bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring the colonization of alluvial deposits using multitemporal UAV RGB‐imagery
Authors: Laslier Marianne , Hubert‐Moy Laurence , Corpetti Thomas , Dufour Simon
Published: September 2019

Aims

(a) Evaluate the potential of Unmanned Aerial Vehicle (UAV) technology for very high resolution monitoring vegetation dynamics. (b) Describe and explain the colonization pattern of dewatered alluvial deposits by vegetation during early successional stages at an intra‐annual scale.

Location

Sélune River, Normandy, France.

Methods

We assessed vegetation cover using models based on UAV imagery and field samples at very fine spatial (cm) and temporal (intra‐annual) scales. A UAV flight was conducted every two months from January to July 2015, and vegetation was measured during image acquisition phases. Vegetation cover was mapped for each image acquisition date (four UAV orthomosaics) using a nonlinear regression model (Support Vector Regression algorithm). Then, the maps of vegetation cover were compared to evaluate the colonization process.

Results

Vegetation cover was predicted from UAV with high accuracy (mean correlation coefficient: 0.90). Analysis of the maps revealed that colonization of the alluvial deposits by vegetation was rapid in spring.

Conclusions

This study shows that intra‐annual vegetation dynamics on alluvial deposits is rapid and that the colonization pattern can be observed in early successional stages. Very high spatial resolution images acquired by UAV can be used to create detailed maps to evaluate vegetation cover development.
The importance of the nitric oxide‐cGMP pathway in age‐related cardiovascular disease: Focus on phosphodiesterase‐1 and soluble guanylate cyclase
Authors: Golshiri Keivan , Ataei Ataabadi Ehsan , Portilla Fernandez Eliana C. , Jan Danser A. H. , Roks Anton J. M.
Published: September 2019

Among ageing‐related illnesses, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality causing one‐third of all deaths worldwide. Ageing evokes a number of functional, pharmacological and morphological changes in the vasculature, accompanied by a progressive failure of protective and homeostatic mechanisms, resulting in target organ damage. Impaired vasomotor, proliferation, migration, antithrombotic and anti‐inflammatory function in both the endothelial and vascular smooth muscle cells are parts of the vascular ageing phenotype. The endothelium regulates these functions by the release of a wide variety of active molecules including endothelium‐derived relaxing factors such as nitric oxide, prostacyclin (PGI2) and endothelium‐derived hyperpolarization (EDH). During ageing, a functional decay of the nitric oxide pathway takes place. Nitric oxide signals to VSMC and other important cell types for vascular homeostasis through the second messenger cyclic guanosine monophosphate (cGMP). Maintenance of proper cGMP levels is an important goal in sustainment of proper vascular function during ageing. For this purpose, different components can be targeted in this signalling system, and among them, phosphodiesterase‐1 (PDE1) and soluble guanylate cyclase (sGC) are crucial. This review focuses on the role of PDE1 and sGC in conditions that are relevant for vascular ageing.
Administering elections in a digital age: Online voting in Ontario municipalities
Authors: Goodman Nicole , Spicer Zachary
Published: September 2019

To date, online voting studies have focused on impacts on political behaviour and voting security. Analyses of impacts on administrators and electoral governance remain sparse internationally and are relegated to overviews in technical reports in Canada (Pammett and Goodman 2013; Goodman and Pyman 2016). Drawing on an original survey of local administrators in Ontario following the 2014 municipal elections, this article explores how online voting impacts election administration. Findings suggest strong satisfaction with online voting, citizen‐centered rationales for adoption, and key differences in challenges and cost based on municipal size. We conclude with implications for the local governance of elections as technology plays a greater role in voting processes.
Evidence for a role of autoinflammation in early-phase psoriasis
Authors: Fanoni D , Venegoni L , Vergani B , Tavecchio S , Cattaneo A , Leone B E , Berti E , Marzano A V
Published: September 2019

Psoriasis is a common, inflammatory immune-mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of the interleukin (IL)-23/IL-17 axis. However, the mechanisms acting in papular lesions of early-phase psoriasis are not fully understood. The aim of this study was to assess the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL-1 over-production that has been recently hypothesized to act in the early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL-1β, IL-17, IL-23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co-localization experiments with immunofluorescence confocal microscopy were conducted. IL-1β was significantly more expressed in psoriasis than in normal skin (P < 0·0001). The chemokine IL-8 was also over-expressed in psoriasis (P = 0·03) while IL-12, IL-17, IL-23, tumour necrosis factor-α and interferon-γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL-1β co-localized mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL-1β over-expression in combination with low expression of cytokines that are predominant in late-phase plaque psoriasis may support the role of autoinflammation in early-phase disease, possibly paving the way to randomized trials with IL-1 antagonists.
Growth factor and receptor malfunctions associated with human genetic deafness
Authors: Naz Sadaf , Friedman Thomas B.
Published: September 2019

A variety of different signaling pathways are necessary for development and maintenance of the human auditory system. Normal hearing allows for the detection of soft sounds within the frequency range of 20 to 20 000 Hz, but more importantly to perceive the human voice frequency band of 250 to 6000 Hz. Loss of hearing is common, and is a clinically heterogeneous disorder that can be caused by environmental factors such as exposure to loud noise, infections and ototoxic drugs. In addition, variants of hundreds of genes have been reported to disrupt processes required for hearing. Noncoding regulatory variants and variants of additional genes necessary for hearing remain to be discovered as many individuals with inherited deafness are without a genetic diagnosis, despite the advent of whole exome sequencing. Here, we discuss in detail some of these deafness‐causing variants of genes encoding a ligand or its receptor. Spotlighted in this review are three growth factor‐receptor‐pairs EDN3/EDNRB, HGF/MET and JAG/NOTCH, which individually are necessary for normal hearing. We also offer our perspective on unanswered questions, future challenges and potential opportunities for treatments emerging from molecular genetic and mechanistic studies of deafness due to these causes.
Lots of loss with little scrutiny: The attrition of habitat critical for threatened species in Australia
Authors: Ward Michelle S. , Simmonds Jeremy S. , Reside April E. , Watson James E. M. , Rhodes Jonathan R. , Possingham Hugh P. , Trezise James , Fletcher Rachel , File Lindsey , Taylor Martin
Published: September 2019

Australia has one of the worst extinction rates of any nation, yet there has been little assessment of the effect of its flagship environmental legislation, the Environment Protection and Biodiversity Conservation Act 1999 (EPBC Act), to prevent species extinction. By coupling remotely sensed forest and woodland data with the distributions of 1,638 terrestrial threatened species, terrestrial migratory species, and threatened ecological communities, we quantified the loss of potential habitat and communities since the EPBC Act came into force in 2000. We found that over 7.7 million ha of potential habitat and communities were cleared in the period 2000–2017. Of this clearing, over 93% was not referred to the Federal Government for assessment, meaning the loss was not scrutinized under the EPBC Act. While 1,390 (84%) species suffered loss, Mount Cooper striped skink, Keighery's macarthuria, and Southern black‐throated finch lost 25, 23, and 10% of potential habitat, respectively. Iconic Australian species, such as koala, also lost ~1 million ha (2.3%) of potential habitat. Our analysis showed that the EPBC Act is ineffective at protecting potential habitat for terrestrial threatened species, terrestrial migratory species, or threatened ecological communities. We recommend that when scientifically determinable, critical habitat is demarcated for listed species and communities, which provides absolute protection that is enforced, monitored, and investigated by the regulator. Without a fundamental change in how environmental law is enforced, Australia faces an increasing extinction rate.
Theology and aging
Authors: Simmons Ernest L.
Published: September 2019

Introduction to the issue on aging.
Allometry of reaching and contact structures in Kukulcania hibernalis (Araneae: Filistatidae)
Authors: Barrantes Gilbert , Madrigal‐Brenes Ruth
Published: September 2019

Large part of the morphological diversity observed across taxa is attributed to the effect of sexual selection; and the static allometry of these structures vary largely from highly positive to negative, depending on their function, and position on the animal's body. In arthropods, information of how sexually selected contact and reaching male structures use during courtship scale on body size is scarce. We tested two complementary hypotheses: the reaching structure hypothesis and the contact‐function hypothesis, in the spider Kukulcania hibernalis. We used the length of the proximal segments of the male pedipalp to test the reaching structure hypothesis, and claw features to test the contact‐function hypothesis. Our results support both hypotheses. Small males have disproportionally longer pedipalps (highly negative allometry) than large males, increasing the probability of small‐bodied males to inseminate even large females. We also found that both distal contact and noncontact homologous structures scaled shallow (slope < 1) on body size, but allometry was significantly shallower for contact than for noncontact distal structures, providing support to the contact‐function hypothesis, and allowing teasing apart the effect of sexual selection on distal contact structures with dual functions.
Processing of performance errors predicts memory formation: Enhanced feedback‐related negativities for corrected versus repeated errors in an associative learning paradigm
Authors: de Bruijn Ellen R. A. , Mars Rogier B. , Hester Rob
Published: September 2019

Learning from errors or negative feedback is crucial for adaptive behavior. FMRI studies have demonstrated enhanced anterior cingulate cortex activity for errors that were later corrected versus repeated errors even when a substantial delay between the error and the opportunity to correct was introduced. We aimed at identifying the electrophysiological correlates of these processes by investigating the feedback‐related negativity (FRN) and stimulus‐locked P3. Participants had to learn and recall the location of 2‐digit targets over consecutive rounds. Feedback was provided in two steps, first a color change indicated a correct or incorrect response (feedback phase) followed by presentation of the correct digit information (re‐encoding phase). Behaviorally, participants improved performance from the first to the third round. FRN amplitudes time‐locked to feedback were enhanced for corrected compared to repeated errors. The P3 in response to re‐encoding did not differ between the two error types. The finding that FRN amplitudes positively predicted memory performance is consistent with the idea that the FRN reflects prediction errors and the need for enhanced cognitive control. Interestingly, this happens early during feedback processing and not at a later time point when re‐encoding of correct information takes place. The prediction error signal reflected in the FRN is usually elicited by performance errors, but may thus also play a role in preparing/optimizing the system for memory formation. This supports the existence of a close link between action control and memory processes even when there is a substantial delay between error feedback and the opportunity to correct the error.
Understanding the effect of competition during evolutionary radiations: an integrated model of phenotypic and species diversification
Authors: Aristide Leandro , Morlon Hélène
Published: September 2019

Competition can drive macroevolutionary change, for example during adaptive radiations. However, we still lack a clear understanding of how it shapes diversification processes and patterns. To better understand the macroevolutionary consequences of competition, as well as the signal left on phylogenetic data, we developed a model linking trait evolution and species diversification in an ecological context. We find four main results: first, competition spurs trait diversity but not necessarily species richness; second, competition produces slowdowns in species diversification even in the absence of explicit ecological limits, but not in phenotypic diversification even in the presence of such limits; third, early burst patterns do not provide a reliable way of testing for adaptive radiations; and fourth, looking for phylogenetic signal in trait data and support for phenotypic models incorporating competition is a better alternative. Our results clarify the macroevolutionary consequences of competition and could help design more powerful tests of adaptive radiations in nature.
Combining genetic crosses and pool targeted DNA‐seq for untangling genomic variations associated with resistance to multiple insecticides in the mosquito Aedes aegypti
Authors: Cattel Julien , Faucon Frédéric , Le Péron Bastien , Sherpa Stéphanie , Monchal Marie , Grillet Lucie , Gaude Thierry , Laporte Frederic , Dusfour Isabelle , Reynaud Stéphane , David Jean‐Philippe
Published: September 2019

In addition to combating vector‐borne diseases, studying the adaptation of mosquitoes to insecticides provides a remarkable example of evolution‐in‐action driving the selection of complex phenotypes. Actually, most resistant mosquito populations show multi‐resistance phenotypes as a consequence of the variety of insecticides employed and of the complexity of selected resistance mechanisms. Such complexity makes the identification of alleles conferring resistance to specific insecticides challenging and prevents the development of molecular assays to track them in the field. Here we showed that combining simple genetic crosses with pool targeted DNA‐seq can enhance the specificity of resistance allele's detection while maintaining experimental work and sequencing effort at reasonable levels. A multi‐resistant population of the mosquito Aedes aegypti was exposed to three distinct insecticides (deltamethrin, bendiocarb and fenitrothion), and survivors to each insecticide were crossed with a susceptible strain to generate three distinct lines. F2 individuals from each line were then segregated based on their survival to two insecticide doses. Hundreds of genes covering all detoxifying enzymes and insecticide targets together with more than 7,000 intergenic regions equally spread over mosquito genome were sequenced from pools of F0 and F2 individuals unexposed or surviving insecticide. Differential coverage analysis identified 39 detoxification enzymes showing an increased gene copy number in association with resistance. Combining an allele frequency filtering approach with a Bayesian FST‐based genome scan identified multiple genomic regions showing strong selection signatures together with 50 nonsynonymous variations associated with resistance. This study provides a simple and cost‐effective approach to improve the specificity of resistance allele's detection in multi‐resistant populations while reducing false positives frequently arising when comparing populations showing divergent genetic backgrounds. The identification of novel DNA resistance markers opens new opportunities for improving the tracking of insecticide resistance in the field.
Multifocal outbreak of equine influenza in vaccinated horses in Argentina in 2018: Epidemiological aspects and molecular characterisation of the involved virus strains
Authors: Olguin‐Perglione C. , Vissani M. A. , Alamos F. , Tordoya M. S. , Barrandeguy M.
Published: September 2019

Background

Equine influenza is an important cause of respiratory disease of horses worldwide. The equine influenza virus (EIV) undergoes antigenic drift through the accumulation of amino acid substitutions in the viral proteins, which may lead to vaccine breakdown.

Objectives

To describe the epidemiological findings and the molecular characteristics of the EIV detected during the multifocal outbreak that occurred in Argentina between March and July 2018 and evidence a vaccine breakdown.

Study design

Observational, descriptive study.

Methods

Virus was detected in nasopharyngeal swabs using real‐time reverse transcriptase PCR (RT‐PCR). Nucleotide and deduced amino acid sequences of the haemagglutinin (HA) and neuraminidase (NA) genes were obtained from EIV positive nasopharyngeal swabs, and phylogenetic analysis was undertaken. Amino acid sequences were compared against the current World Organisation for Animal Health (OIE)‐recommended Florida clade 1 vaccine strain and strain components of vaccines used in Argentina. Serum samples were tested using haemagglutination inhibition test.

Results

Equine influenza virus infection was confirmed using real‐time RT‐PCR and serological testing. The phylogenetic analysis of the HA and NA genes revealed that all the EIV identified during the outbreak belong to the H3N8 subtype, Florida clade 1. Multiple amino acid changes, some of them at antigenic sites, were observed in the circulating virus when compared with the strains included in the most commonly used vaccine in Argentina. Seventy‐six percent of the affected horses had been vaccinated with this vaccine, suggesting the occurrence of vaccine breakdown.

Main limitations

The study does not include antigenic characterisation and full genome sequencing of Argentinian strains, that could provide additional information.

Conclusions

The occurrence of this multifocal equine influenza outbreak in regularly vaccinated horses is a field evidence of vaccine breakdown, reinforcing the necessity of keeping vaccine strains updated according to OIE recommendations. It also underlines the importance of the implementation of appropriate quarantine measures and restriction of horse movement in the face of disease.
The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies
Authors: Knackstedt Rebecca , Knackstedt Thomas , Gatherwright James
Published: September 2019

There is increasing evidence that the intestinal microbiome plays an important role in modulating systemic inflammation and disease. Oral probiotics can modulate the intestinal microbiome and have demonstrated to be efficacious in treating topical skin conditions, such as atopic dermatitis, acne and rosacea. By proxy, exogenous application to the skin of probiotics should also promote a positive bacterial balance to mitigate or potentially eliminate pathologic conditions. The goal of this article was to provide a systematic review of studies that have investigated the role of topical probiotics in mitigating skin conditions. Additionally, skin conditions where dysbiosis has been identified but topical probiotics have not been investigated are discussed. We hope this review both analyses the evidence for the role that topical probiotics could play in topical skin conditions and highlights additional areas in need of research and exploration.
Tree growth declines and mortality were associated with a parasitic plant during warm and dry climatic conditions in a temperate coniferous forest ecosystem
Authors: Bell David M. , Pabst Robert J. , Shaw David C.
Published: September 2019

Insects and pathogens are widely recognized as contributing to increased tree vulnerability to the projected future increasing frequency of hot and dry conditions, but the role of parasitic plants is poorly understood even though they are common throughout temperate coniferous forests in the western United States. We investigated the influence of western hemlock dwarf mistletoe (Arceuthobium tsugense) on large (≥45.7 cm diameter) western hemlock (Tsuga heterophylla) growth and mortality in a 500 year old coniferous forest at the Wind River Experimental Forest, Washington State, United States. We used five repeated measurements from a long‐term tree record for 1,395 T. heterophylla individuals. Data were collected across a time gradient (1991–2014) capturing temperature increases and precipitation decreases. The dwarf mistletoe rating (DMR), a measure of infection intensity, varied among individuals. Our results indicated that warmer and drier conditions amplified dwarf mistletoe effects on T. heterophylla tree growth and mortality. We found that heavy infection (i.e., high DMR) resulted in reduced growth during all four measurement intervals, but during warm and dry intervals (a) growth declined across the entire population regardless of DMR level, and (b) both moderate and heavy infections resulted in greater growth declines compared to light infection levels. Mortality rates increased from cooler‐wetter to warmer‐drier measurement intervals, in part reflecting increasing mortality with decreasing tree growth. Mortality rates were positively related to DMR, but only during the warm and dry measurement intervals. These results imply that parasitic plants like dwarf mistletoe can amplify the impact of climatic stressors of trees, contributing to the vulnerability of forest landscapes to climate‐induced productivity losses and mortality events.
Potential of the Community Counts registry to characterize rare bleeding disorders
Authors: Gupta Sweta , Acharya Suchitra , Roberson Christopher , Lail Alice , Soucie J. Michael , Shapiro Amy
Published: September 2019

Introduction

Rare bleeding disorders (RBDs) comprise of heterogeneous coagulation factor deficiencies and platelet disorders that are underreported worldwide.

Aim

First report on RBD data from United States haemophilia treatment center network (USHTCN).

Methods

A national surveillance system for the federally recognized USHTCN developed in collaboration with the Centers for Disease Control and Prevention (CDC) and American Thrombosis and Haemostasis Network (ATHN) was queried for patients with RBDs. Patient counts were extracted from the HTC Population Profile (HTC PP) component including limited data on patients followed through the USHTCN, and from the Registry component, including patient authorized, detailed clinical data. The prevalence of RBDs in the United States was estimated based on the HTC PP data and compared to the expected national prevalence based on data extrapolated from Orphanet, an international registry.

Results

Based on the estimated prevalence of RBD in the overall 2017 US population, the cases in the HTC network were lower than expected for FI, FII, FX, and FV + FVIII deficiencies by 36%, 61%, 75% and 94%, respectively, and higher than expected for FXIII, FV, FVII, and FXI deficiencies by 7%, 14%, 33% and 185%, respectively. The proportion of RBD patients reported in the HTC PP, enrolled in the Registry, was 10.8%.

Conclusions

There is a clear need to identify individuals with RBDs who could benefit from the comprehensive care provided in the USHTCN. In addition, increased enrolment of people with all RBDs in the Registry is needed to improve knowledge of treatment outcomes of patients with RBDs in the United States.
Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018
Authors: Lee Ju Yup , Kim Nayoung , Nam Ryoung Hee , In Choi Soo , Lee Jung Won , Lee Dong Ho
Published: September 2019

Background

Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea.

Methods

The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method.

Results

An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively).

Conclusions

The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.
THE CONCEPT OF TRANSPARENCY, ITS HISTORY, AND THE THEORY OF BEGRIFFSGESCHICHTE
Authors: Dunstall Andrew
Published: September 2019

In this review essay, I examine the theoretical assumptions required in order to reconstruct an understanding of another historical period. Stefanos Geroulanos has produced a masterful history of mid‐twentieth‐century French thought, and he argues for a significant difference between that period and our own based on the values and ideas associated with the concept of transparency. The book is innovative in both its method and interpretation of the period of 1945–1984. However, despite the suggestive theoretical framework announced at its start, Geroulanos prefers to explore the theoretical content of conceptual history more than to explain how one might go about identifying, understanding, and translating the concepts of a different epoch. In order to contribute to what is already a successful project, I endeavor to extend some of Geroulanos's theoretical sketches through a comparison with Reinhart Koselleck's theory of Begriffsgechichte. Despite some muted criticism of Koselleck from Geroulanos, I argue that the projects share similar commitments, although Geroulanos needs to develop his theoretical premises at greater length, both for a full comparison and in order to complete the critical project that Transparency appears to be undertaking.
Measurement of the mechanical properties of silver and enamel thick films using nanoindentation
Authors: Walch Emmanuel Bastien Tommy , Roos Christian
Published: September 2019

Analyzing material properties of thick film multilayers deposited onto soda‐lime silicate glass raises several challenges since these layers can exhibit complex multiphase microstructures. The mechanical properties of sintered silver and glass enamel thick films have been investigated using nanoindentation methods to provide deeper understanding of the composite stack in‐service failure mechanisms. The spatial distribution of the Young's modulus and hardness have been studied on the cross section of the layers to avoid the influence of surface roughness and underlying glass substrate. The apparent indentation fracture toughness of the layers has been evaluated via SEM and high‐resolution surface topography images of the hardness imprints. A modified Berkovich indenter has been employed to study the elastic and plastic deformation regimes while the fracture deformation regime has been investigated using a cube‐corner indenter. In the enamel layer, copper chromite spinel pigments were found to provide a beneficial effect on the films mechanical performance due to their significantly higher elastic, hardness, and toughness properties compared to the surrounding amorphous phase. The amorphous phase of the enamel layer and the glass substrate has comparable mechanical properties, while the fracture toughness of sintered silver is higher, partially explaining the failure initiation in the enamel layer.
Assessment of the techno‐functionality, starch digestion rates and protein quality of rice flour–whey protein instant powders produced in a twin extruder
Authors: Heredia‐Olea Erick , Contreras‐Alvarado Maria Dolores , Perez‐Carrillo Esther , Rosa‐Millán Julian De la , Serna‐Saldivar Sergio Othón
Published: September 2019

Whey protein concentrate (WPC) is an important raw material for the production of instant beverages due to its protein properties. A central composite design was devised to analyse the effects of thermoplastic extrusion of 2:1 rice flour:WPC blends in physical, chemical–nutritional and functional properties. Three main factors were selected, screw speed (225–375 r.p.m.), conditioning moisture (17%–23%) and temperature (120–180 °C) to evaluate effects on water absorption (WAI) and solubility (WSI) indexes, viscoamylograph cold and final viscosities, in vitro protein and starch digestibilities and starch hydrolysis indexes (HI). A second‐order model showed that linear parameters were significant for all variables studies. Conditioning moisture affected properties more significantly than temperature and screws speed. The best treatment (16% moisture conditioning, 180 °C last barrel zone and screws rotating at 350 r.p.m.) in terms of water solubility had high starch in vitro digestibility and excellent protein quality determined in vitro and in vivo with weanling rats.
Pseudotumours in haemophilia: non‐adherence, under‐reporting bleeds or bad luck?
Authors: Mezhov Veronica , Campbell Sally , Powell Anne , Tran Huyen
Published: September 2019

Pseudotumours are a rare, severe complication of haemophilia which can occur in a spectrum of bones and soft tissues. It consists of an encapsulated blood collection, and as the swelling increases causes compression and eventual slow destruction of surrounding structures. Presented here are two cases of patients with haemophilia and pseudotumours, which demonstrate the heterogeneity of presenting symptoms and of treatment options.
Cancer immune escape: MHC expression in primary tumours versus metastases
Authors: Garrido Federico , Aptsiauri Natalia
Published: September 2019

Tumours can escape T‐cell responses by losing major histocompatibility complex (MHC)/ human leucocyte antigen (HLA) class I molecules. In the early stages of cancer development, primary tumours are composed of homogeneous HLA class I‐positive cancer cells. Subsequently, infiltration of the tumour by T cells generates a vast diversity of tumour clones with different MHC class I expressions. A Darwinian type of T‐cell‐mediated immune selection results in a tumour composed solely of MHC class I‐negative cells. Metastatic colonization is a highly complex phenomenon in which T lymphocytes and natural killer cells play a major role. We have obtained evidence that the MHC class I phenotype of metastatic colonies can be highly diverse and is not necessarily the same as that of the primary tumour. The molecular mechanisms responsible for MHC/HLA class I alterations are an important determinant of the clinical response to cancer immunotherapy. Hence, immunotherapy can successfully up‐regulate MHC/HLA class I expression if the alteration is reversible (‘soft’), leading to T‐cell‐mediated tumour regression. In contrast, it cannot recover this expression if the alteration is irreversible (‘hard’), when tumour cells escape T‐cell‐mediated destruction with subsequent cancer progression. This review summarizes clinical and experimental data on the complexity of immune escape mechanisms used by tumour cells to avoid T and natural killer cell responses. We also provide in‐depth analysis of the nature of MHC/HLA class I changes during metastatic colonization and contribute evidence of the enormous diversity of MHC/HLA class I phenotypes that can be produced by tumour cells during this process.
Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
Authors: Funes Samanta C. , Ríos Mariana , Gómez‐Santander Felipe , Fernández‐Fierro Ayleen , Altamirano‐Lagos María J. , Rivera‐Perez Daniela , Pulgar‐Sepúlveda Raul , Jara Evelyn L. , Rebolledo‐Zelada Diego , Villarroel Alejandra , Roa Juan C. , Mackern‐Oberti Juan P. , Kalergis Alexis M.
Published: September 2019

Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme‐oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL‐Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti‐nuclear antibody‐positive mice throughout 60–70 days, and the clinical score was evaluated. Long‐term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL‐Faslpr lupus‐prone mice. Additionally, decreased levels of anti‐nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone‐loaded tolDCs could improve only some SLE symptoms and reduced anti‐nuclear antibodies. This is the first study to evaluate antigen‐specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.
THIORIDAZINE IN THE TREATMENT OF DEPRESSIVE PATIENTS
Authors: de Jonghe F. E. R. E. R. , Schalken H. F. A. , van der Helm H. J.
Published: September 2019

In a double‐blind study of 44 depressive in‐patients, treatment with placebo appeared to give equally good results as did treatment with thioridazine. Both treatment procedures permitted the additional prescription of chlordiazepoxide when the patient's condition indicated the need for anxiety reduction. The use of chlordiazepoxide was more frequently necessary with treatment with placebo than with treatment with thioridazine.
Recurrent atrial fibrillation/flutter detection after ablation or cardioversion using the AliveCor KardiaMobile device: iHEART results
Authors: Goldenthal Isaac L. , Sciacca Robert R. , Riga Teresa , Bakken Suzanne , Baumeister Maurita , Biviano Angelo B. , Dizon Jose M. , Wang Daniel , Wang Ketty C , Whang William , Hickey Kathleen T. , Garan Hasan
Published: September 2019

Objective

This study evaluated the impact of daily ECG (electrocardiogram) self‐recordings on time to documented recurrent atrial fibrillation (AF) or atrial flutter (AFL) and time to treatment of recurrent arrhythmia in patients undergoing catheter radiofrequency ablation (RFA) or direct current cardioversion (DCCV) for AF/AFL.

Background

AF recurrence rates after RFA and DCCV are 20% to 45% and 60% to 80%, respectively. Randomized trials comparing mobile ECG devices to standard of care have not been performed in an AF/AFL population after treatment.

Methods

Of 262 patients consented, 238 were randomized to either standard of care (123) or to receive the iHEART intervention (115). Patients in the intervention group were provided with and trained to use an AliveCor KardiaMobile ECG monitor, and were instructed to take and transmit daily ECG recordings. Data were collected from transmitted ECG recordings and patients’ electronic health records.

Results

In a multivariate Cox model, the likelihood of recurrence detection was greater in the intervention group (hazard ratio = 1.56, 95% confidence interval [CI]: 1.06‐2.30, P = .024). Hazard ratios did not differ significantly for RFA and DCCV procedures. Recurrence during the first month after ablation strongly predicted later recurrence (hazard ratio = 4.53, 95% CI: 2.05‐10.00, P = .0006). Time from detection to treatment was shorter for the control group (hazard ratio = 0.33, 95% CI: 0.57‐2.92, P < .0001).

Conclusions

The use of mobile ECG self‐recording devices allows for earlier detection of AF/AFL recurrence and may empower patients to engage in shared health decision‐making.
Icariin promotes angiogenesis in glucocorticoid‐induced osteonecrosis of femoral heads: In vitro and in vivo studies
Authors: Yu Huachen , Yue Ju’an , Wang Weiguo , Liu Pei , Zuo Wei , Guo Wanshou , Zhang Qidong
Published: September 2019

The injury and dysfunction of the femoral head microvascular endothelial cells are associated with the pathogenesis of glucocorticoid‐induced osteonecrosis of the femoral head (ONFH). Reports indicate that icariin (ICA) can enhance vascular roles and also inhibit endothelial cell dysfunction. However, it still remains unclear whether ICA can promote angiogenesis in glucocorticoid‐induced ONFH. In this study, we investigate this hypothesis through in vitro and in vivo experiments. Results showed that 0.1 mg/mL hydrocortisone significantly suppressed bone microvascular endothelial cells (BMECs) proliferation while ICA at 10−5 mol/L reversed this inhibition. ICA significantly promoted BMECs migration, tube formation, the angiogenesis‐related cytokines expression and the activation of Akt. Furthermore, ICA enhanced Bcl‐2 expression but diminished Bax expression. According to in vivo results, rats with ICA treatment exhibited a lower ratio of empty lacunae, higher volume of blood vessels and more CD31‐positive cells. This study revealed that ICA promotes angiogenesis of BMECs in vitro and improves femoral head blood vessel volume of rats treated with glucocorticoid, suggesting the efficacy of ICA in the prevention of glucocorticoid‐induced ONFH.
Reciprocal regulation of miR‐206 and IL‐6/STAT3 pathway mediates IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer cells
Authors: Yang Yanhua , Wang Wei , Chang Hong , Han Zenglei , Yu Xinjuan , Zhang Tingguo
Published: September 2019

Persistently activated IL‐6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) in non–small‐cell lung cancer (NSCLC) treatment. miR‐206 has been verified to be dysregulated and plays as a negative regulator in lung cancer. However, whether miR‐206 may overcome IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer remains elusive. In this study, we investigated the role of miR‐206 in IL6‐induced gefitinib‐resistant EGFR‐mutated lung cancer cell lines. We showed that forced miR‐206 expression restored gefitinib sensitivity in IL6‐induced gefitinib‐resistant EGFR‐mutant lung cancer cells by inhibiting IL6/JAK1/STAT3 pathway. Specifically, mechanistic investigations revealed that miR‐206 blocked IL‐6/STAT3 signalling via directly targeting the 3'‐UTR of intracellular IL‐6 messenger RNA. Moreover, IL‐6 induced miR‐206 down‐regulation by reducing the cropping process of primary miR‐206 (pri‐miR‐206) into the Drosha/DGCR8 complex. Taken together, our findings reveal a direct role of miR‐206 in regulating IL‐6/STAT3 pathway and contrarily activated IL‐6/STAT3 signalling mediates the miR‐206 maturation process in gefitinib‐resistant EGFR‐mutant lung cancer cells.
Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats
Authors: Zhou Renpeng , Zhu Fei , Wu Xiaoshan , Song Sujing , Chen Yong , Zhu Chuanjun , Dai Beibei , Qian Xuewen , Wang Ke , Hu Wei , Chen Feihu
Published: September 2019

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that eventually leads to joint deformities and loss of joint function. Previous studies have demonstrated a close relationship between autophagy and the development of RA. Although autophagy and apoptosis are two different forms of programmed death, the relationship between them in relation to RA remains unclear. In this study, we explored the effect of autophagy on apoptosis of articular chondrocytes in vivo and in vitro. Adjuvant arthritis (AA) and acid‐induced primary articular chondrocyte apoptosis were used as in vivo and in vitro models, respectively. Articular chondrocyte autophagy and apoptosis were both observed dynamically in AA rat articular cartilage at different stages (15 days, 25 days and 35 days). Moreover, chondrocyte apoptosis and articular cartilage injury in AA rats were increased by the autophagy inhibitor 3‐methyladenine (3‐MA) and decreased by the autophagy activator rapamycin. In addition, pre‐treatment with 3‐MA increased acid‐induced chondrocyte apoptosis, while pre‐treatment with rapamycin reduced acid‐induced chondrocyte apoptosis in vitro. These results suggest that autophagy might be a potential target for the treatment of RA.
Sperm competitive advantage of a rare mitochondrial haplogroup linked to differential expression of mitochondrial oxidative phosphorylation genes
Authors: Zeh Jeanne A. , Zawlodzki Maya A. , Bonilla Melvin M. , Su‐Keene Eleanor J. , Padua Michael V. , Zeh David W.
Published: September 2019

Maternal inheritance of mitochondria creates a sex‐specific selective sieve through which mitochondrial mutations harmful to males but not females accumulate and contribute to sexual differences in longevity and disease susceptibility. Because eggs and sperm are under disruptive selection, sperm are predicted to be particularly vulnerable to the genetic load generated by maternal inheritance, yet evidence for mitochondrial involvement in male fertility is limited and controversial. Here, we exploit the coexistence of two divergent mitochondrial haplogroups (A and B2) in a Neotropical arachnid to investigate the role of mitochondria in sperm competition. DNA profiling demonstrated that B2‐carrying males sired more than three times as many offspring in sperm competition experiments than A males, and this B2 competitive advantage cannot be explained by female mitochondrial haplogroup or male nuclear genetic background. RNA‐Seq of testicular tissues implicates differential expression of mitochondrial oxidative phosphorylation (OXPHOS) genes in the B2 competitive advantage, including a 22‐fold upregulation of atp8 in B2 males. Previous comparative genomic analyses have revealed functionally significant amino acid substitutions in differentially expressed genes, indicating that the mitochondrial haplogroups differ not only in expression but also in DNA sequence and protein functioning. However, mitochondrial haplogroup had no effect on sperm number or sperm viability, and, when females were mated to a single male, neither male haplogroup, female haplogroup nor the interaction between male/female haplogroup significantly affected female reproductive success. Our findings therefore suggest that mitochondrial effects on male reproduction may often go undetected in noncompetitive contexts and may prove more important in nature than is currently appreciated.
Co‐evolution of cerebral and cerebellar expansion in cetaceans
Authors: Muller Amandine Sophie , Montgomery Stephen Hugh
Published: September 2019

Cetaceans possess brains that rank among the largest to have ever evolved, either in terms of absolute mass or relative to body size. Cetaceans have evolved these huge brains under relatively unique environmental conditions, making them a fascinating case study to investigate the constraints and selection pressures that shape how brains evolve. Indeed, cetaceans have some unusual neuroanatomical features, including a thin but highly folded cerebrum with low cortical neuron density, as well as many structural adaptations associated with acoustic communication. Previous reports also suggest that at least some cetaceans have an expanded cerebellum, a brain structure with wide‐ranging functions in adaptive filtering of sensory information, the control of motor actions, and cognition. Here, we report that, relative to the size of the rest of the brain, both the cerebrum and cerebellum are dramatically enlarged in cetaceans and show evidence of co‐evolution, a pattern of brain evolution that is convergent with primates. However, we also highlight several branches where cortico‐cerebellar co‐evolution may be partially decoupled, suggesting these structures can respond to independent selection pressures. Across cetaceans, we find no evidence of a simple linear relationship between either cerebrum and cerebellum size and the complexity of social ecology or acoustic communication, but do find evidence that their expansion may be associated with dietary breadth. In addition, our results suggest that major increases in both cerebrum and cerebellum size occurred early in cetacean evolution, prior to the origin of the major extant clades, and predate the evolution of echolocation.
When food regimes become hegemonic: Agrarian India through a Gramscian lens
Authors: Brown Trent
Published: September 2019

The concept of food regimes, as developed by Friedmann and McMichael, has proven useful in analysing how systems of food production, distribution, and consumption are linked to cycles of global capital accumulation and identifying the contradictions and conflicts that underlie them. A question that food regime analysis is relatively less able to address, however, is how food regimes become established and endure with the apparent acquiescence of those who are the victims of their contradictions and inequities. In this paper, I argue that a deeper engagement with Gramsci's theory of hegemony may help to address this lacuna in food regime analysis. To illustrate my case, I draw on studies of rural India from the colonial period to the present day, highlighting the ways in which the hegemonic mechanisms of consent and coercion have been crucial to the consolidation of each of the three food regimes identified by Friedmann and McMichael.