bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of spatial structure after temporary herbivore absence in a high‐productivity reed marsh
Authors: Reijers Valérie C. , Cruijsen Peter M. J. M. , Hoetjes Sean C. S. , van den Akker Marloes , Heusinkveld Jannes H. T. , van de Koppel Johan , Lamers Leon P. M. , Olff Han , van der Heide Tjisse
Published: April 2019

Grazing can significantly impact spatial heterogeneity and conservation value of ecosystems. Earlier work revealed that overgrazing may stimulate persistent vegetation collapse in low‐productivity environments where vegetation survives by concentrating scarce resources within its local environment. However, it remains unclear whether grazer fluctuations may cause persistent vegetation changes in high‐productivity systems where dense stands facilitate their own survival by hampering grazer access.

Here, we experimentally tested how the release from grazing by greylag geese (Anser anser) affects spatial vegetation structure in a highly productive, brackish marsh in which dense reed (Phragmites australis) stands and bare roosting areas coexist. Next, we assessed the resilience of the change in vegetation patterning by reintroducing the geese after a 2‐year exclosure period.

During herbivore exclusion, vegetation rapidly colonized the bare areas, while reintroduction of herbivores generated a clear species‐specific response. Specifically, the pioneer species, Bolboschoenus maritimus, was immediately eradicated, while the dense and high structure of P. australis facilitated its own persistence by limiting grazer access. Surface accretion (~1 cm/year) during herbivore exclusion further amplified this herbivore‐inhibiting feedback, because greylag geese primarily rely on waterlogged conditions for grubbing.

Synthesis and applications. Our results indicate that temporary reductions in herbivore numbers may induce persistent unfavourable changes in the spatial structure of a high‐productivity system. It is therefore important to first assess whether vegetation changes are naturally reversible or persistent. If state shifts are indeed persistent, sufficiently high grazer densities must be maintained to warrant the favourable heterogeneous system. If changes in vegetation structure negatively impact grazer densities, active management such as sod cutting or mowing may be required to restore ecosystem structure and functions.
Repetitive desiccation events weaken a salt marsh mutualism
Authors: Derksen‐Hooijberg Marlous , Angelini Christine , Hoogveld Jasper R. H. , Lamers Leon P. M. , Borst Annieke , Smolders Alfons , Harpenslager Sarah Fay , Govers Laura L. , van der Heide Tjisse
Published: April 2019

Salt marshes suffered large‐scale degradation in recent decades. Extreme events such as hot and dry spells contributed significantly to this, and are predicted to increase not only in intensity, but also in frequency under future climate scenarios. Such repetitive extreme events may generate cumulative effects on ecosystem resilience. It is therefore important to elucidate how marsh vegetation responds to repetitive stress, and whether changes in key species interactions can modulate vegetation resilience.

In this study, we investigated how moderate but repetitive desiccation events, caused by the combined effects of drought and high temperatures, affect cordgrass (Spartina alterniflora), the dominant habitat‐forming grass in southeasternUSsalt marshes. In a 4‐month field experiment, we simulated four consecutive desiccation events by periodically excluding tidal flooding and rainfall, while raising temperature. We crossed this desiccation treatment with the presence/absence of ribbed mussels (Geukensia demissa) – a mutualist of cordgrass known to enhance its desiccation resilience – and with grazing pressure by the marsh periwinkle (Littoraria irrorata) that is known to suppress cordgrass’ desiccation resilience.

We found that each subsequent desiccation event deteriorated sediment porewater conditions, resulting in high salinity (53 ppt), low pH‐levels (3.7) and increased porewater Al and Fe concentrations (≈800 μmol/L and ≈1,500 μmol/L) upon rewetting. No effects on porewater chemistry were found as a result of snail grazing, while ribbed mussels strongly mitigated desiccation effects almost to control levels and increased cordgrass biomass by approximately 128%. Importantly, although cordgrass generally appeared healthy above‐ground at the end of the experiment, we found clear negative responses of the repetitive desiccation treatment on cordgrass below‐ground biomass, on proline (osmolyte) levels in shoots and on the number of tillers (−40%), regardless of mussel and/or snail presence.

Synthesis. Even though the mutualism with mussels strongly mitigated chemical effects in the sediment porewater throughout the experiment, mussels could not buffer the adverse ecophysiological effects observed in cordgrass tissue. Our results therefore suggest that although mussels may alleviate desiccation stress, the predicted increased frequency and intensity of hot dry spells may eventually affect saltmarsh resilience by stressing the mutualism beyond its buffering capacity.
KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease
Authors: Zhang Yuan , Zhang Lei , Wang Yu , Ding Han , Xue Sheng , Yu Hua , Hu Longgang , Qi Hongzhao , Wang Yin , Zhu Wenjie , Liu Dacheng , Li Peifeng
Published: April 2019

This study aimed to evaluate the potential of long noncoding RNAs (lncRNAs) as biomarkers for coronary artery disease (CAD). We measured the levels of three atherosclerosis‐ or cardiac‐related lncRNAs in peripheral blood monocyte cells (PBMCs) from 20 CAD patients and 20 non‐CAD control participants using real‐time reverse transcription–polymerase chain reaction (real‐time RT–PCR) methods. We found that the levels of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia‐inducible factor 1 alpha‐antisense RNA 2 (HIF1A‐AS2) and apolipoprotein A‐1 antisense RNA (APOA1‐AS) were significantly increased in CAD patients (KCNQ1OT1 increased by 2.38‐fold, P = 0.00042; HIF1A‐AS2 increased by 2.00‐fold, P = 0.0001; APOA1‐AS increased by 4.52‐fold, P = 0.000048). The area under the ROC curve was 0.865 for KCNQ1OT1, 0.852 for HIF1A‐AS2, and 0.967 for APOA1‐AS. Furthermore, the combination of lncRNAs resulted in a much higher AUC value of 0.990 for the prediction of CAD. Spearman's correlation analysis showed that APOA1‐AS was positively correlated with NT‐proBNP, CKMB, MYO and HsTnT, whereas HIF1A‐AS2 was correlated with NT‐proBNP and HsTnT. Hence, the elevation of KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS predicts CAD and these molecules may be considered as novel biomarkers of CAD.
Australian sugarcane soldier fly's salivary gland transcriptome in response to starvation and feeding on sugarcane crops
Authors: Etebari Kayvan , Lindsay Karel R. , Ward Andrew L. , Furlong Michael J.
Published: April 2019

The soldier fly is an endemic pest of sugarcane in Australia. Small numbers of larvae can cause significant damage to roots and reduce the crop yields. Little is known about the composition and function of the soldier fly salivary gland, its secretions, and their roles in insect‒plant interactions. In this study, we performed transcriptome analysis of the salivary glands of starved and sugarcane root‐fed soldier fly larvae. A total of 31 119 highly expressed assembled contigs were identified in the salivary glands and almost 50% of them showed high levels of similarity to known proteins in Nr databases. Of all the obtained contigs, only 9727 sequences contain an open reading frame of over 100 amino acids. Around 31% of contigs were predicted to encode secretory proteins, including some digestive and detoxifying enzymes and potential effectors. Some known salivary secreted peptides such as serine protease, cysteine proteinase inhibitors, antimicrobial peptides and venom proteins were among the top 100 highly expressed genes. Differential gene expression analysis revealed significant modulation of 850 transcripts in salivary glands upon exposure to plant roots or starvation stress. Here, we identified some venom proteins which were significantly upregulated in the salivary glands of soldier fly larvae exposed to sugarcane roots. In other insects and nematodes some of these proteins have been used to manipulate host plant defense systems and facilitate the invasion of the host plant. These findings provide a further insight into the identification of potential effector proteins involved in soldier fly‒sugarcane interactions.
Extraction of Bioactive Compounds from Pseuderanthemum palatiferum (Nees) Radlk. Using Subcritical Water and Conventional Solvents: A Comparison Study
Authors: Ho Truc Cong , Chun Byung‐Soo
Published: April 2019

The present study investigated the recovery of antioxidative compounds obtained from Pseuderanthemum palatiferum (Nees) Radlk. and their biological activities using subcritical water in comparison with hot water, Soxhlet, and methanol extraction. In this study, high‐performance liquid chromatography (HPLC) and three commonly used assays, that is, 2,2‐diphenyl‐1‐picrylhydrazyl assays, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), and ferric reducing antioxidant power, were employed to measure the number of valuable compounds and their antioxidant capacities, respectively. Additionally, the antimicrobial ability of the various extracts against seven pathogenic bacteria strains was assessed. The results demonstrated that the extracts obtained from subcritical water extraction (SWE) contain the highest amount of saponin (33.82 ± 2.08 mg diosgenin/g), phenolic (34.87 ± 0.29 mg CE/g), and protein (104.66 ± 7.63 mg BSA/g), which are obtained at 170 °C, 190 °C, and 230 °C, respectively. The highest amounts of total sugar and flavonoids (211.73 ± 1.58 mg glucose/g and 20.71 ± 0.42 mg RE/g, respectively) were obtained at lower temperature (130 °C and 130 °C, respectively), and these values were higher than those obtained from hot water, Soxhlet, and methanol extraction. HPLC analysis indicated that the highest amount of apigenin (3.46 ± 0.03 mg/g) and kaempferol (2.43 ± 0.03 mg/g) were obtained by SWE at 170 °C and 190 °C, respectively. Furthermore, the extracts from SWE exhibited higher antimicrobial activity against five of the seven pathogenic bacterial strains tested compared with those obtained from conventional extraction methods. Therefore, subcritical water could be utilized as a cost‐effective and green solvent to extract valuable compounds from P. palatiferum (Nees) Radlk. leaf.

Practical Application

Subcritical water was able to recover more bioactive compounds from the sample, such as phenolics, flavonoids, saponin, protein, and polysaccharides, than conventional solvents. The mixture of polyphenolic–polysaccharide–protein conjugates could be used in further steps, isolation, and purification, and applied to functional food.
Interleukin‐32γ: Possible association with the activity and development of nephritis in patients with systemic lupus erythematosus
Authors: Kwon Oh Chan , Ghang Byeongzu , Lee Eun‐Ju , Hong Seokchan , Lee Chang‐Keun , Yoo Bin , Kim Soohyun , Kim Yong‐Gil
Published: April 2019

Aim

Growing evidence suggests that interleukin (IL)‐32 is a cytokine involved in various autoimmune diseases. We aimed to investigate whether IL‐32γ is involved in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis (LN).

Method

Sera from SLE patients without LN (n = 47), LN patients (n = 19) and healthy controls (n = 10) were collected. The serum concentrations of inflammatory cytokines, including tumor necrosis factor‐α, interferon‐γ, IL‐6, IL‐18, and IL‐32γ, were measured using enzyme‐linked immunosorbent assay. Clinical parameters at the time of sampling were obtained from medical records, and correlations between IL‐32γ and clinical parameters were analyzed by Spearman correlation analysis. Immunohistochemistry evaluating IL‐32 expression was performed in renal tissues of LN patients and healthy controls.

Results

Among the cytokines measured in sera, the level of IL‐32γ was higher in LN patients than in SLE patients without LN and in healthy controls. Among clinical parameters, concentrations of C3/C4 were lower and erythrocyte sedimentation rate, C‐reactive protein, anti‐double‐stranded DNA (anti‐dsDNA) antibodies, and SLE Disease Activity Index‐2000 (SLEDAI‐2K) were higher in LN patients than in SLE patients without LN. IL‐32γ level was negatively correlated with C3/C4 and positively correlated with anti‐dsDNA antibodies and the renal component of SLEDAI‐2K. In LN patients, IL‐32γ level was positively correlated with the activity and chronicity indices. IL‐32 expression was significantly higher in renal tissues of LN patients than in healthy controls.

Conclusion

IL‐32γ could be associated with the activity and development of LN in SLE.
Peptides stimulating synthesis of extracellular matrix used in anti‐ageing cosmetics: Are they clinically tested? A systematic review of the literature
Authors: Michalek Irmina Maria , Lelen‐Kaminska Karolina , Caetano dos Santos Florentino Luciano
Published: April 2019

Peptides stimulating synthesis of extracellular matrix are now commonly used in the production of anti‐ageing cosmetics. However, much uncertainty still exists about the methodology of their clinical assessment. The aim of the study was to review the literature for clinical study designs assessing the efficacy of these peptides. The authors searched systematically publications indexed in PubMed, Scope and Web of Science, according to the PRISMA protocol. Altogether 12 scientific papers, reporting results of 15 independent studies were identified. Out of these 15 studies, only six used a placebo control. Double‐blinding was applied in five out of 15 studies. Nine studies were based on female‐only populations. For the product performance evaluation, most of the studies (10 out of the 15) used image‐based methods. The literature on the topic is sparse. The studies carried out so far have many methodological limitations. Most of the clinical experiments hitherto conducted were non‐double‐blind and used no placebo control. There is a need for better planned and controlled clinical trials in this area.
Great minds think different: Preserving cognitive diversity in an age of gene editing
Authors: Anomaly Jonathan , Gyngell Christopher , Savulescu Julian
Published: April 2019

It is likely that gene editing technologies will become viable in the current century. As scientists uncover the genetic contribution to personality traits and cognitive styles, parents will face hard choices. Some of these choices will involve trade‐offs from the standpoint of the individual's welfare, while others will involve trade‐offs between what is best for each and what is good for all. Although we think we should generally defer to the informed choices of parents about what kinds of children to create, we argue that decisions to manipulate polygenic psychological traits will be much more ethically complicated than choosing Mendelian traits like blood type. We end by defending the principle of regulatory parsimony, which holds that when legislation is necessary to prevent serious harms, we should aim for simple rules that apply to all, rather than micro‐managing parental choices that shape the traits of their children. While we focus on embryo selection and gene editing, our arguments apply to all powerful technologies which influence the development of children.
Fertility desires and reproductive needs of transgender people: Challenges and considerations for clinical practice
Authors: Feigerlová Eva , Pascal Véronique , Ganne‐Devonec Marie‐Odile , Klein Marc , Guerci Bruno
Published: April 2019

The majority of transgender and gender nonconforming persons seeking medical care are of reproductive age. Hormonal treatment and sex reassignment surgery, which are used in the management of gender dysphoria, compromise fertility potential. Children and adolescents with gender dysphoria have specific treatment regimens starting with puberty‐blocking medications. According to international guidelines, fertility preservation should be discussed before any hormonal treatment, although our knowledge on the reproductive needs of transgender and gender nonconforming persons is limited. Recently, some data have emerged on fertility management in some centres for the adult population with gender dysphoria. The goal of this review was to summarize the available evidence on the fertility desires and parental roles of transgender and gender nonconforming people. In light of newly emerging societal challenges, we aim to provide some considerations for clinical practice and suggest further areas of research.
Relating characteristics of global biodiversity targets to reported progress
Authors: Green Elizabeth J. , Buchanan Graeme M. , Butchart Stuart H. M. , Chandler Georgina M. , Burgess Neil D. , Hill Samantha L. L. , Gregory Richard D.
Published: April 2019

To inform governmental discussions on the nature of a revised Strategic Plan for Biodiversity of the Convention on Biological Diversity (CBD), we reviewed the relevant literature and assessed the framing of the 20 Aichi Biodiversity Targets in the current strategic plan. We asked international experts from nongovernmental organizations, academia, government agencies, international organizations, research institutes, and the CBD to score the Aichi Targets and their constituent elements against a set of specific, measurable, ambitious, realistic, unambiguous, scalable, and comprehensive criteria (SMART based, excluding time bound because all targets are bound to 2015 or 2020). We then investigated the relationship between these expert scores and reported progress toward the target elements by using the findings from 2 global progress assessments (Global Biodiversity Outlook and the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services). We analyzed the data with ordinal logistic regressions. We found significant positive relationships (p < 0.05) between progress and the extent to which the target elements were perceived to be measurable, realistic, unambiguous, and scalable. There was some evidence of a relationship between progress and specificity of the target elements, but no relationship between progress and ambition. We are the first to show associations between progress and the extent to which the Aichi Targets meet certain SMART criteria. As negotiations around the post‐2020 biodiversity framework proceed, decision makers should strive to ensure that new or revised targets are effectively structured and clearly worded to allow the translation of targets into actionable policies that can be successfully implemented nationally, regionally, and globally.
Motor function in children with congenital Zika syndrome
Authors: Melo Adriana , Gama Gabriela L , Da Silva Júnior Renan A , De Assunção Paula L , Tavares Jousilene S , Da Silva Mariana B , Costa Kamila N F S , Vânia Mell L , Evangelista Morgana A , De Amorim Melania M R
Published: April 2019

Aim

To evaluate gross motor function and associated factors in children with congenital Zika syndrome (CZS).

Method

Fifty‐nine children (30 males, 29 females) with CZS at a mean (SD) age of 14.7 (3.9), months (range 5–29mo) were evaluated using the Gross Motor Function Measure (GMFM) and classified according to the Gross Motor Function Classification System (GMFCS). Neurological damage was evaluated by neuroimaging. The mothers’ sociodemographic characteristics and general data on the children were obtained from interviews with the mothers and from the children's medical records. Correlational and multiple regression analyses were performed to identify factors associated with these children's motor function.

Results

In 81% of the children, motor function impairment was severe, classified as GMFCS level V. The overall GMFM score ranged from 5 to 210 (median 18; interquartile range 11), with only four children receiving scores in the D and E dimensions. The factors found to affect motor function were the presence of severe malformations of cortical development and small head circumference at birth.

Interpretation

Although motor impairment may be mild in some children, it is generally severe. Severe malformations of cortical development and small head circumference at birth were factors associated with poorer motor function, reflecting the greater severity of brain damage.

What this paper adds

Motor impairment is severe in most children with congenital Zika syndrome (CZS).

Motor skills are adequate or close to adequate for age in 7% of children with CZS.

Severe malformations of cortical development are associated with poor motor control.

Small head circumference at birth is also associated with poor motor control.
No beneficial effects of aspirin on secondary cardiovascular prevention in patients with type 2 diabetes using non‐steroidal anti‐inflammatory drugs
Authors: Tsujimoto Tetsuro , Kajio Hiroshi
Published: April 2019

There is little evidence on whether non‐steroidal anti‐inflammatory drugs (NSAIDs) and aspirin interact in secondary cardiovascular prevention in type 2 diabetic patients. This is an observational study using data from the Action to Control Cardiovascular Risk in Diabetes and Follow‐on studies. Hazard ratios (HRs) for mortality with 95% confidence intervals (95% CIs) were calculated using Cox proportional hazard models to compare time to death in patients using and not using aspirin who were simultaneously using or not using NSAIDs. A total of 3600 type 2 diabetic patients with cardiovascular disease were included. During a mean follow‐up period of 8.8 years, 948 patients died. After adjustments, the risk of all‐cause mortality in patients not using NSAIDs was significantly lower in those using aspirin than in those not using aspirin (HR, 0.81; 95% CI, 0.70‐0.93; P = 0.004). The risk in patients using NSAIDs did not differ significantly between the two groups. There was a significant interaction between aspirin use and NSAIDs use. In type 2 diabetic patients with cardiovascular disease, aspirin use was not beneficial for those using NSAIDs.
Loss of striatal tyrosine‐hydroxylase interneurons impairs instrumental goal‐directed behavior
Authors: Kaminer Jaime , Espinoza Diego , Bhimani Shaznaan , Tepper James M. , Koos Tibor , Shiflett Michael W.
Published: April 2019

The striatum mediates a broad range of cognitive and motor functions. Within the striatum, recently discovered tyrosine hydroxylase expressing interneurons (THINs) provide a source of intrastriatal synaptic connectivity that is critical for regulating striatal activity, yet the role of THIN's in behavior remains unknown. Given the important role of the striatum in reward‐based behaviors, we investigated whether loss of striatal THINs would impact instrumental behavior in mice. We selectively ablated striatal THINs in TH‐Cre mice using chemogenetic techniques, and then tested THIN‐lesioned or control mice on three reward‐based striatal‐dependent instrumental tests: (a) progressive ratio test; (b) choice test following selective‐satiety induced outcome devaluation; (c) outcome reinstatement test. Both striatal‐THIN‐lesioned and control mice acquired an instrumental response for flavored food pellets, and their behavior did not differ in the progressive ratio test, suggesting intact effort to obtain rewards. However, striatal THIN lesions markedly impaired choice performance following selective‐satiety induced outcome devaluation. Unlike control mice, THIN‐lesioned mice did not adjust their choice of actions following a change in outcome value. In the outcome reinstatement test THIN‐lesioned and control mice showed response invigoration by outcome presentation, suggesting the incentive properties of outcomes were not disrupted by THIN lesions. Overall, we found that striatal THIN lesions selectively impaired goal‐directed behavior, while preserving motoric and appetitive behaviors. These findings are the first to describe a function of striatal THINs in reward‐based behavior, and further illustrate the important role for intrastriatal interneuronal connectivity in behavioral functions ascribed to the striatum more generally.
The puzzle of philosophical testimony
Authors: Ranalli Chris
Published: April 2019

An epistemologist tells you that knowledge is more than justified true belief. You trust them and thus come to believe this on the basis of their testimony. Did you thereby come to know that this view is correct? Intuitively, there is something intellectually wrong with forming philosophical beliefs on the basis of testimony, and yet it's hard to see why philosophy should be significantly epistemically different from other areas of inquiry in a way that would fully prohibit belief by testimony. This, I argue, is the puzzle of philosophical testimony. In this paper, I explore the puzzle of philosophical testimony and its ramifications. In particular, I examine the case for pessimism about philosophical testimony—the thesis that philosophical belief on the basis of testimony is impossible or is in some way illegitimate—and I argue that it lacks adequate support. I then consider whether the source of the apparent intellectual wrongness of testimonial‐based philosophical belief is grounded in non‐epistemic norms and goals of philosophical practice itself and argue that such norms are implausible, don't conflict with testimonial‐based philosophical belief, or else are mere disciplinary norms, lacking substantial normative force that would make it wrong to form testimonial‐based philosophical belief.
CFP‐1 interacts with HDAC1/2 complexes in C. elegans development
Authors: Pokhrel Bharat , Chen Yannic , Biro Jonathan Joseph
Published: April 2019

CXXC finger binding protein 1 (CFP‐1) is an evolutionarily conserved protein that binds to non‐methylated CpG‐rich promoters in mammals and Caenorhabditis elegans. This conserved epigenetic regulator is part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET‐2 in C. elegans. Previous studies have indicated the importance of CFP1 in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action of CFP1 is well understood at the organismal level. Here, we have used cfp‐1(tm6369) and set‐2(bn129) C. elegans mutants to investigate the function of CFP‐1 in gene induction and development. We have characterised C. elegansCOMPASS mutants cfp‐1(tm6369) and set‐2(bn129) and found that both cfp‐1 and set‐2 play an important role in the regulation of fertility and development of the organism. Furthermore, we found that both cfp‐1 and set‐2 are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt‐inducible genes. Interestingly, we found that cfp‐1 but not set‐2 genetically interacts with histone deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP‐1 outside of the COMPASS complex. Additionally, we found that cfp‐1 and set‐2 independently regulate fertility and development of the organism. Our results suggest that CFP‐1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within the COMPASS complex. We propose that CFP‐1 could cooperate with the COMPASS complex and/or HDAC1/2 in a context‐dependent manner.
Crystal structure and activation mechanism of DR3 death domain
Authors: Yin Xueying , Li Wenqian , Ma Huan , Zeng Weihong , Peng Chao , Li Yajuan , Liu Muziying , Chen Quan , Zhou Rongbin , Jin Tengchuan
Published: April 2019

Death receptor 3 (DR3) (a.k.a. tumor necrosis factor receptor superfamily 25) plays a key role in the immune system by activating nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling pathway. Here we present the crystal structures of human and mouse DR3 intracellular death domain (DD) at 2.7 and 2.5 Å resolutions, respectively. The mouse DR3 DD adopts a classical six‐helix bundle structure while human DR3 DD displays an extended fold. Though there is one‐amino‐acid difference in the linker between maltose‐binding protein (MBP) tag and DR3 DD, according to our self‐interaction analysis, the hydrophobic interface discovered in MBP–hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. Furthermore, our biochemical analysis indicates that the sequence variation between human and mouse DR3 DD does not affect its structure and function. Small‐angle X‐ray scattering analysis shows the averaged solution structures of both human and mouse MBP‐DR3 DD are the combination of different conformations with different proportion. Through switching to the open conformation, DR3 DD could improve the interaction with downstream element TNFR‐associated death domain (TRADD). Here we propose an activation‐dependent structural rearrangement model: the DD region is folded as the six‐helix bundles in the resting state, while upon extracellular ligand engagement, it switches to the open conformation, which facilitates its self‐association and the recruitment of TRADD. Our results provide detailed insights into the architecture of DR3 DD and the molecular mechanism of activation.

Databases

All refined structure coordinates as well as the corresponding structure factors have been deposited in the PDB under the accession codes 5YGS, 5YEV, 5YGP, 5ZNY, 5ZNZ.
Mucocutaneous manifestations in systemic amyloidosis A retrospective analytical study in a tertiary care center
Authors: Flores‐Bozo Luis‐Rodrigo , Echevarría‐Keel Josune , Domínguez‐Cherit Judith , Esquivel‐Pedraza Lilly , Méndez‐Flores Silvia
Published: April 2019

Background

The mucocutaneous clinical profile of patients with amyloidosis in Latin America has been scarcely reported.

Objective

To describe clinical characteristics of skin and mucosal manifestations in systemic amyloidosis in a tertiary care center in Mexico City.

Methods

A cross sectional, retrospective analytical study was performed in patients with systemic amyloidosis over a 15‐year period. Statistical analysis was done.

Results

A total of 98 patients were included (53 [54%] men; overall median age = 49 years old). Acquired systemic immunoglobulin light chain amyloidosis (AL) was the most common (49%) type, followed by (24.5%) wild‐type transthyretin amyloidosis (H‐TTR) (24.5%), undetermined cases (21%), and reactive systemic amyloidosis (AA) (6.1%). There were mucocutaneous manifestations in 34.7% of cases, mostly multiple myeloma‐related AL (ALMM). Head and neck was the most often affected site (38.2%), and purpuric macules were the most common morphology (44.1%). Mucocutaneous affectation was predominantly observed in AL (50.0%) compared to other types (20.0%) of amyloidosis (P = 0.01). Likewise, involvement of organs was also significantly different among the diverse amyloidosis types (P < 0.05). The most frequent comorbidities were hypertension (18.3%) and hypothyroidism (18.3%).

Conclusion

The clinical spectrum of manifestations in amyloidosis is wide. Involvement of skin and mucosa in amyloidosis is common; significant differences were observed concerning distribution of mucocutaneous amyloid manifestations among the different types of amyloidosis.
Borderline high serum calcium levels are associated with arterial stiffness and 10‐year cardiovascular disease risk determined by Framingham risk score
Authors: Park Byoungjin , Lee Yong‐Jae
Published: April 2019

Recent epidemiological data indicate that the concentration of circulating calcium is related to cardiovascular disease (CVD) mortality. We determined whether serum calcium level is related to arterial stiffness and 10‐year CVD risk calculated by Framingham risk score (FRS). We examined the association of normal‐range serum calcium level with arterial stiffness and FRS in 565 Korean adults participating at the Health Promotion Center of Gangnam Severance Hospital between March 2016 and May 2017. High brachial‐ankle pulse wave velocity (baPWV) was defined as >1460 cm/s, and high FRS was defined as ≥10 percent for 10‐year CVD risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for high baPWV and high FRS were calculated using multiple logistic regression analysis after adjusting for confounding variables. The OR (95% CI) for high baPWV was 3.91 (1.15‐7.36) per 1 mg/dL increment of serum calcium after adjusting for age, sex, body mass index, smoking status, exercise regularity, alcohol consumption, mean blood pressure, fasting plasma glucose, triglyceride, HDL‐cholesterol, C‐reactive protein, γ‐glutamyltransferase, uric acid level, phosphate level, potassium level, and presence of hypertension, diabetes and dyslipidemia medications (P = 0.024). A positive association between serum calcium level and high FRS was also observed after adjusting for the same covariables (OR, 3.54 [95% CI, 1.01‐12.44],P = 0.048). Serum calcium level was independently and positively associated with baPWV and 10‐year CVD risk estimates. Early detection of higher serum calcium level may be important for the assessment of arterial stiffness and future risk of a cardiovascular event.
Therapeutic efficacy of anti‐MMP9 antibody in combination with nab‐paclitaxel‐based chemotherapy in pre‐clinical models of pancreatic cancer
Authors: Awasthi Niranjan , Mikels‐Vigdal Amanda J. , Stefanutti Erin , Schwarz Margaret A. , Monahan Sheena , Smith Victoria , Schwarz Roderich E.
Published: April 2019

Matrix metalloproteinase 9 (MMP9) is involved in the proteolysis of extracellular proteins and plays a critical role in pancreatic ductal adenocarcinoma (PDAC) progression, invasion and metastasis. The therapeutic potential of an anti‐MMP9 antibody (αMMP9) was evaluated in combination with nab‐paclitaxel (NPT)‐based standard cytotoxic therapy in pre‐clinical models of PDAC. Tumour progression and survival studies were performed in NOD/SCID mice. The mechanistic evaluation involved RNA‐Seq, Luminex, IHC and Immunoblot analyses of tumour samples. Median animal survival compared to controls was significantly increased after 2‐week therapy with NPT (59%), Gem (29%) and NPT+Gem (76%). Addition of αMMP9 antibody exhibited further extension in survival: NPT+αMMP9 (76%), Gem+αMMP9 (47%) and NPT+Gem+αMMP9 (94%). Six‐week maintenance therapy revealed that median animal survival was significantly increased after NPT+Gem (186%) and further improved by the addition of αMMP9 antibody (218%). Qualitative assessment of mice exhibited that αMMP9 therapy led to a reduction in jaundice, bloody ascites and metastatic burden. Anti‐MMP9 antibody increased the levels of tumour‐associated IL‐28 (1.5‐fold) and decreased stromal markers (collagen I, αSMA) and the EMT marker vimentin. Subcutaneous tumours revealed low but detectable levels of MMP9 in all therapy groups but no difference in MMP9 expression. Anti‐MMP9 antibody monotherapy resulted in more gene expression changes in the mouse stroma compared to the human tumour compartment. These findings suggest that anti‐MMP9 antibody can exert specific stroma‐directed effects that could be exploited in combination with currently used cytotoxics to improve clinical PDAC therapy.
Healthy eating interventions in adults living with and beyond colorectal cancer: a systematic review
Authors: Aubrey V. , Hon Y. , Shaw C. , Burden S.
Published: April 2019

Background

Rates of cancer survival are increasing, with more people living with and beyond cancer. Lifestyle recommendations for cancer survivors are based largely on extrapolation from cancer prevention recommendations. The present study aimed to systematically review the literature on randomised controlled trials (RCTs) focusing on healthy eating interventions in people with colorectal cancer (CRC).

Methods

A structured search of electronic databases was conducted in March 2018 using medical subject headings (MeSH) and text words related to CRC and diet. The results of the literature searches were uploaded to online software for data management. Titles and abstracts were screened based on the inclusion and exclusion criteria and data were extracted. Quality of data was assessed using the Cochrane Handbook.

Results

Seven studies were identified, including six RCTs and one RCT protocol, with a total of 2233 participants from six studies, of whom 1010 (45%) had CRC. Three studies assessed anthropometrics demonstrating participants who received dietary intervention had a greater reduction in measurements. Six studies assessed changes in dietary components; however, only one demonstrated an increase in dietary fibre. Two studies reported improvements in quality of life favouring dietary intervention groups.

Conclusions

The quality of identified studies was variable, with limited evidence to support dietary intervention improving dietary intake in people living with or after CRC. Studies to date have not been based on robust study design that has combined all dietary interventions linked to CRC. As a result of the heterogeneity of the studies identified, it was difficult to draw strong conclusions.
The barriers and enablers to achieving adequate calcium intake in young adults: a qualitative study using focus groups
Authors: Rouf A. , Clayton S. , Allman‐Farinelli M.
Published: April 2019

Background

Despite the established benefits of calcium consumption, many young Australians are not meeting the recommendations for calcium intake. This is concerning because an adequate calcium consumption is important throughout young adulthood to reach peak bone mass and for the prevention of osteoporosis. Therefore, the present study aimed to explore the barriers and enablers to consuming calcium‐rich foods with young adults.

Methods

Using a semi‐structured question guide, five focus group discussions were conducted with 39 participants [mean (SD) age 22.5 (1.8) years]. Participants were mostly females (n = 29) and enrolled in tertiary education (n = 31). A deductive approach was used to group common ideas into themes. The findings from the focus groups were analysed using the COM‐B framework, which examines the interactions between three key components (i.e. capability, opportunity and motivation).

Results

On examining the young adults' capability to consume a diet adequate in calcium, it was found that young adults had limited knowledge of sources, prevention of disease and recommended amounts. Some participants voiced physical barriers to consumption (lactose intolerance). Opportunity was reported as a physical (availability of calcium‐rich foods), financial and social opportunity. Some participants reported motivation to include dairy as a result of the habit becoming engrained during their childhood under parental influence (automatic motivation), whereas others reflected on a lack of awareness relating to inadequacy and health consequences (reflective motivation).

Conclusions

Although social media was seen to be an acceptable mode of intervention, concerns were raised about the source and credibility of the information. The findings may inform the development of future interventions targeting eating habits of young adults.
Transcriptome landscape of the early Brassica napus seed
Authors: Ziegler Dylan J. , Khan Deirdre , Kalichuk Jenna L. , Becker Michael G. , Belmonte Mark F.
Published: April 2019

Brassica napus L. (canola) is one of the world's most economically important oilseeds. Despite our growing knowledge of Brassica genetics, we still know little about the genes and gene regulatory networks underlying early seed development. In this work, we use laser microdissection coupled with RNA sequencing to profile gene activity of both the maternal and filial subregions of the globular seed. We find subregions of the chalazal end including the chalazal endosperm, chalazal proliferating tissue, and chalazal seed coat, have unique transcriptome profiles associated with hormone biosynthesis and polysaccharide metabolism. We confirm that the chalazal seed coat is uniquely enriched for sucrose biosynthesis and transport, and that the chalazal endosperm may function as an important regulator of the maternal region through brassinosteroid synthesis. The chalazal proliferating tissue, a poorly understood subregion, was specifically enriched in transcripts associated with megasporogenesis and trehalose biosynthesis, suggesting this ephemeral structure plays an important role in both sporophytic development and carbon nutrient balance, respectively. Finally, compartmentalization of transcription factors and their regulatory circuits has uncovered previously unknown roles for the chalazal pole in early seed development.
Cutaneous epitheliotropic lymphoma in a baboon (Papiospp.): A case report and a brief literature review
Authors: Carias Elvira , DeLorenzo Megan , Owston Michael , Gonzalez Olga , Kumar Shyamesh , Dick Jr Edward J.
Published: April 2019

Cutaneous epitheliotropic lymphoma (CEL) has not been reported in non‐human primates. We report the first case of CEL in a 9‐year‐old baboon. The phenotype of the neoplastic cells in this baboon is similar to CEL in humans (CD3+, CD4+, CD8−) and different from dogs (CD3+, CD4−, CD8+).
Mutual Gains? Health‐Related HRM, Collective Well‐Being and Organizational Performance
Authors: Huettermann Hendrik , Bruch Heike
Published: April 2019

Research on the effects of HR management on employees’ psychological well‐being has yielded inconclusive results. Moreover, prior works remain unclear on whether human resource practices specifically aimed at enhancing employee well‐being also benefit organizational performance. Building on signaling theory and conservation of resources theory, our study investigates the relationship between health‐related human resource management (HHRM), employees’ collective well‐being (in terms of collective emotional exhaustion and collective engagement) and organizational performance. Results from a multi‐source field study of top management team members, HR representatives, and 15,952 employees in 88 organizations reveal a positive indirect relationship between HHRM and employees’ collective well‐being, which is mediated by employees’ positive stress mindset. In addition, we find this positive indirect association to depend on the level of transformational leadership climate in organizations. Finally, our findings also show a positive indirect relationship between HHRM and company performance, mediated by employees’ positive stress mindset and collective engagement.
Mortality‐risk‐based apnea–hypopnea index thresholds for diagnostics of obstructive sleep apnea
Authors: Korkalainen Henri , Töyräs Juha , Nikkonen Sami , Leppänen Timo
Published: April 2019

The severity of obstructive sleep apnea is clinically assessed mainly using the apnea–hypopnea index. Based on the apnea–hypopnea index, patients are classified into four severity groups: non‐obstructive sleep apnea (apnea–hypopnea index < 5); mild (5 ≤ apnea–hypopnea index < 15); moderate (15 ≤ apnea–hypopnea index < 30); and severe obstructive sleep apnea (apnea–hypopnea index ≥ 30). However, these thresholds lack solid clinical and scientific evidence. We hypothesize that the current apnea–hypopnea index thresholds are not optimal despite their global use, and aim to assess this clinical shortcoming by optimizing the thresholds with respect to the risk of all‐cause mortality. We analysed ambulatory polygraphic recordings of 1,783 patients with suspected obstructive sleep apnea (mean follow‐up 18.3 years). We simulated 79,079 different threshold combinations in 100 randomized subgroups of the population and studied the relative risk of all‐cause mortality corresponding to each combination and randomization. The optimal thresholds were chosen according to three criteria: (a) the hazard ratios increase linearly between severity groups towards more severe obstructive sleep apnea; (b) each group includes at least 15% of the study population; (c) group sizes decrease with increasing obstructive sleep apnea severity. The risk of all‐cause mortality varied greatly across simulations; the threshold defining non‐obstructive sleep apnea group having the largest effect on the hazard ratios. The apnea–hypopnea index threshold combination of 3‐9‐24 was optimal in most of the subgroups. In conclusion, the assessment of obstructive sleep apnea severity based on the current apnea–hypopnea index thresholds is not optimal. Our novel approach provides methods for optimizing apnea–hypopnea index‐based severity classification, and the revised thresholds better differentiate patients into severity groups, ensuring that an increase in the severity corresponds to an increase in the risk of all‐cause mortality.
New York Yankees and Hollywood Anglos: The persistence of Anglo‐conformity in the American motion picture industry
Authors: Kaufmann Eric , Ballatore Andrea
Published: April 2019

Ideal types have received less attention than membership criteria in the ethnicity and nationalism literature. This article uses crowdsourced genealogical data and onomastics software to show that British Isles surnames and ancestry remain over‐represented among American actors, especially in roles connected with the national narrative. Conformity to the WASP ideal type persists despite the fact American actors are disproportionately born in Los Angeles, New York, and other large cities, where British ancestry is rare. Jewish actors are over‐represented, yet many have Anglo surnames. Compared to athletes and politicians, actors are significantly more likely to have Anglo surnames, especially those in genres depicting the nation. After declining among cohorts of stars born between the 1800s and 1961, the share of British Isles surnames has stabilised and remains in the majority. We argue that despite rising diversity, this reflects the continuing importance of the Anglo‐Protestant ethnic imago for American national identity.
Not all ectomycorrhizal fungal lineages are equal
Authors: Matheny P. Brandon , Fordyce James A.
Published: April 2019

This article is a Commentary on Sato & Toju, 222: 1924–1935.
A systematic review and meta‐analysis of intervention characteristics in postpartum weight management using the TIDieR framework: A summary of evidence to inform implementation
Authors: Lim Siew , Liang Xinyu , Hill Briony , Teede Helena , Moran Lisa J. , O'Reilly Sharleen
Published: April 2019

Postpartum weight retention is a significant contributor to obesity in reproductive‐aged women, but the key implementation characteristics of postpartum weight management interventions have not been systematically identified to inform policy and practice. This study aimed to evaluate the intervention characteristics associated with weight loss in postpartum women using the Template for Intervention Description and Replication (TIDieR) framework. We searched MEDLINE, CINAHL, EMBASE, PSYCINFO, and EBM databases to identify lifestyle intervention RCTs in postpartum women (within 2 years after birth) published up to January 2018. From 4512 studies, 33 studies were included in the systematic review and meta‐analysis (n = 4960 women). Health professional‐delivered interventions had significantly greater weight loss than those delivered by nonhealth professionals (mean difference, 95% confidence interval: (−3.22 kg [−4.83, −1.61] vs −0.99 kg [−1.53, −0.45], P = 0.01 for subgroup differences)). Diet and physical activity combined had significantly greater weight loss compared with physical activity‐only interventions (−3.15 kg [−4.34, −1.96] vs −0.78 kg [−1.73, 0.16], P = 0.009 for subgroup differences). The extent of weight loss was not influenced by intervention intensity (duration, number of sessions) and setting (individual or group).