bluuebunny/crossref_metadata_2025 huggingface dataset:
Angular momentum and heat transport on tidally locked hot Jupiter planets
Authors: Mendonça João M
Published: October 2019

The atmospheric circulation in the upper atmosphere of hot Jupiter planets is strongly influenced by the incoming stellar radiation. In this work, we explore the results from a 3D atmospheric model and revisit the main processes driving the circulation in hot Jupiter planets. We use the angular momentum transport as a diagnostic and carry out a Fourier analysis to identify the atmospheric waves involved. We find that the coupling between the angular momentum transported horizontally by the semidiurnal tide and the mean circulation is the mechanism responsible for producing the strong jet at low latitudes. Our simulations indicate the possible formation of atmospheric indirect cells at low latitudes. The formation of these cells is induced by the presence of the semidiurnal tide that is driven by the stellar irradiation. The tropical circulation has an important impact transporting heat and momentum from the upper towards the lower atmosphere. One of the consequences of this heat and momentum transport is a global increase of the temperature. We show that the initial conditions do not affect the output of the reference simulation. However, when the period of rotation of the planet was increased (Prot > 5 Earth days), vertical transport by stationary waves became stronger, transient waves became non-negligible, and Coriolis influence less dominant, which allowed a steady state with a strong retrograde jet to be stable. We found that at least two statically steady state solutions exist for the same planet parameters.
Automated wind velocity profiling from adaptive optics telemetry
Authors: Laidlaw Douglas J , Osborn James , Morris Timothy J , Basden Alastair G , Gendron Eric , Rousset Gérard , Townson Matthew J , Wilson Richard W
Published: October 2019

Ground-based adaptive optics (AO) systems can use temporal control techniques to greatly improve image resolution. A measure of wind velocity as a function of altitude is needed to minimize the temporal errors associated with these systems. Spatio-temporal analysis of AO telemetry can express the wind velocity profile using the SLODAR technique. However, the limited altitude-resolution of current AO systems makes it difficult to disentangle the movement of independent layers. It is therefore a challenge to create an algorithm that can recover the wind velocity profile through SLODAR data analysis. In this study we introduce a novel technique for automated wind velocity profiling from AO telemetry. Simulated and on-sky centroid data from CANARY - an AO testbed on the 4.2 m William Herschel telescope, La Palma - is used to demonstrate the proficiency of the technique. Wind velocity profiles measured on-sky are compared to contemporaneous measurements from Stereo-SCIDAR, a dedicated high-resolution atmospheric profiler. They are also compared to European centre for medium-range weather forecasts. The software package that we developed to complete this study is open source.
Obscuration properties of mid-IR-selected AGN
Authors: Mountrichas G , Georgantopoulos I , Ruiz A , Kampylis G
Published: October 2019

The goal of this work is to study the obscuration properties of mid-infrared (mid-IR)-selected active galactic nuclei (AGN). For that purpose, we use Wide-field Infrared Survey Explorer (WISE) sources in the Stripe 82–XMM area to identify mid-IR AGN candidates, applying the Assef et al. criteria. Stripe 82 has optical photometry ≈2 times deeper than any single-epoch Sloan Digital Sky Survey (SDSS) region. XMM–Newton observations cover ∼26 deg2. Applying the aforementioned criteria, 1946 IR AGN are selected. ${\sim} 78{{\, \rm per\, cent}}$ have SDSS detection, while 1/3 of them are detected in X-rays, at a flux limit of $\rm {\sim} 5 \times 10^{-15}\, erg\, s^{-1}\, cm^{-2}$. Our final sample consists of 507 IR AGN with X-ray detection and optical spectra. Applying a $r-W2 > 6$ colour criterion, we find that the fraction of optically red AGN drop from 43 per cent for those sources with SDSS detection to $23{{\, \rm per\, cent}}$ for sources that also have X-ray detection. X-ray spectral fitting reveals 40 (${\sim} 8{{\, \rm per\, cent}}$) X-ray absorbed AGN ($N_\mathrm{ H} > 10^{22}\,{\rm cm}^{-2}$). Among the X-ray unabsorbed AGN, there are 70 red systems. To further investigate the absorption of these sources, we construct spectral energy distributions (SEDs) for the total IR AGN sample. SED fitting reveals that ${\sim} 20{{\, \rm per\, cent}}$ of the optically red sources have such colours because the galaxy emission is a primary component in the optical part of the SED, even though the AGN emission is not absorbed at these wavelengths. SED fitting also confirms that $12{{\, \rm per\, cent}}$ of the X-ray unabsorbed IR AGN are optically obscured.
Mitochondrial Metagenomics Reveals the Ancient Origin and Phylodiversity of Soil Mites and Provides a Phylogeny of the Acari
Authors: Arribas Paula , Andújar Carmelo , Moraza María Lourdes , Linard Benjamin , Emerson Brent C , Vogler Alfried P
Published: October 2019

High-throughput DNA methods hold great promise for phylogenetic analysis of lineages that are difficult to study with conventional molecular and morphological approaches. The mites (Acari), and in particular the highly diverse soil-dwelling lineages, are among the least known branches of the metazoan Tree-of-Life. We extracted numerous minute mites from soils in an area of mixed forest and grassland in southern Iberia. Selected specimens representing the full morphological diversity were shotgun sequenced in bulk, followed by genome assembly of short reads from the mixture, which produced >100 mitochondrial genomes representing diverse acarine lineages. Phylogenetic analyses in combination with taxonomically limited mitogenomes available publicly resulted in plausible trees defining basal relationships of the Acari. Several critical nodes were supported by ancestral-state reconstructions of mitochondrial gene rearrangements. Molecular calibration placed the minimum age for the common ancestor of the superorder Acariformes, which includes most soil-dwelling mites, to the Cambrian–Ordovician (likely within 455–552 Ma), whereas the origin of the superorder Parasitiformes was placed later in the Carboniferous-Permian. Most family-level taxa within the Acariformes were dated to the Jurassic and Triassic. The ancient origin of Acariformes and the early diversification of major extant lineages linked to the soil are consistent with a pioneering role for mites in building the earliest terrestrial ecosystems.
Return to Work Following Surgery for Incidental Diffuse Low-Grade Glioma: A Prospective Series With 74 Patients
Authors: Ng Sam , Herbet Guillaume , Moritz-Gasser Sylvie , Duffau Hugues
Published: October 2019

BACKGROUND

Therapeutic strategy concerning incidental low-grade glioma (ILGG) is still debated. Early “prophylactic” surgery has been proposed in asymptomatic patients with favorable neurological and oncological outcomes.

OBJECTIVE

To assess postoperative ability to resume employment following awake surgery in asymptomatic ILGG patients. To assess extent of resection (EOR), timeline for adjuvant oncological treatment, and survival.

METHODS

A total of 74 patients with ILGG who underwent awake surgery with intraoperative mapping were prospectively included, with a minimum follow-up of 12 mo. All clinicoradiological data were collected, and statistical correlations with return to work (RTW) were performed.

RESULTS

A total of 66 patients (97.1%) among 68 patients with preoperative professional activities resumed their employment including 62 (91.2%) within 12 mo. Mean time before RTW was 6.8 mo (median: 6 mo, range: 1-36). Two patients experienced seizure-related legal issues impacting their RTW. Clinicoradiological features did not correlate with RTW apart from postoperative seizures (P = .02). Mean EOR was 95.7%. A total of 43 patients (58.1%) underwent supratotal/total resections. All patients recovered from transient deficits at 3 mo. No patients received consecutive adjuvant treatment. A total of 24 patients (32.4%) were reoperated, 24 patients received chemotherapy, and 7 patients (9.5%) received radiotherapy, on average 73.1 mo after surgery. Mean follow-up was 67 mo (range 12-240). Four patients (5.4%) died during the follow-up.

CONCLUSION

We observed a high rate of RTW (97.1%, including 91.2% within 12 mo) after awake surgery in ILGG patients. Delayed resumption of work was due to employer not clearing them for RTW, personal choice, and, in rare occasions, related to seizures.
Blood Pressure Variability and Optimal Cerebral Perfusion Pressure—New Therapeutic Targets in Traumatic Brain Injury
Authors: Svedung Wettervik Teodor , Howells Timothy , Lewén Anders , Enblad Per
Published: October 2019

BACKGROUND

Optimal cerebral perfusion pressure (CPPopt) is an autoregulatory-oriented target in the neurointensive care (NIC) of patients with traumatic brain injury (TBI), and deviation from CPPopt is associated with poor outcome. We recently found that blood pressure variability (BPV) is associated with deviation from CPPopt.

OBJECTIVE

To evaluate BPV and other variables related to deviation from CPPopt and to evaluate challenges and strategies for autoregulatory-oriented treatment in TBI.

METHODS

Data including arterial blood pressure and intracranial pressure (ICP) from 362 TBI patients treated at the NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2016, were retrospectively analyzed day 2 to 5.

RESULTS

Higher BPV was a strong predictor of both CPP deviation below and above CPPopt after multiple regression analyses. There was no other explanatory variable for CPP deviation above CPPopt, whereas also higher ICP and worse autoregulation (higher pressure reactivity index) were associated with CPP deviation below CPPopt. A higher BPV was, in turn, explained by older age, lower ICP, higher mean arterial blood pressure, and higher slow arterial blood pressure amplitude (0.018-0.067 Hz).

CONCLUSION

BPV was strongly associated with deviation from CPPopt. High age is a risk factor for high BPV and hence CPP insults. Our treatment protocol is focused on avoiding CPP below 60 mm Hg. It is possible that a more restrictive upper level could generate more stable blood pressure and less deviation from CPPopt.
Brain tumors in neurofibromatosis type 1
Authors: Costa Amanda De Andrade , Gutmann David H
Published: October 2019

AbstractAs a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-associated gliomas has been significantly advanced through the use of genetically engineered mice, yielding new targets for therapeutic drug design and evaluation. In addition, Nf1 murine glioma models have served as instructive platforms for defining the cell of origin of these tumors, elucidating the critical role of the tumor microenvironment in determining tumor growth and vision loss, and determining how cancer risk factors (sex, germline NF1 mutation) impact on glioma formation and progression. Moreover, these preclinical models have permitted early phase analysis of promising drugs that reduce tumor growth and attenuate vision loss, as an initial step prior to translation to human clinical trials.
Mechanisms in Science
Authors: Craver Carl , Krickel Beate
Published: October 2019

Many areas of science are animated by the search for mechanisms: experiments are designed to find them, explanations are built to reveal them, models are constructed to describe them, funding is disbursed to prioritize their discovery, and translational research is premised on their value for manipulation and control. Over the last twenty or thirty years, a number of philosophers of science, starting from the biological and neural sciences, have directed attention at the concept of mechanism. They have emphasized that mechanisms play central roles in discovery, explanation, experimentation, modeling, and reduction. At the same time, the idea of mechanism has served for many as a suggestive hint as to the metaphysics of the middle range: covering that domain of phenomena above the size scale of atomic physics and beneath that of planets, encompassing biology, physiology, psychology, and the human and so-called special sciences more generally. What must mechanisms be if they are to play these diverse roles? The term “new mechanism” (to distinguish the modern account from the classical mechanical worldview defended by philosophers such as Descartes or La Mettrie), introduced to describe this research area, runs the risk of homogenizing what has become a heterogeneous body of work, serving many masters and tugging the analysis in many directions at once. Here, we attempt to collect some points of consensus while highlighting areas of productive disagreement and criticism going forward. The authors thank Stuart Glennan and Lindley Darden for feedback on an earlier draft, Sue McKinney for assistance formatting references, and Paola Hernandez-Chavez for support in finding non-English texts.
Evidence-based policy analysis? The strange case of the randomized controlled trials of community-led total sanitation
Authors: Whittington Dale , Radin Mark , Jeuland Marc
Published: October 2019

Our purpose in this paper is to review the findings of 14 randomized controlled trials (RCTs) of community-led total sanitation (CLTS) and recent rural sanitation interventions to assess their usefulness and implications for sanitation policy-making in low- and middle-income countries. The results of the RCT research programme to evaluate CLTS and related sanitation interventions suggest that the magnitude of the treatment effects was much smaller and uncertain than proponents once anticipated. For example, of the ten studies that reported results for reductions in childhood diarrhoea, only three found statistically significant decreases. Surprisingly, the RCT research teams and their funders do not seem to have thought about how their multi-million dollar research agenda would support decision-making on sanitation. Information on the parameters needed for cost-effectiveness analysis or benefit–cost analysis was not collected. However, making reasonable assumptions about the missing information on parameter values, we show that cost–benefit analysis may still ‘save’ CLTS because small treatment effects may still yield net positive economic benefits if the costs of implementing CLTS programmes are modest. We also discuss the need to move beyond the desire for sanitation policies that are proven to be effective globally, and the importance of focusing on analysis of the local sanitation situation. We describe the data needed to make this shift in policy focus from the global to the local level and stress the importance of interdisciplinary communication between the proponents of RCTs and ‘evidence-based policy’, and economists who will be responsible for the economic analysis of investments in CLTS and other sanitation interventions. We also argue that the results of these RCTs highlight the importance of coordinating investments in piped water and sanitation with investments in improved housing.
Genetic and epidemiological characterization of restless legs syndrome in Québec
Authors: Akçimen Fulya , Ross Jay P , Sarayloo Faezeh , Liao Calwing , De Barros Oliveira Rachel , Ruskey Jennifer A , Bourassa Cynthia V , Dion Patrick A , Xiong Lan , Gan-Or Ziv , Rouleau Guy A
Published: October 2019

Currently, a total of 19 genetic loci are associated with the risk for developing RLS. This study aimed to assess these RLS predisposing genetic variants, as well as investigate the epidemiological profile and diagnostic features of individuals with RLS in the Québec population, using an interviewer–administered questionnaire. A total of 18 RLS-associated variants were genotyped in the Québec population-based CARTaGENE cohort. A case–control series consisting of 1,362 RLS cases and 1,379 age-matched unaffected controls was used to conduct a genetic and epidemiological association study that integrated the first four RLS diagnostic features of affected individuals, as well as additional RLS-related questions (e.g. frequency of the symptoms and number of total pregnancies in female). Five RLS-predisposing variants were significantly associated after Bonferroni correction and an additional five variants were nominally associated with RLS (p < 0.05). BTBD9 was the strongest genetic risk factor in our cohort (rs9296249, OR = 1.71, p = 9.57 × 10−10). The patient group that met all four essential diagnostic criteria of RLS provided the most significant genetic findings. These results suggest that employing the questionnaire which included standard diagnostic criteria of RLS could improve the accuracy of the survey-based studies.
Highly multiplexed, fast and accurate nanopore sequencing for verification of synthetic DNA constructs and sequence libraries
Authors: Currin Andrew , Swainston Neil , Dunstan Mark S , Jervis Adrian J , Mulherin Paul , Robinson Christopher J , Taylor Sandra , Carbonell Pablo , Hollywood Katherine A , Yan Cunyu , Takano Eriko , Scrutton Nigel S , Breitling Rainer
Published: October 2019

Synthetic biology utilizes the Design–Build–Test–Learn pipeline for the engineering of biological systems. Typically, this requires the construction of specifically designed, large and complex DNA assemblies. The availability of cheap DNA synthesis and automation enables high-throughput assembly approaches, which generates a heavy demand for DNA sequencing to verify correctly assembled constructs. Next-generation sequencing is ideally positioned to perform this task, however with expensive hardware costs and bespoke data analysis requirements few laboratories utilize this technology in-house. Here a workflow for highly multiplexed sequencing is presented, capable of fast and accurate sequence verification of DNA assemblies using nanopore technology. A novel sample barcoding system using polymerase chain reaction is introduced, and sequencing data are analyzed through a bespoke analysis algorithm. Crucially, this algorithm overcomes the problem of high-error rate nanopore data (which typically prevents identification of single nucleotide variants) through statistical analysis of strand bias, permitting accurate sequence analysis with single-base resolution. As an example, 576 constructs (6 × 96 well plates) were processed in a single workflow in 72 h (from Escherichia coli colonies to analyzed data). Given our procedure’s low hardware costs and highly multiplexed capability, this provides cost-effective access to powerful DNA sequencing for any laboratory, with applications beyond synthetic biology including directed evolution, single nucleotide polymorphism analysis and gene synthesis.
Cover Crop Rotation Effects on Growth and Development, Seedling Disease, and Yield of Corn and Soybean
Authors: Acharya Jyotsna , Moorman Thomas B. , Kaspar Thomas C. , Lenssen Andrew W. , Robertson Alison E.
Published: October 2019

The effects of winter cover crops on root disease and growth of corn and soybeans are poorly understood. A 3-year field experiment investigated the effect of winter cereal rye (Secale cereale L.) and winter camelina (Camelina sativa [L.] Crantz), used either in all three years or in rotation with each other, on corn (Zea mays L.) and soybean (Glycine max. [L.] Merr.) growth, root disease, and yield. Corn following a cover crop of camelina had reduced root disease, a lower Pythium population in seedling roots, and greater growth and yields compared with corn following a rye cover crop. Camelina and rye cover crops before soybean had either a positive or no effect on soybean growth and development, root disease, and yield. Moreover, Pythium clade B populations were greater in corn seedlings after a rye cover crop compared with those following a camelina cover crop, whereas clade F populations were greater on soybean seedlings following a camelina cover crop compared with seedlings following a rye cover crop. A winter camelina cover crop grown before corn had less-negative effects on corn seedling growth, root disease, and final yield than a winter rye cover crop before corn. Neither cover crop had negative effects on soybean, and the cover crop in the preceding spring had no measurable effects on either corn or soybean.
Temporomandibular Joint Herniation: Review of the Literature
Authors: Jo Yong Seok , Cheong Taek Yoon , Han Byung Hyun , Lee Jeon Mi , Kim Sung Huhn , Moon In Seok
Published: October 2019

Objective:

To define clear clinical characteristics and management strategies of herniation of temporomandibular joint (TMJ) into the external auditory canal (EAC).

Data Source:

MEDLINE, PubMed, and EMBASE databases.

Study Selection:

A search was conducted using the keywords “temporomandibular joint” and “herniation” with all of their synonyms. Literature selection criteria included articles published in English, and articles dating back no further than 1970.

Results:

Forty articles regarding 51 cases were eligible for critical appraisal. According to the previously published papers, TMJ herniation has following characteristics; symptoms are nonspecific, but a distinguishable feature is a protruding mass into the EAC that can be seen to appear and disappear as the mouth opens and closes. High-resolution computed tomography scans are sensitive to the bony defect and are helpful in diagnosing TMJ herniation. In the surgical treatment of TMJ herniation, wall reconstruction rather than simple mass excision could be a safe and long-lasting strategy.

Conclusions:

Herniation of TMJ into the EAC is a rare condition, but can be encountered in the clinic at any time. This literature review could be helpful in the diagnosis and treatment of TMJ herniation into the EAC.
The Veterans Affairs Continuous Positive Airway Pressure Use and Diabetic Retinopathy Study
Authors: Smith James Patrick , Cyr Luke G. , Dowd Laura K. , Duchin Kyla S. , Lenihan Priscilla A. , Sprague Jennifer
Published: October 2019

SIGNIFICANCE

Obstructive sleep apnea has been linked to the development and progression of diabetic retinopathy. In this study, diabetic patients compliant with continuous positive airway pressure therapy (CPAP) for sleep apnea were less likely to have retinopathy, emphasizing the benefits and potential therapeutic role of CPAP in individuals with both conditions.

PURPOSE

The aim of this study was to compare the prevalence of diabetic retinopathy in type 2 diabetic patients with obstructive sleep apnea who were compliant with CPAP therapy with those who were not compliant with CPAP therapy.

METHODS

A retrospective cross-sectional review of type 2 diabetic patients using CPAP for obstructive sleep apnea was conducted. The prevalence of retinopathy was identified, and groups with and without retinopathy were compared using univariate analyses and multivariate logistic regression.

RESULTS

The prevalence of retinopathy was 19.6% (n = 321). Retinopathy was significantly less prevalent in those compliant with CPAP (odds ratio, 0.54; 95% confidence interval, 0.31 to 0.94; P = .04). The relationship remained statistically significant when adjusting for other factors known to impact the course of diabetic eye disease.

CONCLUSIONS

Increased CPAP compliance may mitigate the risk of developing diabetic retinopathy in type 2 diabetic patients with obstructive sleep apnea.
Tuning intercellular adhesion with membrane-anchored oligonucleotides
Authors: Hoffecker Ian T. , Arima Yusuke , Iwata Hiroo
Published: October 2019

Adhesive interactions between cells play an integral role in development, differentiation and regeneration. Existing methods for controlling cell–cell cohesion and adhesion by manipulating protein expression are constrained by biological interdependencies, e.g. coupling of cadherins to actomyosin force-feedback mechanisms. We use oligonucleotides conjugated to PEGylated lipid anchors (ssDNAPEGDPPE) to introduce artificial cell–cell adhesion that is largely decoupled from the internal cytoskeleton. We describe cell–cell doublets with a mechanical model based on isotropic, elastic deformation of spheres to estimate the adhesion at the cell–cell interface. Physical manipulation of adhesion by modulating the PEG-lipid to ssDNAPEGDPPE ratio, and conversely treating with actin-depolymerizing cytochalasin D, resulted in decreases and increases in doublet contact area, respectively. Our data are relevant to the ongoing discussion over mechanisms of tissue surface tension and in agreement with models based on opposing cortical and cohesive forces. PEG-lipid modulation of doublet geometries resulted in a well-defined curve indicating continuity, enabling prescriptive calibration for controlling doublet geometry. Our study demonstrates tuning of basic doublet adhesion, laying the foundation for more complex multicellular adhesion control independent of protein expression.
Gestational growth trajectories derived from a dynamic fetal–placental scaling law
Authors: Baller Daniel , Thomas Diana M. , Cummiskey Kevin , Bredlau Carl , Schwartz Nadav , Orzechowski Kelly , Miller Richard C. , Odibo Anthony , Shah Ruchit , Salafia Carolyn M.
Published: October 2019

Fetal trajectories characterizing growth ratesin uterohave relied primarily on goodness of fit rather than mechanistic properties exhibitedin utero. Here, we use a validated fetal–placental allometric scaling law and a first principles differential equations model of placental volume growth to generate biologically meaningful fetal–placental growth curves. The growth curves form the foundation for understanding healthy versus at-risk fetal growth and for identifying the timing of key eventsin utero.
Fungal artillery of zombie flies: infectious spore dispersal using a soft water cannon
Authors: de Ruiter Jolet , Arnbjerg-Nielsen Sif Fink , Herren Pascal , Høier Freja , De Fine Licht Henrik H. , Jensen Kaare H.
Published: October 2019

Dead sporulating female fly cadavers infected by the house fly-pathogenic fungusEntomophthora muscaeare attractive to healthy male flies, which by their physical inspection may mechanically trigger spore release and by their movement create whirlwind airflows that covers them in infectious conidia. The fungal artillery ofE. muscaeprotrudes outward from the fly cadaver, and consists of a plethora of micrometric stalks that each uses a liquid-based turgor pressure build-up to eject a jet of protoplasm and the initially attached spore. The biophysical processes that regulate the release and range of spores, however, are unknown. To study the physics of ejection, we design a biomimetic ‘soft cannon’ that consists of a millimetric elastomeric barrel filled with fluid and plugged with a projectile. We precisely control the maximum pressure leading up to the ejection, and study the cannon efficiency as a function of its geometry and wall elasticity. In particular, we predict that ejection velocity decreases with spore size. The calculated flight trajectories under aerodynamic drag predict that the minimum spore size required to traverse a quiescent layer of a few millimetres around the fly cadaver is approximately 10 µm. This corroborates with the natural size ofE. muscaeconidia (approx. 27 µm) being large enough to traverse the boundary layer but small enough (less than 40 µm) to be lifted by air currents. Based on this understanding, we show how the fungal spores are able to reach a new host.
Finding the direction of lowest resilience in multivariate complex systems
Authors: Weinans Els , Lever J. Jelle , Bathiany Sebastian , Quax Rick , Bascompte Jordi , van Nes Egbert H. , Scheffer Marten , van de Leemput Ingrid A.
Published: October 2019

The dynamics of complex systems, such as ecosystems, financial markets and the human brain, emerge from the interactions of numerous components. We often lack the knowledge to build reliable models for the behaviour of such network systems. This makes it difficult to predict potential instabilities. We show that one could use the natural fluctuations in multivariate time series to reveal network regions with particularly slow dynamics. The multidimensional slowness points to the direction of minimal resilience, in the sense that simultaneous perturbations on this set of nodes will take longest to recover. We compare an autocorrelation-based method with a variance-based method for different time-series lengths, data resolution and different noise regimes. We show that the autocorrelation-based method is less robust for short time series or time series with a low resolution but more robust for varying noise levels. This novel approach may help to identify unstable regions of multivariate systems or to distinguish safe from unsafe perturbations.
Analysis and computations of a non-local thin-film model for two-fluid shear driven flows
Authors: Papageorgiou D. T. , Tanveer S.
Published: October 2019

This paper is concerned with analysis and computations of a non-local thin-film model developed in Kalogirou & Papageorgiou (
J. Fluid Mech.
802
, 5–36, 2016) for a perturbed two-layer Couette flow when the thickness of the more viscous fluid layer next to the stationary wall is small compared to the thickness of the less viscous fluid. Travelling wave solutions and their stability are determined numerically, and secondary bifurcation points are identified in the process. We also determine regions in parameter space where bistability is observed with two branches being linearly stable at the same time. The travelling wave solutions are mathematically justified through a
quasi-solution
analysis in a neighbourhood of an empirically constructed approximate solution. This relies in part on precise asymptotics of integrals of Airy functions for large wave numbers. The primary bifurcation about the trivial state is shown rigorously to be supercritical, and the dependence of bifurcation points, as a function of Reynolds number
R
and the primary wavelength 2
πν
−1/2
of the disturbance, is determined analytically.
The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids
Authors: Turner Natalie , Mikalauskaite Deimante , Barone Krista , Flaherty Kathleen , Senevirathne Gayani , Adachi Noritaka , Shubin Neil H. , Nakamura Tetsuya
Published: October 2019

Appendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centred on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level. The condition in finned vertebrates is not understood. To address this gap in knowledge, we investigated the development of muscles and nerves in unpaired and paired fins of skates and compared them to those of chain catsharks. During skate and shark embryogenesis, cell populations of muscle precursors and associated spinal nerves at the same axial level contribute to both appendages and body wall, perhaps representing an ancestral condition of gnathostome appendicular neuromuscular systems. Remarkably in skates, this neuromuscular bifurcation as well as colinearHoxexpression extend posteriorly to pattern a broad paired fin domain. In addition, we identified migratory muscle precursors (MMPs), which are known to develop into paired appendage muscles withPax3andLbx1gene expression, in the dorsal fins of skates. Our results suggest that muscles of paired fins have evolved via redeployment of the genetic programme of MMPs that were already involved in dorsal fin development. Appendicular neuromuscular systems most likely have emerged as side branches of body wall neuromusculature and have been modified to adapt to distinct aquatic and terrestrial habitats.
The genetics of morphological and behavioural island traits in deer mice
Authors: Baier Felix , Hoekstra Hopi E.
Published: October 2019

Animals on islands often exhibit dramatic differences in morphology and behaviour compared with mainland individuals, a phenomenon known as the ‘island syndrome’. These differences are thought to be adaptations to island environments, but the extent to which they have a genetic basis or instead represent plastic responses to environmental extremes is often unknown. Here, we revisit a classic case of island syndrome in deer mice (
Peromyscus maniculatus
) from British Columbia. We first show that Saturna Island mice and those from neighbouring islands are approximately 35% (approx. 5 g) heavier than mainland mice and diverged approximately 10 000 years ago. We then establish laboratory colonies and find that Saturna Island mice are heavier both because they are longer and have disproportionately more lean mass. These trait differences are maintained in second-generation captive-born mice raised in a common environment. In addition, island–mainland hybrids reveal a maternal genetic effect on body weight. Using behavioural testing in the laboratory, we also find that wild-caught island mice are less aggressive than mainland mice; however, laboratory-raised mice born to these founders do not differ in aggression. Together, our results reveal that these mice have different responses to the environmental conditions on islands—a heritable change in a morphological trait and a plastic response in a behavioural trait.
Primate hippocampus size and organization are predicted by sociality but not diet
Authors: Todorov Orlin S. , Weisbecker Vera , Gilissen Emmanuel , Zilles Karl , de Sousa Alexandra A.
Published: October 2019

The hippocampus is well known for its roles in spatial navigation and memory, but it is organized into regions that have different connections and functional specializations. Notably, the region CA2 has a role in social and not spatial cognition, as is the case for the regions CA1 and CA3 that surround it. Here, we investigated the evolution of the hippocampus in terms of its size and organization in relation to the evolution of social and ecological variables in primates, namely home range, diet and different measures of group size. We found that the volumes within the whole cornu ammonis coevolve with group size, while only the volume of CA1 and subiculum can also be predicted by home range. On the other hand, diet, expressed as a shift from folivory towards frugivory, was shown to not be related to hippocampal volume. Interestingly, CA2 was shown to exhibit phylogenetic signal only against certain measures of group size, but not with ecological factors. We also found that sex differences in the hippocampus are related to body size sex dimorphism. This is in line with reports of sex differences in hippocampal volume in non-primates that are related to social structure and sex differences in behaviour. Our findings support the notion that in primates, the hippocampus is a mosaic structure evolving in line with social pressures, where certain subsections evolve in line with spatial ability too.
Altered trophic interactions in warming climates: consequences for predator diet breadth and fitness
Authors: Bestion Elvire , Soriano-Redondo Andrea , Cucherousset Julien , Jacob Staffan , White Joël , Zinger Lucie , Fourtune Lisa , Di Gesu Lucie , Teyssier Aimeric , Cote Julien
Published: October 2019

Species interactions are central in predicting the impairment of biodiversity with climate change. Trophic interactions may be altered through climate-dependent changes in either predator food preferences or prey communities. Yet, climate change impacts on predator diet remain surprisingly poorly understood. We experimentally studied the consequences of 2°C warmer climatic conditions on the trophic niche of a generalist lizard predator. We used a system of semi-natural mesocosms housing a variety of invertebrate species and in which climatic conditions were manipulated. Lizards in warmer climatic conditions ate at a greater predatory to phytophagous invertebrate ratio and had smaller individual dietary breadths. These shifts mainly arose from direct impacts of climate on lizard diets rather than from changes in prey communities. Dietary changes were associated with negative changes in fitness-related traits (body condition, gut microbiota) and survival. We demonstrate that climate change alters trophic interactions through top-predator dietary shifts, which might disrupt eco-evolutionary dynamics.
Same-day antimicrobial susceptibility test using acoustic-enhanced flow cytometry visualized with supervised machine learning
Authors: Inglis Timothy J. J. , Paton Teagan F. , Kopczyk Malgorzata K. , Mulroney Kieran T. , Carson Christine F.
Published: October 2019

Purpose. Antimicrobial susceptibility is slow to determine, taking several days to fully impact treatment. This proof-of-concept study assessed the feasibility of using machine-learning techniques for analysis of data produced by the flow cytometer-assisted antimicrobial susceptibility test (FAST) method we developed.

Methods. We used machine learning to assess the effect of antimicrobial agents on bacteria, comparing FAST results with broth microdilution (BMD) antimicrobial susceptibility tests (ASTs). We used

Escherichia coli

(1),

Klebsiella pneumoniae

(1) and

Staphylococcus aureus

(2) strains to develop the machine-learning algorithm, an expanded panel including these plus

E. coli

(2),

K. pneumoniae

(3),

Proteus mirabilis

(1),

Pseudomonas aeruginosa

(1),

S. aureus

(2) and

Enterococcus faecalis

(1), tested against FAST and BMD (Sensititre, Oxoid), then two representative isolates directly from blood cultures.

Results. Our data machines defined an antibiotic-unexposed population (AUP) of bacteria, classified the FAST result by antimicrobial concentration range, and determined a concentration-dependent antimicrobial effect (CDE) to establish a predicted inhibitory concentration (PIC). Reference strains of E. coli, K. pneumoniae and

S. aureus

tested with different antimicrobial agents demonstrated concordance between BMD results and machine-learning analysis (CA, categoric agreement of 91 %; EA, essential agreement of 100 %). CA was achieved in 35 (83 %) and EA in 28 (67 %) by machine learning on first pass in a challenge panel of 27 Gram-negative and 15 Gram-positive ASTs. Same-day AST results were obtained from clinical

E. coli

(1) and

S. aureus

(1) isolates.

Conclusions. The combination of machine learning with the FAST method generated same-day AST results and has the potential to aid early antimicrobial treatment decisions, stewardship and detection of resistance.
A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation
Authors: Tsuboyama Kotaro , Osaki Tatsuya , Suzuki-Matsuura Eriko , Kozuka-Hata Hiroko , Okada Yuki , Oyama Masaaki , Ikeuchi Yoshiho , Iwasaki Shintaro , Tomari Yukihide
Published: October 2019

Proteins are typically denatured and aggregated by heat. Exceptions to this principle include highly disordered and heat-resistant proteins found in extremophiles, which help these organisms tolerate extreme conditions such as drying, freezing, and high salinity. In contrast, the functions of heat-soluble proteins in non-extremophilic organisms including humans remain largely unexplored. Here we report that heat-resistant obscure (Hero) proteins, which remain soluble after boiling at 95°C, are widespread in Drosophila and humans. Hero proteins are hydrophilic and highly charged, and function to stabilize various “client” proteins, protecting them from denaturation even under stress conditions such as heat shock, desiccation, and exposure to organic solvents. Hero proteins can also block several different types of pathological protein aggregations in cells and in Drosophila strains that model neurodegenerative diseases. Moreover, Hero proteins can extend lifespan of Drosophila. Our study reveals that organisms naturally use Hero proteins as molecular shields to stabilize protein functions, highlighting their biotechnological and therapeutic potential.
TRIM34 acts with TRIM5 to restrict HIV and SIV capsids
Authors: Ohainle Molly , Kim Kyusik , Keceli Sevnur , Felton Abby , Campbell Ed , Luban Jeremy , Emerman Michael
Published: October 2019

The HIV-1 capsid protein makes up the core of the virion and plays a critical role in early steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a target for host cell factors that act directly to block infection such as TRIM5 and MxB. Several host proteins also play a role in facilitating infection, including in the protection of HIV-1 capsid from recognition by host cell restriction factors. Through an unbiased screening approach, called HIV-CRISPR, we show that the Cyclophilin A-binding deficient P90A HIV-1 capsid mutant becomes highly-sensitized to TRIM5alpha restriction in IFN-treated cells. Further, the CPSF6-binding deficient, N74D HIV-1 capsid mutant is sensitive to restriction mediated by human TRIM34, a close paralog of the well-characterized HIV restriction factor TRIM5. This restriction occurs at the step of reverse transcription, is independent of interferon stimulation and limits HIV-1 infection in key target cells of HIV infection including CD4+ T cells and monocyte-derived dendritic cells. TRIM34 restriction requires TRIM5alpha as knockout or knockdown of TRIM5alpha results in a loss of antiviral activity. TRIM34 can also restrict some SIV capsids. Through immunofluorescence studies, we show that TRIM34 and TRIM5alpha colocalize to cytoplasmic bodies and are more frequently observed to be associated with infecting N74D capsids than with WT capsids. Our results identify TRIM34 as an HIV-1 CA-targeting restriction factor and highlight the potential role for heteromultimeric TRIM interactions in contributing restriction of HIV-1 infection in human cells.
Revisiting australianectocarpus subulatus(phaeophyceae) from the hopkins river: distribution, abiotic environment, and associated microbiota
Authors: Dittami Simon M. , Peters Akira F. , West John , Cariou Thierry , KleinJan Hetty , Burgunter-Delamare Bertille , Prechoux Aurelie , Egan Suhelen , Boyen Catherine
Published: October 2019

Ectocarpusis a genus of common marine brown algae. In 1995 a strain ofEctocarpuswas isolated from Hopkins River Falls, Victoria, Australia, constituting one of few available freshwater or nearly freshwater brown algae, and the only one belonging toEctocarpus. It has since been used as a model to study acclimation and adaptation to low salinities and the role of its microbiota in these processes. However, little is known about the distribution of this strain or whether it represents a stable population. Furthermore, its microbiota may have been impacted by the long period of cultivation.

Twenty-two years after the original finding we searched forEctocarpusin the Hopkins River and surrounding areas. We found individuals with ITS andcox1 sequences identical to the original isolate at three sites upstream of Hopkins River Falls, but none at the original isolation site. The osmolarity of the water at these sites ranged from 74-170 mOsmol, and it was rich in sulfate. The diversity of bacteria associated with the algaein situwas approximately one order of magnitude higher than in previous studies of the original laboratory culture, and 95 alga-associated bacterial strains were isolated fromE. subulatusfilaments on site. In particular,Planctomyceteswere abundantin situbut rare in the laboratory-cultured strain.

Our results confirm thatE. subulatushas stably colonized the Hopkins River, and the newly isolated algal and bacterial strains offer new possibilities to study the adaptation ofEctocarpusto low salinity and its interactions with its microbiome.
ZCWPW1 is recruited to recombination hotspots by PRDM9, and is essential for meiotic double strand break repair
Authors: Wells Daniel , Bitoun Emmanuelle , Moralli Daniela , Zhang Gang , Hinch Anjali Gupta , Donnelly Peter , Green Catherine , Myers Simon R
Published: October 2019

During meiosis, homologous chromosomes pair (synapse) and recombine, enabling balanced segregation and generating genetic diversity. In many vertebrates, recombination initiates with double-strand breaks (DSBs) within hotspots where PRDM9 binds, and deposits H3K4me3 and H3K36me3. However, no protein(s) recognising this unique combination of histone marks have yet been identified.

We identifiedZcwpw1, which possesses H3K4me3 and H3K36me3 recognition domains, as highly co-expressed withPrdm9. Here, we show that ZCWPW1 has co-evolved with PRDM9 and, in human cells, is strongly and specifically recruited to PRDM9 binding sites, with higher affinity than sites possessing H3K4me3 alone. Surprisingly, ZCWPW1 also recognizes CpG dinucleotides, including within many Alu transposons.

MaleZcwpw1homozygous knockout mice show completely normal DSB positioning, but persistent DMC1 foci at many hotspots, particularly those more strongly bound by PRDM9, severe DSB repair and synapsis defects, and downstream sterility. Our findings suggest a model where ZCWPW1 recognition of PRDM9-bound sites on either the homologous, or broken, chromosome is critical for synapsis, and hence fertility.

Graphical Abstract Legend

In humans and other species, recombination is initiated by double strand breaks at sites bound by PRDM9. Upon binding, PRDM9 deposits the histone marks H3K4me3 and H3K36me, but the functional importance of these marks has remained unknown. Here, we show that PRDM9 recruits ZCWPW1, a reader of both these marks, to its binding sites genome-wide. ZCWPW1 does not help position the breaks themselves, but is essential for their downstream repair and chromosome pairing, and ultimately meiotic success and fertility in mice.
A dormant sub-population expressing interleukin-1 receptor characterises anti-estrogen resistant ALDH+ breast cancer stem cells
Authors: Sarmiento-Castro Aida , Caamaño-Gutiérrez Eva , Sims Andrew H. , James Mark I. , Santiago-Gómez Angélica , Eyre Rachel , Clark Christopher , Brown Martha E. , Brooks Michael D. , Hayes Daniel F. , Wicha Max S. , Howell Sacha J. , Clarke Robert B. , Simões Bruno M.
Published: October 2019

Estrogen receptor-positive (ER+) breast tumours are often treated with anti-estrogen (AE) therapies but frequently develop resistance. Cancer Stem Cells (CSCs) with high aldehyde dehydrogenase (ALDH) activity (ALDH+ cells) are reported to be enriched following AE treatment. Here we perform in vitro and in vivo functional CSC assays and gene expression analysis to characterise the ALDH+ population in AE resistant metastatic patient samples and an ER+ cell line. We show that the IL1β signalling pathway is activated in ALDH+ cells and data from single cells reveals that AE treatment selects for IL1R1-expressing ALDH+ cells. Importantly, we demonstrate that increased expression of IL1R1 is observed in the tumours of patients treated with AE therapy and predicts for treatment failure. Single-cell gene expression analysis revealed that at least 2 sub-populations exist within the ALDH+ population, one proliferative and one quiescent. Following AE therapy, the quiescent ALDH+IL1R1+ population is expanded, which suggests CSC dormancy as an adaptive strategy that facilitates treatment resistance. Supporting this, analysis of AE resistant dormant tumours reveals significantly increased expression of ALDH1A1, ALDH1A3 and IL1R1 genes. Thus, we propose that targeting of ALDH+IL1R1+ cells will reverse AE resistance, including in patients with minimal residual disease.