bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic NGS-based approach for contaminant detection and functional inference
Authors: Park Sung-Joon , Onizuka Satoru , Seki Masahide , Suzuki Yutaka , Iwata Takanori , Nakai Kenta
Published: August 2019

Background

Microbial contamination impedes successful biological and biomedical research. Computational approaches utilizing next-generation sequencing (NGS) data offer promising diagnostics to assess the presence of contaminants. However, as host cells are often contaminated by multiple microorganisms, these approaches require careful attention to intra- and interspecies sequence similarities, which have not yet been fully addressed.

Results

We present a computational approach that rigorously investigates the genomic origins of sequenced reads, including those mapped to multiple species that have been discarded in previous studies. Through the analysis of large-scale synthetic and public NGS samples, we approximated that 1,000−100,000 microbial reads prevail when one million host reads are sequenced by RNA-seq. The microbe catalog we established included Cutibacterium as a prevalent contaminant, suggesting that contamination mostly originates from the laboratory environment. Importantly, by applying a systematic method to infer the functional impact of contamination, we revealed that host-contaminant interactions cause profound changes in the host molecular landscapes, as exemplified by changes in inflammatory and apoptotic pathways during Mycoplasma infection.

Conclusions

These findings reinforce the concept that precise determination of the origins and functional impacts of contamination is imperative for quality research and illustrate the usefulness of the proposed approach to comprehensively characterize contamination landscapes.
The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in Yersinia pestis During Planktonic Growth and Growth in Biofilms
Authors: Ritzert Jeremy T. , Minasov George , Embry Ryan , Schipma Matthew J. , Satchell Karla J. F.
Published: August 2019

Cyclic adenosine monophosphate (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1.8 Å crystal structure of the protein-cAMP complex. We found that compared to Escherichia coli Crp, C helix amino acid substitutions in Y. pestis Crp did not impact cAMP dependency of Crp to bind DNA promoters. To investigate Y. pestis Crp-regulated genes during plague pneumonia, we performed RNA-sequencing on both wild-type and Δcrp mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Y. pestis Crp is found to dramatically alter expression of hundreds of genes dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the malT and ptsG promoters and Crp was then linked to Y. pestis growth on maltose as a sole carbon source. Iron-regulation genes ybtA and fyuA were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of Y. pestis infected mice when crp expression is highest in Y. pestis biofilms. Thus, in addition to well-studied pla, other Crp-regulated genes likely have important functions during plague infection.

IMPORTANCE

Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen, Y. pestis, requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of non-glucose sugars, we find the Crp regulates genes for virulence, metal acquisition and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, that responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.
Differential remodeling of the electron transport chain is required to support TLR3 and TLR4 signaling and cytokine production in macrophages
Authors: Ahmed Duale , Roy David , Jaworski Allison , Edwards Alex , Abizaid Alfonso , Kumar Ashok , Golshani Ashkan , Cassol Edana
Published: August 2019

Increasing evidence suggests that mitochondria play a critical role in driving innate immune responses against bacteria and viruses. However, it is unclear if differential reprogramming of mitochondrial function contributes to the fine tuning of pathogen specific immune responses. Here, we found that TLR3 and TLR4 engagement on murine bone marrow derived macrophages was associated with differential remodeling of electron transport chain complex expression. This remodeling was associated with differential accumulation of mitochondrial and cytosolic ROS, which were required to support ligand specific inflammatory and antiviral cytokine production. We also found that the magnitude of TLR3, but not TLR4, responses were modulated by glucose availability. Under conditions of low glucose conditions, TLR3 engagement was associated with increased ETC complex III expression, increased mitochondrial and cytosolic ROS and increased inflammatory and antiviral cytokine production. This amplification was selectively reversed by targeting superoxide production from the outer Q-binding site of the ETC complex III. These results suggest that ligand specific modulation of the ETC may act as a rheostat that fine-tunes innate immune responses via mitochondrial ROS production. Modulation of these processes may represent a novel mechanism to modulate the nature as well as the magnitude of antiviral versus inflammatory immune responses.
Altered immunity of laboratory mice in the natural environment is associated with fungal colonization
Authors: Yeung Frank , Chen Ying-Han , Lin Jian-Da , Leung Jacqueline M. , McCauley Caroline , Devlin Joseph C. , Hansen Christina , Cronkite Alex , Stephens Zac , Drake-Dunn Charlotte , Fulmer Yi , Shopsin Bo , Ruggles Kelly V. , Round June L. , Loke P’ng , Graham Andrea L. , Cadwell Ken
Published: August 2019

The immune systems of free-living mammals such as humans and wild mice display a heightened degree of activation compared with laboratory mice maintained under artificial conditions. Here, we demonstrate that releasing inbred laboratory mice into an outdoor enclosure to mimic life in a natural environment alters the state of immunity. In addition to enhancing the differentiation of T cell populations previously associated with pathogen exposure, we found that outdoor release of mice led to an increase in circulating granulocytes. However, rewilded mice were not infected by pathogens previously implicated in immune activation. Rather, changes to the immune system were associated with an altered composition of the microbiota, and fungi isolated from rewilded mice were sufficient to increase circulating granulocytes. These findings establish an experimental procedure to investigate the impact of the natural environment on immune development and identify a role for sustained fungal exposure in determining granulocyte numbers.
Progressive impairments in executive function in the APP/PS1 model of Alzheimer’s disease as measured by translatable touchscreen testing
Authors: Shepherd A. , Lim J.K.H. , Wong V.H.Y. , Zeleznikow-Johnston A.M. , Churilov L. , Nguyen C.T.O. , Bui B.V. , Hannan A.J. , Burrows E.L.
Published: August 2019

Executive function deficits in Alzheimer’s disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APP/PS1 mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.
Low-frequency Neural Activity Reflects Rule-based Chunking during Speech Listening
Authors: Ding Nai , Jin Peiqing
Published: August 2019

Cortical activity tracks the rhythms of phrases and sentences during speech comprehension, which has been taken as strong evidence that the brain groups words into multi-word chunks. It has prominently been argued, in contrast, that the tracking phenomenon could be explained as the neural tracking of word properties. Here we distinguish these two hypotheses based on novel tasks in which we dissociate word properties from the chunk structure of a sequence. Two tasks separately require listeners to group semantically similar or semantically dissimilar words into chunks. We demonstrate that neural activity actively tracks task-related chunks rather than passively reflecting word properties. Furthermore, without an explicit ‘chunk processing task,’ neural activity barely tracks chunks defined by semantic similarity - but continues to robustly track syntactically well-formed meaningful sentences. These results suggest that cortical activity tracks multi-word chunks constructed by either long-term syntactic rules or temporary task-related rules. The properties of individual words are likely to contribute only in a minor way, contrary to recent claims.
Development of a functional genetic tool for Anopheles gambiae oenocyte characterisation: application to cuticular hydrocarbon synthesis
Authors: Lynd Amy , Balabanidou Vasileia , Grosman Rudi , Maas James , Lian Lu-Yun , Vontas John , Lycett Gareth J.
Published: August 2019

Oenocytes are an insect cell type having diverse physiological functions ranging from cuticular hydrocarbon (CHC) production to insecticide detoxification that may impact their capacity to transmit pathogens. To develop functional genetic tools to studyAnopheles gambiaeoenocytes, we have trapped an oenocyte enhancer to create a transgenic mosquito Gal4 driver line that mediates tissue-specific expression. After crossing with UAS-reporter lines,An. gambiaeoenocytes are fluorescently tagged through all life stages and demonstrate clearly the two characteristic oenocyte cell-types arising during development. The driver was then used to characterise the function of two oenocyte expressedAn. gambiae cyp4ggenes through tissue-specific expression of UAS-RNAi constructs. Silencing ofcyp4g16orcyp4g17caused lethality in pupae of differing timing and penetrance. Survivingcyp4g16knockdown adults showed increased sensitivity to desiccation. Total cuticular hydrocarbon levels were reduced by approximately 80% or 50% in both single gene knockdowns when assayed in young pupa or surviving adults respectively, indicating both genes are required for complete CHC production inAn. gambiaeand demonstrate synergistic activity in young pupae. Comparative CHC profiles were very similar for the two knockdowns, indicating overlapping substrate specificities of the two enzymes. Differences were observed for example with reduced abundance of shorter chain CHCs in CYP4G16 knockdowns, and reduction in longer, branched chained CHCs in CYP4G17 knockdown adults. This is the first time that twocyp4gs have both been shown to be required for complete CHC production in an insect. Moreover, the generation of tagged cells and identification of an enhancer region can expediate oenocyte specific transcriptomics. The novel driver line can also be used to explore oenocyte roles in pheromone production, mating behaviour and longevity in the malaria mosquito.
Lipid metabolism links nutrient-exercise timing to insulin sensitivity in men classified as overweight or obese
Authors: Edinburgh R.M. , Bradley H.E , Abdullah N-F. , Robinson S.L. , Chrzanowski-Smith O.J. , Walhin J-P. , Joanisse S. , Manolopoulos K.N. , Philp A. , Hengist A. , Chabowski A. , Brodsky F.M. , Koumanov F. , Betts J.A. , Thompson D. , Wallis G. A. , Gonzalez J.T.
Published: August 2019

Context

Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. We hypothesised that in men with overweight/obesity, acute exercise beforeversusafter nutrient ingestion would increase whole-body and intramuscular lipid utilization, translating into greater increases in oral glucose insulin sensitivity over 6-weeks of training.

Design and Participants

We showed in men with overweight/obesity (mean±SD for BMI: 30.2±3.5 kg×m-2for acute, crossover study, 30.9±4.5 kg×m-2for randomized, controlled, training study) a single exercise bout beforeversusafter nutrient provision increased lipid utilisation at the whole-body level, but also in both type I (p<0.01) and type II muscle fibres (p=0.02). We then used a 6-week training intervention to show sustained, 2-fold increases in lipid utilisation with exercise beforeversusafter nutrient provision (p<0.01).

Main Outcome Measures

Postprandial glycemia was not differentially affected by exercise training beforevsafter nutrient provision (p>0.05), yet plasma was reduced with exercise training before, but not after nutrient provision (p=0.03), resulting in increased oral glucose insulin sensitivity when training was performed beforeversusafter nutrient provision (25±38vs−21±32 mL×min-1×m-2;p=0.01) and this was associated with increased lipid utilisation during exercise (r=0.50,p=0.02). Regular exercise prior to nutrient provision augmented remodelling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (p<0.05).

Conclusions

Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed beforeversusafter nutrient intake (i.e., in the fasted state) may exert beneficial effects on lipid utilisation and reduce postprandial insulinemia.

Précis

Exercise in the fasted-versusfed-state increased intramuscular and whole-body lipid use, translating into increased muscle adaptation and insulin sensitivity when regularly performed over 6 weeks.
Friends with malefit. The effects of keeping dogs and cats, sustaining animal-related injuries andToxoplasmainfection on health and quality of life
Authors: Flegr Jaroslav , Preiss Marek
Published: August 2019

Many studies show that keeping cats and dogs has a positive impact on humans’ physical and mental health and quality of life. The existence of this “pet phenomenon” is now widely discussed because other studies performed recently have demonstrated a negative impact of owning pets or no impact at all. The main problem of many studies was the autoselection – participants were informed about the aims of the study during recruitment and later likely described their health and wellbeing according to their personal beliefs and wishes, not according to their real status. To avoid this source of bias, we did not mention pets during participant recruitment and hid the pet-related questions among many hundreds of questions in an 80-minute Internet questionnaire. Results of our study performed on a sample of on 10,858 subjects showed that liking cats and dogs has a weak positive association with quality of life. However, keeping pets, especially cats, and even more being injured by pets, were strongly negatively associated with many facets of quality of life. Our data also confirmed that infection by the cat parasiteToxoplasmahad a very strong negative effect on quality of life, especially on mental health. However, the infection was not responsible for the observed negative effects of keeping pets, as these effects were much stronger in 1,527Toxoplasma-free subjects than in the whole population. Any cross-sectional study cannot discriminate between a cause and an effect. However, because of the large and still growing popularity of keeping pets, the existence and nature of the reverse pet phenomenon deserve the outmost attention.
Enhancer architecture sensitizes cell specific responses toNotchgene dose via a bind and discard mechanism
Authors: Kuang Yi , Golan Ohad , Preusse Kristina , Cain Brittany , Salomone Joseph , Campbell Ian , Okwubido-Williams FearGod V. , Hass Matthew R. , Eafergan Natanel , Moberg Kenneth H. , Kovall Rhett A. , Kopan Raphael , Sprinzak David , Gebelein Brian
Published: August 2019

Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage. Here, we show that inserting a single enhancer containing pioneer transcription factor sites coupled to Notch dimer sites can unexpectedly induce a subset ofDrosophila Notchhaploinsufficiency phenotypes in an animal with wild typeNotchgene dose. Mechanistically, this enhancer couples Notch DNA binding to degradation in a Cdk8-dependent, transcription-independent manner. Using mathematical modeling combined with quantitative trait and expression analysis, we show that tissues requiring long duration Notch signals are more sensitive to perturbations in Notch degradation compared to tissues relying upon short duration processes. These findings support a novel “bind and discard” mechanism in which enhancers with specific binding sites promote rapid Notch turnover, reduce Notch-dependent transcription at other loci, and thereby sensitize tissues to gene dose based upon signal duration.
Inhibition of a negative feedback for persistent epithelial cell–cell junction contraction by p21-activated kinase 3
Authors: Uechi Hiroyuki , Kuranaga Erina
Published: August 2019

Actin-mediated mechanical forces are central drivers of cellular dynamics. They generate protrusive and contractile dynamics, the latter of which are induced in concert with myosin II bundled at the site of contraction. These dynamics emerge concomitantly in tissues and even each cell; thus, the tight regulation of such bidirectional forces is important for proper cellular deformation. Here, we show that contractile dynamics can eventually disturb cell–cell junction contraction in the absence of p21-activated kinase 3 (Pak3). Upon Pak3 depletion, contractility induces the formation of abnormal actin protrusions at the shortening junctions, which reduces E-cadherin levels at adherens junctions. Such E-cadherin dilution dissociates myosin II from the contracting junctions, leading to a reduction in junctional tensile forces. Overexpressing E-cadherin restores the association of myosin II at the junctions and junction contraction. Our results suggest that contractility both induces and perturbs junction contraction and that the attenuation of such perturbations by Pak3 facilitates persistent junction shortening.
Model-Based Recommendations for Optimal Surgical Placement of Epiretinal Implants
Authors: Beyeler Michael , Boynton Geoffrey M. , Fine Ione , Rokem Ariel
Published: August 2019

A major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual ‘streaks’ that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to ∼55 %. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.
HA stability regulates H1N1 influenza virus replication and pathogenicity in mice by modulating type I interferon responses in dendritic cells
Authors: Russier Marion , Yang Guohua , Briard Benoit , Meliopoulos Victoria , Cherry Sean , Kanneganti Thirumala-Devi , Schultz-Cherry Stacey , Vogel Peter , Russell Charles J.
Published: August 2019

Hemagglutinin (HA) stability, or the pH at which the HA is activated to cause membrane fusion, has been associated with the replicative fitness, pathogenicity, transmissibility, and interspecies adaptation of influenza A viruses. Here, we investigated several mechanisms by which a destabilizing HA mutation, Y17H (activation pH 6.0), may attenuate virus replication and pathogenicity in DBA/2 mice, compared to wild-type (WT; activation pH 5.5). Extracellular lung pH was measured to be near neutral (pH 6.9–7.5). WT and Y17H viruses had similar environmental stability at pH 7.0; thus, extracellular inactivation was unlikely to attenuate Y17H virus. The Y17H virus had accelerated single-step replication kinetics in MDCK, A549, and Raw264.7 cells. The destabilizing mutation also increased early infectivity and type I interferon (IFN) responses in mouse bone marrow–derived dendritic cells (DCs). In contrast, the HA-Y17H mutation reduced multistep replication in murine airway mNEC and mTEC cultures and attenuated virus replication, virus spread, severity of infection, and cellular infiltration in the lungs of mice. Normalizing virus infection and weight loss in mice by inoculating them with Y17H virus at a dose 500-fold higher than that of WT virus revealed that the destabilized mutant virus triggered the upregulation of more host genes and increased type I IFN responses and cytokine expression in DBA/2 mouse lungs. Overall, HA destabilization decreased virulence in mice by boosting early infection in DCs, resulting in greater activation of antiviral responses, including type I IFN. These studies reveal HA stability may regulate pathogenicity by modulating IFN responses.

Importance

Diverse influenza A viruses circulate in wild aquatic birds, occasionally infecting farm animals. Rarely, an avian- or swine-origin influenza virus adapts to humans and starts a pandemic. Seasonal and many universal influenza vaccines target the HA surface protein, which is a key component of pandemic influenza. Understanding HA properties needed for replication and pathogenicity in mammals may guide response efforts to control influenza. Some antiviral drugs and broadly reactive influenza vaccines that target the HA protein have suffered resistance due to destabilizing HA mutations that do not compromise replicative fitness in cell culture. Here, we show that despite not compromising fitness in standard cell cultures, a destabilizing H1N1 HA stalk mutation greatly diminishes viral replication and pathogenicity in vivo by modulating type I IFN responses. This encourages targeting the HA stalk with antiviral drugs and vaccines as well as reevaluating previous candidates that were susceptible to destabilizing resistance mutations.
The state of child labor protections in 193 countries: Are countries living up to their international commitments?
Authors: de Guzman Chorny Nicolas , Raub Amy , Earle Alison , Heymann Jody
Published: August 2019

Purpose

Nearly every country has committed to protect children from work that could be harmful or interfere with their education by ratifying the International Labour Organization Minimum Age Convention (C138). Yet there is little transparency and accountability around whether countries have followed through on these commitments by passing legislation to protect children from work. The paper aims to discuss these issues.

Design/methodology/approach

This paper reports on analyses conducted of child labor legislation from all 193 United Nations member states to determine whether countries that have committed to ending child labor have taken the first step by passing legislation to protect children and youth from: work that is likely to be hazardous, work that is likely to interfere with their education and work that is harmful to their healthy development.

Findings

Findings show one in five ratifiers legally allow children to do hazardous work, and a similar number permit admission to employment at a young age. Moreover, legislative loopholes significantly undermine the protections that do exist in many countries.

Originality/value

Existing reporting mechanisms sometimes obscure whether central legal protections are in place, make cross-country comparisons difficult and impede the analysis of possible relationships between policies and outcomes across countries. This paper illustrates a novel approach to provide transparency and accountability on whether countries are meeting child labor commitments by using quantitative, globally comparable policy indicators.
Review of 52 cases with Hailey–Hailey disease identified 25 novel mutations in Chinese Han population
Authors: Wang Zhe , Li Lulu , Sun Lele , Mi Zihao , Fu Fanghui , Yu Gongqi , Fu Xian , Liu Hong , Zhang Furen
Published: August 2019

Hailey–Hailey disease (HHD) is a rare autosomal dominant inherited keratosis caused by mutations in ATP2C1. The aim of our study was to identify and analyze the features of the mutations in HHD. We examined 52 Chinese Han cases which were diagnosed as HHD based on their clinical and histological findings. Genomic DNA polymerase chain reaction and direct sequencing of ATP2C1 were performed from peripheral blood samples of the patients and 100 unrelated healthy controls. Twenty‐five novel mutations and 14 recurrent mutations were identified, including 11 (28.2%) missense mutations, nine (23.1%) frame‐shift deletion mutations, eight (20.5%) nonsense mutations, seven (17.9%) splicing mutations and four (10.3%) frame‐shift insertion mutations. Together with ours, all 209 mutations showed a uniform distribution without hotspots or clusters. In addition, there is no specific genotype–phenotype correlation in HHD. Our findings update the spectrum of mutations in ATP2C1.
Successful treatment of interstitial lung disease related to Stevens–Johnson syndrome/toxic epidermal necrolysis overlap with etanercept: A case report and published work review
Authors: Wang Fang , Gao Xuemei , Chen Xiaohong , Tang Xuhua , Chen Haihong , Han Jiande
Published: August 2019

Interstitial lung disease (ILD) is a rare complication of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this study, we present the case of a 33‐year‐old woman who was diagnosed with ILD related to SJS/TEN overlap syndrome. Surprisingly, the patient did not respond to combination therapy with steroids and i.v. immunoglobulin, but rapidly improved after two doses of etanercept treatment. To our knowledge, this is the first case of SJS/TEN‐induced ILD that was successfully treated with etanercept. We reviewed another two cases of ILD associated with SJS/TEN, and found that unlike the other cases, in the present case, ILD occurred early in the course of the disease and rapidly improved after etanercept injection. We discovered that in the present patient, the serum interleukin‐6 level increased during the progressive stage and declined after the initiation of treatment with etanercept.
Dispersal and nutrient limitations of decomposition above the forest floor: Evidence from experimental manipulations of epiphytes and macronutrients
Authors: Gora Evan M. , Lucas Jane M.
Published: August 2019

Decomposition is a major component of global carbon cycling. However, approximately 50% of wood necromass and a small proportion of leaf litter do not contact the forest floor, and the factors that regulate the decomposition above the forest floor are largely untested. We hypothesized that separation from soil resources causes slower decomposition rates above the forest floor. Specifically, we tested whether slower decomposition results from decreased nutrient availability (the nutrient limitation hypothesis) and/or microbial dispersal limitation (the dispersal limitation hypothesis) in the absence of soil resources.

We tested these hypotheses by combining experimental manipulations of epiphytes and macronutrient fertilization with elemental analyses and community metabarcoding (fungi and prokaryotes). Specifically, we compared wood stick and cellulose decomposition among three treatments: an unaltered trunk section, an epiphyte mat, and a ‘removal treatment’ where an epiphyte mat was removed to test the effect of soil resources. We also performed a factorial fertilization experiment to test the effects of nitrogen (N) and phosphorus (P) on the decomposition of suspended cellulose.

Decomposition rates were fastest on the epiphyte mats, intermediate in the removal treatment and slowest in the controls. Phosphorus addition increased decomposition rates in the fertilization experiment, and greater P concentrations, along with some micronutrients, were associated with increased rates of decomposition on the epiphyte mats and in the removal treatments. Locally dispersed fungi dominated the wood stick communities, indicating that fungal dispersal is limited in the canopy, and fungal saprotrophs were associated with increased rates of decomposition on the epiphytes.

These experiments show that slowed decomposition above the forest floor is caused, in part, by separation from soil resources. Moreover, our findings provide support for both the nutrient limitation and dispersal limitation hypotheses and indicate that mechanisms regulating canopy‐level decomposition differ from those documented on the forest floor. This demonstrates the need for a holistic approach to decomposition that considers the vertical position of necromass as it decomposes. Further experimentation is necessary to quantify interactions between community assembly processes, nutrient availability, substrate traits, and microclimate.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Recovery of High Value‐Added Nutrients from Fruit and Vegetable Industrial Wastewater
Authors: Chen Honglin , Zhang Hua , Tian Jinhu , Shi John , Linhardt Robert J. , Ye Tian Ding Xingqian , Chen Shiguo
Published: August 2019

The industrial processing water of fruit and vegetables has raised serious environmental concerns due to the presence of many important bioactive compounds being disposed in the wastewater. Bioactive compounds have great potential for the food industry to optimize their process and to recover these compounds in order to develop value‐added products and to reduce environmental impacts. However, to achieve this goal, some challenges need to be addressed such as safety assurance, technology request, product regulations, cost effectiveness, and customer factors. Therefore, this review aims to summarize the recent advances of bioactive compounds recovery and the current challenges in wastewater from fruit and vegetable processing industry, including fruit and beverage, soybean by‐products, starch and edible oil industry. Moreover, future direction for novel and green technology of bioactive compounds recovery are discussed, and a prospect of bioactive compounds reuse and sustainable development is proposed.
Sexual victimization against transgender women in prison: Consent and coercion in context
Authors: Jenness Valerie , Sexton Lori , Sumner Jennifer
Published: August 2019

In this article, we conjoin two long‐standing lines of inquiry in criminology—the study of prison life and the study of sexual assault—by using original qualitative and quantitative data from 315 transgender women incarcerated in 27 California men's prisons. In so doing, we advance an analysis of the factors and processes that shape their experience of sexual victimization in prison. The results of qualitative analysis of 198 reported incidents of sexual victimization exhibit a range of types of sexual victimization experienced by transgender women in prison and reveal the centrality of relationships to their experiences of victimization. Findings from logistic regression models buttress the qualitative results, highlighting a factor that consistently and powerfully indicates vulnerability to sexual victimization is involvement in consensual sexual relationships with male prisoners. Together, the data demonstrate the prominence of intimate partner violence in prison, complicate the distinction between consent and unwanted sexual experiences in the lives of transgender women in prisons for men, and shine a light on the workings of gender in a total institution that privileges heteronormativity at the expense of the safety of transgender women in prisons for men. We discuss the implications of our findings in light of timely policy concerns.
Enhanced Curcumin Bioavailability through Nonionic Surfactant/Caseinate Mixed Nanoemulsions
Authors: Cuomo Francesca , Perugini Luisa , Marconi Emanuele , Messia Maria Cristina , Lopez Francesco
Published: August 2019

The potential of heterogeneous systems like oil‐in‐water (O/W) nanoemulsions is exploited as an oral delivery system for curcumin, a natural lipophilic compound with numerous health benefits. Two types of O/W nanoemulsions, one stabilized by sodium caseinate (Cas‐O/W), a surface‐active and emulsifying protein, and the other stabilized by a blend of caseinate and Tween 20 (Mix‐O/W), were loaded with the bioactive compound and tested through a simulated gastrointestinal digestion process to evaluate their effects on delivering of curcumin. It was first demonstrated that the amount of curcumin solubilized through Mix‐O/W nanoemulsion was higher than that in Cas‐O/W nanoemulsion. Cas‐O/W nanoemulsions, indeed, at their best, solubilized about 55 µg/mL of curcumin while Mix‐O/W nanoemulsions reached a curcumin concentration around 180 µg/mL. Furthermore, for both the systems an increase of curcumin loading capacity was recorded with the rise of incubation temperature. Finally, after the in vitro simulated digestion process, the potential curcumin bioavailability was evaluated and the data suggested that Mix‐O/W nanoemulsions provided more than twice the amount of curcumin compared to Cas‐O/W nanoemulsions. On balance, the outcomes of this investigation demonstrated that the mixed emulsifier system offered a higher amount of lipophilic compound with a low fat intake compared to nanoemulsions stabilized by sodium caseinate.

Practical Application

The outcomes of this study allow the recognition of the protein/surfactant‐stabilized nanoemulsions as a suitable solution to deliver curcumin. The nanoemulsions proposed here provide a high intake of curcumin, a lipophilic compound, with low fat content. The use of such delivery systems helps to overcome limits in oral bioavailability related with the scarce solubility of some compounds in food preparations and beverages.
Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report
Authors: Kim Je‐Seong , Nam Tai‐Seung , Kim Jieun , Kho Bo‐Gun , Park Cheol‐Kyu , Oh In‐Jae , Kim Young‐Chul
Published: August 2019

Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76‐year‐old man who had been treated with four doses of nivolumab because of non‐small cell lung cancer (NSCLC) presented with proximal‐dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy.
Advancing Precision Medicine for Alcohol Use Disorder: Replication and Extension of Reward Drinking as a Predictor of Naltrexone Response
Authors: Witkiewitz Katie , Roos Corey R. , Mann Karl , Kranzler Henry R.
Published: August 2019

Background

Precision medicine aims to identify those patients who will benefit the most from specific treatments. Recent work found large effects of naltrexone among “reward drinkers,” defined as individuals who drink primarily for the rewarding effects of alcohol. This study sought to replicate and extend these recent findings by examining whether the desire to drink mediated the effect of naltrexone among reward drinkers.

Methods

We conducted a secondary analysis of a 12‐week randomized clinical trial of daily or targeted naltrexone among problem drinkers (n = 163), with a focus on 86 individuals (n = 45 naltrexone and n = 41 placebo) who received daily medication. Interactive voice response technology was used to collect daily reports of drinking and desire to drink. Factor mixture models were used to derive reward and relief phenotypes. Moderation analyses were used to evaluate naltrexone effects, with phenotype as a moderator variable. Multilevel mediation tested average desire to drink as a mediator.

Results

Results indicated 4 phenotypes: low reward/low relief; low reward/high relief; high reward/low relief; and high reward/high relief. There was an interaction between the high reward/low relief subgroup (n = 10) and daily naltrexone versus placebo on drinks per drinking day (DPDD; p = 0.03), percent heavy drinking days (p = 0.004), and daily drinking (p = 0.02). As compared to placebo, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer DPDD (Cohen's d = 2.05) and had a lower proportion of heavy drinking days (Cohen's d = 1.75). As hypothesized, reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among the high reward/low relief drinkers (moderated mediation effect: p = 0.029).

Conclusions

This theory‐driven study replicates the empirical finding that naltrexone is particularly efficacious among high reward/low relief drinkers. Our study brings the field a step closer to the potential of using a precision medicine approach to treating alcohol use disorder.
Does extreme flooding drive vegetation and faunal composition across the Gulf Plains of north‐eastern Australia?
Authors: Crowley Gabriel M. , Preece Noel D.
Published: August 2019

High levels of sub‐speciation in Australian mesic zone taxa have been attributed to the creation of biogeographic barriers by Pleistocene expansion of the arid zone. However, several of these barriers also align with major floodplains. The Carpentarian Barrier in the Gulf Plains (GUP) – one of Australia's most significant biogeographic barriers – experiences extreme floods on a sub‐decadal timescale. These floods rise suddenly, cover thousands of square kilometres to a depth of several metres and can take weeks to subside. We investigated whether these floods have shaped community composition. If this is the case, species that are particularly vulnerable to extreme flooding – understorey animals and woody plants, particularly shrubs – should be under‐represented, and grasslands should be over‐represented on GUP floodplains. We used Akaike selection of logistic models to assess influence of floodplains and other potential drivers on grassland distribution and shrub abundance, and on representation of understorey fauna. We also compared post‐flood faunal records with the bioregional data set to assess influence of the 2009 flood on representation of understorey reptiles. Grasslands and shrub‐free vegetation were significantly over‐represented and understorey fauna significantly under‐represented on floodplains, even when the influences of other factors were taken into account. Understorey Gekkota were absent from – and understorey skinks under‐represented in – recently flooded areas. Hence, floods appear to have shaped community composition on GUP floodplains by selectively displacing and/or destroying woody plants – particularly shrubs – and understorey animals. Our findings demonstrate association rather than causality, but show that further examination of the ecological and biogeographic impacts of extreme flooding is warranted. Influence of floods on the Australian biota should be considered an ongoing ecological and evolutionary driver, and one that is likely to intensify as extreme floods are expected to become more frequent under climate change.
What Factors Determine Whether Small and Medium Enterprises Obtain Credit from the Formal Credit Market? The Case of Vietnam
Authors: Thi Khanh Cao Nguyet
Published: August 2019

Using a survey of Vietnamese small and medium enterprises (SMEs) conducted during 2005–2013, this paper examines the process of applying for a formal loan and the level of satisfaction (credit needs) obtained by SMEs. The empirical results show that banking relationships and the business environment are important factors when applying for and obtaining formal credit. However, positive measures of firms' financial performance, such as a high return on assets score and sales growth, did not have a significant influence on whether firms obtained credit. Formal financial institutions in Vietnam were found to depend too much on collateral assets in assessing whether to supply credit to an SME.
The role of the respectful maternity care model in São Paulo, Brazil: A cross‐sectional study
Authors: Giordano Juliana , Surita Fernanda G.
Published: August 2019

Introduction

The promotion of a positive birth experience has been a main goal of the World Health Organization’s (WHO) recent work on improving maternity care. The purpose of this study was to assess the cesarean rates, the prevalence of birth practices, perinatal outcomes, and maternal satisfaction, in women involved with the respectful maternity care (RMC) support groups in Sao Paulo, Brazil.

Methods

This was a cross‐sectional study of women with low‐risk pregnancies who were assisted by professionals recommended by the RMC groups. An online questionnaire was administered. Variables to assess birth practices were classified as positive, negative, or unspecified according to the WHO guidelines. The Pearson chi‐square tests and odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were computed to assess differences between the groups.

Results

Five‐hundred and eighty women completed the questionnaire. The cesarean rate was 14.7%, and the operative vaginal birth rate was 9.5%. The VBAC rate was 87.1%, and there was no significant difference in risk for cesarean between women with or without a prior cesarean. Of all women, 83.1% had a midwife's assistance and 75.5% hired a doula; 81.4% gave birth in a nonlithotomic position. The practices of enema, fasting and episiotomy were all under 2%. All 5‐minute Apgar scores were ≥7. Most (83.1%) women reported having a positive birth experience.

Conclusions

Woman's engagement with the birth support groups and a transdisciplinary team focused on RMC are key elements to achieve positive perinatal outcomes and high women's satisfaction.
Changing of the guards: Detrital zircon provenance tracking sedimentological reorganization of a post‐Gondwanan rift margin
Authors: Barham Milo , Kirkland Christopher L.
Published: August 2019

Understanding the development of sedimentary systems during continental rifting is important for tracking environmental change and lithospheric processes. Conceptual models have been developed for the sourcing, routing and facies architecture of sediments in rift‐settings, driven in part by quantitative sediment tracking. Here, we present laser ablation split‐stream detrital zircon U/Pb geochronology and Hf‐isotopes for post‐rift (Cretaceous‐Paleogene) clastic sediments from Ocean Drilling Program (ODP) wells and Plio‐Pleistocene palaeoshoreline material, from the southern margin of Australia. Provenance results are contextualized through comparison with well‐characterized source regions and regional pre‐ and syn‐rift sediment reservoirs to track changes associated with Australia‐Antarctica separation during East Gondwana break‐up. The provenance character of the post‐rift sediments studied are distinct from pre‐existing sediment reservoirs and demonstrate termination of previously stable sediment routing systems and a dominance of local basement of the Proterozoic Madura and Coompana provinces (~1.2 Ga and CHUR‐like Hf‐signatures; Moodini Supersuite) in offshore ODP wells. A composite post‐rift Cretaceous?‐Eocene sample in the easternmost well expresses characteristic Phanerozoic zircon age signatures associated with source regions in eastern Australia that are interpreted to reflect inversion in the Ceduna Sub‐basin to the east. Detrital zircon signatures in Plio‐Pleistocene palaeoshoreline sediment are also relatively distinct, indicating derivation from coastal erosion in the Leeuwin Complex (~0.5 and 0.7 Ga subchondritic grains) and Albany–Fraser Orogen (~1.2 Ga subchondritic grains) several hundred, to over a thousand kilometers to the west. Collectively, results highlight the fundamental geological processes associated with rifting that dramatically change the character of sediment provenance via (a) isolation of pre‐existing primary and secondary sources of detritus, (b) development of new source regions in basin compartmentalized highs and localized fault scarps, and (c) establishment of marine and coastal currents that redefine clastic sediment transport.
Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors
Authors: Jo Seri , Kim Hyojin , Kim Suwon , Shin Dong Hae , Kim Mi‐Sun
Published: August 2019

Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a zoonotic virus transmitted between animals and human beings. It causes MERS with high mortality rate. However, no vaccine or specific treatment is currently available. Since antiviral activity of some flavonoids is known, we applied a flavonoid library to probe inhibitory compounds against MERS‐CoV 3C‐like protease (3CLpro). Herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside and helichrysetin were found to block the enzymatic activity of MERS‐CoV 3CLpro. The binding of the four flavonoids was also confirmed independently using a tryptophan‐based fluorescence method. The systematic comparison of the binding affinity of flavonoids made it possible to infer their scaffolds and functional groups required to bind with MERS‐CoV 3CLpro. An induced‐fit docking analysis revealed that S1 and S2 sites play a role in interaction with flavonoids. The experimental and computational study showed that flavonol and chalcone are favourite scaffolds to bind with the catalytic site of MERS‐CoV 3CLpro. It was also deduced that some flavonoid derivatives with hydrophobic or carbohydrate attached to their core structures have a good inhibitory effect. Therefore, we suggest that flavonoids with these characteristics can be used as templates to develop potent MERS‐CoV 3CLpro inhibitors.