bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterisation of a cryptic Golgi complex in Naegleria gruberi
Authors: Herman Emily K. , Yiangou Lyto , Cantoni Diego M. , Miller Christopher N. , Marciano-Cabral Francine , Anthonyrajah Erin , Dacks Joel B. , Tsaousis Anastasios D.
Published: April 2018

Although the Golgi complex has a conserved morphology of flattened stacked cisternae in most eukaryotes, it has lost the stacked organisation in several lineages, raising the question of what range of morphologies is possible for the Golgi. In order to understand this diversity, it is necessary to characterise the Golgi in many different lineages. Here, we identify the Golgi complex in Naegleria, one of the first descriptions of an unstacked Golgi organelle in a non-parasitic eukaryote, other than fungi. We provide a comprehensive list of Golgi-associated membrane trafficking genes encoded in two species of Naegleria and show that nearly all are expressed in mouse-passaged N. fowleri cells. We then study distribution of the Golgi marker (Ng)CopB by fluorescence in Naegleria gruberi, identifying membranous structures that are disrupted by Brefeldin A treatment, consistent with Golgi localisation. Confocal and immunoelectron microscopy reveals that NgCOPB localises to tubular membranous structures. Our data identify the Golgi organelle for the first time in this major eukaryotic lineage, and provide the rare example of a tubular morphology, representing an important sampling point for the comparative understanding of Golgi organellar diversity.

This article has an associated First Person interview with the first author of the paper.
Digestive and locomotor capacity show opposing responses to changing food availability in an ambush predatory fish
Authors: Fu Shi-Jian , Peng Jing , Killen Shaun S.
Published: April 2018

Metabolic rates vary widely within species, but little is known about how variation in the “floor” (i.e. standard metabolic rate in ectotherms; SMR) and “ceiling” (maximum metabolic rate; MMR) for an individual's aerobic scope (AS) are linked with the digestive and locomotor function. Any links among metabolic traits and aspects of physiological performance may also be modulated by fluctuations in food availability. This study followed changes in SMR, MMR, and digestive and locomotor capacity in Southern catfish (Silurus meridionalis) throughout 15 days of food deprivation and 15 days of refeeding. Individuals down-regulated SMR during food deprivation and showed only a 10% body mass decrease during this time. While critical swim speed (Ucrit), was robust to food-deprivation, digestive function decreased after fasting with a reduced peak oxygen uptake during specific dynamic action (SDA) and prolonged SDA duration. During refeeding, individuals displayed rapid growth and digestive function recovered to pre-fasting levels. However, refed fish showed a lower Ucrit than would be expected for their increased body length and in comparison to measures at the start of the study. Reduced swimming ability may be a consequence of compensatory growth: growth rate was negatively correlated with changes in Ucrit during refeeding. Southern catfish down-regulate digestive function to reduce energy expenditure during food deprivation, but regain digestive capacity during refeeding, potentially at the cost of decreased swimming performance. The plasticity of maintenance requirements suggests that SMR is a key fitness trait for in this ambush predator. Shifts in trait correlations with food availability suggest that the potential for correlated selection may depend on context.
Black Carbon Reduces the Beneficial Effect of Physical Activity on Lung Function
Authors: LAEREMANS MICHELLE , DONS EVI , AVILA-PALENCIA IONE , CARRASCO-TURIGAS GLÒRIA , ORJUELA-MENDOZA JUAN PABLO , ANAYA-BOIG ESTHER , COLE-HUNTER TOM , DE NAZELLE AUDREY , NIEUWENHUIJSEN MARK , STANDAERT ARNOUT , VAN POPPEL MARTINE , DE BOEVER PATRICK , INT PANIS LUC
Published: April 2018

Introduction

When physical activity is promoted in urban outdoor settings (e.g., walking and cycling), individuals are also exposed to air pollution. It has been reported that short-term lung function increases as a response to physical activity, but this beneficial effect is hampered when elevated air pollution concentrations are observed. Our study assessed the long-term impact of air pollution on the pulmonary health benefit of physical activity.

Methods

Wearable sensors were used to monitor physical activity levels (SenseWear) and exposure to black carbon (microAeth) of 115 healthy adults during 1 wk in three European cities (Antwerp, Barcelona, London). The experiment was repeated in three different seasons to approximate long-term behavior. Spirometry tests were performed at the beginning and end of each measurement week. All results were averaged on a participant level as a proxy for long-term lung function. Mixed effect regression models were used to analyze the long-term impact of physical activity, black carbon and their interaction on lung function parameters, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow (FEF)25–75, and peak expiratory flow. Interaction plots were used to interpret the significant interaction effects.

Results

Negative interaction effects of physical activity and black carbon exposure on FEV1 (P = 0.07), FEV1/FVC (P = 0.03), and FEF25–75 (P = 0.03) were observed. For black carbon concentrations up to approximately 1 μg·m−3, an additional MET·h−1·wk−1 resulted in a trend toward lung function increases (FEV1, FEV1/FVC, and FEF25–75 increased 5.6 mL, 0.1% and 14.5 mL·s−1, respectively).

Conclusions

We found that lung function improved with physical activity at low black carbon levels. This beneficial effect decreased in higher air pollution concentrations. Our results suggest a greater need to reduce air pollution exposures during physical activity.
Benefits of 8-wk Mindfulness-based Stress Reduction or Aerobic Training on Seasonal Declines in Physical Activity
Authors: MEYER JACOB D. , TORRES ELISA R. , GRABOW MAGGIE L. , ZGIERSKA ALEKSANDRA E. , TENG HAO YANG , COE CHRISTOPHER L. , BARRETT BRUCE P.
Published: April 2018

Mindfulness-based stress reduction (MBSR) and aerobic exercise training (AET) programs improve health and well-being. Exercise participation has been related to mindfulness and may be altered by MBSR training.

Purpose

This study aimed to compare 8 wk of MBSR, AET, and no-treatment control during the fall season on objectively measured physical activity in healthy adults.

Methods

Participants (n = 66) wore an ActiGraph GT3X+ accelerometer for 7 d prerandomization and after 8 wk MBSR or AET interventions, or neither (control). Mean daily minutes (min) of moderate-to-vigorous physical activities (MVPA) were calculated along with weekly time spent in bouts of MVPA ≥10 min (MVPABouts) to assess physical activity sufficient to meet national guidelines. Groups were compared on pairwise changes in outcomes across time. Effect sizes were calculated using Cohen’s d.

Results

Sufficient data (≥3 weekdays, ≥1 weekend day, and ≥10 h·d−1) were obtained from 49 participants (18 MBSR, 14 AET, and 17 control). Daily MVPA decreased in all groups from prerandomization to postintervention (August to November); control decreased 17.9 ± 25.7 min·d−1, MBSR decreased 5.7 ± 7.5 min·d−1, and AET decreased 7.4 ± 14.3 min·d−1 (mean ± SD), without significant differences among the groups (all P > 0.05). MVPABouts decreased 77.3 ± 106.6 min·wk−1 in control and 15.5 ± 37.0 min·wk−1 in MBSR (between-group difference: P = 0.08; d = 0.86), whereas it increased by 5.7 ± 64.1 min·wk−1 in AET (compared with control: P = 0.029; d = 0.97; compared with MBSR; P = 0.564; d = 0.29).

Conclusion

Data from participants in a randomized controlled trial showed that although AET increases MVPA bouts compared with no treatment, MBSR training may also mitigate the influence of shorter day length and cooler weather on participation in physical activities. Future research is needed to determine how MBSR affects exercise to inform interventions. Interventions combining MBSR and exercise may be particularly successful at increasing physical activity participation.
Case Report: Successful treatment of refractory high-flow priapism in a patient with sickle cell disease by selective trans-catheter embolization using an autologous blood clot: A case report
Authors: Tahir Muhammad , Abbas Hiba A. , Tassadaq Tariq
Published: April 2018

Priapism is an abnormal prolonged and persistent penile erection lasting more than 4 h, unrelated to sexual desire, stimulation or activity. The three types of priapism are low-flow, high-flow and stuttering. Patients with sickle cell disease (SCD) have increased risk of low-flow and stuttering priapism, but high-flow priapism is relatively uncommon in SCD. We report a case of non-traumatic refractory high-flow priapism evolving from a stuttering low-flow priapism in a patient with SCD. The patient was successfully treated by super-selective transcatheter embolization of the penile arteries with an autologous blood clot. It is proposed that the super-selective transcatheter embolization of unilateral or bilateral penile arteries with autologous blood clot is a relatively safe and effective non-surgical treatment option for high-flow priapism, even in patients with SCD, and has a low probability of developing erectile dysfunction.
Case Report: First report of Elizabethkingia miricola infection in a patient with cystic fibrosis
Authors: Frost Freddy , Nazareth Dilip
Published: April 2018

Elizabethkingia miricola is a rare non-fermenting Gram-negative rod that has previously been reported to be associated with blood stream and pulmonary abscess infections, but never before in cystic fibrosis (CF). Here we present the first reported case of Elizabethkingia miricola infection in a patient with CF and discuss the management options. We describe a patient with CF in whom we observed clinical and spirometric evidence of pulmonary exacerbation with the associated growth of E. miricola in sputum culture. The period of clinical instability was observed to coincide with the obtainment of four sputum samples from which E. miricola was cultured; improvement was seen following treatment with ciprofloxacin and the subsequent eradication of E. miricola. We conclude that E. miricola is able to survive in the CF lung and in this case was associated with pulmonary exacerbation. Empirical treatment with fluoroquinolones is appropriate, based on our experience.
Typification of the names inTrifoliumdescribed by Gaetano Savi
Authors: Roma-Marzio Francesco , D’Antraccoli Marco , Astuti Giovanni , Maccioni Simonetta , Amadei Lucia , Peruzzi Lorenzo
Published: April 2018

Between 1789 and 1825, Gaetano Savi described elevenTrifoliumnames, ten of which are not yet typified. In order to fix the application of these names, nomenclatural types are designated here and previous typifications are discussed. For eight names (T. bocconei, T. elegans, T. michelianum, T. obscurum, T. praetutianum, T. rigidum, T. sebastiani, T. supinum) we designated a lectotype (two illustrations and six specimens in PI), forT. conicumwe located the holotype in PI, and forT. for–mosumandT. vesiculosuma neotype in PI was selected. For the latter name, also an isoneotype was located in P. Furthermore, we selected an epitype forT. elegansin PI (isoepitype in FI).
MODERN ENGLISH LITERATURE AND ITS TRANSLATION IN RUSSIAN: PROBLEMS OF QUALITY
Authors: Галлямова Мария , Gallyamova Mariya , Баклыкова Татьяна , Baklykova Tat'yana
Published: April 2018

Many researchers in the field of linguistics note that it is quite difficult to find criteria for assessing the quality of a modern literary text. Nevertheless, the result of the translator's work is determined by how fully and successfully he has fulfilled the normative requirements. The object of this article is a comparative analysis of the novel «The Devil wears Prada» by Lauren Weisberger translated M.D. Malkova, T.N. Shabaeva
Self-assessed competence among nurses working in municipal health-care services in Norway
Authors: Hovland Gro , Kyrkjebø Dagrun , Andersen John Roger , Råholm Maj-Britt
Published: April 2018

Demands made on nursing staff are expanding and changing, requiring a broad set of competencies that require evaluation and enhancement in places. This study used the Nurse Competence Scale to measure self-assessed competence among nurses working in three municipal health-care services in Norway. Results indicate that nurses perceive their competence as being satisfactory overall, but there are areas that would benefit from improvement: providing patients' family members with education and guidance, quality assurance, and using research to evaluate and develop services. These competencies could be the focus of departments' future competence plans. The Nurse Competence Scale can be used to assess the impact of training and the efficacy of competence-enhancing actions.
Nursing simulation: a community experience
Authors: Gunowa Neesha Oozageer , Elliott Karen , McBride Michelle
Published: April 2018

The education sector faces major challenges in providing learning experiences so that newly qualified nurses feel adequately prepared to work in a community setting. With this in mind, higher education institutions need to develop more innovative ways to deliver the community-nurse experience to student nurses. This paper presents and explores how simulation provides an opportunity for educators to support and evaluate student performance in an environment that models a complete patient encounter in the community. Following the simulation, evaluative data were collated and the answers analysed to identify key recommendations.
Revision of failed total ankle arthroplasty to a hindfoot fusion
Authors: Ali A. A. , Forrester R. A. , O’Connor P. , Harris N. J.
Published: April 2018

Aims

The aim of this study was to present a series of patients with aseptic failure of a total ankle arthroplasty (TAA) who were treated with fusion of the hindfoot using a nail.

Patients and Methods

A total of 23 TAAs, in 22 patients, were revised for aseptic loosening and balloon osteolysis to a hindfoot fusion by a single surgeon (NH) between January 2012 and August 2014. The procedure was carried out without bone graft using the Phoenix, Biomet Hindfoot Arthrodesis Nail. Preoperative investigations included full blood count, CRP and ESR, and radiological investigations including plain radiographs and CT scans. Postoperative plain radiographs were assessed for fusion. When there was any doubt, CT scans were performed.

Results

The mean follow-up was 13.9 months (4.3 to 37.2). Union occurred at the tibiotalar joint in 22 ankles (95.6%) with one partial union. Union occurred at the subtalar joint in 20 ankles (87%) of cases with two nonunions. The nail broke in one patient with a subtalar nonunion and revision was undertaken. The only other noted complication was one patient who suffered a stress fracture at the proximal aspect of the nail, which was satisfactorily treated conservatively.

Conclusion

This study represents the largest group of patients reported to have undergone revision TAA to fusion of the hindfoot with good results Cite this article: Bone Joint J 2018;100-B:475–9.
Linear, Adaptativo ou Interpretativo? Compreendendo a Dinâmica da Formação de Estratégias em Pequenas Empresas
Authors: Pascuci Lucilaine , Alves Claudinei
Published: April 2018

Este estudo examina como ocorre o processo de formação de estratégias em pequenas empresas, tendo como base a existência de elementos de natureza racional, interpretativa e adaptativa que influenciam este processo. Para tanto, explora-se como tais elementos se intercalam e se complementam caracterizando a formação de estratégias, em um processo dinâmico que influencia como as estratégias surgem e são desenvolvidas em pequenas empresas. Trata-se de um estudo comparativo de natureza qualitativa com abordagem multimétodos. Os dados foram coletados por meio de observação não participante, documentos e entrevistas. Os dados foram analisados por meio da técnica de análise de narrativas. Os principais resultados demonstraram que a formação de estratégias na pequena empresa é caracterizada, predominantemente, por elementos de natureza adaptativa e interpretativa. Quando existentes, elementos de natureza racional estão relacionados a métodos de controle e de apuração de resultados. O processo de formação de estratégias apresentou uma característica cíclica, sendo retroalimentado pelo processo de aprendizagem do pequeno empresário, construído a partir das experiências vivenciadas. Por fim, a dinâmica de elementos de natureza racional, interpretativa e adaptativa permitiu a identificação de um comportamento padrão destes elementos no processo de formação de estratégias em pequenas empresas.
A bi-functional IL-6-HaloTag® as a tool to measure the cell-surface expression of recombinant odorant receptors and to facilitate their activity quantification
Authors: Noe Franziska , Geithe Christiane , Fiedler Julia , Krautwurst Dietmar
Published: April 2018

The functional cell surface expression of recombinant odorant receptors typically has been investigated by expressing N-terminally extended, “tagged” receptors in test cell systems, using antibody-based immunocytochemistry or flow cytometry, and by measuring odorant/receptor-induced cAMP signaling, mostly by an odorant/receptor-induced and cAMP signaling-dependent transcriptional activation of a luciferase-based luminescence assay. In the present protocol, we explain a method to measure the cell-surface expression and signaling of recombinant odorant receptors carrying a bi-functional, N-terminal ‘IL-6-HaloTag®’. IL-6, being a secreted cytokine, facilitates functional cell surface expression of recombinant HaloTag®-odorant receptors, and the HaloTag® protein serves as a highly specific acceptor for cell-impermeant or cell-permeant, fluorophore-coupled ligands, which enable the quantification of odorant receptor expression by antibody-independent, chemical live-cell staining and flow cytometry. Here, we describe how to measure the cell surface expression of recombinant IL-6-HaloTag®-odorant receptors in HEK-293 cells or NxG 108CC15 cells, by live-cell staining and flow cytometry, and how to measure an odorant-induced activation of these receptors by the fast, real-time, luminescence-based GloSensor® cAMP assay.
Histone deacetylase inhibitor-based chromatin precipitation for identification of targeted genomic loci
Authors: W. Hanigan Thomas , M. Danes Jeanne , Y. Taha Taha , Frasor Jonna , A. Petukhov Pavel
Published: April 2018

Histone deacetylase (HDAC) catalyzes the removal of acetyl marks from histones, effectively regulating gene expression. Genome wide chromatin immunoprecipitation (ChIP) studies have shown HDACs are present on numerous active and repressed genes. However, HDAC inhibitors (HDACi) only regulate a small subset of this population in a cell type dependent fashion. To determine genomic locations directly targeted by HDACi, we developed a chromatin precipitation method using a photoreactive HDAC inhibitor probe (photomate). We validate this method by analyzing several canonical HDACi regulated genes, CDKN1A and FOSL1, and compare it to traditional ChIP using HDAC1 antibodies. We show that HDACi target HDACs bound at the promoter regions but not gene bodies, differing from HDAC1 antibody-based ChIP in the case of CDKN1A. This approach is anticipated to be useful for genome wide studies to identify the subset of genes directly regulated by an HDACi in a given cell type.
DNA repair and apoptosis: Roles in radiotherapy-related acute reactions in breast cancer patients
Authors: Batar Bahadir , Mutlu Tuba , Bostanci Merve , Akin Mustafa , Tuncdemir Matem , Bese Nuran , Guven Mehmet
Published: April 2018

Normal tissue reactions are therapy limiting factor for the effectiveness of the radiotherapy in cancer patients. DNA repair and apoptosis are estimated to be critical players of adverse effects in response to radiotherapy. Our aim was to define the association of DNA repair (ERCC1 and XPC) and apoptotic (BCL2, CASP3 and NFKB1) gene expression, DNA damage levels, apoptosis changes and DNA repair gene variations with the risk of acute side effects in breast cancer patients. The study included 100 women with newly diagnosed breast cancer; an experimental case group (n=50) with acute side effects and the control group (n=50) without side effects. Gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Micronucleus (MN) and 8-hydroxy-2"²-deoxyguanosine (8-OHdG) assays were performed to compare the DNA damage levels. Apoptosis was examined by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining. ERCC1 rs3212986 and XPC rs3731055 polymorphisms were genotyped by real-time PCR technique. No significantly correlation of DNA repair and apoptosis gene expression and DNA damage levels with acute side effects in response to radiotherapy. Also, there was no association between apoptosis levels and acute effects. ERCC1 rs3212986 CC genotype showed a protective effect against radiotherapy-induced acute reactions (p<0.001; OR: 0.21; 95% CI= 0.08-0.52). Our results suggest that apoptosis and DNA damage levels are not associated with acute radiosensitivity. DNA repair may affect the risk of acute reactions. Further studies are needed to validate the current findings.
Relation of MPO, MnSOD, NQO1 gene variants in endometrial carcinoma in the line of PCR-RFLP methods
Authors: Bulgurcuoglu Kuran Sibel , Iplik Elif Sinem , Cakmakoglu Bedia , Timirci Kahraman Ozlem , Iyibozkurt Ahmet Cem , Koc Arzu , Ergen Arzu , Gulec Yilmaz Seda , Isbir Turgay
Published: April 2018

Reactive oxygen species (ROS) have been shown to be responsible for inducing DNA damage leading to mutagenesis, carcinogenesis, and cell death if the capacity of the protective antioxidant system is impaired. Endometrial carcinoma is the primary cancer type in the female genital system. The enhanced cell lipid peroxidation and impaired antioxidant enzyme activities observed in patients with endometrial cancer indicate the potential for oxidative injury to cells and cell membranes in such patients. The aim of the study was to investigate the possible association between gene variants of superoxide dismutase (SOD), myeloperoxidase (MPO), and NADPH quinone oxido reductase (NQO1), and their possible role in endometrial cancer in Turkish patients. According to results, MPO G+ genotype and AG genotype were significantly increased in patients compared with controls (P<0.001). We suggest that the MPO polymorphism might be a risk for endometrial cancer.
Isolation and identification of two extremely halophilic archaea from sebkhas in the Algerian Sahara
Authors: Khallef Sakina , Lestini Roxane , Myllykallio Hannu , Houali Karim
Published: April 2018

In Algeria, many salt lakes are to be found spread from southern Tunisia up to the Atlas Mountains in northern Algeria. Oum Eraneb and Ain El beida sebkhas (salt lakes), are located in the Algerian Sahara. The aim of this study was to explore the diversity of the halobacteria in this type of habitats. The physicochemical properties of these shallow saline environments were examined and compared with other hypersaline and marine ecosystems. Both sites were relatively alkaline with a pH around 8.57- 8.74 and rich in salt at 13% and 16% (w/v) salinity for Oum Eraneb and Ain El beida, respectively, with dominant ions of sodium and chloride. The microbial approach revealed the presence of two halophilic archaea, strains JCM13561 and A33T in both explored sebkhas. Growth occurred between 10 and 25% (w/v) NaCl and the isolates grow optimally at 20% (w/v) NaCl. The pH range for growth was 6 to 9.5 with an optimum at pH 7.5 for the first strain and 7 to 9.5 with an optimum pH at 8.5-9 for the second strain. On the basis of 16S rRNA gene sequence analysis, strains JCM13561 and A33T were most closely related to Halorubrum litoreum and Natronorubrum bangense (99% and 96% similarity, respectively).
Effect of Tunceli garlic on some immunological parameters in Cyprinus carpio exposed to chlorpyrifos
Authors: Pala Ayşegül , Åžeker Engin , Yonar M. Enis
Published: April 2018

In this study, the effect of Tunceli garlic (Allium tuncelianium) on hemoglobin (Hb) level, oxidative radical production of neutrophils (Nitoblue tetrazolium assay-NBT activity) and total immunoglobulin (TI) content in carp (Cyprinus carpio) exposed to chlorpyrifos (CPF)  was investigated. The 96 hour LC50 value of CPF on C. carpio was calculated to as 0.230 mg/L. The fishes were exposed to sublethal concentration of chlorpyrifos (1/8 of LC50 value: 0.029 mg/L), and Tunceli garlic (20 and 40 g/kg diet) was simultaneously administered for 21 days. Blood samples were taken from the fishes at 7, 14 and 21 days and analysed to determine the Hb levels, the NBT activity and the TI content. There was a significant decrease in the Hb level, the NBT activity and the TI content of CPF-treated fish. However, Tunceli garlic reversed the Hb level, the NBT activity and the TI content. In conclusion, this study demonstrated that CPF had a negative effect on the immunological values of the fish. The simultaneous administration of Tunceli garlic was neutralised CPF-induced toxicity.
Fertility enhancing efficacy of Cicer arietinum in male albino mice
Authors: Sayed Amany A , Ali Atef A. , Mohamed Hanan R. H.
Published: April 2018

The present study was conducted to investigate the effect of incorporating Cicer arietinum in the diet on the testicular functions of the male mice. Seventy-two mice were divided equally into four groups that were daily fed a diet containing 0, 20, 30 and 50% of C. arietinum seeds, respectively. After 7, 14 and 21 days of starting the experiments, the mice were anesthetized and euthanized to collect the blood, testes, epididymis and seminal vesicles. The present results showed that the increased percentage of C. arietinum in the diet caused significant elevations in the serum levels of testosterone and luteinizing hormone (LH), sperm concentration, sperm motility as well as the testicular levels of antioxidants including glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), in comparison to the controls. On the other hand, marked reductions in the sperm abnormality, testicular levels of malondialdehyde (MDA), the percentage of DNA damage in tail and tail moment (TM) were observed in the mice that received a diet containing C. arietinum as compared to the controls. Both the sperms and testes of the mice fed a diet containing C. arietinum in the diet showed a normal intact appearance of the electrophoresed genomic DNA on agarose, as those of the controls. In conclusion, C. arietinum is not only a safe ingredient in the fast-food but also an enhancer of the testicular functions.
Firing of Putative Dopamine Neurons in Ventral Tegmental Area Is Modulated by Probability of Success during Performance of a Stop-Change Task
Authors: Tennyson Stephen S. , Brockett Adam T. , Hricz Nicholas W. , Bryden Daniel W. , Roesch Matthew R.
Published: April 2018

Response inhibition, the ability to refrain from unwanted actions, is an essential component of complex behavior and is often impaired across numerous neuropsychiatric disorders such as addiction, attention-deficit hyperactivity disorder (ADHD), schizophrenia, and obsessive-compulsive disorder. Accordingly, much research has been devoted to characterizing brain regions responsible for the regulation of response inhibition. The stop-signal task, a task in which animals are required to inhibit a prepotent response in the presence of a STOP cue, is one of the most well-studied tasks of response inhibition. While pharmacological evidence suggests that dopamine (DA) contributes to the regulation of response inhibition, what is exactly encoded by DA neurons during performance of response inhibition tasks is unknown. To address this issue, we recorded from single units in the ventral tegmental area (VTA), while rats performed a stop-change task. We found that putative DA neurons fired less and higher to cues and reward on STOP trials relative to GO trials, respectively, and that firing was reduced during errors. These results suggest that DA neurons in VTA encode the uncertainty associated with the probability of obtaining reward on difficult trials instead of the saliency associated with STOP cues or the need to resolve conflict between competing responses during response inhibition.
BACE1 Mediates HIV-Associated and Excitotoxic Neuronal Damage Through an APP-Dependent Mechanism
Authors: Stern Anna L. , Ghura Shivesh , Gannon Patrick J. , Akay-Espinoza Cagla , Phan Jessica M. , Yee Alan C. , Vassar Robert , Gelman Benjamin B. , Kolson Dennis L. , Jordan-Sciutto Kelly L.
Published: April 2018

HIV-associated neurocognitive disorders (HANDs) share common symptoms with Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Plaques are formed by aggregation of Aβ oligomers, which may be the toxic species in AD pathogenesis, and oligomers are generated by cleavage of amyloid precursor protein (APP) by β-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 inhibitors reverse neuronal loss and cognitive decline in animal models of AD. Although studies have also found evidence of altered APP processing in HIV+patients, it is unknown whether increased BACE1 expression or Aβ oligomer production is a common neuropathological feature of HAND. Moreover, it is unknown whether BACE1 or APP is involved in the excitotoxic, NMDAR-dependent component of HIV-associated neurotoxicityin vitro. Herein, we hypothesize that HIV-associated neurotoxicity is mediated by NMDAR-dependent elevation of BACE1 and subsequent altered processing of APP. Supporting this, we observed elevated levels of BACE1 and Aβ oligomers in CNS of male and female HIV+patients. In a model of HIV-associated neurotoxicity in which rat neurons are treated with supernatants from HIV-infected human monocyte-derived macrophages, we observed NMDAR-dependent elevation of BACE1 protein. NMDA treatment also increased BACE1 and both pharmacological BACE1 inhibition and genetic loss of APP were partially neuroprotective. Moreover, in APP knock-out (APP−/−) mouse neurons, NMDA-induced toxicity was BACE1 independent, indicating that cytotoxicity of BACE1 is dependent upon APP cleavage. Our findings suggest that increased BACE1 and the resultant Aβ oligomer production may contribute to HIV-associated neuropathogenesis and inhibition of BACE1 could have therapeutic potential in HANDs.

SIGNIFICANCE STATEMENTHIV-associated neurocognitive disorders (HANDs) represent a range of cognitive impairments affecting ∼50% of HIV+individuals. The specific causes of HAND are unknown, but evidence suggests that HIV-infected macrophage infiltration into the brain may cause neuronal damage. Herein, we show that neurons treated with conditioned media from HIV-infected macrophages have increased expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protein implicated in Alzheimer's disease pathogenesis. Moreover, inhibition of BACE1 prevented neuronal loss after conditioned media exposure, but had no effect on HIV-associated neurotoxicity in neurons lacking its cleavage target amyloid precursor protein. We also observed increased BACE1 expression in HIV+patient brain tissue, confirming the potential relevance of BACE1 as a therapeutic target in HANDs.
Time Course of Brain Network Reconfiguration Supporting Inhibitory Control
Authors: Popov Tzvetan , Westner Britta U. , Silton Rebecca L. , Sass Sarah M. , Spielberg Jeffrey M. , Rockstroh Brigitte , Heller Wendy , Miller Gregory A.
Published: April 2018

Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test samplen= 96, replication samplen= 237, totalN= 333, both sexes) who performed a color–word Stroop task. Time–frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal–parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation.

SIGNIFICANCE STATEMENTHemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to inherent methodological constraints, much of this research has been unable to characterize the temporal dynamics of such networks (e.g., direction of information flow between nodes). Guided by fMRI research identifying the structure of brain networks supporting inhibitory control, results of EEG source analysis in a test sample (n= 96) and replication sample (n= 237) using effective connectivity and predictive analytics strategies advance a model of inhibitory control by characterizing the precise temporal dynamics by which this network operates and exemplify an approach by which mechanistic models can be developed for other key psychological processes.
Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy
Authors: Rempe Ralf G. , Hartz Anika M.S. , Soldner Emma L.B. , Sokola Brent S. , Alluri Satya R. , Abner Erin L. , Kryscio Richard J. , Pekcec Anton , Schlichtiger Juli , Bauer Björn
Published: April 2018

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamateex vivoand used anin vivo/ex vivoapproach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findingsin vivoin rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A2. Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage.

SIGNIFICANCE STATEMENTThe mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A2, which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden.
Evaluating Risk After a Hazardous Waste Treatment Plant Released Persistent Organic Pollutants: Part 3, Aboriginal Health Risk and Impact
Authors: Guidotti Tee L.
Published: April 2018

On 16 October 1996, a malfunction at the Swan Hills Special Waste Treatment Center (SHSWTC) in Alberta, Canada, released an undetermined quantity of persistent organic pollutants (POPs) into the atmosphere, including polychlorinated biphenyls, dioxins, and furans. The circumstances of exposure are detailed in Part 1, Background and Policy Issues. An ecologically based, staged health risk assessment was conducted in two parts with two levels of government as sponsors. The first, called the Swan Hills Study, is described in Part 2. A subsequent evaluation, described here in Part 3, was undertaken by Health Canada and focused exclusively on Aboriginal residents in three communities living near the lake, downwind, and downstream of the SHSWTC of the area. It was designed to isolate effects on members living a more traditional Aboriginal lifestyle. Aboriginal communities place great cultural emphasis on access to traditional lands and derive both cultural and health benefits from “country foods” such as venison (deer meat) and local fish. The suspicion of contamination of traditional lands and the food supply made risk management exceptionally difficult in this situation. The conclusion of both the Swan Hills and Lesser Slave Lake studies was that although POPs had entered the ecosystem, no effect could be demonstrated on human exposure or health outcome attributable to the incident. However, the value of this case study is in the detail of the process, not the ultimate dimensions of risk. The findings of the Lesser Slave Lake Study have not been published previously and are incomplete.
Particle sources and transport in stratified Nordic coastal seas in the Anthropocene
Authors: Linders Torsten , Infantes Eduardo , Joyce Alyssa , Karlsson Therese , Ploug Helle , Hassellöv Martin , Sköld Mattias , Zetsche Eva-Maria
Published: April 2018

Particles of all origins (biogenic, lithogenic, as well as anthropogenic) are fundamental components of the coastal ocean and are re-distributed by a wide variety of transport processes at both horizontal and vertical scales. Suspended particles can act as vehicles, as well as carbon and nutrient sources, for microorganisms and zooplankton before eventually settling onto the seafloor where they also provide food to benthic organisms. Different particle aggregation processes, driven by turbulence and particle stickiness, composition, abundance and size, impact the transport and sinking behavior of particles from the surface to the seafloor. In deep coastal waters, the deposition, resuspension, and accumulation of particles are driven by particle stickiness, composition and aggregate structure. In contrast, wave-driven and bottom current-driven processes in the nepheloid benthic boundary layer of shallow waters are of greater importance to the settling behavior of particles, while the retention capacity of benthic vegetation (e.g., seagrasses) further influences particle behavior. In this review, we consider the various processes by which particles are transported, as well as their sources and characteristics, in stratified coastal waters with a focus on Nordic seas. The role of particles in diminishing the quality of coastal waters is increasing in the Anthropocene, as particle loading by rivers and surface run-off includes not only natural particles, but also urban and agricultural particles with sorbed pollutants and contaminants of organic, inorganic and microplastic composition. Human activities such as trawling and dredging increase turbidity and further impact the transport of particles by resuspending particles and influencing their vertical and horizontal distribution patterns. An interdisciplinary approach combining physical, chemical and biological processes will allow us to better understand particle transport and its impact on coastal waters and estuaries at an ecosystem level. There is a need for development of novel analytical and characterization techniques, as well as new in situ sensors to improve our capacity to follow particle dynamics from nanometer to millimeter size scales.
Fatores de risco para morte em pacientes com sepse em uma unidade de terapia intensiva
Authors: Prado Patricia Rezende do , Volpáti Natasha Varjão , Gimenes Fernanda Raphael Escobar , Atila Elisabeth , Maggi Luís Eduardo , Amaral Thatiana Lameira Maciel
Published: April 2018

Objetivo: determinar os principais fatores de risco para a morte em pacientes com sepse em uma unidade de terapia intensiva. Métodos: trata-se de uma coorte retrospectiva, onde foram incluídos 124 prontuários de pacientes que tiveram diagnóstico clínico e laboratorial de sepse. A probabilidade condicional de morte foi calculada através do método de Kaplan-Meier; o risco de morte foi estimado pela razão de risco, utilizando modelo de regressão de Cox com p<0,050. Resultados: o foco principal da infecção foi o sistema respiratório. Em relação ao desfecho, morreram 40,3% pacientes com sepse, 73,9% com sepse grave e 69,2% com choque séptico. Os pacientes com sepse abdominal e que utilizaram vasopressores apresentaram maior risco de morte. Conclusão: pacientes sépticos com fonte abdominal de infecção e fazendo uso de agentes vasopressores apresentaram maior risco de morte, enquanto que pacientes traqueostomizados tiveram melhores chances de sobreviver.
Soluble Klotho causes hypomineralization in Klotho-deficient mice
Authors: Minamizaki Tomoko , Konishi Yukiko , Sakurai Kaoru , Yoshioka Hirotaka , Aubin Jane E , Kozai Katsuyuki , Yoshiko Yuji
Published: April 2018

The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (kl/kl) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D inkl/klmice. The same effects were seen in rodent bone modelsin vitro, in which we also detected formation of a sKL complex with FGF23-FGFR and decreasedPhex(gene responsible for X-linked hypophosphatemic rickets (XLH)/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralizationin vitrowas rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.
The impact of infertility diagnosis on embryo-endometrial dialogue
Authors: Parks Jason C , McCallie Blair R , Patton Alyssa L , Al-Safi Zain A , Polotsky Alex J , Griffin Darren K , Schoolcraft William B , Katz-Jaffe Mandy G
Published: April 2018

Initial stages of implantation involve bi-directional molecular crosstalk between the blastocyst and endometrium. This study investigated an association between infertility etiologies, specifically advanced maternal age (AMA) and endometriosis, on the embryo-endometrial molecular dialogue prior to implantation. Co-culture experiments were performed with endometrial epithelial cells (EEC) and cryopreserved day 5 blastocysts (n = 41 ≥ Grade 3BB) donated from patients presenting with AMA or endometriosis, compared to fertile donor oocyte controls. Extracellular vesicles isolated from co-culture supernatant were analyzed for miRNA expression and revealed significant alterations correlating to AMA or endometriosis. Specifically, AMA resulted in 16 miRNAs with increased expression (P ≤ 0.05) and strong evidence for negative regulation toward 206 target genes.VEGFA, a known activator of cell adhesion, displayed decreased expression (P ≤ 0.05), validating negative regulation by 4 of these increased miRNAs: miR-126; 150; 29a; 29b (P ≤ 0.05). In endometriosis patients, a total of 10 significantly altered miRNAs displayed increased expression compared to controls (miR-7b; 9; 24; 34b; 106a; 191; 200b; 200c; 342-3p; 484) (P ≤ 0.05), targeting 1014 strong evidence-based genes. Three target genes of miR-106a (CDKN1A,E2F1andRUNX1) were independently validated. Functional annotation analysis of miRNA-target genes revealed enriched pathways for both infertility etiologies, including disrupted cell cycle regulation and proliferation (P ≤ 0.05). These extracellular vesicle-bound secreted miRNAs are key transcriptional regulators in embryo-endometrial dialogue and may be prospective biomarkers of implantation success. One of the limitations of this study is that it was a stimulated,in vitromodel and therefore may not accurately reflect thein-vivoenvironment.
A province-wide survey on self-reported language proficiency and its influence in global health education
Authors: Mirella Mirella Veras , Pottie Kevin , Welch Vivian , Eslava-Schmalbach Javier H. , Tugwell Peter
Published: April 2018

Objetivo De acuerdo con la literatura, el idioma es el obstáculo más común en el contexto de la atención médica y un factor de riesgo asociado con resultados negativos. El objetivo de este estudio es presentar las diferencias percibidas entre los estudiantes de enfermería que hablan un idioma y aquellos que hablan dos o más (competencia lingüística reportada por ellos mismos) y sus habilidades y necesidades de aprendizaje en salud global.Método Estudio observacional de corte transversal entre estudiantes de enfermería de cinco universidades de Ontario. Se diseñó una encuesta para medir el conocimiento, las habilidades y las necesidades de aprendizaje en salud global.Resultados Se observó que los estudiantes que hablan más de dos idiomas tienen mayor probabilidad de interesarse más en aprender sobre problemas de salud global, los riesgos para la salud y su asociación con los viajes y la migración (p=0,44), así como sobre los determinantes sociales de la salud (p=0,042).Conclusión Es necesario que se brinde capacitación en aprendizaje de otros idiomas a los estudiantes de enfermería para que puedan afrontar las barreras impuestas por el lenguaje en los contextos de atención médica y mejorar la salud global, de manera local e internacional.
Análise dos principais elementos presentes nas missões de hospitais brasileiros de excelência
Authors: Bruno Bruno Rosa Ossanes , Rogério Rogério João Lunkes , Paula Paula De Souza
Published: April 2018

Objetivo Analizar los elementos presentes en las misiones de los hospitales brasileños de excelencia internacional.Métodos Se recolectaron los elementos de la misión en los sitios web de los hospitales brasileños de excelencia internacional.Resultados De los ocho elementos propuestos por Pearce II (1982), los que más se destacaron y que aparecen con más frecuencia en la misión de los hospitales fueron: la mención a productos y servicios y la competencia de los mismos. En el estudio, se identificó, también, la exigencia de elementos no encontrados en ninguna de las misiones analizadas. Estos elementos son: el dominio geográfico; supervivencia, crecimiento o rentabilidad y preocupación por la imagen pública.Conclusiones Así, se percibe que ninguna de las misiones analizadas presentó los ocho elementos propuestos por Pearce II (1982) para llegar a ser eficiente. Este hecho puede afectar el propósito de la organización, el cual se define a través de la misión, comprometiendo el uso de la misión como elemento esencial de la planificación estratégica.