bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-sector approximation method for arteries: the residual stresses of circumferential rings with non-trivial openings
Authors: Sigaeva Taisiya , Destrade Michel , Di Martino Elena S.
Published: July 2019

The opening angle method is a popular choice in biomechanics to estimate residual stresses in arteries. Experimentally, it means that an artery is cut into rings; then the rings are cut axially or radially allowing them to open into sectors; finally, the corresponding opening angles are measured to give residual stress levels by solving an inverse problem. However, for many tissues, for example in pathological tissues, the ring does not open according to the theory into a neat single circular sector, but rather creates an asymmetric geometry, often with abruptly changing curvature(s). This phenomenon may be due to a number of reasons including variation in thickness, microstructure, mechanical properties, etc. As a result, these samples are often eliminated from studies relying on the opening angle method, which limits progress in understanding and evaluating residual stresses in real arteries. With this work, we propose an effective approach to deal with these non-trivial openings of rings. First, we digitize pictures of opened rings to split them into multiple, connected circular sectors. Then we measure the corresponding opening angles for each sub-sector. Subsequently, we can determine the residual stresses for individual sectors in a closed-ring configuration and, thus, approximate the circumferential residual bending effects.
Hot wings: thermal impacts of wing coloration on surface temperature during bird flight
Authors: Rogalla Svana , D'Alba Liliana , Verdoodt Ann , Shawkey Matthew D.
Published: July 2019

Recent studies on bird flight propose that hotter wing surfaces reduce skin friction drag, thereby improving flight efficiency (lift-to-drag ratio). Darker wings may in turn heat up faster under solar radiation than lighter wings. We used three methods to test the impact of colour on wing surface temperature. First, we modelled surface temperature based on reflectance measurements. Second, we used thermal imaging on live ospreys (Pandion haliaetus) to examine surface temperature changes with increasing solar irradiance. Third, we experimentally heated differently coloured wings in a wind tunnel and measured wing surface temperature at realistic flight speeds. Even under simulated flight conditions, darker wings consistently became hotter than pale wings. In white wings with black tips, the temperature differential produced convective currents towards the darker wing tips that could lead to an increase in lift. Additionally, a temperature differential between wing-spanning warm muscles and colder flight feathers could delay the flow separation above the wing, increasing flight efficiency. Together, these results suggest that wing coloration and muscle temperature both play important roles in modulating wing surface temperature and therefore potentially flight efficiency.
Evolution of coordinated punishment to enforce cooperation from an unbiased strategy space
Authors: García Julián , Traulsen Arne
Published: July 2019

The emergence and maintenance of punishment to protect the commons remains an open puzzle in social and biological sciences. Even in societies where pro-social punishing is common, some individuals seek to cheat the system if they see a chance to do so—and public goods are often maintained in spite of cheaters who do not contribute. We present a model accounting for all possible strategies in a public goods game with punishment. While most models of punishment restrict the set of possible behaviours, excluding seemingly paradoxical anti-social strategies from the start, we show that these strategies can play an important role in explaining large-scale cooperation as observed in human societies. We find that coordinated punishment can emerge from individual interactions, but the stability of the associated institutions is limited owing to anti-social and opportunistic behaviour. In particular, coordinated anti-social punishment can undermine cooperation if individuals cannot condition their behaviour on the existence of institutions that punish. Only when we allow for observability and conditional behaviours do anti-social strategies no longer threaten cooperation. This is due to a stable coexistence of a minority supporting pro-social institutions and those who only cooperate if such institutions are in place. This minority of supporters is enough to guarantee substantial cooperation under a wide range of conditions. Our findings resonate with the empirical observation that public goods are resilient to opportunistic cheaters in large groups of unrelated individuals. They also highlight the importance of letting evolution, and not modellers, decide which strategies matter.
The protective and pathogenic roles of IL-17 in viral infections: friend or foe?
Authors: Ma Wen-Tao , Yao Xiao-Ting , Peng Qun , Chen De-Kun
Published: July 2019

Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide. Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication. However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check. Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases. Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses. Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option. Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms. The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.
Novel biomass-derived smoke-like carbon as a supercapacitor electrode material
Authors: Chu Mingxu , Li Mingtang , Han Zhaolian , Cao Jinshan , Li Rui , Cheng Zhiqiang
Published: July 2019

In this present work, smoke-like carbon was successfully fabricated from a bio-waste fungal substrate crude polysaccharide for the first time. The as-prepared products possess smoke-like structures, ultra-high specific surface area (
S
BET
: 2160 m
2
g
−1
) and a high content of micropores (microporous surface area of 60%, with a nanopore size of 0.70 nm), which can increase the specific capacitance, representing a wonderful structure for electrochemical energy storage devices. The as-prepared sample displayed an excellent specific capacitance of 152 F g
−1
at 5 A g
−1
in the three-electrode configuration and exhibited maximal densities of 6.8–10.2 W h kg
−1
under power outputs of 253.4–24.3 kW kg
−1
. We believe that this work demonstrates a simple, green and low-cost route by using agricultural residue to prepare applicable carbon materials for use in energy storage devices.
Generalized regression neural network association with terahertz spectroscopy for quantitative analysis of benzoic acid additive in wheat flour
Authors: Sun Xudong , Liu Junbin , Zhu Ke , Hu Jun , Jiang Xiaogang , Liu Yande
Published: July 2019

Investigations were initiated to develop terahertz (THz) techniques associated with machine learning methods of generalized regression neural network (GRNN) and back-propagation neural network (BPNN) to rapidly measure benzoic acid (BA) content in wheat flour. The absorption coefficient exhibited a maximum absorption peak at 1.94 THz, which generally increased with the content of BA additive. THz spectra were transformed into orthogonal principal component analysis (PCA) scores as the input vectors of GRNN and BPNN models. The best GRNN model was achieved with three PCA scores and
spread
value of 0.2. Compared with the BPNN model, GRNN model to powder samples could be considered very successful for quality control of wheat flour with a correlation coefficient of prediction (
r
p
) of 0.85 and root mean square error of prediction of 0.10%. The results suggest that THz technique association with GRNN has a significant potential to quantitatively analyse BA additive in wheat flour.
Role of pulping process as synergistic treatment on performance of agro-based activated carbons
Authors: Basta Altaf H. , Lotfy Vivian F. , Trens Philippe
Published: July 2019

To recommend the beneficial effect of the pulping process on enhancing agro-wastes as precursors for the production of high-performance activated carbons (ACs), different pulping methods (alkali, sulfite and neutral sulfite) were applied on two available Egyptian agriculture by-products (rice straw and sugar cane bagasse), using the one-step pyrolysis method and H3PO4activating agent. The adsorption performance of the different prepared ACs was evaluated in terms of Iodine Numbers and their sorption properties for removing the methylene blue (MB) from aqueous solutions. The corresponding sorption processes were also analysed using Lagergren first order, pseudo-second order and intraparticle diffusion models. Data revealed that the applied pulping conditions were effective for removing the non-cellulosic constituents of agro-residues. This was demonstrated by the hydrogen/carbon and oxygen/carbon ratios, thermal stability and IR-measurements of the final pulps. These data were effective on the particular sorption properties of RS and SCB-based ACs. Interestingly, the pulping process is a profound modification of the SCB-based fibres, on which it induced a clear increase of the specific surface areas of the corresponding ACs even though they had an impact on the sorption of MB and iodine. These values are superior to the reported data on agro-based ACs with H3PO4activators. Pulping processes therefore play a dual role in the sorption properties of ACs. The first important role is the impact on the specific surface areas and the second impact is a profound modification of the surface chemistry of the ACs. Therefore, SCB-based ACs can be seen as an economical breakthrough product, and an alternative to the high-cost commercial ACs for the purification of industrial wastewaters.
Application of statistical design to evaluate critical process parameters and optimize formulation technique of polymeric nanoparticles
Authors: Sarkar Pradipta , Bhattacharya Saswati , Pal Tapan Kumar
Published: July 2019

In advanced medication, drug-loaded polymeric nanoparticles (NPs) appeared as a novel drug delivery system with lots of advantages over conventional medicines. Despite all the advantages, NPs do not gain popularity for manufacturing hurdles. The study focused on the formulation difficulties and implementation of statistical design to establish an effective model for manufacturing NPs. In this study, physico-chemical properties of the drug and polymer (PLGA) were incorporated to understand the mechanistic insights of nanoformulations. Primarily, the process controlling parameters were screened by Plackett–Burman design and the critical process parameters (Cpp) were further fabricated by Box–Behnken design (BBD). The TLM-PLGA-NPs (telmisartan loaded PLGA NPs) exhibited particle size, encapsulation efficiency and zeta potential of 232.4 nm, 79.21% and −9.92 mV respectively. The NPs represented drug loading of 76.31%. Korsmeyer–Peppas model (R2= 0.925) appeared to be the best fitted model forin vitrorelease kinetics of NPs. The model identified Fickian diffusion of TLM from the polymeric nanoparticles. The ANOVA results of variables indicate that BBD is a suitable model for the development of polymeric NPs. The study successfully identified and evaluated the correlation of significant parameters that were directly or indirectly influencing the formulations which deliberately produce desired nanoparticles with the help of statistical design.
A one-dimensional individual-based mechanical model of cell movement in heterogeneous tissues and its coarse-grained approximation
Authors: Murphy R. J. , Buenzli P. R. , Baker R. E. , Simpson M. J.
Published: July 2019

Mechanical heterogeneity in biological tissues, in particular stiffness, can be used to distinguish between healthy and diseased states. However, it is often difficult to explore relationships between cellular-level properties and tissue-level outcomes when biological experiments are performed at a single scale only. To overcome this difficulty, we develop a multi-scale mathematical model which provides a clear framework to explore these connections across biological scales. Starting with an individual-based mechanical model of cell movement, we subsequently derive a novel coarse-grained system of partial differential equations governing the evolution of the cell density due to heterogeneous cellular properties. We demonstrate that solutions of the individual-based model converge to numerical solutions of the coarse-grained model, for both slowly-varying-in-space and rapidly-varying-in-space cellular properties. We discuss applications of the model, such as determining relative cellular-level properties and an interpretation of data from a breast cancer detection experiment.
Reversible signal transmission in an active mechanical metamaterial
Authors: Browning Alexander P. , Woodhouse Francis G. , Simpson Matthew J.
Published: July 2019

Mechanical metamaterials are designed to enable unique functionalities, but are typically limited by an initial energy state and require an independent energy input to function repeatedly. Our study introduces a theoretical active mechanical metamaterial that incorporates a biological reaction mechanism to overcome this key limitation of passive metamaterials. Our material allows for reversible mechanical signal transmission, where energy is reintroduced by the biologically motivated reaction mechanism. By analysing a coarse-grained continuous analogue of the discrete model, we find that signals can be propagated through the material by a travelling wave. Analysis of the continuum model provides the region of the parameter space that allows signal transmission, and reveals similarities with the well-known FitzHugh–Nagumo system. We also find explicit formulae that approximate the effect of the time scale of the reaction mechanism on the signal transmission speed, which is essential for controlling the material.
Anisotropic bidispersive convection
Authors: Straughan B.
Published: July 2019

This paper investigates thermal convection in an anisotropic bidisperse porous medium. A bidisperse porous medium is one which possesses the usual pores, but in addition, there are cracks or fissures in the solid skeleton and these give rise to a second porosity known as micro porosity. The novelty of this paper is that the macro permeability and the micro permeability are each diagonal tensors but the three components in the vertical and in the horizontal directions may be distinct in both the macro and micro phases. Thus, there are six independent permeability coefficients. A linear instability analysis is presented and a fully nonlinear stability analysis is inferred. Several Rayleigh number and wavenumber calculations are presented and it is found that novel cell structures are predicted which are not present in the single porosity case.
Economic trust in young children
Authors: Rosati Alexandra G. , Benjamin Natalie , Pieloch Kerrie , Warneken Felix
Published: July 2019

Mutually beneficial interactions often require trust that others will reciprocate. Such interpersonal trust is foundational to evolutionarily unique aspects of human social behaviour, such as economic exchange. In adults, interpersonal trust is often assessed using the ‘trust game’, in which a lender invests resources in a trustee who may or may not repay the loan. This game captures two crucial elements of economic exchange: the potential for greater mutual benefits by trusting in others, and the moral hazard that others may betray that trust. While adults across cultures can trust others, little is known about the developmental origins of this crucial cooperative ability. We developed the first version of the trust game for use with young children that addresses these two components of trust. Across three experiments, we demonstrate that 4- and 6-year-olds recognize opportunities to invest in others, sharing more when reciprocation is possible than in a context measuring pure generosity. Yet, children become better with age at investing in trustworthy over untrustworthy partners, indicating that this cooperative skill emerges later in ontogeny. Together, our results indicate that young children can engage in complex economic exchanges involving judgements about interpersonal trust and show increasing sensitivity to appropriate partners over development.
Temperature- versus precipitation-limitation shape local temperature tolerance in a Holarctic freshwater crustacean
Authors: Seefeldt Leonie , Ebert Dieter
Published: July 2019

Species with wide geographical distributions are often adapted locally to the prevailing temperatures. To understand how they respond to ongoing climatic change, we must appreciate the interplay between temperature, seasonality and the organism's life cycle. The temperature experienced by many organisms results from an often-overlooked combination of climate and phenology. Summer-active (high latitude) populations are expected to adapt to local summer temperatures, but this is not expected for populations that outlive the summer in their dormant stage (low latitude, precipitation-limited). We recorded reproduction and survival in genotypes from 123 Holarctic populations ofDaphnia magnaduring a multi-generation thermal ramp experiment. Genotypes from summer-active populations showed a positive relationship between heat tolerance and local summer temperature, whereas winter-active populations did not. These findings are consistent with the hypothesis thatD. magnaadapts to the local temperatures the animals experience during their planktonic phase. We conclude that predicting local temperature adaptation, in particular in the light of climate change, needs to consider the phenology of geographically wide-ranging species.
Capillary Morphogenesis gene 2 mediates multiple pathways of growth factor-induced angiogenesis by regulating endothelial cell chemotaxis
Authors: Cryan Lorna , Tsang Tsz-Ming , Stiles Jessica , Bazinet Lauren , Lee Sai Lun , Garrard Samuel , Roberts Cody , Payne Jessie , Ackroyd P. Christine , Christensen Kenneth A. , Rogers Michael S.
Published: July 2019

Pathological angiogenesis contributes to diseases as varied as cancer and corneal neovascularization. The vascular endothelial growth factor (VEGF) - VEGF receptor 2 (KDR/VEGFR2) axis has been the major target for treating pathological angiogenesis. However, VEGF-targeted therapies exhibit reduced efficacy over time, indicating that new therapeutic strategies are needed. Therefore, identifying new targets that mediate angiogenesis is of great importance. Here, we report that one of the anthrax toxin receptors, capillary morphogenesis gene 2 (ANTXR2/CMG2), plays an important role in mediating angiogenesis induced by both bFGF and VEGF. Inhibiting physiological ligand binding to CMG2 results in significant reduction of corneal neovascularization, endothelial tube formation and cell migration. We also report the novel finding that CMG2 mediates angiogenesis by regulating the direction of endothelial chemotactic migration without affecting overall cell motility.
Bacterially produced GABA protects neurons from degeneration
Authors: Urrutia Arles , Garcia Victor A. , Fuentes Andres , Caneo Mauricio , Legüe Marcela , Urquiza Sebastián , Ugalde Juan , Burdisso Paula , Calixto Andrea
Published: July 2019

Caenorhabditis elegansand its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used inC. elegansas surrogates for neurodegeneration. One of these is aC. elegansstrain expressing a neurotoxic allele of the MEC-4(d) DEG/ENaC channel which causes the progressive degeneration of the touch receptor neurons (TRNs). Using such model, this study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. While degeneration of TRNs was steadily carried and completed at adulthood in the strain routinely used forC. elegansmaintenanceEscherichia coliOP50, it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in theE. coliHT115 strain. HT115 protection was long lasting well into old age of animals and not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of the DAF-16/FOXO transcription factor, a phenomenon previously reported to underlie neuroprotection caused by downregulation of the insulin receptor in this system. Moreover, adaf-16loss of function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) as a metabolite differentially produced betweenE. coliHT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover,in situGABA supplementation or heterologous expression of glutamate decarboxylase inE. coliOP50 conferred neuroprotective activity to this strain. SpecificC. elegansGABA transporters and receptors were required for full HT115-mediated neuroprotection. Together, these results demonstrate that bacterially produced GABA exerts an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis.
Genome-wide, integrative analysis implicates circular RNA dysregulation in autism and the corresponding circular RNA-microRNA-mRNA regulatory axes
Authors: Chen Yen-Ju , Chen Chia-Ying , Mai Te-Lun , Chuang Chih-Fan , Gupta Sachin Kumar , Yen Laising , Wang Yi-Da , Chuang Trees-Juen
Published: July 2019

Circular RNAs (circRNAs), a class of long non-coding RNAs, are known to be enriched in mammalian brain and neural tissues. While the effects of regulatory genetic variants on gene expression in autism spectrum disorder (ASD) have been widely reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in post-mortem brains from individuals with ASD and controls and identified 60 circRNAs and three co-regulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8,170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This result reflects the previous observation that ASD-derived organoids exhibit overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were indeed regulated by an upregulated circRNA (circARID1A) via sponging a downregulated microRNA (miR-204-3p) in human neuronal cells. We provided a systems-level view of landscape of circRNA regulatory networks in ASD cortex samples. We also provided multiple lines of evidence for the functional role of ASD for circRNA dysregulation and a rich set of ASD-associated circRNA candidates and the corresponding circRNA-miRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.
No evidence for functional distinctions across fronto-temporal language regions in their temporal receptive windows
Authors: Blank Idan A. , Fedorenko Evelina
Published: July 2019

The “core language network” consists of left temporal and frontal regions that are selectively engaged in linguistic processing. Whereas the functional differences across these regions have long been debated, many accounts propose distinctions in terms of representational grain-size—e.g., wordsvs.sentences—or processing time-scale, i.e., operating on local linguistic featuresvs.larger spans of input. Indeed, the topography of language regions appears to overlap with a cortical hierarchy reported by Lerner et al. (2011) wherein mid-posterior temporal regions are sensitive to low-level features of speech, surrounding areas—to word-level information, and inferior frontal areas—to sentence-level information and beyond. However, the correspondence between the language network and this hierarchy of “temporal receptive windows” (TRWs) is difficult to establish because the precise anatomical locations of language regions vary across individuals. To directly test this correspondence, we first identified language regions in each participant with a task-based localizer, which confers high functional resolution to the study of TRWs (traditionally based on stereotactic coordinates); then, we characterized regional TRWs with the naturalistic story listening paradigm of Lerner et al. (2011), which augments task-based characterizations of the language network by more closely resembling comprehension “in the wild”. We find no region-by-TRW interactions across temporal and inferior frontal regions, which are all sensitive to both word-level and sentence-level information. Therefore, the language network as a whole constitutes a unique stage of information integration within a broader cortical hierarchy.

Highlights

Language regions are identified with task-based, participant-specific localization.

A progressively scrambled naturalistic story probes regional processing timescales.

Widespread sensitivity to scrambling at the timescales of both words and sentences.

No processing timescale distinctions across temporal and inferior-frontal regions.

These regions all occupy a common, unique stage in a broader processing hierarchy.
Ovarian hormones mediate the prophylactic efficacy of (R,S)-ketamine and (2R,6R)-hydroxynorketamine in female mice
Authors: Chen Briana K. , LaGamma Christina T. , Xu Xiaoming , Deng Shi-Xian , Brachman Rebecca A. , Suckow Raymond F. , Cooper Thomas B. , Landry Donald W. , Denny Christine A.
Published: July 2019

BACKGROUND

Females are more likely than males to develop major depressive disorder (MDD) after exposure to stress. We previously reported that the administration of (R,S)-ketamine before stress can prevent stress-induced depressive-like behavior in male mice but have yet to assess efficacy in female mice or for other compounds, such as the metabolites of (R,S)-ketamine.

METHODS

We administered (R,S)-ketamine or its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) and (2S,6S)-HNK at various doses 1 week before one of a number of stressors, including contextual fear conditioning (CFC), learned helplessness (LH), and chronic immobilization stress (CIS), in male and female 129S6/SvEv mice. To examine the interaction between ovarian hormones and stress resilience, female mice also underwent ovariectomy surgery (OVX) and a hormone replacement protocol prior to drug administration.

RESULTS

(R,S)-ketamine and (2S,6S)-HNK, but not (2R,6R)-HNK, attenuated learned fear in male mice. (R,S)-ketamine and (2R,6R)-HNK, but not (2S,6S)-HNK, significantly reduced stress-induced depressive-like behavior in male and female mice. (R,S)-ketamine and (2R,6R)-HNK) were prophylactically effective at a lower dose (10 mg/kg and 0.025 mg/kg, respectively) in female mice than in male mice (30 mg/kg and 0.075 mg/kg, respectively). Moreover, ovarian-derived hormones were necessary and sufficient for prophylaxis in female mice.

CONCLUSIONS

Our results suggest that prophylactics against stress-induced depressive-like behavior can be developed in a sex-specific manner and that ovarian hormones mediate prophylactic efficacy in females. To our knowledge, this is the first demonstration of the prophylactic efficacy of the metabolites of (R,S)-ketamine in male and female mice.
Point-of-Use Detection of Environmental Fluoride via a Cell-Free Riboswitch-Based Biosensor
Authors: Thavarajah Walter , Silverman Adam D. , Verosloff Matthew S. , Kelley-Loughnane Nancy , Jewett Michael C. , Lucks Julius B.
Published: July 2019

Advances in biosensor engineering have enabled the design of programmable molecular systems to detect a range of pathogens, nucleic acids, and chemicals. Here, we engineer and field-test a biosensor for fluoride, a major groundwater contaminant of global concern. The sensor consists of a cell-free system containing a DNA template that encodes a fluoride-responsive riboswitch regulating genes that produce a fluorescent or colorimetric output. Individual reactions can be lyophilized for long-term storage and detect fluoride at levels above 2 parts per million, the EPA’s most stringent regulatory standard, in both laboratory and field conditions. Through onsite detection of fluoride in a real-world water source, this work provides a critical proof-of-principle for the future engineering of riboswitches and other biosensors to address challenges for global health and the environment.
Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis
Authors: Robinson Andrew P. , Zhang Joanne Zhongyan , Titus Haley E. , Karl Molly , Merzliakov Mikhail , Dorfman Adam R. , Karlik Stephen , Stewart Michael G. , Watt Richard K. , Facer Benjin D. , Facer Jon D. , Christian Noah D. , Ho Karen S. , Hotchkin Michael T. , Mortenson Mark G. , Miller Robert H. , Miller Stephen D.
Published: July 2019

Development of pharmacotherapies that promote remyelination are a high priority for multiple sclerosis (MS) due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of key myelin differentiation markers. Additional in vitro data demonstrated that these gold nanocrystals act via a novel energy metabolism pathway involving the enhancement of key indicators of aerobic glycolysis. In response to gold nanocrystals, co-cultured central nervous system cells exhibited elevated levels of the redox coenzyme nicotine adenine dinucleotide (NAD+), elevated total ATP levels, elevated extracellular lactate levels, and upregulation of myelin-synthesis related genes, collectively resulting in functional myelin generation. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis.

One Sentence Summary

Nanocatalytic activity of clean-surfaced, faceted gold nanocrystals results in robust remyelinating activity in demyelination animal models of multiple sclerosis.
Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins
Authors: Campos Rafael K. , Wijeratne Sagara , Shah Premal , Garcia-Blanco Mariano A. , Bradrick Shelton S.
Published: July 2019

Dengue virus (DENV) and other mosquito-borne flaviviruses are highly dependent on the ribosomal stalk proteins, RPLP1 and RPLP2 (RPLP1/2), for efficient infection. Here, we show that RPLP1/2 function to relieve ribosome pausing within the DENV envelope coding sequence, leading to enhanced protein stability. We used ribosome profiling to evaluate viral and cellular translation in RPLP1/2-depleted cells. This revealed that ribosomes pause in the sequence coding for the N-terminus of the envelope protein, immediately downstream of sequences encoding two adjacent transmembrane domains (TMDs). RPLP1/2 function to enhance ribosome elongation at this position and increase viral protein stability, possibly by improving co-translational folding of DENV proteins. We also analyzed the effects of RPLP1/2 depletion on cellular translation. We find that RPLP1/2 affects ribosome density for a small subset of cellular mRNAs. However, meta-analysis of ribosome positions on all cellular mRNAs revealed slightly increased accumulation of ribosomes downstream of start codons in RPLP1/2-depleted cells, suggesting that RPLP1/2 enhance elongation efficiency. Importantly, we found that ribosome density on mRNAs encoding multiple TMDs was disproportionately affected by RPLP1/2 knockdown, implying a role for RPLP1/2 in transmembrane protein biogenesis. Together, our findings reveal insights into the function of RPLP1/2 in DENV and cellular translation.
Rab11is essential forlglmediated JNK–Dpp signaling in dorsal closure and epithelial morphogenesis inDrosophila
Authors: Nandy Nabarun , Roy Jagat Kumar
Published: July 2019

Dorsal closure inDrosophilaprovides a robust genetic platform providing deep insights into the basic cellular mechanisms that govern epithelial wound healing and morphogenesis. As dorsal closure proceeds, the adjacent epithelia advance contra-laterally involving coordinated cell shape changes in order to successfully accomplish the process. The JNK-Dpp signaling in these cells plays an instrumental role in guiding their fate as gastrulation completes. A huge number of genes have been reported to be involved in the regulation of this core signaling pathway, yet the mechanisms by which they do so is hitherto unclear, which forms the objective of our present study. Here we show thatlgl, which is a potent tumour suppressor gene, conserved across the phyla till humans, regulates the JNK–Dpp pathway in the dorsal closure and epithelial morphogenesis process where in ectopic knockdown of this gene results in the failure of dorsal closure. Interestingly, we also findRab11to be interacting withlglas they together regulate the core JNK-Dpp signaling pathway during dorsal closure and also during pupal thorax closure process. Using the robustGal4-UASsystem of targeted gene expression, we show here thatRab11andlglsynergize to successfully execute the dorsal closure and the similar thorax closure process, ensuring proper spatio-temporal JNK-Dpp signaling.
Fast and robust ancestry prediction using principal component analysis
Authors: Zhang Daiwei , Dey Rounak , Lee Seunggeun
Published: July 2019

Population stratification (PS) is a major confounder in genome-wide association studies (GWAS) and can lead to false positive associations. To adjust for PS, principal component analysis (PCA)-based ancestry prediction has been widely used. Simple projection (SP) based on principal component loading and recently developed data augmentation-decomposition-transformation (ADP), such as LASER and TRACE, are popular methods for predicting PC scores. However, they are either biased or computationally expensive. The predicted PC scores from SP can be biased toward NULL. On the other hand, since ADP requires running PCA separately for each study sample on the augmented data set, its computational cost is high. To address these problems, we develop and propose two alternative approaches, bias-adjusted projection (AP) and online ADP (OADP). Using random matrix theory, AP asymptotically estimates and adjusts for the bias of SP. OADP uses computationally efficient online singular value decomposition, which can greatly reduce the computation cost of ADP. We carried out extensive simulation studies to show that these alternative approaches are unbiased and the computation times can be 10-100 times faster than ADP. We applied our approaches to UK-Biobank data of 488,366 study samples with 2,492 samples from the 1000 Genomes data as the reference. AP and OADP required 7 and 75 CPU hours, respectively, while the projected computation time of ADP is 2,534 CPU hours. Furthermore, when we only used the European reference samples in the 1000 Genomes to infer sub-European ancestry, SP clearly showed bias, unlike the proposed approaches. By using AP and OADP, we can infer ancestry and adjust for PS robustly and efficiently.
Disruption of aRAC1-centred protein interaction network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration
Authors: Kikuchi Masataka , Sekiya Michiko , Hara Norikazu , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi , Iijima Koichi M. , Nakaya Akihiro
Published: July 2019

The molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated cross-talk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, includingRac1, as key players in PDN collapse. Using publicly available gene expression data, we confirmed that the mRNA expression level of theRAC1gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilizedDrosophilaas a genetic model and found that modest knockdown ofRac1in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator ofRAC1in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were upregulated specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y causedRAC1downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.
Evolutionary changes of phosphoenolpyruvate transporter (PPT) during the emergence of C4 photosynthesis
Authors: Lyu Ming-Ju Amy , Wang Yaling , Jiang Jianjun , Chen Genyun , Zhu Xin-Guang
Published: July 2019

C4 photosynthesis is a complex trait, which evolved from its ancestral C3 photosynthesis by recruiting pre-existing genes. The evolutionary history of enzymes involved in the C4 shuttle has been extensively studied. Here we analyze the evolutionary changes of phosphoenolpyruvate (PEP) transporter (PPT) during its recruitment from C3 to C4 photosynthesis. Our analysis shows that 1) among the two PPT paralogs, i.e. PPT1 and PPT2, PPT1 is an ancestral copy while PPT2 is a derived copy; 2) during C4 evolution, PPT1 shifted its expression from predominantly in root to in leaf, and from bundle sheath cell to mesophyll cell, supporting that PPT1 was recruited into C4 photosynthesis; 3) PPT1 gained increased transcript abundance, gained more rapid and long-lasting responses to light during C3 to C4 evolution, while PPT2 lost its responsiveness to light; 4) PPT1 gained a number of new cis-elements during C4 evolution; 5) C4 PPT1 can complement the phenotype of Arabidopsis PPT1 loss-of-function mutant, suggesting that it is a bidirectional transporter and its transport direction did not alter during C4 evolution. We finally discuss mechanistic linkages between these observed changes in PPT1 and C4 photosynthesis evolution.

High light

During the process of C4 photosynthesis evolution, PPT not only experienced changes in its expression location and transcript abundance, but also acquired new cis-elements in its promoter region and accumulated protein variations.
Measuring and Modelling the Emergence of Order in the Mouse Retinocollicular Projection
Authors: Lyngholm Daniel , Sterratt David C. , Hjorth J. J. Johannes , Willshaw David J. , Eglen Stephen J. , Thompson Ian D.
Published: July 2019

In the formation of retinotopic maps both experimental and theoretical work implicate guidance molecules and patterned neuronal activity. A common view is that molecular cues define and activity cues refine mappings. Important insights have come from studies of the retinocollicular projection in transgenic mice, in which cues have been modified either in isolation or in combination. Mostly these have generated descriptions of endpoint mappings. The dynamics of map formation remain under-explored experimentally and computationally. We have quantified changes in the ordering of the mouse retinocollicular projection with age after making local collicular injections of fluorescent microspheres. Contour analysis shows that, at birth (P0), cells from over 80% of the retina converge on a given collicular locus; this percentage falls gradually to P4 then rapidly approaches adult values by P12. Paired injections reveal how the segregation of labelled cells depends both on injection site separation and relative orientation and also age. At P0, large anterior-posterior separations failed to produce segregated label: segregation improved with a similar timecourse to convergence to reach near adult-values by P12. An implementation of a combined activity-molecular model captures these segregation dynamics.

The developmental dynamics were then studied in the nAChR-β2−/− mouse, which has altered patterns of retinal activity in the first postnatal week that results in a more diffuse adult retinal projection. Surprisingly, both measures of map refinement (convergence and segregation) remain largely constant and imprecise in the first postnatal week – only subsequently does the projection begin to refine. Substituting nAChR-β2−/− activity patterns for wild-type patterns [5] into the model failed to capture the biology: refinement was initially faster. By reducing the relative importance of the gradients’ contribution to the model energy (to 15% of normal) we were able to mimic the delayed refinement observed in vivo. Our model therefore predicts the altered activity patterns may affect readout of guidance cues.
Emergence of the subapical domain is associated with the midblastula transition
Authors: Schmidt Anja , Großhans Jörg
Published: July 2019

Epithelial domains and cell polarity are determined by polarity proteins which are associated with the cell cortex in a spatially restricted pattern. Early Drosophila embryos are characterized by a stereotypic dynamic and de novo formation of cortical domains. For example, the subapical domain emerges at the transition from syncytial to cellular development during the first few minutes of interphase 14. The dynamics in cortical patterning is revealed by the subapical markers Canoe/Afadin and ELMO-Sponge, which widely distributed in interphase 13 but subapically restricted in interphase 14. The factors and mechanism determining the timing for the emergence of the subapical domain have been unknown. In this study, we show, that the restricted localization of subapical markers depends on the onset of zygotic gene expression. In contrast to cell cycle remodeling, the emergence of the subapical domain does not depend on the nucleo-cytoplasmic ratio. Thus, we define cortical dynamics and specifically the emergence of the subapical domain as a feature of the midblastula transition.

Author summary

Midblastula transition is a paradigm of a developmental transition. Multiple processes such as cell cycle, cell mobility, onset of zygotic gene expression, degradation of maternal RNA and chromatin structure are coordinated to lead to defined changes in visible morphology. The midblastula transition inDrosophilaembryos is associated with a change from fast nuclear cycles to a cell cycle mode with gap phase and slow replication, a strong increase in zygotic transcription and cellularization. The timing of the processes associated with the midblastula transition are controlled by the onset of zygotic gene expression or the nucleocytoplasmic ratio. Here we define the patterning of cortical domains, i. e. the emergence of a subapical domain as a novel feature of the midblastula transition whose appearance is controlled by the onset of zygotic transcription but not the nucleocytoplasmic ratio. Our findings will help to gain further understanding of the coordination of complex developmental processes during the midblastula transition.
Modern human changes in regulatory regions implicated in cortical development
Authors: Moriano Juan , Boeckx Cedric
Published: July 2019

Recent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes that appeared after the split from the Neanderthal/Denisovan lineage. These regulatory regions exert their functions at early stages of cortical development and control a set of genes among which those related to chromatin regulation stand out. This functional category has not yet figured prominently in modern human evolution studies. Specifically, we find an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT-signaling for the generation and proliferation of intermediate progenitor cells.