bluuebunny/crossref_metadata_2025 huggingface dataset:
High mitochondrial mutation rates inSileneare associated with nuclear-mediated changes in mitochondrial physiology
Authors: Weaver Ryan J. , Carrion Gina , Nix Rachel , Maeda Gerald P. , Rabinowitz Samantha , Iverson Erik N. K. , Thueson Kiley , Havird Justin C.
Published: September 2020

Mitochondrial (mt) respiration depends on proteins encoded both by the mitochondrial and nuclear genomes. Variation in mt-DNA mutation rates exists across eukaryotes, although the functional consequences of elevated mt mutation rates in some lineages remain underexplored. In the angiosperm genusSilene, closely related, ecologically similar species have either ‘fast' or ‘slow' mt-DNA mutation rates. Here, we investigated the functional consequences of elevated mt-DNA mutation rates on mt respiration profiles ofSilenemitochondria. Overall levels of respiration were similar among Species. Fast species had lower respiration efficiency than slow species and relied up to 48% more on nuclear-encoded respiratory enzymes alternative oxidase (AOX) and accessory dehydrogenases (DHex), which participate in stress responses in plants. However, not all fast species showed these trends. Respiratory profiles of some enzymes were correlated, most notably AOX and DHex. We conclude that subtle differences in mt physiology amongSilenelineages with dramatically different mt mutation rates may underly similar phenotypes at higher levels of biological organization, betraying the consequences of mt mutations.
Sydney Leach. 11 April 1924—24 December 2019
Authors: Field D. , Simons J. P. , Cockell Charles
Published: September 2020

Sydney Leach will be remembered as an outstanding and inspirational scientist, an irreplaceable friend to many—artists and musicians as well as academic colleagues. He encouraged and influenced numerous scientists as a mentor. After graduating from King's College London and carrying out war work at Farnborough, he spent all his scientific life based in Paris, working principally at Orsay and, in his later years, at the Observatoire de Paris–Meudon. Sydney was a major influence in establishing chemical physics in France after World War II, founding the highly influential Laboratoire de Photophysique Moléculaire (LPPM) at Orsay, where much of his pioneering work was performed. The ‘Sydney lab’ lives on in the newly created Institut des Sciences Moléculaires d'Orsay. Early experiments often took place at the synchrotron source (ACO, Super-ACO), just a few hundred yards from LPPM. He was a pioneering advocate of synchrotron radiation, and a driving force for its use in spectroscopy and photodynamics, along with free-electron lasers, supersonic jets, coincidence spectroscopy and matrix isolation—techniques that were applied and refined over decades and used to explore fundamental processes such as photoionization, vibronic coupling and radiationless transitions. Sydney's seminal studies of polyatomic molecular ions led him towards fresh horizons in planetary atmospheric and space science. His work opened new vistas in cometary spectroscopy, polycyclic aromatic hydrocarbons, fullerenes and their possible roles in the chemistry of the interstellar medium and, finally, biologically relevant species, helping to instigate the newly developing subject of astrobiology—a perfect example of his sustained prescience in the world of science.
Noise pollution: acute noise exposure increases susceptibility to disease and chronic exposure reduces host survival
Authors: Masud Numair , Hayes Laura , Crivelli Davide , Grigg Stephen , Cable Jo
Published: September 2020

Anthropogenic noise is a pervasive global pollutant that has been detected in every major habitat on the planet. Detrimental impacts of noise pollution on physiology, immunology and behaviour have been shown in terrestrial vertebrates and invertebrates. Equivalent research on aquatic organisms has until recently been stunted by the misnomer of a silent underwater world. In fish, however, noise pollution can lead to stress, hearing loss, behavioural changes and impacted immunity. But, the functional effects of this impacted immunity on disease resistance due to noise exposure have remained neglected. Parasites that cause transmissible disease are key drivers of ecosystem biodiversity and a significant factor limiting the sustainable expansion of the animal trade. Therefore, understanding how a pervasive stressor is impacting host–parasite interactions will have far-reaching implications for global animal health. Here, we investigated the impact of acute and chronic noise on vertebrate susceptibility to parasitic infections, using a model host–parasite system (guppy–
Gyrodactylus turnbulli
). Hosts experiencing acute noise suffered significantly increased parasite burden compared with those in no noise treatments. By contrast, fish experiencing chronic noise had the lowest parasite burden. However, these hosts died significantly earlier compared with those exposed to acute and no noise treatments. By revealing the detrimental impacts of acute and chronic noise on host–parasite interactions, we add to the growing body of evidence demonstrating a link between noise pollution and reduced animal health.
Turning defence into offence? Intrusion of cladoceran brood chambers by a green alga leads to reproductive failure
Authors: Albini Dania , Fowler Mike S. , Llewellyn Carole , Tang Kam W.
Published: September 2020

Microalgae are the foundation of aquatic food webs. Their ability to defend against grazers is paramount to their survival, and modulates their ecological functions. Here, we report a novel anti-grazer strategy in the common green alga
Chlorella vulgaris
against two grazers,
Daphnia magna
and
Simocephalus
sp. The algal cells entered the brood chamber of both grazers, presumably using the brood current generated by the grazer's abdominal appendages. Once inside, the alga densely colonized the eggs, significantly reducing reproductive success. The effect was apparent under continuous light or higher light intensity. The algal cells remained viable following removal from the brood chamber, continuing to grow when inoculated in fresh medium. No brood chamber colonization was found when the grazers were fed the reference diet
Raphidocelis subcapitata
under the same experimental conditions, despite the fact that both algal species were readily ingested by the grazers and were small enough to enter their brood chambers. These observations suggest that
C. vulgaris
can directly inflict harm on the grazers' reproductive structure. There is no known prior example of brood chamber colonization by a microalgal prey; our results point to a new type of grazer–algae interaction in the plankton that fundamentally differs from other antagonistic ecological interactions.
Suppression of the TGF-β pathway by a macrolide antibiotic decreases fibrotic responses by ocular fibroblasts
in vitro
Authors: Stahnke Thomas , Gajda-Deryło Beata , Jünemann Anselm G. , Stachs Oliver , Sterenczak Katharina A. , Rejdak Robert , Beck Julia , Schütz Ekkehard , Möller Steffen , Barrantes Israel , Warsow Gregor , Struckmann Stephan , Fuellen Georg
Published: September 2020

To elucidate and to inhibit post-surgical fibrotic processes after trabeculectomy in glaucoma therapy, we measured gene expression in a fibrotic cell culture model, based on transforming growth factor TGF-β induction in primary human tenon fibroblasts (hTFs), and used Connectivity Map (CMap) data for drug repositioning. We found that specific molecular mechanisms behind fibrosis are the upregulation of actins, the downregulation of CD34, and the upregulation of inflammatory cytokines such as IL6, IL11 and BMP6
.
The macrolide antibiotic Josamycin (JM) reverses these molecular mechanisms according to data from the CMap, and we thus tested JM as an inhibitor of fibrosis. JM was first tested for its toxic effects on hTFs, where it showed no influence on cell viability, but inhibited hTF proliferation in a concentration-dependent manner. We then demonstrated that JM suppresses the synthesis of extracellular matrix (ECM) components. In hTFs stimulated with TGF-β1, JM specifically inhibited α-smooth muslce actin expression, suggesting that it inhibits the transformation of fibroblasts into fibrotic myofibroblasts. In addition, a decrease of components of the ECM such as fibronectin, which is involved in
in vivo
scarring, was observed. We conclude that JM may be a promising candidate for the treatment of fibrosis after glaucoma filtration surgery or drainage device implantation
in vivo
.
Gene flow in the Antarctic bivalve
Aequiyoldia eightsii
(Jay, 1839) suggests a role for the Antarctic Peninsula Coastal Current in larval dispersal
Authors: Muñoz-Ramírez Carlos P. , Barnes David K. A. , Cárdenas Leyla , Meredith Michael P. , Morley Simon A. , Roman-Gonzalez Alejandro , Sands Chester J. , Scourse James , Brante Antonio
Published: September 2020

The Antarctic Circumpolar Current (ACC) dominates the open-ocean circulation of the Southern Ocean, and both isolates and connects the Southern Ocean biodiversity. However, the impact on biological processes of other Southern Ocean currents is less clear. Adjacent to the West Antarctic Peninsula (WAP), the ACC flows offshore in a northeastward direction, whereas the Antarctic Peninsula Coastal Current (APCC) follows a complex circulation pattern along the coast, with topographically influenced deflections depending on the area. Using genomic data, we estimated genetic structure and migration rates between populations of the benthic bivalve
Aequiyoldia eightsii
from the shallows of southern South America and the WAP to test the role of the ACC and the APCC in its dispersal. We found strong genetic structure across the ACC (between southern South America and Antarctica) and moderate structure between populations of the WAP. Migration rates along the WAP were consistent with the APCC being important for species dispersal. Along with supporting current knowledge about ocean circulation models at the WAP, migration from the tip of the Antarctic Peninsula to the Bellingshausen Sea highlights the complexities of Southern Ocean circulation. This study provides novel biological evidence of a role of the APCC as a driver of species dispersal and highlights the power of genomic data for aiding in the understanding of the influence of complex oceanographic processes in shaping the population structure of marine species.
Personality affects dynamics of an experimental pathogen in little brown bats
Authors: Webber Quinn M. R. , Willis Craig K. R.
Published: September 2020

Host behaviour can affect host–pathogen dynamics and theory predicts that certain individuals disproportionately infect conspecifics during an epidemic. Consistent individual differences in behaviour, or personality, could influence this variation with the most exploratory or sociable individuals most likely to spread pathogens. We quantified exploration and sociability in little brown bats (
Myotis lucifugus
) and then experimentally manipulated exposure to a proxy pathogen (i.e. ultraviolet (UV) fluorescent powder) to test two related hypotheses: (i) more sociable and more exploratory individuals would be more likely to transmit infections to other individuals, and (ii) more sociable and more exploratory individuals uninfected with an invading pathogen would be more likely to acquire infections. We captured 10 groups of 16 bats at a time and held each group in an outdoor flight tent equipped with roosting-boxes. We used hole-board and Y-maze tests to quantify exploration and sociability of each bat and randomly selected one individual from each group for ‘infection’ with non-toxic, UV fluorescent powder. Each group of 10 bats was released into the flight tent for 24 h, which represented an experimental infection trial. After 24 h, we removed bats from the trial, photographed each individual under UV light and quantified infection intensity from digital photographs. As predicted, the exploratory behaviour of the experimentally infected individual was positively correlated with infection intensity in their group-mates, while more exploratory females had higher pathogen acquisition. Our results highlight the potential influence of host personality and sex on pathogen dynamics in wildlife populations.
Defence versus growth in a hostile world: lessons from phage and bacteria
Authors: Eriksen Rasmus Skytte , Krishna Sandeep
Published: September 2020

Bacterial communities are often highly diverse with several closely related species (or strains) coexisting together. These bacteria compete for resources and the competitive exclusion principle predicts that all but the fastest-growing bacteria will go extinct. When exposed to phage, it is predicted that bacterial strains with restriction–modification (RM) systems can circumvent the competitive exclusion principle and reach diversity of the order of the phage burst size. We show that with a trade-off between bacterial growth rates and the strength of their RM systems, the diversity of such an ecosystem can further increase several fold beyond the burst size limit. Moreover, we find that the ratio of the growth rate of a bacterial strain to the imperfection of its RM system is an excellent predictor of (i) whether the strain will go extinct or not, and (ii) the biomass of the strain if it survives. In contrast, the growth rate alone is not a determinant of either of these properties. Our work provides a quantitative example of a model ecosystem where the fitness of a species is determined not by growth rate, but by a trade-off between growth and defence against predators.
The ‘Reading the mind in the Eyes' test and emotional intelligence
Authors: Megías-Robles Alberto , Gutiérrez-Cobo María José , Cabello Rosario , Gómez-Leal Raquel , Baron-Cohen Simon , Fernández-Berrocal Pablo
Published: September 2020

The ‘Reading the Mind in the Eyes' test (Eyes Test) has been widely used to measure theory of mind (ToM) or the ability to recognize the thoughts and feelings of others. Although previous studies have analysed its relationship with the ability to perceive emotions, the potential links with more complex emotional abilities remain unclear. The aim of the present research was to analyse the relationship between the Eyes Test and each of the emotional intelligence (EI) branches: perceiving, facilitating, understanding and managing emotions. In addition, we were interested in studying these relationships as a function of the Eyes Test difficulty. Eight hundred and seventy-four participants completed the Eyes Test and the Mayer–Salovey–Caruso Emotional Intelligence Test. A stepwise multiple regression analysis for the total score on the Eyes Test revealed that the best fitting model included the understanding, perceiving and managing emotion branches, with the understanding branch being the one most strongly associated with performance on the Eyes Test. Interestingly, stepwise multiple regression analysis for the easiest items of the Eyes Test revealed the same predictors, but, in the case of the most difficult items only the understanding branch was a predictor. These outcomes were not moderated by the influence of gender. Our findings support the notion that the Eyes Test can be used as a ToM task and that it is associated with complex EI abilities. Limitations and future lines of investigation are discussed.
Debonding waves in gel thin films
Authors: Xu Xianmin , Carme Calderer M. , Doi Masao , Henao Duvan
Published: September 2020

We develop a mathematical model for the sliding of a gel sheet adhered to a moving substrate. The sliding takes place by the motion of detached region between the gel sheet and the substrates, i.e. the propagation of a Schallamach wave. Efficient numerical methods are developed to solve the problem. Numerical examples illustrate that the model can describe the Schallamach wave and are consistent with the existing experiments qualitatively.
Nonlinear MHD Rossby wave interactions and persistent geomagnetic field structures
Authors: Raphaldini Breno , Raupp Carlos F. M.
Published: September 2020

The geomagnetic field presents several stationary features that are thought to be linked to inhomogeneities at the core–mantle boundary. Particularly important stationary structures of the geomagnetic field are the flux lobes, which appear in pairs in mid- to high mid- to high latitudes. A recently discovered stratified layer at the top of the Earth’s core poses important constraints on the dynamics at this layer and on the interaction of the core dynamics and the base of the mantle. In this article, we introduce the linear and nonlinear theories of magnetic Rossby waves in a thin shell at the top of the Earth’s core. We study the nonlinear interaction of these waves in the presence of prescribed forcings at the base of the mantle of both a thermal and a topographic nature. We show that the combined effects of forcing and nonlinear interaction can lead the wave phases to be locked around a particular geographical longitude, generating a quasi- stationary flow pattern with a significant meridional component. The solutions of the system are shown to be analogous to atmospheric blocking phenomena. Therefore, we argue that persistent and long-lived structures of the geomagnetic field, such as the geomagnetic lobes, might be associated with a blocking at the top of the Earth’s core due to nonlinear stationary waves.
How to smooth a crinkled map of space–time: Uhlenbeck compactness for
L
∞
connections and optimal regularity for general relativistic shock waves by the Reintjes–Temple equations
Authors: Reintjes Moritz , Temple Blake
Published: September 2020

We present the authors’ new theory of the RT-equations (‘regularity transformation’ or ‘Reintjes–Temple’ equations), nonlinear elliptic partial differential equations which determine the coordinate transformations which smooth connections
Γ
to optimal regularity, one derivative smoother than the Riemann curvature tensor Riem(
Γ
). As one application we extend Uhlenbeck compactness from Riemannian to Lorentzian geometry; and as another application we establish that regularity singularities at general relativistic shock waves can always be removed by coordinate transformation. This is based on establishing a general multi-dimensional existence theory for the RT-equations by application of elliptic regularity theory in
L

p

spaces. The theory and results announced in this paper apply to arbitrary
L
∞
connections on the tangent bundle

T

M

of arbitrary manifolds

M

, including Lorentzian manifolds of general relativity.
Functional difference equations and eigenfunctions of a Schrödinger operator with
δ
′ −interaction on a circular conical surface
Authors: Lyalinov Mikhail A.
Published: September 2020

Eigenfunctions and their asymptotic behaviour at large distances for the Laplace operator with singular potential, the support of which is on a circular conical surface in three-dimensional space, are studied. Within the framework of incomplete separation of variables an integral representation of the Kontorovich–Lebedev (KL) type for the eigenfunctions is obtained in terms of solution of an auxiliary functional difference equation with a meromorphic potential. Solutions of the functional difference equation are studied by reducing it to an integral equation with a bounded self-adjoint integral operator. To calculate the leading term of the asymptotics of eigenfunctions, the KL integral representation is transformed to a Sommerfeld-type integral which is well adapted to application of the saddle point technique. Outside a small angular vicinity of the so-called singular directions the asymptotic expression takes on an elementary form of exponent decreasing in distance. However, in an asymptotically small neighbourhood of singular directions, the leading term of the asymptotics also depends on a special function closely related to the function of parabolic cylinder (Weber function).
Contact geometry for simple thermodynamical systems with friction
Authors: Simoes Alexandre Anahory , de León Manuel , Valcázar Manuel Lainz , de Diego David Martín
Published: September 2020

By means of the Jacobi structure associated with a contact structure, we use the so-called evolution vector field to propose a new characterization of isolated thermodynamical systems with friction, a simple but important class of thermodynamical systems which naturally satisfy the first and second laws of thermodynamics, i.e. total energy preservation of isolated systems and non-decreasing total entropy, respectively. We completely clarify its qualitative dynamics, the underlying geometrical structures and we also show how to apply discrete gradient methods to numerically integrate the evolution equations for these systems.
Kernel representation of long-wave dynamics on a uniform slope
Authors: Shimozono T.
Published: September 2020

Long-wave propagation on a uniformly sloping beach is formulated as a transient-response problem, with initially stationary water subjected to an incident wave. Both the water surface elevation and the horizontal flow velocity on the slope can be represented as convolutions of the rate of displacement of the water surface at the toe of the slope with a singular kernel function of time and space. The kernel, which is typically expressed in the form of an infinite series, accommodates the dynamic processes of long waves, such as shoaling, reflection, and multiple reflections over the slope and yields exact solutions of the linear shallow water equations for any smooth incident wave. The kernel convolution can be implemented numerically by using double exponential formulas to avoid the kernel singularity. The kernel formulation can be extended readily to nonlinear dynamics
via
the hodograph transform, which in turn enables the instantaneous prediction of nonlinear wave properties and of the occurrence of wave breaking in the near-shore area. This general description of long-wave dynamics provides new insights into the long-studied problem.
Unpacking the Allee effect: determining individual-level mechanisms that drive global population dynamics
Authors: Fadai Nabil T. , Johnston Stuart T. , Simpson Matthew J.
Published: September 2020

We present a solid theoretical foundation for interpreting the origin of Allee effects by providing the missing link in understanding how local individual-based mechanisms translate to global population dynamics. Allee effects were originally proposed to describe population dynamics that cannot be explained by exponential and logistic growth models. However, standard methods often calibrate Allee effect models to match observed global population dynamics without providing any mechanistic insight. By introducing a stochastic individual-based model, with proliferation, death and motility rates that depend on local density, we present a modelling framework that translates particular global Allee effects to specific individual-based mechanisms. Using data from ecology and cell biology, we unpack individual-level mechanisms implicit in an Allee effect model and provide simulation tools for others to repeat this analysis.
A continuum model for the growth of dendritic actin networks
Authors: Abeyaratne Rohan , Purohit Prashant K.
Published: September 2020

Polymerization of dendritic actin networks underlies important mechanical processes in cell biology such as the protrusion of lamellipodia, propulsion of growth cones in dendrites of neurons, intracellular transport of organelles and pathogens, among others. The forces required for these mechanical functions have been deduced from mechano-chemical models of actin polymerization; most models are focused on single growing filaments, and only a few address polymerization of filament networks through simulations. Here, we propose a continuum model of surface growth and filament nucleation to describe polymerization of dendritic actin networks. The model describes growth and elasticity in terms of macroscopic stresses, strains and filament density rather than focusing on individual filaments. The microscopic processes underlying polymerization are subsumed into kinetic laws characterizing the change of filament density and the propagation of growing surfaces. This continuum model can predict the evolution of actin networks in disparate experiments. A key conclusion of the analysis is that existing laws relating force to polymerization speed of single filaments cannot predict the response of growing networks. Therefore, a new kinetic law, consistent with the dissipation inequality, is proposed to capture the evolution of dendritic actin networks under different loading conditions. This model may be extended to other settings involving a more complex interplay between mechanical stresses and polymerization kinetics, such as the growth of networks of microtubules, collagen filaments, intermediate filaments and carbon nanotubes.
Predictive modelling of drop ejection from damped, dampened wings by machine learning
Authors: Alam MD Erfanul , Wu Dazhong , Dickerson Andrew K.
Published: September 2020

The high frequency, low amplitude wing motion that mosquitoes employ to dry their wings inspires the study of drop release from millimetric, forced cantilevers. Our mimicking system, a 10-mm polytetrafluoroethylene cantilever driven through ±1 mm base amplitude at 85 Hz, displaces drops via three principal ejection modes: normal-to-cantilever ejection, sliding and pinch-off. The selection of system variables such as cantilever stiffness, drop location, drop size and wetting properties modulates the appearance of a particular ejection mode. However, the large number of system features complicate the prediction of modal occurrence, and the transition between complete and partial liquid removal. In this study, we build two predictive models based on ensemble learning that predict the ejection mode, a classification problem, and minimum inertial force required to eject a drop from the cantilever, a regression problem. For ejection mode prediction, we achieve an accuracy of 85% using a bagging classifier. For inertial force prediction, the lowest root mean squared error achieved is 0.037 using an ensemble learning regression model. Results also show that ejection time and cantilever wetting properties are the dominant features for predicting both ejection mode and the minimum inertial force required to eject a drop.
Does conspicuousness scale linearly with colour distance? A test using reef fish
Authors: Santiago Carl , Green Naomi F. , Hamilton Nadia , Endler John A. , Osorio Daniel C. , Marshall N. Justin , Cheney Karen L.
Published: September 2020

To be effective, animal colour signals must attract attention—and therefore need to be conspicuous. To understand the signal function, it is useful to evaluate their conspicuousness to relevant viewers under various environmental conditions, including when visual scenes are cluttered by objects of varying colour. A widely used metric of colour difference (Δ
S
) is based on the receptor noise limited (RNL) model, which was originally proposed to determine when two similar colours appear different from one another, termed the discrimination threshold (or just noticeable difference). Estimates of the perceptual distances between colours that exceed this threshold—termed ‘suprathreshold’ colour differences—often assume that a colour's conspicuousness scales linearly with colour distance, and that this scale is independent of the direction in colour space. Currently, there is little behavioural evidence to support these assumptions. This study evaluated the relationship between Δ
S
and conspicuousness in suprathreshold colours using an Ishihara-style test with a coral reef fish,
Rhinecanthus aculeatus
. As our measure of conspicuousness, we tested whether fish, when presented with two colourful targets, preferred to peck at the one with a greater Δ
S
­ from the average distractor colour. We found the relationship between Δ
S
and conspicuousness followed­­ a sigmoidal function, with high Δ
S
colours perceived as equally conspicuous. We found that the relationship between Δ
S
and conspicuousness varied across colour space (i.e. for different hues). The sigmoidal detectability curve was little affected by colour variation in the background or when colour distance was calculated using a model that does not incorporate receptor noise. These results suggest that the RNL model may provide accurate estimates for perceptual distance for small suprathreshold distance colours, even in complex viewing environments, but must be used with caution with perceptual distances exceeding­ ­10 Δ
S
.
The costs and benefits of paternal care in fish: a meta-analysis
Authors: Goldberg Rebecca L. , Downing Philip A. , Griffin Ashleigh S. , Green Jonathan P.
Published: September 2020

Male-only parental care, while rare in most animals, is a widespread strategy within teleost fish. The costs and benefits to males of acting as sole carer are highly variable among fish species making it challenging to determine the selective pressures driving the evolution of male-only care to such a high prevalence. We conducted a phylogenetic meta-analysis to examine the costs and benefits of paternal care across fish species. We found no evidence that providing care negatively affects male condition. In contrast with other taxa, we also found limited evidence that male care has evolved as a strategy to improve offspring survival. Instead, we found that males already caring for a brood are preferred by females and that this preference is strongest in those species in which males work harder to care for larger broods. Thus, in fish, investment in offspring care does not constrain a male's mating success but rather augments it, suggesting that the relatively high prevalence of male-only care in fish may be in part explained by sexual selection through female preference for caring males.
Distribution modelling of an introduced species: do adaptive genetic markers affect potential range?
Authors: Sillero Neftalí , Huey Raymond B. , Gilchrist George , Rissler Leslie , Pascual Marta
Published: September 2020

Biological invasions have increased in the last few decades mostly due to anthropogenic causes such as globalization of trade. Because invaders sometimes cause large economic losses and ecological disturbances, estimating their origin and potential geographical ranges is useful.
Drosophila subobscura
is native to the Old World but was introduced in the New World in the late 1970s and spread widely. We incorporate information on adaptive genetic markers into ecological niche modelling and then estimate the most probable geographical source of colonizers; evaluate whether the genetic bottleneck experienced by founders affects their potential distribution; and finally test whether this species has spread to all its potential suitable habitats worldwide. We find the environmental space occupied by this species in its native and introduced distributions are notably the same, although the introduced niche has shifted slightly towards higher temperature and lower precipitation. The genetic bottleneck of founding individuals was a key factor limiting the spread of this introduced species. We also find that regions in the Mediterranean and north-central Portugal show the highest probability of being the origin of the colonizers. Using genetically informed environmental niche modelling can enhance our understanding of the initial colonization and spread of invasive species, and also elucidate potential areas of future expansions worldwide.
Evaluation of a novel 5 day accelerated 1 Hz repetitive transcranial magnetic stimulation protocol in major depression
Authors: Miron Jean-Philippe , Hyde Molly , Fox Linsay , Sheen Jack , Voetterl Helena , Mansouri Farrokh , Zhou Ryan , Dees Sinjin , Mir-Moghtadaei Arsalan , Blumberger Daniel M. , Daskalakis Zafiris J. , Vila-Rodriguez Fidel , Downar Jonathan
Published: September 2020

BACKGROUND

Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention in major depressive disorder (MDD) but requires daily travel to a treatment clinic over several weeks. Shorter rTMS courses retaining similar effectiveness would thus increase the practicality and scalability of the technique, and therefore its accessibility.

OBJECTIVE

We assessed the feasibility of a novel 5 day accelerated 1 Hz rTMS protocol. We hypothesized that this novel rTMS protocol would be safe and well-tolerated while shortening the overall treatment course.

METHODS

We conducted a prospective, single-arm, open-label feasibility study. Thirty (30) participants received a one-week (5 days) accelerated (8 sessions per day, 40 sessions total) course of 1 Hz rTMS (600 pulses per session, 50-minute intersession interval) over the right dorsolateral prefrontal cortex (R-DLPFC) using a figure-of-eight coil at 120% of the resting motor threshold (rMT). Depression severity was assessed on the Beck Depression Inventory-II (BDI-II) and 17-item Hamilton Rating Scale for Depression (HRSD-17).

RESULTS

Response and remission rates 1 week after treatment were 33.3% and 13.3% respectively and increased to 43.3% and 30.0% at 4 weeks after treatment. No serious adverse events occurred. All participants reported manageable pain levels.

CONCLUSION

1 Hz rTMS administered 8 times daily for 5 days is safe and well-tolerated. Efficacy at the end of the course was similar to a standard daily course of 1 Hz rTMS, and there appears to be an additional delayed effect. Further validation in a randomized trial is required.

ClinicalTrials.gov Identifier:NCT04376697
Ceftazidime Is a Potential Drug to Inhibit SARS-CoV-2 Infection In Vitro by Blocking Spike Protein-ACE2 Interaction
Authors: Lin ChangDong , Li Yue , Yuan MengYa , Huang MengWen , Liu Cui , Du Hui , Pan XingChao , Wen YaTing , Xu Xinyi , Xu Chenqi , Chen JianFeng
Published: September 2020

Coronavirus Disease 2019 (COVID-19) spreads globally as a sever pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cell entry of SARS-CoV-2 mainly depends on binding of the viral spike (S) proteins to angiotensin converting enzyme 2 (ACE2) on host cells. Therefore, repurposing of known drugs to inhibit S protein-ACE2 interaction could be a quick way to develop effective therapy for COVID-19. Using a high-throughput screening system to investigate the interaction between spike receptor binding domain (S-RBD) and ACE2 extracellular domain, we screened 3581 FDA-approved drugs and natural small molecules and identified ceftazidime as a potent compound to inhibit S-RBD–ACE2 interaction by binding to S-RBD. In addition to significantly inhibit S-RBD binding to HPAEpiC cells, ceftazidime efficiently prevented SARS-CoV-2 pseudovirus to infect ACE2-expressing 293T cells. The inhibitory concentration (IC50) was 113.2 μM, which is far below the blood concentration (over 300 μM) of ceftazidime in patients when clinically treated with recommended dose. Notably, ceftazidime is a drug clinically used for the treatment of pneumonia with minimal side effects compared with other antiviral drugs. Thus, ceftazidime has both anti-bacterial and anti-SARS-CoV-2 effects, which should be the first-line antibiotics used for the clinical treatment of COVID-19.
In vitrotranscription using psychrophilic phage VSW-3 RNA polymerase
Authors: Xia Heng , Jiang Yixin , Cheng Rui , Yu Bingbing , Lu Xueling , Wu Hui , Zhu Bin
Published: September 2020

RNA research and applications were underpinned byin vitrotranscription (IVT), while the RNA impurity resulted from the enzymatic reagents severely impede downstream applications. To improve the stability and purity of synthesized RNA we had characterized a novel single-subunit RNA polymerase (RNAP) encoded by a psychrophilic phage VSW-3 from plateau lake to produce RNA at low temperature. The VSW-3 RNAP is capable of carrying outin vitroRNA synthesis at low temperature (4-25°C) to reduce RNA degradation and alleviate the need of costly RNase inhibitor. Compared to routinely used T7 RNAP, VSW-3 RNAP provides comparable yield of transcripts, but is insensitive to class II transcription terminators and synthesizes RNA without redundant 3’ -cis extension. More importantly, through dot-blot detection with the J2 monoclonal antibody, we found that the RNA products synthesized by VSW-3 RNAP contain much lower amount of or virtually no double-stranded RNA (dsRNA) by-products, which are significant in most T7 RNAP products and may cause severe cellular immune response. Combining these advantages, the VSW-3 RNAP is an advantageous enzyme for IVT, especially to produce RNA forin vivouse.
Optimizing automated detection of high frequency oscillations using visual markings does not improve SOZ localization
Authors: Mendoza Trisha , Trevino Casey L. , Shrey Daniel W. , Lin Jack J. , Sen-Gupta Indranil , Lopour Beth A.
Published: September 2020

Objective

High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm’s parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy.

Methods

We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs.

Results

SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization.

Conclusions

SOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization.

Significance

Visual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.
Engineering, Generation and Preliminary Characterization of a Humanized Porcine Sickle Cell Disease Animal Model
Authors: Franks Tobias M. , Haugabook Sharie J. , Ottinger Elizabeth A. , Vermillion Meghan S. , Pawlik Kevin M. , Townes Tim M. , Rogers Christopher S.
Published: September 2020

Mouse models of sickle cell disease (SCD) that faithfully switch from fetal to adult hemoglobin (Hb) have been important research tools that accelerated advancement towards treatments and cures for SCD. Red blood cells (RBCs) in these animals sickledin vivo, occluded small vessels in many organs and resulted in severe anemia like in human patients. SCD mouse models have been valuable in advancing clinical translation of some therapeutics and providing a better understanding of the pathophysiology of SCD. However, mouse models vary greatly from humans in their anatomy and physiology and therefore have limited application for certain translational efforts to transition from the bench to bedside. These differences create the need for a higher order animal model to continue the advancement of efforts in not only understanding relevant underlying pathophysiology, but also the translational aspects necessary for the development of better therapeutics to treat or cure SCD. Here we describe the development of a humanized porcine sickle cell model that like the SCD mice, expresses human ɑ-, β− and γ-globin genes under the control of the respective endogenous porcine locus control regions (LCR). We also describe our initial characterization of the SCD pigs and plans to make this model available to the broader research community.
Frequency Spectra and the Color of Cellular Noise
Authors: Gupta Ankit , Khammash Mustafa
Published: September 2020

The invention of the Fourier integral in the 19th century laid the foundation for modern spectral analysis methods. By decomposing a (time) signal into its essential frequency components, these methods uncovered deep insights into the signal and its generating process, precipitating tremendous inventions and discoveries in many fields of engineering, technology, and physical science. In systems and synthetic biology, however, the impact of frequency methods has been far more limited despite their huge promise. This is in large part due to the difficulties encountered in connecting the underlying stochastic reaction network in the living cell, whose dynamics is typically modelled as a continuous-time Markov chain (CTMC), to the frequency content of the observed, distinctively noisy single-cell trajectories. Here we draw on stochastic process theory to develop a spectral theory and computational methodologies tailored specifically to the computation and analysis of frequency spectra of noisy cellular networks. Specifically, we develop a generic method to obtain accurate Padé approximations of the spectrum from a handful of trajectory simulations. Furthermore, for linear networks, we present a novel decomposition result that expresses the frequency spectrum in terms of its sources. Our results provide new conceptual and practical methods for the analysis and design of noisy cellular networks based on their output frequency spectra. We illustrate this through diverse case studies in which we show that the single-cell frequency spectrum facilitates topology discrimination, synthetic oscillator optimization, cybergenetic controller design, systematic investigation of stochastic entrainment, and even parameter inference from single-cell trajectory data.
The Anti-histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits SARS-CoV-2 Infection in Reconstituted Human Nasal Tissue In Vitro
Authors: Konrat Robert , Papp Henrietta , Szijártó Valéria , Gesell Tanja , Nagy Gábor , Madai Mónika , Zeghbib Safia , Kuczmog Anett , Lanszki Zsófia , Helyes Zsuzsanna , Kemenesi Gábor , Jakab Ferenc , Nagy Eszter
Published: September 2020

Background

The COVID-19 pandemic is an enormous threat for healthcare systems and economies worldwide that urgently demands effective preventive and therapeutic strategies. Unlike the development of vaccines and new drugs specifically targeting SARS-CoV-2, repurposing of approved or clinically tested drugs can provide an immediate solution.

Methods

We applied a novel computational approach to search among approved and clinically tested drugs from the DrugBank database. Candidates were selected based on Shannon entropy homology and predefined activity profiles of three small molecules with proven anti-SARS-CoV activity and a published data set. Antiviral activity of a predicted drug, azelastine, was testedin vitroin SARS-CoV-2 infection assays with Vero E6 monkey kidney epithelial cells and reconstituted human nasal tissue. The effect on viral replication was assessed by quantification of viral genomes by droplet digital PCR.

Findings

The computational approach with four independent queries identified major drug families, most often and in overlapping fashion anti-infective, anti-inflammatory, anti-hypertensive, anti-histamine and neuroactive drugs. Azelastine, an histamine 1 receptor-blocker, was predicted in multiple screens, and based on its attractive safety profile and availability in nasal formulation, was selected for experimental testing. Azelastine significantly reduced cytopathic effect and SARS-CoV-2 infection of Vero E6 cells with an EC50of ∼6 μM both in a preventive and treatment setting. Furthermore, azelastine in a commercially available nasal spray tested at 5-fold dilution was highly potent in inhibiting viral propagation in SARS-CoV-2 infected reconstituted human nasal tissue.

Interpretations

Azelastine, an anti-histamine, available in nasal sprays developed against allergic rhinitis may be considered as a topical prevention or treatment of nasal colonization with SARS-CoV-2. As such, it could be useful in reducing viral spread and prophylaxis of COVID-19. Ultimately, its potential benefit should be proven in clinical studies.

Funding

provided by the Hungarian government to the National Laboratory of Virology and by CEBINA GmbH.
Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning
Authors: Rosa André , Giese Wolfgang , Meier Katja , Alt Silvanus , Klaus-Bergmann Alexandra , Edgar Lowell , Bartels Eireen , Collins Russell , Szymborska-Mell Anna , Coxam Baptiste , Bernabeu Miguel O. , Gerhardt Holger
Published: September 2020

Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are coordinated remains unknown. Here, using the zebrafish trunk vasculature we show that in future veins endothelial cells proliferate more than in future arteries and migrate preferentially towards neighboring arteries. In future arteries endothelial cells show a biphasic migration profile. During sprouting cells move away from the dorsal aorta, during remodelling cells stop or move towards the feeding aorta. The final morphology of blood vessels is thus established by local proliferation and oriented cell migration to and from neighboring vessels. Additionally, we identify WASp to be essential for this differential migration. Loss of WASp leads to irregular distribution of endothelial cells, substantially enlarged veins and persistent arteriovenous shunting. Mechanistically, we report that WASp drives the assembly of junctional associated actin filaments and is required for junctional expression of PECAM-1. Together, our data identify that functional vascular patterning in the zebrafish trunk utilizes differential cell movement regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.
Understanding the photophysics and structural organization of photosynthetic proteins using model lipid membranes assembled from natural plant thylakoids
Authors: Meredith Sophie A. , Yoneda Takuro , Hancock Ashley M. , Connell Simon D. , Evans Stephen D. , Morigaki Kenichi , Adams Peter G.
Published: September 2020

The light-harvesting (LH) biomembranes from photosynthetic organisms perform solar energy absorption and transfer with high efficiency. There is great interest in the nanoscale biophysics of photosynthesis, however, natural membranes are complex and highly curved so can be challenging to study. Here we present model photosynthetic “hybrid membranes” assembled from a combination of natural LH membranes and synthetic lipids deposited into a patterned polymerized lipid template on glass. This arrangement offers many advantages over previous model systems including: a sufficiently complex mixture of natural proteins to mimic the biological processes, a modular self-assembly mechanism, and a stabilizing template promoting the formation of supported lipid bilayers from complex natural membranes with high protein content (that would not otherwise form). These hybrid membranes can be used as a platform to delineate the complex relationship between LH energy pathways and membrane organization. Atomic force microscopy and fluorescence lifetime microscopy revealed that hybrid membranes have an elongated fluorescence lifetime (∼4 ns) compared to native membranes (∼0.5 ns), a direct consequence of reduced protein density and an uncoupling of protein-protein interactions. We observed the real time self-assembly and migration of LH proteins from natural membrane extracts into the hybrid membranes and monitored the photophysical state of the membranes at each stage. Finally, experiments utilizing our hybrid membranes suggest that assays currently used in the photosynthesis community to test the electron transfer activity of Photosystem II may have non-specific interactions with other proteins, implying that new methods are needed for reliable quantification of electron transfers in photosynthesis.