bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism – a role for Ca2+?
Authors: R. Oliveira Sara , Queiroga Cláudia S. F. , Vieira Helena L. A. 
Published: September 2015

AbstractCarbon monoxide (CO) is an endogenously produced gasotransmitter with important biological functions: anti‐inflammation, anti‐apoptosis, vasomodulation and cell metabolism modulation. The most recognized cellular target for CO is the mitochondria. Physiological concentrations of CO generate mitochondrial reactive oxygen species (ROS), which are signalling molecules for CO‐induced pathways. Indeed, small amounts of ROS promote cytoprotection by a preconditioning effect. Furthermore, CO prevents cell death by limiting mitochondrial membrane permeabilization, which inhibits the release of pro‐apoptotic factors into the cytosol; both events are ROS dependent. CO also increases the ability of mitochondria to take up Ca2+. Mitochondrial metabolism is modulated by CO, namely by increasing TCA cycle rate, oxidative phosphorylation and mitochondrial biogenesis, which, in turn, increases ATP production. CO's modulation of metabolism might be important for cellular response to diseases, namely cancer and ischaemic diseases. Finally, another cytoprotective role of CO involves the control of Ca2+ channels. By limiting the activity of T‐type and L‐type Ca2+ channels, CO prevents excitotoxicity‐induced cell death and modulates cell proliferation. Several questions concerning Ca2+ signalling, mitochondria and CO can be asked, for instance whether CO modulation of cell metabolism would be dependent on the mitochondrial Ca2+ uptake capacity, since small amounts of Ca2+ can increase mitochondrial metabolism. Whether CO controls Ca2+ communication between mitochondria and endoplasmic reticulum is another open field of research. In summary, CO emerges as a key gasotransmitter in the control of several cellular functions of mitochondria: metabolism, cell death and Ca2+ signalling.
image
Shear stress induces a longitudinal Ca2+ wave via autocrine activation of P2Y1 purinergic signalling in rat atrial myocytes
Authors: Kim Joon‐Chul , Woo Sun‐Hee 
Published: September 2015

Key points
Cardiac myocytes are subjected to fluid shear stress during the cardiac cycle and haemodynamic disturbance.
A longitudinally propagating, regenerative Ca2+ wave is initiated in atrial myocytes under shear stress.
Here we determine the cellular mechanism for this shear‐induced Ca2+ wave using two‐dimensional confocal Ca2+ imaging combined with pressurized fluid flow.
Our data suggest that shear stress triggers the Ca2+ wave through ryanodine receptors via P2Y1 purinoceptor–phospholipase C‐type 2 inositol 1,4,5‐trisphosphate receptor signal transduction in atrial myocytes, and that this mechanotransduction is activated by gap junction hemichannel‐mediated ATP release.
Shear‐specific mechanotransduction and the subsequent regenerative Ca2+ wave may be one way for atrial myocytes to assess mechanical stimuli directly and alter their Ca2+ signalling accordingly.
AbstractAtrial myocytes are exposed to shear stress during the cardiac cycle and haemodynamic disturbance. In response, they generate a longitudinally propagating global Ca2+ wave. Here, we investigated the cellular mechanisms underlying the shear stress‐mediated Ca2+ wave, using two‐dimensional confocal Ca2+ imaging combined with a pressurized microflow system in single rat atrial myocytes. Shear stress of ∼16 dyn cm−2 for 8 s induced ∼1.2 aperiodic longitudinal Ca2+ waves (∼79 μm s−1) with a delay of 0.2−3 s. Pharmacological blockade of ryanodine receptors (RyRs) or inositol 1,4,5‐trisphosphate receptors (IP3Rs) abolished shear stress‐induced Ca2+ wave generation. Furthermore, in atrial myocytes from type 2 IP3R (IP3R2) knock‐out mice, shear stress failed to induce longitudinal Ca2+ waves. The phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the shear‐induced longitudinal Ca2+ wave. However, pretreating atrial cells with blockers for stretch‐activated channels, Na+−Ca2+ exchanger, transient receptor potential melastatin subfamily 4, or nicotinamide adenine dinucleotide phosphate oxidase did not suppress wave generation under shear stress. The P2 purinoceptor inhibitor suramin, and the potent P2Y1 receptor antagonist MRS 2179, both suppressed the Ca2+ wave, whereas the P2X receptor antagonist, iso‐PPADS, did not alter it. Suppression of gap junction hemichannels permeable to ATP or extracellular application of ATP‐metabolizing apyrase inhibited the wave. Removal of external Ca2+ to enhance hemichannel opening facilitated the wave generation. Our data suggest that longitudinally propagating, regenerative Ca2+ release through RyRs is triggered by P2Y1–PLC–IP3R2 signalling that is activated by gap junction hemichannel‐mediated ATP release in atrial myocytes under shear stress.
Understanding the Association of Human Rhinovirus with Asthma
Authors: Stone Cosby A. , Miller E. Kathryn 
Published: September 2015

ABSTRACT
Human rhinoviruses are ubiquitous seasonal pathogens. They have known associations with first onset of wheezing illnesses in children and with asthma exacerbations in patients of all ages. It is not yet certain whether human rhinoviruses play a direct role in the pathogenesis of asthma by activating deleterious inflammatory responses or if they only serve as a catalyst to accelerate the disease in genetically predisposed individuals. There have been previously demonstrated reductions in the development of the asthmatic phenotype with passive immunization against respiratory syncytial virus; however, in the case of rhinovirus, there are barriers to effective vaccine development, such as the lack of a common antigenic target due to alterations of surface markers among subtypes. It remains to be determined whether certain subtypes of human rhinovirus are more asthmagenic and therefore worthy of greater attention as vaccine candidates, but several studies have suggested that RV-C and certain RV-A strains may be more strongly linked with asthma.
Mapping Type IV Secretion Signals on the Primase Encoded by the Broad-Host-Range Plasmid R1162 (RSF1010)
Authors: Meyer Richard 
Published: September 2015

ABSTRACT

The plasmid R1162 (RSF1010) encodes a primase essential for its replication. This primase makes up the C-terminal part of MobA, a multifunctional protein with the relaxase as a separate N-terminal domain. The primase is also translated separately as the protein RepB′. Here, we map two signals for type IV secretion onto the recently solved structure of RepB′. One signal is located internally within RepB′ and consists of a long α-helix and an adjacent disordered region rich in arginines. The second signal is made up of the same α-helix and a second, arginine-rich region at the C-terminal end of the protein. Successive arginine-to-alanine substitutions revealed that either signal can be utilized by the type IV secretion complex of the plasmid R751. The internal signal also enables conjugal transfer when linked to the relaxase part of MobA. Both signals are similar to those previously identified for type IV secretion substrates in the Vir system of
Agrobacterium tumefaciens
. Moreover, the C-terminal arginine-rich segment of RepB′ has been shown to be secreted by Vir. However, with R751, the signals require MobB, an R1162-encoded accessory protein active in conjugal transfer. The results of two-hybrid assays revealed that MobB interacts, via its membrane-associated domain, with the R751 plasmid coupling protein TraG. In addition, MobB interacts with a region of MobA just outside the RepB′ domain. Therefore, MobB is likely an adaptor that is essential for recognition of the primase-associated signals by the R751 secretion machinery.

IMPORTANCE
For most plasmids, type IV secretion is an intrinsic part of the mechanism for conjugal transfer. Protein relaxases, bound to the 5′ end of the transferring strand, are mobilized into recipient cells by the type IV pathway. In this work, we identify and characterize two signals for secretion in the primase domain of MobA, the relaxase of the IncQ plasmid R1162 (RSF1010). We also show that the adaptor protein MobB is required for engagement of these signals with the R751 coupling protein TraG. These results clarify the location and properties of secretion signals active during the conjugal transfer of plasmid DNA.
First Report of Wohlfahrtiimonaschitiniclastica Isolation from a Patient with Cellulitis in the United States
Authors: de Dios Angel , Jacob Seby , Tayal Amit , Fisher Mark A. , Dingle Tanis C. , Hamula Camille L. 
Published: September 2015

ABSTRACT

We report the first documented isolation of
Wohlfahrtiimonas
chitiniclastica
from a human in the United States. Initially misidentified as
Acinetobacter lwoffii
by Vitek-2, the isolate was subsequently identified as
W
.
chitiniclastica
by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. While the clinical significance of the isolate in this case is unclear, it highlights the superior performance of MALDI-TOF MS for bacterial identification.
Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis
Authors: Lau Susanna K. P. , Lee Kim-Chung , Curreem Shirly O. T. , Chow Wang-Ngai , To Kelvin K. W. , Hung Ivan F. N. , Ho Deborah T. Y. , Sridhar Siddharth , Li Iris W. S. , Ding Vanessa S. Y. , Koo Eleanor W. F. , Wong Chi-Fong , Tam Sidney , Lam Ching-Wan , Yuen Kwok-Yung , Woo Patrick C. Y. 
Published: September 2015

ABSTRACT

Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (
n
= 46) with those of community-acquired pneumonia (CAP) patients (
n
= 30) and controls without active infection (
n
= 30) using ultrahigh-performance liquid chromatography–electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.
One-Step Identification of Five Prominent Chicken Salmonella Serovars and Biotypes
Authors: Zhu Chunhong , Yue Min , Rankin Shelley , Weill François-Xavier , Frey Joachim , Schifferli Dieter M. 
Published: September 2015

ABSTRACT

Based on bacterial genomic data, we developed a one-step multiplex PCR assay to identify
Salmonella
and simultaneously differentiate the two invasive avian-adapted
S. enterica
serovar Gallinarum biotypes Gallinarum and Pullorum, and the most frequent, specific, and asymptomatic colonizers of chickens, serovars Enteritidis, Heidelberg, and Kentucky.
Characterization of a Novel Hepadnavirus in the White Sucker (Catostomus commersonii) from the Great Lakes Region of the United States
Authors: Hahn Cassidy M. , Iwanowicz Luke R. , Cornman Robert S. , Conway Carla M. , Winton James R. , Blazer Vicki S. 
Published: September 2015

ABSTRACT

The white sucker
Catostomus commersonii
is a freshwater teleost often utilized as a resident sentinel. Here, we sequenced the full genome of a hepatitis B-like virus that infects white suckers from the Great Lakes Region of the United States. Dideoxy sequencing confirmed that the white sucker hepatitis B virus (WSHBV) has a circular genome (3,542 bp) with the prototypical codon organization of hepadnaviruses. Electron microscopy demonstrated that complete virions of approximately 40 nm were present in the plasma of infected fish. Compared to avi- and orthohepadnaviruses, sequence conservation of the core, polymerase, and surface proteins was low and ranged from 16 to 27% at the amino acid level. An X protein homologue common to the orthohepadnaviruses was not present. The WSHBV genome included an atypical, presumptively noncoding region absent in previously described hepadnaviruses. Phylogenetic analyses confirmed WSHBV as distinct from previously documented hepadnaviruses. The level of divergence in protein sequences between WSHBV and other hepadnaviruses and the identification of an HBV-like sequence in an African cichlid provide evidence that a novel genus of the family
Hepadnaviridae
may need to be established that includes these hepatitis B-like viruses in fishes. Viral transcription was observed in 9.5% (16 of 169) of white suckers evaluated. The prevalence of hepatic tumors in these fish was 4.9%, and only 2.4% of fish were positive for both virus and hepatic tumors. These results are not sufficient to draw inferences regarding the association of WSHBV and carcinogenesis in white sucker.

IMPORTANCE
We report the first full-length genome of a hepadnavirus from fishes. Phylogenetic analysis of this genome indicates divergence from genomes of previously described hepadnaviruses from mammalian and avian hosts and supports the creation of a novel genus. The discovery of this novel virus may better our understanding of the evolutionary history of hepatitis B-like viruses of other hosts. In fishes, knowledge of this virus may provide insight regarding possible risk factors associated with hepatic neoplasia in the white sucker. This may also offer another model system for mechanistic research.
Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity
Authors: Allonso Diego , Andrade Iamara S. , Conde Jonas N. , Coelho Diego R. , Rocha Daniele C. P. , da Silva Manuela L. , Ventura Gustavo T. , Silva Emiliana M. , Mohana-Borges Ronaldo 
Published: September 2015

ABSTRACT

Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH
in vitro
. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV.

IMPORTANCE
Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the intracellular and the extracellular milieus. Despite the fact that NS1 has been commonly associated with DENV pathogenesis, it plays a pivotal but unknown role in the replication process. In an effort to understand the role of intracellular NS1, we demonstrate that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with NS1. Our results indicate that NS1 increases the glycolytic activity of GAPDH
in vitro
. Interestingly, the GAPDH activity was increased during DENV infection, and NS1 expression alone was sufficient to enhance intracellular GAPDH activity in BHK-21 cells. Overall, our findings suggest that NS1 is an important modulator of cellular energy metabolism by increasing glycolytic flux.
CD8lowCD100−T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection
Authors: Liu Bei , Ma Ying , Zhang Yusi , Zhang Chunmei , Yi Jing , Zhuang Ran , Yu Haitao , Yang Angang , Zhang Yun , Jin Boquan 
Published: September 2015

ABSTRACTHantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8+T cells play a critical role in combating HTNV infections. However, the contributions of different CD8+T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8+T cells characterized by the CD8lowCD100−phenotype in HFRS patients. The CD8lowCD100−subset accounted for a median of 14.3% of the total CD8+T cells in early phase of HFRS, and this percentage subsequently declined in the late phase of infection, whereas this subset was absent in healthy controls. Furthermore, the CD8lowCD100−cells were associated with high activation and expressed high levels of cytolytic effector molecules and exhibited a distinct expression profile of effector CD8+T cells (CCR7+/−CD45RA−CD127highCD27intCD28lowCD62L−). When stimulated with specific HTNV nucleocapsid protein-derived peptide pools, most responding CD8+cells (gamma interferon [IFN-γ] positive and/or tumor necrosis factor alpha [TNF-α] positive) were CD8lowCD100−cells. The frequency of CD8lowCD100−cells among HTNV-specific CD8+T cells was higher in milder cases than in more severe cases. Importantly, the proportion of the CD8lowCD100−subset among CD8+T cells in early phase of HFRS was negatively correlated with the HTNV viral load, suggesting that CD8lowCD100−cells may be associated with viral clearance. The contraction of the CD8lowCD100−subset in late phase of infection may be related to the consistently high expression levels of PD-1. These results may provide new insights into our understanding of CD8+T cell-mediated protective immunity as well as immune homeostasis after HTNV infection in humans.IMPORTANCECD8+T cells play important roles in the antiviral immune response. We found that the proportion of CD8lowCD100−cells among CD8+T cells from HFRS patients was negatively correlated with the HTNV viral load, and the frequency of CD8lowCD100−cells among virus-specific CD8+T cells was higher in milder HFRS cases than in more severe cases. These results imply a beneficial role for the CD8lowCD100−cell subset in viral control during human HTNV infection.
Differential Reovirus-Specific and Herpesvirus-Specific Activator Protein 1 Activation of Secretogranin II Leads to Altered Virus Secretion
Authors: Berard Alicia R. , Severini Alberto , Coombs Kevin M. 
Published: September 2015

ABSTRACTViruses utilize host cell machinery for propagation and manage to evade cellular host defense mechanisms in the process. Much remains unknown regarding how the host responds to viral infection. We recently performed global proteomic screens of mammalian reovirus TIL- and T3D-infected and herpesvirus (herpes simplex virus 1 [HSV-1])-infected HEK293 cells. The nonenveloped RNA reoviruses caused an upregulation, whereas the enveloped DNA HSV-1 caused a downregulation, of cellular secretogranin II (SCG2). SCG2, a member of the granin family that functions in hormonal peptide sorting into secretory vesicles, has not been linked to virus infections previously. We confirmed SCG2 upregulation and found SCG2 phosphorylation by 18 h postinfection (hpi) in reovirus-infected cells. We also found a decrease in the amount of reovirus secretion from SCG2 knockdown cells. Similar analyses of cells infected with HSV-1 showed an increase in the amount of secreted virus. Analysis of the stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) pathway indicated that each virus activates different pathways leading to activator protein 1 (AP-1) activation, which is the known SCG2 transcription activator. We conclude from these experiments that the negative correlation between SCG2 quantity and virus secretion for both viruses indicates a virus-specific role for SCG2 during infection.IMPORTANCEMammalian reoviruses affect the gastrointestinal system or cause respiratory infections in humans. Recent work has shown that all mammalian reovirus strains (most specifically T3D) may be useful oncolytic agents. The ubiquitous herpes simplex viruses cause common sores in mucosal areas of their host and have coevolved with hosts over many years. Both of these virus species are prototypical representatives of their viral families, and investigation of these viruses can lead to further knowledge of how they and the other more pathogenic members of their respective families interact with the host. Here we show that secretogranin II (SCG2), a protein not previously studied in the context of virus infections, alters virus output in a virus-specific manner and that the quantity of SCG2 is inversely related to amounts of infectious-virus secretion. Herpesviruses may target this protein to facilitate enhanced virus release from the host.