bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment of Dynamic Endothelial Ca2+ Signals by the TRPA1 Channel Activator AITC in Rat Cerebral Arteries
Authors: Qian Xun , Francis Michael , Solodushko Viktoriya , Earley Scott , Taylor Mark S. 
Published: August 2012

AbstractObjectiveStimulation of endothelial TRP channels, specifically TRPA1, promotes vasodilation of cerebral arteries through activation of Ca2+‐dependent effectors along the myoendothelial interface. However, presumed TRPA1‐triggered endothelial Ca2+ signals have not been described. We investigated whether TRPA1 activation induces specific spatial and temporal changes in Ca2+ signals along the intima that correlates with incremental vasodilation.MethodsConfocal imaging, immunofluorescence staining, and custom image analysis were employed.ResultsWe found that endothelial cells of rat cerebral arteries exhibit widespread basal Ca2+ dynamics (44 ± 6 events/minute from 26 ± 3 distinct sites in a 3.6 × 104 μm2 field). The TRPA1 activator AITC increased Ca2+ signals in a concentration‐dependent manner, soliciting new events at distinct sites. Origination of these new events corresponded spatially with TRPA1 densities in IEL holes, and the events were prevented by the TRPA1 inhibitor HC‐030031. Concentration‐dependent expansion of Ca2+ events in response to AITC correlated precisely with dilation of pressurized cerebral arteries (p = 0.93 by F‐test). Correspondingly, AITC caused rapid endothelium‐dependent suppression of asynchronous Ca2+ waves in subintimal smooth muscle.ConclusionsOur findings indicate that factors that stimulate TRPA1 channels expand Ca2+ signal‐effector coupling at discrete sites along the endothelium to evoke graded cerebral artery vasodilation.
Stoking the drug target pipeline for human African trypanosomiasis
Authors: Phillips Margaret A. 
Published: August 2012

SummaryTrypanosoma brucei is the causative agent of African sleeping sickness, putting at risk up to 50 million people in sub‐Saharan Africa. Current drug therapies are limited by toxicity and difficult treatment regimes and as the development of vaccines remains unlikely, the identification of better drugs to control this deadly disease is needed. Strategies for the identification of new lead compounds include phenotypic screening or target‐based approaches. Implementation of the latter has been hampered by the lack of defined targets that are both essential and druggable. In this issue of Molecular Microbiology, Jones et al. () report on the characterization of T. brucei pyridoxal kinase (PdxK), an enzyme required for the salvage of vitamin B6, an essential enzymatic cofactor. Genetic knock‐down and small molecule inhibitor studies were used to demonstrate that PdxK is essential for parasite growth both in vitro and in a mouse model, providing both genetic and chemical validation of the target. An enzyme assay compatible with high‐throughput screening (HTS) was developed and the X‐ray crystal structure solved, showing the potential for species selective inhibition. These studies add a greatly needed additional target into the drug discovery pipeline for this deadly parasitic infection.
Activation of the Unfolded Protein Response by 2-Deoxy-
d
-Glucose Inhibits Kaposi's Sarcoma-Associated Herpesvirus Replication and Gene Expression
Authors: Leung Howard J. , Duran Elda M. , Kurtoglu Metin , Andreansky Samita , Lampidis Theodore J. , Mesri Enrique A. 
Published: August 2012

ABSTRACT

Lytic replication of the Kaposi's sarcoma-associated herpesvirus (KSHV) is essential for the maintenance of both the infected state and characteristic angiogenic phenotype of Kaposi's sarcoma and thus represents a desirable therapeutic target. During the peak of herpesvirus lytic replication, viral glycoproteins are mass produced in the endoplasmic reticulum (ER). Normally, this leads to ER stress which, through an unfolded protein response (UPR), triggers phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), resulting in inhibition of protein synthesis to maintain ER and cellular homeostasis. However, in order to replicate, herpesviruses have acquired the ability to prevent eIF2α phosphorylation. Here we show that clinically achievable nontoxic doses of the glucose analog 2-deoxy-
d
-glucose (2-DG) stimulate ER stress, thereby shutting down eIF2α and inhibiting KSHV and murine herpesvirus 68 replication and KSHV reactivation from latency. Viral cascade genes that are involved in reactivation, including the master transactivator (RTA) gene, glycoprotein B, K8.1, and angiogenesis-regulating genes are markedly decreased with 2-DG treatment. Overall, our data suggest that activation of UPR by 2-DG elicits an early antiviral response via eIF2α inactivation, which impairs protein synthesis required to drive viral replication and oncogenesis. Thus, induction of ER stress by 2-DG provides a new antiherpesviral strategy that may be applicable to other viruses.
Proteomic Response of Bacillus subtilis to Lantibiotics Reflects Differences in Interaction with the Cytoplasmic Membrane
Authors: Wenzel Michaela , Kohl Bastian , Münch Daniela , Raatschen Nadja , Albada H. Bauke , Hamoen Leendert , Metzler-Nolte Nils , Sahl Hans-Georg , Bandow Julia E. 
Published: August 2012

ABSTRACT

Mersacidin, gallidermin, and nisin are lantibiotics, antimicrobial peptides containing lanthionine. They show potent antibacterial activity. All three interfere with cell wall biosynthesis by binding lipid II, but they display different levels of interaction with the cytoplasmic membrane. On one end of the spectrum, mersacidin interferes with cell wall biosynthesis by binding lipid II without integrating into bacterial membranes. On the other end of the spectrum, nisin readily integrates into membranes, where it forms large pores. It destroys the membrane potential and causes leakage of nutrients and ions. Gallidermin, in an intermediate position, also readily integrates into membranes. However, pore formation occurs only in some bacteria and depends on membrane composition. In this study, we investigated the impact of nisin, gallidermin, and mersacidin on cell wall integrity, membrane pore formation, and membrane depolarization in
Bacillus subtilis
. The impact of the lantibiotics on the cell envelope was correlated to the proteomic response they elicit in
B. subtilis
. By drawing on a proteomic response library, including other envelope-targeting antibiotics such as bacitracin, vancomycin, gramicidin S, or valinomycin, YtrE could be identified as the most reliable marker protein for interfering with membrane-bound steps of cell wall biosynthesis. NadE and PspA were identified as markers for antibiotics interacting with the cytoplasmic membrane.
Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice
Authors: Singh Shubhra , Dwivedi Richa , Chaturvedi Vinita 
Published: August 2012

ABSTRACT

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of
Mycobacterium tuberculosis
infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters.
Leptospira interrogans Catalase Is Required for Resistance to H
2
O
2
and for Virulence
Authors: Eshghi Azad , Lourdault Kristel , Murray Gerald L. , Bartpho Thanatchaporn , Sermswan Rasana W. , Picardeau Mathieu , Adler Ben , Snarr Brendan , Zuerner Richard L. , Cameron Caroline E. 
Published: August 2012

ABSTRACT

Pathogenic
Leptospira
spp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterized
Leptospira interrogans
catalase (KatE), the only annotated catalase found within pathogenic
Leptospira
species, by assessing its role in resistance to H
2
O
2
-induced oxidative stress and during infection in hamsters. Pathogenic
L. interrogans
bacteria had a 50-fold-higher survival rate under H
2
O
2
-induced oxidative stress than did saprophytic
L. biflexa
bacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenic
Leptospira
species. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation of
katE
in pathogenic
Leptospira
bacteria drastically diminished leptospiral viability in the presence of extracellular H
2
O
2
and reduced virulence in an acute-infection model. Combined, these results suggest that
L. interrogans
KatE confers
in vivo
resistance to reactive oxygen species induced by the host innate immune response.
Cathelicidin Antimicrobial Peptide Expression Is Not Induced or Required for Bacterial Clearance during Salmonella enterica Infection of Human Monocyte-Derived Macrophages
Authors: Strandberg Kristi L. , Richards Susan M. , Gunn John S. 
Published: August 2012

ABSTRACT

Salmonella enterica
serovar Typhimurium is able to resist antimicrobial peptide killing by induction of the PhoP-PhoQ and PmrA-PmrB two-component systems and the lipopolysaccharide (LPS) modifications they mediate. Murine cathelin-related antimicrobial peptide (CRAMP) has been reported to inhibit
S
. Typhimurium growth
in vitro
and
in vivo
. We hypothesize that infection of human monocyte-derived macrophages (MDMs) with
Salmonella enterica
serovar Typhi and
S
. Typhimurium will induce human cathelicidin antimicrobial peptide (CAMP) production, and exposure to LL-37 (processed, active form of CAMP/hCAP18) will lead to upregulation of PmrAB-mediated LPS modifications and increased survival
in vivo
. Unlike in mouse macrophages, in which CRAMP is upregulated during infection,
camp
gene expression was not induced in human MDMs infected with
S
. Typhi or
S
. Typhimurium. Upon infection, intracellular levels of Δ
phoPQ
, Δ
pmrAB
, and PhoP
c
S
. Typhi decreased over time but were not further inhibited by the vitamin D
3
-induced increase in
camp
expression. MDMs infected with wild-type (WT)
S
. Typhi or
S
. Typhimurium released similar levels of proinflammatory cytokines; however, the LPS modification mutant strains dramatically differed in MDM-elicited cytokine levels. Overall, these findings indicate that
camp
is not induced during
Salmonella
infection of MDMs nor is key to
Salmonella
intracellular clearance. However, the cytokine responses from MDMs infected with WT or LPS modification mutant strains differ significantly, indicating a role for LPS modifications in altering the host inflammatory response. Our findings also suggest that
S
. Typhi and
S
. Typhimurium elicit different proinflammatory responses from MDMs, despite being capable of adding similar modifications to their LPS structures.
The Alveolar Epithelial Cell Chemokine Response to Pneumocystis Requires Adaptor Molecule MyD88 and Interleukin-1 Receptor but Not Toll-Like Receptor 2 or 4
Authors: Bello-Irizarry Sheila N. , Wang Jing , Olsen Keith , Gigliotti Francis , Wright Terry W. 
Published: August 2012

ABSTRACT

Pneumocystis
is an opportunistic fungal pathogen that causes pneumonia in a variety of clinical settings. An early step in
Pneumocystis
infection involves the attachment of organisms to alveolar epithelial cells (AECs). AECs produce chemokines in response to
Pneumocystis
stimulation, but the upstream host-pathogen interactions that activate AEC signaling cascades are not well-defined. MyD88 is an adaptor molecule required for activation of proinflammatory signaling cascades following Toll-like receptor (TLR)-dependent recognition of conserved molecular patterns on pathogens. To determine whether the TLR/MyD88 pathway is required for the AEC chemokine response to
Pneumocystis
, wild-type (WT) and MyD88-deficient AECs were incubated with
Pneumocystis
. As expected, WT AECs produced CCL2 and CXCL2 following
Pneumocystis
stimulation. In contrast, MyD88-deficient AECs were severely impaired in their ability to respond to
Pneumocystis
. MyD88-deficient AECs did not display
Pneumocystis
-induced Jun N-terminal protein kinase activation and produced much less chemokine than
Pneumocystis
-stimulated WT AECs. Using a panel of TLR agonists, primary murine AECs were found to respond vigorously to TLR2 and TLR4 agonists. However, the AEC chemokine response to
Pneumocystis
did not require TLR2 or TLR4. Surprisingly, the interleukin-1 receptor (IL-1R) was required for an AEC chemokine response to
Pneumocystis
. The role of MyD88 in early responses during
Pneumocystis
infection was supported by
in vivo
studies demonstrating that MyD88-deficient mice showed impaired
Pneumocystis
-stimulated chemokine production and impaired inflammatory cell recruitment. These data indicate an important role for MyD88 in the AEC inflammatory response to
Pneumocystis
.
Genome Sequence of Rickettsia australis, the Agent of Queensland Tick Typhus
Authors: Dong Xin , El Karkouri Khalid , Robert Catherine , Raoult Didier , Fournier Pierre-Edouard 
Published: August 2012

ABSTRACTRickettsia australisstrain PhillipsTwas isolated in Queensland, Australia, in 1950. It is the tick-borne agent of Queensland tick typhus, a disease endemic in Australia. The 1.29-Mb genome sequence of this bacterium is highly similar to that ofRickettsia akaribut contains two plasmids.
Genome Sequence of Rickettsia conorii subsp. israelensis, the Agent of Israeli Spotted Fever
Authors: Sentausa Erwin , El Karkouri Khalid , Robert Catherine , Raoult Didier , Fournier Pierre-Edouard 
Published: August 2012

ABSTRACTRickettsia conoriisubsp.israelensisis the agent of Israeli spotted fever. The present study reports the draft genome ofRickettsia conoriisubsp.israelensisstrain ISTT CDC1, isolated from aRhipicephalus sanguineustick collected in Israel.
Complete Genome Sequence of Brucella canis Strain HSK A52141, Isolated from the Blood of an Infected Dog
Authors: Kim Jong-So , Jeong Wooseog , Jeoung Hye-Young , Song Jae-Young , Kim Hyungtae , Beak Jeong-Hun , Parisutham Vinuselvi , Lee Sung Kuk , Kim Jong Wan , Kim Ji-Yeon , Jung Suk Chan , Her Moon , An Dong-Jun 
Published: August 2012

ABSTRACTBrucella canisinfection can be clinically inapparent in dogs, and when infection goes unnoticed, there is a chance for dog-to-human transmission. A new strain ofB. caniswas isolated from the blood of an infected dog in order to analyze the pathogenic mechanism, compare genetic properties, and develop new genetic tools for early diagnosis of canine brucellosis. Herein, we report the complete genome sequence of the strainB. canisHSK A52141. This is the second complete genome sequence and biological annotation available for a member ofB. canis.
Genome Sequence of Pectin-Degrading Alishewanella agri, Isolated from Landfill Soil
Authors: Kim Jisun , Jung Jaejoon , Sung Jung-Suk , Chun Jongsik , Park Woojun 
Published: August 2012

ABSTRACTAlishewanella agriBL06T(= KCTC 22400T= JCM 15597T) was isolated from landfill soil in Pohang, South Korea.A. agrishowed the ability to degrade pectin, a structural heteropolysaccharide present in the cell wall of plants. Here we report the genome sequence ofAlishewanella agriBL06T, the second sequenced strain in the genusAlishewanella.
Genome Sequence of Novosphingobium sp. Strain Rr 2-17, a Nopaline Crown Gall-Associated Bacterium Isolated from Vitis vinifera L. Grapevine
Authors: Gan Han Ming , Chew Teong Han , Hudson André O. , Savka Michael A. 
Published: August 2012

ABSTRACTNovosphingobiumsp. strain Rr 2-17 is anN-acyl homoserine lactone (AHL)-producing bacterium isolated from the crown gall tumor of a grapevine. To our knowledge, this is the first draft genome announcement of a plant-associated strain from the genusNovosphingobium.
Genome Sequence of Ralstonia sp. Strain PBA, a Bacterium Involved in the Biodegradation of 4-Aminobenzenesulfonate
Authors: Gan Han Ming , Chew Teong Han , Tay Yea-Ling , Lye Siew Fen , Yahya Adibah 
Published: August 2012

ABSTRACTRalstoniasp. strain PBA was isolated from textile wastewater in a coculture withHydrogenophagasp. strain PBC. Here we present the assembly and annotation of its genome, which may provide further insights into the mechanism of its interaction with strain PBC during 4-aminobenzenesulfonate degradation.
Draft Genome Sequence of Alcaligenes faecalis subsp.faecalisNCIB 8687 (CCUG 2071)
Authors: Phung Le T. , Trimble William L. , Meyer Folker , Gilbert Jack A. , Silver Simon 
Published: August 2012

ABSTRACTAlcaligenes faecalissubsp.faecalisNCIB 8687, the betaproteobacterium from which arsenite oxidase had its structure solved and the first “arsenate gene island” identified, provided a draft genome of 3.9 Mb in 186 contigs (with the largest 15 comprising 90% of the total) for this opportunistic pathogen species.
Genome Sequence of Acinetobacter sp. Strain HA, Isolated from the Gut of the Polyphagous Insect Pest Helicoverpa armigera
Authors: Malhotra Jaya , Dua Ankita , Saxena Anjali , Sangwan Naseer , Mukherjee Udita , Pandey Neeti , Rajagopal Raman , Khurana Paramjit , Khurana Jitendra P. , Lal Rup 
Published: August 2012

ABSTRACTIn this study,Acinetobactersp. strain HA was isolated from the midgut of a fifth-instar larva ofHelicoverpa armigera. Here, we report the draft genome sequence (3,125,085 bp) of this strain that consists of 102 contigs, 2,911 predicted coding sequences, and a G+C content of 41%.
Genome Sequence of Methylobacterium sp. Strain GXF4, a Xylem-Associated Bacterium Isolated from Vitis vinifera L. Grapevine
Authors: Gan Han Ming , Chew Teong Han , Hudson André O. , Savka Michael A. 
Published: August 2012

ABSTRACTMethylobacteriumsp. strain GXF4 is an isolate from grapevine. Here we present the sequence, assembly, and annotation of its genome, which may shed light on its role as a grapevine xylem inhabitant. To our knowledge, this is the first genome announcement of a plant xylem-associated strain of the genusMethylobacterium.
Effects of flashlight guidance on chest compression performance in cardiopulmonary resuscitation in a noisy environment
Authors: You Je Sung , Chung Sung Phil , Chang Chul Ho , Park Incheol , Lee Hye Sun , Kim SeungHo , Lee Hahn Shick 
Published: August 2012

BackgroundIn real cardiopulmonary resuscitation (CPR), noise can arise from instructional voices and environmental sounds in places such as a battlefield and industrial and high-traffic areas. A feedback device using a flashing light was designed to overcome noise-induced stimulus saturation during CPR. This study was conducted to determine whether ‘flashlight’ guidance influences CPR performance in a simulated noisy setting.Materials and methodsWe recruited 30 senior medical students with no previous experience of using flashlight-guided CPR to participate in this prospective, simulation-based, crossover study. The experiment was conducted in a simulated noisy situation using a cardiac arrest model without ventilation. Noise such as patrol car and fire engine sirens was artificially generated. The flashlight guidance device emitted light pulses at the rate of 100 flashes/min. Participants also received instructions to achieve the desired rate of 100 compressions/min. CPR performances were recorded with a Resusci Anne mannequin with a computer skill-reporting system.ResultsThere were significant differences between the control and flashlight groups in mean compression rate (MCR), MCR/min and visual analogue scale. However, there were no significant differences in correct compression depth, mean compression depth, correct hand position, and correctly released compression. The flashlight group constantly maintained the pace at the desired 100 compressions/min. Furthermore, the flashlight group had a tendency to keep the MCR constant, whereas the control group had a tendency to decrease it after 60 s.ConclusionFlashlight-guided CPR is particularly advantageous for maintaining a desired MCR during hands-only CPR in noisy environments, where metronome pacing might not be clearly heard.
Identifying and characterizing the most significant β-glucosidase of the novel species Aspergillus saccharolyticus
Authors: Sørensen Annette , Ahring Birgitte K. , Lübeck Mette , Ubhayasekera Wimal , Bruno Kenneth S. , Culley David E. , Lübeck Peter S. 
Published: August 2012

The newly discovered fungal species Aspergillus saccharolyticus was found to produce a culture broth rich in β-glucosidase activity. In this present work, the main β-glucosidase of A. saccharolyticus responsible for the efficient hydrolytic activity was identified, isolated, and characterized. Ion exchange chromatography was used to fractionate the culture broth, yielding fractions with high β-glucosidase activity and only 1 visible band on an SDS–PAGE gel. Mass spectrometry analysis of this band gave peptide matches to β-glucosidases from aspergilli. Through a polymerase chain reaction approach using degenerate primers and genome walking, a 2919 bp sequence encoding the 860 amino acid BGL1 polypeptide was determined. BGL1 of A. saccharolyticus has 91% and 82% identity with BGL1 from Aspergillus aculeatus and BGL1 from Aspergillus niger , respectively, both belonging to Glycoside Hydrolase family 3. Homology modeling studies suggested β-glucosidase activity with preserved retaining mechanism and a wider catalytic pocket compared with other β-glucosidases. The bgl1 gene was heterologously expressed in Trichoderma reesei QM6a, purified, and characterized by enzyme kinetics studies. The enzyme can hydrolyze cellobiose, p-nitrophenyl-β-d-glucoside, and cellodextrins. The enzyme showed good thermostability, was stable at 50 °C, and at 60 °C it had a half-life of approximately 6 h.
Characterization of antibiotic-resistant and potentially pathogenic Escherichia coli from soil fertilized with litter of broiler chickens fed antimicrobial-supplemented diets
Authors: Merchant Laura E. , Rempel Heidi , Forge Tom , Kannangara Tissa , Bittman Shabtai , Delaquis Pascal , Topp Edward , Ziebell Kim A. , Diarra Moussa S. 
Published: August 2012

The objective of this study was to characterize antimicrobial resistance and virulence determinants of Escherichia coli from soil amended with litter from 36-day-old broiler chickens ( Gallus gallus domesticus ) fed with diets supplemented with a variety of antimicrobial agents. Soil samples were collected from plots before and periodically after litter application in August to measure E. coli numbers. A total of 295 E. coli were isolated from fertilized soil samples between August and March. Antibiotic susceptibility was determined by Sensititre, and polymerase chain reaction was performed to detect the presence of resistance and virulence genes. The results confirmed that E. coli survived and could be quantified by direct plate count for at least 7 months in soil following litter application in August. The effects of feed supplementation were observed on E. coli numbers in November and January. Among the 295 E. coli, the highest antibiotic resistance level was observed against tetracycline and β-lactams associated mainly with the resistance genes tetB and blaCMY-2, respectively. Significant treatment effects were observed for phylogenetic groups, antibiotic resistance profiles, and virulence gene frequencies. Serotyping, phylogenetic grouping, and pulsed-field gel electrophoresis confirmed that multiple-antibiotic-resistant and potentially pathogenic E. coli can survive in soil fertilized with litter for several months regardless of antimicrobials used in the feed.