bluuebunny/crossref_metadata_2025 huggingface dataset:
Eating and conserving bushmeat in Africa
Authors: Wilkie David S. , Wieland Michelle , Boulet Hubert , Le Bel Sebastien , van Vliet Nathalie , Cornelis Daniel , BriacWarnon Vincent , Nasi Robert , Fa Julia E.
Published: November 2016

In Africa, overhunting of tropical wildlife for food remains an intractable issue. Donors and governments remain committed to invest in efforts to both conserve and allow the sustainable use of wildlife. Four principal barriers need to be overcome: (i) communities are not motivated to conserve wildlife long‐term because they have no formal rights to benefit from wildlife, or to exclude others from taking it on their land; (ii) multispecies harvests, typical of bushmeat hunting scenarios, place large‐bodied species at risk of extinction; (iii) wildlife production cannot expand, in the same way that livestock farming can, to meet the expected growth in consumer demand; and (iv) wildlife habitat is lost through conversion to agriculture, housing, transportation networks and extractive industries. In this review, we examine the actors involved in the use of wildlife as food and discuss the possible solutions required to address urban and rural bushmeat consumption. Interventions must tackle use and conservation of wildlife through the application of context‐relevant interventions in a variety of geographies across Africa. That said, for any bushmeat solution to work, there needs to be concurrent and comparable investment in strengthening the effectiveness of protected area management and enforcement of wildlife conservation laws.
Visual system manifestations of Alzheimer's disease
Authors: Kusne Yael , Wolf Andrew B. , Townley Kate , Conway Mandi , Peyman Gholam A.
Published: November 2016

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD.
Preoperative and postoperative measurements of retinal vessel oxygen saturation in patients with different grades of cataracts
Authors: Chen Hui , Lin Haotian , Chen Wan , Zhang Bo , Xiang Wu , Gao Qianying , Chen Weirong , Liu Yizhi
Published: November 2016

Purpose

To assess the retinal vessel blood oxygen saturation preoperatively and postoperatively in patients with different grades of cataracts.

Methods

This study included 40 eyes from 40 patients with senile cataracts ranging from grade 1 to 3. All 40 eyes received standard phacoemulsification and intraocular lens implantation. The mean retinal arterial and venular oxygen saturation (SO2) levels were measured using the Oxymap system prior to, immediately after and 3 months after cataract surgery. The arterial–venular difference (AVD) was calculated as the difference between the arterial and venular saturations. Linear regression analysis was performed to identify the relationship between the lens density grades and changes in the measured retina vessel SO2.

Results

The mean age of the subjects was 64.1 ± 7.8 years, and 14 (35%) were male. The mean SO2 level increased in the retinal arterioles from 90.5 ± 7.8% to 95.0 ± 6.7% immediately postoperatively and to 98.3 ± 5.3% at 3 months after surgery (p < 0.001). The mean venular saturation levels were 43.4 ± 9.7%, 58.0 ± 8.5% and 61.9 ± 6.5% at baseline, immediately after and at 3 months postoperatively, respectively, with a statistically significant increase after surgery (p < 0.001). The mean AVD significantly decreased from 47.1 ± 8.9% before surgery to 37.1 ± 7.3% immediately after and 36.4 ± 6.4% 3 months after surgery (p < 0.02). A linear regression model indicated that denser lens opacity was significantly associated with a larger amplitude of the venular SO2 level and the AVD after cataract surgery: change of venous SO2 = 5.934–0.191 × Age + 13.534 × Lens Grade (age: p = 0.586; lens grade: p < 0.001); change in AVD = −7.438–0.037 × Age + 7.744 × Lens Grade (age: p = 0.917; lens grade: p = 0.031).

Conclusions

Retinal arterial and venular oxygen saturation levels are significantly increased after cataract surgery, and increase rates vary with the preoperative grading of lens density.
The role of retinopathy distribution and other lesion types for the definition of examination intervals during screening for diabetic retinopathy
Authors: Ometto Giovanni , Erlandsen Mogens , Hunter Andrew , Bek Toke
Published: November 2016

Purpose

It has previously been shown that the intervals between screening examinations for diabetic retinopathy can be optimized by including individual risk factors for the development of the disease in the risk assessment. However, in some cases, the risk model calculating the screening interval may recommend a different interval than an experienced clinician. The purpose of this study was to evaluate the influence of factors unrelated to diabetic retinopathy and the distribution of lesions for discrepancies between decisions made by the clinician and the risk model.

Methods

Therefore, fundus photographs from 90 screening examinations where the recommendations of the clinician and a risk model had been discrepant were evaluated. Forty features were defined to describe the type and location of the lesions, and classification and ranking techniques were used to assess whether the features could predict the discrepancy between the grader and the risk model.

Results

Suspicion of tumours, retinal degeneration and vascular diseases other than diabetic retinopathy could explain why the clinician recommended shorter examination intervals than the model. Additionally, the regional distribution of microaneurysms/dot haemorrhages was important for defining a photograph as belonging to the group where both the clinician and the risk model had recommended a short screening interval as opposed to the other decision alternatives.

Conclusions

Features unrelated to diabetic retinopathy and the regional distribution of retinal lesions may affect the recommendation of the examination interval during screening for diabetic retinopathy. The development of automated computerized algorithms for extracting information about the type and location of retinal lesions could be expected to further optimize examination intervals during screening for diabetic retinopathy.
Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat – new insights into the development of delayed cerebral hypoperfusion
Authors: Spray S. , Johansson S. E. , Radziwon‐Balicka A. , Haanes K. A. , Warfvinge K. , Povlsen G. K. , Kelly P. A. T. , Edvinsson L.
Published: November 2016

Aim

Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles.

Methods

Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration–response curves to endothelin‐1 with and without the endothelin B receptor‐selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry.

Results

We observed increased endothelin‐1‐mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin‐1‐mediated contractility was abolished by BQ788, and the vascular smooth muscle cell‐specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia.

Conclusion

Increased endothelin‐1‐mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature.
Topographic variables improve climatic models of forage species abundance in the northeastern United States
Authors: Wang Audrey , Goslee Sarah C. , Miller Douglas A. , Sanderson Matt A. , Gonet Jeffery M.
Published: November 2016

Question

Species distribution modelling has most commonly been applied to presence‐only data and to woody species. Can similar methods be used to create detailed predicted abundance maps for forage species? These predictions would be of great value for agricultural management and land‐use planning.

Location

Northeastern USA.

Methods

We used field data from 31 grazed farms to model abundances for six forage species with three statistical methods: GLM, GAM and Random Forest models. A hierarchical ecological framework encompassing climatic, edaphic and topographic variables related to the plant species requirements for water, light and temperature was used to guide variable selection.

Results

Although many species distribution modelling studies have used only climatic variables, the inclusion of topography greatly improved explanatory power. Edaphic variables contributed little more beyond the information already provided by climate and topography. Random Forest models had higher overall predictive capability, and were used to produce the final potential abundance maps for the six forage species.

Conclusions

Climate‐only predictions may be suitable for state or regional planning, but topographic variables must be included in species distribution models used to support decision‐making at the farm and field scales.
IgG4‐related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis
Authors: Bernreuther Christian , Illies Christopher , Flitsch Jörg , Buchfelder Michael , Buslei Rolf , Glatzel Markus , Saeger Wolfgang
Published: November 2016

IgG4‐related disease is an immune‐mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG‐related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4‐related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4‐related disease and, thus, IgG4‐related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4‐related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4‐positive cells per high power field and a ratio of IgG4/IgG‐positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non‐IgG‐related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4‐related disease in other organs should be modified for IgG4‐related hypophysitis, accordingly.
Age‐related small vessel disease: a potential contributor to neurodegeneration in multiple sclerosis
Authors: Geraldes Ruth , Esiri Margaret M. , DeLuca Gabriele C. , Palace Jacqueline
Published: November 2016

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system wherein, after an initial phase of transient neurological defects, slow neurological deterioration due to progressive neuronal loss ensues. Age is a major determinant of MS progression onset and disability. Over the past years, several mechanisms have been proposed to explain the key drivers of neurodegeneration and disability accumulation in MS. However, the effect of commonly encountered age‐related cerebral vessel disease, namely small vessel disease (SVD), has been largely neglected and constitutes the aim of this review. SVD shares some features with MS, that is, white matter demyelination and brain atrophy, and has been shown to contribute to the neuronal damage seen in vascular cognitive impairment. Several lines of evidence suggest that an interaction between MS and SVD may influence MS‐related neurodegeneration. SVD may contribute to hypoperfusion, reduced vascular reactivity and tissue hypoxia, features seen in MS. Venule and endothelium abnormalities have been documented in MS but the role of arterioles and of other neurovascular unit structures, such as the pericyte, has not been explored. Vascular risk factors (VRF) have recently been associated with faster progression in MS, though the mechanisms are unclear since very few studies have addressed the impact of VRF and SVD on MS imaging and pathology outcomes. Therapeutic agents targeting the microvasculature and the neurovascular unit may impact both SVD and MS and may benefit patients with dual pathology.
Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches
Authors: Cipak Gasparovic Ana , Zarkovic Neven , Zarkovic Kamelija , Semen Khrystyna , Kaminskyy Danylo , Yelisyeyeva Olha , Bottari Serge P.
Published: November 2016

The concept of oxidative stress (OS) that connects altered redox biology with various diseases was introduced 30 years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to ROS is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro‐OS. In order to investigate oxidative and nitro‐OS in human and in live animal models, circulating biomarker assays have been developed. This article provides an overview of key biomarkers used to assess lipid peroxidation and NO/NO2 signalling, thereby stressing the necessity to analyse several OS biomarkers in relation to the overall (aerobic) metabolism and health condition of patients. In addition, the potential interest of heart rate variability as the non‐invasive integrative biomarker of OS is discussed.

Linked Articles

This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
‘I Want to Bring Him from the Aeroplane to Here’: The Meaning of Animals to Children of Refugee or Migrant Backgrounds Resettled in Australia
Authors: Riggs Damien W. , Due Clemence , Taylor Nik
Published: November 2016

Separation from animals with whom children have caring relationships can lead to considerable loss and grief, perhaps especially in the case of migration. This article reports on a thematic analysis of interviews undertaken with children of migrant or refugee backgrounds who had resettled in Australia. Findings suggest that children who spoke about animals framed their experiences in ways that either evoked a sense of loss with regard to animals or referred to animals as engendering a safe haven following resettlement. The article concludes by exploring potential service responses and encourages a focus on animals' needs in the context of migration.
Anthoxanthin Polyphenols Attenuate Aβ Oligomer‐induced Neuronal Responses Associated with Alzheimer's Disease
Authors: Pate Kayla M. , Rogers McCall , Reed John Will , van der Munnik Nicholas , Vance Steven Zebulon , Moss Melissa A.
Published: November 2016

Aims

Epidemiological evidence implicates polyphenols as potential natural therapeutics for Alzheimer's disease (AD). To investigate this prospect, five anthoxanthin polyphenols were characterized for their ability to reduce amyloid‐β (Aβ) oligomer‐induced neuronal responses by two mechanisms of action, modulation of oligomerization and antioxidant activity, as well as the synergy between these two mechanisms.

Methods

Anthoxanthin oligomerization modulation and antioxidant capabilities were evaluated and correlated with anthoxanthin attenuation of oligomer‐induced intracellular reactive oxygen species (ROS) and caspase activation using human neuroblastoma cell treatments designed to isolate these mechanisms of action and to achieve dual‐action.

Results

While modulation of oligomerization resulted in only minor reductions to neuronal responses, anthoxanthin antioxidant action significantly attenuated oligomer‐induced intracellular ROS and caspase activation. Kaempferol uniquely exhibited synergism when the two mechanisms functioned in concert, leading to a pronounced reduction in both ROS and caspase activation.

Conclusions

Together, these findings identify the dominant mechanism by which these anthoxanthins attenuate Aβ oligomer‐induced neuronal responses, elucidate their prospective synergy, and demonstrate the potential of anthoxanthin polyphenols as natural AD therapeutics.
Caregiver‐directed home‐based intensive bimanual training in young children with unilateral spastic cerebral palsy: a randomized trial
Authors: Ferre Claudio L , Brandão Marina , Surana Bhavini , Dew Ashley P , Moreau Noelle G , Gordon Andrew M
Published: November 2016

Aim

To examine the efficacy of caregiver‐directed, home‐based intensive bimanual training in children with unilateral spastic cerebral palsy (USCP) using a randomized control trial.

Method

Twenty‐four children (ages 2y 6mo–10y 1mo; 10 males, 14 females) performed home‐based activities directed by a caregiver for 2 hours per day, 5 days per week, for 9 weeks (total=90h). Cohorts of children were age‐matched into groups and randomized to receive home‐based hand‐arm bimanual intensive therapy (H‐HABIT; n=12) or lower‐limb functional intensive training (LIFT‐control; n=12). Caregivers were trained before the intervention and supervised remotely via telerehabilitation. Dexterity and bimanual hand function were assessed using the Box and Blocks test (BBT) and the Assisting Hand Assessment (AHA) respectively. Caregiver perception of functional goals was measured using the Canadian Occupational Performance Measure (COPM).

Results

H‐HABIT showed greater improvement on the BBT compared to LIFT‐control and no improvement on the AHA. H‐HABIT demonstrated significant improvement in COPM‐Performance compared to LIFT‐control and both groups showed equal improvement in COPM‐Satisfaction.

Interpretation

H‐HABIT improved dexterity and performance of functional goals, but not bimanual performance, in children with USCP compared to a control group receiving intervention of equal intensity/duration that also controlled for increased caregiver attention. Home‐based models provide a valuable, family‐centered approach to achieve increased treatment intensity.
Capturing differences in dental training using a virtual reality simulator
Authors: Mirghani I. , Mushtaq F. , Allsop M. J. , Al‐Saud L. M. , Tickhill N. , Potter C. , Keeling A. , Mon‐Williams M. A. , Manogue M.
Published: November 2016

Virtual reality simulators are becoming increasingly popular in dental schools across the world. But to what extent do these systems reflect actual dental ability? Addressing this question of construct validity is a fundamental step that is necessary before these systems can be fully integrated into a dental school's curriculum. In this study, we examined the sensitivity of the Simodont (a haptic virtual reality dental simulator) to differences in dental training experience. Two hundred and eighty‐nine participants, with 1 (n = 92), 3 (n = 79), 4 (n = 57) and 5 (n = 61) years of dental training, performed a series of tasks upon their first exposure to the simulator. We found statistically significant differences between novice (Year 1) and experienced dental trainees (operationalised as 3 or more years of training), but no differences between performance of experienced trainees with varying levels of experience. This work represents a crucial first step in understanding the value of haptic virtual reality simulators in dental education.
Activity of the anticonvulsant lacosamide in experimental and human epilepsy via selective effects on slow Na+ channel inactivation
Authors: Holtkamp Dominik , Opitz Thoralf , Niespodziany Isabelle , Wolff Christian , Beck Heinz
Published: November 2016

Objective

In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage‐gated sodium channels, and their potent activity in inhibiting high‐frequency firing has been attributed to their strong use‐dependent blocking action. In chronic epilepsy, a loss of use‐dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage‐gated sodium channels. The anticonvulsant drug lacosamide (LCM) also targets sodium channels, but has been shown to preferentially affect sodium channel slow inactivation processes, in contrast to most other anticonvulsants.

Methods

We used whole‐cell voltage clamp recordings in acutely isolated cells to investigate the effects of LCM on transient Na+ currents. Furthermore, we used whole‐cell current clamp recordings to assess effects on repetitive action potential firing in hippocampal slices.

Results

We show here that LCM exerts its effects primarily via shifting the slow inactivation voltage dependence to more hyperpolarized potentials in hippocampal dentate granule cells from control and epileptic rats, and from patients with epilepsy. It is important to note that this activity of LCM was maintained in chronic experimental and human epilepsy. Furthermore, we demonstrate that the efficacy of LCM in inhibiting high‐frequency firing is undiminished in chronic experimental and human epilepsy.

Significance

Taken together, these results show that LCM exhibits maintained efficacy in chronic epilepsy, in contrast to conventional use‐dependent sodium channel blockers such as carbamazepine. They also establish that targeting slow inactivation may be a promising strategy for overcoming target mechanisms of pharmacoresistance.
Structured clinical documentation in the electronic medical record to improve quality and to support practice‐based research in epilepsy
Authors: Narayanan Jaishree , Dobrin Sofia , Choi Janet , Rubin Susan , Pham Anna , Patel Vimal , Frigerio Roberta , Maurer Darryck , Gupta Payal , Link Lourdes , Walters Shaun , Wang Chi , Ji Yuan , Maraganore Demetrius M.
Published: November 2016

Objective

Using the electronic medical record (EMR) to capture structured clinical data at the point of care would be a practical way to support quality improvement and practice‐based research in epilepsy.

Methods

We describe our stepwise process for building structured clinical documentation support tools in the EMR that define best practices in epilepsy, and we describe how we incorporated these toolkits into our clinical workflow.

Results

These tools write notes and capture hundreds of fields of data including several score tests: Generalized Anxiety Disorder‐7 items, Neurological Disorders Depression Inventory for Epilepsy, Epworth Sleepiness Scale, Quality of Life in Epilepsy–10 items, Montreal Cognitive Assessment/Short Test of Mental Status, and Medical Research Council Prognostic Index. The tools summarize brain imaging, blood laboratory, and electroencephalography results, and document neuromodulation treatments. The tools provide Best Practices Advisories and other clinical decision support when appropriate. The tools prompt enrollment in a DNA biobanking study. We have thus far enrolled 231 patients for initial visits and are starting our first annual follow‐up visits and provide a brief description of our cohort.

Significance

We are sharing these EMR tools and captured data with other epilepsy clinics as part of a Neurology Practice Based Research Network, and are using the tools to conduct pragmatic trials using subgroup‐based adaptive designs.
Individual hippocampal subfield assessment indicates that matrix macromolecules and gliosis are key elements for the increased T2 relaxation time seen in temporal lobe epilepsy
Authors: Peixoto‐Santos Jose Eduardo , Kandratavicius Ludmyla , Velasco Tonicarlo Rodrigues , Assirati Joao Alberto , Carlotti Carlos Gilberto , Scandiuzzi Renata Caldo , Salmon Carlos Ernesto Garrido , Santos Antonio Carlos dos , Leite Joao Pereira
Published: November 2016

Objective

Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE.

Methods

Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug‐resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen‐D–related [HLA‐DR]), polarized AQP4, and CSPG.

Results

Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus.

Significance

Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
Anti‐inflammatory drugs decrease infection of brain endothelial cells withEHV‐1 in vitro
Authors: Goehring L. S. , Brandes K. , Ashton L. V. , Wittenburg L. A. , Olea‐Popelka F. J. , Lunn D. P. , Soboll Hussey G.
Published: November 2016

Background

Equine herpesvirus‐associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus‐1 (EHV‐1) during cell‐associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection.

Objectives

Evaluating the role of anti‐inflammatory drugs in decreasing endothelial cell infection withEHV‐1.

Study design

In vitro assay, crossover design, multiple drug testing.

Methods

In vitro modified infectious centre assay using immortalised carotid artery endothelial cells or primary brain endothelial cells with plaque counts per well as outcome. Cells were either anti‐inflammatory drug treated or left untreated.

Results

Significant reduction of plaque count when cells were treated compared with untreated cells. No dose‐dependent effect when drug concentrations were increased to 10× dose. Treatment of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is required for significant plaque count reduction.

Main limitations

In vitro study.

Conclusions

Anti‐inflammatory drugs decrease infection of endothelial cells likely by reducing contact betweenEHV‐1 infectedPBMCand endothelial cells in vitro. The role of adhesion molecules in this process needs further investigation. In vitro results suggest anti‐inflammatory drug therapy duringEHV‐1 infection and viraemia in horses could be clinically relevant.
Syndecans – key regulators of cell signaling and biological functions
Authors: Afratis Nikolaos A. , Nikitovic Dragana , Multhaupt Hinke A. B. , Theocharis Achilleas D. , Couchman John R. , Karamanos Nikos K.
Published: November 2016

Syndecans are a small family of four transmembrane proteoglycans in mammals. They have similar structural organization, consisting of an N‐terminal ectodomain, single transmembrane domain and C‐terminal cytoplasmic domain. Over the years, the association between syndecans and the actin cytoskeleton has been established, which has consequences for the regulation of cell adhesion and migration. Specifically, ecto‐ and cytoplasmic domains are responsible for the interaction with extracellular matrix molecules and intracellular kinases, respectively. These interactions indicate syndecans as key molecules during cancer initiation and progression. Particularly syndecans interact with other cell surface receptors, such as growth factor receptors and integrins, which lead to activation of downstream signaling pathways, which are critical for the cellular behavior. Moreover, this review describes the key role of syndecans in intracellular calcium regulation and homeostasis. The syndecan‐mediated regulation of calcium metabolism is highly correlated with cells’ adhesion phenotype through the actin cytoskeleton and formation of junctions, with implications during differentiation and disease progression.
Cell death‐independent activities of the death receptors CD95, TRAILR1, and TRAILR2
Authors: Siegmund Daniela , Lang Isabell , Wajant Harald
Published: November 2016

Since their identification more than 20 years ago, the death receptors CD95, TRAILR1, and TRAILR2 have been intensively studied with respect to their cell death‐inducing activities. These receptors, however, can also trigger a variety of cell death‐independent cellular responses reaching from the activation of proinflammatory gene transcription programs over the stimulation of proliferation and differentiation to induction of cell migration. The cell death‐inducing signaling mechanisms of CD95 and the TRAIL death receptors are well understood. In contrast, despite the increasing recognition of the biological and pathophysiological relevance of the cell death‐independent activities of CD95, TRAILR1, and TRAILR2, the corresponding signaling mechanisms are less understood and give no fully coherent picture. This review is focused on the cell death‐independent activities of CD95 and the TRAIL death receptors and addresses mainly three questions: (a) how are these receptors linked to noncell death pathways at the molecular level, (b) which factors determine the balance of cell death and cell death‐independent activities of CD95 and the TRAIL death receptors at the cellular level, and (c) what are the consequences of the cell death‐independent functions of these receptors for their role in cancer and inflammatory diseases.
Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity
Authors: Guinzberg Raquel , Díaz‐Cruz Antonio , Acosta‐Trujillo Carlos , Vilchis‐Landeros María Magdalena , Vázquez‐Meza Héctor , Lozano‐Flores Carlos , Chiquete‐Felix Natalia , Varela‐Echavarría Alfredo , Uribe‐Carvajal Salvador , Riveros‐Rosas Héctor , Piña Enrique
Published: November 2016

Spatiotemporal regulation of cAMP within the cell is required to achieve receptor‐specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP‐responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own nondiffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G protein‐coupled receptor (Ado‐GPCR), bound to either A2A or A2B, but not simultaneously to both. Each isoprotein involved in each signaling cascade was identified by measuring changes in cAMP levels after receptor activation, and its participation was confirmed by antibody‐mediated inactivation. A2A‐Ado‐GPCR selective stimulation activates adenylyl cyclase 6 (AC6), which is bound to AKAP79/150, to synthesize cAMP which is used by two other AKAP79/150‐tethered proteins: protein kinase A (PKA) and phosphodiesterase 3A (PDE3A). In contrast, A2B‐Ado‐GPCR stimulation activates D‐AKAP2‐attached AC5 to generate cAMP, which is channeled to two other D‐AKAP2‐tethered proteins: guanine‐nucleotide exchange factor 2 (Epac2) and PDE3B. In both cases, prior activation of PKA or Epac2 with selective cAMP analogs prevents de novo cAMP synthesis. In addition, we show that cAMP does not diffuse between these protein macrocomplexes or ‘signalosomes’. Evidence of coimmunoprecipitation and colocalization of some proteins belonging to each signalosome is presented. Each signalosome constitutes a minimal functional signaling unit with its own machinery to synthesize and regulate a sequestered cAMP pool. Thus, each signalosome is devoted to ensure the transmission of a unique and unequivocal message through the cell.
Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss
Authors: Misumi Kento , Hayashi Akimasa , Shibahara Junji , Arita Junichi , Sakamoto Yoshihiro , Hasegawa Kiyoshi , Kokudo Norihiro , Fukayama Masashi
Published: November 2016

Aims

BAP1 and PBRM1 expression loss has been observed in multiple cancers, including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1 expression in ICC using immunohistochemistry, and analysed its association with clinicopathological and genetic features, including two histological subtypes.

Methods and results

Whole‐section slides of 108 consecutive primary ICC cases were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was observed in 21 (19.4%) and 25 (23.1%) cases, respectively, and partial loss was identified in four (3.7%) and nine (8.4%) cases. In all cases, normal bile ducts were strongly and diffusely positive for both BAP1 and PBRM1. ICC with BAP1 loss showed lower serum CA19‐9 levels, less perineural invasion, rare mucin production, weaker immunoreactivity against S‐100P and stronger immunoreactivity against N‐cadherin and NCAM. IDH mutations were identified more frequently in ICCs with BAP1 loss. All ICC with BAP1 loss corresponded to small‐duct type ICC. Multivariate Cox regression analysis showed that BAP1 loss was an independent prognostic factor for both overall and recurrence‐free survival (P < 0.05). Conversely, PBRM1 loss was found in both small‐duct type and large‐duct type ICC, and was not associated significantly with any specific characteristics, including prognosis.

Conclusion

BAP1 and PBRM1 loss is seen frequently in ICC. ICC with BAP1 loss shares features of small‐duct type ICC.
NLRP3 inflammasome may regulate inflammatory response of human periodontal ligament fibroblasts in an apoptosis‐associated speck‐like protein containing a CARD (ASC)‐dependent manner
Authors: Lu W. L. , Song D. Z. , Yue J. L. , Wang T. T. , Zhou X. D. , Zhang P. , Zhang L. , Huang D. M.
Published: November 2016

Aim

To explore the role of NLRP3 (NACHT [nucleotide‐binding oligomerization], LRR [leucine‐rich repeat] and PYD [pyrin domain] domains‐containing protein 3) inflammasome in the inflammatory response of human periodontal ligament fibroblasts (HPDLFs).

Methodology

The expression of NLRP3 and apoptosis‐associated speck‐like protein containing a CARD (ASC) in inflammatory periapical tissues and HPDLFs was examined by immunohistochemical and immunofluorescent staining. HPDLFs were stimulated with muramyl dipeptide (MDP) and lipopolysaccharide (LPS) from E. coli with or without the silencing of ASC. The expression of NLRP3, ASC and caspase‐1 was examined using quantitative real‐time polymerase chain reaction. The secretion of proinflammatory cytokines, including interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) was measured in the cell supernatant with an enzyme‐linked immunosorbent assay. Data were statistically analysed using independent sample t‐tests.

Results

Immunohistochemistry and immunocytochemistry staining revealed that NLRP3 and ASC were expressed in HPDLFs and inflammatory periapical tissues. MDP and LPS promoted the expression of NLRP3, ASC and caspase‐1 in HPDLFs (P < 0.05). The secretion of proinflammatory cytokines was also increased with MDP and LPS stimulation (P < 0.05). After silencing ASC, the secretion of IL‐1β induced by MDP and LPS was significantly attenuated (P < 0.05).

Conclusion

In HPDLFs, MDP and LPS activated NLRP3 inflammasome and induced IL‐1β secretion. ASC plays an important role in this inflammatory response.
The Problem of Predation in Zoopolis
Authors: Cormier Andrée‐Anne , Rossi Mauro
Published: November 2016

In this article, we argue that the phenomenon of predation is the source of several problems for Donaldson and Kymlicka's account of our duties towards wild and liminal animals. According to them, humans should adopt a general policy of non‐intervention with respect to predatory behaviour involving wild and liminal animals. They justify this recommendation by appealing to the status of those animals as, respectively, members of sovereign communities and denizens of human‐animal societies. Our goal is not to question their recommendation, but to challenge the reasons given in its support. On the one hand, we argue that, insofar as wild animal communities are incapable of dealing with massive predation, they do not possess the competence required for sovereignty. Moreover, we argue that, even if we leave the issue of competence aside, attributing sovereignty rights to communities including both predators and preys may not be the best way to protect wild animals’ fundamental interests. On the other hand, we argue that there exist two important disanalogies between human denizens and liminal animals, which render Donaldson and Kymlicka's denizenship framework problematic. We suggest that the ultimate justification for a general policy of non‐intervention lies in the significant risk of causing greater harm by acting otherwise, due to our limited knowledge and resources.
The general dynamic model of island biogeography revisited at the level of major flowering plant families
Authors: Lenzner Bernd , Weigelt Patrick , Kreft Holger , Beierkuhnlein Carl , Steinbauer Manuel J.
Published: November 2016

Aim

The general dynamic model (GDM) proposed by Whittaker et al. () has become a widely accepted theoretical framework in island biogeography. In this study, we explore whether GDM predictions hold when overall plant diversity is deconstructed into major plant families.

Location

101 islands from 14 oceanic archipelagos world‐wide.

Methods

Occurrence data for all species of nine large, cosmopolitan flowering plant families were used to test predictions derived from the GDM. We analysed the effects of island area and age on species richness as well as number and percentage of single‐island endemic species per family using mixed‐effect models.

Results

Total species and endemic richness as well as the percentage of endemic species showed the predicted hump‐shaped relationship with island age. The overall pattern was mainly driven by few species‐rich plant families. Varying patterns were found for individual families, some of them opposing the general trend. In most cases, native and endemic species richness peaked much earlier in the island life cycle than suggested by the GDM. The contribution of area to the explained variation of all dependent variables was much higher than that of island age.

Main conclusions

The results suggest that biodiversity‐age relationships reported for large taxonomic groups like plants are driven by only a few species‐rich clades. The way these families influence the overall patterns of species richness and endemism is related to family‐specific properties, such as evolutionary history or dispersal strategies. Deviances from the GDM predictions can hence largely be explained by family characteristics and considering taxon‐specific traits may help to further improve the explanatory power of the GDM. Families not following the expectations, like Orchidaceae, may be particularly valuable candidates to unveil so far neglected drivers of island biogeographical patterns.
Protein SUMOylation is Involved in Cell‐cycle Progression and Cell Morphology in Giardia lamblia
Authors: Di Genova Bruno M. , da Silva Richard C. , da Cunha Júlia P.C. , Gargantini Pablo R. , Mortara Renato A. , Tonelli Renata R.
Published: November 2016

The unicellular protozoa Giardia lamblia is a food‐ and waterborne parasite that causes giardiasis. This illness is manifested as acute and self‐limited diarrhea and can evolve to long‐term complications. Successful establishment of infection by Giardia trophozoites requires adhesion to host cells and colonization of the small intestine, where parasites multiply by mitotic division. The tight binding of trophozoites to host cells occurs by means of the ventral adhesive disc, a spiral array of microtubules and associated proteins such as giardins. In this work we show that knock down of the Small Ubiquitin‐like MOdifier (SUMO) results in less adhesive trophzoites, decreased cell proliferation and deep morphological alterations, including at the ventral disc. Consistent with the reduced proliferation, SUMO knocked‐down trophozoites were arrested in G1 and in S phases of the cell cycle. Mass spectrometry analysis of anti‐SUMO immunoprecipitates was performed to identify SUMO substrates possibly involved in these events. Among the identified SUMOylation targets, α‐tubulin was further validated by Western blot and confirmed to be a SUMO target in Giardia trophozoites.
Genetics of adrenocortical tumours
Authors: Åkerström T. , Carling T. , Beuschlein F. , Hellman P.
Published: November 2016

The recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease‐causing mutations have been described for aldosterone‐producing adenomas, cortisol‐producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation. Moreover, compounds that bind specifically to altered proteins may be used as screening targets or therapeutic agents. Regulation of cortisol release by interaction with an altered subunit in adenylate cyclase may be more complex, but may provide a new option for regulating steroid release. Information about derangements in adrenocortical carcinoma is already helpful for determining patient prognosis. With further knowledge, we may be able to identify novel biomarkers that effectively and noninvasively help in differentiating between benign and malignant disease. It is clear that the next few years will provide much novel information that hopefully will aid in the treatment of patients with adrenocortical tumours.
Incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study
Authors: Grönlund O. , Herweijer E. , Sundström K. , Arnheim‐Dahlström L.
Published: November 2016

Objective

To assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease.

Methods

This register‐based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006–2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new‐onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education.

Results

A total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new‐onset autoimmune diseases were observed during 245 807 person‐years at a rate of 22.1 (95% CI 21.5–22.7) new events per 1000 person‐years. In vaccinated girls and women, there were 124 new events during 7848 person‐years at a rate of 15.8 (95% CI 13.2–18.8) per 1000 person‐years. There was no increase in the incidence of new‐onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65–0.93).

Conclusion

In this nationwide study, qHPV vaccination was not associated with increased incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease.
Authors’ response: Letter to the Editor – HPV vaccine and autoimmunity
Authors: Grönlund O. , Herweijer E. , Sundström K. , Arnheim‐Dahlström L.
Published: November 2016

Click here to view the Letter to the Editor by Dr. S. Dahan & Y. Shoenfeld