bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling up: understanding movement from individual differences to population-level dispersal
Authors: Edelsparre Allan H. , Hefley Trevor J. , Rodríguez Marco A. , Fitzpatrick Mark J. , Sokolowski Marla B. 
Published: January 2021

AbstractDispersal is fundamental to life on our planet. Dispersal facilitates colonization of continents and islands. Dispersal mediates gene flow among populations, and influences the rate of spread of invasive species. Theory suggests that individuals consistently differ in dispersal propensity, however determining the relative contributions of environmental factors to individual and population-level dispersal, represent a major challenge to understand the spread of organisms. To address this, we conducted a field experiment usingDrosophila melanogaster.As proxies for individuals with different dispersal propensities, we used wildtype strains of flies with natural variants of theforaginggene, known to influence dispersal in laboratory and field experiments. These included flies withforsalleles known to be less dispersive, flies with theforRalleles which are more dispersive flies as well as an outbred population established from field collected flies. We released approximately 6000 flies of each strain in an experimental arena (100 m × 100 m) in the field and our recaptures were used to determine dispersal of flies over time. To estimate environmental effects on dispersal, we measured temperature, wind direction and wind speed. Using partial-differential equations we combined ecological diffusion with advection to estimate dispersal rates and responses to wind. We found that temperature effects elicited a similar response in high and low dispersal lab strains with dispersal rate increasing with temperature most rapidly at temperatures above 18°C. This was in contrast to outbred flies which remained unresponsive to temperature changes. We also detected a response to wind with advection rates increasing linearly with wind speed for all flies in general. Our results suggest that response to temperature and wind can minimize known differences in behavioural predispositions to disperse. Our results also suggest that the direction and magnitude of wind may play a key role in the colonization and distribution of fly populations. Our findings therefore have implications for forecasting the spread of pests and invasive species as well as pathogens and vectors of disease. Our findings further contribute to the understanding of how the environment can modify behavioural predispositions and to influence population-level dispersal in fly populations in particular and insect species in general.
Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status
Authors: Diboun Ilhame , Wani Sachin , Ralston Stuart H , Albagha Omar M E 
Published: January 2021

AbstractPaget’s Disease of Bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and replication set, comprising of 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through eQTM analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the replication with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.
Encoding-linked pupil response is modulated by expected and unexpected novelty: Implications for memory formation and neurotransmission
Authors: Kafkas Alex 
Published: January 2021

AbstractWhether a novel stimulus is expected or unexpected may have implications for the kind of ensuing encoding and the type of subsequent memory. Pupil response was used in the present study to explore the way expected and unexpected stimuli are encoded and whether encoding-linked pupil response is modulated by expectation. Participants first established a contingency relationship between a series of symbols and the type of stimulus (man-made or natural) that followed each one. At encoding, some of the target stimuli violated the previously established relationship (i.e., unexpected), while the majority conformed to this relationship (i.e., expected). Expectation at encoding had opposite effects on familiarity and recollection, the two types of memory that support recognition, and modulated differently the way pupil responses predicted subsequent memory. Encoding of unexpected novel stimuli was associated with increased pupil dilation as a predictor of subsequent memory type and strength. In contrast, encoding of expected novel stimuli was associated with decreased pupil response (constriction), which was predictive of subsequent memory type and strength. The findings support the close link between pupil response and memory formation, but critically indicate that this is modulated by the type of novelty as defined by expectation. These novel findings have important implications for the encoding mechanisms involved when different types of novelty are detected and is proposed to indicate the operation of different neurotransmitters in memory formation.
Proton receptors regulate synapse-specific reconsolidation in the amygdala
Authors: Koffman Erin E , Kruse Charles M , Singh Kritika , Naghavi FarzanehSadat , Egbo Jennifer , Boateng Sandra , Houdi BA Mark , Lin Boren , Debiec Jacek , Du Jianyang 
Published: January 2021

SUMMARYWhen an extinction procedure is performed within the reconsolidation window, the original aversive memory can be replaced by one that is less traumatic. Recent studies revealed that carbon dioxide (CO2) inhalation during retrieval enhances memory lability. However, the effects of CO2inhalation on the central nervous system can be extensive, and there is lack of evidence suggesting that the effects of CO2are selective to a reactivated memory. We discovered that CO2inhalation paired with memory retrieval potentiates the specific aversive memory trace, resulting in greater memory lability. The specific effects of CO2depend on acid-sensing ion channels (ASICs), the proton receptors that are involved in synaptic transmission and plasticity in the amygdala. In addition, CO2inhalation alters memory lability via synaptic plasticity at selectively targeted synapses. Overall, our results suggest that inhaling CO2during the retrieval event increases the lability of an aversive memory through a synapse-specific reconsolidation process.
Inferring differential subcellular localisation in comparative spatial proteomics using BANDLE
Authors: Crook Oliver M. , Davies Colin T. R. , Breckels Lisa M. , Christopher Josie A. , Gatto Laurent , Kirk Paul D.W. , Lilley Kathryn S. 
Published: January 2021

AbstractThe steady-state localisation of proteins provides vital insight into their function. These localisations are context specific with proteins translocating between different sub-cellular niches upon perturbation of the subcellular environment.Differential localisation, that is a change in the steady-state subcellular location of a protein, provides a step towards mechanistic insight of subcellular protein dynamics. Aberrant localisation has been implicated in a number of pathologies, thusdifferential localisationmay help characterise disease states and facilitate rational drug discovery by suggesting novel targets. High-accuracy high-throughput mass spectrometry-based methods now exist to map the steady-state localisation and re-localisation of proteins. Here, we propose a principled Bayesian approach, BANDLE, that uses these data to compute the probability that a protein differentially localises upon cellular perturbation, as well quantifying the uncertainty in these estimates. Furthermore, BANDLE allows information to be shared across spatial proteomics datasets to improve statistical power. Extensive simulation studies demonstrate that BANDLE reduces the number of both type I and type II errors compared to existing approaches. Application of BANDLE to datasets studying EGF stimulation and AP-4 dependent localisation recovers well studied translocations, using only two-thirds of the provided data. Moreover, we potentially implicate TMEM199 with AP-4 dependent localisation. In an application to cytomegalovirus infection, we obtain novel insights into the rewiring of the host proteome. Integration of high-throughput transcriptomic and proteomic data, along with degradation assays, acetylation experiments and a cytomegalovirus intcractome allows us to provide the functional context of these data.
Astrocyte-derived thrombospondin induces cortical synaptogenesis in a sex-specific manner
Authors: Mazur Anna , Bills Ean H. , Henderson Brandon J. , Risher W. Christopher 
Published: January 2021

AbstractThe regulation of synaptic connectivity in the brain is vital to proper functioning and development of the central nervous system (CNS). Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared to female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to TSP2, which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17β-estradiol production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that TSP-induced synaptogenesis is critical for the development of male but not female cortical synapses, contributing to sex differences in astrocyte-mediated synaptic connectivity.
Neural Correlates of a Trance Process and Alternative States of Consciousness in a Traditional Healer
Authors: Rogerson Rebecca G. , Barnstaple Rebecca , DeSouza Joseph F.X. 
Published: January 2021

AbstractTrance processes are a form of altered states of consciousness (ASC) widely reported across cultures. Entering these states is often linked to auditory stimuli such as singing, chanting, or rhythmic drumming. While scientific research into this phenomenon is relatively nascent, there is emerging interest in investigating the neural correlates of altered states of consciousness such as trance. This report aims to add to this field of ASC through exploring how the perception of an experiencedSangoma--traditional South African healer--entering a trance process correlates to BOLD signal modulation with auditory stimuli. Functional MRI data were analyzed using a General Linear model comparing music versus no music condition multiplied by the percept of experiencing trance (High or Low). Positive BOLD activation was shown in auditory cortex in both hemispheres during a trance process. Other brain regions tightly correlated to trance perception were right parietal, right frontal, and area prostriata (P<0.05, Bonferroni corrected). Orbitofrontal cortex (part of the Default Mode Network) was negatively activated and most correlated with music when trance was high, showing the largest differential between high and low trance perception. This is the first study to directly correlate BOLD signal variations in an expert subject’s percept of trance onset and intensity, providing insight into the neural signature and dynamics of this unique form of ASC. Future studies should examine in greater detail perception of trance processes in expert subjects, adding other neuroimaging modalities to further investigate how these brain regions are modulated by trance expertise.
Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ-9-tetrahydrocannabinol
Authors: Kanyo Richard , Amin Md Ruhul , Locskai Laszlo F. , Bouvier Danika D. , Olthuis Alexandria M. , Allison W. Ted , Ali Declan W. 
Published: January 2021

AbstractIn the light of legislative changes and the widespread use of cannabis as a recreational and medicinal drug, delayed effects of cannabis upon brief exposure during embryonic development are of high interest as early pregnancies often go undetected. Here, zebrafish embryos were exposed to cannabidiol (CBD) and Δ-9-tetrahydrocannabinol l (THC) until the end of gastrulation (1-10 hours post-fertilization) and analyzed later in development (4-5 days post-fertilization). In order to measure neural activity, we implemented CaMPARI (Calcium-Modulated Photoactivatable Ratiometric Integrator) and optimized the protocol for a 96-well format complemented by locomotor analysis. Our results revealed that neural activity was decreased by CBD more than THC. At higher doses, both cannabinoids could dramatically reduce neural activity and locomotor activity. Interestingly, the decrease was more pronounced when CBD and THC were combined. At the receptor level, CBD-mediated reduction of locomotor activity was partially prevented using cannabinoid type 1 and 2 receptor inhibitors. Overall, we report that CBD toxicity occurs via two cannabinoid receptors and is synergistically enhanced by THC exposure to negatively impact neural activity late in larval development. Future studies are warranted to reveal other cannabinoids and receptors involved in this pathway to understand the subsequent health implications of cannabis consumption on fetal development.
The evolution of cold nociception in drosophilid larvae and identification of a neural basis for cold acclimation
Authors: Himmel Nathaniel J. , Letcher Jamin M. , Sakurai Akira , Gray Thomas R. , Benson Maggie N. , Donaldson Kevin J. , Cox Daniel N. 
Published: January 2021

AbstractCold temperatures can be fatal to insects, but many species have evolved the ability to cold acclimate, thereby increasing their cold tolerance. While there is a growing body of knowledge concerning the mechanisms underlying cold tolerance, relatively little is known concerning how insects sense noxious cold (cold nociception), or how cold nociception might function in cold tolerance. It has been previously shown that Drosophila melanogaster larvae perform highly stereotyped, cold-evoked behaviors under the control of noxious cold-sensing neurons (nociceptors) innervating the barrier epidermis. In the present study, we first sought to describe cold-nociceptive behavior among 11 drosophilid species with differing cold tolerances and from differing climates. Behavioral analyses revealed that the predominant cold-evoked response among drosophilid larvae is a head-to-tail contraction (CT) behavior, which is likely inherited from a common ancestor. However, despite lack of phylogenetic signal (suggesting trait lability), the CT behavior was transient and there was no clear evidence that cold sensitivity was related to thermal environment; collectively this suggests that the behavior might not be adaptive. We therefore sought to uncover an alternative way that cold nociception might be protective. Using a combination of cold-shock assays, optogenetics, electrophysiology, and methods to genetically disrupt neural transmission, we demonstrate that cold sensing neurons in Drosophila melanogaster (Class III nociceptors) are sensitized by and critical to cold acclimation. Moreover, we demonstrate that cold acclimation can be optogenetically-evoked, sans cold. Collectively, these findings reveal that cold nociception constitutes a peripheral neural basis for Drosophila larval cold acclimation.Significance StatementMany insects adapt to cold in response to developmental exposure to cool temperatures. While there is a growing body of knowledge concerning the mechanisms underlying cold tolerance, it is unknown how sensory neurons might contribute. Here, we show that noxious cold sensing (cold nociception) is widely present among drosophilid larvae, and that cold-sensing neurons (Class III cold nociceptors) are necessary and sufficient drivers of cold acclimation. This suggests that cold acclimation has, at least in part, a neural basis.
Participation in a Science Festival Promotes Inclusive Science Communication around Autism Spectrum Disorder
Authors: Gunter Chris , Sinha Cynthia B , Jaquess David 
Published: January 2021

AbstractAs a high prevalence disorder with limited information about etiology, autism spectrum disorder (ASD) has been marked by confusion and miscommunication around its causes and treatments. To promote high-quality science communication, we participated in a local science festival, both providing information about the brain and ASD and asking passersby questions about their knowledge of ASD. We then asked the booth staffers to evaluate the program and conducted qualitative analyses of public and staffer responses. Public responses to the question “what would you like to know about autism?” most often concerned how the disorder was diagnosed or defined. In contrast, public responses to the question “what would you like others to know about autism?” centered around educating those unaffected by ASD on how to improve interactions and awareness, mentioning inclusivity and intersectionality, and dispelling negative stereotypes. The staffers overwhelmingly reported that in future years, they would include even more science and allow for more in-depth conversations with interested parties, as well as bringing materials in other languages. These responses are in keeping with a trend for more inclusive science communication, particularly in the field of behavioral health and ASD, and a desire to challenge myths around the condition. We conclude that our science festival interactions brought multiple benefits to public and staff.
Homogenization of a Reaction Diffusion Equation can Explain Influenza A Virus Load Data
Authors: Baabdulla Arwa Abdulla , Now Hesung , Park Ju An , Kim Woo-Jong , Jung Sungjune , Yoo Joo-Yeon , Hillen Thomas 
Published: January 2021

AbstractWe study the influence of spatial heterogeneity on the antiviral activity of mouse embryonic fibroblasts (MEF) infected with influenza A. MEF of typeUbe1L−/−are composed of two distinct sub-populations, the strong type that sustains a strong viral infection and the weak type, sustaining a weak viral load. We present new data on the virus load infection ofUbe1L−/−, which have been micro-printed in a checker board pattern of different sizes of the inner squares. Surprisingly, the total viral load at one day after inoculation significantly depends on the sizes of the inner squares. We explain this observation by using a reaction diffusion model and we show that mathematical homogenization can explain the observed inhomogeneities. If the individual patches are large, then the growth rate and the carrying capacity will be the arithmetic means of the patches. For finer and finer patches the average growth rate is still the arithmetic mean, however, the carrying capacity uses the harmonic mean. While fitting the PDE to the experimental data, we also predict that a discrepancy in virus load would be unobservable after only half a day. Furthermore, we predict the viral load in different inner squares that had not been measured in our experiment and the travelling distance the virions can reach after one day.
MYCoverexpression leads to increased chromatin interactions at superenhancers and c-Myc binding sites
Authors: See Yi Xiang , Chen Kaijing , Fullwood Melissa J. 
Published: January 2021

AbstractThe MYC oncogene encodes for the c-Myc protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. There have been many difficulties in targeting c-Myc, due to its complex network of regulators and the unstructured nature of its protein. Thus, we are interested in looking at the downstream cancer-specific functions of c-Myc. Overexpression of MYC leads to c-Myc binding at active enhancers, resulting in a global transcriptional amplification of active genes. However, the mechanism underlying this c-Myc enhancer invasion has not been well studied. To that end, we performed ChIP-seq, RNA-seq, 4C-seq and SIQHiC (Spike-in Quantitative Hi-C) on the U2OS osteosarcoma cell line with tetracycline-inducible MYC. MYC overexpression in U2OS cells modulated histone acetylation and increased c-Myc binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting c-Myc binding sites. Our results suggest that c-Myc molecules are recruited to and accumulates within zones of high transcription activity, binding first at stable promoter binding sites at low expression levels, then at superenhancer binding sites when overexpressed. At the same time, the recruitment of c-Myc and other transcription factors may stabilize chromatin interactions to increase chromatin contact frequency. The accumulation of c-Myc at cancer-type specific superenhancers may then drive the expression of interacting oncogenes that each cancer is highly reliant on. By elucidating the chromatin landscape of c-Myc driven cancers, we can potentially target these chromatin interactions for cancer therapy, without affecting physiological c-Myc signaling.
Rv3737 is required forMycobacterium tuberculosisgrowthin vitroandin vivoand correlates with bacterial load and disease severity in human tuberculosis
Authors: Li Qing , Peng Zhangli , Fu Xuefeng , Wang Hong , Zhao Zhaoliang , Pang Yu , Chen Ling 
Published: January 2021

AbstractRv3737 is the sole homologue of multifunctional transporter ThrE inMycobacterium tuberculosis(Mtb). In this study, we aimed to investigate whether this transporter participatesin vitroandin vivosurvival ofMtb. To characterize the role of Rv3737, we constructed and characterized anMtbH37RvΔRv3737. This strain was evaluated for altered growth rate and macrophage survival using cell model of infection. In addition, the comparative analysis was conducted to determine the association between Rv3737 mRNA expression and disease severity in active pulmonary TB patients. The H37RvΔRv3737 strain exhibited significant slow growth rate compared to H37Rv-WT strain in standard culture medium. Additionally, the survival rate of H37Rv-WT strain in macrophages was 2 folds higher than that of H37RvΔRv3737 at 72 h. A significant higher level of TNF-α and IL-6 mRNA expression was observed in macrophages infected with H37RvΔRv3737 as compared to H37Rv-WT. Of note, Rv3737 expression was significantly increased in clinicalMtbisolates than H37Rv-WT. The relative expression level of Rv3737 was positively correlated with lung cavity number in TB patients. Similarly, the higher Rv3737 mRNA level resulted in lower C(t) value by Xpert MTB/RIF assay, demonstrating that a positive correlation between Rv3737 expression and bacterial load in TB patients. In conclusion, our data is the first to demonstrate that the transporter Rv3737 is required forin vitrogrowth and survival of bacteria inside macrophages. In addition, the expression level of Rv3737 is associated with bacterial load and disease severity in pulmonary tuberculosis patients.