bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural color in Junonia butterflies evolves by tuning scale lamina thickness
Authors: Thayer Rachel C. , Allen Frances I. , Patel Nipam H. 
Published: March 2019

AbstractIn diverse organisms, nanostructures that coherently scatter light create structural color, but how such structures are built remains mysterious. We investigate the evolution and genetic regulation of butterfly scale laminae, which are simple photonic nanostructures. In a lineage of buckeye butterflies artificially selected for blue wing color, we found that thickened laminae caused a color shift from brown to blue. Deletion of the optix wing patterning gene also altered color via lamina thickening, revealing shared genetic regulation of pigments and lamina thickness. Finally, we show how lamina thickness variation contributes to the color diversity that distinguishes sexes and species throughout the genus Junonia. Thus, quantitatively tuning one dimension of scale architecture facilitates both the microevolution and macroevolution of a broad spectrum of hues. Because the lamina is an intrinsic component of typical butterfly scales, our findings suggest that tuning lamina thickness is a readily accessible mechanism to create structural color across the Lepidoptera.
Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against autoimmune diseases
Authors: Liu Ronghan , Chen Yuehong , Wang Shuya , Cui Yazhou , Zhang Xiangli , Lei Zi-Ning , Hettinghouse Aubryanna , Liu Jody , Fu Wenyu , Chen Zhe-Sheng , Liu Chuanju 
Published: March 2019

SUMMARYTNF-α signaling plays a central role in the pathogenesis of various diseases, particularly autoimmune diseases. Screening of a library composed of FDA approved drugs led to the identification of Terfenadine and its active metabolite Fexofenadine as inhibitors of TNF-α signaling. Both Fexofenadine and Terfenadine inhibited TNF/NF-κB signaling in vitro and in vivo, and ameliorated disease symptoms in various autoimmune disease models, including TNF-α transgenic mice, collagen-induced arthritis, and inflammatory bowel disease. Subsequent studies identified cytosolic phospholipase A2 (cPLA2) as a novel target of Fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished Fexofenadine’s anti-TNF activity. Collectively, these findings not only provide new insights into the understanding of Fexofenadine action and underlying mechanism, but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly autoimmune diseases.
Metatranscriptomics as a tool to identify fungal species and subspecies in mixed communities
Authors: Marcelino Vanesa R. , Irinyi Laszlo , Eden John-Sebastian , Meyer Wieland , Holmes Edward C. , Sorrell Tania C. 
Published: March 2019

AbstractHigh-throughput sequencing (HTS) enables the generation of large amounts of genome sequence data at a reasonable cost. Organisms in mixed microbial communities can now be sequenced and identified in a culture-independent way, usually using amplicon sequencing of a DNA barcode. Bulk RNA-seq (metatranscriptomics) has several advantages over DNA-based amplicon sequencing: it is less susceptible to amplification biases, it captures only living organisms, and it enables a larger set of genes to be used for taxonomic identification. Using a defined mock community comprised of 17 fungal isolates, we evaluated whether metatranscriptomics can accurately identify fungal species and subspecies in mixed communities. Overall, 72.9% of the RNA transcripts were classified, from which the vast majority (99.5%) were correctly identified at the species-level. Of the 15 species sequenced, 13 were retrieved and identified correctly. We also detected strain-level variation within theCryptococcusspecies complexes: 99.3% of transcripts assigned toCryptococcuswere classified as one of the four strains used in the mock community. Laboratory contaminants and/or misclassifications were diverse but represented only 0.44% of the transcripts. Hence, these results show that it is possible to obtain accurate species- and strain-level fungal identification from metatranscriptome data as long as taxa identified at low abundance are discarded to avoid false-positives derived from contamination or misclassifications. This study therefore establishes a base-line for the application of metatranscriptomics in clinical mycology and ecological studies.
Enhanced replication of mouse adenovirus type 1 following virus-induced degradation of protein kinase R (PKR)
Authors: Goodman Danielle E. , Pretto Carla D. , Krepostman Tomas A. , Carnahan Kelly E. , Spindler Katherine R. 
Published: March 2019

AbstractProtein kinase R (PKR) plays a major role in activating host immunity during infection by sensing dsRNA produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eIF2α, halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at a transcriptional or translational level because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicate that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has only been described in six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.ImportanceThe first line of defense in cells during viral infection is the innate immune system, which is activated by different viral products. PKR is a part of this innate immune system and is induced by interferon and activated by dsRNA produced by DNA and RNA viruses. PKR is such an important part of the antiviral response that many viral families have gene products to counteract its activation or the resulting effects of its activity. Although a few RNA viruses degrade PKR, this method of counteracting PKR has not been reported for any DNA viruses. MAV-1 does not encode virus-associated RNAs, a human adenoviral defense against PKR activation. Instead, MAV-1 degrades PKR, and it is the first DNA virus reported to do so. The innate immune evasion by PKR degradation is a previously unidentified way for a DNA virus to circumvent the host antiviral response.
Opposing modulation of Cx26 gap junctions and hemichannels by CO2
Authors: Nijjar Sarbjit , Maddison Daniel , Meigh Louise , de Wolf Elizabeth , Rodgers Thomas , Cann Martin , Dale Nicholas 
Published: March 2019

SummaryCx26 hemichannels open in response to moderate elevations of CO2(PCO255 mmHg) via a carbamylation reaction that depends on residues K125 and R104. Here we investigate the action of CO2on Cx26 gap junctions. Using a dye transfer assay, we found that an elevated PCO2of 55 mmHg greatly delayed the permeation of a fluorescent glucose analogue (NBDG) between HeLa cells coupled by Cx26 gap junctions. However, the mutations K125R or R104A abolished this effect of CO2. Whole cell recordings demonstrated that elevated CO2reduced the Cx26 gap junction conductance (median reduction 5.6 nS, 95% confidence interval, 3.2 to 11.9 nS) but had no effect on Cx26K125Ror Cx31 gap junctions. CO2can cause intracellular acidification, but using 30 mM propionate we found that acidification in the absence of a change in PCO2caused a median reduction in the gap junction conductance of 5.3 nS (2.8 to 8.3 nS). This effect of propionate was unaffected by the K125R mutation (median reduction 7.7 nS, 4.1 to 11.0 nS). pH-dependent and CO2-dependent closure of the gap junction are thus mechanistically independent. Mutations of Cx26 associated with the Keratitis Ichthyosis Deafness syndrome (N14K, A40V and A88V) also abolished the CO2-dependent gap junction closure. Elastic network modelling suggests that the lowest entropy state when CO2is bound, is the closed configuration for the gap junction but the open state for the hemichannel. The opposing actions of CO2on Cx26 gap junctions and hemichannels thus depend on the same residues and presumed carbamylation reaction.
The role of feature-based attention in visual serial dependence
Authors: Fritsche Matthias , de Lange Floris P. 
Published: March 2019

AbstractPerceptual decisions about current sensory input are biased towards input of the recent past – a phenomenon termed serial dependence. Serial dependence may serve to stabilize neural representations in the face of external and internal noise. However, it is unclear under which circumstances previous input attracts subsequent perceptual decisions, and thus, whether serial dependence reflects a broad smoothing or selective stabilization operation. Here, we investigated whether focusing attention on particular features of the previous stimulus modulates serial dependence. We found an attractive bias in orientation estimations when previous and current stimuli had similar orientations, and a repulsive bias when they had dissimilar orientations. The attractive bias was markedly reduced when observers attended to the size, rather than the orientation, of the previous stimulus. Conversely, the repulsive bias for stimuli with large orientation differences was not modulated by feature-based attention. This suggests separate sources of these positive and negative perceptual biases.
GABA-Glutamate supramammillary neurons control theta and gamma oscillations in the dentate gyrus during paradoxical (REM) sleep
Authors: Billwiller Francesca , Castillo Laura , Elseedy Heba , Ivanov Anton Ivanovich , Scapula Jennyfer , Ghestem Antoine , Carponcy Julien , Libourel Paul Antoine , Bras Hélène , Abdelmeguid Nabila ElSayed , Krook-Magnuson Esther , Soltesz Ivan , Bernard Christophe , Luppi Pierre-Hervé , Esclapez Monique 
Published: March 2019

AbstractSeveral studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to fully characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state.Significant statementAn increase of theta and gamma power in the dentate gyrus (DG) is an hallmark of paradoxical (REM) sleep (PS) and is suggested to promote learning and memory consolidation by synchronizing hippocampal networks and increasing its outputs to cortical targets. However the neuronal networks involved in such control of DG activity during PS are poorly understood. The present study identifies a population of GABA/Glutamate neurons in the lateral supramammllary nucleus (SuML) innervating the DG that could support such control during PS. Indeed, we show that activation of these SuML-DG projections increase theta power and frequency as well as gamma power in the DG specifically during PS and modulate activity of a subset of DG granule cells.
Exploiting the unwanted: sulphate reduction enables phosphate recovery from energy-rich sludge during anaerobic digestion
Authors: Lippens Celine , De Vrieze Jo 
Published: March 2019

AbstractAnaerobic digestion is shifting from a single-purpose technology for renewable energy recovery from organic waste streams to a process for integrated resource recovery. The valorisation of high-rate energy- and phosphorus-rich sludge creates the opportunity for their combined recovery. This phosphate is present in a precipitated form in the sludge, and its release into the liquid phase is an important issue before recovery can be achieved. The objective of this research was to exploit the “unwanted” sulphate reduction process for the release of phosphate into the liquid phase during anaerobic digestion, thus, making it available for recovery. Two different treatments were considered,i.e., a control digester and a digester to which sulphate was added, each operated in triplicate for a period of 119 days. The control digester showed stable methane production at 628 ± 103 mL CH4L−1d−1, with a feedstock COD (chemical oxygen demand) conversion efficiency of 89.5 ± 14.6 %. In contrast, the digester with sulphate addition showed a 29.9 ± 15.3 % decrease in methane production, reaching an “inhibited steady state”, but phosphate release into the liquid phase increased with a factor 4.5, compared to the control digester. This inhibited steady state coincided with a clear shift from a Methanosaetaceae to a Methanosarcinaceae dominated methanogenic community. Overall, the sulphate reduction process allows phosphate release during the anaerobic digestion process, yet, at the cost of a reduced methane production rate.
CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors
Authors: Walens Andrea , DiMarco Ashley V. , Lupo Ryan , Kroger Benjamin R. , Damrauer Jeffrey S. , Alvarez James V. 
Published: March 2019

ABSTRACTOver half of breast cancer related deaths are due to recurrence five or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.
A Truly Injectable Neural Stimulation Electrode Made from an In-Body Curing Polymer/Metal Composite
Authors: Trevathan James K. , Baumgart Ian W. , Nicolai Evan N. , Gosink Brian A. , Asp Anders J. , Settell Megan L. , Polaconda Shyam R. , Malerick Kevin D. , Brodnick Sarah K. , Zeng Weifeng , Knudsen Bruce E. , McConico Andrea L. , Sanger Zachary , Lee Jannifer H. , Aho Johnathon M. , Suminski Aaron J. , Ross Erika K. , Lujan J. Luis , Weber Douglas J. , Williams Justin C. , Franke Manfred , Ludwig Kip A. , Shoffstall Andrew J. 
Published: March 2019

AbstractImplanted neural stimulation and recording devices hold vast potential to treat a variety of neurological conditions, but the invasiveness, complexity, and cost of the implantation procedure greatly reduce access to an otherwise promising therapeutic approach. To address this need, we have developed a novel electrode that begins as an uncured, flowable pre-polymer that can be injected around a neuroanatomical target to minimize surgical manipulation. Referred to as the Injectrode, the electrode conforms to target structures forming an electrically conductive interface which is orders of magnitude less stiff than conventional neuromodulation electrodes. To validate the Injectrode, we performed detailed electrochemical and microscopy characterization of its material properties and validated the feasibility of using it to electrically stimulate the nervous system in rats and swine. The silicone-metal-particle composite performed very similarly to pure wire of the same metal (silver) in all measures, including exhibiting a favorable cathodic charge storage capacity (CSCC) and charge injection limits compared to the clinical LivaNova stimulation electrode and silver wire electrodes. By virtue of being simpler than traditional electrode designs, less invasive, and more cost-effective, the Injectrode has the potential to increase the adoption of neuromodulation therapies for existing and new indications.
Fundamental Theory of the Evolution Force (FTEF): Gene Engineering utilizing Synthetic Evolution Artificial Intelligence (SYN-AI)
Authors: Davis L.K. , Uppu R.M. 
Published: March 2019

ABSTRACTThe effects of the evolution force are observable in nature at all structural levels ranging from small molecular systems to conversely enormous biospheric systems. However, the evolution force and work associated with formation of biological structures has yet to be described mathematically or theoretically. In addressing the conundrum, we consider evolution from a unique perspective and in doing so we introduce “The fundamental Theory of the Evolution Force”. Whereby, the driving force of evolution is defined as a compulsion acting at the matter-energy interface that accomplishes genetic diversity while simultaneously conserving structure and function. By proof of concept, we attempt herein to characterize evolution force associated with genomic building block (GBB) formation utilizing synthetic evolution artificial intelligence (SYN-AI). As part of our methodology, we transform the DNA code into time dependent DNA codes based upon DNA hierarchical structural levels that allow evolution by the exchange of genetic information like the swapping of building blocks in a game of Legos. Notably, we not only theorize and mathematical describe the evolution force herein, but have written a set of 14-3-3 docking genes from scratch.
Modeling mechanisms of tremor reduction for essential tremor using symmetric biphasic DBS
Authors: Lee Shane , Asaad Wael F , Jones Stephanie R 
Published: March 2019

AbstractEssential tremor (ET) is the most common movement disorder, in which the primary symptom is a prominent, involuntary 4–10 Hz movement. For severe, medication refractory cases, deep brain stimulation (DBS) targeting the ventral intermediate nucleus of the thalamus (VIM) can be an effective treatment for cessation of tremor and is thought to work in part by disrupting tremor frequency oscillations (TFOs) in VIM. However, DBS is not universally effective and may be further disrupting cerebellar-mediated activity in the VIM. Here, we applied biophysically detailed computational modeling to investigate whether the efficacy of DBS is affected by the mechanism of generation of TFOs or by the pattern of stimulation. We simulated the effects of DBS using standard, asymmetric pulses as well as biphasic, symmetric pulses to understand biophysical mechanisms of how DBS disrupts TFOs generated either extrinsically or intrinsically. The model results suggested that the efficacy of DBS in the VIM is affected by the mechanism of generation of TFOs. Symmetric biphasic DBS reduced TFOs more than standard DBS in both networks, and these effects were stronger in the intrinsic network. For intrinsic tremor frequency activity, symmetric biphasic DBS was more effective at reducing TFOs. Simulated non-tremor signals were also transmitted during symmetric biphasic DBS, suggesting that this type of DBS may help to reduce side effects caused by disruption of the cerebellothalamocortical pathway. Biophysical details in the model provided a mechanistic interpretation of the cellular and network dynamics contributing to these effects that can be empirically tested in future studies.Significance StatementEssential tremor (ET) is a common movement disorder, whose primary symptom is an involuntary rhythmic movement of the limbs or head. An area of the human tha-lamus demonstrates electrical activity that oscillates at the frequencies of tremor, and deep brain stimulation (DBS) in this area can reduce tremor. It is not fully understood how DBS affects tremor frequency activity in the thalamus, and studying different patterns of DBS stimulation may help to clarify these mechanisms. We created a computational model of different shapes of DBS and studied how they reduce different hypothesized generators of tremor frequency activity. A greater understanding of how DBS affects the thalamus may lead to improved treatments to reduce tremor and alleviate side effects in patients with ET.
Modular tissue-specific regulation ofdoublesexunderpins sexually dimorphic development inDrosophila
Authors: Rice Gavin R. , Barmina Olga , Luecke David , Hu Kevin , Arbeitman Michelle , Kopp Artyom 
Published: March 2019

AbstractThe ability of a single genome to produce distinct and often dramatically different male and female forms is one of the wonders of animal development. In most animals, sex-specific phenotypes are shaped by interactions between a sex determination pathway and spatial patterning gene networks. InDrosophila melanogaster, most sexually dimorphic traits are controlled by sex-specific isoforms of thedoublesex(dsx) transcription factor, anddsxexpression is mostly limited to cells that give rise to sexually dimorphic traits. However, it is unknown how this mosaic of “sex-naïve” and “sex-aware” tissues arises. Here, we characterize thecis-regulatory sequences that controldsxexpression in the foreleg, which contains multiple types of sex-specific sensory organs. We find that separate modular enhancers are responsible fordsxexpression in each sexually dimorphic organ. Expression ofdsxin the sex comb is co-regulated by two enhancers with distinct spatial and temporal specificities that are separated by a genitalia-specific enhancer. Thus, the mosaic of sexually dimorphic and monomorphic organs depends on modular regulation ofdsxtranscription by dedicated cell type-specific enhancers.Summary StatementWe identify the modularcis-regulatory elements that direct expression ofdoublesexin sexually dimorphic structures inDrosophilalegs and genitalia. This regulatory landscape provides insight into how cells obtain their sex-specific identity.