bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic Evaluation of Umbilical Disorders in Calves
Authors: Robert Mickaël , Touzot‐Jourde Gwenola , Nikolayenkova‐Topie Olga , Cesbron Nora , Fellah Borhane , Tessier Caroline , Gauthier Olivier 
Published: September 2016

ObjectiveTo describe a laparoscopic technique for evaluating umbilical disorders in calves, including feasibility, visualization of umbilical structures, and related complications.Study DesignProspective clinical study.AnimalsMale calves (15 Holstein, 2 Montbeliard) with umbilical disorders (n=17).MethodsCalves <2 months old with obvious umbilical disease were assessed by clinical examination and ultrasonography of the umbilical structures. Laparoscopic evaluation was performed in dorsal recumbency under subarachnoid lumbosacral anesthesia and sedation. An open insertion technique with short 60 mm cannulas was used after creating 2 portals 10 cm cranial to the umbilicus (one 5 cm left of midline for the laparoscope and one 5 cm right of midline as an instrument portal). After laparoscopy, abnormal tissues were resected by laparotomy during the same anesthetic period.ResultsLaparoscopic evaluation of umbilical structures was performed quickly (mean surgery time 7.1 ± 2.5 minutes). Umbilical structures could be completely visualized in all calves without intraoperative complications. In addition to abnormalities previously detected on ultrasound, laparoscopy enabled detection of adhesions 7 calves that were not suspected on ultrasound, as well as focal enlargements of the umbilical arteries and urachus close to the bladder in 5 calves. Laparoscopy failed to detect abnormalities observed with ultrasound or laparotomy in 4 calves, including small hernias and omphalitis.ConclusionLaparoscopic evaluation of umbilical structures was performed safely and quickly in young calves and allowed complete evaluation of intra‐abdominal umbilical structures and may, therefore, be a useful adjunct to physical examination and ultrasound to fully assess the abdomen in calves.
Conservative Management of Unilateral Fractures of the Mandibular Rami in Horses
Authors: Jansson Nicolai 
Published: September 2016

ObjectiveTo report the outcome of conservative management of unilateral fractures of the mandibular rami in horses.Study DesignRetrospective case series.Animals24 client‐owned horses with unilateral mandibular fracturesMethodsMedical records (January 2000–January 2014) of horses with unilateral mandibular ramus fractures were retrieved. Only conservatively managed horses with follow‐up information were included. Follow‐up information on clinical outcome was retrieved from the medical records (n=11) or obtained by telephone interviews with the owners or trainers (n=13).ResultsTwenty‐three horses (96%) returned to their previous or intended use and had no clinically evident masticatory or fracture healing‐related problems at the time of follow‐up. The owner of 1 horse (4%) reported it had tooth loosening, feed impaction, and masticatory problems.ConclusionConservative management of unilateral fractures of the mandibular rami is a treatment option in horses.
Oral administration of antioxidants improves skin wound healing in diabetic mice
Authors: Pessoa Ana Flávia Marçal , Florim Juliana Costa , Rodrigues Hosana Gomes , Andrade‐Oliveira Vinicius , Teixeira Simone A. , Vitzel Kaio Fernando , Curi Rui , Saraiva Câmara Niels Olsen , Muscará Marcelo N. , Lamers Marcelo Lazzaron , Santos Marinilce Fagundes 
Published: September 2016

AbstractOxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b+ and Ly6G+ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG+/CD206− macrophages whereas CD206+/MIG− macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.
Evaluation of Matrix-Assisted Laser Desorption Ionization−Time of Flight Mass Spectrometry for Identification of Mycobacterium abscessus Subspecies According to Whole-Genome Sequencing
Authors: Luo Liulin , Liu Weijia , Li Bing , Li Mengling , Huang Dongdong , Jing Linjie , Chen Huiping , Yang Jinghui , Yue Jun , Wang Fang , Chu Haiqing , Zhang Zhemin 
Published: September 2016

ABSTRACT

This study was undertaken to evaluate the utility of matrix-assisted laser desorption ionization–time of flight mass spectrometry with the Vitek MS Plus system for identifying
Mycobacterium abscessus
subspecies in order to facilitate more rapid and appropriate therapy. A total of 175 clinical
M. abscessus
strains were identified by whole-genome sequencing analysis: 139
Mycobacterium abscessus
subsp.
abscessus
and 36
Mycobacterium abscessus
subsp.
massiliense
. The research-use-only (RUO) Saramis Knowledge Base database v.4.12 was modified accordingly by adding 40
M. abscessus
subsp.
abscessus
and 19
M. abscessus
subsp.
massiliense
reference spectra to construct subspecies SuperSpectra. A blind test, used to validate the remaining 116 isolates, yielded 99.1% (
n
= 115) reliability and only 0.9% (
n
= 1) error for subspecies identification. Among the two subspecies SuperSpectra, two specific peaks were found for
M. abscessus
subsp.
abscessus
and four specific peaks were found for
M. abscessus
subsp.
massiliense
. Our study is the first to report differential peaks 3,354.4
m
/
z
and 6,711.1
m
/
z
, which were specific for
M. abscessus
subsp.
massiliense
. Our research demonstrates the capacity of the Vitek MS RUO Saramis Knowledge Base database to identify
M. abscessus
at the subspecies level. Moreover, it validates the potential ease and accuracy with which it can be incorporated into the IVD system for the identification of
M. abscessus
subspecies.
Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia
Authors: Arnold Nicole , Girke Thomas , Sureshchandra Suhas , Messaoudi Ilhem 
Published: September 2016

ABSTRACT
Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression.

IMPORTANCE
Many aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection.
The Splicing History of an mRNA Affects Its Level of Translation and Sensitivity to Cleavage by the Virion Host Shutoff Endonuclease during Herpes Simplex Virus Infections
Authors: Sadek Jouliana , Read G. Sullivan 
Published: September 2016

ABSTRACT
During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs) and are translated several times more efficiently than unspliced mRNAs that have the same sequence but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during HSV infection, cells were transfected with plasmids harboring an unspliced renilla luciferase (RLuc) reporter mRNA or RLuc constructs with introns near the 5′ or 3′ end of the gene. After splicing of intron-containing transcripts, all three RLuc mRNAs had the same primary sequence. Upon infection in the presence of actinomycin D, spliced mRNAs were much less sensitive to degradation by copies of Vhs from infecting virions than were unspliced mRNAs. During productive infections (in the absence of drugs), RLuc was expressed at substantially higher levels from spliced than from unspliced mRNAs. Interestingly, the stimulatory effect of splicing on RLuc expression was significantly greater in infected than in uninfected cells. The translational stimulatory effect of an intron during HSV-1 infections could be replicated by artificially tethering various EJC components to an unspliced RLuc transcript. Thus, the splicing history of an mRNA, and the consequent presence or absence of EJCs, affects its level of translation and sensitivity to Vhs cleavage during lytic HSV infections.

IMPORTANCE
Most mammalian mRNAs are spliced. In contrast, of the more than 80 mRNAs harbored by herpes simplex virus 1 (HSV-1), only 5 are spliced. In addition, synthesis of the immediate early protein ICP27 causes partial inhibition of pre-mRNA splicing, with the resultant accumulation of both spliced and unspliced versions of some mRNAs in the cytoplasm. A common perception is that HSV-1 infection necessarily inhibits the expression of spliced mRNAs. In contrast, this study demonstrates two instances in which pre-mRNA splicing actually enhances the synthesis of proteins from mRNAs during HSV-1 infections. Specifically, splicing stabilized an mRNA against degradation by copies of the Vhs endoribonuclease from infecting virions and greatly enhanced the amount of protein synthesized from spliced mRNAs at late times after infection. The data suggest that splicing, and the resultant presence of exon junction complexes on an mRNA, may play an important role in gene expression during HSV-1 infections.
Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis
Authors: Chandrasekharan Jayashree A. , Huang Xiao M. , Hwang Alexander C. , Sharma-Walia Neelam 
Published: September 2016

ABSTRACT

Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using
in vitro
KS and PEL cells as models. The presence of the lipoxin A4 receptor/formyl peptidyl receptor (ALX/FPR) in KS patient tissue sections and
in vitro
KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating
de novo
KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing the levels of NF-κB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene deletion revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral microRNA (miRNA) cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. This study provides a new insight into the potential treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin.

IMPORTANCE
KSHV infection has been shown to upregulate several host proinflammatory factors, which aid in its survival and pathogenesis. The influence of KSHV infection on anti-inflammatory molecules is not well studied. Since current treatment methods for KS and PEL are fraught with unwanted side effects and low efficiency, the search for new therapeutics is therefore imperative. The use of nature's own molecule lipoxin as a drug is promising. This study opens up new domains in KSHV research focusing on how the virus modulates lipoxin secretion and warrants further investigation of the therapeutic potential of lipoxin using
in vitro
cell models for KS and PEL.
The US3 Protein of Pseudorabies Virus Drives Viral Passage across the Basement Membrane in Porcine Respiratory Mucosa Explants
Authors: Lamote Jochen A. S. , Glorieux Sarah , Nauwynck Hans J. , Favoreel Herman W. 
Published: September 2016

ABSTRACT

Passage of the basement membrane (BM), which forms a barrier between the epithelium and the underlying lamina propria, represents an important step in the early pathogenesis of different alphaherpesviruses. Rho GTPase signaling plays an important role in transmigration of cells across the BM during physiological and pathological processes. We reported earlier that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) interferes with Rho GTPase signaling and causes a reorganization of the host cell cytoskeleton, which as a consequence, enhances viral cell-to-cell spread in epithelial cell cultures. Here, using an
ex vivo
system of porcine nasal respiratory mucosa explants that allows to study PRV invasion through the BM, we found that a PRV strain that lacks US3 expression (ΔUS3 PRV) showed a reduced spread in mucosal epithelium and was virtually unable to breach the BM, in contrast to isogenic wild-type (WT) or US3 rescue PRV strains. Interestingly, addition of IPA3, an inhibitor of p21-activated kinases that blocks the effects of US3 on the cytoskeleton, suppressed the ability of WT PRV to spread across the BM. In addition, artificial suppression of RhoA signaling using CPC3 (cell-permeable C3 transferase) to mimic the effects of US3 on Rho GTPase signaling, significantly increased passage of ΔUS3 PRV through the BM, whereas it did not significantly affect BM passage of WT or US3 rescue PRV. In conclusion, these data indicate that US3 plays an important role in PRV mucosal invasion across the BM, which involves its interference with Rho GTPase signaling. This is the first report describing an alphaherpesvirus protein that drives viral BM passage.

IMPORTANCE
Many viruses, including alphaherpesviruses, primarily replicate in epithelial cells of surface mucosae, such as the respiratory mucosa. Some of these viruses breach the basement membrane underlying these epithelial cells to reach underlying connective tissue and blood vessels and invade the host. Hence, epithelial spread and basement membrane passage represent crucial but still poorly understood early steps in (alphaherpes)virus pathogenesis. Here, using
ex vivo
porcine respiratory mucosa explants, we show that the conserved US3 protein of the porcine alphaherpesvirus pseudorabies virus (PRV) is critical for passage of PRV across the basement membrane and contributes to efficient viral epithelial spread. In addition, we show that US3-mediated viral epithelial spread and passage across the basement membrane depend at least in part on the ability of this viral protein to modulate cellular Rho GTPase signaling. This is the first report that identifies an alphaherpesvirus protein that drives viral basement membrane passage.
Structure of Aichi Virus 1 and Its Empty Particle: Clues to Kobuvirus Genome Release Mechanism
Authors: Sabin Charles , Füzik Tibor , Škubník Karel , Pálková Lenka , Lindberg A. Michael , Plevka Pavel 
Published: September 2016

ABSTRACT

Aichi virus 1
(AiV-1) is a human pathogen from the
Kobuvirus
genus of the
Picornaviridae
family. Worldwide, 80 to 95% of adults have antibodies against the virus. AiV-1 infections are associated with nausea, gastroenteritis, and fever. Unlike most picornaviruses, kobuvirus capsids are composed of only three types of subunits: VP0, VP1, and VP3. We present here the structure of the AiV-1 virion determined to a resolution of 2.1 Å using X-ray crystallography. The surface loop puff of VP0 and knob of VP3 in AiV-1 are shorter than those in other picornaviruses. Instead, the 42-residue BC loop of VP0 forms the most prominent surface feature of the AiV-1 virion. We determined the structure of AiV-1 empty particle to a resolution of 4.2 Å using cryo-electron microscopy. The empty capsids are expanded relative to the native virus. The N-terminal arms of capsid proteins VP0, which mediate contacts between the pentamers of capsid protein protomers in the native AiV-1 virion, are disordered in the empty capsid. Nevertheless, the empty particles are stable, at least
in vitro
, and do not contain pores that might serve as channels for genome release. Therefore, extensive and probably reversible local reorganization of AiV-1 capsid is required for its genome release.

IMPORTANCE
Aichi virus 1 (AiV-1) is a human pathogen that can cause diarrhea, abdominal pain, nausea, vomiting, and fever. AiV-1 is identified in environmental screening studies with higher frequency and greater abundance than other human enteric viruses. Accordingly, 80 to 95% of adults worldwide have suffered from AiV-1 infections. We determined the structure of the AiV-1 virion. Based on the structure, we show that antiviral compounds that were developed against related enteroviruses are unlikely to be effective against AiV-1. The surface of the AiV-1 virion has a unique topology distinct from other related viruses from the
Picornaviridae
family. We also determined that AiV-1 capsids form compact shells even after genome release. Therefore, AiV-1 genome release requires large localized and probably reversible reorganization of the capsid.
Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity
Authors: Jiang Zhangtao , Su Chenhe , Zheng Chunfu 
Published: September 2016

ABSTRACT
The interferon-induced protein with tetratricopeptide repeat 3 (IFIT3 or ISG60) is a host-intrinsic antiviral factor that restricts many instances of DNA and RNA virus replication. Herpes simplex virus 1 (HSV-1), a DNA virus bearing a large genome, can encode many viral proteins to counteract the host immune responses. However, whether IFIT3 plays a role upon HSV-1 infection is little known. In this study, we show for the first time that HSV-1 tegument protein UL41, a viral endoribonuclease, plays an important role in inhibiting the antiviral activity of IFIT3. Here, we demonstrated that ectopically expressed IFIT3 could restrict the replication of vesicular stomatitis virus (VSV) but had little effect on the replication of wild-type (WT) HSV-1. Further study showed that WT HSV-1 infection downregulated the expression of IFIT3, and ectopic expression of UL41, but not the immediate-early protein ICP0, notably reduced the expression of IFIT3. The underlying molecular mechanism was that UL41 diminished the accumulation of IFIT3 mRNA to abrogate its antiviral activity. In addition, our results illustrated that ectopic expression of IFIT3 inhibited the replication of UL41-null mutant virus (R2621), and stable knockdown of IFIT3 facilitated its replication. Taking these findings together, HSV-1 was shown for the first time to evade the antiviral function of IFIT3 via UL41.

IMPORTANCE
The tegument protein UL41 of HSV-1 is an endoribonuclease with the substrate specificity of RNase A, which plays an important role in viral infection. Upon HSV-1 infection, interferons are critical cytokines that regulate immune responses against viral infection. Host antiviral responses are significantly boosted or crippled in the presence or absence of IFIT3; however, whether IFIT3 plays a role during HSV-1 infection is still unknown. Our data show for the first time that IFIT3 has little effect on HSV-1 replication, as UL41 decreases the accumulation of IFIT3 mRNA and subverts its antiviral activity. This study identifies IFIT3 as a novel target of the tegument protein UL41 and provides new insight into HSV-1-mediated immune evasion.