bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Raman Spectroscopy and Phase-Contrast Microscopy To Characterize Cold Atmospheric Plasma Inactivation of Individual Bacterial Spores
Authors: Wang Shiwei , Doona Christopher J. , Setlow Peter , Li Yong-qing 
Published: July 2016

ABSTRACT

Raman spectroscopy and phase-contrast microscopy were used to examine calcium dipicolinate (CaDPA) levels and rates of nutrient and nonnutrient germination of multiple individual
Bacillus subtilis
spores treated with cold atmospheric plasma (CAP). Major results for this work include the following: (i) >5 logs of spores deposited on glass surfaces were inactivated by CAP treatment for 3 min, while deposited spores placed inside an impermeable plastic bag were inactivated only ∼2 logs in 30 min; (ii) >80% of the spores treated for 1 to 3 min with CAP were nonculturable and retained CaDPA in their core, while >95% of spores treated with CAP for 5 to 10 min lost all CaDPA; (iii) Raman measurements of individual CAP-treated spores without CaDPA showed differences from spores that germinated with
l
-valine in terms of nucleic acids, lipids, and proteins; and (iv) 1 to 2 min of CAP treatment killed 99% of spores, but these spores still germinated with nutrients or exogenous CaDPA, albeit more slowly and to a lesser extent than untreated spores, while spores CAP treated for >3 min that retained CaDPA did not germinate via nutrients or CaDPA. However, even after 1 to 3 min of CAP treatment, spores germinated normally with dodecylamine. These results suggest that exposure to the present CAP configuration severely damages a spore's inner membrane and key germination proteins, such that the treated spores either lose CaDPA or can neither initiate nor complete germination with nutrients or CaDPA. Analysis of the various CAP components indicated that UV photons contributed minimally to spore inactivation, while charged particles and reactive oxygen species contributed significantly.

IMPORTANCE
Much research has shown that cold atmospheric plasma (CAP) is a promising tool for the inactivation of spores in the medical and food industries. However, knowledge about the effects of plasma treatment on spore properties is limited, especially at the single-cell level. In this study, Raman spectroscopy and phase-contrast microscopy were used to analyze CaDPA levels and kinetics of nutrient- and non-nutrient-germinant-induced germination of multiple individual spores of
Bacillus subtilis
that were treated by a planar CAP device. The roles of different plasma species involved in spore inactivation were also investigated. The knowledge obtained in this study will aid in understanding the mechanism(s) of spore inactivation by CAP and potentially facilitate the development of more effective and efficient plasma sterilization techniques in various applications.
Self-Regulation and Interplay of Rsm Family Proteins Modulate the Lifestyle of Pseudomonas putida
Authors: Huertas-Rosales Óscar , Ramos-González María Isabel , Espinosa-Urgel Manuel 
Published: July 2016

ABSTRACT

In the plant-beneficial bacterium
Pseudomonas putida
KT2440, three genes have been identified that encode posttranscriptional regulators of the CsrA/RsmA family. Their regulatory roles in the motile and sessile lifestyles of
P. putida
have been investigated by generating single-, double-, and triple-null mutants and by overexpressing each protein (RsmA, RsmE, and RsmI) in different genetic backgrounds. The
rsm
triple mutant shows reduced swimming and swarming motilities and increased biofilm formation, whereas overexpression of RsmE or RsmI results in reduced bacterial attachment. However, biofilms formed on glass surfaces by the triple mutant are more labile than those of the wild-type strain and are easily detached from the surface, a phenomenon that is not observed on plastic surfaces. Analysis of the expression of adhesins and exopolysaccharides in the different genetic backgrounds suggests that the biofilm phenotypes are due to alterations in the composition of the extracellular matrix and in the timing of synthesis of its elements. We have also studied the expression patterns of Rsm proteins and obtained data that indicate the existence of autoregulation mechanisms.

IMPORTANCE
Proteins of the CsrA/RsmA family function as global regulators in different bacteria. More than one of these proteins is present in certain species. In this study, all of the RsmA homologs in
P. putida
are characterized and globally taken into account to investigate their roles in controlling bacterial lifestyles and the regulatory interactions among them. The results offer new perspectives on how biofilm formation is modulated in this environmentally relevant bacterium.
AcmB Is an S-Layer-Associated β-
N
-Acetylglucosaminidase and Functional Autolysin in Lactobacillus acidophilus NCFM
Authors: Johnson Brant R. , Klaenhammer Todd R. 
Published: July 2016

ABSTRACT

Autolysins, also known as peptidoglycan hydrolases, are enzymes that hydrolyze specific bonds within bacterial cell wall peptidoglycan during cell division and daughter cell separation. Within the genome of
Lactobacillus acidophilus
NCFM, there are 11 genes encoding proteins with peptidoglycan hydrolase catalytic domains, 9 of which are predicted to be functional. Notably, 5 of the 9 putative autolysins in
L. acidophilus
NCFM are S-layer-associated proteins (SLAPs) noncovalently colocalized along with the surface (S)-layer at the cell surface. One of these SLAPs, AcmB, a β-
N
-acetylglucosaminidase encoded by the gene
lba0176
(
acmB
), was selected for functional analysis.
In silico
analysis revealed that
acmB
orthologs are found exclusively in S-layer- forming species of
Lactobacillus
. Chromosomal deletion of
acmB
resulted in aberrant cell division, autolysis, and autoaggregation. Complementation of
acmB
in the Δ
acmB
mutant restored the wild-type phenotype, confirming the role of this SLAP in cell division. The absence of AcmB within the exoproteome had a pleiotropic effect on the extracellular proteins covalently and noncovalently bound to the peptidoglycan, which likely led to the observed decrease in the binding capacity of the Δ
acmB
strain for mucin and extracellular matrices fibronectin, laminin, and collagen
in vitro
. These data suggest a functional association between the S-layer and the multiple autolysins noncovalently colocalized at the cell surface of
L. acidophilus
NCFM and other S-layer-producing
Lactobacillus
species.

IMPORTANCE
Lactobacillus acidophilus
is one of the most widely used probiotic microbes incorporated in many dairy foods and dietary supplements. This organism produces a surface (S)-layer, which is a self-assembling crystalline array found as the outermost layer of the cell wall. The S-layer, along with colocalized associated proteins, is an important mediator of probiotic activity through intestinal adhesion and modulation of the mucosal immune system. However, there is still a dearth of information regarding the basic cellular and evolutionary function of S-layers. Here, we demonstrate that multiple autolysins, responsible for breaking down the cell wall during cell division, are associated with the S-layer. Deletion of the gene encoding one of these S-layer-associated autolysins confirmed its autolytic role and resulted in reduced binding capacity to mucin and intestinal extracellular matrices. These data suggest a functional association between the S-layer and autolytic activity through the extracellular presentation of autolysins.
Spatial-temporal dynamics and structural determinants of child and maternal mortality in a rural, high HIV burdened South African population, 2000–2014: a study protocol
Authors: Tlou B , Sartorius B , Tanser F 
Published: July 2016

IntroductionChild (infant and under-5) and maternal mortality rates are key indicators for assessing the health status of populations. South Africa's maternal and child mortality rates are high, and the country mirrors the continental trend of slow progress towards its Millennium Development Goals. Rural areas are often more affected regarding child and maternal mortalities, specifically in areas with a high HIV burden. This study aims to understand the factors affecting child and maternal mortality in the Africa Centre Demographic Surveillance Area (DSA) from 2003 to 2014 towards developing tailored interventions to reduce the deaths in resource poor settings. This will be done by identifying child and maternal mortality ‘hotspots’ and their associated risk factors.Methods and analysisThis retrospective study will use data for 2003–2014 from the Africa Centre Demographic Information System (ACDIS) in rural KwaZulu-Natal Province, South Africa. All homesteads in the study area have been mapped to an accuracy of <2 m, all deaths recorded and the assigned cause of death established using a verbal autopsy interview. Advanced spatial-temporal clustering techniques (both regular (Kulldorff) and irregular (FleXScan)) will be used to identify mortality ‘hotspots’. Various advanced statistical modelling approaches will be tested and used to identify significant risk factors for child and maternal mortality. Differences in attributability and risk factors profiles in identified ‘hotspots’ will be assessed to enable tailored intervention guidance/development. This multicomponent study will enable a refined intervention model to be developed for typical rural populations with a high HIV burden.EthicsEthical approval was received from the Biomedical Research Ethics Committee (BREC) of the University of KwaZulu-Natal (BE 169/15).
Quality of harness fit for normal and low birthweight infants observed among newborns in infant car seats
Authors: Brown Julie , Sinn John Kam Hung , Chua Aileen , Clarke Elizabeth Clare 
Published: July 2016

IntroductionChild restraint fit is important for crash protection. For newborns, standards universally require a rear-facing restraint and some upper limit on size, but historically there has been no specification of a lower design limit and there is concern over whether low birthweight infants (LBW) are adequately restrained. The aim of this study was to determine the quality of harness fit for newborns of low and normal weight in a range of modern child restraints.MethodsA convenience sample of infants (1.657–4.455 kg) were recruited from the postnatal ward and special care nursery <1 week from discharge. Infants (n=84) were assessed for harness fit in rear-facing-only restraints, convertible rear/forward restraints and a subset were assessed in a restraint specifically designed to accommodate LBW infants. Measures of harness fit were based on shoulder strap, crotch strap and buckle positioning.ResultsLess than 20% of infants achieved good harness fit, regardless of whether they were categorised as low (<2.5 kg) or normal weight. Rear-facing-only restraints were less likely to provide good fit than convertible restraints, in all measures of fit other than shoulder strap width. The proportions of infants achieving good fit were greater in the restraint designed for LBW infants than other restraint types.ConclusionPoor accommodation continues to be a problem for LBW infants but is rectified in specifically designed restraints. Better specification of harness configuration for all rearward-facing restraints may be required to ensure adequate accommodation of normal birthweight infants.
A population-based incidence of acute large vessel occlusions and thrombectomy eligible patients indicates significant potential for growth of endovascular stroke therapy in the USA
Authors: Rai Ansaar T , Seldon Aaron E , Boo SoHyun , Link Paul S , Domico Jennifer R , Tarabishy Abdul R , Lucke-Wold Noelle , Carpenter Jeffrey S 
Published: July 2016

BackgroundData on large vessel strokes are important for resource allocation and infrastructure development.ObjectiveTo determine an annual incidence of large vessel occlusions (LVOs) and a thrombectomy eligible patient population.MethodsAll patients with acute ischemic stroke discharged over 3 years from a tertiary-level hospital serving a large geographic area were evaluated for an LVO (M1, internal carotid artery terminus, basilar artery). The incidence of LVO was determined for the hospital's 4-county primary service area (PSA, population 210 000) based on each county's discharges and extrapolated to the US population. ‘Thrombectomy eligibility’ for anterior circulation LVOs was based on time (onset <6 hours) and imaging (Alberta Stroke Program Early CT Score (ASPECTS) ≥6). The number of annual thrombectomy procedures was calculated for Medicare and private payer patients using federally available databases.Results1157 patients were discharged from the hospital's PSA, of whom 129 (11.1%, 95% CI 9.5% to 13.1%) had an LVO. This translated into an LVO incidence of 24 per 100 000 people per year (95% CI 20 to 28). 20 per 100 000 people per year had anterior circulation LVOs (95% CI 19 to 22), of whom 10/100 000/year (95% CI 8 to 11) were ‘thrombectomy eligible’. An additional 5/100 000/year (95% CI 3 to 6) presented with favorable ASPECTS after 6 hours of symptom onset. Basilar occlusion incidence was estimated at 4/100 000/year (95% CI 2 to 5). These rates yield 77 569 (95% CI 65 835 to 91 091) new LVOs per year in the USA. An estimated 10 284 mechanical thrombectomy procedures were performed in 2015.ConclusionsThis study estimates an LVO incidence of 24 per 100 000 person-years (95% CI 20 to 28). A current estimated annual thrombectomy rate of three procedures per 100 000 people indicates significant potential increase in the volume of endovascular procedures and the need to develop systems of care.
Use of a pressure sensing sheath: comparison with standard means of blood pressure monitoring in catheterization procedures
Authors: Purdy Phillip D , South Charles , Klucznik Richard P , Liu Kenneth C , Novakovic Robin L , Puri Ajit S , Pride G Lee , Aagaard-Kienitz Beverly , Ray Abishek , Elliott Alan C 
Published: July 2016

PurposeMonitoring of blood pressure (BP) during procedures is variable, depending on multiple factors. Common methods include sphygmomanometer (BP cuff), separate radial artery catheterization, and side port monitoring of an indwelling sheath. Each means of monitoring has disadvantages, including time consumption, added risk, and signal dampening due to multiple factors. We sought an alternative approach to monitoring during procedures in the catheterization laboratory.MethodsA new technology involving a 330 µm fiberoptic sensor embedded in the wall of a sheath structure was tested against both radial artery catheter and sphygmomanometer readings obtained simultaneous with readings recorded from the pressure sensing system (PSS). Correlations and Bland–Altman analysis were used to determine whether use of the PSS could substitute for these standard techniques.ResultsThe results indicated highly significant correlations in systolic, diastolic, and mean arterial pressures (MAP) when compared against radial artery catheterization (p<0.0001), and MAP means differed by <4%. Bland–Altman analysis of the data suggested that the sheath measurements can replace a separate radial artery catheter. While less striking, significant correlations were seen when PSS readings were compared against BP cuff readings.ConclusionsThe PSS has competitive functionality to that seen with a dedicated radial artery catheter for BP monitoring and is available immediately on sheath insertion without the added risk of radial catheterization. The sensor is structurally separated from the primary sheath lumen and readings are unaffected by device introduction through the primary lumen. Time delays and potential complications from radial artery catheterization are avoided.
Transform margins: development, controls and petroleum systems – an introduction
Authors: Nemčok M. , Rybár S. , Sinha S. T. , Hermeston S. A. , Ledvényiová L. 
Published: July 2016

Abstract
This paper provides an overview of the existing knowledge of transform margins including their dynamic development, kinematic development, structural architecture and thermal regime, together with the factors controlling these. This systematic knowledge is used for describing predictive models of various petroleum system concept elements such as source rock, seal rock and reservoir rock distribution, expulsion timing, trapping style and timing, and migration patterns. The paper then introduces individual contributions to this volume and their focus.

Supplementary material:

Location table and map of specific transform examples, structural elements of the Romanche transform margin and glossary of terms used in this article is available at
https://doi.org/10.6084/m9.figshare.c.3276407
Clarence Dutton's geology
Authors: Aalto K. R. 
Published: July 2016

Abstract

Clarence Edward Dutton (1841–1912), a Yale University graduate, served in the Civil War and, as a captain in the United States Army, was detailed for duty with John Wesley Powell's US Geographical and Geological Survey of the Rocky Mountain Region and, later, the US Geological Survey. He spent 10 years in geological research in the Colorado Plateau region, studying its geomorphological and stratigraphic evolution, and coined the term ‘isostasy’. His monograph
Tertiary History of the Grand Cañon District
is renowned for its particular charm, with sublime landscape descriptions and superb illustrations. Dutton later undertook studies in volcanic geology in Hawaii, the Cascades and on the Colorado Plateau. Dutton studied the effects of the catastrophic Charleston earthquake of 31 August 1886 and later engaged in irrigation research in the American West. Dutton critically reviewed many major geological concepts, including the causes of volcanism, earthquakes and, especially, orogeny. His pioneering work on stratigraphy, geomorphology, isostasy and seismology place him at the forefront of nineteenth century researchers and reflects his ability to generalize from field observations and formulate principles that constitute explanations of the observed facts.
Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment
Authors: Zeligs Kristen P. , Neuman Monica K. , Annunziata Christina M. 
Published: July 2016

Abstract
The NF-κB signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-κB can occur as part of the DNA damage response or in response to a large variety of activators, including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-κB signaling is key to immune function and is likely necessary for antitumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-κB. There is growing interest in identifying novel modulators to inhibit NF-κB activity as impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this antiapoptotic signaling pathway to maintain antitumor immune surveillance when applying such therapy to patients. Clin Cancer Res; 22(17); 4302–8. ©2016 AACR.
CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy
Authors: Barker Holly E. , Patel Radhika , McLaughlin Martin , Schick Ulrike , Zaidi Shane , Nutting Christopher M. , Newbold Katie L. , Bhide Shreerang , Harrington Kevin J. 
Published: July 2016

Abstract
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit. CCT244747 abrogated radiation-induced G2 arrest in the p53-deficient HNSCC cell lines, HN4 and HN5, causing cells to enter mitosis with unrepaired DNA damage. The addition of paclitaxel further increased cell kill and significantly reduced tumor growth in an HN5 xenograft model. Importantly, a lower dose of paclitaxel could be used when CCT244747 was included, therefore potentially limiting toxicity. Triple therapy reduced the expression of several markers of radioresistance. Moreover, the more radioresistant HN5 cell line exhibited greater radiation-mediated CHK1 activation and was more sensitive to triple therapy than HN4 cells. We analyzed CHK1 expression in a panel of head and neck tumors and observed that primary tumors from HPV+ patients, who went on to recur postradiotherapy, exhibited significantly stronger expression of total, and activated CHK1. CHK1 may serve as a biomarker for identifying tumors likely to recur and, therefore, patients who may benefit from concomitant treatment with a CHK1 inhibitor and paclitaxel during radiotherapy. Clinical translation of this strategy is under development. Mol Cancer Ther; 15(9); 2042–54. ©2016 AACR.
Targeting the HER Family with Pan-HER Effectively Overcomes Resistance to Cetuximab
Authors: Iida Mari , Bahrar Harsh , Brand Toni M. , Pearson Hannah E. , Coan John P. , Orbuch Rachel A. , Flanigan Bailey G. , Swick Adam D. , Prabakaran Prashanth J. , Lantto Johan , Horak Ivan D. , Kragh Michael , Salgia Ravi , Kimple Randy J. , Wheeler Deric L. 
Published: July 2016

Abstract
Cetuximab, an antibody against the EGFR, has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer, and non–small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do initially respond become refractory, highlighting both intrinsic and acquired resistance to cetuximab as significant clinical problems. To understand mechanistically how cancerous cells acquire resistance, we previously developed models of acquired resistance using the H226 NSCLC and UM-SCC1 HNSCC cell lines. Cetuximab-resistant clones showed a robust upregulation and dependency on the HER family receptors EGFR, HER2, and HER3. Here, we examined pan-HER, a mixture of six antibodies targeting these receptors on cetuximab-resistant clones. In cells exhibiting acquired or intrinsic resistance to cetuximab, pan-HER treatment decreased all three receptors' protein levels and downstream activation of AKT and MAPK. This correlated with decreased cell proliferation in cetuximab-resistant clones. To determine whether pan-HER had a therapeutic benefit in vivo, we established de novo cetuximab-resistant mouse xenografts and treated resistant tumors with pan-HER. This regimen resulted in a superior growth delay of cetuximab-resistant xenografts compared with mice continued on cetuximab. Furthermore, intrinsically cetuximab-resistant HNSCC patient-derived xenograft tumors treated with pan-HER exhibited significant growth delay compared with vehicle/cetuximab controls. These results suggest that targeting multiple HER family receptors simultaneously with pan-HER is a promising treatment strategy for tumors displaying intrinsic or acquired resistance to cetuximab. Mol Cancer Ther; 15(9); 2175–86. ©2016 AACR.