bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Conserved Leucine Zipper Motif in Gammaherpesvirus ORF52 Is Critical for Distinct Microtubule Rearrangements
Authors: Loftus Matthew S. , Verville Nancy , Kedes Dean H. 
Published: June 2017

ABSTRACT
Productive viral infection often depends on the manipulation of the cytoskeleton. Herpesviruses, including rhesus monkey rhadinovirus (RRV) and its close homolog, the oncogenic human gammaherpesvirus Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8), exploit microtubule (MT)-based retrograde transport to deliver their genomes to the nucleus. Subsequently, during the lytic phase of the life cycle, the maturing viral particles undergo orchestrated translocation to specialized regions within the cytoplasm, leading to tegumentation, secondary envelopment, and then egress. As a result, we hypothesized that RRV might induce changes in the cytoskeleton at both early and late stages of infection. Using confocal imaging, we found that RRV infection led to the thickening and acetylation of MTs emanating from the MT-organizing center (MTOC) shortly after viral entry and more pronounced and diffuse MT reorganization during peak stages of lytic gene expression and virion production. We subsequently identified open reading frame 52 (ORF52), a multifunctional and abundant tegument protein, as being the only virally encoded component responsible for these cytoskeletal changes. Mutational and modeling analyses indicated that an evolutionarily conserved, truncated leucine zipper motif near the N terminus as well as a strictly conserved arginine residue toward the C terminus of ORF52 play critical roles in its ability to rearrange the architecture of the MT cytoskeleton. Taken together, our findings combined with data from previous studies describing diverse roles for ORF52 suggest that it likely binds to different cellular components, thereby allowing context-dependent modulation of function.

IMPORTANCE
A thorough understanding of the processes governing viral infection includes knowledge of how viruses manipulate their intracellular milieu, including the cytoskeleton. Altering the dynamics of actin or MT polymerization, for example, is a common strategy employed by viruses to ensure efficient entry, maturation, and egress as well as the avoidance of antiviral defenses through the sequestration of key cellular factors. We found that infection with RRV, a homolog of the human pathogen KSHV, led to perinuclear wrapping by acetylated MT bundles and identified ORF52 as the viral protein underlying these changes. Remarkably, incoming virions were able to supply sufficient ORF52 to induce MT thickening and acetylation near the MTOC, potentially aiding in the delivery viral genomes to the nucleus. Although the function of MT alterations during late stages of infection requires further study, ORF52 shares functional and structural similarities with alphaherpesvirus VP22, underscoring the evolutionary importance of MT cytoskeletal manipulations for this virus family.
Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8
+
T Cell Function and Impaired Viral Clearance
Authors: Lupfer Christopher R. , Stokes Kate L. , Kuriakose Teneema , Kanneganti Thirumala-Devi 
Published: June 2017

ABSTRACT

Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied. Here we show that
Nlrc5
−/−
mice exhibit an altered CD8
+
T cell response during IAV infection compared to that of wild-type (WT) mice.
Nlrc5
−/−
mice have decreased MHC-I expression on hematopoietic cells and fewer CD8
+
T cells prior to infection. NLRC5 deficiency does not affect the generation of antigen-specific CD8
+
T cells following IAV infection; however, a change in epitope dominance is observed in
Nlrc5
−/−
mice. Moreover, IAV-specific CD8
+
T cells from
Nlrc5
−/−
mice have impaired effector functions. This change in the adaptive immune response is associated with impaired viral clearance in
Nlrc5
−/−
mice. Collectively, our results demonstrate an important role for NLRC5 in regulation of antiviral immune responses and viral clearance during IAV infection.

IMPORTANCE
The NOD-like receptor family member NLRC5 is known to regulate expression of MHC-I as well as other genes required for antigen processing. In addition, NLRC5 also regulates various immune signaling pathways. In this study, we investigated the role of NLRC5 during influenza virus infection and found a major role for NLRC5 in restricting virus replication and promoting viral clearance. The observed increases in viral titers in NLRC5-deficient mice correlated with impaired effector CD8
+
T cell responses. Although NLRC5-deficient mice were defective at clearing the virus, they did not show an increase in morbidity or mortality following influenza virus infection because of other compensatory immune mechanisms. Therefore, our study highlights how NLRC5 regulates multiple immune effector mechanisms to promote the host defense during influenza virus infection.
Plasticity and Epitope Exposure of the HIV-1 Envelope Trimer
Authors: Powell Rebecca L. R. , Totrov Maxim , Itri Vincenza , Liu Xiaomei , Fox Alisa , Zolla-Pazner Susan 
Published: June 2017

ABSTRACT
We recently showed that mutations in the HIV-1 envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (MAbs). Here, we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wild-type JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 MAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intraprotomer interactions exposed epitopes in the V2i region (which overlies the α4β7 integrin binding site) and the V3 crown, suggesting general destabilization of the distal region of the trimer apex. In contrast, other glycan mutants, mutations affecting interprotomer interactions, and mutations affecting the CD4bs exposed V3 but not V2i epitopes. These data indicate for the first time that V3 can move independently of V2, with V3 pivoting out from its “tucked” position in the trimer while apparently leaving the V2 apex intact. Notably, none of the mutations exposed V2 epitopes without also exposing V3, suggesting that movement of V2 releases V3. Most mutations increased sensitivity to CD4bs-directed MAbs without exposure of the CD4i epitope, implying these mutations facilitate the trimers' maintenance of an intermediate energy state between open and closed conformations. Taken together, these data indicate that several transient Env epitopes can be rendered more accessible to antibodies (Abs) via specific mutations, and this may facilitate the design of V1V2-targeting immunogens.

IMPORTANCE
Many epitopes of the HIV envelope (Env) spike are relatively inaccessible to antibodies (Abs) compared to their exposure in the open Env conformation induced by receptor binding. However, the reduced infection rate that resulted from the vaccine used in the RV144 HIV-1 vaccine trial was correlated with the elicitation of V2- and V3-directed antibodies. Previously, we identified various mechanisms responsible for destabilizing the V3 loop; here, we determined, via mutation of numerous Env residues, which of these elements maintain the V1V2 loop in an inaccessible state and which expose V1V2 and/or V3 epitopes. Notably, our data indicate that V3 can move independently of V2, but none of the mutations studied expose V2 epitopes without also exposing V3. Additionally, V1V2 can be rendered more accessible to Abs via specific mutations, facilitating the development of engineered V2 immunogens.
Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice
Authors: Lennemann Nicholas J. , Herbert Andrew S. , Brouillette Rachel , Rhein Bethany , Bakken Russell A. , Perschbacher Katherine J. , Cooney Ashley L. , Miller-Hunt Catherine L. , Ten Eyck Patrick , Biggins Julia , Olinger Gene , Dye John M. , Maury Wendy 
Published: June 2017

ABSTRACT
The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.

IMPORTANCE
The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.
Raman-Encoded Molecular Imaging with Topically Applied SERS Nanoparticles for Intraoperative Guidance of Lumpectomy
Authors: Wang Yu “Winston” , Reder Nicholas P. , Kang Soyoung , Glaser Adam K. , Yang Qian , Wall Matthew A. , Javid Sara H. , Dintzis Suzanne M. , Liu Jonathan T.C. 
Published: June 2017

Abstract
Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20% to 50%. Although imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high sensitivity. We have developed a Raman-encoded molecular imaging (REMI) technique in which targeted nanoparticles are topically applied on excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. A first-ever clinical study was performed in which 57 fresh specimens were imaged with REMI to simultaneously quantify the expression of four biomarkers HER2, ER, EGFR, and CD44. Combined detection of these biomarkers enabled REMI to achieve 89.3% sensitivity and 92.1% specificity for the detection of breast carcinoma. These results highlight the sensitivity and specificity of REMI to detect biomarkers in freshly resected tissue, which has the potential to reduce the rate of re-excision procedures in cancer patients. Cancer Res; 77(16); 4506–16. ©2017 AACR.
ІМУНОЛОГІЧНИЙ МОНІТОРИНГ ДОРОСЛОГО НАСЕЛЕННЯ ЛЬВІВЩИНИ ЩОДО КАШЛЮКУ У 2016 РОЦІ
Authors: Ivanchenko N. O. 
Published: June 2017

Мета – провести серологічний моніторинг серед дорослого населення щодо кількісного визначення імуноглобулінів класу G до кашлюку.Матеріали і методи. Дослідження проводились з використанням методу імуноферментного аналізу.Результати досліджень та їх обговорення. Серонегативний прошарок населення становить 50,0 %. Специфічні імуноглобуліни G у високих титрах (понад 50 BU/ml) були виявлені у 3,75 % осіб, що свідчить про період реконвалесценції після кашлюку.Висновки. Використання цього методу підтверджує наявність випадків захворювання на кашлюк серед дорослого населення при недостатній настороженості медичних працівників щодо захворюваності на кашлюк даної вікової групи. Підтверджено об’єктивність і інформативність методу та доцільність його широкого впровадження в практику громадського здоров’я з метою здійснення належного епідеміологічного нагляду.
Die friesischen Wortformen des Etymons Welt (World) in Zeit und Raum: Erb- vs. Lehnlautungen
Authors: Århammar Nils 
Published: June 2017

In this study we classify and analyse the complete Frisian lexical evidence for the notion of ‘world’, based on the West Germanic compound *wer-aldō. This paper is also intended as a contribution to a Frisian supplement to Buck’s Dictionary of Selected Indo-European Synonyms, for which plans were made in the early 1970s; compare the parallel studies on the words for ‘lark’ and ‘wheel’ by the same author. Due to the lack of medieval sources from particular regions, we here have to resort to linguistic reconstruction. This brings with it a considerable degree of uncertainty when judging the lexical evidence of some of the dialects. In the summary of the article the more or less certain Erblautungen wrald and warld and the unambiguous borrowings werelt and welt are discussed synoptically. Included is a conclusion about the intrinsic liability of abstract notions such as ‘world’ to be borrowed. Finally, we consider the possibility of founding a working group for The Frisian C. D. Buck.
Die vorliegende Studie inventarisiert und analysiert sprachhistorisch das gesamte friesische Wortmaterial des Begriffs ‘Weltʼ (‘Worldʼ), das auf dem westgerm. Kompositum *wer-aldō basiert. Es ist zugleich ein Beitrag zu dem Anfang der 70er Jahre propagierten friesischen Supplement zu C. D. Buckʼs Dictionary of Selected Indo-European Synonyms; vgl. die Parallelstudien über den ebenfalls univerbalen Vogelnamen ‘Lerche (Alauda)ʼ und ‘Radʼ (‘Wheelʼ) im Friesischen. Für das Saterländer, Harlinger, Wangerooger und Wurster Ostfriesisch sowie das gesamte Nordfriesisch sind wir mangels mittelalterlicher Überlieferung auf Rekonstruktion angewiesen, was für die Beurteilung der Wortformen dieser Dialekte einen nicht geringen Unsicherheitsfaktor darstellt. In der Zusammenfassung werden die exklusiv friesische Erblautung wrald und das zwieschlächtige (Erb- oder Lehnlautung?) warld sowie die eindeutigen Lehnlautungen werelt und welt abschließend behandelt. Zusätzlich wird der Versuch einer induktiven Schlussfolgerung hinsichtlich der potentiellen Prädisposition von abstrakten Wörtern wie Welt zu Entlehnung unternommen. In der Nachbetrachtung wird die Etablierung einer Arbeitsgemeinschaft The Frisian bzw. Der friesische C. D. Buck in Erwägung gezogen.
This article is in German.
Ice Multiplication by Breakup in Ice–Ice Collisions. Part II: Numerical Simulations
Authors: Phillips Vaughan T. J. , Yano Jun-Ichi , Formenton Marco , Ilotoviz Eyal , Kanawade Vijay , Kudzotsa Innocent , Sun Jiming , Bansemer Aaron , Detwiler Andrew G. , Khain Alexander , Tessendorf Sarah A. 
Published: June 2017

AbstractIn Part I of this two-part paper, a formulation was developed to treat fragmentation in ice–ice collisions. In the present Part II, the formulation is implemented in two microphysically advanced cloud models simulating a convective line observed over the U.S. high plains. One model is 2D with a spectral bin microphysics scheme. The other has a hybrid bin–two-moment bulk microphysics scheme in 3D. The case consists of cumulonimbus cells with cold cloud bases (near 0°C) in a dry troposphere.Only with breakup included in the simulation are aircraft observations of particles with maximum dimensions >0.2 mm in the storm adequately predicted by both models. In fact, breakup in ice–ice collisions is by far the most prolific process of ice initiation in the simulated clouds (95%–98% of all nonhomogeneous ice), apart from homogeneous freezing of droplets. Inclusion of breakup in the cloud-resolving model (CRM) simulations increased, by between about one and two orders of magnitude, the average concentration of ice between about 0° and −30°C. Most of the breakup is due to collisions of snow with graupel/hail. It is broadly consistent with the theoretical result in Part I about an explosive tendency for ice multiplication.Breakup in collisions of snow (crystals >~1 mm and aggregates) with denser graupel/hail was the main pathway for collisional breakup and initiated about 60%–90% of all ice particles not from homogeneous freezing, in the simulations by both models. Breakup is predicted to reduce accumulated surface precipitation in the simulated storm by about 20%–40%.
Physical Factors Influencing Regional Precipitation Variability Attributed Using an Airmass Trajectory Method
Authors: de Leeuw Johannes , Methven John , Blackburn Michael 
Published: June 2017

Abstract
A novel Lagrangian framework is developed to attribute monthly precipitation variability to physical processes. Precipitation variability is partitioned into a combination of five factors: airmass origin location, origin surface temperature variation, ascent intensity, mass fraction of ascending air, and the number of “wet” analysis times per month [&gt;1 mm (6 h)−1]. Precipitation in a target region is linked to “origin” locations of air masses where the water vapor mixing ratio was last set by boundary layer moistening and is a maximum along back trajectories. Applying the technique to the England and Wales region, the factors together account for 83%–89% of the observed summer precipitation variability. The dominant contributor is the number of wet analyses, which is shown to be associated with cyclone statistics. The wettest summer months are mainly associated with anomalous cyclone duration rather than the number of cyclones. In addition, surface temperature and saturation humidity at the origin locations are found to be below their climatological averages (1979–2013). Therefore, the direct thermodynamic effect of anomalous surface temperature on marine boundary layer humidity acts to reduce monthly precipitation anomalies. The decadal precipitation change between phases of the Atlantic multidecadal oscillation is approximately 20% of the interannual variability between summer months. Changes in cyclone statistics have an effect 6 times larger than the direct thermodynamic factor in both monthly and decadal precipitation variability.
Corticosteroid Injection for the Treatment of Morton’s Neuroma: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Trial
Authors: Lizano-Díez Xavier , Ginés-Cespedosa Alberto , Alentorn-Geli Eduard , Pérez-Prieto Daniel , González-Lucena Gemma , Gamba Carlo , de Zabala Santiago , Solano-López Alberto , Rigol-Ramón Pau 
Published: June 2017

Background: The effectiveness of corticosteroid injection for the treatment of Morton’s neuroma is unclear. In addition, most of the studies related to it are case-control or retrospective case series. The purpose of this study was to compare the effectiveness between corticosteroid injection associated with local anesthetic and local anesthetic alone (placebo control group) for the treatment of Morton’s neuroma. Methods: Forty-one patients with a diagnosis of Morton’s neuroma were randomized to receive 3 injections of either a corticosteroid plus a local anesthetic or a local anesthetic alone. The patients and the researcher who collected data were blinded to the treatment groups. The visual analog scale for pain and the American Orthopaedic Foot & Ankle Score (metatarsophalangeal/interphalangeal score) were obtained at baseline, after each injection, and at 3 and 6 months after the last injection. Results: There were no significant between-group differences in terms of pain and function improvement at 3 and 6 months after treatment completion in comparison with baseline values. At the end of the study, 17 (48.5%) patients requested surgical excision of the neuroma: 7 (44%) in the experimental group and 10 (53%) in the control group ( P = 1.0). Conclusion: The injection of a corticosteroid plus a local anesthetic was not superior to a local anesthetic alone in terms of pain and function improvement in patients with Morton’s neuroma. Level of Evidence: Level I, randomized controlled trial.
The frequent and underrecognised co-occurrence of acute exacerbated COPD and depression warrants screening: a systematic review
Authors: Lecheler Leopold , Richter Maximilian , Franzen Daniel P. , Rampini Silvana K. , Cheetham Marcus , Jenewein Josef , Battegay Edouard , Nowak Albina 
Published: June 2017

Patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) and concurrent depression suffer significant psychological stress and decreased quality of life. The aim of this study was to collate data, guidelines and recommendations from publications on the screening and management of depressive mood disorders in patients hospitalised with AECOPD.We systematically searched four databases for publications reporting screening or management of depression in patients hospitalised for AECOPD. The identification of articles was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Out of 1494 original articles screened, 35 met all inclusion criteria. These report a prevalence of depression in AECOPD ranging between 9.5% and 85.6%. Some studies report high postadmission mortality rates for depressive AECOPD patients, and higher readmission rates in depressiveversusnondepressive AECOPD patients. Importantly, none of the 35 publications included suggestions on the screening and management of depression in AECOPD.Depression and AECOPD frequently co-occur, and this worsens outcomes. Yet we did not find recommendations on management, and few interventional studies. Patients hospitalised with AECOPD should be systematically screened for depression and treatment recommendations should be developed for these patients. Randomised studies on how to screen and treat depression in hospitalised AECOPD are necessary.