bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis
Authors: Wheeler Kathleen E. , Grilli Ryan , Centofanti John E. , Martin Janet , Gelinas Celine , Szumita Paul M. , Devlin John W. , Chanques Gerald , Alhazzani Waleed , Skrobik Yoanna , Kho Michelle E. , Nunnally Mark E. , Gagarine Andre , Ergan Begum A. , Fernando Shannon , Price Carrie , Lewin John , Rochwerg Bram
Published: July 2020

Objectives:

This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.

Data Sources:

We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science.

Study Selection:

Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients.

Data Extraction:

We conducted duplicate screening of citations and data abstraction.

Data Synthesis:

Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, –0.88; 95% CI, –1.29 to –0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97–31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86–64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39–to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06–19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32–46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46–77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7–19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67–37.61 mg less; moderate certainty).

Conclusions:

Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.
Study on a Continuous Measurement Method for Unattached Radon Progeny
Authors: Zhang Yuanyuan , Kang Xi , Wang Libing
Published: July 2020

A method that does not require changing wire screens is proposed to achieve continuous measurement of unattached radon progeny. This method uses cumulative activity functions to deduct the influence of previous measurements from the current measurements on the sampling wire screen. The continuous measurement method was compared with a single measurement method, including relative deviations, uncertainties, and fluctuation range, which indicated the effectiveness of the cumulative activity functions applied to the continuous measurement method. The establishment of a continuous measurement method based on alpha spectroscopy provides technical support for the monitoring device.
Randomized Control Trial on the Effectiveness of Collagen Cross-linking on Bullous Keratopathy
Authors: Choy Bonnie Nga Kwan , Ng Alex Lap Ki , Zhu Ming Ming , Liu Catherine Chunling , Xu Sheng , Lai Jimmy Shiu Ming
Published: July 2020

Purpose:

To investigate the long-term effect and safety of collagen cross-linking (CXL) on patients with bullous keratopathy (BK) in a randomized control manner. It is, to our knowledge, the first randomized control study on the effect of CXL on BK.

Methods:

Subjects were randomized to receive CXL as in the standard protocol for treating keratoconus or a placebo treatment. Subjects were assessed at baseline and up to 12 months after treatment. Primary outcomes were central corneal thickness (CCT) and pain scores.

Results:

Forty-two patients with BK participated in the study treatment, 26 subjects were randomized to the CXL group and 16 subjects to the control group. The reduction of CCT in the CXL group was 37.6 and 63.8 μm at 2 and 4 weeks, respectively, which were significantly higher than that in the control group. However, there was no statistical difference in CCT reduction between the 2 groups at 12 weeks and after. There were no consistent advantages in pain score, corneal clarity, and visual acuity over the controls throughout the 1-year follow-up. However, CXL was associated with more recurrent epithelial defect (12%), and 2 of the 3 subjects with epithelial defect required amniotic membrane transplant.

Conclusions:

CXL reduced corneal thickness in the patients with BK, at least for the initial period. However, there were no improvement in pain, corneal clarity, and vision that were of more clinical relevance to the patients. Its short-term benefit was unlikely to outweigh its potential risk of recurrent epithelial defect.
Help-Seeking Behavior of Returning to Work in Healthcare Workers and its Influencing Factors During COVID-19 Subsiding
Authors: Lai Ruying , Tan Li , Lai Xiaoquan , Zhang Xinping , Zhou Qian
Published: July 2020

Objectives:

To explore the level and influencing factors of help-seeking behavior of returning to work in healthcare workers (HCWs).

Methods:

A total of 861 HCWs were surveyed. A structured self-administered questionnaire was used to collect data. Multivariable logistic regression was performed to examine the influencing factors of help-seeking behavior.

Results:

HCWs sought help with respect to COVID-19-diagnosized problem most. Help-seeking intention, problems encountered after return, test for return, work condition during COVID-19, relatives or friends diagnosed or suspected as COVID-19, and socio-demographic characteristics such as occupation, education, title, and marriage status are predictors of help-seeking behavior.

Conclusions:

Education and intervention should lay particular stress on HCWs featured rest at home before return, doctor, lower education and lower title to ensure the safety, accuracy, and quality of work after they return to work for a better occupational environment.
Hepatic veno-occlusive disease development in the hematopoietic stem cell transplantation patients: incidence and associated risk factors, a meta-analysis
Authors: Xia Yangchao , Qin Heping , Yang Jiao
Published: July 2020

Background

Now there are no efficient prophylactic or treatment strategies for hepatic veno-occlusive disease (VOD). Therefore, it is critical to early identify patients at high risk of VOD.

Aim

To analyze the risk factors of VOD in the hematopoietic stem cell transplantation (HSCT) patients.

Methods

A comprehensive search of the population was conducted.

Results

Twenty-one studies with 27 679 HSCT patients were eligible. The incidence of VOD was 15% [95% confidence interval (CI) 13–17%]. The following were the risk factors for VOD: mismatched HLA [odds ratio (OR) 2.34, 95% CI 1.20–4.57, P = 0.01], history of liver disease (OR 2.72, 95% CI 2.03–3.64, P < 0.00001), elevated AST before transplant (OR 2.49, 95% CI 1.49–4.15, P = 0.0005), months from diagnosis to HSCT > 12 months (OR 1.76, 95% CI 1.15–2.69, P = 0.009), previous radiation (OR 1.86, 95% CI 1.49–2.31, P < 0.00001), busulphan (OR 3.69, 95% CI 2.58–5.29, P < 0.00001) and MTX (OR 1.81, 95% CI 1.22–2.69, P = 0.003). There were no significant differences for VOD presentation in the patients with regards to sex, number of HSCT, Karnofsky score <90%, unrelated donor, autologous HSCT, CYA and heparin prophylaxis.

Conclusion

Mismatched HLA, liver disease (history of liver disease, elevated AST), months from diagnosis to HSCT >12 months, previous radiation and use of hepatotoxic drugs (BU and MTX) are the independent risk factors for VOD in the HSCT patients.
Therapeutic Drug Monitoring‐guided High‐dose Infliximab for Infantile‐onset Inflammatory Bowel Disease
Authors: Assa Amit , Dorfman Lev , Shouval Dror S. , Shamir Raanan , Cohen Shlomi
Published: July 2020

Very early‐onset inflammatory bowel disease (IBD) and specifically infantile‐onset IBD patients, are characterized by high rates of extensive colonic involvement and decreased response rate to standard therapeutic regimens, including infliximab (IFX). We present a case series of 4 patients with infantile‐onset IBD achieving clinical and biologic remission, after treatment with therapeutic drug monitoring (TDM)‐guided accelerated high‐dose IFX therapy. All patients were treated with accelerated high‐dose IFX induction of up to 22 mg/kg. In 3 of these patients, accelerated high‐dose IFX was used following failure of intensified standard dose induction. All patients achieved remission following re‐induction.

We suggest that children with infantile‐onset IBD may require a TDM‐guided accelerated high‐dose IFX induction and maintenance treatment in order to achieve and maintain remission. Personalized approach in these patients is essential in order to prevent underdosing and to avoid inappropriate interpretation of treatment failure.
Beyond personal protective equipment: adjunctive methods for control of healthcare-associated respiratory viral infections
Authors: Most Zachary M.
Published: July 2020

Purpose of review

Prevention of nosocomial transmission of respiratory viruses is a priority in all healthcare settings and often achieved with the use of personal protective equipment. Several adjunctive infection prevention methods are in common use but their effectiveness in reducing healthcare-associated respiratory viral infections is unclear. In this review, recent advances regarding the effectiveness of several adjunctive infection prevention methods to reduce healthcare-associated respiratory viral infections are discussed.

Recent findings

Training and education on hand hygiene guidelines, mandatory influenza vaccination for healthcare personnel, access to paid sick leave to reduce ill presenteeism, cohorting of patients with the same infection or clinical syndrome, neuraminidase inhibitor chemoprophylaxis during influenza outbreaks, and enhanced visitor restrictions in pediatric hospitals all have shown some degree of effectiveness in observational or quasi-experimental studies.

Most of the studies evaluating the effect of adjunctive infection prevention methods on healthcare-associated respiratory viral infections are observational or quasi-experimental and are often combined with other interventions. Therefore, it is difficult to determine the precise effectiveness or efficacy of these interventions and more controlled trials are needed. Multimodal infection prevention policies are likely to be most effective in reducing healthcare-associated respiratory viral infections.
The rainfall effect onto solidification and stabilization of heavy metal-polluted sediments
Authors: Sun Yan , Zhang Daofang , Li Feipeng , Tao Hong , Li Moting , Mao Lingchen , Gu Zhujun , Ling Ziyang , Shi Huancong
Published: July 2020

Rainfall makes impacts on the process of solidification/stabilization (S/S) and the long-term safety of solidified matrix. In this study, the effect of rainfall on solidification/stabilization process was investigated by the rainfall test. The unconfined compressive strength (UCS) and toxicity characteristic leaching procedure (TCLP) were adopted to characterize the properties of S/S sediments before and after the rainfall test. The samples cured for 28 days were selected for semi-dynamic leaching tests with a simulated acidic leachant prepared at pH of 2.0, 4.0 and 7.0. The effectiveness of S/S treatment was evaluated by diffusion coefficient (

D
e

) and leachability index (LX). The results indicated that UCS decreased at maximum deterioration rate of 34.23% after 7 days of curing, along with the minimum rate of 7.98% after 28 days by rainfall, with greater than 14 days referred. The rainfall had little effect on the leaching characteristics of heavy metals during the curing process. However, the simulated acid rain made significant impacts on the leaching behaviours of the heavy metals in the S/S materials. All the values of cumulative fraction of leached heavy metals were less than 2.0%, exhibition of good stabilization of cement. Furthermore, the calculated diffusion coefficient (

D
e

) for Cu was 1.28 × 10
1
cm
2
s
–1
, indicating its low mobility of heavy metal ions in S/S sediments. Furthermore, the calculated diffusion coefficients (

D
i

) for Cd, Cu and Pb were 7.44 × 10
−11
, 8.18 × 10
−12
and 7.85 × 10
−12
cm
2
s
–1
, respectively, indicating their relatively low mobility of heavy metal in S/S sediments.
Ontogenetic variability in crystallography and mosaicity of conodont apatite: implications for microstructure, palaeothermometry and geochemistry
Authors: Shohel Mohammad , McAdams Neo E. B. , Cramer Bradley D. , Forbes Tori Z.
Published: July 2020

X-ray diffraction data from Silurian conodonts belonging to various developmental stages of the speciesDapsilodus obliquicostatusdemonstrate changes in crystallography and degree of nanocrystallite ordering (mosaicity) in both lamellar crown tissue and white matter. The exclusive use of a single species in this study, combined with systematic testing of each element type at multiple locations, provided insight into microstructural and crystallographic differentiation between element type (Sa,Sb-c,M) as well as between juveniles and adults. A relative increase in the unit cell dimensionsa/cratio of nanocrystallites during growth was apparent in areas demonstrating single-crystal behaviour, but no such relationship was seen in dominantly polycrystalline areas. Systematic variations in mosaicity were identified, with mosaicity (as a proxy for disorder) increasing during growth, as well as along elements from tip to base. These results provide potential insight into the integrity of conodont apatite as a recorder of palaeoseawater chemistry, as well as demonstrate the need to consider the influence of ontogeny and element type on the use of conodonts in palaeothermometry and geochemical investigations.
Supernovae and transients with circumstellar interaction
Authors: Fraser Morgan
Published: July 2020

It is 30 years since the characteristic signatures of interaction with circumstellar material (CSM) were first observed in a core-collapse supernova. Since then, CSM interaction has been observed and inferred across a range of transients, from the low-energy explosions of low-mass stars as likely electron-capture supernovae, through to the brightest superluminous supernovae. In this review, I present a brief overview of some of the interacting supernovae and transients that have been observed to date, and attempt to classify and group them together in a phenomenological framework.
Contrasting evolutionary responses in two co-distributed species ofGalaxias(Pisces, Galaxiidae) in a river from the glaciated range in Southern Chile
Authors: Victoriano P. F. , Muñoz-Ramírez C. P. , Canales-Aguirre C. B. , Jara A. , Vera-Escalona I. , Burgos-Careaga T. , Muñoz-Mendoza C. , Habit E. M.
Published: July 2020

Life-history traits are among the most important factors affecting population abundance and genetic diversity of species. Here, we analysed the genetic patterns of twoGalaxiasspecies with different life-history traits to investigate how these biological differences impacted their evolution in the Valdivia River basin, Southern Chile. We analysed mitochondrial DNA (mtDNA) sequences from 225 individuals ofGalaxias maculatusand 136 ofG. plateito compare patterns of genetic diversity, structure and demographic growth across the basin.Galaxias maculatuspresented higher genetic diversity and higher genetic structure thanG. platei. Demographic analyses showedG. maculatuskept a higher population size over time, with a signal of demographic expansion in the last 250 kyr. WhereasGalaxias platei, exhibited lower, but constant population size over time. Furthermore, haplotype networks revealed higher lineage diversity inG. maculatuswith a tendency to occupy different areas of the basin. Coalescent simulations ruled out that genetic differences between species could be explained by stochastic processes (genetic drift), suggesting species-specific biological differences as responsible for the observed genetic differences. We discuss how differences in life-history traits and past glaciations interact to shape the evolutionary history of the twoGalaxiasspecies.
Structure and vibrational spectroscopy of lithium and potassium methanesulfonates
Authors: Parker Stewart F. , Revill-Hivet Emilie J. , Nye Daniel W. , Gutmann Matthias J.
Published: July 2020

In this work, we have determined the structures of lithium methanesulfonate, Li(CH3SO3), and potassium methanesulfonate, K(CH3SO3), and analysed their vibrational spectra. The lithium salt crystallizes in the monoclinic space groupC2/mwith two formula units in the primitive cell. The potassium salt is more complex, crystallizing inI4/mwith 12 formula units in the primitive cell. The lithium ion is fourfold coordinated in a distorted tetrahedron, while the potassium salt exhibits three types of coordination: six-, seven- and ninefold. Vibrational spectroscopy of the compounds (including the6Li and7Li isotopomers) confirms that the correlation previously found, that in the infrared spectra there is a clear distinction between coordinated and not coordinated forms of the methanesulfonate ion, is also valid here. The lithium salt shows a clear splitting of the asymmetric S–O stretch mode, indicating a bonding interaction, while there is no splitting in the spectrum of the potassium salt, consistent with a purely ionic material.
Accumulation curves of environmental DNA sequences predict coastal fish diversity in the coral triangle
Authors: Juhel Jean-Baptiste , Utama Rizkie S. , Marques Virginie , Vimono Indra B. , Sugeha Hagi Yulia , Kadarusman  , Pouyaud Laurent , Dejean Tony , Mouillot David , Hocdé Régis
Published: July 2020

Environmental DNA (eDNA) has the potential to provide more comprehensive biodiversity assessments, particularly for vertebrates in species-rich regions. However, this method requires the completeness of a reference database (i.e. a list of DNA sequences attached to each species), which is not currently achieved for many taxa and ecosystems. As an alternative, a range of operational taxonomic units (OTUs) can be extracted from eDNA metabarcoding. However, the extent to which the diversity of OTUs provided by a limited eDNA sampling effort can predict regional species diversity is unknown. Here, by modelling OTU accumulation curves of eDNA seawater samples across the Coral Triangle, we obtained an asymptote reaching 1531 fish OTUs, while 1611 fish species are recorded in the region. We also accurately predict (R² = 0.92) the distribution of species richness among fish families from OTU-based asymptotes. Thus, the multi-model framework of OTU accumulation curves extends the use of eDNA metabarcoding in ecology, biogeography and conservation.
Idiosyncratic perception: a link between acuity, perceived position and apparent size
Authors: Wang Zixuan , Murai Yuki , Whitney David
Published: July 2020

Perceiving the positions of objects is a prerequisite for most other visual and visuomotor functions, but human perception of object position varies from one individual to the next. The source of these individual differences in perceived position and their perceptual consequences are unknown. Here, we tested whether idiosyncratic biases in the underlying representation of visual space propagate across different levels of visual processing. In Experiment 1, using a position matching task, we found stable, observer-specific compressions and expansions within local regions throughout the visual field. We then measured Vernier acuity (Experiment 2) and perceived size of objects (Experiment 3) across the visual field and found that individualized spatial distortions were closely associated with variations in both visual acuity and apparent object size. Our results reveal idiosyncratic biases in perceived position and size, originating from a heterogeneous spatial resolution that carries across the visual hierarchy.
The extension of internal humidity levels beyond the soil surface facilitates mound expansion in
Macrotermes
Authors: Bardunias Paul M. , Calovi Daniel S. , Carey Nicole , Soar Rupert , Turner J. Scott , Nagpal Radhika , Werfel Justin
Published: July 2020

Termites in the genus
Macrotermes
construct large-scale soil mounds above their nests. The classic explanation for how termites coordinate their labour to build the mound, based on a putative cement pheromone, has recently been called into question. Here, we present evidence for an alternate interpretation based on sensing humidity. The high humidity characteristic of the mound's internal environment extends a short distance into the low-humidity external world, in a ‘bubble’ that can be disrupted by external factors like wind. Termites transport more soil mass into on-mound reservoirs when shielded from water loss through evaporation, and into experimental arenas when relative humidity is held at a high value. These results suggest that the interface between internal and external conditions may serve as a template for mound expansion, with workers moving freely within a zone of high humidity and depositing soil at its edge. Such deposition of additional moist soil will increase local humidity, in a feedback loop allowing the ‘interior’ zone to progress further outward and lead to mound expansion.
The direction of genital asymmetry is expressed stochastically in internally fertilizing anablepid fishes
Authors: Torres-Dowdall Julián , Rometsch Sina J. , Kautt Andreas F. , Aguilera Gastón , Meyer Axel
Published: July 2020

Animal genitalia vary considerably across taxa, with divergence in many morphological traits, including striking departures from symmetry. Different mechanisms have been proposed to explain this diversity, mostly assuming that at least some of the phenotypic variation is heritable. However, heritability of the direction of genital asymmetry has been rarely determined. Anablepidae are internally fertilizing fish where the anal fin of males has been modified into an intromittent organ that transfers sperm into the gonopore of females. Males of anablepid fishes exhibit asymmetric genitalia, and both left- and right-sided individuals are commonly found at similar proportions within populations (i.e. antisymmetry). Although this polymorphism was described over a century ago, there have been no attempts to determine if genital asymmetry has a genetic basis and whether the different morphs are accumulating genetic differences, as might be expected since in some species females have also asymmetric gonopores and thereby can only be fertilized by compatible asymmetric males. We address this issue by combining breeding experiments with genome-wide data (ddRAD markers) in representative species of the two anablepid genera with asymmetric genitalia:AnablepsandJenynsia. Breeding experiments showed that all offspring were asymmetric, but their morphotype (i.e. right- or left-sided) was independent of parental morphotype, implying that the direction of asymmetry does not have a strong genetic component. Consistent with this conclusion, association analyses based on approximately 25 000 SNPs did not identify markers significantly associated with the direction of genital asymmetry and there was no evidence of population structure between left- and right-sided individuals. These results suggest that the direction of genital asymmetry in anablepid fishes might be stochastic, a commonly observed pattern in species with antisymmetry in morphological traits.
Natal philopatry increases relatedness within groups of coral reef cardinalfish
Authors: Rueger Theresa , Harrison Hugo B. , Buston Peter M. , Gardiner Naomi M. , Berumen Michael L. , Jones Geoffrey P.
Published: July 2020

A central issue in evolutionary ecology is how patterns of dispersal influence patterns of relatedness in populations. In terrestrial organisms, limited dispersal of offspring leads to groups of related individuals. By contrast, for most marine organisms, larval dispersal in open waters is thought to minimize kin associations within populations. However, recent molecular evidence and theoretical approaches have shown that limited dispersal, sibling cohesion and/or differential reproductive success can lead to kin association and elevated relatedness. Here, we tested the hypothesis that limited dispersal explains small-scale patterns of relatedness in the pajama cardinalfish
Sphaeramia nematoptera
. We used 19 microsatellite markers to assess parentage of 233 juveniles and pairwise relatedness among 527 individuals from 41 groups in Kimbe Bay, Papua New Guinea. Our findings support three predictions of the limited dispersal hypothesis: (i) elevated relatedness within groups, compared with among groups and elevated relatedness within reefs compared with among reefs; (ii) a weak negative correlation of relatedness with distance; (iii) more juveniles than would be expected by chance in the same group and the same reef as their parents. We provide the first example for natal philopatry at the group level causing small-scale patterns of genetic relatedness in a marine fish.
Resolving Cargo-motor-track Interactions in Living Cells with Bifocal Parallax Single Particle Tracking
Authors: Cheng Xiaodong , Chen Kuangcai , Dong Bin , Filbrun Seth L. , Wang Gufeng , Fang Ning
Published: July 2020

Resolving coordinated biomolecular interactions in living cellular environments is vital for understanding the mechanisms of molecular nanomachines. The conventional approach relies on localizing and tracking target biomolecules and/or subcellular organelles labeled with imaging probes. However, it is challenging to gain information on rotational dynamics, which can be more indicative of the work done by molecular motors and their dynamic binding status. Herein, a bifocal parallax single particle tracking method using half-plane point spread functions has been developed to resolve the full-range azimuth angle (0-360°), polar angle, and 3D displacement in real time under complex living cell conditions. Using this method, quantitative rotational and translational motion of the cargo in a 3D cell cytoskeleton was obtained. Not only well-known active intracellular transport and free diffusion were observed but new interactions, tight attachment and tethered rotation, were discovered for better interpretation of the dynamics of cargo-motor-track interactions at various types of microtubule intersections.

Significance Statement

Translation and rotational motion of cargo during pauses at the microtubule intersections in living cells were revealed by high-accuracy three-dimensional single particle rotational tracking. The current study demonstrates the potential of studying coordinated interactions in living cellular environments by resolving characteristic rotational motions.
A two-step approach to testing overall effect of gene-environment interaction for multiple phenotypes
Authors: Majumdar Arunabha , Burch Kathryn S. , Sankararaman Sriram , Pasaniuc Bogdan , Gauderman W. James , Witte John S.
Published: July 2020

While gene-environment (GxE) interactions contribute importantly to many different phenotypes, detecting such interactions requires well-powered studies and has proven difficult. To address this, we combine two approaches to improve GxE power: simultaneously evaluating multiple phenotypes and using a two-step analysis approach. Previous work shows that the power to identify a main genetic effect can be improved by simultaneously analyzing multiple related phenotypes. For a univariate phenotype, two-step methods produce higher power for detecting a GxE interaction compared to single step analysis. Therefore, we propose a two-step approach to test for an overall GxE effect for multiple phenotypes. Using simulations we demonstrate that, when more than one phenotype has GxE effect (i.e., GxE pleiotropy), our approach offers substantial gain in power (18% – 43%) to detect an aggregate-level GxE effect for a multivariate phenotype compared to an analogous two-step method to identify GxE effect for a univariate phenotype. We applied the proposed approach to simultaneously analyze three lipids, LDL, HDL and Triglyceride with the frequency of alcohol consumption as environmental factor in the UK Biobank. The method identified two independent genome-wide significant signals of an overall GxE effect on the vector of lipids.
Wild rice (O. latifolia) from natural ecosystems in the Pantanal region of Brazil: host toFusarium incarnatum-equisetispecies complex and highly contaminated by zearalenone
Authors: Tralamazza Sabina Moser , Piacentini Karim Cristina , Savi Geovana Dagostim , Carnielli-Queiroz Lorena , de Carvalho Fontes Lívia , Martins Camila Siedlarczyk , Corrêa Benedito , Rocha Liliana Oliveira
Published: July 2020

We assessed the mycobiota diversity and mycotoxin levels present in wild rice (Oryza latifolia) from the Pantanal region of Brazil; fundamental aspects of which are severely understudied as an edible plant from a natural ecosystem. We found a variety of fungal species contaminating the rice samples; the most frequent genera beingFusarium, NigrosporaandCladosporium(35.9%, 26.1% and 15%, respectively). Within theFusariumgenus, the wild rice samples were mostly contaminated by theFusarium incarnatum-equisetispecies complex (FIESC) (80%) along withFusarium fujikuroispecies complex (20%). Phylogenetic analysis supported multiple FIESC species and gave strong support to the presence of two previously uncharacterized lineages within the complex (LN1 and LN2). Deoxynivalenol (DON) and zearalenone (ZEA) chemical analysis showed that most of the isolates were DON/ZEA producers and some were defined as high ZEA producers, displaying abundant ZEA levels over DON (over 19 times more). Suggesting that ZEA likely has a key adaptive role for FIESC in wild rice (O. latifolia). Mycotoxin determination in the rice samples revealed high frequency of ZEA, and 85% of rice samples had levels >100 μg/kg; the recommended limit set by regulatory agencies. DON was only detected in 5.2% of the samples. Our data shows that FIESC species are the main source of ZEA contamination in wild rice and the excessive levels of ZEA found in the rice samples raises considerable safety concerns regarding wild rice consumption by humans and animals.
MATHEMATICAL MODELING OF RETINAL DEGENERATION: AEROBIC GLYCOLYSIS IN A SINGLE CONE
Authors: Camacho Erika , Dobreva Atanaska , Larripa Kamila , Rǎdulescu Anca , Schmidt Deena , Trejo Imelda
Published: July 2020

Cell degeneration, including that resulting in retinal diseases, is linked to metabolic issues. In the retina, photoreceptor degeneration can result from imbalance in lactate production and consumption as well as disturbances to pyruvate and glucose levels. To identify the key mechanisms in metabolism that may be culprits of this degeneration, we use a nonlinear system of differential equations to mathematically model the metabolic pathway of aerobic glycolysis in a healthy cone photoreceptor. This model allows us to analyze the levels of lactate, glucose, and pyruvate within a single cone cell. We perform numerical simulations, use available metabolic data to estimate parameters and fit the model to this data, and conduct a sensitivity analysis using two different methods (LHS/PRCC and eFAST) to identify pathways that have the largest impact on the system. Using bifurcation techniques, we find that the system has a bistable regime, biologically corresponding to a healthy versus a pathological state. The system exhibits a saddle node bifurcation and hysteresis. This work confirms the necessity for the external glucose concentration to sustain the cell even at low initial internal glucose levels. It also validates the role ofβ-oxidation of fatty acids which fuel oxidative phosphorylation under glucose- and lactate-depleted conditions, by showing that the rate ofβ-oxidation of ingested outer segment fatty acids in a healthy cone cell must be low. Model simulations reveal the modulating effect of external lactate in bringing the system to steady state; the bigger the difference between external lactate and initial internal lactate concentrations, the longer the system takes to achieve steady state. Parameter estimation for metabolic data demonstrates the importance of rerouting glucose and other intermediate metabolites to produce glycerol 3-phosphate (G3P), thus increasing lipid synthesis (a precursor to fatty acid production) to support their high growth rate. While a number of parameters are found to be significant by one or both of the methods for sensitivity analysis, the rate ofβ-oxidation of ingested outer segment fatty acids is shown to consistently play an important role in the concentration of glucose, G3P, and pyruvate, whereas the extracellular lactate level is shown to consistently play an important role in the concentration of lactate and acetyl coenzyme A. The ability of these mechanisms to affect key metabolites’ variability and levels (as revealed in our analyses) signifies the importance of inter-dependent and inter-connected feedback processes modulated by and affecting both the RPE’s and cone’s metabolism.
The global and local distribution of RNA structure throughout the SARS-CoV-2 genome
Authors: Tavares Rafael de Cesaris Araujo , Mahadeshwar Gandhar , Pyle Anna Marie
Published: July 2020

SARS-CoV-2 is the causative viral agent of COVID-19, the disease at the center of the current global pandemic. While knowledge of highly structured regions is integral for mechanistic insights into the viral infection cycle, very little is known about the location and folding stability of functional elements within the massive, ~30kb SARS-CoV-2 RNA genome. In this study, we analyze the folding stability of this RNA genome relative to the structural landscape of other well-known viral RNAs. We present an in-silico pipeline to locate regions of high base pair content across this long genome and also identify well-defined RNA structures, a method that allows for direct comparisons of RNA structural complexity within the several domains in SARS-CoV-2 genome. We report that the SARS-CoV-2 genomic propensity to stable RNA folding is exceptional among RNA viruses, superseding even that of HCV, one of the most highly structured viral RNAs in nature. Furthermore, our analysis reveals varying levels of RNA structure across genomic functional regions, with accessory and structural ORFs containing the highest structural density in the viral genome. Finally, we take a step further to examine how individual RNA structures formed by these ORFs are affected by the differences in genomic and subgenomic contexts. The conclusions reported in this study provide a foundation for structure-function hypotheses in SARS-CoV-2 biology, and in turn, may guide the 3D structural characterization of potential RNA drug targets for COVID-19 therapeutics.
It matters who you know, down below: Different mycorrhizal fungal communities differentially affect plant phenolic defences against herbivory
Authors: Frew Adam , Wilson Bree A. L.
Published: July 2020

Arbuscular mycorrhizal (AM) fungi are ubiquitous symbionts of most terrestrial plants. These fungi not only provide their host plants with access to nutrients and resources but are known to augment plant defences against insect herbivores. Relatively little is known about the role of AM fungal diversity and community assembly on the expression of plant defence traits. Here, we report how plant (Triticum aestivum) phenolic-based resistance to insect herbivory is differentially affected by different AM fungal communities. An inoculant of four AM fungal species and a field-sourced native AM fungal community increased plant phenolics by 47.9% and 50.2%, respectively, compared to plants inoculated with only one fungal species. Correspondingly, the performance (relative growth rate) of the insect herbivore was 36% and 61.3% lower when feeding on plants associated with these AM fungal communities. Furthermore, there was a negative correlation between foliar phenolics and herbivore growth. We propose that AM fungal community assembly can drive insect herbivore performance by affecting phenolic-based defence mechanisms.
Three hallmarks of malaria-induced selection in human genomes
Authors: Tennessen Jacob A. , Duraisingh Manoj T.
Published: July 2020

Malaria has plausibly been the single strongest selective pressure on our species. Many of the best-characterized cases of adaptive evolution in humans are in genes tied to malaria resistance. However, the complex evolutionary patterns at these genes are poorly captured by standard scans for non-neutral evolution. Here we present three new statistical tests for selection based on population genetic patterns that are observed more than once among key malaria resistance loci. We assess these tests using forward-time evolutionary simulations and apply them to global whole-genome sequencing data from humans, and thus we show that they are effective at distinguishing selection from neutrality. Each test captures a distinct evolutionary pattern, here called Divergent Haplotypes, Repeated Shifts, and Arrested Sweeps, associated with a particular period of human prehistory. We clarify the selective signatures at known malaria-relevant genes and identify additional genes showing similar adaptive evolutionary patterns. Among our top outliers, we see a particular enrichment for genes involved in erythropoiesis and for genes previously associated with malaria resistance, consistent with a major role for malaria in shaping these patterns of genetic diversity. Polymorphisms at these genes are likely to impact resistance to malaria infection and contribute to ongoing host-parasite coevolutionary dynamics.
Auditory detection is modulated by theta phase of silent lip movements
Authors: Biau Emmanuel , Wang Danying , Park Hyojin , Jensen Ole , Hanslmayr Simon
Published: July 2020

Audiovisual speech perception relies, among other things, on our expertise to map a speaker’s lip movements with speech sounds. This multimodal matching is facilitated by salient syllable features that align lip movements and acoustic envelope signals in the 4 - 8 Hz theta band. Although non-exclusive, the predominance of theta rhythms in speech processing has been firmly established by studies showing that neural oscillations track the acoustic envelope in the primary auditory cortex. Equivalently, theta oscillations in the visual cortex entrain to lip movements, and the auditory cortex is recruited during silent speech perception. These findings suggest that neuronal theta oscillations may play a functional role in organising information flow across visual and auditory sensory areas. We presented silent speech movies while participants performed a pure tone detection task to test whether entrainment to lip movements directs the auditory system and drives behavioural outcomes. We showed that auditory detection varied depending on the ongoing theta phase conveyed by lip movements in the movies. In a complementary experiment presenting the same movies while recording participants’ electro-encephalogram (EEG), we found that silent lip movements entrained neural oscillations in the visual and auditory cortices with the visual phase leading the auditory phase. These results support the idea that the visual cortex entrained by lip movements filtered the sensitivity of the auditory cortex via theta phase synchronisation.
A fluorescent l-2-hydroxyglutarate biosensor
Authors: Kang Zhaoqi , Zhang Manman , Gao Kaiyu , Zhang Wen , Liu Yidong , Xiao Dan , Guo Shiting , Ma Cuiqing , Gao Chao , Xu Ping
Published: July 2020

l-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation ofl-2-HG metabolism remains poorly understood and a regulator specifically responded tol-2-HG has never been identified. Based on the genomic neighborhood analysis of the gene encodingl-2-HG oxidase (LhgO), LhgR, which represses the transcription oflhgO, was identified inPseudomonas putidaW619 in this study. LhgR was demonstrated to recognizel-2-HG as its specific effector molecule, and this allosteric transcription factor was then used as a biorecognition element for construction ofl-2-HG-sensing FRET sensor. The newly developedl-2-HG sensor can conveniently monitor the concentrations ofl-2-HG in various biological samples. In addition to bacteriall-2-HG generation during carbon starvation, biological functions of thel-2-HG dehydrogenase and hypoxia inducedl-2-HG accumulation were also revealed by using thel-2-HG sensor in human cells.
The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli
Authors: Cazzola Hélène , Lemaire Laurine , Acket Sébastien , Prost Elise , Duma Luminita , Erhardt Marc , Čechová Petra , Trouillas Patrick , Mohareb Fady , Rossi Claire , Rossez Yannick
Published: July 2020

EnterohemorrhagicEscherichia coli(EHEC) O157:H7 is a major cause of foodborne gastrointestinal illness. The adhesion of EHEC on host tissues is the first step enabling bacterial colonization. Adhesins like fimbriae and flagella mediate this mechanism. Here, we studied the interaction of the bacterial flagellum with the host cell’s plasma membrane using Giant Unilamellar Vesicles (GUVs) as a biologically relevant model. Cultured cell lines contain many different molecular components including proteins and glycoproteins. In contrast, with GUVs we can characterize the bacterial mode of interaction solely with a defined lipid part of the cell membrane. Bacterial adhesion on GUVs was dependent on the presence of the flagellar filament and its motility. By testing different phospholipid head groups, the nature of the fatty acid chains or the liposome curvature, we found that lipid packing is a key parameter to enable bacterial adhesion. Using HT-29 cells grown in the presence of polyunsaturated fatty acid (α-linolenic acid) or saturated fatty acid (palmitic acid), we found that α-linolenic acid reduced adhesion of wild type EHEC but not of a non-flagellated mutant. Finally, our results reveal that the presence of flagella is advantageous for the bacteria to bind to lipid rafts. We speculate that polyunsaturated fatty acids prevent flagellar adhesion on membrane bilayers and play a clear role for optimal host colonization. Flagella-mediated adhesion to plasma membranes has broad implications to host-pathogen interactions.

Importance

Bacterial adhesion is a crucial step to allow bacteria to colonize their hosts, invade tissues and form biofilm. EnterohemorrhagicE. coliO157:H7 is a human pathogen and the causative agent of diarrhea and hemorrhagic colitis. Here, we use biomimetic membrane models and cell lines to decipher the impact of lipid content of the plasma membrane on enterohemorrhagic E.coliflagella-mediated adhesion. Our findings provide evidence that polyunsaturated fatty acid (α-linolenic acid) inhibits E.coliflagella adhesion to the plasma membrane in a mechanism separate from its antimicrobial and anti-inflammatory functions. In addition, we confirm that cholesterol-enriched lipid microdomains, often called lipid rafts are important in bacterial adhesion. These findings significantly strengthen plasma membrane adhesion via bacterial flagella in an important human pathogen. This mechanism represents a promising target for the development of novel anti-adhesion therapies.
Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation
Authors: Bastos André M. , Donoghue Jacob A. , Brincat Scott L. , Mahnke Meredith , Yanar Jorge , Correa Josefina , Waite Ayan S. , Lundqvist Mikael , Roy Jefferson , Brown Emery N. , Miller Earl K.
Published: July 2020

The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little spiking, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation “awakened” anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.
Adaptation of theRomanomermis culicivoraxCCA-adding enzyme to miniaturized armless tRNA substrates
Authors: Hennig Oliver , Philipp Susanne , Bonin Sonja , Rollet Kévin , Kolberg Tim , Jühling Tina , Betat Heike , Sauter Claude , Mörl Mario
Published: July 2020

The mitochondrial genome of the nematodeRomanomermis culicivoraxencodes for miniaturized hairpin-like tRNA molecules that lack D- as well as T-arms, strongly deviating from the consensus cloverleaf. The single tRNA nucleotidyltransferase of this organism is fully active on armless tRNAs, while the human counterpart is not able to add a complete CCA-end. Transplanting single regions of theRomanomermisenzyme into the human counterpart, we identified a beta-turn element of the catalytic core that – when inserted into the human enzyme - confers full CCA-adding activity on armless tRNAs. This region, originally identified to position the 3’-end of the tRNA primer in the catalytic core, dramatically increases the enzyme’s substrate affinity. While conventional tRNA substrates bind to the enzyme by interactions with the T-arm, this is not possible in the case of armless tRNAs, and the strong contribution of the beta-turn compensates for an otherwise too weak interaction required for the addition of a complete CCA-terminus. This compensation demonstrates the remarkable evolutionary plasticity of the catalytic core elements of this enzyme to adapt to unconventional tRNA substrates.