. G. , Ulbrich Pavel , Ruml Tomáš 
Published: February 2016

ABSTRACT

The Gag polyprotein of retroviruses drives immature virus assembly by forming hexameric protein lattices. The assembly is primarily mediated by protein-protein interactions between capsid (CA) domains and by interactions between nucleocapsid (NC) domains and RNA. Specific interactions between NC and the viral RNA are required for genome packaging. Previously reported cryoelectron microscopy analysis of immature Mason-Pfizer monkey virus (M-PMV) particles suggested that a basic region (residues RKK) in CA may serve as an additional binding site for nucleic acids. Here, we have introduced mutations into the RKK region in both bacterial and proviral M-PMV vectors and have assessed their impact on M-PMV assembly, structure, RNA binding, budding/release, nuclear trafficking, and infectivity using
in vitro
and
in vivo
systems. Our data indicate that the RKK region binds and structures nucleic acid that serves to promote virus particle assembly in the cytoplasm. Moreover, the RKK region appears to be important for recruitment of viral genomic RNA into Gag particles, and this function could be linked to changes in nuclear trafficking. Together these observations suggest that in M-PMV, direct interactions between CA and nucleic acid play important functions in the late stages of the viral life cycle.

IMPORTANCE
Assembly of retrovirus particles is driven by the Gag polyprotein, which can self-assemble to form virus particles and interact with RNA to recruit the viral genome into the particles. Generally, the capsid domains of Gag contribute to essential protein-protein interactions during assembly, while the nucleocapsid domain interacts with RNA. The interactions between the nucleocapsid domain and RNA are important both for identifying the genome and for self-assembly of Gag molecules. Here, we show that a region of basic residues in the capsid protein of the betaretrovirus Mason-Pfizer monkey virus (M-PMV) contributes to interaction of Gag with nucleic acid. This interaction appears to provide a critical scaffolding function that promotes assembly of virus particles in the cytoplasm. It is also crucial for packaging the viral genome and thus for infectivity. These data indicate that, surprisingly, interactions between the capsid domain and RNA play an important role in the assembly of M-PMV.