bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Microbiological Aspects of β-Lactam Resistance in Staphylococcus lugdunensis
Authors: McHardy Ian H. , Veltman Jennifer , Hindler Janet , Bruxvoort Katia , Carvalho Marissa M. , Humphries Romney M. 
Published: December 2016

ABSTRACT

Antimicrobial susceptibility results from broth microdilution MIC testing of 993
Staphylococcus lugdunensis
isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three β-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of
blaZ
PCR. The medical records of 62 patients from whom
S. lugdunensis
was isolated, including 31 penicillin-susceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of
S. lugdunensis
isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of β-lactamase compared to the
blaZ
PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with
blaZ
PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other β-lactams, trimethoprim-sulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of
S. lugdunensis
are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message.
Coelomycetous Fungi in the Clinical Setting: Morphological Convergence and Cryptic Diversity
Authors: Valenzuela-Lopez Nicomedes , Sutton Deanna A. , Cano-Lira José F. , Paredes Katihuska , Wiederhold Nathan , Guarro Josep , Stchigel Alberto M. 
Published: December 2016

ABSTRACT

Human infections by coelomycetous fungi are becoming more frequent and range from superficial to systemic dissemination. Traumatic implantation of contaminated plant material is the most common cause. The typical morphological feature of these fungi is the production of asexual spores (conidia) within fruiting bodies called conidiomata. This study aimed to determine the distribution of the coelomycetes in clinical samples by a phenotypic and molecular study of a large set of isolates received from a U.S. reference mycological institution and by obtaining the
in vitro
antifungal susceptibility pattern of nine antifungals against a selected group of isolates. A total of 230 isolates were identified by sequencing the D1 and D2 domains of the large subunit (LSU) nuclear ribosomal RNA (nrRNA) gene and by morphological characterization. Eleven orders of the phylum
Ascomycota
were identified:
Pleosporales
(the largest group; 66.1%),
Botryosphaeriales
(19.57%),
Glomerellales
(4.35%),
Diaporthales
(3.48%),
Xylariales
(2.17%),
Hysteriales
and
Valsariales
(0.87%), and
Capnodiales
,
Helotiales
,
Hypocreales
and
Magnaporthales
(0.43% each). The most prevalent species were
Neoscytalidium dimidiatum
,
Paraconiothyrium
spp.,
Phoma herbarum
,
Didymella heteroderae
, and
Epicoccum sorghinum
. The most common anatomical site of isolation was superficial tissue (66.5%), followed by the respiratory tract (17.4%). Most of the isolates tested were susceptible to the majority of antifungals, and only flucytosine showed poor antifungal activity.
Cryo-electron Microscopy Study of the Genome Release of the Dicistrovirus Israeli Acute Bee Paralysis Virus
Authors: Mullapudi Edukondalu , Füzik Tibor , Přidal Antonín , Plevka Pavel 
Published: December 2016

ABSTRACT

Viruses of the family
Dicistroviridae
can cause substantial economic damage by infecting agriculturally important insects. Israeli acute bee paralysis virus (IAPV) causes honeybee colony collapse disorder in the United States. High-resolution molecular details of the genome delivery mechanism of dicistroviruses are unknown. Here we present a cryo-electron microscopy analysis of IAPV virions induced to release their genomes
in vitro
. We determined structures of full IAPV virions primed to release their genomes to a resolution of 3.3 Å and of empty capsids to a resolution of 3.9 Å. We show that IAPV does not form expanded A particles before genome release as in the case of related enteroviruses of the family
Picornaviridae
. The structural changes observed in the empty IAPV particles include detachment of the VP4 minor capsid proteins from the inner face of the capsid and partial loss of the structure of the N-terminal arms of the VP2 capsid proteins. Unlike the case for many picornaviruses, the empty particles of IAPV are not expanded relative to the native virions and do not contain pores in their capsids that might serve as channels for genome release. Therefore, rearrangement of a unique region of the capsid is probably required for IAPV genome release.

IMPORTANCE
Honeybee populations in Europe and North America are declining due to pressure from pathogens, including viruses. Israeli acute bee paralysis virus (IAPV), a member of the family
Dicistroviridae
, causes honeybee colony collapse disorder in the United States. The delivery of virus genomes into host cells is necessary for the initiation of infection. Here we present a structural cryo-electron microscopy analysis of IAPV particles induced to release their genomes. We show that genome release is not preceded by an expansion of IAPV virions as in the case of related picornaviruses that infect vertebrates. Furthermore, minor capsid proteins detach from the capsid upon genome release. The genome leaves behind empty particles that have compact protein shells.
Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids
Authors: He Susu , Chandler Michael , Varani Alessandro M. , Hickman Alison B. , Dekker John P. , Dyda Fred 
Published: December 2016

ABSTRACT

The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing
Enterobacteriaceae
(CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.

IMPORTANCE
The spread of antibiotic resistance among Gram-negative bacteria is a serious public health threat, as it can critically limit the types of drugs that can be used to treat infected patients. In particular, carbapenem-resistant members of the
Enterobacteriaceae
family are responsible for a significant and growing burden of morbidity and mortality. Here, we report on the mechanisms underlying the evolution of several plasmids carried by previously sequenced clinical
Enterobacteriaceae
isolates from the National Institutes of Health Clinical Center (NIH CC). Our ability to track genetic rearrangements that occurred within resistance plasmids was dependent on accurate annotation of the mobile genetic elements within the plasmids, which was greatly aided by access to long-read DNA sequencing data and knowledge of their mechanisms. Mobile genetic elements such as transposons and integrons have been strongly associated with the rapid spread of genes responsible for antibiotic resistance. Understanding the consequences of their actions allowed us to establish unambiguous evolutionary relationships between plasmids in the analysis set.
School shootings during 2013–2015 in the USA
Authors: Kalesan Bindu , Lagast Kinan , Villarreal Marcos , Pino Elizabeth , Fagan Jeffrey , Galea Sandro 
Published: December 2016

BackgroundData on the factors associated with school shootings in the USA are limited. The public conversation has often suggested several factors that may be linked to these events, however with little empirical support. Aiming to fill this gap, we describe the characteristics of school shooting incidents in the USA between 2013 and 2015 and explore whether four factors that represent domains of firearm policy, educational policy and epidemiological risk factors for intentional firearm injuries-background check (BC) policies, per capita mental health expenditures (MHE), K-12 education expenditure (KEE) and urbanicity—were associated with school shootings during this period.MethodsWe searched LexisNexis, a newspaper and broadcast media databases for school shooting incidents from 1 January 2013 to 31 December 2015. Presence of BC laws was extracted from legal information in LexisNexis. State-level covariates of per capita MHE (2013), KEE (2013) and urbanicity (2010) rates were obtained from publicly available data sources. We used negative binomial regression models accounting for clustering by state to explore unadjusted associations between the BC laws, state-level covariates and school shootings to report IRR and 95% CI.ResultsWe documented 154 school shootings (35, 55 and 64 each year). In unadjusted models, BC for firearm purchase (IRR=0.55, 95% CI 0.39 to 0.76), ammunition purchase (IRR=0.11, 95% CI 0.05 to 0.27), log per capita MHE (IRR=0.58, 95% CI 0.37 to 0.90), log per-capita KEE (IRR=0.09, 9% CI 0.02 to 0.29) and urbanicity (IRR=0.97, 95% CI 0.96 to 0.99) were associated with school shooting.ConclusionsSchool shootings are less likely in states with BC laws, higher MHE and KEE, and with greater per cent urban population.
Spectral and spatial tuning of onset and offset response functions in auditory cortical fields A1 and CL of rhesus macaques
Authors: Ramamurthy Deepa L. , Recanzone Gregg H. 
Published: December 2016

The mammalian auditory cortex is necessary for spectral and spatial processing of acoustic stimuli. Most physiological studies of single neurons in the auditory cortex have focused on the onset and sustained portions of evoked responses, but there have been far fewer studies on the relationship between onset and offset responses. In the current study, we compared spectral and spatial tuning of onset and offset responses of neurons in primary auditory cortex (A1) and the caudolateral (CL) belt area of awake macaque monkeys. Several different metrics were used to determine the relationship between onset and offset response profiles in both frequency and space domains. In the frequency domain, a substantial proportion of neurons in A1 and CL displayed highly dissimilar best stimuli for onset- and offset-evoked responses, although even for these neurons, there was usually a large overlap in the range of frequencies that elicited onset, and offset responses and distributions of tuning overlap metrics were mostly unimodal. In the spatial domain, the vast majority of neurons displayed very similar best locations for onset- and offset-evoked responses, along with unimodal distributions of all tuning overlap metrics considered. Finally, for both spectral and spatial tuning, a slightly larger fraction of neurons in A1 displayed nonoverlapping onset and offset response profiles, relative to CL, which supports hierarchical differences in the processing of sounds in the two areas. However, these differences are small compared with differences in proportions of simple cells (low overlap) and complex cells (high overlap) in primary and secondary visual areas. NEW & NOTEWORTHY In the current study, we examine the relationship between the tuning of neural responses evoked by the onset and offset of acoustic stimuli in the primary auditory cortex, as well as a higher-order auditory area—the caudolateral belt field—in awake rhesus macaques. In these areas, the relationship between onset and offset response profiles in frequency and space domains formed a continuum, ranging from highly overlapping to highly nonoverlapping.
Functional characterization and spatial clustering of visual cortical neurons in the predatory grasshopper mouse Onychomys arenicola
Authors: Scholl Benjamin , Pattadkal Jagruti J. , Rowe Ashlee , Priebe Nicholas J. 
Published: December 2016

Mammalian neocortical circuits are functionally organized such that the selectivity of individual neurons systematically shifts across the cortical surface, forming a continuous map. Maps of the sensory space exist in cortex, such as retinotopic maps in the visual system or tonotopic maps in the auditory system, but other functional response properties also may be similarly organized. For example, many carnivores and primates possess a map for orientation selectivity in primary visual cortex (V1), whereas mice, rabbits, and the gray squirrel lack orientation maps. In this report we show that a carnivorous rodent with predatory behaviors, the grasshopper mouse ( Onychomys arenicola), lacks a canonical columnar organization of orientation preference in V1; however, neighboring neurons within 50 μm exhibit related tuning preference. Using a combination of two-photon microscopy and extracellular electrophysiology, we demonstrate that the functional organization of visual cortical neurons in the grasshopper mouse is largely the same as in the C57/BL6 laboratory mouse. We also find similarity in the selectivity for stimulus orientation, direction, and spatial frequency. Our results suggest that the properties of V1 neurons across rodent species are largely conserved. NEW & NOTEWORTHY Carnivores and primates possess a map for orientation selectivity in primary visual cortex (V1), whereas rodents and lagomorphs lack this organization. We examine, for the first time, V1 of a wild carnivorous rodent with predatory behaviors, the grasshopper mouse ( Onychomys arenicola). We demonstrate the cellular organization of V1 in the grasshopper mouse is largely the same as the C57/BL6 laboratory mouse, suggesting that V1 neuron properties across rodent species are largely conserved.
Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations
Authors: Newton Adam J. H. , Wall Mark J. , Richardson Magnus J. E. 
Published: December 2016

Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue environment and experimentally verify our key predictions.
A Myc Activity Signature Predicts Poor Clinical Outcomes in Myc-Associated Cancers
Authors: Jung MoonSun , Russell Amanda J. , Liu Bing , George Joshy , Liu Pei Yan , Liu Tao , DeFazio Anna , Bowtell David D.L. , Oberthuer André , London Wendy B. , Fletcher Jamie I. , Haber Michelle , Norris Murray D. , Henderson Michelle J. 
Published: December 2016

Abstract
Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here, we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan–Meier and multivariate Cox regression analyses and was further validated in 42 primary neuroblastomas using qPCR. Cell lines with high MYC, MYCN, and/or MYCL1 gene expression exhibited elevated expression of the signature genes. Survival analysis showed that the signature was associated with poor outcome independently of well-defined prognostic factors in neuroblastoma, breast cancer, DLBCL, and medulloblastoma. In EOC, the 18-gene Myc activity signature was capable of identifying a group of patients with poor prognosis in a "high-MYCN" molecular subtype but not in the overall cohort. The predictive ability of this signature was reproduced using qPCR analysis of an independent cohort of neuroblastomas, including a subset of tumors without MYCN amplification. These data reveal an 18-gene Myc activity signature that is highly predictive of poor prognosis in diverse Myc-associated malignancies and suggest its potential clinical application in the identification of Myc-driven tumors that might respond to Myc-targeted therapies. Cancer Res; 77(4); 971–81. ©2016 AACR.
An Essential Role of Maspin in Embryogenesis and Tumor Suppression
Authors: Dzinic Sijana H. , Bernardo M. Margarida , Li Xiaohua , Fernandez-Valdivia Rodrigo , Ho Ye-Shih , Mi Qing-Sheng , Bandyopadhyay Sudeshna , Lonardo Fulvio , Vranic Semir , Oliveira Daniel S.M. , Bonfil R. Daniel , Dyson Gregory , Chen Kang , Omerovic Almasa , Sheng Xiujie , Han Xiang , Wu Dinghong , Bi Xinling , Cabaravdic Dzenana , Jakupovic Una , Wahba Marian , Pang Aaron , Harajli Deanna , Sakr Wael A. , Sheng Shijie 
Published: December 2016

Abstract
Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities. Specifically, maspin-deficient mice exhibited pulmonary adenocarcinoma, myoepithelial hyperplasia of the mammary gland, hyperplasia of luminal cells of dorsolateral and anterior prostate, and atrophy of luminal cells of ventral prostate and stratum spinosum of epidermis. These cancer phenotypes were accompanied by increased inflammatory stroma. These mice also displayed the autoimmune disorder alopecia aerate. Overall, our findings defined context-specific tumor suppressor roles for maspin in a clinically relevant model to study maspin functions in cancer and other pathologies. Cancer Res; 77(4); 886–96. ©2017 AACR.
Platelets as a novel source of Gremlin-1: Implications for thromboinflammation
Authors: Chatterjee Madhumita , Behrendt Alexander , Schmid Martina , Beck Sandra , Schneider Martina , Mack Andreas , Müller Iris , Geisler Tobias , Gawaz Meinrad 
Published: December 2016

SummaryPlatelets mediating haemostasis-thrombosis are central players in coronary artery disease (CAD). We characterised platelets as a novel source of Gremlin-1. Platelets express Gremlin-1 like inflammatory and endothelial cells. Gremlin-1 co-localised with P-selectin containing randomly distributed α–granules under resting state, which were peripheralised following platelet activation or adhesion over fibrinogen-coated surface. Gremlin-1 release upon activation with ADP, CRP, and TRAP was detected as enhanced surface expression; also in activated platelet supernatant as detected by Western Blot following CRP activation and by ELISA upon activation with ADP, CRP, PAR-1, and PAR4 agonist. Recombinant (rh)Gremlin-1 synergistically enhanced CRP-triggered intracellular calcium mobilisation, ADP-TRAP induced platelet activation, aggregation, and thrombin-activation triggered apoptosis; also thrombus formation ex vivo. Intracellular localisation of macrophage migration inhibitory factor (MIF) and Gremlin-1 a high-affinity binding partner and functional antagonist of MIF were found in intracoronary thrombus sections from acute coronary syndrome (ACS) patients and showed moderate overlap in α-granules of platelets. Intra-platelet Gremlin-1 levels were significantly decreased in ACS patients as compared to stable CAD (n=235). rhGremlin-1 also counteracted the anti-apoptotic and anti-thrombotic effects of rhMIF on platelets. Platelet-derived-Gremlin-1 prompted monocyte migration, facilitated adhesion under static and dynamic arterial flow conditions to collagen-adherent activated platelets; supported monocyte survival against BH-3-mimetic–induced apoptosis and macrophage differentiation in monocyte-platelet co-culture system, which were counteracted upon Gremlin-1 neutralisation. Thus platelet derived Gremlin-1 might contribute to the elevated circulating levels of Gremlin-1 in ACS and serve as a thrombo-inflammatory mediator in cardiovascular pathophysiologies.
LA CULTURA DE LA VIOLENCIA
Authors: Bentancor Milton Hernán 
Published: December 2016

A atual literatura hispano-americana percorre caminhos que se fazem necessários como expressãoartística posterior aotodo-poderoso“Boom”. Nesses novos caminhos aparecem nomes, obras e técnicas que oferecem novas perspectivas para o trabalho criativo, tanto no tocante à temática quanto no que diz respeito às vozes que se escutam. Neste artigo, desejamos analisar como a cultura latino-americana se tem impregnado de violência - nas suas mais diversas formas - e como essa violência se reflete na criação literária de diversos autores.