bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metacommunities, fitness and gradual evolution
Authors: Priklopil Tadeas , Lehmann Laurent 
Published: January 2021

AbstractWe analyze the evolution of a multidimensional quantitative trait in a class structured focal species interacting with other species in a wider metacommunity. The evolutionary dynamics in the focal species as well as the ecological dynamics of the whole metacommunity is described as a continuous time process with birth, physiological development, dispersal, and death given as rates that can depend on the state of the whole metacommunity. This can accommodate complex local community and global metacommunity environmental feedbacks owing to inter- and intra-specific interactions, as well as local environmental stochastic fluctuations. For the focal species, we derive a fitness measure for a mutant allele affecting class-specific trait expression. Using classical results from geometric singular perturbation theory, we provide a detailed proof that if the effect of the mutation on phenotypic expression is small (“weak selection”), the large system of dynamical equations needed to describe selection on the mutant allele in the metacommunity can be reduced to a single ordinary differential equation on the arithmetic mean mutant allele frequency that is of constant sign. This invariance on allele frequency entails the mutant either dies out or will out-compete the ancestral resident (or wild) type. Moreover, the directional selection coefficient driving arithmetic mean allele frequency can be expressed as an inclusive fitness effect calculated from the resident metacommunity alone, and depends, as expected, on individual fitness differentials, relatedness, and reproductive values. This formalizes the Darwinian process of gradual evolution driven by random mutation and natural selection in spatially and physiologically class structured metacommunities.
Genotypic variation in soil penetration by maize roots is negatively related to ethylene-induced thickening
Authors: Vanhees Dorien J. , Schneider Hannah M. , Loades Kenneth W. , Bengough A. Glyn , Bennett Malcolm J. , Pandey Bipin K. , Brown Kathleen M. , Mooney Sacha J. , Lynch Jonathan P. 
Published: January 2021

AbstractRadial expansion is a classic response of roots to mechanical impedance that has generally been assumed to aid penetration. We analysed the response of maize nodal roots to impedance to test the hypothesis that radial expansion is not related to the ability of roots to cross a compacted soil layer. Genotypes varied in their ability to cross the compacted layer, and those with a steeper approach to the compacted layer or less radial expansion in the compacted layer were more likely to cross the layer and achieve greater depth. Root radial expansion was due to cortical cell size expansion, while cortical cell file number remained constant. Genotypes and nodal root classes that exhibited radial expansion upon encountering the compacted soil layer also thickened in response to exogenous ethylene in hydroponic culture, i.e. radial expansion in response to ethylene was correlated with the thickening response to impedance in soil. We propose that ethylene insensitive roots, i.e. those that do not thicken and are able to overcome impedance, have a competitive advantage under mechanically impeded conditions as they can maintain their elongation rates. We suggest that prolonged exposure to ethylene could function as a stop signal for axial root growth.
In vitromaturation ofToxoplasma gondiibradyzoites in human myotubes and their metabolomic characterization
Authors: Christiansen Céline , Maus Deborah , Hoppenz Ellen , Murillo-León Mateo , Hoffmann Tobias , Scholz Jana , Melerowicz Florian , Steinfeldt Tobias , Seeber Frank , Blume Martin 
Published: January 2021

AbstractThe apicomplexan parasiteToxoplasma gondiiforms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, currentin vitromodels do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-basedin vitroculture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms ofT. gondiithese tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages ofT. gondiiunder defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.
Multi-metabolomics using imaging mass spectrometry and liquid chromatography-tandem mass spectrometry for spatially characterizing monoterpene indole alkaloids secreted from roots
Authors: Nakabayashi Ryo , Takeda-Kamiya Noriko , Yamada Yutaka , Mori Tetsuya , Uzaki Mai , Nirasawa Takashi , Toyooka Kiminori , Saito Kazuki 
Published: January 2021

AbstractPlants release specialized (secondary) metabolites from their roots to communicate with other organisms, including soil microorganisms. The spatial behavior of such metabolites around these roots can help us understand roles for the communication; however, currently they are unclear because soil-based studies are complex. Here, we established a multi-metabolomics approach using imaging mass spectrometry (IMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially assign metabolites under laboratory conditions using agar. In a case study usingCatharanthus roseus, we showed that 58 nitrogen (N)-containing metabolites are released from the roots into the agar. For the metabolite assignment, we used15N-labeled and nonlabeled LC-MS/MS data, previously reported. Four metabolite ions were identified using authentic standard compounds as derived from monoterpene indole alkaloids (MIAs) such as ajmalicine, catharanthine, serpentine, and yohimbine. An alkaloid network analysis using dot products and spinglass methods characterized five clusters to which the 58 ions belong. The analysis clustered ions from the indolic skeleton-type MIAs to a cluster, suggesting that other communities may represent distinct metabolite groups. For future chemical assignments of the serpentine community, key fragmentation patterns were characterized using the15N-labeled and nonlabeled MS/MS spectra.
Proapoptotic RHG genes and mitochondria play a key non-apoptotic role in remodelling theDrosophilasensory system
Authors: Mukherjee Amrita , Pop Sinziana , Kondo Shu , Williams Darren W 
Published: January 2021

AbstractCaspases are best known for their role in programmed cell death but have also been found to be important in several non-apoptotic phenomena such as cell fate specification, cell migration and terminal differentiation. The dynamics of such sub-lethal caspase events and the molecular mechanisms regulating them are still largely unknown. As more tools for visualizing and manipulating caspase activationin vivobecome available, greater insights into this biology are being made. Using a new and sensitivein vivoeffector caspase probe, called SR4VH, we demonstrate that effector caspases are activated in pruning sensory neurons earlier than previously thought and that the level of caspase activation in these neurons is consistently lower than in neurons undergoing cell death. We reveal that Grim and Reaper, two of the four pro-apoptotic RHG proteins, are required for sensory neuron pruning and that disrupting the dynamics of the mitochondrial network prevents effector caspase activation in both pruning and dying sensory neurons. Overall, our findings demonstrate that a sublethal deployment of the ‘apoptotic machinery’ is critical for remodelling dendrites and also reveal a direct link between mitochondria and sensory neuron cell deathin vivo.
Social boldness correlates with brain gene expression in male green anoles
Authors: Kabelik David , Julien Allison R. , Ramirez Dave , O’Connell Lauren A. 
Published: January 2021

AbstractWithin populations, some individuals tend to exhibit a bold or shy social behavior phenotype relative to the mean. The neural underpinnings of these differing phenotypes – also described as syndromes, personalities, and coping styles – is an area of ongoing investigation. Although a social decision-making network has been described across vertebrate taxa, most studies examining activity within this network do so in relation to exhibited differences in behavioral expression. Our study instead focuses on constitutive gene expression in bold and shy individuals by isolating baseline gene expression profiles that influence social boldness predisposition, rather than those reflecting the results of social interaction and behavioral execution. We performed this study on male green anole lizards (Anolis carolinensis), an established model organism for behavioral research, which provides a crucial comparison group to investigations of birds and mammals. After identifying subjects as bold or shy through repeated reproductive and agonistic behavior testing, we used RNA sequencing to compare gene expression profiles between these groups within various forebrain, midbrain, and hindbrain regions. The ventromedial hypothalamus had the largest group differences in gene expression, with bold males having increased expression of neuroendocrine and neurotransmitter receptor and calcium channel genes compared to shy males. Conversely, shy males express more integrin alpha-10 in the majority of examined regions. There were no significant group differences in physiology or hormone levels. Our results highlight the ventromedial hypothalamus as an important center of behavioral differences across individuals and provide novel candidates for investigations into the regulation of individual variation in social behavior phenotype.
Genetic control of pluripotency epigenome determines differentiation bias in mouse embryonic stem cells
Authors: Byers Candice , Spruce Catrina , Fortin Haley J. , Czechanski Anne , Munger Steven C. , Reinholdt Laura G. , Skelly Daniel A. , Baker Christopher L. 
Published: January 2021

AbstractGenetically diverse pluripotent stem cells (PSCs) display varied, heritable responses to differentiation cues in the culture environment. By harnessing these disparities through derivation of embryonic stem cells (ESCs) from the BXD mouse genetic reference panel, along with C57BL/6J (B6) and DBA/2J (D2) parental strains, we demonstrate genetically determined biases in lineage commitment and identify major regulators of the pluripotency epigenome. Upon transition to formative pluripotency using epiblast-like cells (EpiLCs), B6 quickly dissolves naïve networks adopting gene expression modules indicative of neuroectoderm lineages; whereas D2 retains aspects of naïve pluripotency with little bias in differentiation. Genetic mapping identifies 6 majortrans-acting loci co-regulating chromatin accessibility and gene expression in ESCs and EpiLCs, indicating a common regulatory system impacting cell state transition. These loci distally modulate occupancy of pluripotency factors, including TRIM28, P300, and POU5F1, at hundreds of regulatory elements. Onetrans-acting locus on Chr 12 primarily impacts chromatin accessibility in ESCs; while in EpiLCs the same locus subsequently influences gene expression, suggesting early chromatin priming. Consequently, the distal gene targets of this locus are enriched for neurogenesis genes and were more highly expressed when cells carried B6 haplotypes at this Chr 12 locus, supporting genetic regulation of biases in cell fate. Spontaneous formation of embryoid bodies validated this with B6 showing a propensity towards neuroectoderm differentiation and D2 towards definitive endoderm, confirming the fundamental importance of genetic variation influencing cell fate decisions.
Ubx orchestrates tissue identity through regional and bidirectional changes to chromatin accessibility
Authors: Loker Ryan , Sanner Jordyn E. , Mann Richard S. 
Published: January 2021

AbstractHox proteins are homeodomain transcription factors that diversify serially homologous segments along the animal body axis, as revealed by the classic bithorax phenotype ofDrosophila melanogasterwhere mutations inUltrabithorax(Ubx) transform the third thoracic segment into the likeness of the second thoracic segment. To specify segment identity we show that Ubx both increases and decreases chromatin accessibility, coinciding with its role as both an activator and repressor of transcription. Surprisingly, whether Ubx functions as an activator or repressor differs depending on the proximal-distal position in the segment and the availability of Hox cofactors. Ubx-mediated changes to chromatin accessibility positively and negatively impact the binding of Scalloped (Sd), a transcription factor that is required for appendage development in both segments. These findings reveal how a single Hox protein can modify complex gene regulatory networks to transform the identity of an entire tissue.
Multiple RNA regulatory pathways coordinate the activity and expression pattern of a conserved germline RNA-binding protein
Authors: Albarqi Mennatallah M.Y. , Ryder Sean P. 
Published: January 2021

AbstractRNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, controlling the translation and stability of parental transcripts to control cell fate specification events prior to zygotic gene activation. The KH-domain RBP MEX-3 is conserved from nematode to human. It was first discovered inCaenorhabditis elegans, where it is essential for anterior cell fate and embryo viability. Here, we show thatmex-3mRNA is itself regulated by several RBPs to define its unique germline spatiotemporal expression pattern. We also show that both poly(A) tail length control and translational regulation contribute to this expression pattern. Though the 3’UTR is sufficient to establish the germline expression pattern, we show that it is not essential for reproduction. An allelic series of 3’UTR deletion variants identifies repressing regions of the UTR and show that the expression pattern is not precisely coupled to reproductive health. Together, our results define the pathways that govern the spatiotemporal regulation of this highly conserved germline RBP and suggest that redundant mechanisms control MEX-3 function when RNA regulation is compromised.
The Cardiolipin Transacylase Tafazzin Regulates Basal Insulin Secretion and Mitochondrial Function in Pancreatic Islets from Mice
Authors: Cole Laura K. , Agarwal Prasoon , Doucette Christine , Fonseca Mario , Xiang Bo , Sparagna Genevieve C. , Seshadri Nivedita , Vandel Marilyne , Dolinsky Vernon W. , Hatch Grant M. 
Published: January 2021

ABSTRACTObjectiveTafazzin (TAZ) is a cardiolipin (CL) biosynthetic enzyme important for maintaining mitochondrial function. TAZ impacts both the species and content of CL in the inner mitochondrial membrane which are essential for normal cellular respiration. In pancreatic β-cells, mitochondrial function is closely associated with insulin secretion. However, the role of TAZ and CL in the secretion of insulin from pancreatic islets remains unknown.MethodsMale 4-month-old doxycycline-inducible TAZ knock-down (TAZ KD) mice and wild-type littermate controls were utilized. Immunohistochemistry was used to assess β-cell morphology in whole pancreas sections, whileex vivoinsulin secretion, CL content, RNA-Seq analysis and mitochondrial oxygen consumption were measured from isolated islet preparations.ResultsEx vivoinsulin secretion under non-stimulatory low-glucose concentrations was reduced ∼52% from islets isolated from TAZ KD mice. Mitochondrial oxygen consumption under low-glucose conditions was also reduced ∼58% in islets from TAZ KD animals. TAZ-deficiency in pancreatic islets was associated with significant alteration in CL molecular species and reduced oxidized CL content. In addition, RNA-Seq of isolated islets showed that TAZ KD increased expression of extracellular matrix genes which are linked to pancreatic fibrosis, activated stellate cells and impaired β-cell function.ConclusionThese data indicate a novel role for TAZ in regulating normal β-cell function, particularly under low-glucose conditions.
Protein Phosphatase 1 regulates atypical mitotic and meiotic division inPlasmodiumsexual stages
Authors: Zeeshan Mohammad , Pandey Rajan , Subudhi Amit Kumar , Ferguson David J. P. , Kaur Gursimran , Rashpa Ravish , Nugmanova Raushan , Brady Declan , Bottrill Andrew R. , Vaughan Sue , Brochet Mathieu , Bollen Mathieu , Pain Arnab , Holder Anthony A. , Guttery David S. , Tewari Rita 
Published: January 2021

AbstractPP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell and ultrastructural imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show thatPlasmodiumPP1 is implicated in both mitotic exit and, potentially, establishing cell polarity during zygote development in the mosquito midgut, suggesting that small molecule inhibitors of PP1 should be explored for blocking parasite transmission.
Phospholipids Uniquely Modify Secondary Structure of α-Synuclein Oligomers
Authors: Dou Tianyi , Zhou Lei , Kurouski Dmitry 
Published: January 2021

ABSTRACTParkinson disease (PD) is a severe neurological disorder that affects more than a million people in the U.S. alone. A hallmark of PD is the formation of intracellular α-synuclein (α-Syn) protein aggregates called Lewy bodies (LBs). Although this protein does not have a particular localization in the central neural system, α-Syn aggregates are primarily found in certain areas of midbrain, hypothalamus and thalamus. Microscopic analysis of LBs revealed fragments of lipid-rich membranes, organelles and vesicles. These and other pieces of experimental evidence suggest α-Syn aggregation can be triggered by lipids. In this study, we used atomic force microscope Infrared (AFM-IR) spectroscopy to investigate structural organization of individual α-Syn oligomers grown in the presence of two different phospholipids vesicles. AFM-IR is a modern optical nanoscopy technique that has single-molecule sensitivity and sub-diffraction spatial resolution. Our results show that α-Syn oligomers grown in the presence of phosphatidylcholine have distinctly different structure than oligomers grown in the presence on phosphatidylserine. We infer that this occurs because of specific charges adopted by lipids, which in turn governs protein aggregation. We also found that protein to phospholipid ratio makes a substantial impact on the structure of α-Syn oligomers. These findings demonstrate that α-Syn is far more complex than expected from the perspective of structural organization of oligomeric species.
Actin dependent membrane polarization reveals the mechanical nature of the neuroblast polarity cycle
Authors: LaFoya Bryce , Prehoda Kenneth E. 
Published: January 2021

AbstractThe Par complex directs fate determinant segregation from the apical membrane of asymmetrically dividingDrosophilaneuroblasts. While the physical interactions that recruit the Par complex have been extensively studied, little is known about how the membrane itself behaves during polarization. We examined the membrane dynamics of neuroblasts and surrounding cells using a combination of super-resolution and time lapse imaging, revealing cellular-scale movements of diverse membrane features during asymmetric division cycles. Membrane domains that are distributed across the neuroblast membrane in interphase become polarized in early mitosis, where they mediate formation of cortical patches of the Par protein aPKC. Membrane and protein polarity cycles are precisely synchronized and are generated by extensive actin dependent forces that deform the surrounding tissue. In addition to suggesting a role for the membrane in asymmetric division, our results reveal the mechanical nature of the neuroblast polarity cycle.
Tonic activity in lateral habenula neurons promotes disengagement from reward-seeking behavior
Authors: Sleezer Brianna J. , Post Ryan J. , Bulkin David A. , Ebitz R. Becket , Lee Vladlena , Han Kasey , Warden Melissa R. 
Published: January 2021

SUMMARYSurvival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to aversion and negative valence, but its role in regulating the balance between reward-seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long disengagements from reward-seeking behavior, whether due to repeated reward omission or following sufficient consumption of reward. Further, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt re-engagement. We find no evidence for similar tonic activity fluctuations in ventral tegmental area (VTA) dopamine neurons. Our findings implicate the LHb as a key mediator of disengagement from reward-seeking behavior in multiple contexts and argue against the idea that the LHb contributes to decisions solely by signaling aversion.