bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nature-based solution in practice: ecological and economic modelling shows pollinators outperform agrochemicals in oilseed crop production
Authors: Catarino Rui , Bretagnolle Vincent , Perrot Thomas , Vialloux Fabien , Gaba Sabrina
Published: May 2019

Abstrat

Nature-based agriculture, reducing dependency on chemical inputs, requires using ecological principles for sustainable agro-ecosystems, balancing ecology, economics and social justice. There is growing evidence that pollinator-dependent crops with high insect pollination service can give higher yields. However, the interacting effects between insect pollination and agricultural inputs on crop yields and farm economics remain to be established to reconcile food production with biodiversity conservation. We investigated the effects of insect pollination and agricultural inputs on oilseed rape (Brassica napusL.). We show that not only yield but also gross margins are 16-40% higher in fields with higher pollinator abundance than in fields with reduced pollinator abundance. This effect is however strongly reduced by pesticides use. Higher yields may be achieved by either increasing agrochemicals (reducing pests) or increasing bee abundance, but crop economic returns was only increased by the latter, because pesticides did not increase yields while their costs reduced gross margins.
Machine learning-based detection of insertions and deletions in the human genome
Authors: Curnin Charles , Goldfeder Rachel L. , Marwaha Shruti , Bonner Devon , Waggott Daryl ,   Undiagnosed Diseases Network, Wheeler Matthew T. , Ashley Euan A.
Published: May 2019

Insertions and deletions (indels) make a critical contribution to human genetic variation. While indel calling has improved significantly, it lags dramatically in performance relative to single-nucleotide variant calling, something of particular concern for clinical genomics where larger scale disruption of the open reading frame can commonly cause disease. Here, we present a machine learning-based approach to the detection of indel breakpoints called Scotch. This novel approach improves sensitivity to larger variants dramatically by leveraging sequencing metrics and signatures of poor read alignment. We also introduce a meta-analytic indel caller, called Metal, that performs a “smart intersection” of Scotch and currently available tools to be maximally sensitive to large variants. We use new benchmark datasets and Sanger sequencing to compare Scotch and Metal to current gold standard indel callers, achieving unprecedented levels of precision and recall. We demonstrate the impact of these improvements by applying this tool to a cohort of patients with undiagnosed disease, generating plausible novel candidates in 21 out of 26 undiagnosed cases. We highlight the diagnosis of one patient with a 498-bp deletion in HNRNPA1 missed by traditional indel-detection tools.
The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)
Authors: Sparks A. M. , Watt K. , Sinclair R. , Pilkington J. G. , Pemberton J. M. , McNeilly T. N. , Nussey D. H. , Johnston S. E.
Published: May 2019

Host-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection is likely to shape the outcome of these interactions, with important consequences for the fitness of both host and parasite. However, little is known about how genetic variation contributes to variation in immune responses under natural conditions. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematodeTeladorsagia circumcinctain the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable, ranging from 0.21 to 0.39 in lambs and from 0.23 to 0.57 in adults. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively; this region was adjacent to two candidate loci, the Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex on chromosome 18. Adult IgE levels and lamb IgG levels were associated with the major histocompatibility complex (MHC) on chromosome 20. This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.

Author summary

Host-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection shapes the outcome of these interactions, with important consequences for the ability of the host and parasite to survive and reproduce. However, little is known about how much genes contribute to variation in immune responses under natural conditions. Our study investigates the genetic architecture of variation in three antibody types, IgA, IgE and IgG in a wild population of Soay sheep on the St Kilda archipelago in North-West Scotland. Using data collected over 26 years, we show that antibody levels have a heritable basis in lambs and adults and are stable over lifetime of individuals. We also identify several genomic regions with large effects on immune responses. Our study offers the first insights into the genetic control of immunity in a wild population, which is essential to understand how immune profiles vary in challenging natural conditions and how natural selection maintains genetic variation in complex immune traits.
A toxin-antidote CRISPR gene drive system for regional population modification
Authors: Champer Jackson , Lee Yoo Lim , Yang Emily , Liu Chen , Clark Andrew G. , Messer Philipp W.
Published: May 2019

Engineered gene drives have been suggested as a mechanism for rapidly spreading genetic alterations through a population. One promising type of drive is the CRISPR homing drive, which has recently been demonstrated in several organisms. However, such drives face a major obstacle in the form of resistance against the drive that typically evolves rapidly. In addition, homing-type drives are generally self-sustaining, meaning that a drive would likely spread to all individuals of a species even when introduced at low frequency in a single location. Here, we develop a new form of CRISPR gene drive, the Toxin-Antidote Recessive Embryo (TARE) drive, which successfully limits resistance by targeting a recessive lethal gene while providing a recoded sequence to rescue only drive-carrying individuals. Our computational modeling shows that such a drive will have threshold-dependent dynamics, spreading only when introduced above a frequency threshold that depends on the fitness cost of the drive. We demonstrate such a drive in Drosophila with 88-95% transmission to the progeny of female drive heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. Our results suggest that TARE drives constitute promising candidates for the development of effective, regionally confined population modification drives.
Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network
Authors: Cleuren Yamila N. Torres , Ewe Chee Kiang , Chipman Kyle C. , Mears Emily , Wood Cricket G. , Al-Alami Coco A.E. , Alcorn Melissa R. , Turner Thomas L. , Joshi Pradeep M. , Snell Russell G. , Rothman Joel H.
Published: May 2019

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into theC. elegansendoderm GRN. While some natural variants show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement andvice-versa,suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.
Modularity and evolution of flower shape: the role of efficiency, development, and spandrels inErica
Authors: Reich Dieter , Berger Andreas , von Balthazar Maria , Chartier Marion , Sherafati Mahboubeh , Klingenberg Christian P. , Manafzadeh Sara , Staedler Yannick M.
Published: May 2019

Three hypotheses can explain floral modularity: the attraction-reproduction, the efficiency, and the developmental hypotheses.

In order to test these hypotheses and understand if pollination specialisation and pollination syndrome influence floral modularity, we focussed on the genusErica: we gathered 3D data from flowers of species with diverse pollination syndromes via Computed Tomography, and analysed their shape via geometric morphometrics. In order to provide an evolutionary framework for our results we tested the evolutionary mode of floral shape, size, and integration under pollination syndrome regimes, and - for the first time-reconstructed the high-dimensional floral shape of their most recent common ancestor.

We demonstrate, for the first time, that the modularity of generalist flowers depends on development and that of specialists is linked to efficiency: in bird syndrome flower, efficiency modules were associated with pollen deposition and receipt, whereas in long-proboscid fly syndrome, they were associated with restricting the access to the floral reward. Only shape PC1 showed selection towards multiple optima, suggesting that PC1 was co-opted by evolution to adapt flowers to novel pollinators. Whole floral shape followed an OU model of evolution, and demonstrated relatively late differentiation.

Flower shape modularity thus crucially depends on pollinator specialisation and class.
Multi-Scale Network Regression for Brain-Phenotype Associations
Authors: Xia Cedric Huchuan , Ma Zongming , Cui Zaixu , Bzdok Danilo , Bassett Danielle S. , Satterthwaite Theodore D. , Shinohara Russell T. , Witten Daniela M.
Published: May 2019

Complex brain networks are increasingly characterized at different scales, including global summary statistics, community connectivity, and individual edges. While research relating brain networks to demographic and behavioral measurements has yielded many insights into brain-phenotype relationships, common analytical approaches only consider network information at a single scale, thus failing to incorporate rich information present at other scales. Here, we designed, implemented, and deployed Multi-Scale Network Regression (MSNR), a penalized multivariate approach for modeling brain networks that explicitly respects both edge- and community-level information by assuming a low rank and sparse structure, both encouraging less complex and more interpretable modeling. Capitalizing on a large neuroimaging cohort (n = 1, 051), we demonstrate that MSNR recapitulates interpretable and statistically significant association between functional connectivity patterns with brain development, sex differences, and motion-related artifacts. Notably, compared to single-scale methods, MSNR achieves a balance between prediction performance and model complexity, with improved interpretability. Together, by jointly exploiting both edge- and community-level information, MSNR has the potential to yield novel insights into brain-behavior relationships.
Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants
Authors: Wang Lu , Chu Chin-Yi , McCall Matthew N. , Slaunwhite Christopher , Holden-Wiltse Jeanne , Corbett Anthony , Falsey Ann R. , Topham David J. , Caserta Mary T. , Mariani Thomas J , Walsh Edward E. , Qiu Xing
Published: May 2019

Background

A substantial number of infants infected with RSV develop severe symptoms requiring hospitalization. We currently lack accurate biomarkers that are associated with severe illness.

Method

We defined airway gene expression profiles based on RNA sequencing from nasal brush samples from 106 full-tem previously healthy RSV infected subjects during acute infection (day 1-10 of illness) and convalescence stage (day 28 of illness). All subjects were assigned a clinical illness severity score (GRSS). Using AIC-based model selection, we built a sparse linear correlate of GRSS based on 41 genes (NGSS1). We also built an alternate model based upon 13 genes associated with severe infection acutely but displaying stable expression over time (NGSS2).

Results

NGSS1 is strongly correlated with the disease severity, demonstrating a naïve correlation (ρ) of ρ=0.935 and cross-validated correlation of 0.813. As a binary classifier (mild versus severe), NGSS1 correctly classifies disease severity in 89.6% of the subjects following cross-validation. NGSS2 has slightly less, but comparable, accuracy with a cross-validated correlation of 0.741 and classification accuracy of 84.0%.

Conclusion

Airway gene expression patterns, obtained following a minimally-invasive procedure, have potential utility for development of clinically useful biomarkers that correlate with disease severity in primary RSV infection.
Accessible and reproducible mass spectrometry imaging data analysis in Galaxy
Authors: Föll Melanie Christine , Moritz Lennart , Wollmann Thomas , Stillger Maren Nicole , Vockert Niklas , Werner Martin , Bronsert Peter , Rohr Karl , Grüning Björn Andreas , Schilling Oliver
Published: May 2019

Background

Mass spectrometry imaging is increasingly used in biological and translational research as it has the ability to determine the spatial distribution of hundreds of analytes in a sample. Being at the interface of proteomics/metabolomics and imaging, the acquired data sets are large and complex and often analyzed with proprietary software or in-house scripts, which hinder reproducibility. Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many MSI researchers.

Findings

We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis. Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration. Further, we created hands-on training material for use cases in proteomics and metabolomics. To demonstrate the utility of our tools, we re-analyzed a publicly available N-linked glycan imaging dataset. By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.

Conclusion

The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access together with high levels of reproducibility and transparency.
Inheritance of seed and rhizosphere microbial communities through plant–soil feedback and soil memory
Authors: Kong Hyun Gi , Song Geun Cheol , Ryu Choong‐Min
Published: May 2019

Since the discovery of the role of microbes in the phytobiome, microbial communities (microbiota) have been identified and characterized based on host species, development, distribution, and condition. The microbiota in the plant rhizosphere is believed to have been established prior to seed germination and innate immune development. However, the microbiota in seeds has received little attention. Although our knowledge of the distribution of microbiota in plant seeds and rhizosphere is currently limited, the impact of these microbiota is likely to be greater than expected. This minireview suggests a new function of microbial inheritance from the seed to root and from the first generation of plants to the next. Surprisingly, recruitment and accumulation of microbiota by biotic and abiotic stresses affect plant immunity in the next generation through plant–soil feedback and soil memory. To illustrate this process, we propose a new term called ‘microbiota‐induced soil inheritance (MISI).’ A comprehensive understanding of MISI will provide novel insights into plant–microbe interactions and plant immunity inheritance.
Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways
Authors: Jiang Ming , Zhou Li‐Yang , Xu Nan , An Qing
Published: May 2019

Background

Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown.

Methods

Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299.

Results

Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone.

Conclusion

HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC.
Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2
Authors: Drissi Ichrak , Deschamps Chloé , Fouquet Grégory , Alary Rachel , Peineau Stéphane , Gosset Philippe , Sueur Harold , Marcq Ingrid , Debuysscher Véronique , Naassila Mickael , Vilpoux Catherine , Pierrefiche Olivier
Published: May 2019

Ethanol (EtOH) induces cognitive impairment through modulation of synaptic plasticity notably in the hippocampus. The cellular mechanism(s) of these EtOH effects may range from synaptic signaling modulation to alterations of the epigenome. Previously, we reported that two binge‐like exposures to EtOH (3 g/kg, ip, 9 h apart) in adolescent rats abolished long‐term synaptic depression (LTD) in hippocampus slices, induced learning deficits, and increased N‐methyl‐d‐aspartate (NMDA) receptor signaling through its GluN2B subunit after 48 hours. Here, we tested the hypothesis of EtOH‐induced epigenetic alterations leading to modulation of GluN2B and GluN2A NMDA receptor subunits. Forty‐two days old rats were treated with EtOH or the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB, 600 mg/kg, ip) injected alone or 30 minutes before EtOH. After 48 hours, learning was tested with novel object recognition while synaptic plasticity and the role of GluN2A and GluN2B subunits in NMDA‐fEPSP were measured in CA1 field of hippocampus slices. LTD and memory were impaired 48 hours after EtOH and NMDA‐fEPSP analysis unraveled changes in the GluN2A/GluN2B balance. These results were associated with an increase in histone deacetylase (HDAC) activity and HDAC2 mRNA and protein while Ac‐H4K12 labelling was decreased. EtOH increases expression of HDAC2 and mRNA level for GluN2B subunit (but not GluN2A), while HDAC2 modulates the promoter of the gene encoding GluN2B. Interestingly, NaB pretreatment prevented all the cellular and memory‐impairing effects of EtOH. In conclusion, the memory‐impairing effects of two binge‐like EtOH exposure involve NMDA receptor‐dependent LTD deficits due to a GluN2A/GluN2B imbalance resulting from changes in GluN2B expression induced by HDAC2.
Endocannabinoid contributions to alcohol habits and motivation: Relevance to treatment
Authors: Gianessi Carol A. , Groman Stephanie M. , Thompson Summer L. , Jiang Ming , van der Stelt Mario , Taylor Jane R.
Published: May 2019

Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self‐administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown. Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice. We found that administration of the novel diacyl glycerol lipase inhibitor DO34, which decreases the biosynthesis of the endocannabinoid 2‐arachidonoyl glycerol (2‐AG), reduced habitual responding for ethanol and ethanol approach behaviors. Moreover, administration of the endocannabinoid transport inhibitor AM404 or the cannabinoid receptor type 1 antagonist AM251 produced similar reductions in habitual responding for ethanol and ethanol approach behaviors. Notably, AM404 was also able to reduce ethanol seeking and consumption in mice that were insensitive to lithium chloride‐induced devaluation of ethanol. Conversely, administration of JZL184, a monoacyl glycerol lipase inhibitor that increases levels of 2‐AG, increased motivation to respond for ethanol on a progressive ratio schedule of reinforcement. These results demonstrate an important role for endocannabinoid signaling in the motivation to seek ethanol, in ethanol‐motivated habits, and suggest that pharmacological manipulations of endocannabinoid signaling could be effective therapeutics for treating alcohol use disorder.
Understanding and using time series analyses in addiction research
Authors: Beard Emma , Marsden John , Brown Jamie , Tombor Ildiko , Stapleton John , Michie Susan , West Robert
Published: May 2019

Time series analyses are statistical methods used to assess trends in repeated measurements taken at regular intervals and their associations with other trends or events, taking account of the temporal structure of such data. Addiction research often involves assessing associations between trends in target variables (e.g. population cigarette smoking prevalence) and predictor variables (e.g. average price of a cigarette), known as a multiple time series design, or interventions or events (e.g. introduction of an indoor smoking ban), known as an interrupted time series design. There are many analytical tools available, each with its own strengths and limitations. This paper provides addiction researchers with an overview of many of the methods available (GLM, GLMM, GLS, GAMM, ARIMA, ARIMAX, VAR, SVAR, VECM) and guidance on when and how they should be used, sample size det ermination, reporting and interpretation. The aim is to provide increased clarity for researchers proposing to undertake these analyses concerning what is likely to be acceptable for publication in journals such as Addiction. Given the large number of choices that need to be made when setting up time series models, the guidance emphasizes the importance of pre‐registering hypotheses and analysis plans before the analyses are undertaken.
Management of patients with follicular lymphoma treated first line with obinutuzumab
Authors: Opat Stephen , Dickinson Michael , Cheah Chan Yoon , Tam Constantine , Boulos Joy , Thorburn Alison Nicole , Trotman Judith
Published: May 2019

Recently, obinutuzumab was included in the Australian Pharmaceutical Benefits Scheme for use in first line, advanced or bulky stage 2, follicular lymphoma, providing more immunochemotherapy treatment options available than ever before. Rituximab with chemotherapy has been the standard of care since reimbursement in the late 1990s; however, obinutuzumab‐based regimens have shown superior progression‐free survival in comparison to rituximab‐based options, albeit at an increased risk of grade ≥3 adverse events. As median overall survival approaches 20 years or more, the long‐term effects and sequencing of any strategy should be considered. Here we discuss the considerations for selection of front‐line therapy, based on evidence and local Australian clinician experience, in the management of first line follicular lymphoma.
Effect of intravenous dexamethasone on postoperative pain after spinal anaesthesia – a systematic review with meta‐analysis and trial sequential analysis
Authors: Heesen M. , Rijs K. , Hilber N. , Eid K. , Al‐Oweidi A. , Rossaint R. , Klimek M.
Published: May 2019

There are data suggesting that intravenous dexamethasone has an effect on postoperative analgesia when given during single‐shot spinal anaesthesia. However, the research literature is equivocal. We performed a systematic literature search followed by conventional meta‐analysis (random effects model). We used trial sequential analysis to control for type‐1 and ‐2 statistical errors. We also performed a leave‐one‐out meta‐analysis for our primary outcome, the consumption of intravenous morphine in the first 24 postoperative hours. We applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the level of evidence. We obtained data from 1133 patients, reported in 17 trials. Reporting quality was high, with low risk of bias. Dexamethasone use was associated with a significant reduction in 24‐h morphine consumption, the mean difference (95%CI) being −4.01 (−5.01 to −3.01) mg, 6 trials, 326 participants, I2 = 0%. Trial sequential analysis showed that there was firm evidence for the primary outcome, and leave‐one‐out meta‐analysis showed that our result was not driven by one single trial. The GRADE evaluation showed a high level of evidence, suggesting that further studies are unlikely to alter the result. The time to first analgesic request (95%CI) was significantly prolonged by 86.62 (10.62–162.62) min, I2 = 93%, in the dexamethasone group. For other secondary outcomes including number of patients requiring rescue analgesia, or visual analogue scale pain scores, we found no evidence of a significant difference between the treatment arms. We report a high level of evidence that intravenous dexamethasone improves postoperative analgesia after spinal anaesthesia.
Acute decrease in plasma testosterone and appetite after either glucose or protein beverages in adolescent males
Authors: Schwartz Alexander , Hunschede Sascha , Lacombe Russel John Scott , Chatterjee Diptendu , Sánchez‐Hernández Diana , Kubant Ruslan , Bazinet Richard Paul , Hamilton Jill K. , Anderson Gerald Harvey
Published: May 2019

Objective

Chronic testosterone blood concentrations associate with food intake (FI), but acute effects of testosterone on appetite and effect of protein and glucose consumption on testosterone response have had little examination.

Methods

In a randomized, crossover study, twenty‐three adolescent (12‐18 years old) males were given beverages containing either: (a) whey protein (1 g/kg body weight), (b) glucose (1 g/kg body weight) or (c) a calorie‐free control (C). Plasma testosterone, luteinizing hormone (LH), GLP‐1 (active), ghrelin (acylated), glucose, insulin and subjective appetite were measured prior (0) and at 20, 35 and 65 minutes after the consumption of the beverage. FI at an ad libitum pizza meal was assessed at 85 minutes.

Results

Testosterone decreased acutely to 20 minutes after both protein and glucose with the decrease continuing after protein but not glucose to 65 minutes (P = 0.0382). LH was also decreased by both protein and glucose, but glucose had no effect at 20 minutes in contrast to protein (P < 0.001). Plasma testosterone concentration correlated positively with LH (r = 0.58762, P < 0.0001) and negatively with GLP‐1 (r = −0.50656, P = 0.0003). No associations with appetite, ghrelin or glycaemic markers were found. Food intake was not affected by treatments.

Conclusion

Protein or glucose ingestion results in acute decreases in both plasma testosterone and LH in adolescent males. The physiological significance of this response remains to be determined as no support for testosterone's role in acute regulation of food intake was found.
Transforming growth factor beta‐induced p.(L558P) variant is associated with autosomal dominant lattice corneal dystrophy type IV in a large cohort of Spanish patients
Authors: Campos‐Mollo Ezequiel , Varela‐Conde Yago , Arriola‐Villalobos Pedro , Cabrera‐Beyrouti Rubén , Benítez‐del‐Castillo José‐Manuel , Maldonado Miguel J. , Escribano Julio
Published: May 2019

Importance

Rare transforming growth factor beta‐induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features.

Background

The purpose of this study was to analyse TGFBI gene variants and genotype‐phenotype correlations in a cohort affected by atypical stromal CD.

Design

Retrospective cohort study (from May 2014 to September 2017).

Participants

Thirty‐five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included.

Methods

Corneal phenotypes were assessed by slit‐lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing.

Main Outcome Measures

p.(L558P) variant of TGFBI gene.

Results

The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late‐onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep‐mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families.

Conclusions and Relevance

To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior‐posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.
Likelihood of needing facial bone augmentation in the anterior maxilla of Chinese Asians: A cone beam computed tomography virtual implant study
Authors: Zhou Yiqun , Si Misi , Liu Yuelian , Wu Mengjie
Published: May 2019

Background

The perfect position and axis of an implant is often limited by the morphology of the alveolar ridge, especially in Asians.

Purpose

The aim of this study was to investigate the frequency at which ideal implant placement position in the anterior maxilla of Chinese Asians would require facial bone augmentation given by an initial facial bone profile.

Materials and Methods

Implants were virtually placed in 303 sites without tooth loss in the anterior maxilla. The incidence and characters of implant facial plate fenestration were analyzed. If there was no facial fenestration, the thinnest buccal plate (TB) amount adjacent to the implant was measured and recorded.

Results

A total of 79 (26.07%) sites showed fenestrations. The mean length, width, and area of exposure in the fenestration sites were 2.94 ± 1.67 mm, 1.52 ± 0.97 mm, and 2.84 ± 3.13 mm2, respectively. In the nonfenestrated sites, the TB of facial bone around the virtual implants was 1.10 ± 0.78 mm. Among the 224 nonfenestrated sites, 126 sites had a TB of less than 1 mm.

Conclusions

It can be concluded that the initial facial bone profile should be considered when designing restorations and choosing an optimal implant position in the anterior maxilla.
Microscope and micro‐camera assessment of Schneiderian membrane perforation via transcrestal sinus floor elevation: A randomized ex vivo study
Authors: Gargallo‐Albiol Jordi , Sinjab Khaled H. , Barootchi Shayan , Chan Hsun‐Liang , Wang Hom‐Lay
Published: May 2019

Objective

We sought to assess the effectiveness of using a microscope and non‐invasive camera for assessing sinus membrane perforations during transcrestal sinus floor elevation (TSFE).

Materials and methods

Five fresh human cadaver heads corresponding to eight maxillary sinuses (six bilateral and two unilateral) underwent 4 TSFEs per sinus (a total of 32 single site elevations). Each elevation was randomly assigned to receive a three or six mm membrane elevation height (MEH). A microscope and micro‐camera were used to assess the sinus membrane perforation. Afterwards, radiological and clinical membrane perforation assessments were performed. The statistical analysis results are expressed using the means, standard deviations, range values of the residual ridge height (RRH), residual ridge width (RRW), sinus membrane thickness (SMT) and incidence of perforation (IoP). Generalized linear methods were used to test for the correlation of RRH and MEH to the microscope and micro‐camera perforation assessments and the correlation of microscope and micro‐camera assessments with the post‐operative CBCT and crestal liquid evaluation.

Results

The cumulative percentage of IoP was 40.62%, (23.07% with 3 mm MEH, and 76.92% with 6 mm MEH, p < 0.05). The perforation assessed using either the microscope or micro‐camera coincided with the post‐operative CBCT and crestal liquid assessment in 87.55% sites. No significant correlation was found between the microscope or micro‐camera assessments with RRH or MEH.

Conclusion

Application of a microscope and micro‐camera during transcrestal sinus floor elevation may allow the detection of the integrity of the Schneiderian membrane with greater than 85% accuracy in this ex vivo model.
A meta‐analysis of randomized controlled trials in targeted treatments of chronic thromboembolic pulmonary hypertension
Authors: Zhang Jing , Li Jing‐Meng , Huang Zan‐Sheng , Xu Jian‐Cheng , Fan Ye
Published: May 2019

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) results in a progressively worsening course associated with substantial morbidity and mortality. The purpose of this comprehensive study was to determine the clinical efficacy of targeted therapeutic interventions for this disease.

Methods

We searched Medline, Embase, Cochrane databases and Pubmed for relevant clinical studies. Randomized controlled trials comparing the effects of targeted treatments to control in CTEPH population were included. Pooled estimates were calculated using a random effect model. Heterogeneity was determined using the I2 statistic.

Results

This analysis included 6 studies with a total of 565 patients. We found that targeted treatments approved for pulmonary arterial hypertension (PAH) were associated with a larger improvement in exercise capacity, haemodynamic parameters, functional status and clinical symptom. There were no statistically significant differences associated with targeted treatments compared with control in all‐cause mortality and safety outcomes.

Conclusions

This is the first systematic review and meta‐analysis of randomized controlled trials revealing a positive role of PAH‐targeted therapies in CTEPH. Future larger randomized trials with a focus on long‐term clinical outcomes are urgently needed.
Comparing Teachers’ Job Satisfaction across Countries: A Multiple‐Pairwise Measurement Invariance Approach
Authors: Zieger Laura , Sims Sam , Jerrim John
Published: May 2019

There is much interest in comparing latent traits, such as teacher job satisfaction, in large international surveys. However, different countries respond to questionnaires in different languages and interpret the questions through different cultural lenses, raising doubts about the psychometric equivalence of the measurements. Making valid comparisons depends on the latent traits displaying scalar measurement invariance. Unfortunately, this condition is rarely met across many countries at once. Different approaches that maximize the utility of such surveys, but remain faithful to the principles of measurement invariance testing, are therefore needed. This article illustrates one such approach, involving multiple‐pairwise comparisons. This enables us to compare teacher job satisfaction in England to 17 of the countries that participated in TALIS 2013. Teacher job satisfaction in England was as low, or lower, than all of the 17 comparable countries.
Parallel plasticity of mating songs and preferences in the field cricket Gryllus rubens
Authors: Beckers Oliver M. , Murphey Katherine J. , Pease Jacob R. , Norman Nicholas
Published: May 2019

In animal communication systems, matching mating signals and preferences enable species identification and successful reproduction. In some species, the environment introduces substantial variation in signals and/or preferences. Only a few studies have tested how the match between signals and preferences is maintained despite phenotypic variation. Signal–preference coupling in the context of phenotypic plasticity is the focus of this study. The bivoltine cricket Gryllus rubens displays seasonal differences in the pulse rate of its mating songs. The seasonal effect on other fine‐temporal characters of the songs besides pulse rate, such as pulse and interval duration, duty cycle, as well as the dominant frequency, is not known and is described in the first part of the study for a Kentucky population. In the second part of the study, we tested preferences of spring and fall females to determine whether they match the seasonal plasticity of male songs using single‐speaker phonotaxis experiments. We found that fall songs had a faster pulse rate, shorter pulse and interval durations, and a higher dominant frequency than spring songs. Female preferences shifted in parallel with male song plasticity, that is, spring females preferred the spring song and fall females the fall song. In addition, female responsiveness to male song was plastic as well, that is, fall females were significantly more responsive than spring females. The parallel plasticity of male songs and female preferences facilitates successful communication despite the environmentally induced variation. The potential origin and function of behavioral plasticity in G. rubens are discussed.
Governance interactions in small‐scale fisheries market chains: Examples from the Asia‐Pacific
Authors: Steenbergen Dirk J. , Fabinyi Michael , Barclay Kate , Song Andrew M. , Cohen Philippa J. , Eriksson Hampus , Mills David J.
Published: May 2019

Small‐scale fisheries are subject to various governing institutions operating at different levels with different objectives. At the same time, small‐scale fisheries increasingly form part of domestic and international market chains, with consequent effects for marine environments and livelihoods of the fishery‐dependent. Yet there remains a need to better understand how small‐scale fisheries market chains interact with the range of governance institutions that influence them. In this paper, we examine how multiple governance systems function along market chains, in order to identify opportunities for improved multiscale governance. We use three small‐scale fisheries with varying local to global market chains operating in the Asia‐Pacific region to develop a framework for analysis. Drawing from Interactive Governance theory we identify governing systems that have come to operate at particular sections in each market chain. We recognize four institutions that shape the governance over the length of the chain; namely those centred on (a) government, (b) private sector and pricing, (c) decentralized multistakeholder management and (d) culture and social relations. The framework shows how diverse arrangements of these governing institutions emerge and take effect along market chains. In doing so, we seek to move away from prescribed “ideals” of universal governing arrangements for fisheries and their market chains, and instead illuminate how governing systems function interactively across multiple scales.
Is TNF inhibitor exposure a risk factor for amyotrophic lateral sclerosis?
Authors: Petitpain Nadine , Devos David , Bagheri Haleh , Rocher Fanny , Gouraud Aurore , Masmoudi Kamel , Coquerel Antoine
Published: May 2019

TNFα modulation has been reported to be either beneficial or detrimental in amyotrophic lateral sclerosis (ALS) and therefore appears as a key issue. We analysed the relationship between TNFα inhibitor (TNFi) exposure and ALS. We performed descriptive analysis of ALS reports in patients treated with TNFi, registered in the French Pharmacovigilance Database (FPvD) and disproportionality analyses by the ‘case’/’non‐case’ method in FPvD and worldwide database (Vigibase®). The 8 retrieved ALS cases from the FPvD were 5 with limb‐onset and 3 with bulbar‐onset forms, in patients aged 43–75 years old, mainly treated for inflammatory rheumatism. The time to onset of the first symptoms ranged from 12 to 108 months, and the cumulative TNFi exposure before the diagnosis ranged from 12 to 120 months. TNFi was discontinued and thereafter survival ranged between 12 and 20 months. Disproportionality analyses showed significant associations between TNFi exposure and ALS in the FPvD and Vigibase® (160 ALS cases), regardless comparators. A putative association between TNFi and ALS must be interpreted cautiously, but TNFi could act as a predisposing or risk factor. TNFi should therefore be avoided in patients with a known risk of ALS and discontinued in the case of neurological signs of ALS.
Global patterns of intraspecific leaf trait responses to elevation
Authors: Midolo Gabriele , De Frenne Pieter , Hölzel Norbert , Wellstein Camilla
Published: May 2019

Elevational gradients are often used to quantify how traits of plant species respond to abiotic and biotic environmental variations. Yet, such analyses are frequently restricted spatially and applied along single slopes or mountain ranges. Since we know little on the response of intraspecific leaf traits to elevation across the globe, we here perform a global meta‐analysis of leaf traits in 109 plant species located in 4 continents and reported in 71 studies published between 1983 and 2018. We quantified the intraspecific change in seven morpho‐ecophysiological leaf traits along global elevational gradients: specific leaf area (SLA), leaf mass per area (LMA), leaf area (LA), nitrogen concentration per unit of area (Narea), nitrogen concentration per unit mass (Nmass), phosphorous concentration per unit mass (Pmass) and carbon isotope composition (δ13C). We found LMA, Narea, Nmass and δ13C to significantly increase and SLA to decrease with increasing elevation. Conversely, LA and Pmass showed no significant pattern with elevation worldwide. We found significantly larger increase in Narea, Nmass, Pmass and δ13C with elevation in warmer regions. Larger responses to increasing elevation were apparent for SLA of herbaceous compared to woody species, but not for the other traits. Finally, we also detected evidences of covariation across morphological and physiological traits within the same elevational gradient. In sum, we demonstrate that there are common cross‐species patterns of intraspecific leaf trait variation across elevational gradients worldwide. Irrespective of whether such variation is genetically determined via local adaptation or attributed to phenotypic plasticity, the leaf trait patterns quantified here suggest that plant species are adapted to live on a range of temperature conditions. Since the distribution of mountain biota is predominantly shifting upslope in response to changes in environmental conditions, our results are important to further our understanding of how plants species of mountain ecosystems adapt to global environmental change.
Divergent long‐term trends and interannual variation in ecosystem resource use efficiencies of a southern boreal old black spruce forest 1999–2017
Authors: Liu Peng , Black T. Andrew , Jassal Rachhpal S. , Zha Tianshan , Nesic Zoran , Barr Alan G. , Helgason Warren D. , Jia Xin , Tian Yun , Stephens Jilmarie J. , Ma Jingyong
Published: May 2019

Long‐term trends in ecosystem resource use efficiencies (RUEs) and their controlling factors are key pieces of information for understanding how an ecosystem responds to climate change. We used continuous eddy covariance and microclimate data over the period 1999–2017 from a 120‐year‐old black spruce stand in central Saskatchewan, Canada, to assess interannual variability, long‐term trends, and key controlling factors of gross ecosystem production (GEP) and the RUEs of carbon (CUE = net primary production [NPP]/GEP), light (LUE = GEP/absorbed photosynthetic radiation [APAR]), and water (WUE = GEP/evapotranspiration [E]). At this site, annual GEP has shown an increasing trend over the 19 years (p < 0.01), which may be attributed to rising atmospheric CO2 concentration. Interannual variability in GEP, aside from its increasing trend, was most strongly related to spring temperatures. Associated with the significant increase in annual GEP were relatively small changes in NPP, APAR, and E, so that annual CUE showed a decreasing trend and annual LUE and WUE showed increasing trends over the 19 years. The long‐term trends in the RUEs were related to the increasing CO2 concentration. Further analysis of detrended RUEs showed that their interannual variation was impacted most strongly by air temperature. Two‐factor linear models combining CO2 concentration and air temperature performed well (R2~0.60) in simulating annual RUEs. LUE and WUE were positively correlated both annually and seasonally, while LUE and CUE were mostly negatively correlated. Our results showed divergent long‐term trends among CUE, LUE, and WUE and highlighted the need to account for the combined effects of climatic controls and the ‘CO2 fertilization effect’ on long‐term variations in RUEs. Since most RUE‐based models rely primarily on one resource limitation, the observed patterns of relative change among the three RUEs may have important implications for RUE‐based modeling of C fluxes.