bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capillary Driven Fluid Flow in Medical Devices
Authors: O’Leary Fiachra A. , Griffin Philip C. 
Published: March 2014

Microscale fluid dynamics has played a significant role in the development of many applications in the medical diagnostic sector and in recent years many devices have implemented advances in this field. Capillary driven assays are commonly used in diagnostic areas, such as, cardiac risk, fertility, drug abuse and infectious diseases1. Typically a platform is used where bodily fluids or samples are taken, filtered and by means of small microchannels, transported and mixed with a variety of antibodies2. In order to perform correctly, these antibodies need to bind to the proteins in the fluid. It is therefore essential that the exposure of the proteins to the antibodies is maximized. To achieve this, capillary dimensions can be altered to obtain the required flow rates and exposure times3. This paper focuses on controlling these parameters.
In this paper, a study was conducted in which the flows in four straight rectangular microchannels of varying cross sectional areas were assessed. The four microchannels were fabricated from an epoxy material. The microchannel widths varied from 100μm to 1000μm with each channel having a dept of 200μm. The four microchannels had aspect ratios of 0.5, 1, 2 and 10. The microchannels were sealed using a heat sealing hydrophilic tape. Fluid velocity rates were measured experimentally using an X-Stream XS-4 high speed camera at 500 frames per second. Preliminary contact angle results between water and the epoxy material gave a contact angle of 81.5 degrees +/− 6 degrees. Computational models of the four microchannels were performed using a Volume Of Fluid (VOF) model in Fluent 6.2.16, a commercially available CFD code. The computational models had four boundary types: pressure inlet, pressure outlet, epoxy wall and hydrophilic tape wall. The inlet boundary has an initial pressure applied to it, capillary pressure between the water and air interface in the microchannel. It was found that as the dimensions of the microchannels increased, the governing equations were less accurate in predicting the experimental fluid velocity in the microchannels.
Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines
Authors: Boyd Mary Adetinuke , Tennant Sharon M. , Saague Venant A. , Simon Raphael , Muhsen Khitam , Ramachandran Girish , Cross Alan S. , Galen James E. , Pasetti Marcela F. , Levine Myron M. 
Published: March 2014

ABSTRACTInvasiveSalmonellainfections for which improved or new vaccines are being developed include enteric fever caused bySalmonella entericaserovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidalSalmonella(NTS) serovars, particularlyS. entericaserovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developedin vitroassays to quantify serum bactericidal antibody (SBA) activity induced byS. Typhi,S. Paratyphi A,S. Typhimurium, andS. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. ForS. Enteritidis,S. Typhimurium, andS. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast,S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administeredS. Typhimurium,S. Enteritidis, andS. Paratyphi A but notS. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited bySalmonellavaccine candidates.
Posttraumatic Brain Abscess Caused by Aeromonas hydrophila
Authors: Mahabeer Yesholata , Khumalo Amanda , Kiratu Erastus , Mlisana Koleka 
Published: March 2014

ABSTRACT

Posttraumatic brain abscesses are usually caused by Gram-negative bacilli, notably
Enterobacteriaceae
and
Staphylococcus aureus
. Although
Aeromonas hydrophila
is a recognized cause of trauma-related sepsis, it has not been previously isolated from posttraumatic brain abscesses. We describe the first case of
Aeromonas hydrophila
brain abscess.
High Rates of Infection with Novel Enterovirus Variants in Wild Populations of Mandrills and Other Old World Monkey Species
Authors: Nguyen Dung Van , Harvala Heli , Ngole Eitel Mpoudi , Delaporte Eric , Woolhouse Mark E. J. , Peeters Martine , Simmonds Peter 
Published: March 2014

ABSTRACT

Enteroviruses (EVs) are a genetically and antigenically diverse group of viruses infecting humans. A mostly distinct set of EV variants have additionally been documented to infect wild apes and several, primarily captive, Old World monkey (OWM) species. To investigate the prevalence and genetic characteristics of EVs infecting OWMs in the wild, fecal samples from mandrills (
Mandrillus sphinx
) and other species collected in remote regions of southern Cameroon were screened for EV RNA. Remarkably high rates of EV positivity were detected in
M. sphinx
(100 of 102 screened),
Cercocebus torquatus
(7/7), and
Cercopithecus cephus
(2/4), with high viral loads indicative of active infection. Genetic characterization in VP4/VP2 and VP1 regions allowed EV variants to be assigned to simian species H (
EV-H
) and
EV-J
(including one or more new types), while seven matched simian
EV-B
variants, SA5 and EV110 (chimpanzee). Sequences from the remaining 70 formed a new genetic group distinct in VP4/2 and VP1 region from all currently recognized human or simian EV species. Complete genome sequences were obtained from three to determine their species assignment. In common with
EV-J
and the
EV-A
A13 isolate, new group sequences were chimeric, being most closely related to
EV-A
in capsid genes and to
EV-B
in the nonstructural gene region. Further recombination events created different groupings in 5′ and 3′ untranslated regions. While clearly a distinct EV group, the hybrid nature of new variants prevented their unambiguous classification as either members of a new species or as divergent members of
EV-A
using current International Committee on Taxonomy of Viruses (ICTV) assignment criteria.

IMPORTANCE
This study is the first large-scale investigation of the frequency of infection and diversity of enteroviruses (EVs) infecting monkeys (primarily mandrills) in the wild. Our findings demonstrate extremely high frequencies of active infection (95%) among mandrills and other Old World monkey species inhabiting remote regions of Cameroon without human contact. EV variants detected were distinct from those infecting human populations, comprising members of enterovirus species B, J, and H and a large novel group of viruses most closely related to species A in the P1 region. The viral sequences obtained contribute substantially to our growing understanding of the genetic diversity of EVs and the existence of interspecies chimerism that characterizes the novel variants in the current study, as well as in previously characterized species A and J viruses infecting monkeys. The latter findings will contribute to future development of consensus criteria for species assignments in enteroviruses and other picornavirus genera.
Emergence and Evolution of Avian H5N2 Influenza Viruses in Chickens in Taiwan
Authors: Lee Chang-Chun David , Zhu Huachen , Huang Pei-Yu , Peng Liuxia , Chang Yun-Cheng , Yip Chun-Hung , Li Yao-Tsun , Cheung Chung-Lam , Compans Richard , Yang Chinglai , Smith David K. , Lam Tommy Tsan-Yuk , King Chwan-Chuen , Guan Yi 
Published: March 2014

ABSTRACT
Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003.

IMPORTANCE
H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the Eurasian gene pool. The unusually high similarity of the chicken H5N2 viruses to the Mexican vaccine strain suggests that these viruses might have been introduced to Taiwan by using inadequately inactivated or attenuated vaccines. These chicken H5N2 viruses are developing varying levels of pathogenicity that could lead to significant consequences for the local poultry industry. These findings emphasize the need for strict quality control and competent oversight in the manufacture and usage of avian influenza virus vaccines and indicate that alternatives to widespread vaccination may be desirable.
Envelope Proteins Derived from Naturally Integrated Hepatitis B Virus DNA Support Assembly and Release of Infectious Hepatitis Delta Virus Particles
Authors: Freitas Natalia , Cunha Celso , Menne Stephan , Gudima Severin O. 
Published: March 2014

ABSTRACT

A natural subviral agent of human hepatitis B virus (HBV), hepatitis delta virus (HDV), requires only the envelope proteins from HBV in order to maintain persistent infection. HBV surface antigens (HBsAgs) can be produced either by HBV replication or from integrated HBV DNA regardless of replication. The functional properties of the integrant-generated HBsAgs were examined using two human hepatocellular carcinoma-derived cell lines, Hep3B and PLC/PRF/5, that contain HBV integrants but do not produce HBV virions and have no signs of HBV replication. Both cell lines were able to support HDV replication and assembly/egress of HDV virions. Neither of the cell lines was able to produce substantial amounts of the pre-S1-containing HDV particles. HDV virions assembled in PLC/PRF/5 cells were able to infect primary human hepatocytes, while Hep3B-derived HDV appeared to be noninfectious. These results correlate with the findings that the entire open reading frame (ORF) for the large (L) envelope protein that is essential for infectivity is present on HBV RNAs from PLC/PRF/5 cells, while an L protein ORF that was truncated and fused to inverted precore sequences was found using RNAs from Hep3B cells. This study demonstrates for the first time that at least some of the HBV DNA sequence naturally integrated during infection can produce functional small and large envelope proteins capable of the formation of infectious HDV virions. Our data indicate that
in vivo
chronic HDV infection can persist in the absence of HBV replication (or when HBV replication is profoundly suppressed) if functional envelope proteins are supplied from HBV integrants.

IMPORTANCE
The study addresses the unique mechanism of HDV persistence in the absence of ongoing HBV replication, advances our understanding of HDV-HBV interactions, and supports the implementation of treatments directly targeting HDV for HDV/HBV-infected individuals.
An Epistatic Relationship between the Viral Protein Kinase UL97 and the
UL133-UL138
Latency Locus during the Human Cytomegalovirus Lytic Cycle
Authors: Li Gang , Rak Michael , Nguyen Christopher C. , Umashankar Mahadevaiah , Goodrum Felicia D. , Kamil Jeremy P. 
Published: March 2014

ABSTRACT

We report that
UL133-UL138
(
UL133/8
), a transcriptional unit within the UL
b
′ region (UL
b
′) of the human cytomegalovirus (HCMV) genome, and UL97, a viral protein kinase encoded by HCMV, play epistatic roles in facilitating progression of the viral lytic cycle. In studies with HCMV strain TB40/E, pharmacological blockade or genetic ablation of UL97 significantly reduced the levels of mRNA and protein for IE2 and viral early and early-late genes during a second wave of viral gene expression that commenced at between 24 and 48 h postinfection. These effects were accompanied by significant defects in viral DNA synthesis and viral replication. Interestingly, deletion of
UL133/8
likewise caused significant defects in viral DNA synthesis, viral gene expression, and viral replication, which were not exacerbated upon UL97 inhibition. When
UL133/8
was restored to HCMV laboratory strain AD169, which otherwise lacks the locus, the resulting recombinant virus replicated similarly to the parental virus. However, during UL97 inhibitor treatment, the virus in which
UL133/8
was restored showed significantly exacerbated defects in viral DNA synthesis, viral gene expression, and production of infectious progeny virus, thus recapitulating the differences between wild-type TB40/E and its
UL133/8
-null derivative. Phenotypic evaluation of mutants null for specific open reading frames within
UL133/8
revealed a role for UL135 in promoting viral gene expression, viral DNA synthesis, and viral replication, which depended on UL97. Taken together, our findings suggest that UL97 and UL135 play interdependent roles in promoting the progression of a second phase of the viral lytic cycle and that these roles are crucial for efficient viral replication.

IMPORTANCE
A unique feature of the herpesviruses, such as human cytomegalovirus (HCMV), is that they can undergo latency, a state during which the virus silences its gene expression, which allows lifelong viral persistence in immunocompetent hosts. We have uncovered an unexpected link between a cluster of HCMV genes involved in latency,
UL133-UL138
, and a virally encoded protein kinase, UL97, which plays crucial roles in manipulating the cell cycle during HCMV lytic replication. Although viral immediate early (IE) gene expression is essential for HCMV lytic replication, the activation of IE gene expression in latently infected cells is not sufficient to result in production of infectious virus. Our findings here and in an accompanying study (
M. Umashankar, M. Rak, F. Bughio, P. Zagallo, K. Caviness, and F. D. Goodrum
, J. Virol. 88:5987–6002, 2014) show that proteins expressed from the
UL133-UL138
latency locus and UL97 play interdependent roles in overcoming checkpoints that restrict the viral lytic replication cycle, findings which suggest intriguing implications for establishment of and reactivation from HCMV latency.
Sp100 Isoform-Specific Regulation of Human Adenovirus 5 Gene Expression
Authors: Berscheminski Julia , Wimmer Peter , Brun Juliane , Ip Wing Hang , Groitl Peter , Horlacher Tim , Jaffray Ellis , Hay Ron T. , Dobner Thomas , Schreiner Sabrina 
Published: March 2014

ABSTRACTPromyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating capabilities of Sp100A and simultaneously limit repression by Sp100B, -C, and -HMG, adenoviruses (Ads) employ several features to selectively and individually target these isoforms. Ads induce relocalization of Sp100B, -C, and -HMG from PML-NBs prior to association with viral replication centers. In contrast, Sp100A is kept at the PML tracks that surround the newly formed viral replication centers as designated sites of active transcription. We concluded that the host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression. Ad-dependent loss of Sp100 SUMOylation is another crucial part of the virus repertoire to counteract intrinsic immunity by circumventing Sp100 association with HP1, therefore limiting chromatin condensation. We provide evidence that Ad selectively counteracts antiviral responses and, at the same time, benefits from PML-NB-associated components which support viral gene expression by actively recruiting them to PML track-like structures. Our findings provide insights into novel strategies for manipulating transcriptional regulation to either inactivate or amplify viral gene expression.IMPORTANCEWe describe an adenoviral evasion strategy that involves isoform-specific and active manipulation of the PML-associated restriction factor Sp100. Recently, we reported that the adenoviral transactivator E1A targets PML-II to efficiently activate viral transcription. In contrast, the PML-associated proteins Daxx and ATRX are inhibited by early viral factors. We show that this concept is more intricate and significant than originally believed, since adenoviruses apparently take advantage of specific PML-NB-associated proteins and simultaneously inhibit antiviral measures to maintain the viral infectious program. Specifically, we observed Ad-induced relocalization of the Sp100 isoforms B, C, and HMG from PML-NBs juxtaposed with viral replication centers. In contrast, Sp100A is retained at Ad-induced PML tracks that surround the newly formed viral replication centers, acting as designated sites of active transcription. The host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression.
Cocirculation of Three Hemagglutinin and Two Neuraminidase Subtypes of Avian Influenza Viruses in Huzhou, China, April 2013: Implication for the Origin of the Novel H7N9 Virus
Authors: Han Jiankang , Wang Lili , Liu Jia , Jin Meihua , Hao Fangyuan , Zhang Peng , Zhang Zhao , Wen Dong , Wu Xiaofang , Liu Guangtao , Ji Lei , Xu Deshun , Zhou Dongming , Leng Qibin , Lan Ke , Zhang Chiyu 
Published: March 2014

ABSTRACT
We detected three avian influenza hemagglutinin (HA) subtypes (H7, H9, and H5) and two neuraminidase (NA) subtypes (N9 and N2), as well as H7N9-related H9N9 reassortant intermediates, cocirculating among poultry in Huzhou, China, during April 2013. The results of our study reveal not only that Huzhou is one of the geographic origins of the novel H7N9 virus but also that cocirculation poses a potential threat to humans in the future.
Mechanisms of RIG-I-Like Receptor Activation and Manipulation by Viral Pathogens
Authors: Gack Michaela U. 
Published: March 2014

ABSTRACT
RIG-I-like receptors (RLRs) play important roles in the host defense to numerous viral pathogens. Since they were discovered, much light has been shed on the molecular details of how these cytoplasmic viral RNA receptors sense viral infection and orchestrate antiviral innate immunity. Intriguingly, in addition to viral RNA binding, a series of posttranslational modifications (PTMs) is required for the rapid activation of RLRs and, inversely, for the prevention of aberrant innate immune signaling. Recent discoveries have shown that viruses manipulate the PTMs of RLRs to escape innate immune detection. This article highlights some of these recent findings in this fast-evolving field.
Antagonistic Determinants Controlling Replicative and Latent States of Human Cytomegalovirus Infection
Authors: Umashankar Mahadevaiah , Rak Michael , Bughio Farah , Zagallo Patricia , Caviness Katie , Goodrum Felicia D. 
Published: March 2014

ABSTRACT

The mechanisms by which viruses persist and particularly those by which viruses actively contribute to their own latency have been elusive. Here we report the existence of opposing functions encoded by genes within a polycistronic locus of the human cytomegalovirus (HCMV) genome that regulate cell type-dependent viral fates: replication and latency. The locus, referred to as the
UL133-UL138
(
UL133/8
) locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. As part of the UL
b
′ region of the genome, the
UL133/8
locus is lost upon serial passage of clinical strains of HCMV in cultured fibroblasts and is therefore considered dispensable for replication in this context. Strikingly, we could not reconstitute infection in permissive fibroblasts from bacterial artificial chromosome clones of the HCMV genome where
UL135
alone was disrupted. The loss of
UL135
resulted in complex phenotypes and could ultimately be overcome by infection at high multiplicities. The requirement for
UL135
but not the entire locus led us to hypothesize that another gene in this locus suppressed virus replication in the absence of
UL135
. The defect associated with the loss of
UL135
was largely rescued by the additional disruption of the
UL138
latency determinant, indicating a requirement for
UL135
for virus replication when
UL138
is expressed. In the CD34
+
hematopoietic progenitor model of latency, viruses lacking only
UL135
were defective for viral genome amplification and reactivation. Taken together, these data indicate that
UL135
and
UL138
comprise a molecular switch whereby
UL135
is required to overcome
UL138
-mediated suppression of virus replication to balance states of latency and reactivation.

IMPORTANCE
Mechanisms by which viruses persist in their host remain one of the most poorly understood phenomena in virology. Herpesviruses, including HCMV, persist in an incurable, latent state that has profound implications for immunocompromised individuals, including transplant patients. Further, the latent coexistence of HCMV may increase the risk of age-related pathologies, including vascular disease. The key to controlling or eradicating HCMV lies in understanding the molecular basis for latency. In this work, we describe the complex interplay between two viral proteins, pUL135 and pUL138, which antagonize one another in infection to promote viral replication or latency, respectively. We previously described the role of pUL138 in suppressing virus replication for latency. Here we demonstrate a role of pUL135 in overcoming pUL138-mediated suppression for viral reactivation. From this work, we propose that pUL135 and pUL138 constitute a molecular switch balancing states of latency and reactivation.