bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commentary: Next-Generation Epidemiology: Using Real-Time Core Genome Multilocus Sequence Typing To Support Infection Control Policy
Authors: Dekker John P. , Frank Karen M. 
Published: September 2016

ABSTRACT

Multidrug-resistant bacteria are responsible for substantial morbidity and mortality worldwide. Tracking the nosocomial spread of resistant bacteria is critical to infection control. Mellmann et al. (J. Clin. Microbiol. 54:2874–2881, 2016,
http://dx.doi.org/10.1128/JCM.00790-16
) have described prospective whole-genome sequencing with core genome multilocus sequencing typing (cgMLST) analysis for real-time surveillance and have addressed the practical aspects of implementing this type of operation in the hospital setting.
Rationally Designed Vaccines Targeting the V2 Region of HIV-1 gp120 Induce a Focused, Cross-Clade-Reactive, Biologically Functional Antibody Response
Authors: Zolla-Pazner Susan , Powell Rebecca , Yahyaei Sara , Williams Constance , Jiang Xunqing , Li Wei , Lu Shan , Wang Shixia , Upadhyay Chitra , Hioe Catarina E. , Totrov Max , Kong Xiangpeng 
Published: September 2016

ABSTRACT
Strong antibody (Ab) responses against V1V2 epitopes of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope (Env) correlated with reduced infection rates in studies of HIV, simian-human immunodeficiency virus (SHIV), and simian immunodeficiency virus (SIV). In order to focus the Ab response on V1V2, we used six V1V2 sequences and nine scaffold proteins to construct immunogens which were tested using various immunization regimens for their ability to induce cross-reactive and biologically active V2 Abs in rabbits. A prime/boost immunization strategy was employed using gp120 DNA and various V1V2-scaffold proteins. The rabbit polyclonal Ab responses (i) were successfully focused on the V1V2 region, with weak or only transient responses to other Env epitopes, (ii) displayed broad cross-reactive binding activity with gp120s and the V1V2 regions of diverse strains from clades B, C, and E, (iii) included V2 Abs with specificities similar to those found in HIV-infected individuals, and (iv) remained detectable ≥1 year after the last boosting dose. Importantly, sera from rabbits receiving V1V2-scaffold immunogens displayed Ab-dependent cellular phagocytosis whereas sera from rabbits receiving only gp120 did not. The results represent the first fully successful example of reverse vaccinology in the HIV vaccine field with rationally designed epitope scaffold immunogens inducing Abs that recapitulate the epitope specificity and biologic activity of the human monoclonal Abs from which the immunogens were designed. Moreover, this is the first immunogenicity study using epitope-targeting, rationally designed vaccine constructs that induced an Fc-mediated activity associated with protection from infection with HIV, SIV, and SHIV.

IMPORTANCE
Novel immunogens were designed to focus the antibody response of rabbits on the V1V2 epitopes of HIV-1 gp120 since such antibodies were associated with reduced infection rates of HIV, SIV, and SHIV. The vaccine-induced antibodies were broadly cross-reactive with the V1V2 regions of HIV subtypes B, C and E and, importantly, facilitated Fc-mediated phagocytosis, an activity not induced upon immunization of rabbits with gp120. This is the first immunogenicity study of vaccine constructs that focuses the antibody response on V1V2 and induces V2-specific antibodies with the ability to mediate phagocytosis, an activity that has been associated with protection from infection with HIV, SIV, and SHIV.
Herpes Simplex Virus 1 Enters Human Keratinocytes by a Nectin-1-Dependent, Rapid Plasma Membrane Fusion Pathway That Functions at Low Temperature
Authors: Sayers Charlotte L. , Elliott Gillian 
Published: September 2016

ABSTRACT

Herpes simplex virus 1 (HSV-1) infects humans through stratified epithelia that are composed primarily of keratinocytes. The route of HSV-1 entry into keratinocytes has been the subject of limited investigation, but it is proposed to involve pH-dependent endocytosis, requiring the gD-binding receptor nectin-1. Here, we have utilized the nTERT human keratinocyte cell line as a new model for dissecting the mechanism of HSV-1 entry into the host. Although immortalized, these cells nonetheless retain normal growth and differentiation properties of primary cells. Using short interfering RNA (siRNA) depletion studies, we confirm that, despite nTERT cells expressing high levels of the alternative gD receptor HVEM, HSV-1 requires nectin-1, not HVEM, to enter these cells. Strikingly, virus entry into nTERT cells occurred with unusual rapidity, such that maximum penetration was achieved within 5 min. Moreover, HSV-1 was able to enter keratinocytes but not other cell types at temperatures as low as 7°C, conditions where endocytosis was shown to be completely inhibited. Transmission electron microscopy of early entry events at both 37°C and 7°C identified numerous examples of naked virus capsids located immediately beneath the plasma membrane, with no evidence of virions in cytoplasmic vesicles. Taken together, these results imply that HSV-1 uses the nectin-1 receptor to enter human keratinocyte cells via a previously uncharacterized rapid plasma membrane fusion pathway that functions at low temperature. These studies have important implications for current understanding of the relationship between HSV-1 and its relevant
in vivo
target cell.

IMPORTANCE
The gold standard of antiviral treatment for any human virus infection is the prevention of virus entry into the host cell. In the case of HSV-1, primary infection in the human begins in the epidermis of the skin or the oral mucosa, where the virus infects keratinocytes, and it is therefore important to understand the molecular events involved in HSV-1 entry into this cell type. Nonetheless, few studies have looked specifically at entry into these relevant human cells. Our results reveal a new route for virus entry that is specific to keratinocytes, involves rapid entry, and functions at low temperatures. This may reflect the environmental conditions encountered by HSV-1 when entering its host through the skin and emphasizes the importance of studying virus-host interactions in physiologically relevant cells.
Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s
Authors: Gu Qinyong , Zhang Zeli , Cano Ortiz Lucía , Franco Ana Cláudia , Häussinger Dieter , Münk Carsten 
Published: September 2016

ABSTRACT

Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (
Felis catus
) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain.

IMPORTANCE
Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in
Felidae
.
Transition into and out of daylight saving time and spontaneous delivery: a population-based study
Authors: László Krisztina D , Cnattingius Sven , Janszky Imre 
Published: September 2016

ObjectiveTo investigate whether the circadian rhythm disruption following the transition into and out of daylight saving time (DST) is associated with an increased risk of spontaneous delivery.DesignWe compared the number of spontaneous deliveries in the Swedish Medical Birth Register during the week after the change to and the week after the change from DST (exposure periods) with the average number of spontaneous deliveries in the control period, defined as the week before and the week after each exposure period.SettingSweden, 1993–2006.Primary and secondary outcome measuresThe primary outcomes were the weekly and the daily number of spontaneous deliveries in the exposure and the control periods. In secondary analyses we also compared the mean length of pregnancy of the women with spontaneous deliveries in the exposure and control periods.ResultsThe number of deliveries during the week after the transition into or out of DST was similar to that in the comparison period (18 519 observed vs 18 434 expected in case of the spring shift and 19 073 observed vs 19 122 expected in case of the autumn shift); the corresponding incidence ratio and 95% CIs were 1.005 (0.990 to 1.019) and 0.997 (0.983 to 1.012), respectively. There were no differences in the length of gestation of the deliveries in the exposure and the control periods.ConclusionsOur results do not support the hypothesis that a minor circadian rhythm disruption is associated with an increased short-term risk of spontaneous delivery.
Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo
Authors: Rao Shreyas S. , Bushnell Grace G. , Azarin Samira M. , Spicer Graham , Aguado Brian A. , Stoehr Jenna R. , Jiang Eric J. , Backman Vadim , Shea Lonnie D. , Jeruss Jacqueline S. 
Published: September 2016

Abstract
The onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(ϵ-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b+Gr1hiLy6C− cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b+Gr1hiLy6C− cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. Cancer Res; 76(18); 5209–18. ©2016 AACR.
Molecular or Metabolic Reprograming: What Triggers Tumor Subtypes?
Authors: Eason Katherine , Sadanandam Anguraj 
Published: September 2016

Abstract
Tumor heterogeneity is reflected and influenced by genetic, epigenetic, and metabolic differences in cancer cells and their interactions with a complex microenvironment. This heterogeneity has resulted in the stratification of tumors into subtypes, mainly based on cancer-specific genomic or transcriptomic profiles. Subtyping can lead to biomarker identification for personalized diagnosis and therapy, but stratification alone does not explain the origins of tumor heterogeneity. Heterogeneity has traditionally been thought to arise from distinct mutations/aberrations in “driver” oncogenes. However, certain subtypes appear to be the result of adaptation to the disrupted microenvironment caused by abnormal tumor vasculature triggering metabolic switches. Moreover, heterogeneity persists despite the predominance of single oncogenic driver mutations, perhaps due to second metabolic or genetic “hits.” In certain cancer types, existing subtypes have metabolic and transcriptomic phenotypes that are reminiscent of normal differentiated cells, whereas others reflect the phenotypes of stem or mesenchymal cells. The cell-of-origin may, therefore, play a role in tumor heterogeneity. In this review, we focus on how cancer cell–specific heterogeneity is driven by different genetic or metabolic factors alone or in combination using specific cancers to illustrate these concepts. Cancer Res; 76(18); 5195–200. ©2016 AACR.
Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite?
Authors: Adamski Piotr , Sikora Joanna , Sikora Adam , Karczmarska-Wódzka Aleksandra , Marszał Michat , Boinska Joanna , Laskowska Ewa , Obońska Ewa , Fabiszak Tomasz , Kubica Jacek , Koziński Marek , Ostrowska Małgorzata 
Published: September 2016

SummaryAim of this study was assessment of the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of selected platelet function tests. In a single-centre, cohort study, patients with myocardial infarction underwent blood sampling following a 180 mg ticagrelor loading dose intake (predose, 1, 2, 3, 4, 6, 12, 24 hours postdose) to perform pharmacokinetic and pharmacodynamic assessments. Platelet reactivity was evaluated using the VASP-assay, the VerifyNow device and the Multiplate analyzer. Analysis of 36 patients revealed high negative correlations between ticagrelor concentrations and platelet reactivity evaluated with all three platelet function tests (the VASP-assay: RS=-0.722; p<0.0001; the VerifyNow device: RS=-0.715; p<0.0001; the Multiplate analyzer: RS=-0.722; p<0.0001), with no significant differences between correlation coefficients. Similar results were found for AR-C124910XX. Platelet reactivity values assessed with all three methods generally correlated well with each other; however, a significantly higher correlation (p<0.02) was demonstrated between the VerifyNow and Multiplate tests (RS=0.707; p<0.0001) than in other assay combinations (the VASP-assay and the VerifyNow device: RS=0.595; p<0.0001; the VASP-assay and the Multiplate analyzer: RS=0.588; p<0.0001). With respect to the recognition of high platelet reactivity, we found higher measurement concordance between the VerifyNow and Multiplate tests compared with other assay combinations, while for low platelet reactivity, only results of the VerifyNow and Multiplate assay were related to each other. Platelet reactivity measurements performed with the VASP, VerifyNow and Multiplate tests show comparably strong negative correlations with ticagrelor and AR-C124910XX concentrations.Study registration: ClinicalTrials.gov identifier NCT02690454.
Leaping frogs (Anura: Ranixalidae) of the Western Ghats of India: An integrated taxonomic review
Authors: Dahanukar Neelesh , Modak Nikhil , Krutha Keerthi , Nameer P. O. , Padhye Anand D. , Molur Sanjay 
Published: September 2016

Leaping frogs of the family Ranixalidae are endemic to the Western Ghats of India and are currently placed in a single genus, Indirana. Based on specimens collected from their entire range and a comprehensive study of type material defining all known species, we propose a revised taxonomy for the leaping frogs using an integrative approach including an analysis of the mitochondrial 16S rRNA and nuclear rhodopsin genes, as well as multivariate morphometrics. Both genetic and morphological analyses suggest that the genus Indirana is paraphyletic and a distinct monophyletic group, Walkerana gen. nov is described herein. The new genus is separated from Indirana sensu stricto by an apomorphic character state of reduced webbing, with one phalange free on the first and second toe (vs. no free phalanges), two phalanges free on the third and fifth toe (vs. one free phalange), and three phalanges free on the fourth toe (vs. 2–2½ phalanges free). This review includes (i) identification of lectotypes and redescription of three species of the genus Walkerana; (ii) identification of lectotypes for Indirana beddomii and I. semipalmata and their redescription; (iii) redescription of I. brachytarsus and I. gundia; and (iv) descriptions of four new species, namely, I. duboisi and I. tysoni from north of the Palghat gap, and I. yadera and I. sarojamma from south of the Palghat gap; and (iv) a key to the genera and species in the family Ranixalidae.
Macroreentrant Loop in Ventricular Tachycardia From the Left Posterior Fascicle
Authors: Liu Qiang , Shehata Michael , Jiang Ruhong , Yu Lu , Chen Shiquan , Zhu Jun , Ehdaie Ashkan , Sovari Ali A. , Cingolani Eugenio , Chugh Sumeet S. , Jiang Chenyang , Wang Xunzhang 
Published: September 2016

Background—
The underlying mechanisms of reentry during left posterior fascicular ventricular tachycardia (LPF-VT) remain unclear. The purpose of this study is to describe the components of LPF-VT reentry circuit and their electrophysiological properties.

Methods and Results—
Fourteen consecutive patients with LPF-VT underwent electrophysiology study and radiofrequency ablation. Via a multipolar electrode catheter placed from a retrograde aortic approach, a sharp inflection, high-frequency potential (P1) was detected in 9 patients (64%). The ranges of length and velocity of recorded P1 were 9 to 30 mm and 0.5 to 1.2 mm/ms, respectively. Macroreentry involving the ventricular myocardium was confirmed to be the mechanism in all patients by premature ventricular stimuli delivery or entrainment of LPF-VT with progressive fusion, or both. During LPF-VT, the earliest left posterior fascicle (LPF, P2) was considered to be the site of connection between P1 and P2, and the site of the earliest P2 along the left posterior ventricular septum correlated well with the His-ventricular interval during tachycardia. Radiofrequency ablation focused on the P1 potentials (9 patients with a recorded P1) or earliest P2 (5 patients without a recorded P1) was successful in all 14 patients. After 4.5±3.0 months of follow-up, no patients had recurrence of LPF-VT.

Conclusions—
The LPF-VT macroreentrant loop involves the ventricular myocardium, a part of the LPF, a slow conduction zone, and in certain cases, a specially conducting P1 fiber. The His-ventricular interval during LPF-VT correlates with multiple electrophysiological measures and is a useful marker for identification of the optimal ablation site.
Global Distribution of Gravity Wave Sources and Fields in the Martian Atmosphere during Equinox and Solstice Inferred from a High-Resolution General Circulation Model
Authors: Kuroda Takeshi , Medvedev Alexander S. , Yiğit Erdal , Hartogh Paul 
Published: September 2016

Abstract
Results of simulations with a new high-resolution Martian general circulation model (MGCM) (T106 spectral resolution, or ~67-km horizontal grid size) have been analyzed to reveal global distributions of gravity waves (GWs) during the solstice and equinox periods. They show that shorter-scale harmonics progressively dominate with height, and the body force per unit mass (drag) they impose on the larger-scale flow increases. Mean magnitudes of the drag in the middle atmosphere are tens of meters per second per sol, while instantaneously they can reach thousands of meters per second per sol. Inclusion of small-scale GW harmonics results in an attenuation of the wind jets in the middle atmosphere and in the tendency of their reversal. GW energy in the troposphere due to the shortest-scale harmonics is concentrated in the low latitudes for both seasons and is in a good agreement with observations. The vertical fluxes of wave horizontal momentum are directed mainly against the larger-scale wind. Orographically generated GWs contribute significantly to the total energy of small-scale disturbances and to the drag created by the latter. These waves strongly decay with height, and thus the nonorographic GWs of tropospheric origin dominate near the mesopause. The results of this study can be used to better constrain and validate GW parameterizations in MGCMs.
All-Sky Microwave Radiance Assimilation in NCEP’s GSI Analysis System
Authors: Zhu Yanqiu , Liu Emily , Mahajan Rahul , Thomas Catherine , Groff David , Van Delst Paul , Collard Andrew , Kleist Daryl , Treadon Russ , Derber John C. 
Published: September 2016

AbstractThe capability of all-sky microwave radiance assimilation in the Gridpoint Statistical Interpolation (GSI) analysis system has been developed at the National Centers for Environmental Prediction (NCEP). This development effort required the adaptation of quality control, observation error assignment, bias correction, and background error covariance to all-sky conditions within the ensemble–variational (EnVar) framework. The assimilation of cloudy radiances from the Advanced Microwave Sounding Unit-A (AMSU-A) microwave radiometer for ocean fields of view (FOVs) is the primary emphasis of this study.In the original operational hybrid 3D EnVar Global Forecast System (GFS), the clear-sky approach for radiance data assimilation is applied. Changes to data thinning and quality control have allowed all-sky satellite radiances to be assimilated in the GSI. Along with the symmetric observation error assignment, additional situation-dependent observation error inflation is employed for all-sky conditions. Moreover, in addition to the current radiance bias correction, a new bias correction strategy has been applied to all-sky radiances. In this work, the static background error variance and the ensemble spread of cloud water are examined, and the levels of cloud variability from the ensemble forecast in single- and dual-resolution configurations are discussed. Overall, the all-sky approach provides more realistic simulated brightness temperatures and cloud water analysis increments, and improves analysis off the west coasts of the continents by reducing a known bias in stratus. An approximate 10% increase in the use of AMSU-A channels 1–5 and a 12% increase for channel 15 are also observed. The all-sky AMSU-A radiance assimilation became operational in the 4D EnVar GFS system upgrade of 12 May 2016.