bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative process-based model for biomass and yield estimation of hardneck garlic (Allium sativum)
Authors: Yun Kyungdahm , Shin Minji , Moon Kyung Hwan , Kim Soo-Hyung 
Published: November 2021

AbstractWe introduce an integrative process-driven crop model for garlic (Allium sativum). Building on our previous model that simulated key phenological, morphological, and physiological features of a garlic plant, the new garlic model provides comprehensive and integrative estimations of biomass accumulation and yield formation under diverse environmental conditions. This model also showcases an application of Cropbox to develop a comprehensive crop model. Cropbox is a crop modeling framework featuring declarative modeling language and unified simulation interface for building and improving crop models. Using Cropbox, we first evaluated the model performance against three datasets with an emphasis on biomass and yield measured under different environmental conditions and growing seasons. We then applied the model to simulate optimal planting dates under future climate conditions for assessing climate adaptation strategies between two contrasting locations in South Korea: the current growing region (Gosan) and an unfavorable cold winter region (Chuncheon, Gangwon-do). The model simulated the growth and development of a southern-type cultivar (Namdo, Jeju-do) reasonably well. Under RCP (Representative Concentration Pathway) scenarios, an overall delay in optimal planting date from a week to a month and a slight increase in potential yield were expected in Gosan. Expansion of growing region to northern area including Chuncheon was expected due to mild winter temperatures in the future and may allow Namdo cultivar production in more regions. The predicted optimal planting date in the new region was similar to the current growing region that favors early fall planting. Our new integrative garlic model provides mechanistic, process-driven crop responses to environmental cues and can be useful for assessing climate impacts and identifying crop specific climate adaptation strategies for the future.
Corticostriatal dynamics underlying components of binge-like eating in mice
Authors: Hildebrandt Britny A. , Fisher Hayley , LaPalombara Zoe , Young Michael E. , Ahmari Susanne E. 
Published: November 2021

AbstractBinge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. Despite the substantial negative impact of BE on psychological and physiological health, its underlying neural mechanisms are largely unknown. Other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. Additionally, previous pre-clinical and clinical work has highlighted an imbalance between goal-directed and habitual responding in BE. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions associated with habitual behavior– the infralimbic cortex (IL) and dorsolateral striatum (DLS)– in a robust pre-clinical model for BE. Female C57BL/6 mice (N=32) were randomized to receive: 1) intermittent (daily, 2-hour) binge-like access to palatable food (BE mice), or 2) continuous, non-intermittent (24-hour) access to palatable food (non-BE mice). In vivo calcium imaging was performed via fiber photometry at baseline and after chronic (4 weeks) engagement in the model for BE. Feeding behaviors (feeding bout onset/offset) during the recordings were captured using lickometers which generated TTL outputs for precise alignment of behavior to neural data. IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity at feeding onset and offset at the chronic timepoint when compared to baseline. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset at the chronic timepoint compared to non-BE mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.Significance StatementBinge eating is a chronic and repetitive eating behavior that is associated with poor physiological and psychosocial outcomes. Despite the negative impact of binge eating, little is known about the neurobiological mechanisms contributing to the chronic course and persistence of the behavior. To investigate potential neural mechanisms underlying binge eating, we are using approaches developed to monitor neural activity in rodents. This study is the first to identify longitudinal changes in neural activity within regions of the prefrontal cortex and dorsal striatum during binge-like eating behavior in mice. Findings from this work could inform targeted biological treatments for binge eating.
Repeats Mimic Pathogen-Associated Patterns Across a Vast Evolutionary Landscape
Authors: Šulc Petr , Gioacchino Andrea Di , Solovyov Alexander , Marhon Sajid A. , Sun Siyu , Lindholm Håvard T , Chen Raymond , Hosseini Amir , Jiang Hua , Ly Bao-Han , Mehdipour Parinaz , Abdel-Wahab Omar , Vabret Nicolas , LaCava John , De Carvalho Daniel D. , Monasson Rémi , Cocco Simona , Greenbaum Benjamin D. 
Published: November 2021

ABSTRACTAn emerging hallmark across human diseases – such as cancer, autoimmune and neurodegenerative disorders – is the aberrant transcription of typically silenced repetitive elements. Once active, a subset of repeats may be capable of “viral mimicry”: the display of pathogen-associated molecular patterns (PAMPs) that can, in principle, bind pattern recognition receptors (PRRs) of the innate immune system and trigger inflammation. Yet how to quantify the landscape of viral mimicry and how it is shaped by natural selection remains a critical gap in our understanding of both genome evolution and the immunological basis of disease. We propose a theoretical framework to quantify selective forces on virus-like features as the entropic cost a sequence pays to hold a non-self PAMP and show our approach can predict classes of viral-mimicry within the human genome and across eukaryotes. We quantify the breadth and conservation of viral mimicry across multiple species for the first time and integrate selective forces into predictive evolutionary models. We show HSATII and intact LINE-1 (L1) are under selection to maintain CpG motifs, and specific Alu families likewise maintain the proximal presence of inverted copies to form double-stranded RNA (dsRNA). We validate our approach by predicting high CpG L1 ligands of L1 proteins and the innate receptorZCCHC3, and dsRNA present both intracellularly and as MDA5 ligands. We conclude viral mimicry is a general evolutionary mechanism whereby genomes co-opt pathogen-associated features generated by prone repetitive sequences, likely offering an advantage as a quality control system against transcriptional dysregulation.
Zinc finger antiviral protein (ZAP) activity in mammalian and avian hosts in CpG and UpA-mediated restriction of RNA viruses and investigation of ZAP-mediated shaping of host transcriptome compositions
Authors: Odon Valerie , Fiddaman Steven R , Smith Adrian L. , Simmonds Peter 
Published: November 2021

ABSTRACTThe ability of zinc finger antiviral protein (ZAP) to recognise and respond to RNA virus sequences with elevated frequencies of CpG dinucleotides has been proposed as a functional part of the vertebrate innate immune antiviral response. It has been further proposed that ZAP activity shapes compositions of cytoplasmic mRNA sequences to avoid self-recognition, particularly mRNAs for interferons (IFNs) and IFN-stimulated genes highly expressed when ZAP is upregulated during the antiviral state. We investigated the ZAP functional activity in different species of mammals and birds, and potential downstream effects of differences in CpG and UpA dinucleotide representations in host transcriptomes and in RNA viruses that infect them. Cell lines from different bird orders showed variability in restriction of influenza A virus and echovirus 7 replicons with elevated CpG frequencies and none restricted UpA-high mutants, in marked contrast to mammalian cell lines. Given this variability, we compared CpG and UpA representation in coding regions of ISGs and IFNs with the total cellular transcriptome to determine whether differences in ZAP activity shaped dinucleotide compositions of highly expressed genes during the antiviral state. While type 1 IFN genes typically showed often profound suppression of CpG and UpA frequencies, there was no over-suppression of CpGs or UpAs in ISGs in any species, irrespective of underlying ZAP activity. Similarly, mammalian and avian RNA virus genome sequences were compositionally equivalent as were IAV serotypes recovered from ducks, chickens and humans. Overall, we found no evidence for host variability in ZAP function impacting compositions of antiviral genes.
Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development
Authors: Johnson Clare T , Dias de Abreu Gabriel H , Mackie Ken , Lu Hui-Chen , Bradshaw Heather B 
Published: November 2021

AbstractMaternal cannabis use during lactation may expose developing infants to cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD). CBs modulate lipid signaling molecules in the central nervous system in age- and cell-dependent ways, but their influence on the lipid composition of breastmilk has yet to be established. This study investigates the effects of THC, CBD, or their combination on milk lipids by analyzing the stomach contents of CD1 mouse pups that have been nursed by dams injected with CBs on postnatal days (PND) 1-10 collected 2 hours after the last injection on PND10. HPLC/MS/MS was used to identify and quantify over 80 endogenous lipid species and cannabinoids in pup stomach contents. We show that CBs differentially accumulate in milk, lead to widespread decreases in free fatty acids, decreases in N-acyl methionine species, increases N-linoleoyl species, as well as modulate levels of endogenous CBs (eCBs) AEA, 2-AG, and their structural congeners. Our data indicate the passage of CBs to pups through breast milk and that maternal CB exposure alters breast milk lipid compositions.
Ras protein abundance correlates with Ras isoform mutation patterns in cancer
Authors: Hood Fiona E. , Sahraoui Yasmina M. , Jenkins Rosalind E. , Prior Ian A. 
Published: November 2021

ABSTRACTActivating mutations of Ras genes are often observed in cancer. The protein products of the three Ras genes are almost identical. However, for reasons that remain unclear, KRAS is far more frequently mutated than the other Ras isoforms in cancer and RASopathies. We have quantified HRAS, NRAS, KRAS4A and KRAS4B protein abundance across a large panel of cell lines and healthy tissues. We observe consistent patterns of KRAS>NRAS>>HRAS protein expression in cells that correlate with the rank order of Ras mutation frequencies in cancer. Our data provide support for the model of a sweet-spot of Ras dosage mediating isoform-specific contributions to cancer and development. However, they challenge the notion that rare codons mechanistically underpin the predominance of KRAS mutant cancers. Finally, direct measurement of mutant versus wildtype KRAS protein abundance revealed a frequent imbalance that may suggest additional non-gene duplication mechanisms for optimizing oncogenic Ras dosage.
Diverse environmental perturbations reveal the evolution and context-dependency of genetic effects on gene expression levels
Authors: Lea Amanda J. , Peng Julie , Ayroles Julien F. 
Published: November 2021

AbstractThere is increasing appreciation that human complex traits are determined by poorly understood interactions between our genomes and daily environments. These “genotype x environment” (GxE) interactions remain difficult to map at the organismal level, but can be uncovered using molecular phenotypes. To do so at large-scale, we profiled transcriptomes across 12 cellular environments using 544 immortalized B cell lines from the 1000 Genomes Project. We mapped the genetic basis of gene expression across environments and revealed a context-dependent genetic architecture: the average heritability of gene expression levels increased in treatment relative to control conditions and, on average, each treatment revealed expression quantitative trait loci (eQTL) at 11% of genes. In total, 22% of all eQTL were context-dependent, and this group was enriched for trait- and disease-associated loci. Further, evolutionary analyses revealed that positive selection has shaped GxE loci involved in responding to immune challenges and hormones, but not man-made chemicals, suggesting there is reduced opportunity for selection to act on responses to molecules recently introduced into human environments. Together, our work highlights the importance of considering an exposure’s evolutionary history when studying and interpreting GxE interactions, and provides new insight into the evolutionary mechanisms that maintain GxE loci in human populations.
An End-to-End Deep Learning Speech Coding and Denoising Strategy for Cochlear Implants
Authors: Gajecki Tom , Nogueira Waldo 
Published: November 2021

ABSTRACTCochlear implant (CI) users struggle to understand speech in noisy conditions. To address this problem, we propose a deep learning speech denoising sound coding strategy that estimates the CI electric stimulation patterns out of the raw audio data captured by the micro-phone, performing end-to-end CI processing. To estimate the relative denoising performance differences between various approaches, we compared this technique to a classic Wiener filter and to a convTasNet. Speech enhancement performance was assessed by means of signal-to-noise-ratio improvement and the short-time objective speech intelligibility measure. Additionally, 5 CI users were evaluated for speech intelligibility in noise to assess the potential benefits of each algorithm. Our results show that the proposed method is capable of replacing a CI sound coding strategy while preserving its general use for every listener and performing speech enhancement in noisy environments, without sacrificing algorithmic latency.
Conservation Genomics of Urban Populations of Streamside Salamander (Ambystoma barbouri)
Authors: Hubbs N. Wade , Hurt Carla R. , Niedzwiecki John , Leckie Brian , Withers David 
Published: November 2021

AbstractIn Tennessee, populations of the state endangered Streamside Salamander (Ambystoma barbouri) are in decline as their distribution lies mostly within rapidly developing areas in the Nashville Basin. Information regarding the partitioning of genetic variation among populations ofA. barbouri,and the taxonomic status of these populations relative to northern populations and their congener, the smallmouth salamander (A. texanum), have important implications for management and conservation of this species. Here we combined mitochondrial sequencing and genome-wide single nucleotide polymorphism (SNP) data generated using Genotyping-by-Sequencing (GBS) to investigate patterns of genetic variation within Tennessee populations ofA. barbouri, to assess their relationship to populations in Kentucky, and to examine their phylogenetic relationship to the closely relatedA. texanum. Results from phylogenetic reconstructions reveal a complex history of TennesseeA. barbouripopulations with regards to northern populations, unisexualA. barbouri,andA. texanum. Patterns of mitochondrial sequence variation suggest thatA. barbourimay have originated within Tennessee and expanded north multiple times into Kentucky, Ohio, Indiana and West Virginia. Phylogenetic reconstructions based on genome-wide SNP data contradict results based on mitochondrial DNA and correspond to geographic and taxonomic boundaries. Variation in allele frequencies at SNP genotypes, as identified by multivariate analyses and Bayesian assignment tests, identified three evolutionary significant units (ESUs) forA. barbouriwithin the state of Tennessee. Collectively, these results emphasize the need for prioritizing conservation needs of Tennessee populations ofA. barbourito ensure the long-term persistence of this species.
Neuromodulation enables temperature robustness and coupling between fast and slow oscillator circuits in Cancer borealis
Authors: Städele Carola , Stein Wolfgang 
Published: November 2021

AbstractAcute temperature changes can disrupt neuronal activity and coordination with severe consequences for animal behavior and survival. Nonetheless, two rhythmic neuronal circuits in the crustacean stomatogastric ganglion (STG) and their coordination are maintained across a broad temperature range. However, it remains unclear how this temperature robustness is achieved. Here, we dissociate temperature effects on the rhythm generating circuits from those of upstream ganglia. We demonstrate that heat-activated factors extrinsic to the rhythm generators are essential to the slow gastric mill rhythm’s temperature robustness and contribute to the temperature response of the fast pyloric rhythm. The gastric mill rhythm crashed when only the STG circuits were heated. It could be restored when upstream ganglia were heated in addition, and the activity of the peptidergic modulatory projection neuron (MCN1) increased. Correspondingly, MCN1’s neuropeptide transmitter stabilized the rhythm and maintained it over a broad temperature range. Extrinsic neuromodulation is thus essential for the oscillatory circuits in the STG and enables neural circuits to maintain function in temperature-compromised conditions. In contrast, integer coupling between pyloric and gastric mill rhythms was independent of whether extrinsic inputs and STG pattern generators were temperature-matched or not, demonstrating that the temperature robustness of the coupling is enabled by properties intrinsic to the rhythm generators. However, at near-crash temperature, integer coupling was maintained only in some animals but was absent in others. This was true despite regular rhythmic activity in all animals, supporting that degenerate circuit properties result in idiosyncratic responses to environmental challenges.
SHIP164 is a Chorein Motif Containing Lipid Transport Protein that Controls Membrane Dynamics and Traffic at the Endosome-Golgi Interface
Authors: Hanna Michael G. , Suen Patreece , Wu Yumei , Reinisch Karin M. , De Camilli Pietro 
Published: November 2021

ABSTRACTCellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred in bulk from one membrane to another at membrane contact sites, and thus independently of vesicular traffic. Here we show that SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with these proteins and is localized on a subpopulation of vesicle clusters in the early endocytic pathway whose membrane cargo includes the cation-independent mannose-6-phosphate receptor (MPR) and ATG9. Loss of SHIP164 disrupts retrograde traffic of these organelles to the Golgi complex. Our findings raise the possibility that bulk transfer of lipids to endocytic membranes may play a role in their traffic.
Rational control of structural off-state heterogeneity in a photoswitchable fluorescent protein provides switching contrast enhancement
Authors: Adam Virgile , Hadjidemetriou Kyprianos , Jensen Nickels , Shoeman Robert L. , Woodhouse Joyce , Aquila Andrew , Banneville Anne-Sophie , Barends Thomas R. M. , Bezchastnov Victor , Boutet Sébastien , Byrdin Martin , Cammarata Marco , Carbajo Sergio , Christou Nina Eleni , Coquelle Nicolas , De la Mora Eugenio , El Khatib Mariam , Chicano Tadeo Moreno , Doak R. Bruce , Fieschi Franck , Foucar Lutz , Glushonkov Oleksandr , Gorel Alexander , Grünbein Marie Luise , Hilpert Mario , Hunter Mark , Kloos Marco , Koglin Jason E. , Lane Thomas J. , Liang Mengning , Mantovanelli Angela , Nass Karol , Kovacs Gabriela Nass , Owada Shigeki , Roome Christopher M. , Schirò Giorgio , Seaberg Matthew , Stricker Miriam , Thépaut Michel , Tono Kensuke , Ueda Kiyoshi , Uriarte Lucas M. , You Daehyun , Zala Ninon , Domratcheva Tatiana , Jakobs Stefan , Sliwa Michel , Schlichting Ilme , Colletier Jacques-Philippe , Bourgeois Dominique , Weik Martin 
Published: November 2021

AbstractReversibly photoswitchable fluorescent proteins are essential markers for advanced biological imaging, and optimization of their photophysical properties underlies improved performance and novel applications. Here we establish a link between photoswitching contrast, a key parameter that largely dictates the achievable resolution in nanoscopy applications, and chromophore conformation in the non-fluorescent state of rsEGFP2, a widely employed label in REversible Saturable OpticaL Fluorescence Transitions (RESOLFT) microscopy. Upon illumination, the cis chromophore of rsEGFP2 isomerizes to two distinct off-state conformations, trans1 and trans2, located on either side of the V151 side chain. Reducing or enlarging the side chain at this position (V151A and V151L variants) leads to single off-state conformations that exhibit higher and lower switching contrast, respectively, compared to the rsEGFP2 parent. The combination of structural information obtained by serial femtosecond crystallography with high-level quantum chemical calculations and with spectroscopic and photophysical data determined in vitro suggests that the changes in switching contrast arise from blue- and red-shifts of the absorption bands associated to trans1 and trans2, respectively. Thus, due to elimination of trans2, the V151A variants of rsEGFP2 and its superfolding variant rsFolder2 display a more than two-fold higher switching contrast than their respective parent proteins, both in vitro and in E. coli cells. The application of the rsFolder2-V151A variant is demonstrated in RESOLFT nanoscopy. Our study rationalizes the connection between structural and photophysical chromophore properties and suggests a means to rationally improve fluorescent proteins for nanoscopy applications.