bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study: Acute Lumbar Paraspinal Compartment Syndrome in an Austere Military Environment
Authors: Allen Pete , Pugh Jackson , Blau Alexander
Published: October 2020

The incidence of compartment syndrome of the lumbar paraspinal muscles is exceedingly rare. Approximately 24 hours following a high-intensity kettlebell swing workout, a 33-year-old Sailor presented to the medical department on board a forward deployed Wasp-class amphibious assault ship with increasing discomfort in his middle and lower back, and evidence of rhabdomyolysis. Discomfort quickly turned to unrelenting pain coupled with dorsal paresthesias and rigidity in the paraspinal muscles. He was taken emergently to the operating room, where his paraspinal muscles were released via fasciotomy. As a result of limited resources aboard the deployed ship, a negative pressure wound dressing was fashioned using the supplies available aboard the ship. Following 3 days of the negative pressure wound therapy, muscle bulging decreased substantially, and the skin was closed. After 4 weeks of physical therapy, he returned to full duty.
Antiretroviral Therapy Anchor-based Trends in Body Mass Index Following Treatment Initiation Among Military Personnel with HIV
Authors: Kline Maj David A , Daniels Colton , Xu Xiaohe , Sunil Thankam , Ganesan Anuradha , Agan Brian K , Colombo Rhonda E , Kronmann Karl C , Blaylock Jason M , Okulicz Jason F , Markelz A Elizabeth
Published: October 2020

Introduction

Weight gain and obesity in people living with HIV have been associated with increased risk for non-AIDS-related comorbidities, and integrase strand transfer inhibitor (INSTI)-based regimens may lead to comparatively more weight gain than other regimens. We evaluated body mass index (BMI) following antiretroviral therapy (ART) initiation among participants in the U.S. Military HIV Natural History Study (NHS).

Materials and Methods

NHS participants with available baseline weight and height data initiating ART from 2006 to 2017 were considered for analysis. Antiretroviral therapy was categorized by anchor class to include INSTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Linear growth-curve modeling was used to predict BMI changes from ART initiation through 2 years of follow-up in participants stratified by baseline BMI (<25 vs ≥25 kg/m2) at ART start and anchor drug class. These models were adjusted for demographic- and HIV-related characteristics.

Results

Of 961 NHS participants started on initial ART between 2006 and 2017, 491 men who had available baseline BMI data and were virally suppressed (<200 c/mL) at 1 and 2 years of follow-up were included. Overall, the predicted BMI increased at each time point over 2 years regardless of baseline BMI. There was a trend toward less weight gain for non-INSTI regimens regardless of demographic- or HIV-related factors (−0.65 kg/m2/yr, P = .070). In participants with BMI <25, all regimens were associated with BMI gains except in those with high viral load (≥100,000 copies/mL) started on PI regimens (−1.91 kg/m2/yr, P = .000; n = 13). For those participants with BMI ≥25, only INSTI- and PI-based regimens were significantly associated with increased BMI (INSTI 0.54 kg/m2/y, P = .000; PI 0.39 kg/m2/yr, P = .006). Non-nucleoside reverse transcriptase inhibitors were not associated with weight gain regardless of race- or HIV-related characteristics. African Americans with BMI ≥25 were more likely to gain weight as compared to Whites (0.99 kg/m2/yr, P = .016). Specific anchor drug-based predictions revealed that only INSTI use among African Americans was significantly associated with BMI gains (1.85 kg/m2/yr, P = .007); NNRTI- and PI-related weight change was not significant as compared to Whites.

Conclusions

In our cohort of young military members with HIV infection, those with BMI <25 experienced BMI gains across all ART classes. Among those with BMI ≥25, African Americans on INSTI regimens had the greatest BMI gains. Further studies are needed to determine whether NNRTI regimens should be considered in certain individuals at risk for INSTI-associated weight gain.
Prevalence and Correlates of Cryptosporidium Infections in Kenyan Children With Diarrhea and Their Primary Caregivers
Authors: Deichsel Emily L , Hillesland Heidi K , Gilchrist Carol A , Naulikha Jaqueline M , McGrath Christine J , Van Voorhis Wesley C , Rwigi Doreen , Singa Benson O , Walson Judd L , Pavlinac Patricia B
Published: October 2020

Background

Cryptosporidium is a leading cause of diarrhea in Sub-Saharan Africa and is associated with substantial morbidity and mortality in young children.

Methods

  We analyzed data from children aged 6–71 months presenting to 2 public hospitals in Western Kenya with acute diarrhea and their primary caregivers, including detection of Cryptosporidium by quantitative polymerase chain reaction (PCR) and immunoassay analysis in stool samples from both children and their caregivers. Associations between potential transmission sources and child/caregiver Cryptosporidium infection were evaluated using prevalence ratios (PRs). Secondary analyses evaluated host and clinical risk factors of child/caregiver Cryptosporidium infection.

Results

Among 243 child–caregiver pairs enrolled, 77 children (32%) and 57 caregivers (23%) had Cryptosporidium identified by either immunoassay or PCR. Twenty-six of the 243 child–caregiver pairs (11%) had concordant detection of Cryptosporidium. Cryptosporidium infection in children was associated with detection of Cryptosporidium in caregivers (adjusted PR [aPR], 1.8; 95% CI, 1.2 to 2.6; P = .002) and unprotected water source (aPR, 2.0; 95% CI, 1.3 to 3.2; P = .003). Risk factors for Cryptosporidium detection in caregivers included child Cryptosporidium infection (aPR, 2.0; 95% CI, 1.3 to 3.0; P = .002) as well as cow (aPR, 3.1; 95% CI, 1.4 to 7.0; P = .02) and other livestock ownership (aPR, 2.6; 95% CI, 1.1 to 6.3; P = .03) vs no livestock ownership. Recent diarrhea in caregivers and children was independently associated with child and caregiver Cryptosporidium infections, respectively.

Conclusions

Our results are consistent with the hypothesis that Cryptosporidium transmission can occur directly between child–caregiver dyads as well as through other pathways involving water and livestock. Additional research into caregivers as a source of childhood Cryptosporidium infection is warranted.
A qualitative exploration of 14 to 17-year old adolescents’ views of early and preventative mental health support in schools
Authors: Spencer Liam , McGovern Ruth , Kaner Eileen
Published: October 2020

Background

Preventative interventions may be effective in reducing and preventing symptoms of mental ill health in children and young people. However, there is a paucity of research in this area that explores the views of young people. This paper reports on a qualitative study to inform the future development of attractive and appropriate early and preventative school-based mental health interventions.

Methods

Semi-structured interviews were conducted with a purposive sample of 12 young people aged 14–17 in North East England. Interviews were audio-recorded, transcribed, anonymised and analysed following a thematic approach.

Results

Four key themes were identified, relevant to those providing, designing and commissioning early and preventative mental health interventions in schools: ‘mental health literacy’, ‘risk factors for wellbeing decline’, ‘experience of school-based support’ and ‘recommendations for future support’.

Conclusions

Young people have varying levels of mental health literacy, but are able to identify academic stress, bullying and the transition from primary to secondary school as leading causes of worry. Young people want more regular and in-depth mental health education, tailored levels of support in school and improved training for teachers.
Evaluation of the pharmacokinetics and efficacy of transdermal flunixin for pain mitigation following castration in goats
Authors: Graves Meggan T , Schneider Liesel , Cox Sherry , Caldwell Marc , Krawczel Peter , Lee Amanda , Lear Andrea
Published: October 2020

The mitigation of pain associated with common management procedures is a rising concern among veterinarians, producers and consumers. Nonsteroidal anti-inflammatory drugs are vital compounds for this purpose due to their cost, convenience, and efficacy. A transdermal formulation of flunixin meglumine (FM) was approved for the treatment of pain in cattle; however, the efficacy has yet to be determined for small ruminants. The current study had two aims: 1) to determine the pharmacokinetics of transdermal flunixin meglumine (TD FM) in bucklings and 2) to evaluate pain mitigation by TD FM following castration. To evaluate pharmacokinetics, 12 male goats (mean age = 6 mo) received 2.2 mg/kg of FM IV (n = 6) or 3.3 mg/kg TD FM (n = 6). Plasma FM concentrations were measured. The mean Cmax, Tmax, and harmonic mean half-life for TD FM were 1.09 ± 0.65 μg/mL, 5.50 ± 2.95 h, and 7.16 ± 2.06 h, respectively. To evaluate the efficacy of pain mitigation, 18 goats were randomly assigned to three treatment groups: 1) TD FM and castration (FM CAST) (n = 6); 2) transdermal placebo and castration (PL CAST) (n = 6); and 3) TD FM and sham castration (SHAM) (n = 6). Plasma samples were collected at 0, 12, 24, 36, 48, 72, and 96 h to assess cortisol and prostaglandin E2 (PGE2). Daily dry matter intake (DMI) was recorded and body weight was measured at the beginning and end of the study. Thermography (IRT) images of the scrotum, as well as heart rate (HR), respiratory rate (RR), and rectal temperature, were taken twice daily. Separate mixed analysis of variance models were used to test the effects of treatment, time, and their interaction on mean body temperature, IRT, HR, and RR. Autoregressive covariance structure was utilized to account for repeated measures and individual goat DMI prior to the study was added as a covariate. There were no differences in vital parameters, IRT measurements, cortisol, or PGE2 in animals receiving either TD FM or placebo following castration (P > 0.05). DMI had a treatment by hour interaction and was significantly higher in FM CAST and SHAM groups than the PL CAST group (P = 0.04). Goats in the SHAM group gained weight throughout the study, whereas goats in all other groups lost weight (P = 0.02). Results indicate that TD FM may mitigate pain as demonstrated by increased DMI; however, a single dose may not be sufficient to reduce physiological indicators of pain associated with castration in goats.
Impact of beef carcass size on chilling rate, pH decline, display color, and tenderness of top round subprimals
Authors: Lancaster Jessica M , Buseman Brianna J , Weber Tanya M , Nasados James A , Richard Ron P , Murdoch Gordon K , Price William J , Colle Michael J , Bass Phillip D
Published: October 2020

Beef carcass weights in the United States have continued to increase over the past 30 yr. As reported by the United States Department of Agriculture, grid-based carcass weight discounts begin when carcasses exceed 408 kg. Despite weight discounts, beef carcass weights continue to increase. At the same time, an increased prevalence of discoloration and color variability in top round subprimals has been observed throughout the industry which may be influenced by the increases in carcass weights. The objectives of this study were to assess the effects of beef carcass size and its relationship to chill time, color, pH, and tenderness of the beef top round. In the current study, eight industry average weight beef carcasses (AW, 341–397 kg) and eight oversized beef carcasses (OW, exceeding 432 kg) were evaluated. Temperatures and pH measurements were observed on both sides of all carcasses for the initial 48 h postharvest at a consistent superficial and deep anatomical location of the respective top rounds. Carcasses were fabricated into subprimals at 48 h and top rounds were aged at 2 °C for an additional 12 d. The superficial location of both AW and OW carcasses cooled at a faster rate (P < 0.01) than the deep locations. The deep location of OW carcasses had a lower pH and a more rapid (P < 0.01) initial pH decline. Quantitative color of steaks from OW carcasses had greater mean L* (lightness; P = 0.01) and initial b* (yellowness; P < 0.01) values. The delayed temperature decline and the accelerated pH decline of the deep location of the top round of OW carcasses occur at different rates than AW carcasses. Delayed rate of cooling leads to irreversible impacts on steak appearance of top round steaks fabricated from OW beef carcasses when compared with AW carcasses.
Expression and localization of SWEETs inPopulusand the effect ofSWEET7overexpression in secondary growth
Authors: Zhang Li , Wang Lijuan , Zhang Jin , Song Cai , Li Yu , Li Jianbo , Lu Mengzhu
Published: October 2020

In trees, wood formation needs carbon import from the photosynthetic source tissues. Sugar transporters play important roles in carbohydrate transport into wood-forming cells. Sugars will eventually be exported transporters (SWEETs) play essential roles in many physiological processes. However, the roles of this family in the growth and development of woody plants have not been systematically investigated. In this study, 27 SWEET genes were identified in the Populus trichocarpa genome. These SWEET genes were classified into four clades based on their phylogenetic relationships, gene structures, conserved motifs and chromosomal locations. Representative SWEET members from each clade were selected for further studies. The PagSWEETs of Populus alba × Populus glandulosa were localized to plasma membrane, vacuolar, endoplasmic reticulum or Golgi. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that PagSWEETs have distinct expression patterns in various tissues, and PagSWEET5, 7, 10b, 10c, 15b, 17a and 17c exhibited high expression levels in stems. PagSWEET7 is localized to the cytoplasmic membrane and specifically expressed in the phloem as detected by histochemical GUS ($\beta $ - glucuronidase) assays. Xylem production and xylem sugar content were greater in developing wood of PagSWEET7 overexpression than wild-type lines. Collectively, these results provide valuable information for further investigating functions of PagSWEET genes, and identify PagSWEET7 as a candidate gene for using biotechnology to modify the wood formation in poplar.
Global DNA Methylation in Cord Blood and Neurodevelopmental Outcome at 18 Months of Age among Intrauterine Growth Restricted and Appropriate for Gestational Age Infants
Authors: Gurugubelli Krishna Rao , Ballambattu Vishnu Bhat , Bobby Zacheriah
Published: October 2020

Background

Intrauterine growth restriction (IUGR) is associated with faltered growth and development later in life. Alteration in DNA methylation may occur among IUGR babies and it can have bearing on the outcome.

Objectives

To compare the DNA methylation in the cord blood among IUGR and appropriate for gestational age (AGA) babies and find it is association with their neurodevelopmental outcome at 18 months of age.

Methodology

Genomic DNA methylation among 40 IUGR and equal number of AGA neonates was estimated by using 5-mC ELISA kit in the cord blood. Infants were assessed at birth and their anthropometric measurements were taken. They were regularly followed up and assessed for neurodevelopment outcome till 18 months of age using DASII (Developmental Assessment Scale for Indian Infants). DNA methylation was correlated with neurodevelopmental outcome. Numbers and percentages were used for categorical data. Mean and SD were used for continuous variables. The significant mean difference between IUGR and AGA was determined by independent Student t-test. To study the association between the DNA methylation and outcome, Spearman correlation was used. A p < 0.05 was considered as statistically significant.

Results

Significant difference in DNA methylation was observed between IUGR and AGA infants (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p < 0.001). Anthropometry (weight, length and head circumference) at birth was significantly decreased among IUGR infants. Hospital stay was significantly longer for IUGR infants. Motor (IUGR: 89.98 ± 18.77; AGA: 101.75 ± 9.62; p < 0.001), and mental (IUGR: 90.81 ± 11.13; AGA: 105.71 ± 7.20; p < 0.001) scores were significantly decreased among IUGR compared with AGA neonates at 18 months of follow-up. Global DNA methylation had a significant positive correlation with mental score but not with motor developmental score.

Conclusion

IUGR babies had lower motor and mental score compared with AGA babies. Cord blood global DNA methylation significantly correlated with mental development score but not with motor development at 18 months of age.
Using a betting game to reveal the rich nature of visual working memories
Authors: Jabar Syaheed B. , Sreenivasan Kartik K. , Lentzou Stergiani , Kanabar Anish , Brady Timothy F. , Fougnie Daryl
Published: October 2020

When we ask people to hold a color in working memory, what do they store? Do they remember colors as point estimates (e.g. a particular shade of red) or are memory representations richer, such as uncertainty distributions over feature space? We developed a novel paradigm (a betting game) to measure the nature of working memory representations. Participants were shown a set of colored circles and, after a brief memory delay, asked about one of the objects. Rather than reporting a single color, participants placed multiple bets to create distributions in color space. The dispersion of bets was correlated with performance, indicating that participants’ internal uncertainty guided bet placement. Furthermore, relative to the first response, memory performance improved when averaging across multiple bets, showing that memories contain more information than can be conveyed in a single response. Finally, information about the item in memory was present in subsequent responses even when the first response would generally be classified as a guess or report of an incorrect item, suggesting that such failures are not all-or-none. Thus, memory representations are more than noisy point estimates; they are surprisingly rich and probabilistic.
Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229E
Authors: Kistler Kathryn E. , Bedford Trevor
Published: October 2020

Seasonal coronaviruses (OC43, 229E, NL63 and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here, we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively-selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.
The evolution of social learning as phenotypic cue integration
Authors: Kuijper Bram , Leimar Olof , Hammerstein Peter , McNamara John M. , Dall Sasha R. X.
Published: October 2020

Most analyses of the origins of cultural evolution focus on when and where social learning prevails over individual learning, overlooking the fact that there are other developmental inputs that influence phenotypic fit to the selective environment. This raises the question how the presence of other cue ‘channels’ affects the scope for social learning. Here, we present a model that considers the simultaneous evolution of (i) multiple forms of social learning (involving vertical or horizontal learning based on either prestige or conformity biases) within the broader context of other evolving inputs on phenotype determination, including (ii) heritable epigenetic factors, (iii) individual learning, (iv) environmental and cascading maternal effects, (v) conservative bet-hedging and (vi) genetic cues. In fluctuating environments that are autocorrelated (and hence predictable), we find that social learning from members of the same generation (horizontal social learning) explains the large majority of phenotypic variation, whereas other cues are much less important. Moreover, social learning based on prestige biases typically prevails in positively autocorrelated environments, whereas conformity biases prevail in negatively autocorrelated environments. Only when environments are unpredictable or horizontal social learning is characterised by an intrinsically low information content, other cues such as conservative bet-hedging or vertical prestige biases prevail.
A Network Medicine Approach to Drug Repurposing for Chronic Pancreatitis
Authors: Golden Megan , Wilson Jabe
Published: October 2020

Despite decades of clinical investigations, there is currently no effective treatment for patients diagnosed with Chronic Pancreatitis (CP). Computational drug repurposing holds promise to rapidly identify therapeutics which may prove efficacious against the disease. Using a literature-derived knowledge graph, we train multiple machine learning models using embeddings based on i) the network topology of regulation bipartite networks, ii) protein primary structures and iii) molecule substructures. Using these models, we predict approved drugs that down-regulate the disease, and assess their proposed respective drug targets and mechanism of actions. We analyse the highest predicted drugs and find a diverse range of regulatory mechanisms including inhibition of fibrosis, inflammation, immmune response, oxidative stress and calcium homeostasis. Notably, we identify resiniferatoxin, a potent analogue of capsaicin, as a promising repurposable candidate due to its antiinflammatory properties, nociceptive pain suppression, and regulation of calcium homeostatis (through potentiation of mutant cystic fibrosis transmembrane conductance regulator (CFTR)). Resiniferatoxin may also regulate intracellular acinar Ca2+ via agonism of transient receptor potential vanilloid subfamily member 6 (TRPV6). We believe the potential of this repurposable drug warrants furtherin silicoandin vitrotesting, particularly the affect of the TRPV6 agonism on disease pathogenesis.
Binding of regulatory proteins to nucleosomes is modulated by dynamic histone tails
Authors: Peng Yunhui , Li Shuxiang , Onufriev Alexey , Landsman David , Panchenko Anna R.
Published: October 2020

Despite histone tails’ critical roles in epigenetic regulation, little is known about mechanisms of how histone tails modulate the nucleosomal DNA solvent accessibility and recognition of nucleosomes by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full human nucleosome, totaling 26 microseconds of molecular dynamics simulations. We explore the histone tail binding with the nucleosomal and linker DNA and observe rapid conformational transitions between bound and unbound states allowing us to estimate kinetic and thermodynamic properties of the histone tail-DNA interactions. Different histone types exhibit distinct, although conformationally heterogeneous, binding modes and each histone type occludes specific DNA regions from the solvent. Using a comprehensive set of experimental data on nucleosome structural complexes, we find that majority of the studied nucleosome-binding proteins and histone tails target mutually exclusive regions on nucleosomal or linker DNA around the super-helical locations ±1, ±2, and ±7. This finding is explained within the generalized competitive binding and tail displacement models of partners recruitment to nucleosomes. Finally, we demonstrate the crosstalk between different histone post-translational modifications, where charge-altering modifications and mutations typically suppress tail-DNA interactions and enhance histone tail dynamics.
Revisiting the phosphotyrosine binding pocket of Fyn SH2 domain led to the Identification of novel SH2 superbinders
Authors: Li Shuhao , Zou Yang , Zhao Dongping , Yin Yuqing , Song Jingyi , He Ningning , Liu Huadong , Qian Dongmeng , Li Lei , Huang Haiming
Published: October 2020

Protein engineering through directed evolution is an effective way to obtain proteins with novel functions with the potential applications as tools for diagnosis or therapeutics. Many natural proteins, largely antibodies as well as some non-antibody proteins, have undergone directed evolution in vitro in the test tubes in the laboratories around the world, resulted in the numerous protein variants with novel or enhanced functions. In this study, we constructed a Fyn SH2 variant library by randomizing the 8 variable residues in its phosphotyrosine (pTyr) binding pocket. Selection of this library by a pTyr peptide from MidT antigen led to the identification of SH2 variants with enhanced affinities to the peptide, compared to the wild type SH2, by EC50 assay. Fluorescent polarization (FP) was then applied to quantify the binding affinity of the newly identified SH2 variants. As a result, three SH2 variants, named V3, V13 and V24, have comparable binding affinities with the previously identified SH2 triple-mutant superbinder (refer to Trm). Biolayer Interferometry (BLI) assay was employed to disclose the kinetics of the binding of these SH2 superbinders, in addition to the wild type SH2, to the phosphotyrosine peptide. The results indicated that all the SH2 superbinders have two-orders increase of the dissociation rate when binding the pTyr peptide while there was no significant change in their associate rates. The previously identified SH2 superbinder Trm as well as the V13 and V24 discovered in this study have cross-reactivity with the sulfotyrosine (sTyr) containing peptide while the wild type SH2 does not. Intriguingly, though binding the pTyr peptide with comparable affinity with other SH2 superbinders, the V3 does not bind to the sTyr peptide, implying it binds to the pTyr peptide with a different pattern from the other superbinders. The newly identified superbinders could be utilized as tools for the identification of pTyr-containing proteins from tissues under different physiological or pathophysiological conditions and may have the potential in the therapeutics.
Metformin strongly affects gut microbiome composition in high-fat diet-induced type 2 diabetes mouse model of both sexes
Authors: Silamiķele Laila , Silamiķelis Ivars , Ustinova Monta , Kalniņa Zane , Elbere Ilze , Petrovska Ramona , Kalniņa Ineta , Kloviņš Jānis
Published: October 2020

Effects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mice models, as most of the existing studies have focused on males only.

Our study aimed to examine metformin-induced alterations in gut microbiome diversity and composition of high-fat diet-induced type 2 diabetes mouse model, employing a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups. We performed shotgun metagenomic sequencing using DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment.

We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species abundances increased. In contrast, no significant changes were observed in control diet-fed mice.We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while, in females, the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.
A novel cost framework reveals evidence for competitive selection in the evolution of complex traits during plant domestication
Authors: Allaby Robin G , Stevens Chris J , Fuller Dorian Q
Published: October 2020

Most models of selection incorporate some notion of environmental degradation where the majority of the population becomes less fit with respect to a character resulting in pressure to adapt. Such models have been variously associated with an adaptation cost, the substitution load. Conversely, adaptative mutations that represent an improvement in fitness in the absence of environmental change have generally been assumed to be associated with negligible cost. However, such adaptations could represent a competitive advantage that diminishes resource availability for others and so induces a cost. This type of adaptation in the form of seedling competition has been suggested as a mechanism for increases in seed size during domestication, a trait associated with the standard stabilizing selection model. We present a novel cost framework for competitive selection that demonstrates significant differences in behaviour to environmental based selection in intensity, intensity over time and directly contrasts to the expectations of the standard model. Grain metrics of nine archaeological crops fit a mixed model in which episodes of competitive selection often emerge from shifting optimum episodes of stabilizing selection, highlighting the potential prevalence of the mechanism outlined here and providing a fundamental insight into the factors driving domestication.
Flapjack: a data management and analysis tool for genetic circuit characterization
Authors: Feliú Guillermo Yáñez , Gómez Benjamín Earle , Berrocal Verner Codoceo , Silva Macarena Muñoz , Nuñez Isaac N. , Matute Tamara F. , Medina Anibal Arce , Vidal Gonzalo , Céspedes Carlos Vidal , Dahlin Jonathan , Federici Fernán , Rudge Timothy J.
Published: October 2020

Characterization is fundamental to the design, build, test, learn (DBTL) cycle for engineering synthetic genetic circuits. Components must be described in such a way as to account for their behavior in a range of contexts. Measurements and associated metadata, including part composition, constitute the test phase of the DBTL cycle. These data may consist of measurements of thousands of circuits, measured in hundreds of conditions, in multiple assays potentially performed in different labs and using different techniques. In order to inform the learn phase this large volume of data must be filtered, collated, and analyzed. Characterization consists of using this data to parameterize models of component function in different contexts, and combining them to predict behaviors of novel circuits. Tools to store, organize, share, and analyze large volumes of measurement and metadata are therefore essential to linking the test phase to the build and learn phases, closing the loop of the DBTL cycle. Here we present such a system, implemented as a web app with a backend data registry and analysis engine. An interactive frontend provides powerful querying, plotting and analysis tools, and we provide a REST API and Python package for full integration with external build and learn software. All measurements are associated to circuit part composition via SBOL. We demonstrate our tool by characterizing a range of genetic components and circuits according to composition and context.
Investigating epithelial-mesenchymal heterogeneity of tumors and circulating tumor cells with transcriptomic analysis and biophysical modeling
Authors: Bocci Federico , Mandal Susmita , Tejaswi Tanishq , Jolly Mohit Kumar
Published: October 2020

Introduction

Cellular heterogeneity along the Epithelial-Mesenchymal Plasticity (EMP) spectrum is a paramount feature observed in tumors and circulating tumor cells (CTCs). High-throughput techniques now offer unprecedented details on this variability at a single-cell resolution. Yet, there is no current consensus about how EMP in tumors propagates to that in CTCs. To investigate the relationship between EMP associated heterogeneity of tumors and that of CTCs, we integrated transcriptomic analysis and biophysical modeling.

Methods

We apply three EMT (Epithelial-Mesenchymal Transition) scoring metrics to multiple tumor samples and CTC datasets from several cancer types. Moreover, we develop a biophysical model that couples EMT associated phenotypic switching in a primary tumor with cell migration. Finally, we integrate EMT transcriptomic analysis andin silicomodeling to evaluate the predictive power of several measurements of tumor aggressiveness, including tumor EMT score, CTC EMT score, fraction of CTC clusters found in circulation, and CTC cluster size distribution.

Results

Analysis of high-throughput datasets reveals a pronounced heterogeneity without a well-defined relation between EMT traits in tumors and CTCs. Moreover, mathematical modeling predicts different phases where CTCs can be less, equally, or more mesenchymal than primary tumor depending on the dynamics of phenotypic transition and cell migration. Consistently, various datasets of CTC cluster size distribution from different cancer types are fitted onto different regimes of the model. By further constraining the model with experimental measurements of tumor EMT score, CTC EMT score, and fraction of CTC cluster in bloodstream, we show that none of these assays alone can provide sufficient information to predict the other variables.

Conclusions

By integrating analysis of single cell gene expression andin silicomodeling, we propose that the relationship between EMT progression in tumors and CTCs can be variable, and in general, predicting one from the other may not be as straightforward as tacitly assumed.
Characterizing the demographic history and prion protein variation to infer susceptibility to chronic wasting disease in a naïve population of white-tailed deer (Odocoileus virginianus)
Authors: Haworth Sarah E , Nituch Larissa , Northrup Joseph M , Shafer Aaron BA
Published: October 2020

Assessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human-dominated landscapes, often with contrasting effects. White-tailed deer (deer) are expanding in the northern part of their range following decreasing winter severity and increasing forage availability. Chronic wasting disease (CWD), a prion disease affecting cervids, is likewise expanding and represents a major threat to deer and other cervids. We obtained tissue samples from free-ranging deer across their native range in Ontario, Canada which has yet to detect CWD in wild populations of cervids. We used high-throughput sequencing to assess neutral genomic variation, and variation in the PRNP gene that is partly responsible for the protein misfolding when deer contract CWD. Neutral variation revealed a high number of rare alleles and no population structure, and demographic models suggested a rapid historical population expansion. Allele frequencies of PRNP variants associated with CWD susceptibility and disease progression were evenly distributed across the landscape and consistent with deer populations not infected with CWD. We then estimated the selection coefficient of CWD, with simulations showing an observable and rapid shift in PRNP allele frequencies that coincides with the start of a novel CWD epidemic. Sustained surveillance of genomic and PRNP variation can be a useful tool for CWD-free regions where deer are managed for ecological and economic benefits.
Molecular mechanisms of LC3-associated phagocytosis in the macrophage response toParacoccidioidesspp
Authors: de Oliveira Getúlio Pereira , de Sousa Herdson Renney , de Melo Gorgonha Kaio César , dos Santos Borges Tatiana Karla , Rangel Kellyanne Teixeira , Fabricant Scott , Gustavo Fernanda Cristina Koser , Friaça Lucas Fraga , Neto Angelo Rossi , Hurtado Fabián Andrés , Paes Hugo Costa , Casadevall Arturo , Silva-Pereira Ildinete , Albuquerque Patrícia , Felipe Maria Sueli Soares , Nicola André Moraes
Published: October 2020

Paracoccidiomycosis is a systemic fungal infection that is endemic in Latin America. The etiologic agents are thermodimorphic fungi from theParacoccidiodesgenus, which are facultative intracellular parasites of macrophages. LC3-associated phagocytosis (LAP), a noncanonical form of autophagy, is important in the immune response to similar pathogens, so we sought to determine the role LAP plays in the macrophage response toParacoccidioidesspp. By immunofluorescence, we found that LC3 was recruited to phagosomes containingParacoccidioidesspp. in both RAW264.7 and J774.16 cell lines and in bone marrow-derived macrophages. Interference with autophagy using RNAi againstATG5reduced the antifungal activity of J774.16 cells, showing that LC3 recrutiment is important for proper control of the fungus by macrophages. Finally, we used pharmacological Syk kinase and NAPH oxidase inhibitors, which inhibit signalling pathways necessary for macrophage LAP againstAspergillus fumigatusandCandida albicans, to dissect part of the signaling pathways that trigger LAP againsParacoccidioidesspp. Interestingly, these inhibitors did not decrease LAP againstP. brasiliensis, possibly due to differences in the fungal cell surface compositions. These observations suggest a potential role for autophagy as target for host-directed paracoccidioidomycosis therapies.
“My little piece of the planet”: the multiplicity of well-being benefits from allotment gardening
Authors: Dobson Miriam Clare , Reynolds Christian , Warren Philip H. , Edmondson Jill L.
Published: October 2020

Purpose

Participation in urban horticulture (UH) is increasing in popularity, and evidence is emerging about the wide range of social and environmental benefits “grow your own” can also provide. UH can increase mental and physical well-being, as well as improve nature connectedness, social capital and community cohesion.

Design/methodology/approach

This study focusses on allotments, which is one of the dominant forms of UH that takes place in the United Kingdom. 163 volunteers in England and Wales participated in keeping a year-long allotment diary as part of a citizen science project investigating activities on allotment gardens. This study examines the unprompted comments that 96 of these gardeners offered as observations when visiting their allotment plots.

Findings

Participants recorded high levels of social and community activities including the sharing of surplus food produce, knowledge exchange, awareness and interaction with wildlife, emotional connection to their allotment, appreciation of time spent outside and aesthetic delight in the natural world around them.

Originality/value

At a time when waiting lists for allotment plots in the United Kingdom are on the rise, and allotment land is subject to multiple pressures from other forms of development, this study demonstrates that these spaces are important sites not only for food production but also health, social capital and environmental engagement.
Barriers to integrating building information modelling (BIM) and lean construction practices on construction mega-projects: a Delphi study
Authors: Evans Martin , Farrell Peter
Published: October 2020

Purpose

The construction industry encounters substantial challenges in its evolution towards sustainable development and in the adoption of building information modelling (BIM) technology and lean construction (LC) practices on construction mega-projects. This research aims to investigate the critical barriers encountered by key construction stakeholders in their efforts to integrate BIM and LC in the construction mega-projects.

Design/methodology/approach

A two-round Delphi survey shaped the foundation of aggregating consensus between an expert panel that examined a set of 28 barriers resulting from a detailed analysis of the extant literature. Descriptive and inferential statistical tests were exploited for data analysis, and interrater agreement analysis was used to elaborated and validate results.

Findings

The research concluded that the key barriers by descending order of significance are lack of mandatory BIM and LC industry standards and regulations by the government, resistance of the industry to change from traditional practices to LeanBIM, high cost of software licenses and training and running of BIM.

Originality/value

The research findings and the proposed mitigation strategy will enhance the application of BIM and LC practices in construction mega-projects and allow project key stakeholders to place emphasis on tackling the crucial challenges and barriers identified in this research.
Exploring flexible home arrangements – an interview study of workers who live in vans
Authors: Duff Angus J. , Rankin Scott B.
Published: October 2020

Purpose

The purpose of this study is to understand the lived experience of workers who live in vans to explore how work and non-work interact when one's living environment is mobile.

Design/methodology/approach

In this qualitative study, semi-structured interviews were carried out with 18 participants. Thematic analysis of interview transcripts, coded while listening to each interview recording, provided a rich account of the interaction of work and non-work life domains.

Findings

Several themes were identified, including seeing the van as a home, hidden or disclosed identity stemming from living in a van, financial freedom, career freedom and work/non-work synchronization. Overall, findings suggest that flexible home arrangements, the relocation of one's home to adapt to work, aligned work and non-work domains to positively impact their overall work and non-work satisfaction, providing career freedom and expanded career opportunities.

Research limitations/implications

The understanding of workers who live in vans broadens one’s understanding of mobile work and the work/non-work interface, providing insight into the dual alignment of work and home to accommodate each other, which the authors term work/non-work synchronization.

Originality/value

This is one of the first studies to consider van living from a work and career perspective and for the first time conceptualizes the notion of flexible home arrangements.
Testing the precautionary argument after the Lucky Dragon incident
Authors: Dörries Matthias
Published: October 2020

Purpose

This paper uses a historical case study, the controversy over the possibility of climatic extremes caused by hydrogen bomb tests on Pacific Ocean atolls during the 1950s, to show how, in a context of few scientific data and high uncertainty, political affiliations and public concerns shaped two types of argumentation, the “energy” and the “precautionary” arguments.

Design/methodology/approach

Systematic analysis of publications 1954–1956: scientific and semiscientific articles, publications of C.-N. Martin and contemporary newspaper articles, especially from the Asia–Pacific region.

Findings

First, epistemological and scientific reasoning about the likelihood of extreme natural events aligned to political convictions and pressure. Second, a geographical and social distribution of arguments: the relativizing “energy argument” prevailed in English-language scientific journals, while the “precautionary argument” dominated in popular journals and newspapers published worldwide. Third, while the “energy argument” attained general scientific consensus within two years, it lost out in the long run. The proponents of the “precautionary argument” raised relevant research questions that, though first rejected in the 1950s, later exposed the fallacies of the “energy argument” (shown for the case of the climatologist William W. Kellogg).

Originality/value

In contrast to the existing secondary literature, this paper presents a balanced view of the weaknesses and strengths of two lines of arguments in the 1950s. Further, this historical study sheds light on how once-discarded scientific theories may ultimately be reconsidered in a completely different political and scientific context, thus justifying the original precautionary argument.
The reception and use of John Dewey's educational ideas by Hu Shi in the Early Republic of China
Authors: Zhao Kang
Published: October 2020

Purpose

Some studies have claimed that Chinese thinker Hu Shi (or Hu Shih) received and responded to John Dewey's educational ideas only at a theoretical level and did little for education at a practical level. This paper reexamines Hu's reception of Dewey's ideas with a focus on how he used those ideas to solve China's educational and social problems during the late 1910s and 1920s.

Design/methodology/approach

This paper draws upon what Schriewer (2012) has called “theories of reception.” Rather than focusing on the international dissemination of ideas and knowledge, this approach emphasizes the reception of foreign ideas from the perspective and needs of the receiver, interpreter and/or reader who apprehends such ideas within a particular socio–cultural context.

Findings

This paper finds that Hu not only received — and examined — Dewey's educational ideas in a systematic way, but also used them pragmatically to reform China's systems of education as part of the New Culture Movement after 1919.

Originality/value

This research offers a new understanding of Hu's reception of Dewey's educational ideas. It shows that Hu was not merely a “thinker” in the field of education but also a “doer” who sought to apply Dewey's ideas in practice. This new view allows us to reevaluate Hu's role in the modernization of Chinese education.
Antecedents of corporate reputation with employees in higher education institutions: a systematic review
Authors: Rashid Sufyan , Mustafa Hasrina
Published: October 2020

Purpose

The purpose of this paper is to provide a systematic review of studies on antecedents of the corporate reputation of higher education institutions (HEIs) from the perspectives of employees

Design/methodology/approach

The approach is an examination of previous literature on antecedents of corporate reputation in HEIs, published between 2010 and 2020.

Findings

The findings show that general and specific factors of corporate reputation in HEIs are being employed as strategic tools to survive the competitive nature of the higher education landscape.

Originality/value

Factors of corporate reputation in HEIs from the perspectives of employees are an understudied area with little academic literature available.