bluuebunny/crossref_metadata_2025 huggingface dataset:
Static and dynamic calibration of torsional spring constants of cantilevers
Authors: Labuda Aleksander , Cao Changhong , Walsh Tim , Meinhold Jieh , Proksch Roger , Sun Yu , Filleter Tobin
Published: September 2018

A method for calibrating the dynamic torsional spring constant of cantilevers by directly measuring the thermally driven motion of the cantilever with an interferometer is presented. Random errors in calibration were made negligible (<1%) by averaging over multiple measurements. The errors in accuracy of ±5% or ±10% for both of the cantilevers calibrated in this study were limited only by the accuracy of the laser Doppler vibrometer (LDV) used to measure thermal fluctuations. This is a significant improvement over commonly used methods that result in large and untraceable errors resulting from assumptions made about the cantilever geometry, material properties, and/or hydrodynamic physics of the surroundings. Subsequently, the static torsional spring constant is determined from its dynamic counterpart after careful LDV measurements of the torsional mode shape, backed by finite element analysis simulations. A meticulously calibrated cantilever is used in a friction force microscopy experiment that measures the friction difference and interfacial shear strength (ISS) between graphene and a silicon dioxide AFM probe. Accurate calibration can resolve discrepancies between different experimental methods, which have contributed to a large scatter in the reported friction and ISS values in the literature to date.
Existence of electron acoustic solitary waves in relativistic limit
Authors: Jana Sayanee , Karmakar Mithun , Chakrabarti Nikhil
Published: September 2018

The nonlinear relativistic dynamics of electron acoustic waves (EAWs) in collisionless, unmagnetized plasma comprising cold inertial electrons, hot Boltzmann distributed electrons, and stationary ions are studied. The Sagdeev pseudopotential technique is employed to discuss the effect of equilibrium plasma species density and temperature of the hot electrons on the relativistic solitary wave solutions. In exploring the electron acoustic soliton characteristics, we encounter only negative polarity solitons which are found to exist in a restricted range of the physical parameter space of the system. In addition, we extend our analysis to demonstrate the wave breaking phenomena of EAW and estimate the maximum sustainable electric field amplitude of this mode considering the relativistic electron mass variation effect.
Heavily overdamped resonance structurally engineered in a grating metasurface for ultra-broadband acoustic absorption
Authors: Lee Taehwa , Iizuka Hideo
Published: September 2018

We derive a heavily overdamping condition for nearly frequency-independent unity absorption in a periodic structure consisting of harmonic oscillators impinged by acoustic waves. We show that the condition is fulfilled by an acoustic metasurface consisting of a metal grating covered with a polydimethylsiloxane layer, which exhibits high absorption (>80%) over a wide range of frequencies (∼more than three octaves). We find that the grating metasurface enables us to structurally engineer the system loss rate without introducing a more lossy material. The analytic model excellently captures the absorption characteristics of the metasurface observed in numerical results.
Merging bands of polarization convertors by suppressing Fano resonance
Authors: Fu Xinmin , Wang Jiafu , Fan Ya , Feng Mingde , Yan Mingbao , Li Yongfeng , Chen Hongya , Zhang Jieqiu , Qu Shaobo
Published: September 2018

In this letter, we propose to extend the bandwidth of polarization conversion (PC) by merging the bands of different polarization converters. Intuitively, it is quite natural that the bands of two polarization converters be merged if they are close enough. Unfortunately, there is always a narrow band with low efficiency between the two bands, which results from Fano resonance. We establish a theoretical model to analyze the underlying mechanism of the Fano resonance. We find that the Fano resonance can be suppressed by reducing the resonant frequency of the converter operating at a higher frequency band. In this way, the anti-symmetric surface current can be eliminated and the two PC bands can be merged as a wide band. We designed, fabricated, and measured a prototype. Both the simulation and experimental results verify this method. This work provides an effective alternative to the design of wide-band or even ultra-wideband polarization converters.
Symmetric polynomials, generalized Jacobi-Trudi identities and τ-functions
Authors: Harnad J. , Lee Eunghyun
Published: September 2018

An element [Φ]∈GrnH+,F of the Grassmannian of n-dimensional subspaces of the Hardy space H+=H2, extended over the field F = C(x1, …, xn), may be associated to any polynomial basis ϕ = {ϕ0, ϕ1, ⋯ } for C(x). The Plücker coordinates Sλ,nϕ(x1,…,xn) of [Φ], labeled by partitions λ, provide an analog of Jacobi’s bi-alternant formula, defining a generalization of Schur polynomials. Applying the recursion relations satisfied by the polynomial system ϕ to the analog {hi(0)} of the complete symmetric functions generates a doubly infinite matrix hi(j) of symmetric polynomials that determine an element [H]∈Grn(H+,F). This is shown to coincide with [Φ], implying a set of generalized Jacobi identities, extending a result obtained by Sergeev and Veselov [Moscow Math. J. 14, 161–168 (2014)] for the case of orthogonal polynomials. The symmetric polynomials Sλ,nϕ(x1,…,xn) are shown to be KP (Kadomtsev-Petviashvili) τ-functions in terms of the power sums [x] of the xa’s, viewed as KP flow variables. A fermionic operator representation is derived for these, as well as for the infinite sums ∑λSλ,nϕ([x])Sλ,nθ(t) associated to any pair of polynomial bases (ϕ, θ), which are shown to be 2D Toda lattice τ-functions. A number of applications are given, including classical group character expansions, matrix model partition functions, and generators for random processes.
Colleters in the vegetative axis of Aechmea blanchetiana (Bromeliaceae): anatomical, ultrastructural and functional aspects
Authors: Ballego-Campos Igor , Paiva Elder Antônio Sousa
Published: September 2018

Colleters are common among eudicotyledons, but few records exist for monocotyledons and other groups of plants. For Bromeliaceae, mucilage secretions that protect the young portions of the plant have been observed only in the reproductive axis, and little is known about the secretory systems behind this or even other kind of secretions in the family. We aimed to describe, for the first time, the occurrence of colleters associated with the vegetative shoot of Aechmea blanchetiana (Baker) L.B.Sm., and elucidate aspects of their structure, ultrastructure and secretory activity. Samples of various portions of the stem axis were prepared according to standard methods for light and electron microscopy. Colleters were found compressed in the axillary portion of leaves and in all leaf developmental stages. Secretory activity, however, was found to be restricted to young and unexpanded leaves. The colleters displayed a flattened hand-like shape formed by a multiseriate stalk and an expanded secretory portion bearing elongated marginal cells. Ultrastructural data confirmed that the secretory role of the colleters is consistent with mucilaginous secretion. The functional roles of the colleters are discussed with regard to environmental context and intrinsic features of the plant, such as the presence of a water-impounding tank.
Differentiation in leaf epidermis
Authors: Shanks R
Published: September 2018

Microphotometric studies of the leaf epidermis of four monocotyledons indicate
that differentiation is accompanied by DNA increases. High polyploidy (over 16-ploid)
may be reached in epidermal cells of Galtonia candicans. DNA is approximately
paralleled by total nuclear protein increases.
The large nucleolus apparently contains most of the nuclear RNA of Galtonia,
except at mitosis, when chromosomal RNA becomes apparent. Nucleolar volume increases
rapidly at first until the cell is midway in development, when it levels off or may
even fall. The nucleolus buds and loses volume in mature guard cells. Cell elongation,
and DNA and protein increases, cease at maturity.
The final state of differentiation may be related to the initial supply of nucleolar
and cytoplasmic material received at mitosis, as well as to environmental differences
such as position between or over veins.
Simple stomata may result from the early initiation of polyploidy in epidermal
cells, and suppression of induction by guard cells.
Observations on the origin of Chloroplasts and Mitochondria in the leaf cells of higher plants
Authors: Vesk M , Mercer FV , Possingham JV
Published: September 2018

The chloroplasts and mitochondria in embryonic and mature mesophyll cells
of maize, spinach, and barley were studied by electron microscopy. The observations
are discussed in relation to theories of organelle status and origins. Some of the e!ectron
micrographs can be interpreted as showing that mitochondria arise from chloroplasts
in mature leaf cells, and lend support to the view, based on cinephotomicrographic
studies, that interconversions between chloroplasts and mitochondria like bodies
occur in living mature leaf cells. In contrast, other electron micrographs can be interpreted
as showing that mitochondria do not arise from chloroplasts, and that the cinephotographic
observations refer to pre-existing mitochondria that have been enclosed
previously by the deformable chloroplast. Electron micrographs of developing cells,
in which the number of organelles increases, do not support the possibility of interconversions
of organelles in young cells. To the contrary, the data for the young cells
suggest that both organelles undergo divisions, supporting the view that the organelles
are autonomous bodies. Some of the difficulties of correlating and interpreting electron
microscope and light microscope observations of the same events are stressed.
Growth of heath vegetation. I. Annual growth curves of two heath ecosystems in Australia
Authors: Groves RH , Specht RL
Published: September 2018

The dry matter production, following fire, of two heath ecosystems in Australia
is presented. The communities are: (i) heath on deep sand; (ii) heath on groundwater
podzol.
In both ecosystems, rapid regrowth occurs followed by a period of reduced
growth when short-lived perennials compete with longer-lived nanophanerophytes.
A second phase of rapid growth has been demonstrated for the sand heath, which
reaches a maximum biomass at 25-50 years after a fire. On the ground-water podzol,
however, resources of soil water and nutrients are seasonably more variable, competition
from rhizomatous monocotyledons is very vigorous, and, within 4-5 years
from burning, no further increase in biomass has as yet been observed.
The floristics and flowering times of the two ecosystems in the same climate of
Wilson's Promontory, Victoria, are compared. Small differences are itemized.
Early stages of plant succession following the complete felling and burning of Eucalyptus regnans forest in the Florentine Valley, Tasmania
Authors: Cremer KW , Mount.A.B .
Published: September 2018

Permanent milacre quadrats were stsdied on a mnge of sites burnt in vario.;s
years. All the recent burns occurred in March.
Low herbs, predominantly bryophytes, colonized about 90% of the ground
12 months after burning, and 99 % 6 months later. Marchantia polymorpha was one of
the earliest colonizers. On the wetter sites it covered up to 75 % of the ground 14 years
after burning, and then declined rapidly. Marchantia growing in exposed places tended
to be killed during summer.
The fire mosses, Funaria hygrometrica and Ceratodon purpureus, colonized
most of the ground not covered by Marchantia and reached peaks of 30-84% cover
about 2 years after the fire. After 5 years the fire mosses had almost disappeared.
Polytrichum juniperinum succeeded Marchantia and the fire mosses, reaching its peak
(38-90 %) about 4 years after burning. Practically all of the low herbs tend to disappear
when the taller vegetation becomes dense.
The taller vegetation tends to be successively dominated in time by herbaceous
fire-weeds, ferns, and woody perennials. Senecio minimus, the most abundant fire-weed,
reached up to 79 %cover 2 years after burning, but died suddenly after reaching its peak.
The development of ferns depended largely on the abundance of rhizomes
surviving the fire (abundance before the fire, nature of fire). Histiopteris incisa and
Hypolepis rugulosa were typical of sites which had carried rain-forest understoreys.
Pteridium esculentum was initially limited to sites which had carried wet sclerophyll
understoreys, but tended to replace the other ferns within 10 years on all but the most
sheltered, moist sites. Although patchy at first, the ferns covered 50% of some areas
within 4 years. Their expansion and persistence seems to be limited mainly by competition
from taller plants.
Most of the woody plants germinated within a few months after the fire from
seed which was either stored in the ground or shed from nearby trees (depending on
the species). Availability of seed and intensity of browsing by native game appear
to be the two main factors which determined the abundance of established woody
plants. Under favourable conditions the woody plants became dominant so early that
the fern stage was by-passed. Intensive browsing was able to delay the dominance
of woody plants, often for many years.
Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT
Authors: Zhang Yuan-Wei , Tavoulari Sotiria , Sinning Steffen , Aleksandrova Antoniya A. , Forrest Lucy R. , Rudnick Gary
Published: September 2018

Significance

Membrane transport proteins are responsible for moving substrates, such as nutrients, vitamins, drugs, and signaling molecules across cellular membranes. A subset of these proteins, the ion-coupled transporters, use a transmembrane ion gradient to drive energetically unfavorable substrate movement from a lower concentration on one side of the membrane to a higher concentration on the other side. They do this by coupling the movement of substrate and ions in the same or the opposite direction. Coupled transport requires conformational changes that occur exclusively or predominantly when specific conditions of ion and substrate binding are met. This work identifies, for a family of Na
+
-coupled neurotransmitter transporters, how the rules controlling these conformational changes are encoded in the transporter structure.
Plastid terminal oxidase requires translocation to the grana stacks to act as a sink for electron transport
Authors: Stepien Piotr , Johnson Giles N.
Published: September 2018

Significance

Growing concerns about food security and changing climates make the identification of stress-tolerance traits a priority. Here we show that the activation of the plastid terminal oxidase, via its relocation within the thylakoid membrane, can induce a protective sink for electron transport. We have thus identified an unexpected mechanism for protein activation and opened avenues for engineering plant stress tolerance.
Americans’ occupational status reflects the status of both of their parents
Authors: Hout Michael
Published: September 2018

American workers’ occupational status strongly reflects the status of their parents. Men and women who grew up in a two-earner or father-breadwinner family achieved occupations that rose 0.5 point for every one-point increase in their parents’ statuses (less if their father was absent). Gender differences were small in two-earner families and mother-only families, but men’s status persisted more when the father was the sole breadwinner. Intergenerational persistence did not change in the time the data cover (1994–2016). Absolute mobility declined for recent birth cohorts; barely half the men and women born in the 1980s were upwardly mobile compared with two-thirds of those born in the 1940s. The results as described hold for a socioeconomic index (SEI) that scores occupation according to the average pay and credentials of people in the occupation. Most results were the same when occupations were coded by different criteria, but SEI produced the smallest gender differences.
Glutamate-activated BK channel complexes formed with NMDA receptors
Authors: Zhang Jiyuan , Guan Xin , Li Qin , Meredith Andrea L. , Pan Hui-Lin , Yan Jiusheng
Published: September 2018

Significance

Large-conductance BK channels are dually activated by voltage and Ca
2+
and play a powerful integrative role in regulating cellular excitability and Ca
2+
signaling in neurons. However, BK channels have a requirement of high intracellular free Ca
2+
concentrations for activation under physiological conditions, and the Ca
2+
sources for their activation are not well understood. In this work, we establish that BK channels physically form protein complexes with Ca
2+
-permeable NMDA receptors via their obligatory BKα and GluN1 subunits. The activation mechanism and function of postsynaptic BK channels at synapses remain largely unknown. We found that postsynaptic BK channels in medial perforant path-dentate gyrus granule cell synapses are activated by NMDA receptor-mediated Ca
2+
influx and modulate excitatory synaptic transmission.
PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling
Authors: Gassaway Brandon M. , Petersen Max C. , Surovtseva Yulia V. , Barber Karl W. , Sheetz Joshua B. , Aerni Hans R. , Merkel Jane S. , Samuel Varman T. , Shulman Gerald I. , Rinehart Jesse
Published: September 2018

Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C ε (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high-fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high-fat diet-induced hepatic insulin resistance. Here, we employed a systems-level approach to uncover additional signaling pathways involved in high-fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high-fat–fed, and high-fat–fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation. This was followed by a functional siRNA-based screen to determine which dynamically regulated phosphoproteins may be involved in canonical insulin signaling. Direct PKCε substrates were identified by motif analysis of phosphoproteomics data and validated using a large-scale in vitro kinase assay. These substrates included the p70S6K substrates RPS6 and IRS1, which suggested cross talk between PKCε and p70S6K in high-fat diet-induced hepatic insulin resistance. These results identify an expanded set of proteins through which PKCε may drive high-fat diet-induced hepatic insulin resistance that may direct new therapeutic approaches for T2D.
Nanoscale remodeling of ryanodine receptor cluster size underlies cerebral microvascular dysfunction in Duchenne muscular dystrophy
Authors: Pritchard Harry A. T. , Pires Paulo W. , Yamasaki Evan , Thakore Pratish , Earley Scott
Published: September 2018

Significance

Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disease that results from mutations in the gene encoding dystrophin. The effects of the disease on cardiac and skeletal muscle have been intensely investigated, but much less is known about how DMD impacts vascular smooth muscle cells (SMCs). Using superresolution nanoscopy, we demonstrate that clusters of ryanodine receptors (RyR2s) on the sarcoplasmic reticulum (SR) of cerebral artery SMCs from themdxmouse model of DMD are larger compared with controls. Increased RyR2 cluster size is associated with augmented SR Ca2+release and Ca2+-activated K+channel activity, resulting in impaired vasoconstriction of cerebral microvessels. Our findings demonstrate that remodeling of RyR2 clusters at the molecular level results in cerebral microvascular dysfunction during DMD.
Morphological transitions of elastic filaments in shear flow
Authors: Liu Yanan , Chakrabarti Brato , Saintillan David , Lindner Anke , du Roure Olivia
Published: September 2018

Significance

Elastic filaments and semiflexible polymers occur ubiquitously in biophysical systems and are key components of many complex fluids, yet our understanding of their conformational dynamics under flow is incomplete. Here, we report on experimental observations of actin filaments in simple shear and characterize their various dynamical regimes from tumbling to buckling and snaking. Numerical simulations accounting for elastohydrodynamics as well as Brownian fluctuations show perfect agreement with measurements. Using a reduced-order theoretical model, we elucidate the unexplained mechanism for the transition to snaking. Our results pave the way for a better understanding of biophysical processes, as well as the rheology of sheared soft materials, and provide a theoretical framework for the exploration of the dynamics of dilute and semidilute suspensions.
Structural fluctuations cause spin-split states in tetragonal (CH
3
NH
3
)PbI
3
as evidenced by the circular photogalvanic effect
Authors: Niesner Daniel , Hauck Martin , Shrestha Shreetu , Levchuk Ievgen , Matt Gebhard J. , Osvet Andres , Batentschuk Miroslaw , Brabec Christoph , Weber Heiko B. , Fauster Thomas
Published: September 2018

Significance

Lead halide perovskites are successfully used in thin-film solar cells, with efficiencies on the laboratory scale exceeding 22%. The electronic structure underlying their exceptional phototransport properties is complex because of the organic–inorganic character of the materials, their mechanical softness, and the strong spin–orbit coupling induced by the constituting heavy elements. Calculations predict that a dynamical Rashba effect could enhance the lifetimes and diffusion lengths of photocarriers in perovskite solar cells. The dynamical Rashba effect is characterized by spin splittings in the band structure at elevated temperatures, induced by local structural disorder. The mechanism should be general to structurally flexible materials composed of heavy elements, making those potentially attractive for both optoelectronics and spintronics.
Decreased water activity in nanoconfinement contributes to the folding of G-quadruplex and i-motif structures
Authors: Jonchhe Sagun , Pandey Shankar , Emura Tomoko , Hidaka Kumi , Hossain Mohammad Akter , Shrestha Prakash , Sugiyama Hiroshi , Endo Masayuki , Mao Hanbin
Published: September 2018

Significance

Nanocavities in cellular compartments or molecular assemblies are commonplace in nature. Nanoconfinement has demonstrated significant effects on the folding of biomolecules, which is mediated by hydration waters. Therefore, understanding the property of water molecules in nanocavities is instrumental to elucidate the confinement effect. By exploiting the known numbers of waters lost during the folding of DNA G-quadruplex and i-motif structures, we quantified that water activities decreased within smaller DNA origami nanocages. This effect is more pronounced than that induced by cosolutes such as polyethylene glycol (PEG). In addition, loss of water molecules during the folding of G-quadruplex and i-motif governs the folding of biomolecules in nanoconfinement.
Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures
Authors: Käufer Christopher , Chhatbar Chintan , Bröer Sonja , Waltl Inken , Ghita Luca , Gerhauser Ingo , Kalinke Ulrich , Löscher Wolfgang
Published: September 2018

Significance

Viral encephalitis is a frequent medical emergency, often resulting in acute seizures and brain damage, which reduce quality of life, promote the development of epilepsy, and can cause death. The relative roles of activation of microglia, the brain-resident innate immune cells, versus invasion of blood-borne immune cells such as monocytes in the acute and chronic consequences of viral encephalitis are only incompletely understood. Here we show that lack of the chemokine receptors CCR2 or CX3CR1, which regulate the responses of myeloid cells such as monocytes and microglia, prevents hippocampal damage but not seizures in a mouse model of viral encephalitis. Treatment strategies aimed at inhibiting peripheral immune cells from entering the brain during encephalitis could reduce brain damage.
Origin of the emergent fragile-to-strong transition in supercooled water
Authors: Shi Rui , Russo John , Tanaka Hajime
Published: September 2018

Significance

Upon cooling, the liquid dynamics generally slow down, with a rate that either keeps constant for a strong liquid or monotonically increases for a fragile one. However, water, silica, and some metallic liquids do not obey this general rule and the rate exhibits a maximum. This unusual phenomenon is known as the fragile-to-strong transition and its origin remains very controversial. Here we show that the fragility of water is only apparent and that it originates from a crossover between a high-temperature liquid without locally favored structures and a low-temperature one full of them, both of which have Arrhenius dynamics. Given its generality, this explanation of dynamic anomalies may be common to any liquids having a tendency to form locally favored structures.
A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum
Authors: Suárez Rodrigo , Paolino Annalisa , Fenlon Laura R. , Morcom Laura R. , Kozulin Peter , Kurniawan Nyoman D. , Richards Linda J.
Published: September 2018

Significance

The neocortex is a hallmark of mammalian evolution, and connections between both hemispheres integrate bilateral functions. In eutherians (e.g., rodents and humans), interhemispheric circuits course via the corpus callosum and share a similar connectome throughout species. Noneutherian mammals (i.e., monotremes and marsupials), however, did not evolve a corpus callosum; therefore, whether the eutherian connectome arose as consequence of callosal evolution or instead reflects ancient connectivity principles remains unknown. We studied monotreme and marsupial interhemispheric neocortical connectomes and compared these with eutherian datasets. This revealed interhemispheric connectivity features shared across mammals, with or without a corpus callosum, suggesting that an ancient connectome originated at least 80 million years before callosal evolution.
Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy
Authors: Ho Peggy P. , Lahey Lauren J. , Mourkioti Foteini , Kraft Peggy E. , Filareto Antonio , Brandt Moritz , Magnusson Klas E. G. , Finn Eric E. , Chamberlain Jeffrey S. , Robinson William H. , Blau Helen M. , Steinman Lawrence
Published: September 2018

Significance

Duchenne muscular dystrophy is a genetic disorder in which mutations in the dystrophin gene causes severe muscle wasting. A proposed treatment method involves systemic gene replacement therapy to introduce a functional dystrophin gene to the skeletal and cardiac muscles of the patient via rAAV6. A potentially serious problem may arise from immune recognition of dystrophin and the accompanying adeno-associated viral (AAV) vector. This unwanted immunity could interfere with successful long-term dystrophin expression by muscle cells. To suppress the unwanted immune response, a DNA vaccine was engineered to dampen immunity to both dystrophin and AAV6 capsid. Development of this engineered plasmid aims to improve gene replacement therapy and to overcome problems inherent with unwanted immunity to the encoded protein and to the delivery vector.
Evolution of metazoan morphological disparity
Authors: Deline Bradley , Greenwood Jennifer M. , Clark James W. , Puttick Mark N. , Peterson Kevin J. , Donoghue Philip C. J.
Published: September 2018

Significance

We attempt to quantify animal “bodyplans” and their variation within Metazoa. Our results challenge the view that maximum variation was achieved early in animal evolutionary history by nonuniformitarian mechanisms. Rather, they are compatible with the view that the capacity for fundamental innovation is not limited to the early evolutionary history of clades. We perform quantitative tests of the principal hypotheses of the molecular mechanisms underpinning the establishment of animal bodyplans and corroborate the hypothesis that animal evolution has been permitted or driven by gene regulatory evolution.
Ultrahigh-throughput functional profiling of microbiota communities
Authors: Terekhov Stanislav S. , Smirnov Ivan V. , Malakhova Maja V. , Samoilov Andrei E. , Manolov Alexander I. , Nazarov Anton S. , Danilov Dmitry V. , Dubiley Svetlana A. , Osterman Ilya A. , Rubtsova Maria P. , Kostryukova Elena S. , Ziganshin Rustam H. , Kornienko Maria A. , Vanyushkina Anna A. , Bukato Olga N. , Ilina Elena N. , Vlasov Valentin V. , Severinov Konstantin V. , Gabibov Alexander G. , Altman Sidney
Published: September 2018

Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of the host organisms. Furthermore, exotic sources of microbiota represent an unexplored niche to discover microbial secondary metabolites. However, establishing the bacterial functionality is complicated by an intricate web of interactions inside the microbiome. Here we apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of the entire oral microbial community of the Siberian bear to isolate
Bacillus
strains demonstrating antimicrobial activity against
Staphylococcus aureus
. Genome mining allowed us to identify antibiotic amicoumacin A (Ami) as responsible for inhibiting the growth of
S. aureus
. Proteomics and metabolomics revealed a unique mechanism of
Bacillus
self-resistance to Ami, based on a subtle equilibrium of its deactivation and activation by kinase AmiN and phosphatase AmiO, respectively. We developed uHT quantitative single-cell analysis to estimate antibiotic efficacy toward different microbiomes and used it to determine the activity spectra of Ami toward human and Siberian bear microbiota. Thus, uHT microfluidic droplet platform activity profiling is a powerful tool for discovering antibiotics and quantifying external influences on a microbiome.
Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms
Authors: Shen Kuang , Sabatini David M.
Published: September 2018

Significance

Amino acids are basic building blocks for all organisms and are essential for cell growth and proliferation. Cells use a set of protein machines to sense the availability of amino acids to carry out basic responses. In particular, the mTORC1 pathway is a central sensor of amino acids in mammalian cells. Residing on the lysosomal surface upon activation, mTORC1 processes signals from the upstream Rag GTPases and stimulates downstream effectors through phosphorylation cascades. Ragulator and SLC38A9 are key components of the lysosomal branch of the amino acid-sensing machinery upstream of the Rag GTPases, but how they regulate the Rag GTPases at the molecular level remains poorly understood. Here we used kinetic analyses to define their functions.
VPS13: A lipid transfer protein making contacts at multiple cellular locations
Authors: Gao Mingming , Yang Hongyuan
Published: September 2018

The evolutionarily conserved VPS13 proteins localize to multiple membrane contact sites though their function and regulation has been elusive. Bean et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201804111) found that competitive adaptors control the different localizations of yeast Vps13p, while Kumar et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201807019) provide biochemical and structural evidence for VPS13 proteins in the nonvesicular transport of phospholipids.
Prediction of protein group function by iterative classification on functional relevance network
Authors: Khan Ishita K , Jain Aashish , Rawi Reda , Bensmail Halima , Kihara Daisuke
Published: September 2018

Motivation

Biological experiments including proteomics and transcriptomics approaches often reveal sets of proteins that are most likely to be involved in a disease/disorder. To understand the functional nature of a set of proteins, it is important to capture the function of the proteins as a group, even in cases where function of individual proteins is not known. In this work, we propose a model that takes groups of proteins found to work together in a certain biological context, integrates them into functional relevance networks, and subsequently employs an iterative inference on graphical models to identify group functions of the proteins, which are then extended to predict function of individual proteins.

Results

The proposed algorithm, iterative group function prediction (iGFP), depicts proteins as a graph that represents functional relevance of proteins considering their known functional, proteomics and transcriptional features. Proteins in the graph will be clustered into groups by their mutual functional relevance, which is iteratively updated using a probabilistic graphical model, the conditional random field. iGFP showed robust accuracy even when substantial amount of GO annotations were missing. The perspective of ‘group’ function annotation opens up novel approaches for understanding functional nature of proteins in biological systems.

Availability and implementation: http://kiharalab.org/iGFP/

Supplementary information

Supplementary data are available at Bioinformatics online.
A graphical model for skewed matrix-variate non-randomly missing data
Authors: Zhang Lin , Bandyopadhyay Dipankar
Published: September 2018

Epidemiological studies on periodontal disease (PD) collect relevant bio-markers, such as the clinical attachment level (CAL) and the probed pocket depth (PPD), at pre-specified tooth sites clustered within a subject’s mouth, along with various other demographic and biological risk factors. Routine cross-sectional evaluation are conducted under a linear mixed model (LMM) framework with underlying normality assumptions on the random terms. However, a careful investigation reveals considerable non-normality manifested in those random terms, in the form of skewness and tail behavior. In addition, PD progression is hypothesized to be spatially-referenced, i.e. disease status at proximal tooth-sites may be different from distally located sites, and tooth missingness is non-random (or informative), given that the number and location of missing teeth informs about the periodontal health in that region. To mitigate these complexities, we consider a matrix-variate skew-$t$ formulation of the LMM with a Markov graphical embedding to handle the site-level spatial associations of the bivariate (PPD and CAL) responses. Within the same framework, the non-randomly missing responses are imputed via a latent probit regression of the missingness indicator over the responses. Our hierarchical Bayesian framework powered by relevant Markov chain Monte Carlo steps addresses the aforementioned complexities within an unified paradigm, and estimates model parameters with seamless sharing of information across various stages of the hierarchy. Using both synthetic and real clinical data assessing PD status, we demonstrate a significantly improved fit of our proposition over various other alternative models.
Microaggression and everyday resistance in narratives of refugee resettlement
Authors: El-Bialy Rowan , Mulay Shree
Published: September 2018

The mental health of resettled refugees is not only affected by the trauma they experience before and while fleeing persecution, but also by experiences during the resettlement process. Drawing on a qualitative study of refugees’ experiences of mental wellbeing in a small Canadian city this paper documents participants’ experiences of microaggression and everyday resistance. In our analysis, we refer to the metaphor of uprooting that is often used to describe the totality of refugee displacement. In our expansion of the metaphor, microaggression re-uproots resettled refugees by challenging their right to be where they are. Using acts of everyday resistance, participants in our sample attempted to set down roots in the resettlement context despite microaggressions. Participants’ acts of everyday resistance are captured under five themes: rejecting victimhood, rejecting burden narratives, ignorance as an explanation, the transience of vulnerability, and setting down roots. This study contributes to the literature that de-emphasizes the vulnerability narrative of refugee mental health by demonstrating the role of personal agency in refugees’ experiences of their own wellbeing.
Should Sex Be Considered an Effect Modifier in the Evaluation of Influenza Vaccine Effectiveness?
Authors: Chambers Catharine , Skowronski Danuta M , Rose Caren , Serres Gaston De , Winter Anne-Luise , Dickinson James A , Jassem Agatha , Gubbay Jonathan B , Fonseca Kevin , Drews Steven J , Charest Hugues , Martineau Christine , Petric Martin , Krajden Mel
Published: September 2018

We investigated sex as a potential modifier of influenza vaccine effectiveness (VE) between 2010–2011 and 2016–2017 in Canada. Overall VE was 49% (95% confidence interval [CI], 43% to 55%) for females and 38% (95% CI, 28% to 46%) for males (absolute difference [AD], 11%; P = .03). Sex differences were greatest for influenza A(H3N2) (AD, 17%; P = .07) and B(Victoria) (AD, 20%; P = .08) compared with A(H1N1)pdm09 (AD, 10%; P = .19) or B(Yamagata) (AD, –3%; P = .68). They were also more pronounced in older adults ≥50 years (AD, 19%; P = .03) compared with those <20 years (AD, 4%; P = .74) or 20–49 years (AD, –1%; P = .90) but with variation by subtype/lineage. More definitive investigations of VE by sex and age are warranted to elucidate these potential interactions.
Saving Water with a Nudge (or Two): Evidence from Costa Rica on the Effectiveness and Limits of Low-Cost Behavioral Interventions on Water Use
Authors: Miranda Juan Jose , Datta Saugato , Zoratto Laura
Published: September 2018

The study uses a randomized controlled trial to test the impact of simple, inexpensive, and nonpersonalized behavioral interventions (or “nudges”) on water consumption in the context of a developing country. A descriptive social norm intervention using neighborhood comparisons reduces average water consumption in the first two postintervention months by 4.9 percent relative to the control group, while a planning postcard intervention reduces consumption by 4.8 percent. A descriptive social norm intervention using a town-level comparison also reduces water consumption by 3.2 percent, but this effect is not statistically significant. Finally, the study's one-time interventions continue to generate statistically significant reductions in water use for up to four months after they are implemented.
An inhibitor-interaction intermediate of HIV-1 protease, revealed by Isothermal Titration Calorimetry and NMR spectroscopy
Authors: Khan Shahid N , Persons John D , Guerrero Michel , Ilina Tatiana V. , Oda Masayuki , Ishima Rieko
Published: September 2018

Some of drug-resistant mutants of HIV-1 protease (PR), such as a clinically-relevant drug- resistant PR mutant (Flap+(I54V)) containing L10I, G48V, I54V and V82A mutations, produce significant changes in the balance between entropy and enthalpy of the drug-PR interactions, compared to the wild-type (WT) PR. Here, to gain a comprehensive understanding of the entropy-enthalpy compensation effects, we compared nuclear magnetic resonance (NMR), fluorescence spectroscopy and isothermal titration calorimetry (ITC) data of a WT PR with Flap+(I54V)and related mutants: (1) Flap+(I54V); (2) Flap+(I54A)which evolves from Flap+(I54V)in the continued presence of inhibitor yet does not exhibit entropy-enthalpy compensation; and (3) Flap+(I54), a control mutant that contains only L10I, G48V and V82A mutations. Our data indicate that WT and Flap+(I54A)show enthalpy-driven inhibitor-interaction, while Flap+(I54)and Flap+(I54V)exhibit entropy-driven inhibitor interaction. Interestingly, Flap+(I54A)exhibited significantly slower heat flow in the competitive ITC experiment with a strong binder, darunavir, and a weak binder, acetyl-pepstatin, but did not exhibit such slow heat flow in the direct inhibitor-titration experiments. NMR confirmed replacement of the weak binder by the strong binder in a competitive manner. This difference in the heat flow of the competitive binding experiment compared to the direct experiment can only be explained by assuming an inhibitor-bound intermediate pathway. A similar, but attenuated, tendency for slow heat flow was also detected in the competitive experiment with WT. Overall, our data suggests that an inhibitor-bound intermediate affects the entropy-enthalpy compensation of inhibitor-PR interaction.
Eps8 is a convergence point integrating EGFR and integrin trafficking and crosstalk
Authors: Paul Nikki R , Thomas Joanna R , Maldonado Horacio , Wolanska Katarzyna I , Koper Ewa J , Humphries Jonathan D , Byron Adam , George Adams , Allen Nathan , Prior Ian A , Streuli Charles H , Humphries Martin J , Morgan Mark R
Published: September 2018

Crosstalk between adhesion and growth factor receptors plays a critical role in tissue morphogenesis and repair, and aberrations contribute substantially to neoplastic disease. However, the mechanisms by which adhesion and growth factor receptor signalling are integrated, spatially and temporally, are unclear.

We used adhesion complex enrichment coupled with quantitative proteomic analysis to identify rapid changes to adhesion complex composition and signalling following growth factor stimulation. Bioinformatic network and ontological analyses revealed a substantial decrease in the abundance of adhesion regulatory proteins and co-ordinators of endocytosis within 5 minutes of EGF stimulation. Together these data suggested a mechanism of EGF-induced receptor endocytosis and adhesion complex turnover.

Combinatorial interrogation of the networks allowed a global and dynamic view of adhesion and growth factor receptor crosstalk to be assembled. By interrogating network topology we identified Eps8 as a putative node integrating α5β1 integrin and EGFR functions. Importantly, EGF stimulation promoted internalisation of both α5β1 and EGFR. However, perturbation of Eps8 increased constitutive internalisation of α5β1 and EGFR; suggesting that Eps8 constrains α5β1 and EGFR endocytosis in the absence of EGF stimulation. Consistent with this, Eps8 regulated Rab5 activity and was required for maintenance of adhesion complex organisation and for EGF-dependent adhesion complex disassembly. Thus, by co-ordinating α5β1 and EGFR trafficking mechanisms, Eps8 is able to control adhesion receptor and growth factor receptor bioavailability and cellular contractility.

We propose that during tissue morphogenesis and repair, Eps8 functions to spatially and temporally constrain endocytosis, and engagement, of α5β1 and EGFR in order to precisely co-ordinate adhesion disassembly, cytoskeletal dynamics and cell migration.
More partners, more ranges: generalist legumes spread more easily around the globe
Authors: Harrison Tia L. , Simonsen Anna K. , Stinchcombe John R. , Frederickson Megan E.
Published: September 2018

How does mutualism affect range expansion? On one hand, mutualists might thrive in new habitats thanks to the resources, stress tolerance, or defense provided by their partners. On the other, specialized mutualists might fail to find compatible partners beyond their range margins, limiting further spread. A recent global analysis of legume ranges found that non-symbiotic legumes have been successfully introduced to more ranges than legumes that form symbioses with rhizobia, but there is still abundant unexplained variation in introduction success within symbiotic legumes. Here, we test the hypothesis that generalist legumes have spread to more introduced ranges than specialist legumes. We used published data and rhizobial 16S rRNA sequences from GenBank to quantify the number of rhizobia partners that associate with each of 159 legume species, spanning the legume phylogeny and the globe. We found that generalist legumes occur in more introduced ranges than specialist legumes, suggesting that among mutualists, specialization hinders range expansions.
mTADA: a framework for analyzing de novo mutations in multiple traits
Authors: Nguyen Hoang T. , Dobbyn Amanda , Buxbaum Joseph , Pinto Dalila , Purcell Shaun M , Sullivan Patrick F , He Xin , Stahl Eli A.
Published: September 2018

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. In addition, approaches that consider multiple traits can aid in the characterization of shared genetic etiology among those traits. In recent years, parent-offspring trio studies have reported an enrichment ofde novomutations (DNMs) in neuropsychiatric disorders. The analysis of DNM data in the context of neuropsychiatric disorders has implicated multiple putatively causal genes, and a number of reported genes are shared across disorders. However, a joint analysis method designed to integrate de novo mutation data from multiple studies has yet to be implemented. We here introduce multi pi e-trait TAD A (mTADA) which jointly analyzes two traits using DNMs from non-overlapping family samples. mTADA uses two single-trait analysis data sets to estimate the proportion of overlapping risk genes, and reports genes shared between and specific to the relevant disorders. We applied mTADA to >13,000 trios for six disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), developmental disorders (DD), intellectual disability (ID), epilepsy (EPI), and congenital heart disease (CHD). We report the proportion of overlapping risk genes and the specific risk genes shared for each pair of disorders. A total of 153 genes were found to be shared in at least one pair of disorders. The largest percentages of shared risk genes were observed for pairs of DD, ID, ASD, and CHD (>20%) whereas SCZ, CHD, and EPI did not show strong overlaps In risk gene set between them. Furthermore, mTADA identified additional SCZ, EPI and CHD risk genes through integration with DDde novomutation data. For CHD, using DD information, 31 risk genes with posterior probabilities > 0.8 were identified, and 20 of these 31 genes were not in the list of known CHD genes. We find evidence that most significant CHD risk genes are strongly expressed in prenatal stages of the human genes. Finally, we validated our findings for CHD and EPI in independent cohorts comprising 1241 CHD trios, 226 CHD singletons and 197 EPI trios. Multiple novel risk genes identified by mTADA also had de novo mutations in these independent data sets. The joint analysis method introduced here, mTADA, is able to identify risk genes shared by two traits as well as additional risk genes not found through single-trait analysis only. A number of risk genes reported by mTADA are identified only through joint analysis, specifically when ASD, DD, or ID are one of the two traits examined. This suggests that novel genes for the trait or a new trait might converge to a core gene list of the three traits.