bluuebunny/crossref_metadata_2025 huggingface dataset:
Ticks (Acari: Ixodidae) and lice (Phthiraptera: Trichodectidae) infesting free-living coatis (Nasua nasua Linnaeus, 1766) with sylvatic and synanthropic habits in the Atlantic rainforest of Southern Brazil
Authors: Magalhães-Matos Paulo Cesar , Moraes Marcela Figueredo Duarte , Valim Jaqueline Rodrigues de Almeida , Castro Gustavo Nunes de Santana , Santos Priscilla Nunes dos , Manier Bruna Sampaio Martins Land , Fonseca Adivaldo Henrique da
Published: May 2017

This research describes the infestation by ticks and lice in free-living coatis (Nasua nasua Linnaeus, 1766) with sylvatic and synanthropic habits living at the Iguaçu National Park (INP), state of Parana, southern Brazil. During the months of September 2014 and from March to April 2015, ticks and lice were collected from 86 free-living coatis from INP. Among the animals analyzed, 99% (85/86) were infested with ectoparasites, Amblyomma spp. larvae (n=23), nymphs of Amblyomma brasiliense (n=77), Amblyomma coelebs (n=427) and Haemaphysalis juxtakochi (n=6) being observed, as well as Amblyomma ovale adults (n=46). Lice were found in lower prevalence (13%, 11/86), nymphs (n=31) and adults (n=9) of Neotrichodectes pallidus. Summary results show feral coatis with sylvatic and synanthropic habits as competent hosts for ixodid ticks and lice, arthropods responsible for the transmission of pathogens for carnivores, others wildlife and humans. This paper presents the first record of H. juxtakochi infesting coatis in Brazil.
To the systematics of the subgenus Hesperomyobia Bochkov, 1997 (Acariformes: Myobiidae: Radfordia)
Authors: Bochkov Andre V.
Published: May 2017

A new myobiid mite species Radfordia (Hesperomyobia) akodon sp. nov. is described from Akodon varius Thomas (Rodentia: Cricetidae: Sigmodontinae) from Bolivia. This new species is known only from a female which differs from those of Radfordia (H.) sigmodontis Radford from Sigmodon hispidus Ray and Ord, and Radfordia (H.) sigmomys Bochkov and Fain from Sigmodon alstoni (Thomas) by the following features. In R. (H.) akodon sp. nov., setae vi are 50 μm long and 7 μm wide (vs. 10–12 μm long and 2 μm wide in R. sigmodontis, and 23–25 μm long and 2 μm wide in R. sigmomys), dorsal idiosomal setae si, se, c1, c2, d1, and d2 are 5–10 μm wide (vs. 2–3 μm wide in R. sigmodontis and R. sigmomys), and setae e1 are 2.6 times longer than f1 (vs. subequal in R. sigmodontis and R. sigmomys). In addition, Radfordia (Hesperomyobia) vandenberghi Fain and Lukoschus is newly recorded herein from Oligoryzomys flavescens (Waterhouse) and Oligoryzomys sp. (Rodentia: Cricetidae: Sigmodontinae) in Bolivia. It is suggested that this mite species is associated exclusively with hosts of the genus Oligoryzomys Bangs.
Chemical composition and properties of MoAl thin films deposited by sputtering from MoAl compound targets
Authors: Lorenz Roland , O'Sullivan Michael , Sprenger Dietmar , Lang Bernhard , Mitterer Christian
Published: May 2017

Molybdenum-based thin films are widely used as back-contact layers in solar cells, as interconnect material or diffusion barriers in microelectronics, or as gate and source/drain lines in thin film transistor liquid crystal displays. Within this work, the sputter behavior of three different molybdenum-aluminum compound targets with Al contents of 24, 37, and 49 at. % manufactured by cold gas spraying as well as the chemical composition, the microstructure, and the properties of the deposited thin films have been investigated. The increase in the Al content in the targets results in an increasing deposition rate of the films. The fine-columnar films are characterized by the formation of a body-centered cubic solid solution resulting in an electrical resistivity increasing from 100 μΩ cm for 10 at. % Al to more than 200 μΩ cm for 30 at. % Al. Monte Carlo simulations of sputtering and gas phase transport indicate that the observed large deviations of the chemical compositions of the films with respect to the target are mainly caused by aluminum losses due to gas phase scattering.
The perception of emotion and focus prosody with varying acoustic cues in cochlear implant simulations with varying filter slopes
Authors: van de Velde Daan J. , Schiller Niels O. , van Heuven Vincent J. , Levelt Claartje C. , van Ginkel Joost , Beers Mieke , Briaire Jeroen J. , Frijns Johan H. M.
Published: May 2017

This study aimed to find the optimal filter slope for cochlear implant simulations (vocoding) by testing the effect of a wide range of slopes on the discrimination of emotional and linguistic (focus) prosody, with varying availability of F0 and duration cues. Forty normally hearing participants judged if (non-)vocoded sentences were pronounced with happy or sad emotion, or with adjectival or nominal focus. Sentences were recorded as natural stimuli and manipulated to contain only emotion- or focus-relevant segmental duration or F0 information or both, and then noise-vocoded with 5, 20, 80, 120, and 160 dB/octave filter slopes. Performance increased with steeper slopes, but only up to 120 dB/octave, with bigger effects for emotion than for focus perception. For emotion, results with both cues most closely resembled results with F0, while for focus results with both cues most closely resembled those with duration, showing emotion perception relies primarily on F0, and focus perception on duration. This suggests that filter slopes affect focus perception less than emotion perception because for emotion, F0 is both more informative and more affected. The performance increase until extreme filter slope values suggests that much performance improvement in prosody perception is still to be gained for CI users.
Test–retest repeatability of human speech biomarkers from static and real-time dynamic magnetic resonance imaging
Authors: Töger Johannes , Sorensen Tanner , Somandepalli Krishna , Toutios Asterios , Lingala Sajan Goud , Narayanan Shrikanth , Nayak Krishna
Published: May 2017

Static anatomical and real-time dynamic magnetic resonance imaging (RT-MRI) of the upper airway is a valuable method for studying speech production in research and clinical settings. The test–retest repeatability of quantitative imaging biomarkers is an important parameter, since it limits the effect sizes and intragroup differences that can be studied. Therefore, this study aims to present a framework for determining the test–retest repeatability of quantitative speech biomarkers from static MRI and RT-MRI, and apply the framework to healthy volunteers. Subjects (n = 8, 4 females, 4 males) are imaged in two scans on the same day, including static images and dynamic RT-MRI of speech tasks. The inter-study agreement is quantified using intraclass correlation coefficient (ICC) and mean within-subject standard deviation (σe). Inter-study agreement is strong to very strong for static measures (ICC: min/median/max 0.71/0.89/0.98, σe: 0.90/2.20/6.72 mm), poor to strong for dynamic RT-MRI measures of articulator motion range (ICC: 0.26/0.75/0.90, σe: 1.6/2.5/3.6 mm), and poor to very strong for velocities (ICC: 0.21/0.56/0.93, σe: 2.2/4.4/16.7 cm/s). In conclusion, this study characterizes repeatability of static and dynamic MRI-derived speech biomarkers using state-of-the-art imaging. The introduced framework can be used to guide future development of speech biomarkers. Test–retest MRI data are provided free for research use.
Between-speaker variability in temporal organizations of intensity contours
Authors: He Lei , Dellwo Volker
Published: May 2017

Intensity contours of speech signals were sub-divided into positive and negative dynamics. Positive dynamics were defined as the speed of increases in intensity from amplitude troughs to subsequent peaks, and negative dynamics as the speed of decreases in intensity from peaks to troughs. Mean, standard deviation, and sequential variability were measured for both dynamics in each sentence. Analyses showed that measures of both dynamics were separately classified and between-speaker variability was largely explained by measures of negative dynamics. This suggests that parts of the signal where intensity decreases from syllable peaks are more speaker-specific. Idiosyncratic articulation may explain such results.
Using envelope modulation to explain speech intelligibility in the presence of a single reflection
Authors: Muralimanohar Ramesh Kumar , Kates James M. , Arehart Kathryn H.
Published: May 2017

A single reflection is the simplest simulation of reverberation and provides insights into more complex scenarios of listening in rooms. This paper presents an analysis of the effects of a single reflection as its delay and intensity are systematically varied. The changes to the envelope modulations are analyzed using not only the traditional within-auditory-band analysis approach but also an across-band spectro-temporal analysis using cepstral correlation coefficients. The use of an auditory model allowed the extension of the simulations to include sensorineural hearing loss. Short delays did not interfere with the envelope modulations at low modulation rates (<16 Hz) and impact predicted intelligibility, while longer delays caused substantial distortion at these rates. The patterns of envelope modulation distortions caused by a single reflection were shown to be similar in models of normal hearing and hearing impairment.
Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy
Authors: Wong Terence T. W. , Zhang Ruiying , Hai Pengfei , Zhang Chi , Pleitez Miguel A. , Aft Rebecca L. , Novack Deborah V. , Wang Lihong V.
Published: May 2017

A photoacoustic microscope system provides label-free multilayered histology-like imaging of unprocessed human breast specimens.
Busting myths of origin
Authors: Gibbons Ann
Published: May 2017

Despite their tales of origin, most people are the mixed descendants of many migrations.
Blocking promiscuous activation at cryptic promoters directs cell type–specific gene expression
Authors: Kim Jongmin , Lu Chenggang , Srinivasan Shrividhya , Awe Stephan , Brehm Alexander , Fuller Margaret T.
Published: May 2017

Blocking somatic genes to make sperm

To generate cells with a specific identity, only a subset of genes is used. Most studies focus on factors that turn on cell type–specific gene expression. However, mechanisms are also needed to block expression of genes that specify other cell lineages. Kim
et al.
identified such a mechanism in the
Drosophila
male germ line. A multiple–zinc finger protein and a chromatin remodeler were found to act together to block transcription from cryptic promoters. These factors prevented aberrant gene expression and enabled proper differentiation in the adult sperm stem cell lineage.

Science
, this issue p.
717
21st-century rise in anthropogenic nitrogen deposition on a remote coral reef
Authors: Ren Haojia , Chen Yi-Chi , Wang Xingchen T. , Wong George T. F. , Cohen Anne L. , DeCarlo Thomas M. , Weigand Mira A. , Mii Horng-Sheng , Sigman Daniel M.
Published: May 2017

From air to shining sea

Nitrogen is an essential nutrient for phytoplankton growth. Nitrogen is primarily supplied to the surface ocean by mixing from below. However, as fertilizer use and combustion of fossil fuels rise, the atmosphere is expected to become an increasingly important source. Ren
et al.
measured nitrogen isotopes in organic matter from a South China Sea coral (see the Perspective by Boyle). Their findings suggest that atmospheric deposition of anthropogenic nitrogen began right at the end of the 20th century. This pathway now supplies nearly one quarter of the annual nitrogen input to the surface ocean in this region.

Science
, this issue p.
749
; see also p.
700
Bragg coherent diffractive imaging of single-grain defect dynamics in polycrystalline films
Authors: Yau Allison , Cha Wonsuk , Kanan Matthew W. , Stephenson G. Brian , Ulvestad Andrew
Published: May 2017

Watching defects in heated thin films

The response of materials to external conditions depends on small-scale features such as defects and grain boundaries. Yau
et al.
heated gold thin films and used coherent x-ray diffractive imaging to track how these microstructures developed during grain growth (see the Perspective by Suter). The technique allowed nondestructive visualization of the features in three dimensions. The method should help link external stimuli to material response through changes in microstructure, thereby allowing development of novel materials through microstructural engineering.

Science
, this issue p.
739
; see also p.
704
Hydrolytically stable fluorinated metal-organic frameworks for energy-efficient dehydration
Authors: Cadiau Amandine , Belmabkhout Youssef , Adil Karim , Bhatt Prashant M. , Pillai Renjith S. , Shkurenko Aleksander , Martineau-Corcos Charlotte , Maurin Guillaume , Eddaoudi Mohamed
Published: May 2017

Drying natural gas efficiently

Natural gas must be purified before it can be transported. The preparation process also includes a drying step to remove water. Microporous adsorbents such as zeolites are used for this purpose, but they often need to be heated to temperatures up to 250°C to remove the water so that they can be reused. Cadiau
et al.
describe a fluorinated metal-organic framework containing nickel metal centers that can remove water from gas streams but that can be regenerated by heating to only 105°C.

Science
, this issue p.
731
Defining the topography of a planetary body
Authors: Burr Devon
Published: May 2017

River and landscape topography, combined, can reveal the geologic history of a planet
Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array
Authors: Bannantine John P. , Campo Joseph J. , Li Lingling , Randall Arlo , Pablo Jozelyn , Praul Craig A. , Raygoza Garay Juan Antonio , Stabel Judith R. , Kapur Vivek
Published: May 2017

Johne's disease, a chronic gastrointestinal inflammatory disease caused byMycobacterium aviumsubspeciesparatuberculosis, is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. Given the close phylogenetic relationship betweenM. aviumsubsp.paratuberculosisand the human pathogenMycobacterium tuberculosis, here, we applied a whole-proteomeM. tuberculosisprotein array to identify seroreactive and diagnosticM. aviumsubsp.paratuberculosisantigens. A genome-scale pairwise analysis of amino acid identity levels between orthologous proteins inM. aviumsubsp.paratuberculosisandM. tuberculosisshowed an average of 62% identity, with more than half the orthologous proteins sharing >75% identity. Analysis of theM. tuberculosisprotein array probed with sera fromM. aviumsubsp.paratuberculosis-infected cattle showed antibody binding to 729M. tuberculosisproteins, with 58% of them having ≥70% identity toM. aviumsubsp.paratuberculosisorthologs. The results showed that only 4 of the top 40 seroreactiveM. tuberculosisantigens were orthologs of previously reportedM. aviumsubsp.paratuberculosisantigens, revealing the existence of a large number of previously unrecognized candidate diagnostic antigens. Enzyme-linked immunosorbent assay (ELISA) testing of 20M. aviumsubsp.paratuberculosisrecombinant proteins, representing reactive and nonreactiveM. tuberculosisorthologs, further confirmed that theM. tuberculosisarray has utility as a screening tool for identifying candidate antigens for Johne's disease diagnostics. Additional ELISA testing of field serum samples collected from dairy herds around the United States revealed that MAP2942c had the strongest seroreactivity with Johne's disease-positive samples. Collectively, our studies have considerably expanded the number of candidateM. aviumsubsp.paratuberculosisproteins with potential utility in the next generation of rationally designed Johne's disease diagnostic assays.
Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus
Authors: Urakami Akane , Sakurai Atsuko , Ishikawa Momoko , Yap Moh Lan , Flores-Garcia Yevel , Haseda Yasunari , Aoshi Taiki , Zavala Fidel P. , Rossmann Michael G. , Kuno Sachiko , Ueno Ryuji , Akahata Wataru
Published: May 2017

Virus-like particles (VLPs) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner and is thus capable of inducing strong immune responses against any inserted antigen. Furthermore, by mimicking the structure of the immature form of the virus, we altered our VLP'sin vivodynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of thePlasmodium falciparummalaria parasite as an antigen and demonstrated that our VLP-based vaccine elicits strong immune responses against CSP in animals. The sera from immunized monkeys protected mice from malaria infection. Likewise, mice vaccinated withP. yoeliiCSP-containing VLPs were protected from an infectious sporozoite challenge. Hence, our uniquely engineered VLP platform can serve as a blueprint for the development of vaccines against other pathogens and diseases.
A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin Resistance and Eradication of Infection at a High Rate
Authors: Beckman Erin , Saracino Ilaria , Fiorini Giulia , Clark Courtney , Slepnev Vladimir , Patel Denise , Gomez Clarissa , Ponaka Reddy , Elagin Vecheslav , Vaira Dino
Published: May 2017

Clarithromycin-based regimens are commonly used as a first-line therapy for
Helicobacter pylori
-positive patients; however, resistance to clarithromycin has led to treatment failures. The aim of this study was to evaluate the feasibility of using stool samples to detect the presence of
H. pylori
DNA while concurrently detecting mutations associated with resistance to clarithromycin. For this purpose, total DNA was extracted from 294 raw stool specimens from
H. pylori
-positive and -negative patients. TaqMan real-time PCR amplification was used to detect the presence of
H. pylori
as well as to predict the phenotype of the organism and the related outcome for patients treated with clarithromycin. Clarithromycin resistance was determined upon analysis of the PCR result. Patients were also tested by a urea breath test and were subjected to esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease test, in order to obtain a consensus patient infection status. Of 294 total stool samples, 227 were deemed true positive. The sensitivity of
H. pylori
detection by PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed point mutations associated with clarithromycin resistance (A2142C, A2142G, A2143G). The final correlation of the mutant genotypes as determined by sequencing with the eradication of infection was 86%. We found that
Helicobacter pylori
DNA can be detected in human stool specimens with high sensitivity and can therefore be used to determine the presence of the bacterium without obtaining a biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted without obtaining a biopsy sample, facilitating the choice of the right therapeutic approach.
Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers
Authors: Bosch Thijs , Lutgens Suzanne P. M. , Hermans Mirjam H. A. , Wever Peter C. , Schneeberger Peter M. , Renders Nicole H. M. , Leenders Alexander C. A. P. , Kluytmans Jan A. J. W. , Schoffelen Annelot , Notermans Daan , Witteveen Sandra , Bathoorn Erik , Schouls Leo M.
Published: May 2017

In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive
Enterobacteriaceae
is low. Here, we report an outbreak of NDM-1-producing
Klebsiella pneumoniae
infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers (HCCs). Next-generation sequencing was performed on 250 carbapenemase-producing
Enterobacteriaceae
isolates, including 42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most outbreak isolates were
K. pneumoniae
(
n
= 26) and
Escherichia coli
(
n
= 11), but 5 isolates comprising three other
Enterobacteriaceae
species were also cultured. The 26
K. pneumoniae
isolates had sequence type 873 (ST873), as did 7 unrelated
K. pneumoniae
isolates originating from five geographically dispersed HCCs. The 33 ST873 isolates that clustered closely together using whole-genome multilocus sequence typing (wgMLST) carried the same plasmids and had limited differences in the resistome. The 11
E. coli
outbreak isolates showed great variety in STs, did not cluster using wgMLST, and showed considerable diversity in resistome and plasmid profiles. The
bla
NDM-1
gene-carrying plasmid present in the ST873
K. pneumoniae
isolates was found in all the other
Enterobacteriaceae
species cultured at the outbreak location and in a single
E. coli
isolate from another HCC. We describe a hospital outbreak with an NDM-1-producing
K. pneumoniae
strain from an unknown source that was also found in patients from five other Dutch HCCs in the same time frame without an epidemiological link. Interspecies transfer of the resistance plasmid was observed in other
Enterobacteriaceae
species isolated at the outbreak location and in another HCC.
Reactive Oxygen Species-Mediated c-Jun NH
2
-Terminal Kinase Activation Contributes to Hepatitis B Virus X Protein-Induced Autophagy via Regulation of the Beclin-1/Bcl-2 Interaction
Authors: Zhong Linmao , Shu Wangqin , Dai Wangbin , Gao Bo , Xiong Sidong
Published: May 2017

Autophagy is closely associated with the regulation of hepatitis B virus (HBV) replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated biological processes, has been demonstrated to be crucial for autophagy induction by HBV. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain elusive. In the present investigation, we demonstrated that HBx induced autophagosome formation independently of the class I phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway. In contrast, the class III PI3K(VPS34)/beclin-1 pathway was revealed to be critical for HBx-induced autophagosome formation. Further study showed that HBx did not affect the level of VPS34 and beclin-1 expression but inhibited beclin-1/Bcl-2 association, and c-Jun NH2-terminal kinase (JNK) signaling was found to be important for this process. Moreover, it was found that HBx treatment led to the generation of reactive oxygen species (ROS), and inhibition of ROS activity abrogated both JNK activation and autophagosome formation. Of importance, ROS-JNK signaling was also revealed to play an important role in HBV-induced autophagosome formation and subsequent HBV replication. These data may provide deeper insight into the mechanisms of autophagy induction by HBx and help in the design of new therapeutic strategies against HBV infection.

IMPORTANCE
HBx plays a key role in diverse HBV-associated biological processes, including autophagy induction. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain elusive. In the present investigation, we found that HBx induced autophagy independently of the class I PI3K/AKT/mTOR signaling pathway, while the class III PI3K(VPS34)/beclin-1 pathway was revealed to be crucial for this process. Further data showed that ROS-JNK activation by HBx resulted in the release of beclin-1 from its association with Bcl-2 to form a complex with VPS34, thus enhancing autophagosome formation. Of importance, ROS-JNK signaling was also demonstrated to be critical for HBV replication via regulation of autophagy induction. These data help to elucidate the molecular mechanisms of autophagy induction by HBx/HBV and might be useful for designing novel therapeutic approaches to HBV infection.
Virus-Like Vesicles of Kaposi's Sarcoma-Associated Herpesvirus Activate Lytic Replication by Triggering Differentiation Signaling
Authors: Gong Danyang , Dai Xinghong , Xiao Yuchen , Du Yushen , Chapa Travis J. , Johnson Jeffrey R. , Li Xinmin , Krogan Nevan J. , Deng Hongyu , Wu Ting-Ting , Sun Ren
Published: May 2017

Virus-like vesicles (VLVs) are membrane-enclosed vesicles that resemble native enveloped viruses in organization but lack the viral capsid and genome. During the productive infection of tumor-associated gammaherpesviruses, both virions and VLVs are produced and are released into the extracellular space. However, studies of gammaherpesvirus-associated VLVs have been largely restricted by the technical difficulty of separating VLVs from mature virions. Here we report a strategy of selectively isolating VLVs by using a Kaposi's sarcoma-associated herpesvirus (KSHV) mutant that is defective in small capsid protein and is unable to produce mature virions. Using mass spectrometry analysis, we found that VLVs contained viral glycoproteins required for cellular entry, as well as tegument proteins involved in regulating lytic replication, but lacked capsid proteins. Functional analysis showed that VLVs induced the expression of the viral lytic activator RTA, initiating KSHV lytic gene expression. Furthermore, employing RNA sequencing, we performed a genomewide analysis of cellular responses triggered by VLVs and found that PRDM1, a master regulator in cell differentiation, was significantly upregulated. In the context of KSHV replication, we demonstrated that VLV-induced upregulation of PRDM1 was necessary and sufficient to reactivate KSHV by activating its RTA promoter. In sum, our study systematically examined the composition of VLVs and demonstrated their biological roles in manipulating host cell responses and facilitating KSHV lytic replication.

IMPORTANCE
Cells lytically infected with tumor-associated herpesviruses produce a high proportion of virus-like vesicles (VLVs). The composition and function of VLVs have not been well defined, largely due to the inability to efficiently isolate VLVs that are free of virions. Using a cell system capable of establishing latent KSHV infection and robust reactivation, we successfully isolated VLVs from a KSHV mutant defective in the small capsid protein. We quantitatively analyzed proteins and microRNAs in VLVs and characterized the roles of VLVs in manipulating host cells and facilitating viral infection. More importantly, we demonstrated that by upregulating PRDM1 expression, VLVs triggered differentiation signaling in targeted cells and facilitated viral lytic infection via activation of the RTA promoter. Our study not only demonstrates a new strategy for isolating VLVs but also shows the important roles of KSHV-associated VLVs in intercellular communication and the viral life cycle.
Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER) and Bud off from the ER to the Golgi Compartment in COPII Vesicles
Authors: Syed Gulam H. , Khan Mohsin , Yang Song , Siddiqui Aleem
Published: May 2017

Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle (LVP).
In vitro
studies have demonstrated the importance of apolipoproteins in HCV secretion and infectivity, leading to the notion that HCV coopts the secretion of very-low-density lipoprotein (VLDL) for its egress. However, the mechanisms involved in virus particle assembly and egress are still elusive. The biogenesis of VLDL particles occurs in the endoplasmic reticulum (ER), followed by subsequent lipidation in the ER and Golgi compartment. The secretion of mature VLDL particles occurs through the Golgi secretory pathway. HCV virions are believed to latch onto or fuse with the nascent VLDL particle in either the ER or the Golgi compartment, resulting in the generation of LVPs. In our attempt to unravel the collaboration between HCV and VLDL secretion, we studied HCV particles budding from the ER
en route
to the Golgi compartment in COPII vesicles. Biophysical characterization of COPII vesicles fractionated on an iodixanol gradient revealed that HCV RNA is enriched in the highly buoyant COPII vesicle fractions and cofractionates with apolipoprotein B (ApoB), ApoE, and the HCV core and envelope proteins. Electron microscopy of immunogold-labeled microsections revealed that the HCV envelope and core proteins colocalize with apolipoproteins and HCV RNA in Sec31-coated COPII vesicles. Ultrastructural analysis also revealed the presence of HCV structural proteins, RNA, and apolipoproteins in the Golgi stacks. These findings support the hypothesis that HCV LVPs assemble in the ER and are transported to the Golgi compartment in COPII vesicles to embark on the Golgi secretory route.

IMPORTANCE
HCV assembly and release accompany the formation of LVPs that circulate in the sera of HCV patients and are also produced in an
in vitro
culture system. The pathway of HCV morphogenesis and secretion has not been fully understood. This study investigates the exact site where the association of HCV virions with host lipoproteins occurs. Using immunoprecipitation of COPII vesicles and immunogold electron microscopy (EM), we characterize the existence of LVPs that cofractionate with lipoproteins, viral proteins, RNA, and vesicular components. Our results show that this assembly occurs in the ER, and LVPs thus formed are carried through the Golgi network by vesicular transport. This work provides a unique insight into the HCV LVP assembly process within infected cells and offers opportunities for designing antiviral therapeutic cellular targets.
De Novo
Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
Authors: Setoh Yin Xiang , Prow Natalie A. , Peng Nias , Hugo Leon E. , Devine Gregor , Hazlewood Jessamine E. , Suhrbier Andreas , Khromykh Alexander A.
Published: May 2017

The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus’s ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive-strand RNA viruses.
Improving inpatient care for older adults: Implementing Dementia Commissioning for Quality and Innovation (CQUIN)
Authors: Harrison Judith R
Published: May 2017

Dementia is a common condition, and people with dementia occupy around 25% of hospital beds. Commissioning for Quality and Innovation (CQUIN) is an NHS payment framework that links part of English healthcare providers' income to quality improvement. The dementia CQUIN goals are designed to encourage the recognition of dementia in hospital. The Royal Surrey County Hospital, Guildford, introduced new procedures to meet the dementia CQUIN targets. Adherence to the changes was a problem. This project aimed to improve hospital's implementation strategy. At baseline, completion rates for dementia CQUIN assessments were just 27%. Interventions were informed by semi-structured interviews with junior doctors and dementia leads in neighbouring trusts. Progress was measured by regular audits and interventions were made over several months. Changes suggested by junior doctors and nurses proved very effective, and involving the multidisciplinary team produced the most significant improvement. Gradual progress was made until we achieved and maintained 90% completion for dementia assessments. In conclusion, we made changes to working practices to achieve the CQUIN targets and promoted quality care for older adults. Our experience highlighted the importance of involving multidisciplinary frontline staff in the design of service changes.
Impact of expedited partner therapy (EPT) implementation on chlamydia incidence in the USA
Authors: Mmeje Okeoma , Wallett Sarah , Kolenic Giselle , Bell Jason
Published: May 2017

Objectives

The diagnosis and treatment of Chlamydia trachomatis infection is important in preventing persistent or recurrent infection. Expedited partner therapy (EPT) is the favoured and supported method for STI treatment of the Centers for Disease Control and Prevention when the provider cannot be assured that all recent sexual partner(s) will seek therapy. EPT is legally permissible in 38 states and is endorsed by healthcare organisations to decrease the rates of chlamydia and gonorrhoea infection. Our study investigated the impact of EPT legal status (permissible, potentially allowable or prohibited) on C. trachomatis infection rates for each state.

Methods

Our ecological study modelled the number of reported chlamydia cases from 2000 to 2013 as a function of year, legal status and the interaction between year and legality. We used a negative binomial regression model that included state fixed effects (including the District of Columbia) to account for both the repeated measures per state and state-specific characteristics that could not be measured for inclusion in this study. The lagged number of C. trachomatis cases was included as a covariate and each state's total population for a given year was included in the model as an exposure parameter. States were designated Y (EPT permissible), N (EPT prohibited) and M (EPT potentially allowable), and the legal status of each state could vary over time.

Results

Each legal category saw an increase in the incidence rate of C. trachomatis infection, but on average, the incidence rate for states with prohibitive EPT legislation grew significantly faster over time compared with the rate for the states where EPT was permissible. The average increase in predicted incidence rates per year for states with Y, N and M legal status were 14.1 (95% CI (12.0 to 16.2)), 17.5 (95% CI (15.9 to 19.2)) and 16.8 (95% CI (15.0 to 18.6)) cases per 100 000 persons per year, respectively, when controlling for state-specific effects.

Conclusions

Our model suggests that a lack of EPT legislation is associated with an increase in STI rates. States with potentially allowable EPT legislation as of 2013 (n=8) should consider permitting EPT as a component of a multipronged strategy for treatment of sexual partners to prevent C. trachomatis infection.
The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders
Authors: Kim Hyeon-Jeong , Kim Sanghwa , Lee Ah Young , Jang Yoonjeong , Davaadamdin Orkhonselenge , Hong Seong-Ho , Kim Jun Sung , Cho Myung-Haing
Published: May 2017

This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.
Evodiamine Prevents Glioma Growth, Induces Glioblastoma Cell Apoptosis and Cell Cycle Arrest through JNK Activation
Authors: Wu Wen-Shin , Chien Chih-Chiang , Liu Kao-Hui , Chen Yen-Chou , Chiu Wen-Ta
Published: May 2017

Evodiamine (EVO) is an active medicinal compound derived from the traditional herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has several beneficial biological properties, including anticancer and anti-inflammatory activities. However, the in vitro and in vivo anticancer activities of EVO against the growth of glioblastoma cells remain undefined. EVO induced significant decreases in the viability of U87 and C6 glioma cells, but not of primary astrocytes, according with the occurrence of apoptotic characteristics including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage, and hypodiploid cells. The disruption of the mitochondrial membrane potential (MMP) was detected, and it was found that the peptidyl caspase-9 inhibitor, Z-LEHD-FMK, significantly prevented glioma cells from EVO-induced apoptosis. Increased c-Jun N-terminal kinase (JNK) protein phosphorylation by EVO was observed, and the addition of JNK inhibitors, SP600125 and JNKI inhibited the EVO-induced apoptosis was inhibited. Additionally, EVO treatment induced G2/M arrest with increased polymerized tubulin protein expression in U87 and C6 cells. Elevated expressions of the cyclin B1, p53, and phosphorylated (p)-p53 proteins were detected in EVO-treated glioma cells, and these were inhibited by JNK inhibitors. An in vivo study showed that EVO significantly reduced the growth of gliomas elicited by the subcutaneous injection of U87 cells with increases in cyclin B1, p53, and p-p53 protein expressions in tumors. An analysis of eight EVO-related chemicals showed that alkyl groups at position 14 in EVO are important for its anti-glioma effects which involve both apoptosis and G2/M arrest. Evidence is provided that supports EVO induction of apoptosis and G2/M arrest via the activation of JNK-mediated gene expression and disruption of MMP in glioblastoma cells. EVO was shown to penetrate the blood–brain barrier; EVO is therefore predicted to be a promising compound for the chemotherapy of glioblastomas and deserves further investigations.
Production efficiency and radioisotopic purity of 99mTc formed using the (p,2n) reaction on a highly enriched 100Mo target
Authors: Szkliniarz Katarzyna , Sitarz Mateusz , Jastrzębski Jerzy , Choiński Jarosław , Jakubowski Andrzej , Kapinos Kamil , Kisieliński Maciej , Stolarz Anna , Trzcińska Agnieszka , Wojtkowska Jolanta , Zipper Wiktor
Published: May 2017

The [Formula: see text]Tc isomer was produced using the [Formula: see text] reaction on highly enriched [Formula: see text]Mo samples. The Thick Target Yields were determined in the energy range from 16 MeV to 26 MeV and compared with the values calculated using the most recent cross-section recommendations from the literature. The generated impurities were also determined. It was shown that for 99.815 ± 0.010% enriched samples, only reactions induced on [Formula: see text]Mo are of importance. The ratio of the number of atoms of [Formula: see text]Tc to all produced Tc nuclei was studied as a function of irradiation time and bombarding energy.
CHARACTERIZING FRACTAL BASIN BOUNDARIES FOR PLANAR SWITCHED SYSTEMS
Authors: ZHANG YONGXIANG
Published: May 2017

This paper is to introduce some analytical tools to characterize the properties of fractal basin boundaries for planar switched systems (with time-dependent switching). The characterizing methods are based on the view point of limit sets and prime ends. By constructing the auxiliary dynamical system, the fractal basin boundaries of planar switched systems can be proved if every diverging path in the basin of associated auxiliary system has the entire basin boundary as its limit set. Fractal property is also verified if every prime end that is defined in the basin of associated auxiliary system is a prime end of type 3 and all other prime ends are of type 1. Bifurcations of fractal basin boundary are investigated by analyzing what types of prime ends in the basin are involved. The fractal basin boundary of switched system is also described by the indecomposable continuum.
QUASI-LOWER DIMENSION AND QUASI-LIPSCHITZ MAPPING
Authors: CHEN HAIPENG , DU YALI , WEI CHUN
Published: May 2017

In this paper, we show that the lower dimension is not invariant under quasi-Lipschitz mapping, and then we find an invariant named the quasi-lower dimension. We also compute the quasi-lower dimension of a class of sets defined by digit restrictions, and then give an example to distinguish the quasi-lower dimension and other dimensions.
Market States and Momentum: Evidence from the Dhaka Stock Exchange
Authors: Khan Mostafa Saidur Rahim
Published: May 2017

This study examines the momentum effect in the Dhaka Stock Exchange (DSE) listed stock returns on the basis of market states. Momentum profits are found to be significantly positive in UP market states but insignificant in DOWN market states. Momentum profits evident in UP market states are also found to revert in the long term. The evidence of short term momentum and long term reversal hold true even after adjusting for risks. In addition to short-term momentum and long-term reversal, regression coefficients also provide evidence for a positive but nonlinear relationship between momentum profits and market states. Maximum momentum profits are found at the median market performance not at the peak. Findings of this study suggest that investors’ overreaction causes momentum profits in the DSE.
On the relaxed mean-field stochastic control problem
Authors: Bahlali Khaled , Mezerdi Meriem , Mezerdi Brahim
Published: May 2017

This paper is concerned with optimal control problems for systems governed by mean-field stochastic differential equation, in which the control enters both the drift and the diffusion coefficient. We prove that the relaxed state process, associated with measure valued controls, is governed by an orthogonal martingale measure rather than a Brownian motion. In particular, we show by a counter example that replacing the drift and diffusion coefficient by their relaxed counterparts does not define a true relaxed control problem. We establish the existence of an optimal relaxed control, which can be approximated by a sequence of strict controls. Moreover, under some convexity conditions, we show that the optimal control is realized by a strict control.
Parameter estimation via homogenization for stochastic dynamical systems with oscillating coefficients
Authors: Zhang Xinyong , Wang Hui , Zhang Yanjie , Lin Haokun
Published: May 2017

This paper is devoted to studying parameter estimation for a class of stochastic dynamical systems with oscillating coefficients. We show that the homogenized systems faithfully capture the dynamical quantities such as mean exit time and escape probability. Exacting data from observations on the mean exit time (or escape probability) of the original systems, we try to fit the mean exit time (or escape probability) of the homogenized systems by least square method. In this way, we can accurately estimate the unknown parameter in the drift under appropriate assumptions. Furthermore, we conduct some numerical experiments to illustrate our method.
Spectral invariants for monotone Lagrangians
Authors: Leclercq Rémi , Zapolsky Frol
Published: May 2017

Since spectral invariants were introduced in cotangent bundles via generating functions by Viterbo in the seminal paper [73], they have been defined in various contexts, mainly via Floer homology theories, and then used in a great variety of applications. In this paper we extend their definition to monotone Lagrangians, which is so far the most general case for which a “classical” Floer theory has been developed. Then, we gather and prove the properties satisfied by these invariants, and which are crucial for their applications. Finally, as a demonstration, we apply these new invariants to symplectic rigidity of some specific monotone Lagrangians.
The importance of detailed geological characterization for future expanded use of gas storage in the sustainable energy context
Authors: Otto Bernward
Published: May 2017

In order to accurately model the subsurface of a new salt cavern gas storage facility at the Jemgum site in the Lower Saxony Basin (NW Germany), modern 3D pre-stack depth-migrated seismic data were utilized during an early planning stage. Gas storage projects are often regarded purely as engineering projects. However, the involvement of geoscientists provided an opportunity to further add operational value to the project by applying state-of-the-art geological modelling techniques. As part of the site characterization, a new generic workflow was developed to facilitate a more time-efficient creation of a static, multi-
z
-valued salt interface, essential for modelling of any complex salt structure. Uncertainties related to the reconstruction of salt interface meshes were analysed accordingly and used to quantitatively determine spatial uncertainties of the final static depth model. Furthermore, seismic-attribute images were created which enabled the detection of a mid-Miocene fluvial system evident at shallow depths of just 100–300 m below mean sea level. The study demonstrates that seismic data, targeting Rotliegend gas sands at depths of more than 4000 m, can be very beneficial to better understand the near-surface hydrogeological processes for gas storage.
FXYD5 (dysadherin) may mediate metastatic progression through regulation of the β-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model
Authors: Lubarski-Gotliv Irina , Dey Kuntal , Kuznetsov Yuri , Kalchenco Vecheslav , Asher Carol , Garty Haim
Published: May 2017

FXYD5 is a Na+-K+-ATPase regulator, expressed in a variety of normal epithelia. In parallel, it has been found to be associated with several types of cancer and effect lethal outcome by promoting metastasis. However, the molecular mechanism underlying FXYD5 mediated invasion has not yet been identified. In this study, using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA significantly inhibited lung cancer metastasis, without having a substantial effect on primary tumor growth. Our study reveals that FXYD5 participates in multiple stages of metastatic development and exhibits more than one mode of E-cadherin regulation. We provide the first evidence that FXYD5-related morphological changes are mediated through its interaction with Na+-K+-ATPase. Experiments in cultured 4T1 cells have indicated that FXYD5 expression may downregulate the β1 isoform of the pump. This behavior could have implications on both transcellular interactions and intracellular events. Further studies suggest that differential localization of the adaptor protein Annexin A2 in FXYD5-expressing cells may correlate with matrix metalloproteinase 9 secretion and adhesion changes in 4T1 wild-type cells.