bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confocal microscopy reveals in planta dynamic interactions between pathogenic, avirulent and non‐pathogenic Pseudomonas syringae strains
Authors: Rufián José S. , Macho Alberto P. , Corry David S. , Mansfield John W. , Ruiz‐Albert Javier , Arnold Dawn L. , Beuzón Carmen R. 
Published: January 2017

SummaryRecent advances in genomics and single‐cell analysis have demonstrated the extraordinary complexity reached by microbial populations within their hosts. Communities range from complex multispecies groups to homogeneous populations differentiating into lineages through genetic or non‐genetic mechanisms. Diversity within bacterial populations is recognized as a key driver of the evolution of animal pathogens. In plants, however, little is known about how interactions between different pathogenic and non‐pathogenic variants within the host impact on defence responses, or how the presence within a mixture may affect the development or the fate of each variant. Using confocal fluorescence microscopy, we analysed the colonization of the plant apoplast by individual virulence variants of Pseudomonas syringae within mixed populations. We found that non‐pathogenic variants can proliferate and even spread beyond the inoculated area to neighbouring tissues when in close proximity to pathogenic bacteria. The high bacterial concentrations reached at natural entry points promote such interactions during the infection process. We also found that a diversity of interactions take place at a cellular level between virulent and avirulent variants, ranging from dominant negative effects on proliferation of virulent bacteria to in trans suppression of defences triggered by avirulent bacteria. Our results illustrate the spatial dynamics and complexity of the interactions found within mixed infections, and their potential impact on pathogen evolution.
Silibinin Treatment Inhibits the Growth of Hedgehog Inhibitor‐Resistant Basal Cell Carcinoma Cells via Targeting EGFR‐MAPK‐Akt and Hedgehog Signaling
Authors: Dheeraj Arpit , Rigby Cynthia M. , O'Bryant Cindy L. , Agarwal Chapla , Singh Rana P. , Deep Gagan , Agarwal Rajesh 
Published: January 2017

AbstractBasal cell carcinoma (BCC) is the most common skin malignancy. Deregulated hedgehog signaling plays a central role in BCC development; therefore, hedgehog inhibitors have been approved to treat locally advanced or metastatic BCC. However, the development of resistance to hedgehog inhibitors is the major challenge in effective treatment of this disease. Herein, we evaluated the efficacy of a natural agent silibinin to overcome resistance with hedgehog inhibitors (Sant‐1 and GDC‐0449) in BCC cells. Silibinin (25–100 μm) treatment for 48 h strongly inhibited growth and induced death in ASZ001, Sant‐1‐resistant (ASZ001‐Sant‐1) and GDC‐0449‐resistant (ASZ001‐GDC‐0449) BCC cells. Furthermore, colony‐forming ability of ASZ001, ASZ001‐Sant‐1 and ASZ001‐GDC‐0449 cells was completely inhibited by silibinin treatment. Molecular analysis showed that silibinin treatment decreased the level of phosphorylated EGFR (Tyrosine 1173) and total EGFR in ASZ001‐Sant‐1 cells, key signaling molecules responsible for BCC resistance toward hedgehog inhibitors. Further, silibinin treatment decreased the phosphorylated Akt (Serine 473), phosphorylated ERK1/2 (Threonine 202/Tyrosine 204), cyclin D1 and Gli‐1 level but increased the SUFU expression in ASZ001‐Sant‐1‐resistant cells. Silibinin treatment of ASZ001‐Sant‐1‐resistant cells also decreased bcl‐2 but increased cleaved caspase 3 and PARP cleavage, suggesting induction of apoptosis. Together, these results support silibinin use to target hedgehog inhibitor‐resistant BCC cells.
The effect of cooling to different subzero temperatures on dog sperm cryosurvival
Authors: Alcantar‐Rodriguez A , Medrano A 
Published: January 2017

ContentsThe objective was to assess the effect of cooling to different subzero temperatures around ice formation (−5°C) on dog sperm cryosurvival and plasma membrane fluidity. Semen was centrifuged, and sperm were resuspended in a Tris‐egg yolk medium (3% glycerol). Diluted sperm were cooled from 22 to 5°C, and then, a Tris‐egg yolk medium containing 7% glycerol was added (final concentration of 5% glycerol and 200 × 106 cells/ml). Sperm were packaged in 0.5‐ml plastic straws, and equilibration was done 16 hr at 5°C before freezing. I. Straws (n = 47) at 5°C were exposed to nitrogen vapours to determine the freezing point. II. Other straws (from different ejaculates) processed as mentioned, were further cooled to −3, −5 or −7°C and immediately rewarmed in a water bath at 37°C. Motility, plasma membrane functionality and acrosome integrity were assessed. III. Other straws (from different ejaculates) processed as mentioned were further cooled to −3 or −5°C, frozen over nitrogen vapours and stored in liquid nitrogen for one month. Straws were thawed in a water bath at 38°C for 30 s. Motility, plasma membrane functionality, plasma membrane integrity, acrosome integrity, capacitation status and plasma membrane fluidity were assessed. Ice nucleation temperature was −14.3 ± 2.05°C (mean ± SD); cooling to +5, −3, −5 and −7°C, without freezing, produces no differences on sperm quality between target temperatures; cooling to +5, −3, and −5°C produced no differences on sperm survival and plasma membrane fluidity after freeze–thawing. In conclusion, cooling of dog spermatozoa to different subzero temperatures did not improve sperm cryosurvival and had no effect on plasma membrane fluidity after thawing.
The Macroeconomics Effects of Government Spending Under Fiscal Foresight
Authors: Jooste Charl , Naraidoo Ruthira 
Published: January 2017

AbstractConsumption and output responses to fiscal shocks are studied in a model with fiscal foresight. Fiscal foresight reduces both output multipliers and consumption. However, key features such as sticky wages, credit constrained households and elastic labour supply, are able to generate both sizeable output multipliers and positive consumption, in effect preserving key Keynesian effects. This model fits a developing economy like South Africa well since it is able to capture transparent communication of government as well as control for credit constrained consumption and sticky wages.
Update on radiotherapy in gynaecological malignancies
Authors: Reed Nicholas S , Sadozye Azmat H 
Published: January 2017

Key content

This article reviews the changing role of adjuvant radiation therapy in gynaecological cancer, with emphasis on data from recent clinical trials.

The evolution of practice with modern technology is improving the delivery of radiation, which has the potential to escalate doses, reduce toxicity and improve outcome.

Radiation is infrequently used in ovarian cancer but in selected patients may provide good palliation.

Late toxicity and survivorship issues are now recognised as important factors and there is a need to modify treatments to improve this.

Learning objectives

To learn and understand the changing uses of adjuvant radiation therapy in gynaecological cancer.

To understand the changing practice of brachytherapy, especially with the use of imaging to allow adaptive therapy.

To understand the use of high technology to improve the delivery of radiation therapy in gynaecological cancers with potential for dose escalation with improved outcome and reduced toxicities.

To understand the developments in brachytherapy and the use of computerised technologies and adaptive treatments.
Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin
Authors: Ud‐Din Sara , Bayat Ardeshir 
Published: January 2017

AbstractTissue repair models are essential to explore the pathogenesis of wound healing and scar formation, identify new drug targets/biomarkers and to test new therapeutics. However, no animal model is an exact replicate of the clinical situation in man as in addition to differences in the healing of animal skin; the response to novel therapeutics can be variable when compared to human skin. The aim of this review is to evaluate currently available non‐animal wound repair models in human skin, including: in silico, in vitro, ex vivo, and in vivo. The appropriate use of these models is extremely relevant to wound‐healing research as it enables improved understanding of the basic mechanisms present in the wound healing cascade and aid in discovering better means to regulate them for enhanced healing or prevention of abnormal scarring. The advantage of in silico models is that they can be used as a first in virtue screening tool to predict the effect of a drug/stimulus on cells/tissues and help plan experimental research/clinical trial studies but remain theoretical until validated. In vitro models allow direct quantitative examination of an effect on specific cell types alone without incorporating other tissue‐matrix components, which limits their utility. Ex vivo models enable immediate and short‐term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis of a stimulus in the living human subject before/during/after exposure to a stimulus. Despite clear advantages, there remains a lack of standardisation in design, evaluation and follow‐up, for acute/chronic wounds and scars in all models. In conclusion, ideal models of wound healing research are desirable and should mimic not only the structure but also the cellular and molecular interactions, of wound types in human skin. Future models may also include organ/skin‐on‐a‐chip with potential application in wound healing research.
Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat
Authors: Hosford Patrick S. , Millar Julian , Ramage Andrew G. , Marina Nephtali 
Published: January 2017

New Findings
What is the central question of this study?
Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity‐dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously.

What is the main finding and its importance?
Using fast‐cyclic voltammetry, we found that changes in local tissue in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension.

The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation‐induced changes in local tissue () in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of were performed using a novel application of fast‐cyclic voltammetry, which allows higher temporal resolution of O2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in in the cNTS, characterized by a rapid decrease in (‘initial dip’) followed by a post‐stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post‐ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In conclusion, neural activity‐dependent changes in tissue oxygen in brainstem cardiovascular autonomic centres are significantly impaired in animals with arterial hypertension.
Diagnóstico y medicación: la práctica médica en el Hospital Psiquiátrico del Valle entre 1956-1970
Authors: Sanchez Salcedo Jose Fernando 
Published: January 2017

<p> </p><p>A mediados del siglo XX, se lleva a cabo en Colombia un cambio institucional en el diagnóstico y el tratamiento de la locura. Surgen nuevas concepciones sobre la enfermedad mental, y se crean departamentos de Psiquiatría, tanto en las antiguas como en las recién inauguradas facultades de Medicina, que implementan nuevos tratamientos, influenciados por la Psiquiatría norteamericana. Siguiendo una línea de investigación historiográfica, el presente trabajo busca describir, a través de la revisión de 308 historias clínicas como fuente principal, el tipo de diagnósticos y el tratamiento utilizado en el proceso de transición del Asilo de Cali a hospital psiquiátrico, ocurrido entre 1956 y 1970. Entre los principales hallazgos se destaca la institucionalización de un conjunto de prácticas médicas que revela una clara influencia de la Psiquiatría norteamericana. En lo que respecta al tratamiento, las historias muestran el uso recurrente de nuevos fármacos antipsicóticos, combinados con terapias de electrochoque, ergoterapia y psicoterapia.</p>
Reliability of a New Medicine Ball Throw Power Test
Authors: Sayers Mark G.L. , Bishop Stephen 
Published: January 2017

The purpose of this study was to examine the reliability of a new upper body medicine ball push-press (MBP-P) test. Twenty-three strength trained volunteers performed a series of supine MBP-P throws using loads representing 5% and10% of their 5RM bench press (5 repetitions at each load). Throws were performed on a force platform (2000 Hz), with medicine ball kinematic data collected using a high-speed motion capture (500 Hz). Testing was repeated after 7–10 days to quantify intertest reliability. Maximal force (Fmax), impulse at Fmax, time to Fmax, and maximum rate of force development (RFDmax) were all calculated from the force platform outputs, with maximum ball velocity (Velmax) and maximum ball acceleration (Accelmax) developed from the kinematic data. Reliability was assessed using intraclass correlation (ICC), coefficient of variation (%CV), and typical error. Medicine ball kinematic variables were more reliable (CV% = 2.6–5.3, ICC = 0.87–0.95) than the various force platform derived power variables (CV% = 7.9–26.7, ICC = 0.51–0.90). The MBP-P test produces reliable data and can be used to quantify many standard power based measures, with the key findings have implications for athletic populations requiring high velocity, light load upper body pushing power.
Negative Autogenous Control of the Master Type III Secretion System Regulator HrpL inPseudomonas syringae
Authors: Waite Christopher , Schumacher Jörg , Jovanovic Milija , Bennett Mark , Buck Martin 
Published: January 2017

ABSTRACTThe type III secretion system (T3SS) is a principal virulence determinant of the model bacterial plant pathogenPseudomonas syringae. T3SS effector proteins inhibit plant defense signaling pathways in susceptible hosts and elicit evolved immunity in resistant plants. The extracytoplasmic function sigma factor HrpL coordinates the expression of most T3SS genes. Transcription ofhrpLis dependent on sigma-54 and the codependent enhancer binding proteins HrpR and HrpS forhrpLpromoter activation.hrpLis oriented adjacently to and divergently from the HrpL-dependent genehrpJ, sharing an intergenic upstream regulatory region. We show that association of the RNA polymerase (RNAP)-HrpL complex with thehrpJpromoter element imposes negative autogenous control onhrpLtranscription inP. syringaepv.tomatoDC3000. ThehrpLpromoter was upregulated in a ΔhrpLmutant and was repressed by plasmid-bornehrpL. In a minimalEscherichia colibackground, the activity of HrpL was sufficient to achieve repression of reconstitutedhrpLtranscription. This repression was relieved if both the HrpL DNA-binding function and thehrp-box sequence of thehrpJpromoter were compromised, implying dependence upon thehrpJpromoter. DNA-bound RNAP-HrpL entirely occluded the HrpRS and partially occluded the integration host factor (IHF) recognition elements of thehrpLpromoterin vitro, implicating inhibition of DNA binding by these factors as a cause of negative autogenous control. A modest increase in the HrpL concentration caused hypersecretion of the HrpA1 pilus protein but intracellular accumulation of later T3SS substrates. We argue that negative feedback on HrpL activity fine-tunes expression of the T3SS regulon to minimize the elicitation of plant defenses.IMPORTANCEThe United Nations Food and Agriculture Organization has warned that agriculture will need to satisfy a 50% to 70% increase in global food demand if the human population reaches 9 billion by 2050 as predicted. However, diseases caused by microbial pathogens represent a major threat to food security, accounting for over 10% of estimated yield losses in staple wheat, rice, and maize crops. Understanding the decision-making strategies employed by pathogens to coordinate virulence and to evade plant defenses is vital for informing crop resistance traits and management strategies. Many plant-pathogenic bacteria utilize the needle-like T3SS to inject virulence factors into host plant cells to suppress defense signaling.Pseudomonas syringaeis an economically and environmentally devastating plant pathogen. We propose that the master regulator of its entire T3SS gene set, HrpL, downregulates its own expression to minimize elicitation of plant defenses. Revealing such conserved regulatory strategies will inform future antivirulence strategies targeting plant pathogens.
Estimated reductions in cardiovascular and gastric cancer disease burden through salt policies in England: an IMPACTNCDmicrosimulation study
Authors: Kypridemos Chris , Guzman-Castillo Maria , Hyseni Lirije , Hickey Graeme L , Bandosz Piotr , Buchan Iain , Capewell Simon , O'Flaherty Martin 
Published: January 2017

ObjectiveTo estimate the impact and equity of existing and potential UK salt reduction policies on primary prevention of cardiovascular disease (CVD) and gastric cancer (GCa) in England.DesignA microsimulation study of a close-to-reality synthetic population. In the first period, 2003–2015, we compared the impact of current policy against a counterfactual ‘no intervention’ scenario, which assumed salt consumption persisted at 2003 levels. For 2016–2030, we assumed additional legislative policies could achieve a steeper salt decline and we compared this against the counterfactual scenario that the downward trend in salt consumption observed between 2001 and 2011 would continue up to 2030.SettingSynthetic population with similar characteristics to the non-institutionalised population of England.ParticipantsSynthetic individuals with traits informed by the Health Survey for England.Main measureCVD and GCa cases and deaths prevented or postponed, stratified by fifths of socioeconomic status using the Index of Multiple Deprivation.ResultsSince 2003, current salt policies have prevented or postponed ∼52 000 CVD cases (IQR: 34 000–76 000) and 10 000 CVD deaths (IQR: 3000–17 000). In addition, the current policies have prevented ∼5000 new cases of GCa (IQR: 2000–7000) resulting in about 2000 fewer deaths (IQR: 0–4000). This policy did not reduce socioeconomic inequalities in CVD, and likely increased inequalities in GCa. Additional legislative policies from 2016 could further prevent or postpone ∼19 000 CVD cases (IQR: 8000–30 000) and 3600 deaths by 2030 (IQR: −400–8100) and may reduce inequalities. Similarly for GCa, 1200 cases (IQR: −200–3000) and 700 deaths (IQR: −900–2300) could be prevented or postponed with a neutral impact on inequalities.ConclusionsCurrent salt reduction policies are powerfully effective in reducing the CVD and GCa burdens overall but fail to reduce the inequalities involved. Additional structural policies could achieve further, more equitable health benefits.
Impairments, activity limitations and participation restrictions experienced in the first year following a critical illness: protocol for a systematic review
Authors: Ohtake Patricia J , Coffey Scott Jacqueline , Hinman Rana S , Lee Alan Chong , Smith James M 
Published: January 2017

IntroductionCritical illness requiring intensive care unit (ICU) management is a life-altering event with ∼25% of ICU survivors experiencing persistent reductions in physical functioning, impairments in mental health, cognitive dysfunction and decreased quality of life. This constellation of problems is known as ‘postintensive care syndrome’ (PICS) and may persist for months and/or years. The purpose of this systematic review is to identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU, using the International Classification of Functioning, Disability and Health framework to elucidate the impairments of body functions and structures, activity limitations and participation restrictions.Methods and analysisMedline (Ovid), Cochrane Database of Systematic Reviews (Ovid), Cochrane Central Register of Controlled Trials (Ovid), PubMed, CINAHL (EBSCO), Web of Science and EMBASE will be systematically searched for observational studies reporting the physical impairments of body functions and structures, activity limitations and participation restrictions associated with PICS. Two reviewers will assess the articles for eligibility according to prespecified selection criteria, after which an independent reviewer will perform data extraction which will be validated by a second independent reviewer. Quality appraisal will be performed by two independent reviewers. Outcomes of the included studies will be summarised in tables and in narrative format and meta-analyses will be conducted where appropriate.Ethics and disseminationFormal ethical approval is not required as no primary data is collected. This systematic review will identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU and will be disseminated through a peer-reviewed publication and at conference meetings, to inform practice and future research on the physical problems associated with PICS.Trial registration numberCRD42015023520.