bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a Bridge to the Community: An Integrated Knowledge Translation Approach to Improving Participation in Community-Based Exercise for People After Stroke
Authors: Bird Marie-Louise , Mortenson B William , Chu Francis , Acerra Nicole , Bagnall Eric , Wright Angela , Hayley Karen , Yao Jennifer , Eng Janice J
Published: January 2019

Background

People who have had a stroke and are living in the community have low levels of physical activity, which reduces their functional capacity and increases risks of developing secondary comorbid conditions. Exercise delivered in community centers can address these low levels of physical activity; however, implementing evidence-based programs to meet the needs of all community stakeholders is challenging.

Objectives

The objective of this study was to determine implementation factors to facilitate participation in relevant exercise and physical activity for people with chronic health conditions, like stroke.

Design

The design consisted of a qualitative observational study using an integrated knowledge translation approach.

Methods

Supported by an integrated knowledge translation approach, a series of focus groups—with stakeholder group representation that included people who had had a stroke and care partners, community organizations (ie, support groups, community center staff), health care providers, and exercise deliverers—was conducted. During the focus groups, participants provided perspectives on factors that could influence implementation effectiveness. Focus groups were recorded, transcribed, and thematically analyzed.

Results

Forty-eight stakeholders participated. Based on the themes, a new implementation model that describes the importance of relationships between community centers, clinicians, and people who have had a stroke is proposed. The development of partnerships facilitates the implementation and delivery of exercise programs for people with ongoing health needs. These partnerships address unmet needs articulated in the focus groups and could fill a gap in the continuity of care.

Conclusions

Data from this study support the need for the community sector to offer a continuing service in partnership with the health system and people with chronic health needs. It indicates the potential of clinicians to partner with people with chronic health conditions and empower them to improve participation in relevant health behaviors, like community-based exercise.
Biological Control of Fusarium Crown and Root Rot of Wheat by Streptomyces Isolates – It’s Complicated
Authors: Winter Mark , Samuels Peter L. , Otto-Hanson Lindsey K. , Dill-Macky Ruth , Kinkel Linda L.
Published: January 2019

The predominant causal agents of Fusarium crown and root rot (FCR) of wheat, along with Fusarium pseudograminearum, are F. graminearum and F. culmorum. Members of the Gram-positive bacterial genus Streptomyces have been shown to inhibit isolates of the genus Fusarium, and Fusarium spp. isolates are also able to inhibit Streptomyces isolates in vitro. However, little is known about these complex antagonistic interactions and the potential for inhibitory Streptomyces to reduce FCR of wheat. The aim of this study was to analyze whether inhibitory Streptomyces isolates affect FCR of wheat and reduce root and stem base colonization by Fusarium culmorum. We enriched sterilized potting soil with spore suspensions of two Streptomyces isolates, inoculated the soil with F. culmorum-colonized wheat straw, and planted pre-germinated wheat seedlings. At 4 weeks, F. culmorum-inoculated plants had significant FCR symptoms on roots and showed reduced fresh weight of roots and above-ground plant biomass compared with the non-inoculated controls. Enrichment of soil with an inhibitory Streptomyces isolate reduced F. culmorum DNA in roots and stem bases by 75% compared with inoculation with F. culmorum alone. Interestingly, co-inoculation of F. culmorum with a non-inhibitory Streptomyces isolate led to the highest levels F. culmorum DNA in stem base tissue and greatest Streptomyces densities (CFU per g of soil) in the rhizosphere. In vitro assays revealed that F. culmorum showed a strong inhibitory activity against the pathogen-inhibitory Streptomyces isolate but not against the non-inhibitory isolate. In vitro tests with a larger set of 17 Streptomyces and five Fusarium spp. isolates revealed that there was little variation among Fusarium spp. isolates in capacities to inhibit the collection of Streptomyces isolates. In contrast, the sensitivity to inhibition by pathogenic Fusarium spp. isolates varied widely among Streptomyces isolates. The results of this study suggest the potential of Streptomyces isolates for biocontrol of FCR of wheat, while highlighting the specificity of Streptomyces−Fusarium interactions. Broader understanding of the variation in susceptibility within Fusarium spp. populations to Streptomyces inhibition and vice versa are needed to advance the potential for successful biological control.
Biological, Pathological, and Molecular Characteristics of a New Potyvirus, Dendrobium Chlorotic Mosaic Virus, Infecting Dendrobium Orchid
Authors: Huang Chih-Hung , Tai Chia-Hsing , Lin Ruey-Song , Chang Chung-Jan , Jan Fuh-Jyh
Published: January 2019

Dendrobium smillieae is one of the popular orchids in Taiwan. This report describes a new potyvirus tentatively named Dendrobium chlorotic mosaic virus (DeCMV) causing chlorotic and mosaic symptoms in D. smillieae. Enzyme-linked immunosorbent assay (ELISA) tests using six antisera against orchid-infecting viruses revealed that only a monoclonal antibody against the potyvirus group reacted positively with crude saps prepared from a symptomatic dendrobium orchid. Potyvirus-like, flexuous, filamentous particles were observed under an electron microscope, measuring approximately 700 to 800 nm in length and 11 to 12 nm in diameter. Sequence analyses revealed that DeCMV coat protein gene shared 59.6 to 66.0% nucleotide sequence identity and 57.6 to 66.0% amino acid sequence identity, whereas the DeCMV complete genome shared 54.1 to 57.3% nucleotide sequence identity and 43.7 to 49.5% amino acid sequence identity with those other known potyviruses. These similarity levels were much lower than the criteria set for species demarcation in potyviruses. Thus, DeCMV can be considered a new potyvirus. The whole DeCMV genome contains 10,041 nucleotides (GenBank accession no. MK241979) and encodes a polyprotein that is predicted to produce 10 proteins by proteolytic cleavage. In a pathogenicity test, results of inoculation assays demonstrated that DeCMV can be transmitted to dendrobium orchids by grafting and mechanical inoculation, as verified by ELISA and western blot analyses using the DeCMV polyclonal antiserum and by reverse transcription polymerase chain reaction using the coat protein gene-specific primers. The inoculated orchids developed similar chlorotic and mosaic symptoms. In conclusion, DeCMV is a novel orchid-infecting potyvirus, and this is the first report of a new potyvirus that infects dendrobium orchids in Taiwan.
Survey Research
Authors: Story David A. , Tait Alan R.
Published: January 2019

Surveys provide evidence on practice, attitudes, and knowledge. However, conducting good survey research is harder than it looks. The authors aim to provide guidance to both researchers and readers in conducting and interpreting survey research. Like all research, surveys should have clear research question(s) using the smallest possible number of high-quality, essential, survey questions (items) that will interest the target population. Both researchers and readers should put themselves in the position of the respondents. The survey questions should provide reproducible results (reliable), measure what they are supposed to measure (valid), and take less than 10 min to answer. Good survey research reports provide results with valid and reliable answers to the research question with an adequate response rate (at least 40%) and adequate precision (margin of error ideally 5% or less). Possible biases among those who did not respond (nonresponders) must be carefully analyzed and discussed. Quantitative results can be combined with qualitative results in mixed-methods research to provide greater insight.
Characterizing the Natural History of Acute Radiation Syndrome of the Gastrointestinal Tract: Combining High Mass and Spatial Resolution Using MALDI-FTICR-MSI
Authors: Carter Claire L. , Hankey Kim G. , Booth Catherine , Tudor Gregory L. , Parker George A. , Jones Jace W. , Farese Ann M. , MacVittie Thomas J. , Kane Maureen A.
Published: January 2019

The acute radiation syndrome of the gastrointestinal tract has been histologically characterized, but the molecular and functional mechanisms that lead to these cellular alterations remain enigmatic. Mass spectrometry imaging is the only technique that enables the simultaneous detection and cellular or regional localization of hundreds of biomolecules in a single experiment. This current study utilized matrix-assisted laser desorption/ionization mass spectrometry imaging for the molecular characterization of the first natural history study of gastrointestinal acute radiation syndrome in the nonhuman primate. Jejunum samples were collected at days 4, 8, 11, 15, and 21 following 12-Gy partial-body irradiation with 2.5% bone marrow sparing. Mass spectrometry imaging investigations identified alterations in lipid species that further understanding of the functional alterations that occur over time in the different cellular regions of the jejunum following exposure to high doses of irradiation. Alterations in phosphatidylinositol species informed on dysfunctional epithelial cell differentiation and maturation. Differences in glycosphingolipids of the villi epithelium that would influence the absorptive capacity and functional structure of the brush border membrane were detected. Dichotomous alterations in cardiolipins indicated altered structural and functional integrity of mitochondria. Phosphatidylglycerol species, known regulators of toll-like receptors, were detected and localized to regions in the lamina propria that contained distinct immune cell populations. These results provide molecular insight that can inform on injury mechanism in a nonhuman primate model of the acute radiation syndrome of the gastrointestinal tract. Findings may contribute to the identification of therapeutic targets and the development of new medical countermeasures.
Chinese Children's Experience When the Mother Has Breast Cancer
Authors: Huang Xiaoyan , Lee Susan , Hu Yan , Gao Hongyun , O'Connor Margaret
Published: January 2019

Background

A large number of women with breast cancer may have children younger than 18 years. When the mother has breast cancer, children may experience various concerns.

Objective

The aim of this study was to explore Chinese children's experience when confronted with maternal breast cancer from the perspectives of both children and their mothers.

Methods

Forty mothers with breast cancer were interviewed individually to talk about the experience of their children. In addition, 8 children aged 8 to 18 years were interviewed directly to share their experience, and 6 of them drew pictures to express their feelings.

Results

Six themes were identified: “They were discussing it”—being informed of maternal breast cancer; “What about me if my mother dies?”—children's feelings and concerns; “Grandmother took care of me”—impact on daily life; “Mother did not smile anymore”—impact on mother and family; “I am happy to help”—pleasing their mother; and “I did not tell others”—hiding emotions.

Conclusions

When their mother was diagnosed with breast cancer, Chinese children experienced various negative feelings, although their daily life was not profoundly affected because of grandparents' help. However, children's concerns may be underestimated by their mothers. Fathers and grandparents also played an important role in the interactions with children.

Implications for Practice

Mothers in China need to understand their children's reactions in order to help them cope with the illness. Children's experiences should be further explored. The understanding of children from the perspectives of fathers and grandparents also requires further research.
Single Intra-articular Platelet-Rich Plasma Versus Corticosteroid Injections in the Treatment of Adhesive Capsulitis of the Shoulder
Authors: Barman Apurba , Mukherjee Somnath , Sahoo Jagannatha , Maiti Rituparna , Rao Parnandi Bhaskar , Sinha Mithilesh Kumar , Sahoo Dibyajyoti , Tripathy Sujit Kumar , Patro Binod Kumar , Bag Nerbadyswari Deep
Published: January 2019

Objective

The aim of the study was to compare the effects of single intra-articular platelet-rich plasma (PRP) and corticosteroid (CS) injections in patients with adhesive capsulitis of the shoulder.

Design

Patients aged 18–70 yrs of either sex, diagnosed with adhesive capsulitis of shoulder, with less than 6-mo duration, were included. In intra-articular corticosteroid (IA-CS, control) group, 30 patients received a single injection (4 ml) of IA-CS and in IA-PRP (test) group, 30 patients received single IA-PRP injection (4 ml) into the glenohumeral joint under ultrasound guidance. All patients were prospectively followed for 12 wks.

Results

Twenty-eight patients in IA-PRP group and 27 in IA-CS group finished the entire 12-wk study period. At 12 wks, decrements in visual analog scale and total shoulder pain and disability index scores, in IA-PRP group, were 58.4 and 55.1, compared with 48.7 and 45.8 in IA-CS group. In range of movement, IA-PRP group showed significant improvement in passive abduction (−50.4 vs. −39.4), internal (−36.8 vs. −25.8), and external rotations (−35.4 vs. −25.9) compared with IA-CS group, respectively. No major complications were observed in any patients.

Conclusions

At 12-wk follow-up, a single dose of IA-PRP injection was found to be more effective than an IA-CS injection, in terms of improving pain, disability, and shoulder range of movement in patients with adhesive capsulitis of the shoulder.
Is Adherence to a Gluten-Free Diet by Adult Patients With Celiac Disease Influenced by Their Knowledge of the Gluten Content of Foods?
Authors: Paganizza Stefania , Zanotti Renzo , D'Odorico Anna , Scapolo Paola , Canova Cristina
Published: January 2019

The aim of this study was to investigate adherence to a gluten-free diet and potentially associated factors, focusing on the relationship between adherence and knowledge of the gluten content of foods and of celiac disease in general. A questionnaire was completed by adult patients diagnosed with celiac disease including demographics, dietary practices, sources of information, and attitude to the disease. Their knowledge of disease and gluten-free diet was assessed using a newly developed scale comprising 31 statements on celiac disease in general and foods appropriate in a gluten-free diet. A validated questionnaire was used to measure adherence to diet. One hundred four patients with celiac disease took part in the study, 65% of them reported strictly adhering to a gluten-free diet. Factors associated with adherence were membership of the Italian Celiac Association and receiving support from this association, Internet, and social media. Patients' knowledge regarding celiac disease and gluten-free diet was generally poor: one patient answered all questions correctly. Knowledge of celiac disease and gluten-free diet was strongly and significantly associated with adherence to a gluten-free diet. The association between knowledge of celiac disease and gluten-free diet in patients with celiac disease and their adherence to the diet suggests the promotion of education and behavioral programs.
Lactulose Management of Minimal Hepatic Encephalopathy
Authors: Zucker Donna M. , Redulla Rhoda
Published: January 2019

Minimal hepatic encephalopathy has been shown to increase risk of involvement in road traffic accidents and alter quality of life. This systematic review focused on the role of nonabsorbable disaccharides for the management of minimal hepatic encephalopathy. Randomized clinical trials that evaluated medical management of minimal hepatic encephalopathy were considered for inclusion. Individual studies compared lactulose with usual care and lactulose with probiotics and l-ornithine-l-aspartate. The outcome for examination was the neuropsychiatric test for cognitive function. Search strategies outlined by the Johanna Briggs Institute were used, and articles and references of selected articles were reviewed according to that methodology. Meta-analyses and narrative synthesis of the included studies were undertaken. Treatment of minimal hepatic encephalopathy with lactulose, probiotics, or l-ornithine-l-aspartate was seen to be equally effective in reducing abnormal tests at 1, 3, and 12 months post-treatment. All patients with minimal hepatic encephalopathy should be screened using a neuropsychiatric test and receive treatment as needed. Treatment can delay or eliminate risky automobile accidents and harm to self. Lactulose, probiotics, and l-ornithine-l-aspartate are a low-cost alternative compared with antibiotic treatment.
Male sexual signal predicts phenotypic plasticity in offspring: implications for the evolution of plasticity and local adaptation
Authors: Kelly Patrick W. , Pfennig David W. , de la Serna Buzón Sofia , Pfennig Karin S.
Published: January 2019

In a rapidly changing world, understanding the processes that influence a population's ability to respond to natural selection is critical for identifying how to preserve biodiversity. Two such processes are phenotypic plasticity and sexual selection. Whereas plasticity can facilitate local adaptation, sexual selection potentially impedes local adaptation, especially in rapidly changing or variable environments. Here we hypothesize that, when females preferentially choose males that sire plastic offspring, sexual selection can actually facilitate local adaptation to variable or novel environments by promoting the evolution of adaptive plasticity. We tested this hypothesis by evaluating whether male sexual signals could indicate plasticity in their offspring and, concomitantly, their offspring's ability to produce locally adapted phenotypes. Using spadefoot toads (Spea multiplicata) as our experimental system, we show that a male sexual signal predicts plasticity in his offspring's resource-use morphology. Specifically, faster-calling males (which are preferred by females) produce more plastic offspring; such plasticity, in turn, enables these males' offspring to respond adaptively to the spadefoots’ highly variable environment. The association between a preferred male signal and adaptive plasticity in his offspring suggests that female mate choice can favour the evolution and maintenance of phenotypic plasticity and thereby foster adaptation to a variable environment.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Life-history trade-offs and limitations associated with phenotypic adaptation under future ocean warming and elevated salinity
Authors: Jarrold Michael D. , Chakravarti Leela J. , Gibbin Emma M. , Christen Felix , Massamba-N'Siala Gloria , Blier Pierre U. , Calosi Piero
Published: January 2019

Little is known about the life-history trade-offs and limitations, and the physiological mechanisms that are associated with phenotypic adaptation to future ocean conditions. To address this knowledge gap, we investigated the within- and trans-generation life-history responses and aerobic capacity of a marine polychaete,
Ophryotrocha labronica,
to elevated temperature and elevated temperature combined with elevated salinity for its entire lifespan. In addition, transplants between treatments were carried out at both the egg mass and juvenile stage to identify the potential influence of developmental effects. Within-generation, life-history trade-offs caused by the timing of transplant were only detected under elevated temperature combined with elevated salinity conditions. Polychaetes transplanted at the egg mass stage grew slower and had lower activities of energy metabolism enzymes but reached a larger maximum body size and lived longer when compared with those transplanted as juveniles. Trans-generation exposure to both elevated temperature and elevated temperature and salinity conditions restored 20 and 21% of lifespan fecundity, respectively. Trans-generation exposure to elevated temperature conditions also resulted in a trade-off between juvenile growth rates and lifespan fecundity, with slower growers showing greater fecundity. Overall, our results suggest that future ocean conditions may select for slower growers. Furthermore, our results indicate that life-history trade-offs and limitations will be more prevalent with the shift of multiple global change drivers, and thus there will be greater constraints on adaptive potential.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Depletion of hemoglobin transcripts and long read sequencing improves the transcriptome annotation of the polar bear (Ursus maritimus)
Authors: Byrne Ashley , Supple Megan A. , Volden Roger , Laidre Kristin L. , Shapiro Beth , Vollmers Christopher
Published: January 2019

Transcriptome studies evaluating whole blood and tissues are often confounded by overrepresentation of highly abundant transcripts. These abundant transcripts are problematic as they compete with and prevent the detection of rare RNA transcripts, obscuring their biological importance. This issue is more pronounced when using long-read sequencing technologies for isoform-level transcriptome analysis, as they have relatively lower throughput compared to short-read sequencers. As a result long-read based transcriptome analysis is prohibitively expensive for non-model organisms. While there are off-the-shelf kits available for select model organisms capable of depleting highly abundant transcripts for alpha (HBA) and beta (HBB) hemoglobin, they are unsuitable for non-model organisms. To address this, we have adapted the recent CRISPR/Cas9 based depletion method (Depletion of Abundant Sequences by Hybridization) for long-read full-length cDNA sequencing approaches that we call Long-DASH. Using a recombinant Cas9 protein with appropriate guide RNAs, full-length hemoglobin transcripts can be depleted in-vitro prior to performing any short- and long-read sequencing library preparations. Using this method, we sequenced depleted full-length cDNA in parallel using both our Oxford Nanopore Technology (ONT) based R2C2 long-read approach, as well as the Illumina short-read based Smart-seq2 approach. To showcase this, we have applied our methods to create an isoform-level transcriptome from whole blood samples derived from three polar bears (Ursus maritimus). Using Long-DASH, we succeeded in depleting hemoglobin transcripts and generated deep Smart-seq2 Illumina datasets and 3.8 million R2C2 full-length cDNA consensus reads. Applying Long-DASH with our isoform identification pipeline, Mandalorion we discovered ~6,000 high-confidence isoforms and a number of novel genes. This indicates there is a high diversity of gene isoforms within Ursus maritimus not yet reported. This reproducible and straightforward approach has not only improved the polar bear transcriptome annotations but will serve as the foundation for future efforts to investigate transcriptional dynamics within the 19 polar bear subpopulations around the Arctic.
Applications of Machine Learning in Decision Analysis for Dose Management for Dofetilide
Authors: Levy Andrew E. , Biswas Minakshi , Weber Rachel , Tarakji Khaldoun , Chung Mina , Noseworthy Peter A. , Newton-Cheh Christopher , Rosenberg Michael A.
Published: January 2019

Initiation of the antiarrhythmic medication dofetilide requires an FDA-mandated 3 days of telemetry monitoring due to heightened risk of toxicity within this time period. Although a recommended dose management algorithm for dofetilide exists, there is a range of real-world approaches to dosing the medication. In this multicenter investigation, we examined the decision process for dose adjustment of dofetilide during the observation period using machine-learning approaches, including supervised, unsupervised, and reinforcement learning applications. Logistic regression approaches identified any dose-adjustment as a strong negative predictor of successful loading (i.e., discharged on dofetilide) of the medication (OR 0.19, 95%CI 0.12 – 0.31, p < 0.001 for discharge on dofetilide), indicating that these adjustments are strong determinants of whether patients “tolerate” the medication. Using multiple supervised approaches, including regularized logistic regression, random forest, boosted gradient decision trees, and neural networks, we were unable to identify any model that predicted dose adjustments better than a naïve approach. A reinforcement-learning algorithm, in contrast, predicted which patient characteristics and dosing decisions that resulted in the lowest risk of failure to be discharged on the medication. Future studies could apply this algorithm prospectively to examine improvement over standard approaches.
Flexible pivoting of dynamin PH-domain catalyzes fission: Insights into molecular degrees of freedom
Authors: Baratam K. K. , Jha K. , Srivastava A.
Published: January 2019

The neuronal dynamin1 functions in the release of synaptic vesicles by orchestrating the process of GTPase-dependent membrane fission. Dynamin1 associates with the plasma membrane-localized phosphatidylinositol-4,5-bisphosphate (PIP2) with its centrally-located pleckstrin homology domain (PHD). The PHD is dispensable as fission can be managed, albeit at much slower rates, even when the PHD-PIP2 interaction is replaced by a generic polyhistidine- or polylysine-lipid interaction. However, even when the PHD is present, the length of the dynamin scaffold and in turn the membrane remodeling and fission rates are severely restricted with mutations such as I533A on membrane-interacting variable loop 1 (VL1) of PHD. These observations suggest that PIP2-containing membrane interactions of PHD could have evolved to expedite fission to fulfill the requirement of rapid kinetics of synaptic vesicle recycling. Here, we use a suite of multiscale modeling approaches that combine atomistic molecular dynamics simulations, mixed resolution membrane mimetic models, coarse-grained molecular simulations and advanced free-energy sampling methods (metadynamics and umbrella sampling) to explore PHD-membrane interactions. Our results reveal that: (a) the binding of PHD to PIP2-containing membranes modulates the lipids towards fission-favoring conformations and softens the membrane, (b) that PHD engages another loop (VL4) for membrane association, which acts as an auxiliary pivot and modulates the orientation flexibility of PHD on the membrane – a mechanism we believe may be important for high fidelity dynamin collar assembly on the membrane. (c) Through analyses of our trajectories data and free-energy calculations on membrane-bound WT and mutant systems, we also identify key residues on multiple VLs that stabilizes PHD membrane association. And we suggest experiments to explore the ability of PHD to associate with membrane in orientations that favors faster fission. Together, these insights provide a molecular-level understanding of the “catalytic” role of the PHD in dynamin-mediated membrane fission.

SIGNIFICANCE

Dynamin, a large multi-domain GTPase, remodels the membrane by self-assembling onto the neck of a budding vesicle and induces fission by its energy driven conformational changes. In this work, we use multi-scale molecular simulations to probe the role of dynamin’s pleckstrin-homology domain (PHD), which facilitates membrane interactions. Notably, PHD is dispensable for fission as is the case with extant bacterial and mitochondrial dynamins. However, reconstitution experiments suggest that the functional role of PHD in neuronal-membrane goes beyond that of an adaptor domain as it possibly ‘expedites’ the fission reaction during synaptic vesicle recycling. We provide a molecular-dynamics picture of how PHDs make membranes more pliable for fission and suggest new insights into the molecular-level processes driving the expedited fission behavior.
Inhibiting IFT dynein with ciliobrevin in C. elegans chemosensory cilia
Authors: Mijalkovic Jona , Peterman Erwin J.G.
Published: January 2019

Cytoplasmic dyneins play a role in a myriad of cellular processes, such as retrograde intracellular transport and cell division. Small-molecule cytoplasmic dynein antagonists, ciliobrevins, have recently been developed as tools to acutely probe cytoplasmic dynein function. Although widely used to investigate cytoplasmic dynein 1, far fewer studies explore the effect of ciliobrevin on cytoplasmic dynein 2 or IFT dynein. Here, we use ciliobrevin A to partially disrupt IFT dynein in the chemosensory cilia of living C. elegans. Acute, low-concentration ciliobrevin treatment results in shortening of cilia and reduction of transport velocity in both directions. After longer exposure to ciliobrevin, we find concentration-dependent motor accumulations and axonemal deformations. We propose that maintenance of ciliary length requires a high fraction of active IFT-dynein motors, while structural integrity can be preserved by only a few active motors.
Extinctions in marine plankton preceded by stabilizing selection
Authors: Weinkauf Manuel F. G. , Bonitz Fabian G. W. , Martini Rossana , Kučera Michal
Published: January 2019

Unless they adapt, populations facing persistent stress are threatened by extinction. Theoretically, populations facing stress can react by either disruption, increasing trait variation, or stabilisation, decreasing trait variation. In the short term, the more economical response is stabilisation, because it quickly transfers a large part of the population closer to a new ecological optimum. However, canalisation is deleterious in the face of persistently increasing stress because it reduces variability and thus decreases the ability to react to further change in stress. Understanding how natural populations react to intensifying stress reaching terminal levels is key to assessing their resilience to environmental change such as that caused by global warming. Because extinctions are hard to predict, observational data on the adaptive reaction of populations facing extinction are rare. In this study, we make use of the glacial salinity rise in the Red Sea as a natural experiment allowing us to analyse the reaction of planktonic Foraminifera to stress escalation in the geological past. We analyse morphological trait state and variance in two species across a salinity rise leading to their local extinction. One species reacted by stabilisation in shape and size, detectable several thousand years prior to extinction. The second species reacted by trait divergence, but each of the two divergent populations remains stable or reacted by further stabilisation. These observations indicate that the default reaction of the studied Foraminifera is stabilisation and that stress escalation did not lead to the local emergence of adapted forms. Inability to breach the global adaptive threshold would explain why communities of Foraminifera, and many other groups of marine plankton, reacted to Quaternary climate change by faithfully tracking their zonally shifting environments. It also means that populations of marine species adapted to response by migration, when exposed to stress outside of the adaptive range, will be at risk of extinction.
The fitness cost of a congenital heart defect shapes its genetic architecture
Authors: Akhirome Ehiole , Regmi Suk D. , Magnan Rachel A. , Ugwu Nelson , Qin Yidan , Schulkey Claire E. , Cheverud James M. , Jay Patrick Y.
Published: January 2019

Background

In newborns, severe congenital heart defects are rarer than mild ones. The reason why is unknown, but presumably related to a liability threshold that rises with the severity of a defect. Because the same genetic mutation can cause different defects, other variables may contribute to pushing an individual past a defect-specific liability threshold. We consider here how variables in the genetic architecture of a heart defect depend upon its fitness cost, as defined by the likelihood of survival to reproductive age in natural history studies.

Methods

We phenotyped ~10,000Nkx2-5+/-newborn mice, a model of human congenital heart disease, from two inbred strain crosses. Genome-wide association analyses detected loci that modify the risk of an atrial septal defect, membranous or muscular ventricular septal defect, or atrioventricular septal defect. The number of loci, heritability and quantitative effects on risk of pairwise (G×GNkx) and higher-order (G×G×GNkx) epistasis between the loci andNkx2-5mutation were examined as a function of the fitness cost of a defect.

Results

Nkx2-5+/-mice have pleiotropic heart defects; about 70% have normal hearts. The model recapitulates the epidemiological relationship between the severity and incidence of a heart defect. Neither the number of modifier loci nor heritability depends upon the severity of a defect, but G×GNkxand G×G×GNkxeffects on risk do. Interestingly, G×G×GNkxeffects are three times more likely to suppress risk when the genotypes at the first two loci are homozygous and from the same, rather than opposite strains in a cross. Syn- and anti-homozygous genotypes at G×G×GNkxinteractions can have an especially large impact on the risk of an atrioventricular septal defect.

Conclusions

Given a modestly penetrant mutation, epistasis contributes more to the risk of severe than mild congenital heart defect. Conversely, genetic compatibility between interacting genes, as indicated by the protective effects of syn-homozygosity at G×G×GNkxinteractions, plays a newfound role in the robustness of cardiac development. The experimental model offers practical insights into the nature of genetic risk in congenital heart disease. The results more fundamentally address a longstanding question regarding how mutational robustness could arise from natural selection.
Exosome labeling by lipophilic dye PKH26 results in significant increase in vesicle size
Authors: Dehghani Mehdi , Gulvin Shannon M. , Flax Jonathan , Gaborski Thomas R.
Published: January 2019

Exosomes are membrane vesicles secreted by cells and distributed widely in all biofluids. Exosomes can modulate the biological activities of cells in a paracrine or endocrine manner, in part by transferring their content, such as miRNA, following uptake in recipient cells. Fluorescent labelling of exosomes is a commonly used technique for understanding their cellular targeting and biodistribution. Lipophilic fluorescent dyes such as those in the PKH family have been widely used for exosome labelling. One concern with the use of lipophilic dyes is an increase in the exosome size due to membrane fusion or intercalation. This size shift alone may undermine the validity of exosomes tracing studies as small changes in the size of inorganic nanoparticles are known to affect their cellular uptake and biodistribution. Here, the possibility of minimizing the size shift of PKH labelled exosomes was systematically studied by changing the labelling condition. Unfortunately, the size shift towards larger particles was observed in all the PKH labelling conditions, including those where the labelled exosomes were below the fluorescent detection limit. As opposed to lipophilic dyes, no significant shift in the size of labelled exosomes was detected with protein binding dyes. Since the size shifts identified in all the PKH labelling conditions are likely to affect the cellular uptake and biodistribution, PKH may not be a reliable technique for exosomes tracking.
Draft genome sequence of the Solanum aethiopicum provides insights into disease resistance, drought tolerance and the evolution of the genome
Authors: Song Bo , Song Yue , Fu Yuan , Kizito Elizabeth Balyejusa , Kabod Pamela Nahamya , Liu Huan , Kamenya Sandra Ndagire , Muthemba Samuel , Kariba Robert , Li Xiuli , Wang Sibo , Cheng Shifeng , Muchugi Alice , Jamnadass Ramni , Shapiro Howard-Yana , Deynze Allen Van , Yang Huanming , Wang Jian , Xu Xun , Odeny Damaris Achieng , Liu Xin
Published: January 2019

Background

S. aethiopicum is a close relative to S. melongena and has been routinely used to improve disease resistance in S. melongena. However, these efforts have been greatly limited by the lack of a reference genome and the clear understanding of the genes involved during biotic and abiotic stress response.

Results

We present here a draft genome assembly of S. aethiopicum of 1.02 Gb in size, which is predominantly occupied by repetitive sequences (76.2%), particularly long terminal repeat elements. We annotated 37,681 gene models including 34,905 protein-coding genes. We observed an expansion of resistance genes through two rounds of amplification of LTR-Rs, occurred around 1.25 and 3.5 million years ago, respectively. The expansion also occurred in gene families related to drought tolerance. A number of 14,995,740 SNPs are identified by re-sequencing 65 S. aethiopicum genotypes including “Gilo” and “Shum” accessions, 41,046 of which are closely linked to resistance genes. The domestication and demographic history analysis reveals selection of genes involved in drought tolerance in both “Gilo” and “Shum” groups. A pan-genome of S. aethiopicum with a total of 36,250 protein-coding genes was assembled, of which 1,345 genes are missing in the reference genome.

Conclusions

Overall, the genome sequence of S. aethiopicum increases our understanding of the genomic mechanisms of its extraordinary disease resistance and drought tolerance. The SNPs identified are available for potential use by breeders. The information provided here will greatly accelerate the selection and breeding of the African eggplant as well as other crops within the Solanaceae family.
The molecular clock of Mycobacterium tuberculosis
Authors: Menardo F. , Duchêne S. , Brites D. , Gagneux S.
Published: January 2019

The molecular clock and its phylogenetic applications to genomic data have changed how we study and understand one of the major human pathogens, Mycobacterium tuberculosis (MTB), the causal agent of tuberculosis. Genome sequences of MTB strains sampled at different times are increasingly used to infer when a particular outbreak begun, when a drug resistant clone appeared and expanded, or when a strain was introduced into a specific region. Despite the growing importance of the molecular clock in tuberculosis research, there is a lack of consensus as to whether MTB displays a clocklike behavior and about its rate of evolution. Here we performed a systematic study of the MTB molecular clock on a large genomic data set (6,285 strains), covering most of the global MTB diversity and representing different epidemiological settings. We found wide variation in the degree of clocklike structure among data sets, indicating that sampling times are sometimes insufficient to calibrate the clock of MTB. For data sets with temporal structure, we found that MTB genomes accumulate between 1×10−8 and 5×10−7 nucleotide changes per-site-per-year, which corresponds to 0.04 – 2.2 SNPs per-genome-per-year. Contrary to what expected, these estimates were not dependent on the time of the calibration points as they did not change significantly when we used epidemiological isolates (sampled in the last 40 years) or ancient DNA samples (about 1,000 years old) to calibrate the tree. Additionally, the uncertainty and the discrepancies in the results of different methods were often large, highlighting the importance of using different methods, and of considering carefully their assumptions and limitations.

Significance Statement

One of the major recent advancement in evolutionary biology is the development of statistical methods to infer the past evolutionary history of species and populations with genomic data. In the last five years, many researchers have used the molecular clock to study the evolution of Mycobacterium tuberculosis, a bacterial pathogen that causes tuberculosis and is responsible for millions of human deaths every year. The application of the molecular clock to tuberculosis is extremely useful to understand the evolution of drug resistance, the spread of different strains and the origin of the disease. Since some of these studies found contrasting results, we performed a systematic analysis of the molecular clock of MTB. This study will provide an important guideline for future analyses of tuberculosis and other organisms.
Nuclear pore density controls heterochromatin reorganization during senescence
Authors: Boumendil Charlene , Hari Priya , Olsen Karl C.F. , Acosta Juan Carlos , Bickmore Wendy A.
Published: January 2019

During oncogene-induced senescence (OIS), heterochromatin is lost from the nuclear periphery and forms internal senescence-associated heterochromatin foci (SAHFs). We show that an increased nuclear pore density during OIS is responsible for SAHF formation. In particular, the nucleoporin TPR is necessary for both formation and maintenance of SAHFs. Loss of SAHFs does not affect cell cycle arrest but abrogates the senescence-associated secretory phenotype—a program of inflammatory cytokine gene activation. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and demonstrate the importance of heterochromatin organization for a specific gene activation program.
ZOO: an automatic data-collection system for high-throughput structure analysis in protein microcrystallography
Authors: Hirata Kunio , Yamashita Keitaro , Ueno Go , Kawano Yoshiaki , Hasegawa Kazuya , Kumasaka Takashi , Yamamoto Masaki
Published: January 2019

Owing to the development of brilliant microfocus beamlines, rapid-readout detectors and sample changers, protein microcrystallography is rapidly becoming a popular technique for accessing structural information from complex biological samples. However, the method is time-consuming and labor-intensive and requires technical expertise to obtain high-resolution protein crystal structures. At SPring-8, an automated data-collection system named ZOO has been developed. This system enables faster data collection, facilitates advanced data-collection and data-processing techniques, and permits the collection of higher quality data. In this paper, the key features of the functionality put in place on the SPring-8 microbeam beamline BL32XU are described and the major advantages of this system are outlined. The ZOO system will be a major driving force in the evolution of the macromolecular crystallography beamlines at SPring-8.
Self-efficacy and workplace well-being: moderating role of sustainability practices
Authors: Singh Sanjay Kumar , Pradhan Rabindra Kumar , Panigrahy Nrusingh Prasad , Jena Lalatendu Kesari
Published: January 2019

Purpose

How psychological variables especially self-efficacy plays significant role to attain workplace well-being is yet to be explained. The extant literature calls for further research works in the field of sustainability practices to bridge the gap between self-efficacy and workplace well-being. The purpose of this paper is to extend the literature of workplace well-being while scientifically examining the moderating role of sustainability practices.

Design/methodology/approach

The study collected data from 527 full-time executives of Indian public and private manufacturing industries. The authors performed moderated regression analysis through a series of hierarchical models to test the hypotheses of the study.

Findings

The result indicates positive relationship between self-efficacy and workplace well-being. Furthermore, the result suggests that the relationship between self-efficacy and workplace well-being was stronger among executives with high level of sustainability practices and vice versa.

Research limitations/implications

The cross-sectional sample of executives employed in Indian manufacturing organizations limits the generalizability of the findings.

Practical implications

HR functionaries and senior management may benefit by closely examining their sustainability practices along with their employees perceived ability to address workplace well-being.

Originality/value

The study contributes to extend the literature on self-efficacy and workplace well-being. This research work is one of the first few studies to examine the moderating effect of sustainability practices.
Modelling and analysis of barriers affecting the implementation of lean green agile manufacturing system (LGAMS)
Authors: Sindhwani Rahul , Mittal Varinder Kumar , Singh Punj Lata , Aggarwal Ankur , Gautam Nishant
Published: January 2019

Purpose

Many types of research have already investigated the lean, green or agile manufacturing systems in a discrete manner or as combinations of two of them. In today’s competitive scenario, if industry wants to perpetuate its name in the market, then it has to supervene proper thinking and smart approach. Therefore, the combination of lean, green and agile manufacturing systems can provide better and beneficial results. The purpose of this paper is to discern the barriers to the combined lean green agile manufacturing system (LGAMS), understand their interdependence and develop a framework to enhance LGAMS by using total interpretive structural modeling (TISM) and MICMAC (Matriced’ Impacts Croise’s Multiplication Appliquée a UN Classement) Analysis.

Design/methodology/approach

This paper uses TISM methodology and MICMAC analysis to deduce the interrelationships between the barriers and rank them accordingly. A total of 13 barriers have been identified through extensive literature review and discussion with experts.

Findings

An integrated LGAMS has been presented that balances the lean, green and agile paradigms and can help supply chains become more efficient, streamlined and sustainable. Barriers are identified while referring to all three strategies to showcase the clear relevance. TISM models the barriers in different levels showcasing direct and important transitive relations. Further, MICMAC analysis distributes the barriers in four clusters in accordance with their driving and dependence power.

Research limitations/implications

The inferences have been drawn from a model developed on the basis of inputs from a small fraction of the industry and academia and may show variations when considering the whole industry.

Practical implications

The outcome of this research can contribute to bringing the change to the manufacturing systems used in most developing nations. Also, top managers considering adoption of LGAMS can be cautious of the most influential barriers.

Originality/value

A TISM-based model of the barriers to an integrated LGAMS has been proposed with evaluation of the influence of the barriers.