bluuebunny/crossref_metadata_2025 huggingface dataset:
Canonical analytical solutions of wave-induced thermoelastic attenuation
Authors: Carcione José M , Gei Davide , Santos Juan E , Fu Li-Yun , Ba Jing
Published: January 2020

Thermoelastic attenuation is similar to wave-induced fluid-flow attenuation (mesoscopic loss) due to conversion of the fast P wave to the slow (Biot) P mode. In the thermoelastic case, the P- and S-wave energies are lost because of thermal diffusion. The thermal mode is diffusive at low frequencies and wave-like at high frequencies, in the same manner as the Biot slow mode. Therefore, at low frequencies, that is, neglecting the inertial terms, a mathematical analogy can be established between the diffusion equations in poroelasticity and thermoelasticity. We study thermoelastic dissipation for spherical and cylindrical cavities (or pores) in 2-D and 3-D, respectively, and a finely layered system, where, in the latter case, only the Grüneisen ratio is allowed to vary. The results show typical quality-factor relaxation curves similar to Zener peaks. There is no dissipation when the radius of the pores tends to zero and the layers have the same properties. Although idealized, these canonical solutions are useful to study the physics of thermoelasticity and test numerical algorithm codes that simulate thermoelastic dissipation.
On strong stability of explicit Runge–Kutta methods for nonlinear semibounded operators
Authors: Ranocha Hendrik
Published: January 2020

Explicit Runge–Kutta methods are classical and widespread techniques in the numerical solution of ordinary differential equations (ODEs). Considering partial differential equations, spatial semidiscretizations can be used to obtain systems of ODEs that are solved subsequently, resulting in fully discrete schemes. However, certain stability investigations of high-order methods for hyperbolic conservation laws are often conducted only for the semidiscrete versions. Here, strong stability (also known as monotonicity) of explicit Runge–Kutta methods for ODEs with nonlinear and semibounded (also known as dissipative) operators is investigated. Contrary to the linear case it is proven that many strong-stability-preserving (SSP) schemes of order 2 or greater are not strongly stable for general smooth and semibounded nonlinear operators. Additionally, it is shown that there are first-order-accurate explicit SSP Runge–Kutta methods that are strongly stable (monotone) for semibounded (dissipative) and Lipschitz continuous operators.
All that glitters: Federal Court of Canada issues Canada's first website blocking order against GoldTV
Authors: Crowne Emir
Published: January 2020

Bell Media Inc. v GoldTV.Biz (2019) FC 1432, 15 November 2019

On 15 November 2019, the Federal Court of Canada issued Canada’s first website blocking order in a copyright case.
Syrian Refugees in Canada and Transculturalism: Relationship between Media, Integration and Identity
Authors: Mohamed Eid , Bastug Mehmet
Published: January 2020

The process of integration of Syrian newcomers into Canada is multifaceted. The Canadian government, in its efforts to welcome refugees, has provided services that smooth this process over on many fronts. While financial and support services are essential to feelings of comfort, safety and security, feelings of identity and belonging constitute a never-ending process. In a globalized world, country of residence can easily change, but attachment to issues in the country of origin enlists a much more complex relationship. This article seeks to explore Syrian newcomers’ pre-migration and post-migration experiences and the influence of such experiences on their sense of belonging and identification. This article also seeks to understand their media-consumption habits. In doing so, the level of involvement of Syrian refugees in issues of host society versus issues in Syria or the Arab world becomes apparent. Through highlighting their level of involvement, this research hopes to uncover the feelings of responsibility to democratic change and the revolutionary process in Syria.
Effect of Blood Pressure Variability During the Acute Period of Subarachnoid Hemorrhage on Functional Outcomes
Authors: Ascanio Luis C , Enriquez-Marulanda Alejandro , Maragkos Georgios A , Salem Mohamed M , Alturki Abdulrahman Y , Ravindran Krishnan , Fehnel Corey R , Hanafy Khalid , Ogilvy Christopher S , Thomas Ajith J , Moore Justin M
Published: January 2020

BACKGROUND

The association of blood pressure variation with poor outcomes in aneurysmal subarachnoid hemorrhage (aSAH) is unknown.

OBJECTIVE

To evaluate the association of systolic blood pressure (SBP) variation and clinical outcomes in aSAH.

METHODS

We conducted a retrospective chart review of all aSAH patients treated at an academic institution between 2007 and 2016. Patient demographics, aSAH characteristics, and blood pressure observations for the first 24 h of admission in 4-h intervals were obtained. SBP variability metrics assessed were mean, standard deviation, maximum, minimum, peak, trough, coefficient of variation, and successive variation. The primary outcome was a composite of the modified Rankin scale as good (0-2) or poor (3-6) at last follow-up. Comparisons between outcome groups were performed. Logistic regression models for each significant SBP metric controlling for potential confounders were constructed.

RESULTS

The study population was 202 patients. The mean age was 57 yr; 66% were female. The median follow-up time was 18 mo; 57 (29%) patients had a poor outcome. Patients with poor outcomes had higher standard deviation (17.1 vs 14.7 mmHg, P = .01), peak (23.5 vs 20.0 mmHg, P = .02), trough (22.6 vs 19.2 mmHg, P < .01), coefficient of variation (13.9 vs 11.8 mmHg, P < .01), and lower minimum SBP (101.4 vs 108.4, P < .01). The logistic regression showed that every 1-mmHg increase in the minimum SBP increased the odds of good outcomes (odds ratio = 1.03; 95% CI = 1.001-1.064; P = .04). Models including other SBP metrics were not significant.

CONCLUSION

Hypotension was found to be independently associated with poor outcomes in patients with aSAH.
Association of a Remotely Offered Infectious Diseases eConsult Service With Improved Clinical Outcomes
Authors: Tande Aaron J , Berbari Elie F , Ramar Priya , Ponamgi Shiva P , Sharma Umesh , Philpot Lindsey , O’Horo John C
Published: January 2020

We performed a case–control study to evaluate an electronic, asynchronous infectious diseases consultative service at 2 rural hospitals within our health system. Patients with consultation via this platform (n = 100) had a significantly decreased odds of death at 30 days compared with propensity-matched controls (n = 300; adjusted odds ratio, 0.3; 95% confidence interval, 0.2–0.7; P = .003).
Cu∥-loaded polydopamine coatings with in situ nitric oxide generation function for improved hemocompatibility
Authors: Zhou Lei , Li Xin , Wang Kebing , Shen Fangyu , Zhang Lu , Li Peichuang , Shang Tengda , Wang Jin , Huang Nan
Published: January 2020

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells, and it has many functions, such as maintaining cardiovascular homeostasis, regulating vasodilation, inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system. Insufficient NO release is often observed in the pathological environment, for instance atherosclerosis. It was discovered that NO could be released from the human endogenous NO donor by many compounds, and these methods can be used for the treatment of certain diseases in the blood system. In this work, a series of copper-loaded polydopamine (PDA) coatings were produced through self-polymerization time for 24, 48 and 72 h. The chemical composition and structure, coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative, X-ray photoelectron spectroscopy, ellipsometry atomic force microscopy and water contact angles. The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copper-loaded coating has glutathione peroxidase-like activity, and it has the capability of catalyzing NO releasing from GSNO. The surface of the coating showed desirable hemocompatibility, the adhesion and activation of platelets were inhibited on the copper-loaded coatings. At the same time, the formation of the thrombosis was also suppressed. These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.
H. G. Wells and the Fin-de-Siècle Gustatory Paradox
Authors: Valentine Colton
Published: January 2020

Beginning with a little-studied scene linking H. G. Wells’s ‘A Misunderstood Artist’ to Joris-Karl Huysmans’s À Rebours, this essay argues that a shared gustatory paradox runs from Huysmanian decadence, through the theories of Edwin Lankester and Max Nordau and into Wells’s writings. In each case, both a pragmatic and an aesthetic relationship to food can signify degeneration. The argument has three major stakes. The first is to reconstruct a robust intertextual relation between the oeuvres of Huysmans and Wells. The second is to complicate readings that cast two of Wells’s scientific romances, The Time Machine and The War of the Worlds, as mouthpieces for imperialist or (pseudo)scientific discourses (Anger, Brantlinger, Budd, Gailor, Gregory, Hendershot, Pick). The third is to build on recent studies of food representation in nineteenth-century literature and propose a novel interpretive method (Cozzi, Gyman, Lee). Taking up William Greenslade’s proposal that fictions construct a ‘network of resistances’ to discursive myths, I argue that gustatory scenes show Wells’s ‘network’ operating in a curious way. They neither kowtow to degeneration nor assume Greenslade’s active role of a ‘critical, combative humanist’. Instead, they give contradictory depictions of moralized eating that play out the myth’s structural paradox.
Functional characterization and expression patterns of PnATX genes under different abiotic stress treatments in Populus
Authors: Xu Zhiru , Huang Jiahuan , Qu Chunpu , Chang Ruhui , Chen Jinyuan , Wang Qi , Xi Qi , Song Yang , Sun Qi , Yang Chuanping , Liu Guanjun
Published: January 2020

The copper chaperone ATX1 has been investigated previously in the herbaceous plants Arabidopsis and rice. However, the molecular mechanisms of ATX1 underlying copper transport and functional characteristics in the woody plant Populus are poorly understood. In this study, PnATX1 and PnATX2 of Populus simonii × P. nigra were identified and characterized. Sequence analysis showed that PnATXs contained the metal-binding motif MXCXXC in the N-terminus and a lysine-rich region. Phylogenetic analysis of ATX protein sequences revealed that PnATXs were clustered in the same group as AtATX1. PnATX proteins were localized in the cytoplasm and nucleus. Tissue-specific expression analysis showed that PnATX1 and PnATX2 were expressed in all analyzed tissues and, in particular, expressed to a higher relative expression level in young leaves. Quantitative real-time PCR analysis indicated that each PnATX gene was differentially expressed in different tissues under treatments with copper, zinc, iron, jasmonate and salicylic acid (SA). The copper-response element GTAC, methyl jasmonate and salicylic acid responsiveness elements and other cis-acting elements were identified in the PnATX1 and PnATX2 promoters. Expression of β-glucuronidase driven by the PnATX1 promoter was observed in the apical meristem of 7-day-old Arabidopsis transgenic seedlings, and the signal strength was not influenced by deficient or excessive copper conditions. Both PnATX1 and PnATX2 functionally rescued the defective phenotypes of yeast atx1Δ and sod1Δ strains. Under copper excess and deficiency conditions, transgenic Arabidopsis atx1 mutants harboring 35S::PnATX constructs exhibited root length and fresh weight similar to those of the wild type and higher than those of Arabidopsis atx1 mutants. Superoxide dismutase activity decreased in transgenic lines compared with that of atx1 mutants, whereas peroxidase and catalase activities increased significantly under excess copper. The results provide a basis for elucidating the role of Populus PnATX genes in copper homeostasis.
The importance of conduction versus convection in heat pulse sap flow methods
Authors: Forster Michael A
Published: January 2020

Heat pulse methods are a popular approach for estimating sap flow and transpiration. Yet, many methods are unable to resolve the entire heat velocity measurement range observable in plants. Specifically, the Heat Ratio (HRM) and Tmax heat pulse methods can only resolve slow and fast velocities, respectively. The Dual Method Approach (DMA) combines optimal data from HRM and Tmax to output the entire range of heat velocity. However, the transition between slow and fast methods in the DMA currently does not have a theoretical solution. A re-consideration of the conduction/convection equation demonstrated that the HRM equation is equivalent to the Péclet equation which is the ratio of conduction to convection. This study tested the hypothesis that the transition between slow and fast methods occurs when conduction/convection, or the Péclet number, equals one, and the DMA would be improved via the inclusion of this transition value. Sap flux density was estimated via the HRM, Tmax and DMA methods and compared with gravimetric sap flux density measured via a water pressure system on 113 stems from 15 woody angiosperm species. When the Péclet number ≤ 1, the HRM yielded accurate results and the Tmax was out of range. When the Péclet number > 1, the HRM reached a maximum heat velocity at approximately 15 cm hr −1 and was no longer accurate, whereas the Tmax yielded accurate results. The DMA was able to output accurate data for the entire measurement range observed in this study. The linear regression analysis with gravimetric sap flux showed an r2 of 0.541 for HRM, 0.879 for Tmax and 0.940 for DMA. With the inclusion of the Péclet equation, the DMA resolved the entire heat velocity measurement range observed across 15 taxonomically diverse woody species. Consequently, the HRM and Tmax are redundant sap flow methods and have been superseded by the DMA.
Relationship Between Sudden Death Syndrome caused by Fusarium virguliforme and Soybean Yield: A Meta-Analysis
Authors: Kandel Yuba R. , Bradley Carl A. , Chilvers Martin I. , Mathew Febina M. , Tenuta Albert U. , Smith Damon L. , Wise Kiersten A. , Mueller Daren S.
Published: January 2020

In total, 52 uniform field experiments were conducted in Illinois, Indiana, Iowa, Michigan, South Dakota, and Wisconsin in the United States and Ontario, Canada from 2013 to 2017 comparing crop protection products against sudden death syndrome (SDS) of soybean. Data were analyzed using meta-analytic models to summarize the relationship between foliar disease index (FDX) and yield. For each study, correlation and regression analyses were performed separately to determine three effect sizes: Fisher’s transformation of correlation coefficients (Z r ), intercept (β0), and slope (β1). Random- and mixed-effect meta-analyses were used to summarize the effect sizes. Study- and location-specific moderator variables FDX (low < 10% and high ≥ 10%), date of planting (early = prior to 7 May, conventional = 7 to 21 May, and late = after 21 May) cultivar (susceptible and partially resistant to SDS), study location, and growing season were used as fixed effects. The overall mean effect sizes of transformed correlation coefficient [Formula: see text] r was −0.41 and different from zero (P < 0.001), indicating that yield was negatively correlated with FDX. The [Formula: see text] r was affected by disease level (P < 0.01) and cultivar (P = 0.02), with a greater effect at higher disease levels and with susceptible cultivars. The mean [Formula: see text] 0 was 4,121 kg/ha and mean [Formula: see text] 1 was −21 kg/ha/% FDX and were different from zero (P < 0.01). Results from these data indicate that, for every unit of FDX increase, yield was decreased by 0.5%. Study locations and year affected the [Formula: see text] 0 , whereas none of the moderator variables significantly affected [Formula: see text] 1.
Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin
Authors: Höllhumer Roland , Watson Stephanie , Beckingsale Peter
Published: January 2020

Purpose:

Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution.

Methods:

A retrospective case series.

Results:

Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was <6/18 in all 6 cases because of irregular astigmatism and stromal haze. Thinning, vascularization, and scarring of the residual host tissue were noted.

Conclusions:

Substitution of dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.
Management of Descemet Membrane Detachment After Forceps Birth Injury
Authors: Kancherla Swarupa , Shue Ann , Pathan Mohammad Faizan , Sylvester Christin L. , Nischal Ken K.
Published: January 2020

Purpose:

To describe the clinical signs of Descemet membrane (DM) detachment due to forceps-related birth injury and its subsequent management using optical coherence tomography.

Methods:

Case report.

Results:

A 3-day-old term infant presented with left eye corneal clouding and a definitive history of traumatic forceps-assisted delivery. Despite topical therapy, corneal clouding persisted, necessitating an examination under anesthesia using ultrasound and handheld optical coherence tomography. This revealed not only a tear in DM but also a large detachment. Injection of air alone failed to achieve apposition of DM to the posterior stroma. Apposition was achieved only after penetration of the overlying cornea with the needle of a 10-0 nylon suture and release of clear viscous fluid. The cornea cleared within the first week and continued in the months to follow.

Conclusions:

Prolonged corneal edema should alert the physician to probable DM detachment after forceps-related birth injury. Injecting air alone may not be sufficient to reattach the detached DM.
Lactobacillus mulieris sp. nov., a new species of Lactobacillus delbrueckii group
Authors: Rocha Joana , Botelho João , Ksiezarek Magdalena , Perovic Svetlana Ugarcina , Machado Miguel , Carriço João André , Pimentel Lígia L. , Salsinha Sofia , Rodríguez-Alcalá Luís M. , Pintado Manuela , Ribeiro Teresa G. , Peixe Luísa
Published: January 2020

One Gram-stain-positive, non-motile, non-spore-forming, catalase-negative, and coccobacilli-shaped strain, designated c10Ua161MT, was isolated from a urine sample from a reproductive-age healthy woman. Comparative 16S rRNA gene sequence analysis indicated that strain c10Ua161MT belonged to the genus

Lactobacillus

. Phylogenetic analysis based on pheS and rpoA gene sequences strongly supported a clade encompassing strains c10Ua161MT and eight other strains from public databases, distinct from currently recognized species of the genus Lactobacillus. In silico Average Nucleotide Identity (ANI) and Genome-to-Genome Distance Calculator (GGDC), showed 87.9 and 34.3 % identity to the closest relative

Lactobacillus jensenii

, respectively. The major fatty acids of strain c10Ua161MT were C18 : 1ω9c (65.0%), C16 : 0 (17.8%), and summed feature 8 (10.2 %; comprising C18 : 1ω7c, and/or C18 : 1ω6c). The DNA G+C content of the strains is 34.2 mol%. On the basis of data presented here, strain c10Ua161MT represents a novel species of the genus

Lactobacillus

, for which the name Lactobacillus mulieris sp. nov. is proposed. The type strain is c10Ua161MT (=CECT 9755T=DSM 108704T).
Using relative brain size to better understand trophic interactions and phenotypic plasticity of invasive lionfish (Pterois volitans)
Authors: Becker McKenna
Published: January 2020

Predator-prey dynamics provide critical insight into overall coral reef health. It has been shown that predator-prey relationships link the relative brain size of predators to their prey. Predation pressure forces prey to use decision-making skills that require higher cognition by inspecting and identifying predators and then adjusting their behavior to achieve the highest chance for survival. However, the predation pressure that prey face outweighs the pressure predators face to find prey, resulting in prey having larger relative brain sizes than their predators. There is little data on the relative brain size of fishes with few natural predators such asPterois volitans. This study compared the brain mass to body mass ratio ofPterois volitans, which have very few natural predators and thus very little predation pressure, to the brain mass to body mass ratio of their prey, possible predators, competitors, and taxonomically similar fish. Lionfish had a significantly smaller relative brain size than their predators, prey, and competitors, but was not significantly smaller than taxonomically similar fish. These results demonstrate that the morphological anti-predator adaptation of venomous spines causes little predation pressure. Thus, lionfish do not use the same cognitive skills as other prey or predators and, in turn, have smaller relative brain sizes.
CYTOTOXIC ACTIVITY OF A NEW ISOFORM L-AMINO ACID OXIDASE (BALT-LAAO-II) FROMBothrops alternatus(URUTU) SNAKE VENOM IN HUMAN LEUKEMIC HL60 CELLS
Authors: Heleno Maurício Aurelio Gomes , Nowill Alexandre , de Carvalho João Ernesto , Suni-Curasi Diego L. , Vilca-Quispe Julissa , Ponce-Fuentes Emilio Alberto , Obando-Pereda Gustavo Alberto , Ponce-Soto Luis Alberto
Published: January 2020

In this work we describe the isolation of a new isoform L-amino acid oxidase (LAAO) referred to as Balt-LAAO-II fromBothrops alternatussnake venom, which was highly purified using a combination of molecular exclusion (Sephadex G-75) and RP-HPLC chromatographics steps. When analyzed by SDS-PAGE, the purified Balt-LAAO-II presented a molecular weight of ∼66 kDa. The N-terminal amino acid sequence and internal peptide sequences showed close structural homology to other snake venom L-amino acid oxidases.

This enzyme inducesin vitrocytotoxicity on cultured human leukemic HL60 cells. Cells were grown in RPMI medium and were incubated with isoform Balt-LAAO-II (1, 10 and 100 μg/mL) for up to 72 h. All three concentrations of venom markedly decreased the cell viability from 6 h onwards based on the staining with propidium iodide, the reduction of 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and the uptake of neutral red.

Flow cytometry showed that all isoform Balt-LAAO-II and whole venom concentrations induced apoptosis after 2-6 h of incubation. Morphological analysis of cells incubated with isoform Balt-LAAO-II and whole venom showed cell rounding and lysis that increased with the venom concentration and duration of incubation. These results show that isoform Balt-LAAO-II from venomBothrops alternatusis cytotoxic to cultured HL60 cells and suggest that this damage may involve apoptotic and oxidative stress pathways.
E. coliadhesion and biofilm formation on polydimethylsiloxane are independent of substrate stiffness
Authors: Arias Sandra L. , Devorkin Joshua , Civantos Ana , Allain Jean Paul
Published: January 2020

Bacterial adhesion and biofilm formation on the surface of biomedical devices is a detrimental process that compromises patient safety and material functionality. Several physicochemical factors are involved in biofilm growth, including the surface properties. Among those, material stiffness has recently been suggested to influence microbial adhesion and biofilm growth in a variety of polymers and hydrogels. However, no clear consensus exists about the role of material stiffness on biofilm initiation and whether very compliant substrates are deleterious to bacterial cell adhesion. Here, by systematically tuning substrate topography and stiffness while keeping the surface free energy of polydimethylsiloxane substrates constant, we show that topographical patterns at the micron and submicron scale impart unique properties to the surface that are independent of the material stiffness. The current work provides a better understanding of the role of material stiffness on bacterial physiology and may constitute a cost-effective and simple strategy to reduce bacterial attachment and biofilm growth even in very compliant and hydrophobic polymers.
Alfalfa leaf curl virus is efficiently acquired by its aphid vector Aphis craccivora but inefficiently transmitted
Authors: Ryckebusch Faustine , Peterschmitt Michel , Granier Martine , Sauvion Nicolas
Published: January 2020

Alfalfa leaf curl virus (ALCV) is the first geminivirus for which an aphid transmission was reported. Transmission by Aphis craccivora was determined previously to be highly specific and circulative. Using various complementary techniques, the transmission journey of ALCV was monitored from its uptake in an infected plant tissue up to the head of its vector. ALCV was shown to be restricted in the phloem using fluorescent in situ hybridization (FISH) and electropenetrography (EPG) monitoring of virus acquisition. Furthermore, the virus is heterogeneously distributed in the phloem as revealed by FISH and qPCR quantification of the viral DNA acquired by aphids monitored by EPG. In spite of the efficient ingestion of viral DNA, about 106 in a 15-hour feeding on ALCV infected plants, the individual transmission rate was at a maximum of 12%. Transmission success was related to a critical viral accumulation, around 1.6×107 viral DNA copies per insect, a threshold that needs generally more than 48 hours to be reached. Moreover, whereas the amount of acquired virus does not decrease over time in the whole aphid body, it decreased in hemolymph and heads. ALCV was not detected in progenies of viruliferous aphids and had no effect on aphid fitness. Compared to geminiviruses transmitted by whiteflies or leafhoppers or to luteovirus transmitted by aphids, the transmission efficiency of ALCV by A. craccivora is low. This result is discussed in relation to the aphid vector of this geminivirus and the agroecological features of alfalfa, a hardy perennial host plant.
A scalable method for estimating the regional polygenicity of complex traits
Authors: Johnson Ruth , Burch Kathryn S. , Hou Kangcheng , Paciuc Mario , Pasaniuc Bogdan , Sankararaman Sriram
Published: January 2020

A key question in human genetics is understanding the proportion of SNPs modulating a particular phenotype or the proportion of susceptibility SNPs for a disease, termedpolygenicity. Previous studies have observed that complex traits tend to be highly polygenic, opposing the previous belief that only a handful of SNPs contribute to a trait. Beyond these genome-wide estimates, the distribution of polygenicity across genomic regions as well as the genomic factors that affect regional polygenicity remain poorly understood. A reason for this gap is that methods for estimating polygenicity utilize SNP effect sizes from GWAS. However, estimating regional polygenicity from GWAS effect sizes involves untangling the correlation between SNPs due to LD, leading to intractable computations for even a small number of SNPs. In this work, we propose a scalable method, BEAVR, to estimate the regional polygenicity of a trait given marginal effect sizes from GWAS and LD information. We implement a Gibbs sampler to estimate the posterior distribution of the regional polygenicity and derive a fast, algorithmic update to circumvent the computational bottlenecks associated with LD. The runtime of our algorithm is 𝒪(MK) forMSNPs andKsusceptibility SNPs, where the number of susceptibility SNPs is typicallyK≪M. By modeling the full LD structure, we show that BEAVR provides unbiased estimates of polygenicity compared to previous methods that only partially model LD. Finally, we show how estimates of regional polygenicity for BMI, eczema, and high cholesterol provide insight into the regional genetic architecture of each trait.
Single-Cell Electrophysiological Measurements Reveal Bacterial Membrane Potential Dynamics during Extracellular Electron Transfer
Authors: Pirbadian Sahand , Chavez Marko S. , El-Naggar Mohamed Y.
Published: January 2020

Extracellular electron transfer (EET) allows microorganisms to gain energy by linking intracellular reactions to external surfaces ranging from natural minerals to the electrodes of bioelectrochemical renewable energy technologies. In the past two decades, electrochemical techniques have been used to investigate EET in a wide range of microbes, with emphasis on dissimilatory metal-reducing bacteria, such asShewanella oneidensisMR-1, as model organisms. However, due to the typically bulk nature of these techniques, they are unable to reveal the subpopulation variation in EET or link the observed electrochemical currents to energy gain by individual cells, thus overlooking the potentially complex spatial patterns of activity in bioelectrochemical systems. Here, to address these limitations, we use the cell membrane potential as a bioenergetic indicator of EET byS. oneidensisMR-1 cells. Using a fluorescent membrane potential indicator duringin vivosingle-cell level fluorescence microscopy in a bioelectrochemical reactor, we demonstrate that membrane potential strongly correlates with the electrode potential, produced current, and position of cells relative to the electrodes. The high spatial and temporal resolution of the reported technique can be used to study the single-cell level dynamics of EET not only on electrode surfaces, but also during respiration of other solid-phase electron acceptors.
The Mathematics Underlying Eeg Oscillations Propagation
Authors: Tozzi Arturo , Bormashenko Edward , Jausovec Norbert
Published: January 2020

Whenever one attempts to comb a hairy ball flat, there will always be at least one tuft of hair at one point on the ball. This seemingly worthless sentence is an informal description of the hairy ball theorem, an invaluable mathematical weapon that has been proven useful to describe a variety of physical/biological processes/phenomena in terms of topology, rather than classical cause/effect relationships. In this paper we will focus on the electrical brain field – electroencephalogram (EEG). As a starting point we consider the recently-raised observation that, when electromagnetic oscillations propagate with a spherical wave front, there must be at least one point where the electromagnetic field vanishes. We show how this description holds also for the electric waves produced by the brain and detectable by EEG. Once located these zero-points in EEG traces, we confirm that they are able to modify the electric wave fronts detectable in the brain. This sheds new light on the functional features of a nonlinear, metastable nervous system at the edge of chaos, based on the neuroscientific model of Operational Architectonics of brain-mind functioning. As an example of practical application of this theorem, we provide testable previsions, suggesting the proper location of transcranial magnetic stimulation’s coils to improve the clinical outcomes of drug-resistant epilepsy.
mosaicFlye: Resolving long mosaic repeats using long error-prone reads
Authors: Bankevich Anton , Pevzner Pavel
Published: January 2020

Long-read technologies revolutionized genome assembly and enabled resolution ofbridged repeats(i.e., repeats that are spanned by some reads) in various genomes. However, the problem of resolvingunbridged repeats(such as long segmental duplications in the human genome) remains largely unsolved, making it a major obstacle towards achieving the goal of complete genome assemblies. Moreover, the challenge of resolving unbridged repeats is not limited to eukaryotic genomes but also impairs assemblies of bacterial genomes and metagenomes. We describe the mosaicFlye algorithm for resolving complex unbridged repeats based on differences between various repeat copies and show how it improves assemblies of the human genome as well as bacterial genomes and metagenomes. In particular, we show that mosaicFlye results in a complete assembly of both arms of the human chromosome 6.
Novel phylogeny of angiosperms inferred from whole-genome microsynteny analysis
Authors: Zhao Tao , Xue Jiayu , Kao Shu-min , Li Zhen , Zwaenepoel Arthur , Schranz M. Eric , Van de Peer Yves
Published: January 2020

Despite the wealth of genomic and transcriptomic data of pivotal angiosperm species, the phylogenetic relationships of flowering plants are still not fully resolved. Microsynteny, or the conservation of relative gene order, has been recognized as a valuable and alternative phylogenetic character to sequence-based characters (nucleotides or amino acids). Here, we present a novel approach for phylogenetic tree reconstruction based on genome-wide synteny network data. We generated and analyzed synteny networks from 123 species from 52 families across 31 orders of flowering plants, including several lineages for which phylogenetic relationships are ambiguous. We obtained a stable and highly resolved phylogeny that is largely congruent with sequence-based phylogenies. However, our results unveiled several novel relationships for some key clades, such as magnoliids sister to monocots, Vitales as sister to core-eudicots, and Saxifragales sister to Santalales, in turn both sister to Caryophyllales. Our results highlight that phylogenies based on genome structure and organization are complementary to sequence-based phylogenies and provide alternative hypotheses of angiosperm relationships to be further tested.
Simple and efficient measurement of transcription initiation and transcript levels with STRIPE-seq
Authors: Policastro Robert A. , Raborn R. Taylor , Brendel Volker P. , Zentner Gabriel E.
Published: January 2020

Accurate mapping of transcription start sites (TSSs) is key for understanding transcriptional regulation. However, current protocols for genome-wide TSS profiling are laborious and/or expensive. We present Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a simple, rapid, and cost-effective protocol for sequencing capped RNA 5’ ends from as little as 50 ng total RNA. Including depletion of uncapped RNA and SPRI bead cleanups, a STRIPE-seq library can be constructed in about five hours. We demonstrate application of STRIPE-seq to TSS profiling in yeast and human cells and show that it can also be effectively used for measuring transcript levels and differential gene expression analysis. In conjunction with our ready-to-use computational analysis workflows, STRIPE-seq is a straightforward, efficient means by which to probe the landscape of transcriptional initiation.
Cold exposure distinctively modulates parathyroid and thyroid hormones in cold-acclimatized and non-acclimatized humans
Authors: Kovaničová Zuzana , Kurdiová Tímea , Baláž Miroslav , Štefanička Patrik , Varga Lukáš , Kulterer Oana C. , Betz Matthias J. , Haug Alexander R. , Burger Irene A. , Kiefer Florian W. , Wolfrum Christian , Ukropcová Barbara , Ukropec Jozef
Published: January 2020

Context

Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood.

Objective

To investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans.

Design

Cross-sectional study examining acute response to ice-water swimming and to experimental non-shivering thermogenesis (NST) induction in individuals acclimatized and non-acclimatized to cold. Seasonal variation in energy metabolism of ice-water swimmers and associations between circulating PTH and molecular components of thermogenic program in brown adipose tissue (BAT) of neck-surgery patients were evaluated.

Setting

Clinical Research Center.

Patients, Participants

Ice-water swimmers (winter swim n=15, NST-induction n=6), non-acclimatized volunteers (NST-induction, n=11, elective neck surgery n = 36).

Main Outcomes and Results

In ice-water swimmers, PTH and TSH increased in response to 15min winter swim, while activation of NST failed to regulate PTH and lowered TSH. In non-acclimatized men, NST-induction decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT 18F-FDG uptake was found across the two populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively withUCP1/UCP1,PPARGC1AandDIO2in BAT from neck surgery patients.

Conclusions

Regulation of PTH and thyroid hormones during cold exposure in humans depends on the cold acclimatization level and/or cold stimulus intensity. Role of PTH in NST is substantiated by its positive relationships with whole-body metabolic preference for lipids, BAT volume and UCP1 content.
Genetically encoded split luciferase biosensors to measure endosome disruption in real time in live cells
Authors: Kilchrist Kameron V. , Tierney J. William , Duvall Craig L.
Published: January 2020

Endosomal escape is a critical step in intracellular delivery of biomacromolecular drugs, but quantitative, high throughput study of endosomal vesicle disruption remains elusive. We designed two genetically encoded split luciferase “turn on” reporters that can be assayed rapidly in well plates on live cells using a luminometer. Both systems use non-luminescent N-terminal and C-terminal luciferase fragments which can reconstitute a functional luminescent enzyme when they are held in proximity by their fusion partners. The first system uses Gal8 and CALCOCO2 fused to these fragments, which interact following endosome disruption and facilitate complementation of the split luciferase fragments to produce significant luminescence when luciferin is added. The second system uses the N-terminal carbohydrate recognition domain of Gal8 (G8-NCRD) fused to both luciferase fragments. Following endosome disruption, G8-NCRD binds to exposed glycans inside endosomes, concentrating both fragments there to reconstitute active luciferase. Additionally, and in contrast to recently reported Gal8 intracellular tracking with fluorescent microscopy, these split luciferase-based assays enable simultaneous identification and downselection of cytotoxic test conditions because the luciferase reaction requires intracellular ATP. Further, we demonstrate that the lead luminescent cell line is more sensitive to detection of endosomal disruption at lower doses of an endosome disrupting drug carrier than the previously reported Gal8-YFP fluorescent system. These systems represent a first-in-class luminescent assay to detect endosome disruption in high throughput while excluding toxic formulations. Endosome disruption screening with these “turn on” systems has potential as a tool in the discovery and development of intracellular biologic drug delivery formulations.

Graphical Abstract
Proteome specialization of anaerobic fungi during ruminal degradation of recalcitrant plant fiber
Authors: Hagen Live H. , Brooke Charles G. , Shaw Claire , Norbeck Angela D. , Piao Hailan , Arntzen Magnus Ø. , Brewer Heather , Copeland Alex , Isern Nancy , Shukla Anil , Roux Simon , Lombard Vincent , Henrissat Bernard , O’Malley Michelle A. , Grigoriev Igor V. , Tringe Susannah , Mackie Roderick , Pasa-Tolic Ljiljana , Pope Phillip B. , Hess Matthias
Published: January 2020

The rumen harbors a complex microbial mixture of archaea, bacteria, protozoa and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 hours in nylon bags within the rumen of cannulated dairy cows. Across a gene catalogue covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of polysaccharides such as hemicellulose, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8 and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks ofin siturecalcitrant fiber deconstruction, and importantly, suggests that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.
Wheelchair user’s voice: a pilot study in Indonesia
Authors: Vasquez Stephanie Gabela , D’Innocenzo Megan E. , Pearlman Jon , Zigler Christy , Mendez Yasmin Garcia , Rozen Perth , Dewi Eviana Hapsari , Praptoraharjo Ignatius
Published: January 2020

There is a significant unmet need for appropriate wheelchairs worldwide. As a whole, studies suggest that appropriate wheelchairs have a positive impact on the quality of life and health of wheelchair users, which is consistent with the goals and outcomes in more resourced settings, and that when services are provided along with the wheelchair, the positive impact is increased. The gaps in previous research, along with the global focus on evidence-based decision making, were strong motivators for carrying out a study that contrasted the outcomes associated with different types of wheelchair service provision strategies. This study used a sample of participants randomly selected from a waitlist (N= 142) or people who used wheelchairs as their primary means of mobility. Two different groups were included, the 8-Steps group and the Standard of Care (SOC)group. The 8-Steps group (N= 118) received wheelchairs from service providers trained using the World Health Organization (WHO) 8-Step process and the SOC group (N=24) received hospital-style wheelchairs and standard care. Interviews were conducted at baseline and a follow up 3-6 months after distribution, to collect data using the following tools: International Society of Wheelchair Professionals (ISWP) Minimum Uniform Data Set (MUD), Wheelchair Skills Test Questionnaire (WST-Q), and Life Satisfaction Questionnaire (LiSAT-11), and Breakdown and Adverse Consequences Questionnaire (BAC-Q).Across-group statistical comparisons were not attempted. The majority of participants from the 8-Steps group used their wheelchair every day for more than 8 hours a day. In contrast, the SOC group used their wheelchairs less than 6 hours a day. Both groups traveled less than 500 meters per day. Participants’ WST-Q scores were low, <65%, at both baseline and endline, with a significant decrease at endline. No significant differences were found when comparing device satisfaction across wheelchairs types. The majority (n=87; 72.7%) of 8-Steps group participants reported performing wheelchair maintenance. Less than half (n=9; 37.5%) of the SOC group reported performing maintenance activities. For both groups, the most reported maintenance activity was wiping or washing the wheelchair, and most wheelchair repairs were performed by the study participant or a family member. The results of this study demonstrate the importance of the WHO 8-steps training package for wheelchair provision. Further studies, training services, and wheelchair skills are needed in low and middle-income countries for both wheelchair users and service providers.
Iterative Refinement of Cellular Identity from Single-Cell Data Using Online Learning
Authors: Gao Chao , Preissl Sebastian , Luo Chongyuan , Castanon Rosa , Sandoval Justin , Rivkin Angeline , Nery Joseph R. , Behrens Margarita M. , Ecker Joseph R. , Ren Bing , Welch Joshua D.
Published: January 2020

Recent experimental advances have enabled high-throughput single-cell measurement of gene expression, chromatin accessibility and DNA methylation. We previously used integrative non-negative matrix factorization (iNMF) to jointly learn interpretable low-dimensional representations from multiple single-cell datasets using dataset-specific and shared metagene factors. These factors provide a principled, quantitative definition of cellular identity and how it varies across biological contexts. However, datasets exceeding 1 million cells are now widely available, creating computational barriers to scientific discovery. For instance, it is no longer feasible to analyze large datasets using standard pipelines on a personal computer with limited memory capacity. Moreover, there is a need for an algorithm capable of iteratively refining the definition of cellular identity as efforts to create a comprehensive human cell atlas continually sequence new cells.

To address these challenges, we developed an online learning algorithm for integrating large and continually arriving single-cell datasets. We extended previous online learning approaches for NMF to minimize the expected cost of a surrogate function for the iNMF objective. We also derived a novel hierarchical alternating least squares algorithm for iNMF and incorporated it into an efficient online algorithm. Our online approach accesses the training data as mini-batches, decoupling memory usage from dataset size and allowing on-the-fly incorporation of new datasets as they are generated. The online implementation of iNMF converges much more quickly using a fraction of the memory required for the batch implementation, without sacrificing solution quality. Our new approach processes 1.3 million single cells from the entire mouse embryo on a laptop in 25 minutes using less than 500 MB of RAM. We also analyze large datasets without downloading them to disk by streaming them over the internet on demand. Furthermore, we construct a single-cell multi-omic cell atlas of the mouse motor cortex by iteratively incorporating eight single-cell RNA-seq, single-nucleus RNA-seq, single-nucleus ATAC-seq, and single-nucleus DNA methylation datasets generated by the BRAIN Initiative Cell Census Network.

Our approach obviates the need to recompute results each time additional cells are sequenced, dramatically increases convergence speed, and allows processing of datasets too large to fit in memory or on disk. Most importantly, it facilitates continual refinement of cell identity as new single-cell datasets from different biological contexts and data modalities are generated.