bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface displacements of Aso volcano after the 2016 Kumamoto earthquake based on SAR interferometry: implications for dynamic triggering of earthquake–volcano interactions
Authors: Yamada Wataru , Ishitsuka Kazuya , Mogi Toru , Utsugi Mitsuru
Published: April 2019

The 2016 Kumamoto earthquake involved a series of events culminating in an Mw 7.0 main shock on 2016 April 16; the main-shock fault terminated in the caldera of Aso volcano. In this study, we estimated surface displacements after the 2016 Kumamoto earthquake using synthetic aperture radar interferometry analysis of 16 Phased Array Type L-band Synthetic Aperture Radar-2 images acquired from 2016 April 18 to 2017 June 12 and compared them with four images acquired before the earthquake. Ground subsidence of about 8 cm was observed within about a 3 km radius in the northwestern part of Aso caldera. Because this displacement was not seen in data acquired before the 2016 Kumamoto earthquake, we attribute this displacement to the 2016 Kumamoto earthquake. Furthermore, to estimate the source depth of the surface displacement, we applied the Markov chain Monte Carlo method to a spherical source model and obtained a source depth of about 4.8 km. This depth and position are nearly in agreement with the top of a low-resistivity area previously inferred from magnetotelluric data; this area is thought to represent a deep hydrothermal reservoir. We concluded that this displacement is due to the migration of magma or aqueous fluids.
1989–2019: From democratic to abusive constitutional borrowing
Authors: Dixon Rosalind , Landau David
Published: April 2019

Constitutional borrowing looks very different today than it did thirty years ago: where in 1989, post-Soviet and Eastern European states were looking west for ideas and inspiration, today they are increasingly looking “eastward”—i.e. to Russia, China, and Singapore—for models of constitutional government. When they do look west, we argue, they are also doing so in increasingly “abusive ways”—i.e. in superficial, shallow, acontextual, or anti-purposive ways designed to use liberal democratic ideas and models not as inspiration but as justification for the erosion of minimum democratic norms and guarantees. This new mix of East-West influence is thus distinctly troubling from the perspective of a commitment to constitutional democracy.
Detections and constraints on white dwarf variability from time-series GALEX observations
Authors: Rowan D M , Tucker M A , Shappee B J , Hermes J J
Published: April 2019

We search for photometric variability in more than 23 000 known and candidate white dwarfs (WDs), the largest ultraviolet survey compiled for a single study of WDs. We use gphoton, a publicly available calibration/reduction pipeline, to generate time-series photometry of WDs observed by GALEX. By implementing a system of weighted metrics, we select sources with variability due to pulsations and eclipses. Although GALEX observations have short baselines (≤30 min), we identify intrinsic variability in sources as faint as Gaia G = 20 mag. With our ranking algorithm, we identify 48 new variable WDs in archival GALEX observations. We detect 40 new pulsators: 36 have hydrogen-dominated atmospheres (DAVs), including one possible massive DAV, and four are helium-dominated pulsators (DBVs). We also detect eight new eclipsing systems; five are new discoveries, and three were previously known spectroscopic binaries. We perform synthetic injections of the light curve of WD 1145+017, a system with known transiting debris, to test our ability to recover similar systems. We find that the 3σ maximum occurrence rate of WD 1145+017-like transiting objects is $\le 0.5{{\ \rm per\ cent}}$.
Predictors of Return to Normal Neurological Function After Surgery for Moderate and Severe Degenerative Cervical Myelopathy: An Analysis of A Global AOSpine Cohort of Patients
Authors: De la Garza Ramos Rafael , Nouri Aria , Nakhla Jonathan , Echt Murray , Gelfand Yaroslav , Patel Smruti K , Nasser Rani , Cheng Joseph S , Yassari Reza , Fehlings Michael G
Published: April 2019

BACKGROUND

Multiple studies have established the safety and efficacy of surgical intervention for degenerative cervical myelopathy (DCM). Although the main goal of surgery is symptom stabilization, a subset of patients achieves remarkable improvements.

OBJECTIVE

To identify predictors of return to normal neurological function after surgery for moderate or severe DCM.

METHODS

This is an analysis of 2 prospective multicenter studies (the AOSpine CSM-North America and CSM-International studies) conducted between 2005 and 2011. For patients with complete preoperative magnetic resonance imaging (MRI) and 2-yr follow-up, characteristics were compared between those who achieved a modified Japanese Orthopaedic Association (mJOA) score of 18 at 2 yr (no signs of myelopathy) vs controls. Only patients with baseline mJOA ≤ 14 (moderate and severe myelopathy) were included to minimize ceiling effects.

RESULTS

A total of 51 patients (20.3%) out of 251 with moderate or severe baseline myelopathy achieved an mJOA score of 18 at 2 yr. On stepwise multiple logistic regression analysis, T1-weighted (T1W1)-hypointensity (odds ratio [OR] 0.10; 95% confidence interval [CI], 0.01-0.79; P = .03) and longer walking time on the 30-m walking test (OR 0.95; 95% CI, 0.92-0.99; P = .03) were independent predictors of outcome, with an area under the curve of 0.71 for the model.

CONCLUSION

In this study, T1W-hypointensity on MRI and longer walking time were found to predict a less likelihood of achieving return to normal neurological function after surgery for moderate or severe DCM. These findings may provide useful information for patient counseling and perioperative expectations.
Gamma Knife Radiosurgery for Multiple Sclerosis-Associated Trigeminal Neuralgia
Authors: Helis Corbin A , McTyre Emory , Munley Michael T , Bourland J Daniel , Lucas John T , Cramer Christina K , Tatter Stephen B , Laxton Adrian W , Chan Michael D
Published: April 2019

BACKGROUND

Trigeminal neuralgia in the setting of multiple sclerosis (MS-TN) is a challenging condition to manage that is commonly treated with Gamma Knife radiosurgery (GKRS; Elekta AB). However, data regarding the efficacy of this treatment are somewhat limited, particularly for repeat GKRS.

OBJECTIVE

To report outcomes of GKRS for MS-TN from a cohort study.

METHODS

Retrospective review of our GKRS database identified 77 cases of unilateral MS-TN (UMSTN) in 74 patients treated with GKRS between 2001 and 2016, with 37 cases undergoing repeat GKRS. Background medical history, treatment outcomes and complications, and dosimetric data were obtained by retrospective chart reviews and telephone interviews.

RESULTS

Eighty-two percent of UMSTN cases achieved Barrow Neurological Institute (BNI) IIIb or better pain relief following initial GKRS for a median duration of 1.1 yr. Estimated rates of pain relief at 1, 3, and 5 yr were 51, 39, and 29% respectively. Eighty-eight percent achieved BNI IIIb or better pain relief after repeat GKRS for a median duration of 4.0 yr. Estimated rates of pain relief at 1 and 3 yr were 70 and 54%, respectively. Median doses for initial and repeat GKRS were 85 and 80 Gy to the 100% isodose line, respectively. Those with MS-TN had a shorter duration of BNI IIIb or better pain relief after initial (4.6 vs 1.1 yr), but not repeat GKRS (3.8 vs 4.0 yr) compared to a historical cohort from our institution.

CONCLUSION

GKRS is an effective, well-tolerated treatment for patients with MS-TN. More durable relief is often achieved with repeat GKRS.
Racialized Equity Labor, University Appropriation and Student Resistance
Authors: Lerma Veronica , Hamilton Laura T , Nielsen Kelly
Published: April 2019

We coin the term “racialized equity labor” to describe the often uncompensated efforts of people of color to address systematic racism and racial marginalization within organizations. Using a year-long ethnographic and interview study of a majority-minority public university, we focus specifically on the racialized equity labor of college students who, like many faculty and staff of color, often labor to make their campuses comfortable and functional for historically underrepresented populations. We identify a cycle of racialized labor appropriation whereby: 1) people of color identify problems in the racial environment of their organizations and work to solve them; 2) leadership responds by blocking efforts and/or denying issues; 3) external and/or internal pressures force introspection and push leaders to resolve an organizational threat (e.g., to the university’s public image of diversity); and finally, 4) leadership appropriates racialized equity labor, and in doing so converts it into a diluted diversity initiative. Those engaged in racialized equity labor may resist appropriation, but the cycle takes a toll on activists. The ways in which organizations respond to racialized equity labor offers insight into the reproduction of racial inequities, despite the hard work of people of color to create meaningful racial change.
Molecular modelling as the spark for active learning approaches for interdisciplinary biology teaching
Authors: Taly A. , Nitti F. , Baaden M. , Pasquali S.
Published: April 2019

We present here an interdisciplinary workshop on the subject of biomolecules offered to undergraduate and high school students with the aim of boosting their interest toward all areas of science contributing to the study of life. The workshop involves mathematics, physics, chemistry, computer science and biology. Based on our own areas of research, molecular modelling is chosen as the central axis as it involves all disciplines. To provide a strong biological motivation for the study of the dynamics of biomolecules, the theme of the workshop is the origin of life. All sessions are built around active pedagogy, including games, and a final poster presentation.
Coarse-grained dynamic RNA titration simulations
Authors: Pasquali S. , Frezza E. , Barroso da Silva F. L.
Published: April 2019

Electrostatic interactions play a pivotal role in many biomolecular processes. The molecular organization and function in biological systems are largely determined by these interactions. Owing to the highly negative charge of RNA, the effect is expected to be more pronounced in this system. Moreover, RNA base pairing is dependent on the charge of the base, giving rise to alternative secondary and tertiary structures. The equilibrium between uncharged and charged bases is regulated by the solution pH, which is therefore a key environmental condition influencing the molecule’s structure and behaviour. By means of constant-pH Monte Carlo simulations based on a fast proton titration scheme, coupled with the coarse-grained model HiRE-RNA, molecular dynamic simulations of RNA molecules at constant pH enable us to explore the RNA conformational plasticity at different pH values as well as to compute electrostatic properties as local p
K
a
values for each nucleotide.
Cross-over in the dynamics of polymer confined between two liquids of different viscosity
Authors: Giunta Giuliana , Carbone Paola
Published: April 2019

Using molecular dynamics simulations, we analysed the polymer dynamics of chains of different molecular weights entrapped at the interface between two immiscible liquids. We showed that on increasing the viscosity of one of the two liquids the dynamic behaviour of the chain changes from a Zimm-like dynamics typical of dilute polymer solutions to a Rouse-like dynamics where hydrodynamic interactions are screened. We observed that when the polymer is in contact with a high viscosity liquid, the number of solvent molecules close to the polymer beads is reduced and ascribed the screening effect to this reduced number of polymer–solvent contacts. For the longest chain simulated, we calculated the distribution of loop length and compared the results with the theoretical distribution developed for solid/liquid interfaces. We showed that the polymer tends to form loops (although flat against the interface) and that the theory works reasonably well also for liquid/liquid interfaces.
Quantifying dissipation in actomyosin networks
Authors: Floyd Carlos , Papoian Garegin A. , Jarzynski Christopher
Published: April 2019

Quantifying entropy production in various active matter phases will open new avenues for probing self-organization principles in these far-from-equilibrium systems. It has been hypothesized that the dissipation of free energy by active matter systems may be optimized, leading to system trajectories with histories of large dissipation and an accompanying emergence of ordered dynamical states. This interesting idea has not been widely tested. In particular, it is not clear whether emergent states of actomyosin networks, which represent a salient example of biological active matter, self-organize following the principle of dissipation optimization. In order to start addressing this question using detailed computational modelling, we rely on the MEDYAN simulation platform, which allows simulating active matter networks from fundamental molecular principles. We have extended the capabilities of MEDYAN to allow quantification of the rates of dissipation resulting from chemical reactions and relaxation of mechanical stresses during simulation trajectories. This is done by computing precise changes in Gibbs free energy accompanying chemical reactions using a novel formula and through detailed calculations of instantaneous values of the system’s mechanical energy. We validate our approach with a mean-field model that estimates the rates of dissipation from filament treadmilling. Applying this methodology to the self-organization of small disordered actomyosin networks, we find that compact and highly cross-linked networks tend to allow more efficient transduction of chemical free energy into mechanical energy. In these simple systems, we observe that spontaneous network reorganizations tend to result in a decrease in the total dissipation rate to a low steady-state value. Future studies might carefully test whether the dissipation-driven adaptation hypothesis applies in this instance, as well as in more complex cytoskeletal geometries.
MS2 bacteriophage capsid studied using all-atom molecular dynamics
Authors: Farafonov Vladimir S. , Nerukh Dmitry
Published: April 2019

The all-atom model of an MS2 bacteriophage particle without its genome (the capsid) was built using high-resolution cryo-electron microscopy (EM) measurements for initial conformation. The structural characteristics of the capsid and the dynamics of the surrounding solution were examined using molecular dynamics simulation. The model demonstrates the overall preservation of the cryo-EM structure of the capsid at physiological conditions (room temperature and ions composition). The formation of a dense anion layer near the inner surface and a diffuse cation layer near the outer surface of the capsid was detected. The flow of water molecules and ions across the capsid through its pores were quantified, which was considerable for water and substantial for ions.
Linking Gaussian process regression with data-driven manifold embeddings for nonlinear data fusion
Authors: Lee Seungjoon , Dietrich Felix , Karniadakis George E. , Kevrekidis Ioannis G.
Published: April 2019

In statistical modelling with Gaussian process regression, it has been shown that combining (few) high-fidelity data with (many) low-fidelity data can enhance prediction accuracy, compared to prediction based on the few high-fidelity data only. Such information fusion techniques for multi-fidelity data commonly approach the high-fidelity model
f
h
(
t
) as a function of
two
variables (
t
,
s
), and then use
f
l
(
t
) as the
s
data. More generally, the high-fidelity model can be written as a function of several variables (
t
,
s
1
,
s
2
….); the low-fidelity model
f
l
and, say, some of its derivatives can then be substituted for these variables. In this paper, we will explore mathematical algorithms for multi-fidelity information fusion that use such an approach towards improving the representation of the high-fidelity function with only a few training data points. Given that
f
h
may not be a simple function—and sometimes not even a function—of
f
l
, we demonstrate that using additional functions of
t
, such as derivatives or shifts of
f
l
, can drastically improve the approximation of
f
h
through Gaussian processes. We also point out a connection with ‘embedology’ techniques from topology and dynamical systems. Our illustrative examples range from instructive caricatures to computational biology models, such as Hodgkin–Huxley neural oscillations.
From quantum to subcellular scales: multi-scale simulation approaches and the SIRAH force field
Authors: Machado Matías R. , Zeida Ari , Darré Leonardo , Pantano Sergio
Published: April 2019

Modern molecular and cellular biology profits from astonishing resolution structural methods, currently even reaching the whole cell level. This is encompassed by the development of computational methods providing a deep view into the structure and dynamics of molecular processes happening at very different scales in time and space. Linking such scales is of paramount importance when aiming at far-reaching biological questions. Computational methods at the interface between classical and coarse-grained resolutions are gaining momentum with several research groups dedicating important efforts to their development and tuning. An overview of such methods is addressed herein, with special emphasis on the SIRAH force field for coarse-grained and multi-scale simulations. Moreover, we provide proof of concept calculations on the implementation of a multi-scale simulation scheme including quantum calculations on a classical fine-grained/coarse-grained representation of double-stranded DNA. This opens the possibility to include the effect of large conformational fluctuations in chromatin segments on, for instance, the reactivity of particular base pairs within the same simulation framework.
Multi-resolution simulations of intracellular processes
Authors: Erban Radek , Harris Sarah , Potestio Raffaello
Published: April 2019

This is an introduction to the Thematic Issue of
Interface Focus
containing papers by speakers of the Theo Murphy International Scientific Meeting on ‘Multi-resolution simulations of intracellular processes’
Respiratory disease and lower pulmonary function as risk factors for subsequent dementia: a systematic review with meta-analysis
Authors: Russ Tom C. , Kivimäki Mika , Batty G. David
Published: April 2019

Background

In addition to affecting the oxygen supply to the brain, pulmonary function is a marker of multiple insults throughout life (including smoking, illness, and socioeconomic deprivation). By meta-analysing existing studies, we tested the hypothesis that lower pulmonary function and respiratory illness are linked to an elevated risk of dementia.

Aims

To review the best available evidence, taken from longitudinal studies, for pulmonary function and respiratory disease as risk factors of dementia.

Method

We conducted a systematic review of longitudinal studies using PubMed until April 1st, 2019 and, where possible, pooled results in random-effects meta-analyses.

Results

We identified eleven studies relating pulmonary function to later dementia risk, and eleven studies of respiratory illness and dementia (including one which studied both). The lowest quartile of lung function measure Forced Expiratory Volume in one second (FEV1) compared with the highest was associated with a 1.5-fold (1.51, 95%CI 0.94-2.42) increased dementia risk (Ntotal=127,710, 3 studies). Respiratory illness was also associated with increased dementia risk to a similar degree (1.54, 1.30-1.81, Ntotal=288,641, 11 studies).

Conclusions

Individuals with poor pulmonary function are at increased risk of dementia. The extent to which the association between poor pulmonary function and dementia is causal remains unclear.
A multi-omic analysis of optineurin proteinopathy in a yeast model suggests the involvement of lipid metabolism in Amyotrophic Lateral Sclerosis
Authors: Bean Daniel M. , Hnatova Silvia , Mülleder Michael , Magalhães Sandra , Nightingale Daniel J. H. , Lilley Kathryn S. , Ralser Markus , Nunes Alexandra , Goodfellow Brian J. , Oliver Stephen G.
Published: April 2019

Amyotrophic Lateral Sclerosis (ALS) is an incurable fatal neurodegenerative disease for which the precise mechanisms of toxicity remain unclear despite some significant advances in our understanding of the underlying genetic basis. A holistic, integrated view of cellular changes will be critical to understanding the processes of neurodegeneration and the development of effective treatments. Mutant forms of optineurin (a ubiquitin-binding protein involved in autophagy, membrane trafficking, and NF-κB activation) are found associated with cytoplasmic inclusions containing TDP43 or SOD1 in some ALS patients. We have taken a multi-omics approach to understand the cellular response to OPTN overexpression in a yeast model of ALS. We found that genetic interaction screens and metabolomics provided parallel, highly complementary data on OPTN toxicity. Genetic enhancers of OPTN toxicity in yeast relate directly to the native function of OPTN in vesicular trafficking and intracellular transport, suggesting the human OPTN protein is functional when expressed in yeast even though there is no yeast ortholog. Crucially, we find that the genetic modifiers and the metabolic response are distinct for different ALS-linked genes expressed in yeast. This lends strong support to the use of yeast as a model system and omics platform to study ALS.
Untangling the Indonesian tangle net fishery: describing a data-poor fishery targeting large threatened rays (Order Batoidea)
Authors: D’Alberto Brooke M. , White William T. , Chin Andrew , Dharmadi  , Simpfendorfer Colin A.
Published: April 2019

Shark-like rays (Order Rhinopristiformes) are among the most threatened families of marine fish. Yet little is known about their populations, as these rays are normally taken as opportunistic catch in fisheries targeting other species and are thus poorly reported. One exception is the Indonesian tangle net fishery, which targets shark-like rays.

Market surveys of Muara Angke landing site in Jakarta, north-western Java (including one frozen shipment from Benoa Harbour, Bali), were conducted between 2001 and 2005, and recorded landed catch for this fishery. Recent catch data from Indonesian Capture Fisheries (2017 – 2018) were also examined to provide contemporary information about landed catch.

1,559 elasmobranchs (sharks and rays) were recorded, comprised of 24 species of rays and nine species of sharks. The most abundant species landed were the pink whipray Pateobatis fai and the bottlenose wedgefish Rhynchobatus australiae, the latter being the main target species.

Catch composition varied based on differences in species catchability and may also be indicative of localized declines. The fishery was highly selective for larger sized individuals, however smaller size classes of target species were also caught in other Indonesian fisheries resulting in fishing pressure across all age classes.

Evidence of substantial declines in global landings of wedgefish species, and the observed shift in catch composition in the Indonesian tangle net fishery, increases concerns about the status of shark-like rays and stingrays in Indonesia.
Compartmental Modeling Software: a fast, discrete stochastic framework for biochemical and epidemiological simulation
Authors: Lorton Christopher W. , Proctor Joshua L. , Roh Min K. , Welkhoff Philip A.
Published: April 2019

The compartmental modeling software (CMS) is an open source computational framework that can simulate discrete, stochastic reaction models which are often utilized to describe complex systems from epidemiology and systems biology. In this article, we report the computational requirements, the novel input model language, the available numerical solvers, and the output file format for CMS. In addition, the CMS code repository also includes a library of example model files, unit and regression tests, and documentation. Two examples, one from systems biology and the other from computational epidemiology, are included that highlight the functionality of CMS. We believe the creation of computational frameworks such as CMS will advance our scientific understanding of complex systems as well as encourage collaborative efforts for code development and knowledge sharing.
Lifestyle and biological factors influence the relationship between mental health and low-grade inflammation
Authors: Gialluisi A , Bonaccio M , Di Castelnuovo A , Costanzo S , De Curtis A , Sarchiapone M , Cerletti C , Donati MB , de Gaetano G , Iacoviello L ,   on behalf of the Moli-Sani Study Investigators
Published: April 2019

Mental health modulates the risk of common chronic conditions like cardiovascular disease, cancer and diabetes. Although inflammation is thought to partly explain this link, its relation with mental health is still unclear and largely unexplored.

We investigated three scales assessing psychological resilience (CD-RISC), depression symptoms (PHQ8) and mental wellbeing (SF36-MCS) in an Italian adult population cohort (Nmax=16,952). We performed stepwise generalized linear models to test the association between each scale and INFLA-score, a composite blood-based inflammation index. At each step, a class of potential mediators was included in the model, namely health conditions, lifestyle factors, or both (full model). Full model analysis was also conducted on single blood markers involved in the inflammatory process.

In the baseline model, we observed significant associations of PHQ8 (standardized β=0.024, p=8.9×10−3) and SF36-MCS (β = −0.021, p=7×10−3) with INFLA-score. These associations survived adjustment for health conditions but not for lifestyle factors, which explained 81% and 17% of the association with PHQ8 and SF36-MCS, respectively. Significant associations (p<4.2×10−3) after mediator adjustment were observed for single low-grade inflammation markers, including platelet distribution width (with PHQ8 and CD-RISC), granulocyte-and neutrophil-to-lymphocyte ratios, monocyte and lymphocyte fractions (with SF36-MCS).

These findings suggest that the relationship between mental health and low-grade inflammation is largely influenced by lifestyle. However, the associations with specific biomarkers related to inflammation are partly independent and might be explained by biological factors. Interestingly, these associations are in line with recent blood transcriptomic analyses of depressed subjects, reporting up- and down-regulation of genes related to innate and adaptive immunity, respectively.
A pilot Study: Auditory Steady-State Responses (ASSR) can be measured in human Fetuses using fetal Magnetoencephalography (fMEG)
Authors: Niepel Dorothea , Krishna Bhargavi , Siegel Eric R. , Draganova Rossitza , Preissl Hubert , Govindan Rathinaswamy B. , Eswaran Hari
Published: April 2019

Background

Auditory steady-state responses (ASSRs) are ongoing evoked brain responses to continuous auditory stimuli that play a role for auditory processing of complex sounds and speech perception. Transient auditory event-related responses (AERRs) have previously been recorded using fetal magnetoencephalography (fMEG) but involve different neurological pathways. Previous studies in children and adults demonstrated that the cortical components of the ASSR are significantly affected by state of consciousness and by maturational changes in neonates and young infants. To our knowledge, this is the first study to investigate ASSRs in human fetuses.

Methods

47 fMEG sessions were conducted with 24 healthy pregnant women in three gestational age groups (30–32 weeks, 33–35 weeks and 36–39 weeks). The stimulation consisted of amplitude-modulated (AM) tones with a duration of one second, a carrier frequency (CF) of 500 Hz and a modulation frequency (MF) of 27 Hz or 42 Hz. Both tones were presented in a random order with equal probability adding up to 80–100 repetitions per tone. The ASSR across trials was quantified by assessing phase synchrony in the cortical signals at the stimulation frequency.

Results and Conclusion

Ten out of 47 recordings were excluded due to technical problems or maternal movements. Analysis of the included 37 fetal recordings revealed a statistically significant response for the phase coherence between trials for the MF of 27 Hz but not for 42 Hz. An exploratory subgroup analysis moreover suggested an advantage in detectability for fetal behavioral state 2F (active asleep) compared to 1F (quiet asleep) detected using fetal heart rate. In conclusion, with the present study it was possible to detect human fetal ASSRs for the first time. These findings warrant further investigations of the developing fetal brain.
Seasonal zonation patterns of the sandy beach bivalveDonax deltoides(Bivalvia: Donacidae) in subtropical eastern Australia
Authors: Totterman Stephen
Published: April 2019

Seasonal low tide zonation patterns of the sandy beach bivalveDonax deltoidesare described from eleven beaches in subtropical eastern Australia. Ten low tide transects were sampled at equal along shore intervals along the length of each beach. Three quadrats were sampled at each of seven across shore levels on each transect, from the high tide drift line, across the intertidal zone and to the bottom of the low tide swash zone. Zone counts showed thatD. deltoidesshifted towards the low tide swash zone in summer and buried in the intertidal zone in winter. It is proposed thatD. deltoidesmoves down shore in summer to avoid thermal stress in the intertidal zone. This seasonal pattern is important when planning surveys for this species.
Elimination of HSV-2 infected cells is mediated predominantly by paracrine effects of tissue-resident T cell derived cytokines
Authors: Roychoudhury Pavitra , Swan David A , Duke Elizabeth , Corey Lawrence , Zhu Jia , Davé Veronica , Spuhler Laura Richert , Lund Jennifer M. , Prlic Martin , Schiffer Joshua T.
Published: April 2019

The mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in the human genital tract despite low tissue-resident CD8+ T-cell density (TRM) are unknown. We analyzed shedding episodes during chronic HSV-2 infection: viral clearance always occurred within 24 hours of detection even if viral load exceeded 107HSV DNA copies; surges in granzyme B and interferon-γoccurred within the early hours after reactivation. We next developed a mathematical model of an HSV-2 genital ulcer to integrate mechanistic observations of TRMin situproliferation, trafficking, cytolytic effects and cytokine alarm signaling from murine studies with viral kinetics, histopathology and lesion size data from humans. A sufficiently high density of HSV-2 specific TRMpredicted rapid contact-mediated elimination of infected cells. At lower TRMdensities, TRMmust initiate a rapidly diffusing, polyfunctional cytokine response in order to eliminate of a majority of infected cells and eradicate briskly spreading HSV-2 infection.

One Sentence Summary

Control of herpes simplex virus-2 is primarily mediated by rapidly diffusing cytokines secreted by tissue-resident T cells.
Investigating the role of behaviour in the genetic risk for schizophrenia
Authors: Maxwell Jessye , Socrates Adam , Glanville Kylie P. , Forti Marta Di , Murray Robin M. , Vassos Evangelos , O’Reilly Paul F.
Published: April 2019

The notion that behaviour may be on a causal path from genetics to psychiatric disorders, such as schizophrenia, highlights a potential for practical interventions. Motivated by this, we test the association between schizophrenia (SCZ) polygenic risk scores (PRS) and 420 behavioural traits (personality, psychological, lifestyle, nutritional) in a psychiatrically healthy sub-cohort of the UK Biobank. Higher schizophrenia PRS was associated with a range of traits, including lower verbal-numerical reasoning (P= 6×10−61), higher nervous feelings (P= 2×10−51) and higher self-reported risk-taking (P= 2×10−41). We follow-up the risk-taking association, hypothesising that the association may be due to a genetic propensity for risk-taking leading to greater migration, urbanicity or drug-taking – reported environmental risk factors for schizophrenia, and all positively associated with risk-taking in these data. However, schizophrenia PRS was also associated with traits, such as tea drinking (P= 2×10−34), that are highly unlikely to be on a causal path to schizophrenia. We depict four causal relationships that may in theory underlie such PRS-trait associations and illustrate ways of testing for each. For example, we contrast PRS-trait trends in the healthy sub-cohort to the corresponding trait values of medicated and non-medicated individuals diagnosed with schizophrenia, allowing some differentiation of mediation-by-behaviour, disease-onset effects and treatment effects. However, dedicated follow-up studies and new methods are required to fully disentangle these relationships. Thus, while we urge caution in interpretation of simple PRS cross-trait associations, we propose that well-designed PRS analyses can contribute to identifying behaviours on the causal path from genetics to disease.
Clinical and Cost Effectiveness of Two “New” Lynch Syndrome Case Finding Protocols in Endometrial Cancer Population Contrasted with the IHC-based Protocol
Authors: Gudgeon James M. , Varner Michael W. , Hashibe Mia , Williams Marc S.
Published: April 2019

Purpose

To investigate the effectiveness and costs of two Lynch syndrome screening protocols among endometrial cancer (EC) patients and compare to an immunohistochemistry (IHC)–based protocol.

Methods

Analytic models were developed to represent the two protocols: a brief cancer family history questionnaire (bFHQ) and direct-to-sequencing of the germline. Data from reviews of published literature, augmented by local data and expert opinion were used to populate the model representing the number of women diagnosed in the U.S. in 2018. Multiple analyses employing simulation modeling were performed to estimate a variety of clinical and economic outcomes.

Results

Under conditions considered here to be plausible, the bFHQ is expected to miss 58% (min./max. = 24 to 80%) of LS index cases, a direct-to-sequencing protocol to miss 30% (min./max. = 6% to 53%), and the IHC-based protocol based on previous analysis 58% (min./max. = 33 to 80%). When direct costs of testing and genetic counseling are added to the models, the total screening program costs for the bFHQ protocol are substantially lower at all sequencing price points than the other protocols. For example, at the low end of the sequencing price point (ie, $250), the total cost of screening programs for IHC, bFHQ, and sequencing are $22.9 million, $5.3 million, and $13.8 million, respectively. The best estimate of the break-even price of sequencing, when the cost of the program is equivalent between the IHC and sequencing protocols, is about $635.

Conclusion

The bFHQ and direct-to-sequencing LS screening protocols are more effective and cost effective at identifying LS index cases than the standard IHC-based protocol under the conditions represented in our models. These estimates of various outcome metrics of the three LS index case finding protocols may help stakeholders make decisions of the use of limited healthcare dollars.
Hippocampal theta codes for distances in semantic and temporal spaces
Authors: Solomon Ethan A. , Lega Bradley C. , Sperling Michael R. , Kahana Michael J.
Published: April 2019

ABSTRACT

The medial temporal lobe (MTL) is known to support episodic memory and spatial navigation, raising the possibility that its true function is to form “cognitive maps” of any kind of information. Studies in humans and animals support the idea that the hippocampal theta rhythm (4-8 Hz) is key to this mapping function, as it has been repeatedly observed during spatial navigation tasks. If episodic memory and spatial navigation are two sides of the same coin, we hypothesized that theta oscillations would also reflect relations between explicitly nonspatial items, such as words. We asked 189 neurosurgical patients to perform a verbal free-recall task, of which 96 had indwelling electrodes placed in the MTL. Subjects were instructed to remember short lists of sequentially-presented nouns. We found that hippocampal theta power and connectivity during item retrieval coded for semantic distances between words, as measured using word2vec-derived subspaces. Additionally, hippocampal theta indexed temporal distances between words after filtering lists on recall performance, to ensure adequate dynamic range in time. Theta effects were only noted for semantic subspaces of 1-dimension, indicating a substantial compression of the possible semantic feature space. These results lend further support to our growing confidence that the MTL forms cognitive maps of arbitrary representational spaces, reconciling longstanding differences between the spatial and episodic memory literatures.
The cryptic impacts of invasion: Functional homogenization of tropical ant communities by invasive fire ants
Authors: Wong Mark K. L. , Guénard Benoit , Lewis Owen T.
Published: April 2019

Invasive insects represent major threats to ecosystems worldwide. Yet their effects on the functional dimension of biodiversity, measured as the diversity and distribution of traits, are overlooked. Such measures often determine the resilience of ecological communities and the ecosystem processes they modulate. The fire ant Solenopsis invicta is a highly problematic invasive species occurring on five continents. Its impacts on the taxonomic diversity of native ant communities have been studied but its impacts on their functional diversity are unknown. Comparing invaded and uninvaded plots in tropical grasslands of Hong Kong, we investigated how the presence of S. invicta affects the diversity and distribution of ant species and traits within and across communities, the functional identities of communities, and functionally unique species. We calculated the functional diversity of individual species, including the trait variation from intraspecific polymorphisms, and scaled up these values to calculate functional diversity at the community level. Invasion had only limited effects on species richness and functional richness, which were 13% and 8.5% lower in invaded communities respectively. In contrast, invasion had pronounced effects on taxonomic and functional composition due to turnover in species and trait values. Furthermore, invaded communities were functionally more homogeneous, displaying 23% less turnover and 56% more redundancy than uninvaded communities, as well as greater clustering and lower divergence in trait values. Invaded communities had fewer functionally-unique individuals and were characterized by ant species with narrower heads and bodies and shorter mandibles. Our results suggest that studies based only on taxonomic measures of diversity or indices describing trait variety risk underestimating the full ramifications of invasions. Investigating the diversity and distributions of traits at species, community and landscape levels can reveal the cryptic impacts of alien species which, despite causing little taxonomic change, may substantially modify the structure and functioning of ecological communities.
CNCC: An analysis tool to determine genome-wide DNA break end structure at single-nucleotide resolution
Authors: Szlachta Karol , Raimer Heather M , Comeau Laurey D. , Wang Yuh-Hwa
Published: April 2019

DNA double-stranded breaks (DSBs) are potentially deleterious events in a cell. The end structures (blunt, 3’- and 5’-overhangs) at sites of double-stranded breaks contribute to the fate of their repair and provide critical information for consequences of the damage. Here, we describe the use of a coverage-normalized cross correlation analysis (CNCC) to process high-precision genome-wide break mapping data, and determine genome-wide break end structure distributions at single-nucleotide resolution. For the first time, on a genome-wide scale, our analysis revealed the increase in the 5’ to 3’ end resection following etoposide treatment, and the global progression of the resection due to the removal of DNA topoisomerase II cleavage complexes. Further, our method distinguished the change in the pattern of DSB end structure with increasing doses of the drug. The ability of this method to determine DNA break end structures withouta prioriknowledge of break sequences or genomic position should have broad applications in understanding genome instability.
The Positive End of the Polygenic Score Distribution for ADHD: A Low Risk or a Protective Factor?
Authors: Li James J.
Published: April 2019

Background

Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood.

Methods

Participants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N=7,088; mean age=29, s.d.=1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health and physical health were assessed during in-home interviews.

Results

Individuals at the lowest end of the ADHD PGS distribution (i.e., lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17-19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high PGS groups.

Conclusions

Findings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.
Comparing and Validating Automated Tools for Individualized Electric Field Simulations in the Human Head
Authors: Puonti Oula , Saturnino Guilherme B. , Madsen Kristoffer H. , Thielscher Axel
Published: April 2019

Comparing electric field simulations from individualized head models against in-vivo recordings is important for direct validation of computational field modeling for transcranial brain stimulation and brain mapping techniques such as electro- and magnetoencephalography. This also helps to improve simulation accuracy by pinning down the factors having the largest influence on the simulations. Here we compare field simulations from four different automated pipelines, against intracranial voltage recordings in an existing dataset of 14 epilepsy patients. We show that ignoring uncertainty in the simulations leads to a strong bias in the estimated linear relationship between simulated and measured fields. In addition, even though the simulations between the pipelines differ notably, this is not reflected in the correlation with the measurements. We discuss potential reasons for this apparent mismatch and propose a new Bayesian regression analysis of the data that yields unbiased estimates enabling robust conclusions to be reached.
Production of high cellulase yields from polypore fungi in solid-state fermentation using green tea waste
Authors: Nguyen KA , Penkhrue W , Lumyong S
Published: April 2019

Polypores are diverse macrofungi that have been extensively studied for their enzyme production capabilities. Presently, these enzymes are being used for many industrial purposes. However, the high-cost associated with their production is the main barrier to their broader application. This work aimed to study the optimal medium and conditions by using solid state fermentation. Seven polypore strains were used for cellulase activity screening. The fermentation experiments were carried out in 250 mL Erlenmeyer flasks with green tea waste as a substrate. Notably, Microporus sp. KA038 showed the best level of activity of 81.8 IU/gds. Various parameters such as temperature on growth, moisture content, nitrogen source, initial pH value, inoculum size and incubation time were considered to determine the optimal conditions for cellulase production. The optimal medium consisted of green tea leaves as a carbon source, beef extract as an organic nitrogen source, and NH4H2PO4 as an inorganic nitrogen source, while pH 7.0 and an incubation temperature of 30°C for 4 days resulted in a high enzyme yield with Microporus sp. KA038.
Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver
Authors: Liu Bingdong , Pan Xiaohan , Yao Liheng , Chen Shujie , Liu Zhihong , Han Mulan , Yin Yulong , Xu Guohuan , Wan Dan , Dai Xiaoshuang , Sun Jia , Pan Jiyang , Zhang Huabing , Wang Wei , Liu Li , Xie Liwei
Published: April 2019

Iron is an essential trace mineral for the growth, systemic metabolism, and immune response. Imbalance of tissue iron absorption and storage leads to various diseases. The excessive iron accumulation is associated with inflammation and cancer while iron deficiency leads to growth retardation. Studies investigated in Kenyan infants and school children suggests that both low and high iron intake result in dysbiosis of gut microbiota. This would lead to the disruption of microbial diversity, an increase of pathogen abundance and the induction of intestinal inflammation. Despite this progress, in-depth studies investigating the relationship between iron availability and gut microbiota is not completely explored. In the current study, we established a murine model to study the connection between iron and microbiota by feeding mice with either iron-deprived or -fortified diet. To identify key microbiota related to iron levels, we combined the 16S rRNA amplicon sequencing with the innovated bioinformatic algorithms, such as RDA, co-occurrence, and machine learning to identify key microbiota. Manipulation of iron levels in the diet leads to systemic iron dysregulation and dysbiosis of gut microbiota. The bioinformatic algorithms used here detect five key bacteria that correlate with systemic iron levels. Leveraging on these key microbiotas, we also established a prediction model which could precisely distinguish the individual under either iron-deprived or iron-fortified physiological condition to further prove the link between microbiota and systemic iron homeostasis. This innovated and non-invasive approach could be potentially used for the early diagnosis and therapy of iron-dysregulation related diseases, e.g. anemia, inflammatory disease, fibrosis, and cancers.