bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient ischaemic dilation and post-stress wall motion abnormality increase risk in patients with less than moderate ischaemia: analysis of the REFINE SPECT registry
Authors: Miller Robert J H , Hu Lien-Hsin , Gransar Heidi , Betancur Julian , Eisenberg Evann , Otaki Yuka , Sharir Tali , Fish Mathews B , Ruddy Terrence D , Dorbala Sharmila , Carli Marcelo Di , Einstein Andrew J , Kaufmann Philipp A , Sinusas Albert J , Miller Edward J , Bateman Timothy , Germano Guido , Tamarappoo Balaji K , Dey Damini , Berman Daniel S , Slomka Piotr J
Published: June 2019

Aims 

Ischaemia on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is strongly associated with cardiovascular risk. Transient ischaemic dilation (TID) and post-stress wall motion abnormalities (WMA) are non-perfusion markers of ischaemia with incremental prognostic utility. Using a large, multicentre SPECT MPI registry, we assessed the degree to which these features increased the risk of major adverse cardiovascular events (MACE) in patients with less than moderate ischaemia.

Methods and results 

Ischaemia was quantified with total perfusion deficit using semiautomated software and classified as: none (<1%), minimal (1 to <5%), mild (5 to <10%), moderate (10 to <15%), and severe (≥15%). Univariable and multivariable Cox proportional hazard analyses were used to assess associations between high-risk imaging features and MACE. We included 16 578 patients, mean age 64.2 and median follow-up 4.7 years. During follow-up, 1842 patients experienced at least one event. Patients with mild ischaemia and TID were more likely to experience MACE compared with patients without TID [adjusted hazard ratio (HR) 1.42, P = 0.023], with outcomes not significantly different from patients with moderate ischaemia without other high-risk features (unadjusted HR 1.15, P = 0.556). There were similar findings in patients with post-stress WMA. However, in multivariable analysis of patients with mild ischaemia, TID (adjusted HR 1.50, P = 0.037), but not WMA, was independently associated with increased MACE.

Conclusion 

In patients with mild ischaemia, TID or post-stress WMA identify groups of patients with outcomes similar to patients with moderate ischaemia. Whether these combinations identify patients who may derive benefit from revascularization deserves further investigation.
Marital Status and Dementia: Evidence from the Health and Retirement Study
Authors: Liu Hui , Zhang Zhenmei , Choi Seung-won , Langa Kenneth M
Published: June 2019

Objectives

We provide one of the first population-based studies of variation in dementia by marital status in the United States.

Method

We analyzed data from the Health and Retirement Study (2000–2014). The sample included 15,379 respondents (6,650 men and 8,729 women) aged 52 years and older in 2000 who showed no evidence of dementia at the baseline survey. Dementia was assessed using either the modified version of the Telephone Interview for Cognitive Status (TICS) or the proxy’s assessment. Discrete-time hazard regression models were estimated to predict odds of dementia.

Results

All unmarried groups, including the cohabiting, divorced/separated, widowed, and never married, had significantly higher odds of developing dementia over the study period than their married counterparts; economic resources and, to a lesser degree, health-related factors accounted for only part of the marital status variation in dementia. For divorced/separated and widowed respondents, the differences in the odds of dementia relative to married respondents were greater among men than among women.

Discussion

These findings will be helpful for health policy makers and practitioners who seek to better identify vulnerable subpopulations and to design effective intervention strategies to reduce dementia risk.
Tomato Plant Flavonoids Increase Whitefly Resistance and Reduce Spread of Tomato yellow leaf curl virus
Authors: Yao Qixi , Peng Zhengke , Tong Hong , Yang Fengbo , Xing Gaoshan , Wang Linjiang , Zheng Jiangjie , Zhang Youjun , Su Qi
Published: June 2019

Tomato yellow leaf curl virus (TYLCV), a begomovirus (genus Begomovirus) is the causal agent of tomato yellow leaf curl disease (TYLCD), which causes severe damage to tomato (Solanum lycopersicum) crops throughout tropical and subtropical regions of the world. TYLCV is transmitted by the whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in a circulative and persistent manner. Our previous studies showed that tomato flavonoids deter B. tabaci oviposition, but the effects of tomato flavonoids on the settling and feeding behavior of B. tabaci and on its transmission of TYLCV are unknown. Using two near-isogenic tomato lines that differ greatly in flavonoid levels, we found that high flavonoid production in tomato deterred the landing and settling of B. tabaci. Moreover, electrical penetration graph studies indicated that high flavonoid levels in tomato reduced B. tabaci probing and phloem-feeding efficiency. As a consequence, high flavonoid levels in tomato reduced the primary and secondary spread of TYLCV. The results indicate that tomato flavonoids provide antixenosis resistance against B. tabaci and that the breeding of such resistance in new varieties could enhance TYLCD management.
The Impact of Varying Financial Incentives on Data Quality in Web Panel Surveys
Authors: Spreen Thomas Luke , House Lisa A , Gao Zhifeng
Published: June 2019

This study assesses whether varying contingent financial incentives in a web panel survey altered respondent behavior. A sample of US web panel participants were randomly assigned to cash incentive levels ranging from $0.50 to $3.00 awarded upon completion of an online survey gauging preferences for fresh strawberries. The analytical results indicate that increased contingent incentives had no clear association with the eligibility or break-off rates. Increased incentives reduced the incidence of trap question failure among a subset of qualified respondents. Responses of respondents flagged as unqualified to complete the survey, or qualified but inattentive, consistently differed from other qualified respondents on many survey items over a range of incentive levels. Overall, the results suggest increased contingent incentives yield limited improvements in the behavior of web panel respondents.
Gender and Health
Authors: Gorman Bridget K. , Solazzo Alexa
Published: June 2019

The relationship between gender and health has received considerable research study over the last several decades, within sociology but also related fields in social sciences, public health, and medicine. This body of scholarship documents both similarity and difference between the health experience of men and women across the life course. Gender-based health patterns are dependent upon the health outcome examined, as life expectancy is shorter among men while women experience higher rates of various non-fatal functional problems and chronic medical conditions. Gender differences also exist in mental health outcomes and participation in various healthy and unhealthy behaviors, including utilization of health care services. Yet these associations are not uniform and can differ when various population subgroups are compared. As such, a growing body of scientific work argues for the need to apply an intersectional lens to the study of gender and health, and this work details how various cross-cutting identities (e.g., age, racial/ethnicity identity, social class, sexual orientation) intersect with gender to shape health outcomes. More recently, scholars have begun to assess how non-binary measures of gender identity relate to health status, and thus a small but increasing body of research explores whether and how health status varies for cisgender and transgender adults. While a substantial amount of attention has been given to describing the nuances of how gender relates to health status, the gender-health literature is also characterized by robust discussion of the factors that contribute to gender patterns in health status, including but not limited to socioeconomic status, relationships and care work, differential experiences in medical care treatment, masculinity, stress and social supports, and health behaviors. Altogether, this article introduces the reader to classic works and reviews, theoretical perspectives, and key descriptive and explanatory papers that represent the body of scholarship examining how gender relates to health status.
E. Lucy Braun
Authors: Gilliam Frank S.
Published: June 2019

Emma Lucy Braun (b. 1889–d. 1971) was one of the more influential plant ecologists of the 20th century. She is known primarily for her seminal book, Deciduous Forests of Eastern North America, first published in 1950 with later facsimile reprintings. Although this book tends to overshadow her other accomplishments, those contributions to the fields of plant ecology and taxonomy are quite notable and considerable in themselves; she was a pioneer in conservation biology, she published numerous papers in prominent ecological journals (including Ecology, Ecological Monographs, and Botanical Review), and she was a distinguished plant taxonomist (author of The Woody Plants of Ohio). She actively contributed to and was a member of several notable scientific and ecological societies, including the American Association for the Advancement of Science, the Ecological Society of America, the Botanical Society of America, the American Society of Plant Taxonomists, and the British Ecological Society. The broad biogeographic range of her interests contrasts with the provinciality of her academic pedigree; she was educated, and then a long-standing faculty member, at the University of Cincinnati, her city of birth. Beginning with the degrees of B.A. (1910?), M.A. (1912), and Ph.D. (1914). She was appointed assistant and instructor of botany in 1914 and rose through the ranks to full professor of botany. She retired as professor emerita in 1948, although her retirement years were remarkably productive with the publication of three books and several noteworthy papers. In 1950, she became the first woman president of the Ecological Society of America and the only woman to hold that office until 1986. With graduate research experience in both geology (M.A.) and botany (Ph.D.), she was one of the earlier in the field to not only embrace the multidisciplinary nature of ecology, but also use it to advance the field. In addition to her earned degrees, she was awarded an honorary D.Sc. from the University of Cincinnati in 1964.
Good Fences Make Good Neighbors: Human Immunodeficiency Virus and Vascular Disease
Authors: Mayne Elizabeth S , Louw Susan
Published: June 2019

Cardiovascular disease, venous thrombosis, and microvascular disease in people with HIV (PWH) is predicted to increase in an aging HIV-infected population. Endothelial damage and dysfunction is a risk factor for cardiovascular events in PWH and is characterized by impaired vascular relaxation and decreased nitric oxide availability. Vascular disease has been attributed to direct viral effects, opportunistic infections, chronic inflammation, effects of antiretroviral therapy, and underlying comorbid conditions, like hypertension and use of tobacco. Although biomarkers have been examined to predict and prognosticate thrombotic and cardiovascular disease in this population, more comprehensive validation of risk factors is necessary to ensure patients are managed appropriately. This review examines the pathogenesis of vascular disease in PWH and summarizes the biomarkers used to predict vascular disease in this population.
The Rise of Covenant-lite Lending and Implications for the UK’s Corporate Insolvency Law Toolbox
Authors: Paterson Sarah
Published: June 2019

This article is, so far as the author is aware, the first to examine in detail the implications of the explosion of covenant-lite loans for English corporate insolvency law. Covenant-lite loans lack certain early warning mechanisms that have traditionally been found in loans to heavily indebted borrowers. Concerns about the implications of covenant-lite loans have been raised in the broadcast and print media, and by economists and central banks in England and the United States. This is an issue that matters to us all. This article argues that covenant-lite lending means that lenders and borrowers may start restructuring negotiations when the scale of the distress is acute, implicating operational and financial liabilities. It provides a detailed analysis of the additional corporate insolvency law tools which may be needed as a result, and explains why this analysis is relevant for the detailed working out of current corporate insolvency law reform proposals.
The Path to Pistoia: Urban Hygiene Before the Black Death*
Authors: Geltner G
Published: June 2019

When the Black Death struck Western Europe in late 1347, city dwellers across the region were already practising public health, in part by building, maintaining and monitoring infrastructures whose prophylactic value emerged from the experience of intensified urbanization. The demands of a new urban metabolism, evident from the twelfth century, prompted numerous cities, including Pistoia, to develop preventative health programmes in anticipation of and in response to diverse threats. The latter certainly included famine, floods, pestilence and war, but Pistoians and others were no less concerned by routine matters such as burials, food quality, travel and work safety, artisanal pollution and domestic waste disposal. All of these were recognized as impacting people’s health, based on the medical and natural-philosophical theories prevalent at the time, and their management took into consideration not only climactic conditions and multi-species behaviour, but also the smooth functioning of sites such as wells, canals, bridges and roads. The political value that municipalities and other stakeholders began to place on the upkeep of these sites exceeded their economic function and thus questions the seminal role that scholars tend to attribute to the second plague pandemic in public health history. It also demonstrates how a key aspect of Euro-American modernity continues to shape interpretations of urban and health histories and suggests a broader path for historicizing community prophylactics.
Persons with Complex Regional Pain Syndrome Renegotiate Social Roles and Intimacy: A Qualitative Study
Authors: Packham Tara L , Wainio Kaitlyn , Wong Ming-Kin
Published: June 2019

Objective

Persons with complex regional pain syndrome often experience allodynia, where touch is painful. Allodynia is associated with poor prognosis, but the impacts on roles, activities, social relationships, and intimacy remain unclear. There is a need to examine intimacy in complex regional pain syndrome from a lived experience perspective.

Methods

We conducted a secondary analysis of cognitive debriefing interview data from 44 persons with complex regional pain syndrome who completed a patient-reported questionnaire. Using interpretive description and thematic analysis, we analyzed items and responses addressing allodynia, relationships, and intimacy.

Results

Two themes were developed to understand intimacy related to the pain experience: a renegotiated social identity and participation and a reinvented intimate self. These themes included elements of a) loss of control, b) loss of shared experiences, c) feeling that their condition was misunderstood, d) a need for self-preservation, e) altered self-concept, and e) the concept of intimacy is broader than sexuality. Our findings suggest that complex regional pain syndrome has pervasive impacts on relationships and intimacy that merit discussion with their health care team.

Conclusions

Persons with persistent pain need to be supported in roles and activities that allow them to express intimacy in their everyday lives.
‘Where and how do you buy medicines?’ A pilot survey of consumption strategies among the public in Sweden
Authors: Lundin S , Liu R
Published: June 2019

Background

Substandard and falsified (SF) medical products are a major danger to public health. They affect every region of the world, and have been identified in all major therapeutic categories. Studies from medicine, pharmacology, law and public health dominate this research area with a focus on the supply side. However, the spread of SF medical products cannot be fully understood without information about the demand side or a sociocultural perspective on market formation. The aim of this short report is to present findings from a pilot study that examines the attitudes of the Swedish public regarding consumption of medicines.

Methods

We conducted a pilot survey in 2016 ‘Where and how do you buy medicines?’ using LimeSurvey, an open-source online survey software. In total 155 respondents completed the survey.

Results

The majority of respondents turn to doctors within healthcare for prescription-only medicines (POM). Simultaneously, some respondents would consider buying POMs without prior contact with experts even if medicines may come from unsafe sources.

Conclusions

There is a tendency that people move away from formal healthcare towards an unregulated market. In parallel, people’s approach to doctors becomes more personalized and pragmatic than in former patriarchal relationships. Risk becomes a negotiable concept.
Relationships between digestible energy and metabolizable energy in current feedlot diets1
Authors: Hales Kristin E
Published: June 2019

It is commonplace that metabolizable energy (ME) is calculated from digestible energy (DE) as DE × 0.82. However, recent published literature suggests that the relationship between DE and ME is variable depending on the type of diet used, and is typically > 0.90 when high-concentrate diets are fed. Literature means were compiled from 23 respiration calorimetry studies where total fecal and urine collections were conducted and gaseous energy was measured. The relationship between experimentally observed and predicted ME (DE × 0.82) was evaluated using these previously reported treatment means. Additionally, a previously published linear regression equation for predicting ME from DE was also evaluated using a residual analysis. Published (Hales, K. E., A. P. Foote, T. M. Brown-Brandl, and H. C. Freetly. 2017. The effects of feeding increasing concentrations of corn oil on energy metabolism and nutrient balance in finishing beef steers. J. Anim. Sci. 95:939–948. doi:10.2527/jas.2016.0902 and Hemphill, C. N., T. A. Wickersham, J. E. Sawyer, T. M. Brown-Brandl, H. C. Freetly, and K. E. Hales. 2018. Effects of feeding monensin to bred heifers fed in a drylot on nutrient and energy balance. J. Anim. Sci. 96:1171–1180. doi:10.1093/jas/skx030) and unpublished data (K. E. Hales, unpublished data) were used to develop a new equation for estimating ME from DE (megacalories/kilogram [Mcal/kg] of DM; ME = −0.057 ± 0.022 DE2 + 1.3764 ± 0.1197 DE – 0.9483 ± 0.1605; r2 = 0.9671, root mean square error = 0.12; P < 0.01 for intercept, P < 0.01 for linear term, and P < 0.01 for quadratic term). To establish a maximum biological threshold for the conversion of DE to ME, individual animal data were used (n = 234) to regress the ME:DE on DE concentration (1.53 to 3.79 Mcal DE/kg). When using experimentally derived data and solving for the first derivative, the maximum biological threshold for the conversion of DE to ME was 3.65 Mcal DE/kg. Additionally, the quadratic regression (equation 1) was used to predict ME from a wide range of DE (1.8 to 4.6 Mcal/kg). The ME:DE ratio was then calculated by dividing predicted ME by DE. The maximum biological threshold for the conversion of DE to ME was estimated by solving for the first derivative and was 3.96 Mcal DE/kg. In conclusion, this review suggests that the relationship between DE and ME is not static, especially in high-concentrate diets. The equation presented here is an alternative that can be used for the calculation of ME from DE in current feedlot diets, but it is not recommended for use in high-forage diets. The maximization of ME in current diets, maximum biological threshold, occurs between 3.65 and 3.96 Mcal DE/kg in the diet, which based on these data is approximately 3.43 to 3.65 Mcal/kg of ME consumption.
‘Candidatus Phytoplasma mali’ Genome Encodes a Protein that Functions as an E3 Ubiquitin Ligase and Could Inhibit Plant Basal Defense
Authors: Strohmayer Alisa , Moser Mirko , Si-Ammour Azeddine , Krczal Gabi , Boonrod Kajohn
Published: June 2019

Phytoplasmas are the causative agent of numerous diseases of plant species all over the world, including important food crops. The mode by which phytoplasmas multiply and behave in their host is poorly understood and often based on genomic data. We used yeast two-hybrid screening to find new protein–protein interactions between the causal agent of apple proliferation ‘Candidatus Phytoplasma mali’ and its host plant. Here, we report that the ‘Ca. P. mali’ strain PM19 genome encodes a protein PM19_00185 that interacts with at least six different ubiquitin-conjugating enzymes (UBC; E2) of Arabidopsis thaliana. An in vitro ubiquitination assay showed that PM19_00185 is enzymatically active as E3 ligase with A. thaliana E2 UBC09 and Malus domestica E2 UBC10. We show that a nonhost bacteria (Pseudomonas syringae pv. tabaci) can grow in transgenic A. thaliana plant lines expressing PM19_00185. A connection of phytoplasma effector proteins with the proteasome proteolytic pathway has been reported before. However, this is, to our knowledge, the first time that a phytoplasma effector protein with E3 ligase activity has been reported.
Small-Molecule Screens Reveal Novel Haustorium Inhibitors in the Root Parasitic Plant Triphysaria versicolor
Authors: Wang Yaxin , Steele Daniel , Murdock Maylin , Lai Seigmund , Yoder John
Published: June 2019

Root parasitic weeds in Orobanchaceae pose a tremendous threat to agriculture worldwide. We used an in vitro assay to screen libraries of small molecules for those capable of inhibiting or enhancing haustorium development in the parasitic plant Triphysaria versicolor. Several redox-modifying molecules and one structural analog of 2,6-dimethoxybenzoquine (DMBQ) inhibited haustorium development in the presence of the haustorium-inducing factor DMBQ, some of these without apparent growth inhibition to the root. Triphysaria seedlings were able to acclimate to some of these redox inhibitors. Transcript levels of four early-stage haustorium genes were differentially influenced by inhibitors. These novel haustorium inhibitors highlight the importance of redox cycling for haustorium development and suggest the potential of controlling parasitic weeds by interrupting early-stage redox-signaling pathways.
Individualization of Migraine Prevention
Authors: Kisler Lee B. , Weissman-Fogel Irit , Coghill Robert C. , Sprecher Elliot , Yarnitsky David , Granovsky Yelena
Published: June 2019

Objective:

Finding an effective preventive agent for the individual migraineur is often long and frustrating. An individual-specific, efficacy-predicting tool would be invaluable in directing, shortening, and improving this process. As the serotonin-norepinephrine reuptake inhibitor duloxetine is a pain modulator, we hypothesized that pronociceptivity will directly predict drug efficacy, so that the more pronociceptive the patient is, the more efficacious the drug. Therefore, we used psychophysical pain measures to predict duloxetine efficacy in migraine prevention.

Methods:

Fifty-five migraineurs participated: 27 received duloxetine and 28 nonactive placebo. Responses to painful stimuli, conditioned pain modulation, and temporal summation of pain were measured before treatment. Treatment outcome measures included changes in attack frequency, migraine days, pain levels, and a reported self-estimate of migraine improvement at weeks 4 and 5. To examine treatment effects, the outcome measures were compared with pretreatment levels. Treatment by the psychophysical-predictor effect on treatment outcome was examined in separate regression models.

Results:

Duloxetine was more efficacious than placebo in migraine prevention, as indicated by the patient’s estimation of migraine improvement (duloxetine: 52.3±30.4%; placebo: 26.0±27.3%;P=0.001). Further, this measure, in the duloxetine group, was predicted by higher pretreatment pain ratings for tonic heat pain (P=0.012); greater pain sensitivity at baseline predicted greater percent of migraine improvement in duloxetine (r=0.47;P=0.013), but not in placebo (r=−0.36;P=0.060).

Discussion:

Our results suggest how personalized medicine can be applied to designing appropriate migraine prevention treatment. Psychophysical testing can reveal and characterize pronociceptive migraineurs, who seem to be more likely than non–pronociceptive ones to benefit from migraine prevention with serotonin-norepinephrine reuptake inhibitors.
The Efficacy of Outpatient Pulmonary Rehabilitation After Bilateral Lung Transplantation
Authors: Candemir Ipek , Ergun Pinar , Kaymaz Dicle , Demir Neşe , Taşdemir Filiz , Sengul Fatma , Egesel Nurcan , Yekeler Erdal
Published: June 2019

Purpose:

Pulmonary rehabilitation (PR) is advocated in the pre- and post–lung transplantation (LTx) periods. However, there is limited literature on the benefit of PR post-LTx. The aim of this study was to investigate the efficacy of an outpatient, multidisciplinary, comprehensive PR program in bilateral LTx recipients in the early period after LTx.

Method:

Twenty-three LTx recipients were referred to the PR center. Change in incremental and endurance shuttle walk tests, hand and quadriceps strength, respiratory muscle strength (maximum inspiratory/expiratory pressure), dyspnea (Medical Research Council score), quality of life (St George's Respiratory Questionnaire, Chronic Respiratory Questionnaire), and psychological status (Hospital Anxiety Depression Scale) were compared pre- and post-PR.

Results:

Seventeen of 23 (74%) recipients completed PR, comprising 15 male and 2 female patients whose median age was 51 yr. The initiation of the program was 75 ± 15 d after LTx. The incremental shuttle walk test distance was predicted as 23% before PR and it increased to 36% after PR (P < .001); the endurance shuttle walk test distance also increased (P < .01). Significant improvement was seen in upper and lower extremity strength, and St George's Respiratory Questionnaire and Chronic Respiratory Questionnaire scores and Hospital Anxiety Depression Scale scores reflected less anxiety and depressive symptoms. Furthermore, body mass and fat-free mass indices, maximum inspiratory pressure, and maximum expiratory pressure improved significantly. There was no significant change in forced expiratory volume in the first second of expiration, forced vital capacity, or Medical Research Council scores.

Conclusion:

This study demonstrated that patients who attended PR within 3 mo of bilateral LTx showed improvements in exercise capacity, respiratory muscle strength, quality of life, body composition, and psychological status.
Topical Nifedipine for the Treatment of Pressure Ulcer: A Randomized, Placebo-Controlled Clinical Trial
Authors: Zolfagharnezhad Hedieh , Khalili Hossein , Mohammadi Mostafa , Niknam Somayeh , Vatanara Alireza
Published: June 2019

Background:

Effect of nifedipine on pressure ulcer (PU) healing has not been evaluated in the human subjects yet.

Study question:

In this study, the effect of topical application of nifedipine 3% ointment on PU healing in critically ill patients was investigated.

Study design:

This was a randomized, double-blind, placebo-controlled clinical.

Measures and outcomes:

In this study, 200 patients with stage I or II PU according to 2-digit Stirling Pressure Ulcer Severity Scale were randomized to receive topical nifedipine 3% ointment or placebo twice daily for 14 days. Changes in the size and stage of the ulcers were considered as primary outcome of the study. The stage of the ulcers at baseline and on day 7 and day 14 of study was determined by using 2-digit stirling scale. In addition, the surface area of the wounds was estimated by multiplying width by length.

Results:

In total, 83 patients in each group completed the study. The groups were matched for the baseline stage and size of PUs. Mean decrease in the stage of PU in the nifedipine group was significantly higher than the placebo group on day 7 (−1.71 vs. −0.16, respectively, P < 0.001) and day 14 (−0.78 vs. −0.09, respectively, P < 0.001). Furthermore, the mean decrease in the surface area of PU was significantly higher in the nifedipine group compared with the placebo group on day 7 (−1.44 vs. −0.32, respectively, P < 0.001) and day 14 (−2.51 vs. −0.24, respectively, P < 0.001) of study.

Conclusions:

Topical application of nifedipine 3% ointment for 14 days significantly improved the healing process of stage I or II PUs in critically ill patients.
Structure of F
1
-ATPase from the obligate anaerobe
Fusobacterium nucleatum
Authors: Petri Jessica , Nakatani Yoshio , Montgomery Martin G. , Ferguson Scott A. , Aragão David , Leslie Andrew G. W. , Heikal Adam , Walker John E. , Cook Gregory M.
Published: June 2019

The crystal structure of the F
1
-catalytic domain of the adenosine triphosphate (ATP) synthase has been determined from the pathogenic anaerobic bacterium
Fusobacterium nucleatum
. The enzyme can hydrolyse ATP but is partially inhibited. The structure is similar to those of the F
1
-ATPases from
Caldalkalibacillus thermarum
, which is more strongly inhibited in ATP hydrolysis, and in
Mycobacterium smegmatis
, which has a very low ATP hydrolytic activity. The β
E
-subunits in all three enzymes are in the conventional ‘open’ state, and in the case of
C. thermarum
and
M. smegmatis
, they are occupied by an ADP and phosphate (or sulfate), but in
F. nucleatum
, the occupancy by ADP appears to be partial. It is likely that the hydrolytic activity of the
F. nucleatum
enzyme is regulated by the concentration of ADP, as in mitochondria.
Species-specific calcification response of Caribbean corals after 2-year transplantation to a low aragonite saturation submarine spring
Authors: Martinez Ana , Crook Elizabeth D. , Barshis Daniel J. , Potts Donald C. , Rebolledo-Vieyra Mario , Hernandez Laura , Paytan Adina
Published: June 2019

Coral calcification is expected to decline as atmospheric carbon dioxide concentration increases. We assessed the potential of
Porites astreoides
,
Siderastrea siderea
and
Porites porites
to survive and calcify under acidified conditions in a 2-year field transplant experiment around low pH, low aragonite saturation (Ω
arag
) submarine springs. Slow-growing
S. siderea
had the highest post-transplantation survival and showed increases in concentrations of Symbiodiniaceae, chlorophyll
a
and protein at the low Ω
arag
site. Nubbins of
P. astreoides
had 20% lower survival and higher chlorophyll
a
concentration at the low Ω
arag
site. Only 33% of
P. porites
nubbins survived at low Ω
arag
and their linear extension and calcification rates were reduced. The density of skeletons deposited after transplantation at the low Ω
arag
spring was 15–30% lower for all species. These results suggest that corals with slow calcification rates and high Symbiodiniaceae, chlorophyll
a
and protein concentrations may be less susceptible to ocean acidification, albeit with reduced skeletal density. We postulate that corals in the springs are responding to greater energy demands for overcoming larger differences in carbonate chemistry between the calcifying medium and the external environment. The differential mortality, growth rates and physiological changes may impact future coral species assemblages and the reef framework robustness.
Bacteria from natural populations transfer plasmids mostly towards their kin
Authors: Dimitriu Tatiana , Marchant Lauren , Buckling Angus , Raymond Ben
Published: June 2019

Plasmids play a key role in microbial ecology and evolution, yet the determinants of plasmid transfer rates are poorly understood. Particularly, interactions between donor hosts and potential recipients are understudied. Here, we investigate the importance of genetic similarity between naturally co-occurringEscherichia coliisolates in plasmid transfer. We uncover extensive variability, spanning over five orders of magnitude, in the ability of isolates to donate and receive two different plasmids, R1 and RP4. Overall, transfer is strongly biased towards clone-mates, but not correlated to genetic distance when donors and recipients are not clone-mates. Transfer is limited by the presence of a functional restriction-modification system in recipients, suggesting sharing of strain-specific defence systems contributes to bias towards kin. Such restriction of transfer to kin sets the stage for longer-term coevolutionary interactions leading to mutualism between plasmids and bacterial hosts in natural communities.
Bioaccumulation of heavy metals in commercially important fish species from the tropical river estuary suggests higher potential child health risk than adults
Authors: Ahmed A. S. Shafiuddin , Sultana Sharmin , Habib Ahasan , Ullah Hadayet , Musa Najiah , Rahman Md. Mahfujur , Sarker Md. Shafiqul Islam
Published: June 2019

The Karnaphuli, a major river of Bangladesh, located off the coast of Chittagong in the Bay of Bengal is largely exposed to the heavy metal pollutants, which may be toxic to humans and aquatic fauna. The estuary is a striking example of a site where human pressure and ecological values collide with each other. In spite of being a major supplier of fish food for local community, there has been no study carried out to date to assess the potential human health risk due to heavy metal contamination in the fish species from this estuary. Therefore, the aim of present study was to assess bioaccumulation status and the potential human health risk evaluation for local consumers. Six commercially important fish species, Apocryptes bato, Pampus chinensis, Hyporhamphus limbatus, Liza parsia, Mugil cephalus, and Tenualosa toil from the Karnaphuli River estuary were collected to analyze heavy metals concentration level. Heavy metals As, Pb, Cd, Cr and Cu were detected from the samples using inductively coupled plasma mass spectrometry (Model: ELAN9000, Perkin-Elmer, Germany). The hierarchy of the measured concentration level of the metals was as follows: Pb (mean: 13.88, range: 3.19 - 6.19) > Cu (mean: 12.10, range: 10.27 - 16.41) > As (mean: 4.89, range: 3.19 – 6.19) > Cr (mean: 3.36, range: 2.46 – 4.17) > Cd (mean: 0.39, range: 0.21 - 0.74). The Fulton’s condition factor denoted that organisms were particularly in better ‘condition’ and most of the species were in positive allometric growth. The Bioaccumulation factors (BAFs) observed in the species of the contaminants were organized in the following ranks: Cu (1971.42) > As (1042.93) > Pb (913.66) > Cr (864.99) > Cd (252.03), and among all the specimens, demersal fish, A. bato corresponded to the maximum bio-accumulative organism. Estimated daily intake (EDI), target hazard quotient (THQ) and carcinogenic risk (CR) assessed for human health risk implications suggest that the values are within the acceptable threshold for all sorts of consumers. Hence none of them would experience non-carcinogenic and carcinogenic health effect for the ingestion of the fishes. However, children are shown to be largely susceptible than adults to non-carcinogenic and carcinogenic health effect due to the consumption of fish. Therefore, an appropriate guidlines and robust management measures needed to be taken to restore the estuarine health condition for greater benefit of the quality of fish products for local consumption.

Graphical abstract
Graph analytics for phenome-genome associations inference
Authors: Cirillo Davide , Garcia-Gasulla Dario , Cortés Ulises , Valencia Alfonso
Published: June 2019

Motivation

Biological ontologies, such as the Human Phenotype Ontology (HPO) and the Gene Ontology (GO), are extensively used in biomedical research to find enrichment in the annotations of specific gene sets. However, the interpretation of the encoded information would greatly benefit from methods that effectively interoperate between multiple ontologies providing molecular details of disease-related features.

Results

In this work, we present a statistical framework based on graph theory to infer direct associations between HPO and GO terms that do not share co-annotated genes. The method enables to map genotypic features to phenotypic features thus providing a valid tool for bridging functional and pathological annotations. We validated the results by (a) supporting evidence of known drug-target associations (PanDrugs), protein-protein physical and functional interactions (BioGRID and STRING), and common pathways (Reactome); (b) comparing relationships inferred from early ontology releases with knowledge contained in the latest versions.

Applications

We applied our method to improve the interpretation of molecular processes involved in pathological conditions, illustrating the applicability of our predictions with a number of biological examples. In particular, we applied our method to expand the list of relevant genes from standard functional enrichment analysis of high-throughput experimental results in the context of comorbidities between Alzheimer’s disease, Lung Cancer and Glioblastoma. Moreover, we analyzed pathways linked to predicted phenotype-genotype associations getting insights into the molecular actors of cellular senescence in Proteus syndrome.

Availability

https://github.com/dariogarcia/phenotype-genotype_graph_characterization
Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics
Authors: Aso Yoshinori , Ray Robert , Long Xi , Cichewicz Karol , Ngo Teri-TB , Sharp Brandi , Christoforou Christina , Lemire Andrew , Hirsh Jay , Litwin-Kumar Ashok , Rubin Gerald M.
Published: June 2019

Animals employ multiple and distributed neuronal networks with diverse learning rules and synaptic plasticity dynamics to record distinct temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso & Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO’s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.
Regulation of terminal hypertrophic chondrocyte differentiation inPrmt5mutant mice modeling infantile idiopathic scoliosis
Authors: Liu Zhaoyang , Ramachandran Janani , Vokes Steven A , Gray Ryan S
Published: June 2019

Idiopathic scoliosis (IS) is the most common type of musculoskeletal defect effecting children and is classified by age of onset, location, and degree of spine curvature. Although rare, the onset of IS during infancy is the more severe and rapidly progressive form of the disease, leading to increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remain elusive. Here, we show that PRMT5 is critical for the regulation of terminal hypertrophic chondrocyte differentiation in the spine and models infantile IS in mouse. Conditional ablation of PRMT5 in osteochondral progenitors led to impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of several markers of endochondral ossification revealed increased COLX andIhhexpression and a dramatic reduction ofMmp13and RUNX2 expression in the intervertebral disc and vertebral growth plate. Furthermore, we demonstrate that PRMT5 function in committed chondrogenic lineages is required for regulation of COLX expression in the adult spine. Together, our results establish PRMT5 as a critical regulator of hypertrophic chondrocyte differentiation and endochondral bone formation in spine development and maintenance.
Long non-coding RNA expression levels modulate cell-type specific splicing patterns by altering their interaction landscape with RNA-binding proteins
Authors: Porto Felipe Wendt , Daulatabad Swapna Vidhur , Janga Sarath Chandra
Published: June 2019

Background

Recent developments in our understanding of the interactions between long non-coding RNAs (lncRNAs) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks.

Results

Analysis of alternative splicing events across 39 lncRNA knockdown and wildtype RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 11630 skipped exon events and 5895 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockdown were specific to the cell type, in tandem, the functions annotated to the genes affected by alternative splicing across each lncRNA knockdown also displayed cell type specificity. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions, to observe cell type specific alternative splice event RBP binding preference.

Conclusions

Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs, and their downstream functions. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.
Theoretical study of the properties of X-ray diffraction moiré fringes. II. Illustration of angularly integrated moiré images
Authors: Yoshimura Jun-ichi
Published: June 2019

Using a theory of X-ray diffraction moiré fringes developed in a previous paper, labelled Part I [Yoshimura (2015). Acta Cryst. A71, 368–381], the X-ray moiré images of a silicon bicrystal having a weak curvature strain and an interspacing gap, assumed to be integrated for an incident-wave angular width, are simulation-computed over a wide range of crystal thicknesses and incident-wave angular width, likely under practical experimental conditions. Along with the simulated moiré images, the graphs of characteristic quantities on the moiré images are presented for a full understanding of them. The treated moiré images are all of rotation moiré. Mo Kα1 radiation and the 220 reflection were assumed in the simulation. The results of this simulation show that fringe patterns, which are significantly modified from simple straight fringes of rotation moiré, appear in some ranges of crystal thicknesses and incident-wave angular width, due to a combined effect of Pendellösung oscillation and an added phase difference from the interspacing gap, under the presence of a curvature strain. The moiré fringes which slope to the perpendicular direction to the diffraction vector in spite of the assumed condition of rotation moiré, and fringe patterns where low-contrast bands are produced with a sharp bend of fringes arising along the bands are examples of the modified fringe pattern. This simulation study provides a wide theoretical survey of the type of bicrystal moiré image produced under a particular condition.
Using a machine learning approach to determine the space group of a structure from the atomic pair distribution function
Authors: Liu Chia-Hao , Tao Yunzhe , Hsu Daniel , Du Qiang , Billinge Simon J. L.
Published: June 2019

A method is presented for predicting the space group of a structure given a calculated or measured atomic pair distribution function (PDF) from that structure. The method utilizes machine learning models trained on more than 100 000 PDFs calculated from structures in the 45 most heavily represented space groups. In particular, a convolutional neural network (CNN) model is presented which yields a promising result in that it correctly identifies the space group among the top-6 estimates 91.9% of the time. The CNN model also successfully identifies space groups for 12 out of 15 experimental PDFs. Interesting aspects of the failed estimates are discussed, which indicate that the CNN is failing in similar ways as conventional indexing algorithms applied to conventional powder diffraction data. This preliminary success of the CNN model shows the possibility of model-independent assessment of PDF data on a wide class of materials.
Modeling and performance analysis of machining fixture for near-net-shaped jet engine blade
Authors: Wang Hui , Peng Jingsong , Zhao Bing , Zhang Xin-Dong , Yu Jie , Li Yuan , Wang Mao-Min
Published: June 2019

Purpose

Near-net-shaped processes of jet engine blade have better performance in both reducing the material waste during production and improving work reliability in service, while the geometric features of blade, both sculptured surface and thin-walled shape, make the precise machining of blade challenging and difficult owing to its dynamics behaviors under complex clamping and machining loads. This paper aims to present a fundamental approach on modeling and performance analysis of the blade–fixture system.

Design/methodology/approach

A computerized framework on the complex blade–fixture dynamic behavior has been developed. Theoretical mechanic analysis on blade fixturing and machining is proposed with an especial emphasis on the boundary conditions of the blade–fixture system. Then the finite element analysis (FEA) method is used to simulate the variation trend of preloads, stiffness and blade distortion. The strong influence of parameters of workpiece–fixture configuration on blade distortion and machining error is investigated.

Findings

With a case of real jet engine blade machining, the experimental results and theoretical predictions suggest good agreement on their variation tendency. The loaded pressure of clamps has a critical influence on the total stiff performance of the blade–fixture system, and the profile error of the blade contributes much to the inconsistency in geometric dimension and surface integrity of blades’ machining. In the end, the results also validate the effectiveness of this methodology to predict and improve the performance of the blade–fixture configuration design.

Originality/value

The adaptive machining of near-net-shaped jet engine blade is a new high-performance manufacturing technology in aerospace production. This study provides a fundamental methodology for the performance analysis of blade-fixture system, to clear the variation law of blade distortion during preloading and machining, which will contribute to minimize the machining error and improve productivity.