bluuebunny/crossref_metadata_2025_split huggingface dataset:
YtfB, an OapA Domain-Containing Protein, Is a New Cell Division Protein in Escherichia coli
Authors: Jorgenson Matthew A. , Young Kevin D. 
Published: April 2018

ABSTRACT

While screening the Pfam database for novel peptidoglycan (PG) binding modules, we identified the OapA domain, which is annotated as a LysM-like domain. LysM domains bind PG and mediate localization to the septal ring. In the Gram-negative bacterium
Escherichia coli
, an OapA domain is present in YtfB, an inner membrane protein of unknown function but whose overproduction causes cells to filament. Together, these observations suggested that YtfB directly affects cell division, most likely through its OapA domain. Here, we show that YtfB accumulates at the septal ring and that its action requires the division-initiating protein FtsZ and, to a lesser extent, ZipA, an early recruit to the septalsome. While the loss of YtfB had no discernible impact, a mutant lacking both YtfB and DedD (a known cell division protein) grew as filamentous cells. The YtfB OapA domain by itself also localized to sites of division, and this localization was enhanced by the presence of denuded PGs. Finally, the OapA domain bound PG, though binding did not depend on the formation of denuded glycans. Collectively, our findings demonstrate that YtfB is a cell division protein whose function is related to cell wall hydrolases.

IMPORTANCE
All living cells must divide in order to thrive. In bacteria, this involves the coordinated activities of a large number of proteins that work in concert to constrict the cell. Knowing which proteins contribute to this process and how they function is fundamental. Here, we identify a new member of the cell division apparatus in the Gram-negative bacterium
Escherichia coli
whose function is related to the generation of a transient cell wall structure. These findings deepen our understanding of bacterial cell division.
A Bead-Based Flow Cytometric Assay for Monitoring Yersinia pestis Exposure in Wildlife
Authors: Chandler Jeffrey C. , Baeten Laurie A. , Griffin Doreen L. , Gidlewski Thomas , DeLiberto Thomas J. , Petersen Jeannine M. , Pappert Ryan , Young John W. , Bevins Sarah N. 
Published: April 2018

ABSTRACT

Yersinia pestis
is the causative agent of plague and is considered a category A priority pathogen due to its potential for high transmissibility and the significant morbidity and mortality it causes in humans.
Y. pestis
is endemic to the western United States and much of the world, necessitating programs to monitor for this pathogen on the landscape. Elevated human risk of plague infection has been spatially correlated with spikes in seropositive wildlife numbers, particularly rodent-eating carnivores, which are frequently in contact with the enzootic hosts and the associated arthropod vectors of
Y. pestis
. In this study, we describe a semiautomated bead-based flow cytometric assay developed for plague monitoring in wildlife called the F1 Luminex plague assay (F1-LPA). Based upon Luminex/Bio-Plex technology, the F1-LPA targets serological responses to the F1 capsular antigen of
Y. pestis
and was optimized to analyze antibodies eluted from wildlife blood samples preserved on Nobuto filter paper strips. In comparative evaluations with passive hemagglutination, the gold standard tool for wildlife plague serodiagnosis, the F1-LPA demonstrated as much as 64× improvement in analytical sensitivity for F1-specific IgG detection and allowed for unambiguous classification of IgG status. The functionality of the F1-LPA was demonstrated for coyotes and other canids, which are the primary sentinels in wildlife plague monitoring, as well as felids and raccoons. Additionally, assay formats that do not require species-specific immunological reagents, which are not routinely available for several wildlife species used in plague monitoring, were determined to be functional in the F1-LPA.
Emerging Multidrug-Resistant Candida duobushaemulonii Infections in Panama Hospitals: Importance of Laboratory Surveillance and Accurate Identification
Authors: Ramos Ruben , Caceres Diego H. , Perez Marilyn , Garcia Nicole , Castillo Wendy , Santiago Erika , Borace Jovanna , Lockhart Shawn R. , Berkow Elizabeth L. , Hayer Lizbeth , Espinosa-Bode Andres , Moreno Jose , Jackson Brendan R. , Moran Jackeline , Chiller Tom , de Villarreal Gloriela , Sosa Nestor ,   the Red Nacional de Vigilancia Epidemiologica en Microbiologia Clinica Alexis Solis Osvaldo Cisterna Mellisa Herrera Nayarith Rojas Ana Samudio Lisbeth Wong, Vallabhaneni Snigdha 
Published: April 2018

ABSTRACT

Candida duobushaemulonii
, a yeast closely related to
Candida auris
, is thought to cause infections in rare cases and is often misidentified. In October 2016, the Panamanian Ministry of Health implemented laboratory surveillance for
C. auris
. Suspected
C. auris
isolates were forwarded to the national reference laboratory for identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry and antifungal susceptibility testing. Between November 2016 and May 2017, 17 of 36 (47%) isolates suspected to be
C. auris
were identified as
C. duobushaemulonii.
These 17 isolates were obtained from 14 patients at six hospitals. Ten patients, including three children, had bloodstream infections, and MICs for fluconazole, voriconazole, and amphotericin B were elevated. No resistance to echinocandins was observed.
C. duobushaemulonii
causes more invasive infections than previously appreciated and poses a substantial problem, given its resistance to multiple antifungals. Expanded laboratory surveillance is an important step in the detection and control of such emerging pathogens.
Electrostatic Interactions between Hendra Virus Matrix Proteins Are Required for Efficient Virus-Like-Particle Assembly
Authors: Liu Yu Chih , Grusovin Julian , Adams Timothy E. 
Published: April 2018

ABSTRACT

Hendra virus
(HeV) is a zoonotic paramyxovirus belonging to the genus
Henipavirus
. HeV is highly pathogenic, and it can cause severe neurological and respiratory illnesses in both humans and animals, with an extremely high mortality rate of up to 70%. Among the genes that HeV encodes, the matrix (M) protein forms an integral part of the virion structure and plays critical roles in coordinating viral assembly and budding. Nevertheless, the molecular mechanism of this process is not fully elucidated. Here, we determined the crystal structure of HeV M to 2.5-Å resolution. The dimeric structural configuration of HeV M is similar to that of Newcastle disease virus (NDV) M and is fundamental to protein stability and effective virus-like-particle (VLP) formation. Analysis of the crystal packing revealed a notable interface between the α1 and α2 helices of neighboring HeV M dimers, with key residues sharing degrees of sequence conservation among henipavirus M proteins. Structurally, a network of electrostatic interactions dominates the α1-α2 interactions, involving residues Arg57 from the α1 helix and Asp105 and Glu108 from the α2 helix. The disruption of the α1-α2 interactions using engineered charge reversal substitutions (R57E, R57D, and E108R) resulted in significant reduction or abrogation of VLP production. This phenotype was reversible with an R57E E108R mutant that was designed to partly restore salt bridge contacts. Collectively, our results define and validate previously underappreciated regions of henipavirus M proteins that are crucial for productive VLP assembly.

IMPORTANCE
Hendra virus is a henipavirus associated with lethal infections in humans. It is classified as a biosafety level 4 (BSL4) agent, and there are currently no preventive or therapeutic treatments available against HeV. Vital to henipavirus pathogenesis, the structural protein M has been implicated in viral assembly and budding, as well as host-virus interactions. However, there is no structural information available for henipavirus M, and the basis of M-driven viral assembly is not fully elucidated. We demonstrate the first three-dimensional structure of a henipavirus M protein. We show the dimeric organization of HeV M as a basic unit for higher-order oligomerization. Additionally, we define key regions/residues of HeV M that are required for productive virus-like-particle formation. These findings provide the first insight into the mechanism of M-driven assembly in henipavirus.
E1B-55K-Mediated Regulation of RNF4 SUMO-Targeted Ubiquitin Ligase Promotes Human Adenovirus Gene Expression
Authors: Müncheberg Sarah , Hay Ron T. , Ip Wing H. , Meyer Tina , Weiß Christina , Brenke Jara , Masser Sawinee , Hadian Kamyar , Dobner Thomas , Schreiner Sabrina 
Published: April 2018

ABSTRACT
Human adenovirus (HAdV) E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in nonpermissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 ubiquitin ligase complex that targets antiviral host substrates for proteasomal degradation. Recently, we reported that the PML-NB-associated factor Daxx represses efficient HAdV productive infection and is proteasomally degraded via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which remained to be established. RNF4, a cellular SUMO-targeted ubiquitin ligase (STUbL), induces ubiquitinylation of specific SUMOylated proteins and plays an essential role during DNA repair. Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction of the infected cell to support RNF4/Daxx association, promoting Daxx PTM and thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNA interference resulted in blocking the proper establishment of viral replication centers and significantly diminished viral gene expression. These results provide a model for how HAdV antagonize the antiviral host responses by exploiting the functional capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive factor during lytic infection and a novel candidate for future therapeutic antiviral intervention strategies.

IMPORTANCE
Daxx is a PML-NB-associated transcription factor that was recently shown to repress efficient HAdV productive infection. To counteract this antiviral measurement during infection, Daxx is degraded via a novel pathway including viral E1B-55K and host proteasomes. This virus-mediated degradation is independent of the classical HAdV E3 ubiquitin ligase complex, which is essential during viral infection to target other host antiviral substrates. To maintain a productive viral life cycle, HAdV E1B-55K early viral protein inhibits the chromatin-remodeling factor Daxx in a SUMO-dependent manner. In addition, viral E1B-55K protein recruits the STUbL RNF4 and sequesters it into the insoluble fraction of the infected cell. E1B-55K promotes complex formation between RNF4- and E1B-55K-targeted Daxx protein, supporting Daxx posttranslational modification prior to functional inhibition. Hence, RNF4 represents a novel host factor that is beneficial for HAdV gene expression by supporting Daxx counteraction. In this regard, RNF4 and other STUbL proteins might represent novel targets for therapeutic intervention.
The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C
Authors: Wang Di , Ge Xinna , Chen Dongjie , Li Jie , Cai Yueqi , Deng Jin , Zhou Lei , Guo Xin , Han Jun , Yang Hanchun 
Published: April 2018

ABSTRACTThe recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-SCHM) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-SBJ) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SPBJ) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3′ untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTRBJ) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants.IMPORTANCEThe recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.
Application of outpatient cardiac testing among emergency department patients with syncope
Authors: Cook Olivia G , Mukarram Muhammad A , Kim Soo-Min , Arcot Kirtana , Nemnom Marie-Joe , Taljaard Monica , Sivilotti Marco L A , Rowe Brian H , Thiruganasambandamoorthy Venkatesh 
Published: April 2018

Objectives2.6% of ED syncope patients will suffer cardiac serious adverse events (SAEs) within 30 days of disposition, and outpatient cardiac testing can improve patient safety. The objective is to determine whether outpatient cardiac testing for ED syncope patients is being appropriately ordered after discharge. To this end, we describe the proportion of high-risk and non-high (low and medium)-risk ED syncope patients as per the Canadian Syncope Risk Score (CSRS) who have a SAE after ED discharge, and the proportion referred for outpatient cardiac testing.MethodsOur multicentre prospective cohort study enrolled adult syncope patients between 2010 and 2014 in five academic EDs. We collected patient characteristics, disposition, CSRS predictors, outpatient referrals and testing results (Holter, echocardiography), and 30-day adjudicated SAE (death due to unknown/cardiac cause, myocardial infarction, arrhythmia and structural heart disease). We used descriptive statistics (mean, SD) to report our results.ResultsOf 3584 enrolled patients (mean age 50.9 years, 57.7% women), 800 patients (22.3%) received an outpatient referral. Of these 800 patients, 40.3% of the non-high-risk patients (305/756) and 54.5% of the high-risk patients (24/44) received outpatient cardiac testing. Of all patients who received cardiac testing, five (1.5%; 95% CI 0.6% to 3.5%) suffered outpatient SAE (60.0% arrhythmias). Of all patients who did not receive cardiac testing, four patients (0.9%; 95% CI 0.3% to 2.2%) suffered SAE (all arrhythmias). Of the 20 (45.5%) high-risk patients who did not receive testing, two patients (10.0%; 95% CI 2.8% to 30.1%) suffered arrhythmias outside the hospital, while among the 451 (59.7%) non-high-risk patients, only two (0.4%; 95% CI 0.1% to 1.6%) suffered outpatient arrhythmias.ConclusionOutpatient cardiac testing is largely underused, especially among high-risk ED syncope patients. Better guidelines for outpatient cardiac testing are needed, as the practice is highly variable and mismatched with patient risk.
Maternal depression is associated with injuries in children aged 2–4 years: the Pelotas 2004 Birth Cohort
Authors: Siqueira Barcelos Raquel , da Silva dos Santos Iná , Matijasevich Alicia , Anselmi Luciana , Barros Fernando Celso 
Published: April 2018

IntroductionInjuries during childhood, which mostly consist of falls, burns, drowning, poisonings and car crashes, are among the main causes of death among children and young adults in several countries.ObjectivesTo investigate the association between maternal depression and the incidence of injuries during childhood.MethodsIn 2004, children who were born in the municipality of Pelotas, Brazil, were enrolled in a population-based birth cohort, with evaluations at birth and at 3, 12, 24 and 48 months of age. Maternal depression during pregnancy was evaluated at the time of delivery. At 12 and 24 months post partum, the Edinburgh Postnatal Depression Scale (EPDS) was used. The injuries incidence rates at ages of 24–48 months and the crude and adjusted IRRs were calculated with 95% CI through Poisson’s regression.ResultsA total of 3533 children were analysed. The incidence of injuries was higher among children whose mothers presented depressive symptoms during pregnancy and at 12 and 24 months compared with those whose mothers did not present any symptoms. In the adjusted analysis, the IRR among girls whose mothers presented depressive symptoms during pregnancy and EPDS ≥13 at 12 and 24 months was 1.31 (1.15–1.50); and, among boys, 1.18 (1.03–1.36).InterpretationMaternal depression is associated with higher incidence of injuries between 24 and 48 months of age, in both sexes.
Effects of anterior compartment fasciotomy on intramuscular compartment pressure in patients with chronic exertional compartment syndrome
Authors: Roscoe David , Roberts A J , Hulse D , Shaheen A F , Hughes M P , Bennet A N 
Published: April 2018

BackgroundPatients with chronic exertional compartment syndrome (CECS) have pain during exercise that usually subsides at rest. Diagnosis is usually confirmed by measurement of intramuscular compartment pressure (IMCP) following exclusion of other possible causes. Management usually requires fasciotomy but reported outcomes vary widely. There is little evidence of the effectiveness of fasciotomy on IMCP. Testing is rarely repeated postoperatively and reported follow-up is poor. Improved diagnostic criteria based on preselection and IMCP levels during dynamic exercise testing have recently been reported.Objectives(1) To compare IMCP in three groups, one with classical symptoms and no treatment and the other with symptoms of CECS who have been treated with fasciotomy and an asymptomatic control group. (2) Establish if differences in IMCP in these groups as a result of fasciotomy relate to functional and symptomatic improvement.MethodsTwenty subjects with symptoms of CECS of the anterior compartment, 20 asymptomatic controls and 20 patients who had undergone fasciotomy for CECS were compared. All other possible diagnoses were excluded using rigorous inclusion criteria and MRI. Dynamic IMCP was measured using an electronic catheter wire before, during and after participants exercised on a treadmill during a standardised 15 min exercise challenge. Statistical analysis included t-tests and analysis of variance.ResultsFasciotomy results in reduced IMCP at all time points during a standardised exercise protocol compared with preoperative cases. In subjects responding to fasciotomy, there is a significant reduction in IMCP below that of preoperative groups (P<0.001). Postoperative responders to fasciotomy have no significant differences in IMCP from asymptomatic controls (P=0.182).ConclusionFasciotomy reduces IMCP in all patients. Larger studies are required to confirm that the reduction in IMCP accounts for differences in functional outcomes and pain reductions seen in postoperative patients with CECS.
Bridging the gap: using ‘Paired Learning’ to improve clinician/management understanding
Authors: Monaghan Hannah , Swenson Connie , Kerins Joanne , Sloan Sue 
Published: April 2018

BackgroundLeadership in the National Health Service (NHS) embraces two distinct groups: managers and clinicians, often arriving with differing backgrounds, skill sets and outlook. ‘Bridging the gap’ between the two, with a relational paired learning (PL) approach, has been run in NHS Lothian for 4 years (three cohorts) to positively impact the organisation and its leadership.MethodsIn the initial pilot six doctors and six general managers were paired together. Subsequently cohorts expanded with doctors paired with other senior managers, including the Director of eHealth, a non-executive member of the NHS Lothian Board and shadowing of the Chairman of NHS Lothian. All cohorts used PL ‘Contracts’ for their work together and then engaged in conversation, shadowing and reflection. Preprogramme and postprogramme questionnaires and postprogramme interviews explored the effect of PL on ‘preparedness’ for leadership and an understanding of the role and ethos of the corresponding group, and the running of the programme.ResultsThe questionnaires and interviews have shown that the programme had a positive impact on preparedness to lead, and participants described a shift in attitudes with increased understanding of the ‘other’ group and increased ability to work collaboratively together in the future. The ‘Trainee Management Forum’ was developed as a result of PL collaborative working and provides regular engagement and learning for junior doctors and managers at all levels of the organisation.ConclusionNHS Lothian PL has been impactful for those involved and is perceived to add value to the organisation, with further cohorts of doctors and managers continuing to engage with this opportunity.
Effects of ultra-thin Si-fin body widths upon SOI PMOS FinFETs
Authors: Liaw Yue-Gie , Chen Chii-Wen , Liao Wen-Shiang , Wang Mu-Chun , Zou Xuecheng 
Published: April 2018

Nano-node tri-gate FinFET devices have been developed after integrating a 14 Å nitrided gate oxide upon the silicon-on-insulator (SOI) wafers established on an advanced CMOS logic platform. These vertical double gate (FinFET) devices with ultra-thin silicon fin (Si-fin) widths ranging from 27 nm to 17 nm and gate length down to 30 nm have been successfully developed with a 193 nm scanner lithography tool. Combining the cobalt fully silicidation and the CESL strain technology beneficial for PMOS FinFETs was incorporated into this work. Detailed analyses of [Formula: see text]–[Formula: see text] characteristics, threshold voltage [Formula: see text], and drain-induced barrier lowering (DIBL) illustrate that the thinnest 17 nm Si-fin width FinFET exhibits the best gate controllability due to its better suppression of short channel effect (SCE). However, higher source/drain resistance [Formula: see text], channel mobility degradation due to dry etch steps, or “current crowding effect” will slightly limit its transconductance [Formula: see text] and drive current.
MatConvNet
Authors: Vedaldi Andrea , Lux Mathias , Bertini Marco 
Published: April 2018

MatConvNet is an open source MATLAB toolbox implementing Convolutional Neural Networks (CNNs) for computer vision and multimedia applications, developed by the same authors of the famed VLFeat library. Both libraries have associated papers that have been presented within the Open Source Software Competition track of ACM Multimedia: "MatConvNet: Convolutional Neural Networks for MATLAB" [1] and "Vlfeat: an open and portable library of computer vision algorithms" [2]. At present, the MatConvNet paper is the second most cited ACM Multimedia paper, according to Google Scholar.
The pros of this toolbox is its simplicity, thanks to the integration with MATLAB environment, efficiency thanks to the use of GPUs and CuDNN libraries, and the fact that it can run and learn state-of-the-art CNNs. After all it has been developed by the same people that brought VGG-16 and VGG-19 CNNs...
Many pre-trained CNNs for image classification (e.g. ResNet), segmentation, face recognition (e.g. VGG Face), object (e.g. Fast-R CNN) and text detection (e.g. VGG Text) are available in the model zoo.