bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro
Reconstitution of Functional Type III Protein Export and Insights into Flagellar Assembly
Authors: Terashima Hiroyuki , Kawamoto Akihiro , Tatsumi Chinatsu , Namba Keiichi , Minamino Tohru , Imada Katsumi 
Published: June 2018

ABSTRACT

The type III secretion system (T3SS) forms the functional core of injectisomes, protein transporters that allow bacteria to deliver virulence factors into their hosts for infection, and flagella, which are critical for many pathogens to reach the site of infection. In spite of intensive genetic and biochemical studies, the T3SS protein export mechanism remains unclear due to the difficulty of accurate measurement of protein export
in vivo
. Here, we developed an
in vitro
flagellar T3S protein transport assay system using an inverted cytoplasmic membrane vesicle (IMV) for accurate and controlled measurements of flagellar protein export. We show that the flagellar T3SS in the IMV fully retains export activity. The flagellar hook was constructed inside the lumen of the IMV by adding purified component proteins externally to the IMV solution. We reproduced the hook length control and export specificity switch in the IMV consistent with that seen in the native cell. Previous
in vivo
analyses showed that flagellar protein export is driven by proton motive force (PMF) and facilitated by ATP hydrolysis by FliI, a T3SS-specific ATPase. Our
in vitro
assay recapitulated these previous
in vivo
observations but furthermore clearly demonstrated that even ATP hydrolysis by FliI alone can drive flagellar protein export. Moreover, this assay showed that addition of the FliH
2
/FliI complex to the assay solution at a concentration similar to that in the cell dramatically enhanced protein export, confirming that the FliH
2
/FliI complex in the cytoplasm is important for effective protein transport.

IMPORTANCE
The type III secretion system (T3SS) is the functional core of the injectisome, a bacterial protein transporter used to deliver virulence proteins into host cells, and bacterial flagella, critical for many pathogens. The molecular mechanism of protein transport is still unclear due to difficulties in accurate measurements of protein transport under well-controlled conditions
in vivo
. We succeeded in developing an
in vitro
transport assay system of the flagellar T3SS using inverted membrane vesicles (IMVs). Flagellar hook formation was reproduced in the IMV, suggesting that the export apparatus in the IMV retains a protein transport activity similar to that in the cell. Using this system, we revealed that ATP hydrolysis by the T3SS ATPase can drive protein export without PMF.
A Novel Adaptation Mechanism Underpinning Algal Colonization of a Nuclear Fuel Storage Pond
Authors: MeGraw Victoria E. , Brown Ashley R. , Boothman Christopher , Goodacre Royston , Morris Katherine , Sigee David , Anderson Lizzie , Lloyd Jonathan R. 
Published: June 2018

ABSTRACTGeochemical analyses alongside molecular techniques were used to characterize the microbial ecology and biogeochemistry of an outdoor spent nuclear fuel storage pond at Sellafield, United Kingdom, that is susceptible to seasonal algal blooms that cause plant downtime. 18S rRNA gene profiling of the filtered biomass samples showed the increasing dominance of a species closely related to the algaHaematococcus pluvialis, alongside 16S rRNA genes affiliated with a diversity of freshwater bacteria, includingProteobacteriaandCyanobacteria. High retention of137Cs and90Sr on pond water filters coincided with high levels of microbial biomass in the pond, suggesting that microbial colonization may have an important control on radionuclide fate in the pond. To interpret the unexpected dominance ofHaematococcusspecies during bloom events in this extreme environment, the physiological response ofH. pluvialisto environmentally relevant ionizing radiation doses was assessed. Irradiated laboratory cultures produced significant quantities of the antioxidant astaxanthin, consistent with pigmentation observed in pond samples. Fourier transform infrared (FT-IR) spectroscopy suggested that radiation did not have a widespread impact on the metabolic fingerprint ofH. pluvialisin laboratory experiments, despite the 80-Gy dose. This study suggests that the production of astaxanthin-rich encysted cells may be related to the preservation of theHaematococcusphenotype, potentially allowing it to survive oxidative stress arising from radiation doses associated with the spent nuclear fuel. The oligotrophic and radiologically extreme conditions in this environment do not prevent extensive colonization by microbial communities, which play a defining role in controlling the biogeochemical fate of major radioactive species present.IMPORTANCESpent nuclear fuel is stored underwater in large ponds prior to processing and disposal. Such environments are intensively radioactive but can be colonized by microorganisms. Colonization of such inhospitable radioactive ponds is surprising, and the survival mechanisms that microbes use is of fundamental interest. It is also important to study these unusual ecosystems, as microbes growing in the pond waters may accumulate radionuclides present in the waters (for bioremediation applications), while high cell loads can hamper management of the ponds due to poor visibility. In this study, an outdoor pond at the U.K. Sellafield facility was colonized by a seasonal bloom of microorganisms, able to accumulate high levels of137Cs and90Sr and dominated by the algaHaematococcus. This organism is not normally associated with deep water bodies, but it can adapt to radioactive environments via the production of the pigment astaxanthin, which protects the cells from radiation damage.
Changing epidemiology of assault victims in an emergency department participating in information sharing with police: a time series analysis
Authors: Boyle Adrian A , Martin Michael S , Ahmed Haroon , Snelling Katrina , Dean Jonathon , Price James 
Published: June 2018

IntroductionViolent injury places a large burden on the NHS. We had implemented information sharing in our ED in 2007 and aimed to see which patient groups were most affected by information sharing, as this would provide clues as to how this complex intervention works.MethodsRetrospective time series study of all the assault victims presenting for ED care between 2005 and 2014 at a single ED in England.Results10 328 patients presented during the study period. There was a 37% decrease in the number of patients presenting after assault, consistent with national trends. The proportions of people arriving by ambulance, and the proportion of men did not change during the study period. There were no important changes in the age of our assault patients in this study. Greater, disproportionate, decreases in rates of violence were seen in patients who presented at the weekend up (incidence rate ratio (IRR)=0.57, 95% CI 0.50 to 0.64) versus weekdays (IRR=0.72; 95% CI 0.62 to 0.83) There were also disproportionately greater decreases over the study period in patients who were discharged with no hospital follow-up (IRR=0.51, 95% CI 0.45 to 0.56) versus those leading to either an inpatient admission (IRR=1.05, 95% CI 0.84 to 1.31) or outpatient follow-up (IRR=1.23, 95% CI 0.93 to 1.64).ConclusionsThe epidemiology of violent injury at our institution has changed over the last 10 years and is most marked in a reduction of visits at the weekend, and in those who leave without follow up.
Late Wisconsinan grounding zones of the Laurentide Ice Sheet margin off the Québec North Shore (NW Gulf of St Lawrence)
Authors: Lajeunesse P. , Dietrich P. , Ghienne J.-F. 
Published: June 2018

Abstract
Swath bathymetry data and seismic profiles collected in the NW Gulf of St Lawrence reveal a series of wedge-shaped depositional systems interpreted as grounding zone wedges (GZWs). Some segments of the GZWs change locally to form frontal moraines, or morainal banks, and subaqueous ice-contact fans, reflecting changes in either the nature of the ice margin or the rate of sediment input. These grounding zones (GZ) of the ice margin extend laterally along three isobaths at depths of 180 (GZ1), 120 (GZ2) and 80 (GZ3) m (±20 m) along the Québec North Shore shelf, the 120 m-deep GZ2 system being traceable over a distance of >300 km. Associated GZWs can occur in three geometries along a same isobath system: curvilinear, lobate and shelf-break. GZ systems were built during three distinct stages of stabilization of the marine-based southeastern margin of the Laurentide Ice Sheet following its rapid retreat across the deeper waters of the Laurentian Channel in the Gulf of St Lawrence after 14.8 cal ka BP. The occurrence of GZ along distinct isobaths indicates that bathymetry exerted a strong control on ice stabilization during deglaciation by reducing the relative water depth at the ice margin and thereby the buoyancy and rate of iceberg calving. However, fluctuations and re-advances of the ice margin are also recorded by the overprinting of a portion of the GZ2 system by the younger GZ3 system, potentially suggesting an additional response to climate-driven forcing.
Causal Inference in Cancer Epidemiology: What Is the Role of Mendelian Randomization?
Authors: Yarmolinsky James , Wade Kaitlin H. , Richmond Rebecca C. , Langdon Ryan J. , Bull Caroline J. , Tilling Kate M. , Relton Caroline L. , Lewis Sarah J. , Davey Smith George , Martin Richard M. 
Published: June 2018

Abstract
Observational epidemiologic studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) uses genetic variants to proxy modifiable exposures to generate more reliable estimates of the causal effects of these exposures on diseases and their outcomes. MR has seen widespread adoption within cardio-metabolic epidemiology, but also holds much promise for identifying possible interventions for cancer prevention and treatment. However, some methodologic challenges in the implementation of MR are particularly pertinent when applying this method to cancer etiology and prognosis, including reverse causation arising from disease latency and selection bias in studies of cancer progression. These issues must be carefully considered to ensure appropriate design, analysis, and interpretation of such studies. In this review, we provide an overview of the key principles and assumptions of MR, focusing on applications of this method to the study of cancer etiology and prognosis. We summarize recent studies in the cancer literature that have adopted a MR framework to highlight strengths of this approach compared with conventional epidemiological studies. Finally, limitations of MR and recent methodologic developments to address them are discussed, along with the translational opportunities they present to inform public health and clinical interventions in cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 995–1010. ©2018 AACR.
Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Authors: Bonazzoli Elena , Predolini Federica , Cocco Emiliano , Bellone Stefania , Altwerger Gary , Menderes Gulden , Zammataro Luca , Bianchi Anna , Pettinella Francesca , Riccio Francesco , Han Chanhee , Yadav Ghanshyam , Lopez Salvatore , Manzano Aranzazu , Manara Paola , Buza Natalia , Hui Pei , Wong Serena , Litkouhi Babak , Ratner Elena , Silasi Dan-Arin , Huang Gloria S. , Azodi Masoud , Schwartz Peter E. , Schlessinger Joseph , Santin Alessandro D. 
Published: June 2018

Abstract
Purpose: Uterine serous carcinoma (USC) is a rare and aggressive variant of endometrial cancer. Whole-exome sequencing (WES) studies have recently reported c-Myc gene amplification in a large number of USCs, suggesting c-Myc as a potential therapeutic target. We investigated the activity of novel BET bromodomain inhibitors (GS-5829 and GS-626510, Gilead Sciences Inc.) and JQ1 against primary USC cultures and USC xenografts.
Experimental Design: We evaluated c-Myc expression by qRT-PCR in a total of 45 USCs including fresh-frozen tumor tissues and primary USC cell lines. We also performed IHC and Western blot experiments in 8 USC tumors. USC cultures were evaluated for sensitivity to GS-5829, GS-626510, and JQ1 in vitro using proliferation, viability, and apoptosis assays. Finally, the in vivo activity of GS-5829, GS-626510, and JQ1 was studied in USC-ARK1 and USC-ARK2 mouse xenografts.
Results: Fresh-frozen USC and primary USC cell lines overexpressed c-Myc when compared with normal tissues (P = 0.0009 and 0.0083, respectively). High c-Myc expression was found in 7 of 8 of primary USC cell lines tested by qRT-PCR and 5 of 8 tested by IHC. In vitro experiments demonstrated high sensitivity of USC cell lines to the exposure to GS-5829, GS-626510, and JQ1 with BET inhibitors causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis). In comparative in vivo experiments, GS-5829 and/or GS-626510 were found more effective than JQ1 at the concentrations/doses used in decreasing tumor growth in both USC-ARK1 and USC-ARK2 mouse xenograft models.
Conclusions: GS-5829 and GS-626510 may represent novel, highly effective therapeutics agents against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Clinical studies with GS-5829 in patients with USC harboring chemotherapy-resistant disease are warranted. Clin Cancer Res; 24(19); 4845–53. ©2018 AACR.
Two Weeks' Notice from Allogeneic Sources
Authors: Anczurowski Mark , Hirano Naoto 
Published: June 2018

Abstract
A novel pipeline for neoantigen-specific T-cell receptor (TCR) identification has been validated in ovarian cancer, making use of HLA-matched allogeneic healthy donor T cells. This workflow allows for the identification of tumor-specific TCRs 2 weeks after antigen-specific stimulation and eliminates problematic patient-to-patient variation in the selection of neoantigen-specific TCRs. Clin Cancer Res; 24(21); 5195–7. ©2018 AACR.
See related article by Matsuda et al., p. 5357
Effectiveness, Costs and Patient Acceptance of a Conventional and a Biological Treatment Approach for Carious Primary Teeth in Children
Authors: BaniHani Alaa , Deery Chris , Toumba Jack , Duggal Monty 
Published: June 2018

<b><i>Background:</i></b> Over the last years, conventional restorations for the treatment of active carious lesions (CL) in primary teeth have been challenged and a more biological approach has been suggested. This approach involves less invasive techniques that alter the environment of the CL isolating it from the cariogenic biofilm and substrate. <b><i>Aim:</i></b> To investigate the cost-effectiveness and patient acceptance of 2 treatment approaches for the treatment of deep CLs in primary teeth in children. <b><i>Methods:</i></b> This was a retrospective/prospective cohort study carried out in 2 UK specialist hospital settings. Data on cost-effectiveness was extracted retrospectively from clinical dental records of 246 patients aged 4–9 years. A prospective study design was used to explore patient acceptance of the 2 treatment approaches. One hundred and ten patients aged 4–9 years and their carers completed 2 questionnaires on treatment acceptance. <b><i>Results:</i></b> In total, 836 primary teeth that had received treatment with either approach were included. More than 2 thirds (75.7%) of the restorations in the conventional approach were of non-selective removal to hard dentine followed by pulpotomy (24.3%). In the biological approach, most of the restorations were stainless steel crowns placed with the Hall Technique (95%) followed by selective removal to firm dentine (5%). The majority of the primary teeth remained asymptomatic after a follow-up period of up to 77 months; 95.3% in the conventional and 95.8% in the biological arm. When the treatment costs were analysed, a statistically significant difference was found between the mean costs of the 2 approaches with a mean difference of GBP 45.20 (Pound Sterling; <i>p</i> &#x3c; 0.001), in favour of the biological approach. The majority of the children and carers were happy with the conventional or biological restorations. <b><i>Conclusion:</i></b> Although both approaches had similar successful outcomes, the biological approach consisting mainly of Hall Technique was associated with reduced treatment costs. Both approaches were accepted favourably by the children and carers.
Assessing the Surgical Experience to Identify Risk Factors Associated with Severe Retinopathy of Prematurity and Laser Intervention
Authors: Torr Carrie , Yoder Bradley , Beachy Joanna 
Published: June 2018

<b><i>Background:</i></b> Retinopathy of prematurity (ROP) is a known complication of preterm birth and one of the leading causes of blindness. Known risk factors include low gestational age (GA), birth weight, and oxygen exposure. It is unknown if there are surgical risk factors associated with severe ROP. <b><i>Objectives:</i></b> Identify risk factors of a neonatal surgical exposure associated with laser therapy for ROP. <b><i>Methods:</i></b> Institutional review of 76 infants with GA ≤27 weeks or birth weight ≤800 g. Infant demographics and details of surgical experience were collected. Infants who underwent a surgical procedure were analyzed to identify risk factors associated with laser treatment for severe ROP. Surgical and nonsurgical infants were compared to assess if the rate of laser intervention differed among institutions/published data. Data were analyzed using the Mann-Whitney U test, unpaired <i>t</i> test, OR and Fischer’s exact test. <b><i>Result:</i></b> Out of 49 surgical infants, 11 underwent laser intervention. Infants undergoing laser had surgery at an earlier postmenstrual age (PMA; 31.5 [29.3–39.4] weeks vs. 38.1 [31.3–42.5] weeks, <i>p</i> = 0.01), were more likely to have an exploratory laparotomy (adjusted odds ratio 1.3 [1.04–1.64], <i>p</i> = 0.02), and to undergo more surgical procedures (3 vs. 2, <i>p</i> = 0.04). <b><i>Conclusion:</i></b> At our institution, preterm infants who undergo a surgical procedure prior to 32 weeks PMA and those having ≥3 surgeries were at a higher risk for progressing to laser intervention. Additional studies with larger sample sizes are needed to assess if the risk factors we have identified remain significant and to identify other possible risk factors.
Insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil)
Authors: Cividini Flor Ismael , Ribeiro Flor Jandira Chacha , Furtado Paulo Sérgio Do Nascimento 
Published: June 2018

Abstract. Insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil). Galls are changes in the pattern of growth and development of plant tissues or organs in response to the action of an inducing organism, usually an insect. The goal of the present study was to inventory the insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil). The collections were carried out along all the trails, totaling 16 hours of sampling. Forty-three morphotypes of insect galls were found in 24 plant species (18 genera and 15 families). Sapindaceae and Euphorbiaceae were the most richness host plant families. Six new records of host plant species are presented: Senefeldera verticillata (Vell.) Croizat. (Euphorbiaceae), Inga acuminata (Fabaceae), Ocotea elegans (Lauraceae), Ouratea stipulata (Ochnaceae), Psychotria nuda (Rubiaceae) and Cestrum intermedium (Solanaceae). Most of the galls occurred on leaves (n = 21) and stems (n = 18), followed by buds (n = 2), two gall morphotypes occurred simultaneously on leaves and stems. One-chambered galls were more frequent (n = 31), as well as glabrous galls (n = 33). The gallers belong to three insect orders: Diptera (Cecidomyiidae), Hemiptera, and Lepidoptera. The associated fauna comprised parasitoids (Hymenoptera), inquilines (Hemiptera and Coleoptera) and successors (Isoptera and Acari).
Tea Consumption and Longitudinal Change in High‐Density Lipoprotein Cholesterol Concentration in Chinese Adults
Authors: Huang Shue , Li Junjuan , Wu Yuntao , Ranjbar Sareh , Xing Aijun , Zhao Haiyan , Wang Yanxiu , Shearer Gregory C. , Bao Le , Lichtenstein Alice H. , Wu Shouling , Gao Xiang 
Published: June 2018

Background

The relation between tea consumption and age‐related changes in high‐density lipoprotein cholesterol (
HDL
‐C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in
HDL
‐C concentrations.

Methods and Results

Baseline (2006) tea consumption was assessed via a questionnaire, and plasma
HDL
‐C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol‐lowering agents both at baseline (2006) and during the follow‐up period (2006–2012). The associations between baseline tea consumption and rate of change in
HDL
‐C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of
HDL
‐C concentrations (
P
‐trend <0.0001) in the fully adjusted model. The adjusted mean difference in the HDL‐C decreased rate was 0.010 (95% confidence interval, 0.008, 0.012) mmol/L per year for tea consumers versus nonconsumers (never or less than once/month group). Interactions between tea consumption and age, sex, lifestyle scores, and metabolic syndrome (all
P
‐interaction <0.0001) were identified. The associations between greater tea consumption and slower decrease in
HDL
‐C concentrations were more pronounced in men, individuals aged 60 or older, individuals with a lower lifestyle score, and individuals with metabolic syndrome (all
P
‐trend <0.0001).

Conclusions

Tea consumption was associated with slower age‐related decreases in
HDL
‐C concentrations during 6 years of follow‐up.

Clinical Trial Registration

URL
:
www.chictr.org
. Unique identifier: Chi
CTR
‐
TNRC
‐11001489.
Human-Tiger (Re)Negotiations
Authors: Doubleday Kalli F. 
Published: June 2018

Abstract
This case study explores the reintroduction of tigers to Sariska Tiger Reserve in Rajasthan, India, highlighting how the (re)negotiation between people and tigers is a struggle rooted in place and territory, with boundaries co-constructed by human and nonhuman actors. While the reintroduction came only three years after the official admission of complete species loss, tigers as a dominant force on the landscape were absent for more than a decade in some places. Accordingly, the people of Sariska see the reintroduced tigers as foreigners without place-knowledge and as disturbers of the interspecies boundaries created by the interactions of Sariska’s original tigers and many generations of local people. This study speaks to conservation sciences and animal geography to contribute to the scientific knowledge of the human dimensions of rewilding, still a nascent area of restoration ecology specifically in the case of apex predators in the global south.
Outlaws or Protected? DNA, Hybrids, and Biopolitics in a Finnish Wolf-Poaching Case
Authors: Peltola Taru , Heikkilä Jari 
Published: June 2018

AbstractBy analyzing a 2015 Finnish court case on wolf poaching, we discuss how wild animals are categorized, gain legal status based on their species identification, and affect the categorization of humans either as poachers or hunters concerned about the genetic purity of the species. The court had to evaluate the reliability, accuracy, and relevance of scientific knowledge to distinguish “pure” wolves from hybrids. Dealing with complicated questions of canid species identification, the court decision took a position in the debate on what to conserve in a world which escapes simple categorizations. Hence, we interpret the case as an example ofbiopolitics, addressing the challenges and tensions of governing life by differentiating between valued and less valued, killable and threatened lifeforms, and human responsibilities towards them.