bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Drosophila HP1 family is associated with active gene expression across chromatin contexts
Authors: Schoelz John M. , Feng Justina X. , Riddle Nicole C. 
Published: February 2020

ABSTRACTDrosophila Heterochromatin Protein 1a (HP1a) is essential for heterochromatin formation and is involved in transcriptional silencing. However, certain loci require HP1a to be transcribed properly. One model posits that HP1a acts as a transcriptional silencer within euchromatin while acting as an activator within heterochromatin. However, HP1a has been observed as an activator of a set of euchromatic genes. Therefore, it is not clear whether, or how, chromatin context informs the function of HP1 proteins. To understand the role of HP1 proteins in transcription, we examined the genome-wide binding profile of HP1a as well as two other Drosophila HP1 family members, HP1B and HP1C, to determine whether coordinated binding of these proteins is associated with specific transcriptional outcomes. We found that HP1 proteins share a majority of their endogenous binding targets. These genes are marked by active histone modifications and are expressed at higher levels than non-target genes in both heterochromatin and euchromatin. In addition, HP1 binding targets displayed increased RNA polymerase pausing compared to non-target genes. Specifically, co-localization of HP1B and HP1C was associated with the highest levels of polymerase pausing and gene expression. Analysis of HP1 null mutants suggests these proteins coordinate activity at transcription start sites (TSSs) to regulate transcription. Depletion of HP1B or HP1C alters expression of protein-coding genes bound by HP1 family members. Our data broadens understanding of the mechanism of transcriptional activation by HP1a and highlights the need to consider particular protein-protein interactions, rather than broader chromatin context, to predict impacts of HP1 at TSSs.
Convergent Evolution of Conserved Mitochondrial Pathways Underlies Repeated Adaptation to Extreme Environments
Authors: Greenway Ryan , Barts Nick , Henpita Chathurika , Brown Anthony P. , Rodriguez Lenin Arias , Rodríguez Peña Carlos M. , Arndt Sabine , Lau Gigi Y. , Murphy Michael P. , Wu Lei , Lin Dingbo , Shaw Jennifer H. , Kelley Joanna L. , Tobler Michael 
Published: February 2020

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S)—a toxicant that impairs mitochondrial function—across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H2S in sulfide springP. mexicana, but not ancestral lineages from nonsulfidic habitats, due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H2S tolerance in different populations is likely caused by a combination of selection on standing genetic variation andde novomutations. At a macroevolutionary scale, H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes of genes associated with H2S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and—in some instances—codons are implicated in H2S adaptation in lineages that span 40 million years of evolution.Significance StatementSome organisms can tolerate environments lethal for most others, but we often do not know what adaptations allow them to persist and whether the same mechanisms underly adaptation in different lineages exposed to the same stressors. Investigating fish inhabiting springs rich in toxic hydrogen sulfide (H2S), we show that tolerance is mediated by the modification of pathways that are inhibited by H2S and those that can detoxify it. Sulfide spring fishes across multiple genera have evolved similar modifications of toxicity targets and detoxification pathways, despite abundant lineage-specific variation. Our study highlights how constraints associated with the physiological consequences of a stressor limit the number of adaptive solutions and lead to repeatable evolutionary outcomes across organizational and evolutionary scales.
Dpp and Hedgehog promote the Glial response to neuronal damage in the developing Drosophila Visual system
Authors: Velarde Sergio B. , Quevedo Alvaro , Estella Carlos , Baonza Antonio 
Published: February 2020

AbstractDamage in the nervous system induces a stereotypical response that is mediated by glial cells. Here, we use the eye disc to explore the mechanisms involved in promoting glial cell response after neural injuries. We demonstrate that eye glia cells rapidly respond to neuronal injury by increasing in number and undergoing morphological changes, which grant them phagocytic abilities. We found that this glial response is controlled by the activity of the long-range signalling pathways,decapentaplegic(dpp) andhedgehog(hh). These pathways are activated in the damaged region and their functions are necessary for inducing glial cell proliferation and migration to the eye discs. The latter of these two processes depends on the function of the JNK pathway, which is cooperatively activated bydppandhhsignalling.
Basal leakage in oscillation: coupled transcriptional and translational control using feed-forward loops
Authors: Joanito Ignasius , Yan Ching-Cher Sanders , Chu Jhih-Wei , Wu Shu-Hsing , Hsu Chao-Ping 
Published: February 2020

AbstractThe circadian clock is a complex system that plays many important roles in most organisms. Previously, many mathematical models have been used to sharpen our understanding of theArabidopsisclock. However, these models are mostly dependent on transcriptional regulation, and the importance of post-translational regulation is still rarely discussed from theoretical aspects. In this study, we built a series of simplified oscillators with different regulations to study the importance of post-translational regulation (specifically, 26S proteasome degradation) in the clock system. We found that a simple transcriptional-based oscillator can already generate sustained oscillation, but the oscillation can be easily destroyed in the presence of transcriptional leakage. Coupling post-translational control with transcriptional-based oscillator in a feed-forward loop will greatly improve the robustness of the oscillator in the presence of basal leakage. Using these general models, we were able to replicate the increased variability observed in the E3 ligase mutant for both plant and mammalian clocks. With this insight, we also predict a plausible regulator of several E3 ligase genes in the plant’s clock. Thus, our results provide insights into and the plausible importance in coupling transcription and post-translation controls in the clock system.Author summaryFor circadian clocks, several current models had successfully captured the essential dynamic behavior of the clock system mainly with transcriptional regulation. Previous studies have shown that the 26s (1, 2) proteasome degradation controls are important in maintaining the stability of circadian rhythms. However, how the loss-of-function or over-expression mutant of this targeted degradations lead to unstable oscillation is still unclear. In this work, we investigate the importance of coupled transcriptional and post-translational feedback loop in the circadian oscillator. With general models our study indicate that the unstable behavior of degradation mutants could be caused by the increase in the basal level of the clock genes. We found that coupling a non-linear degradation control into this transcriptional based oscillator using feed-forward loop improves the robustness of the oscillator. Using this finding, we further predict some plausible regulators of Arabidopsis’s E3 ligase protein such as COP1 and SINAT5. Hence, our results provide insights on the importance of coupling transcription and post-translation controls in the clock system.
A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels
Authors: Lundberg Arian , Lindström Linda S. , Parker Joel S. , Löverli Elinor , Perou Charles M. , Bergh Jonas , Tobin Nicholas P. 
Published: February 2020

AbstractBackgroundPan-cancer genomic analyses based on the magnitude of pathway activity are currently lacking. Focusing on the cell cycle, we examined the DNA mutations and chromosome arm-level aneuploidy within tumours with low, intermediate and high cell cycle activity.Patients and methodsMatching mRNA, gene mutational status, chromosomal arm-level aberrations and clinico-pathological data was assembled from pan-cancer studies of 9,515 patients with 32 different cancers. Cell cycle activity was estimated from mRNA data using the cell cycle score (CCS) signature. Barplots were used to visualise mutation and chromosomal aberration frequency within CCS subgroups. Kaplan-Meier and multivariable Cox-regression analyses were used to determine survival differences between CCS subgroups.ResultsCell cycle activity varied broadly across and within all cancers.TP53andPIK3CAmutations were common in all CCS subgroups but with increasing frequency as cell cycle activity levels increased (P< 0.001). Mutations inBRAFand gains in 16p were less frequent CCS high tumours (P< 0.001). In Kaplan-Meier analysis, patients whose tumours were CCS Low had a longer PFI relative to intermediate or high (P< 0.001) and this significance remained in multivariable analysis (CCS intermediate: HR = 1.37; 95% CI 1.17 – 1.60, CCS high: 1.54; 1.29 – 1.84, CCS Low = Ref).ConclusionsCell cycle activity varies across and within cancers and whilst similar DNA alterations can be found at all activity levels, some notable exceptions exist. These data also demonstrate that independent prognostic information can be derived on a pan-cancer level from a simple measure of cell cycle activity.
Polycystin-2 (TRPP2) Regulates Primary Cilium Length in LLC-PK1 Renal Epithelial Cells
Authors: Perez Paula L. , Scarinci Noelia , Cantiello Horacio F. , del Rocío Cantero María 
Published: February 2020

AbstractPolycystin-2 (PC2, TRPP2) is a Ca2+permeable non-selective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). PC2 is present in different cell locations, including the primary cilium of renal epithelial cells. Little is known, however, as to whether PC2 contributes to the structure of the primary cilium. Here, we explored the effect(s) of external Ca2+, PC2 channel blockers, andPKD2gene silencing on the length of primary cilia in wild type LLC-PK1 renal epithelial cells. To identify primary cilia and measure their length, confluent cell monolayers were fixed and immuno-labeled with an anti-acetylated α-tubulin antibody. Although primary cilia length measurements did not follow a Normal distribution, data were normalized by Box-Cox transformation rendering statistical difference under all experimental conditions. Cells exposed to high external Ca2+(6.2 mM) decreased a 13.5% (p < 0.001) primary cilia length as compared to controls (1.2 mM Ca2+). In contrast, the PC2 inhibitors amiloride (200 μM) and LiCl (10 mM), both increased primary ciliary length by 33.2% (p < 0.001), and 17.4% (p < 0.001), respectively.PKD2gene silencing by siRNA also elicited a statistically significant, 10.3% (p < 0.001) increase in primary cilia length, as compared to their respective scrambled RNA transfected cells. The data indicate that maneuvers that either regulate PC2 function or gene expression, modify the length of primary cilia in renal epithelial cells. Proper regulation of PC2 function in the primary cilium may be essential in the onset of mechanisms that trigger cyst formation in ADPKD.Significance StatementPolycystin-2 (PC2, TRPP2) is a Ca2+permeable non-selective cation channel causing the autosomal dominant polycystic kidney disease (ADPKD). The importance of intact cilia and of fully functional polycystins in the onset of ADPKD cyst formation, point to yet unknown signaling mechanisms occurring within this organelle. We determined that the extracellular Ca2+concentration, PC2 channel blockers, andPKD2gene silencing, all contribute to the length of primary cilia in wild type LLC-PK1 renal epithelial cells. The data indicate that proper regulation of PC2 function in the primary cilium may be essential in the onset of mechanisms that trigger cyst formation in ADPKD.
Infra-slow modulation of fast beta/gamma oscillations in the mouse visual system
Authors: Orlowska-Feuer Patrycja , Allen Annette Elisabeth , Brown Timothy Matthew , Szkudlarek Hanna Jowita , Lucas Robert James , Storchi Riccardo 
Published: February 2020

ABSTRACTInfra-slow (<0.02 Hz) and fast beta/gamma (20 – 100 Hz) oscillations in neurophysiological activity have been widely found in the subcortical visual system. While it is well established that fast beta/gamma oscillations are involved in visual processing, the role (if any) of infra-slow oscillations is currently unknown. One possibility is that infra-slow oscillations exert influence by modulating the amplitude of fast oscillations, yet the extent to which these different oscillations arise independently and interact remains unknown. We addressed these questions by recordingin vivospontaneous activity from subcortical visual system of visually intact mice, and animals whose retinal network was disrupted by advanced rod/cone degeneration (rd/rd cl) or melanopsin loss(Opn4-/-We found many neurons expressing only one type of oscillation, and indeed fast oscillations were absent inrd/rd cl.Conversely, neurons co-expressing the two oscillations were also common, and were encountered more often than expected by chance in visually intact but notOpn4-/-mice. Finally, where they co-occurred we found that beta/gamma amplitude was modulated by the infra-slow rhythm. Our data thus reveal that: 1.) infra-slow and beta-gamma oscillations are separable phenomena; and 2.) that they actively co-occur in a subset of neurones in which the phase of infra-slow oscillations define beta-gamma oscillation amplitude. These findings suggest that infra-slow oscillations could influence vision by modulating beta-gamma oscillations, and raise the possibility that disruptions in these oscillatory behaviours contribute to vision dysfunction in retinal dystrophy.KEY POINTS SUMMARYNeurophysiological activity in the subcortical visual system fluctuates in both infra-slow and fast oscillatory ranges, however the level of co-occurrence and potential functional interaction of these rhythms is unknown.Analyzing dark-adapted spontaneous activity in the mouse subcortical visual system, we find that these two types of oscillation interact uniquely through a population of neurons expressing both rhythms.Genetic ablation of rod/cone signaling potentiates infra-slow and abolishes fast beta/gamma oscillations while genetic ablation of melanopsin substantially diminishes the interaction between these two rhythms.Our results indicate that in an intact visual system the phase of infra-slow modulates fast beta/gamma oscillations.Thus one possible impact of infra-slow oscillations in vision is to guide visual processing by interacting with fast narrowband oscillations.
Copper nanoparticle application enhances plant growth and grain yield in maize under drought stress conditions
Authors: Nguyen Dong Van , Nguyen Huong Mai , Le Nga Thanh , Nguyen Kien Huu , Le Huong Mai , Nguyen Anh Trung , Dinh Ngan Thi Thu , Hoang Son Anh , Ha Chien Van 
Published: February 2020

ABSTRACTAbiotic stresses, including drought, detrimentally affect the growth and productivity of many economically important crop plants, leading to significant yield losses, which can result in food shortages and threaten the sustainability of agriculture. Balancing between plant growth and stress responses is one of the most important characters for agricultural application to maximize plant production. In this study, we initially report that copper nanoparticle priming positively regulates drought stress responses in maize. The copper nanoparticle priming plants displayed enhanced drought tolerance indicated by their higher leaf water content and plant biomass under drought as compared with water-treated plants. Moreover, our data showed that the treatment of copper nanoparticle on plants increased anthocyanin, chlorophyll and carotenoid contents compared to water-treated plants under drought stress conditions. Additionally, histochemical analyses with nitro blue tetrazolium and 3,3’-diaminobenzidine revealed that reactive oxygen species accumulation of priming plants was decreased as a result of enhancement of reactive oxygen species scavenging enzyme activities under drought. Furthermore, our comparative yield analysis data indicated applying copper nanoparticle to plant increased total seed number and grain yield under drought stress conditions. Our data provided the evidences that copper nanoparticle regulates plant protective mechanisms associated with drought tolerance, which is a promising approach for the production of drought tolerant crop plants.
A self-initiated cue-reward learning procedure for neural recording in rodents
Authors: Reverte Ingrid , Volz Stephen , Alhazmi Fahd H. , Kang Mihwa , Kaufman Keith , Chan Sue , Jou Claudia , Iordanova Mihaela D. , Esber Guillem R. 
Published: February 2020

AbstractBackgroundSingle-unit recording in Pavlovian conditioning tasks requires the use of within-subject designs as well as sampling a considerable number of trials per trial type and session, which increases the total trial count. Pavlovian conditioning, on the other hand, requires a long average intertrial interval (ITI) relative to cue duration for cue-specific learning to occur. These requirements combined can make the session duration unfeasibly long.New MethodTo circumvent this issue, we developed a self-initiated variant of the Pavlovian magazine-approach procedure in rodents. Unlike the standard procedure, where the animals passively receive the trials, the self-initiated procedure grants animals agency to self-administer and self-pace trials from a predetermined, pseudorandomized list. Critically, whereas in the standard procedure the typical ITI is in the order of minutes, our procedure uses a much shorter ITI (10 s).ResultsDespite such a short ITI, discrimination learning in the self-initiated procedure is comparable to that observed in the standard procedure with a typical ITI, and superior to that observed in the standard procedure with an equally short ITI.Comparison with Existing Method(s)The self-initiated procedure permits delivering 100 trials in a ∼1-h session, almost doubling the number of trials safely attainable over that period with the standard procedure.ConclusionsThe self-initiated procedure enhances the collection of neural correlates of cue-reward learning while producing good discrimination performance. Other advantages for neural recording studies include ensuring that at the start of each trial the animal is engaged, attentive and in the same location within the conditioning chamber.
Characterization of nuclear mitochondrial insertions in the whole genomes of primates
Authors: Dayama Gargi , Zhou Weichen , Prado-Martinez Javier , Marques-Bonet Tomas , Mills Ryan E. 
Published: February 2020

ABSTRACTThe transfer and integration of whole and partial mitochondrial genomes into the nuclear genomes of eukaryotes is an ongoing process that has facilitated the transfer of genes and contributed to the evolution of various cellular pathways. Many previous studies have explored the impact of these insertions, referred to as NumtS, but have focused primarily on older events that have become fixed and are therefore present in all individual genomes for a given species. We previously developed an approach to identify novel Numt polymorphisms from next generation sequence data and applied it to thousands of human genomes. Here, we extend this analysis to 79 individuals of other great ape species including chimpanzee, bonobo, gorilla, orang-utan and also an old world monkey, macaque. We show that recent Numt insertions are prevalent in each species though at different apparent rates, with chimpanzees exhibiting a significant increase in both polymorphic and fixed Numt sequences as compared to other great apes. We further assessed positional effects in each species in terms of evolutionary time and rate of insertion and identified putative hotspots on chromosome 5 for Numt integration, providing insight into both recent polymorphic and older fixed reference NumtS in great apes in comparison to human events.
Poxvirus-encoded TNF receptor homolog dampens inflammation and protects the host from uncontrolled lung pathology and death during respiratory infection
Authors: Al Rumaih Zahrah , Tuazon Kels Ma. Junaliah , Ng Esther , Pandey Pratikshya , Pontejo Sergio M. , Alejo Alí , Alcamí Antonio , Chaudhri Geeta , Karupiah Gunasegaran 
Published: February 2020

AbstractEctromelia virus (ECTV) causes mousepox, a surrogate mouse model for smallpox caused by variola virus in humans. Both viruses encode tumor necrosis factor receptor (TNFR) homologs termed cytokine response modifier (Crm) proteins, containing a TNF-binding domain and a chemokine-binding domain termed smallpox virus-encoded chemokine receptor (SECRET) domain. Infection of ECTV-resistant C57BL/6 mice with an ECTV CrmD deletion mutant resulted in uniform mortality due to excessive TNF secretion and dysregulated inflammatory cytokine production but viral load was not affected. CrmD dampened lung pathology, leukocyte recruitment and inflammatory cytokines including TNF, IL-6, IL-10 and IFN-γ. Blockade of IL-6, IL-10R or TNF function with monoclonal antibodies reduced lung pathology and provided 60-100% protection from an otherwise lethal infection. IFN-γ caused lung pathology only when both the TNF-binding and SECRET domains were deleted but it was neither necessary nor sufficient to cause pathology when only the CrmD SECRET domain was expressed by virus.