bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prey speed up, predators slow down: non-consumptive effects on movement behavior of a ciliate predator-prey pair
Authors: Daugaard Uriah , Furrer Reinhard , Petchey Owen L. 
Published: November 2021

AbstractNon-consumptive effects (NCEs) of predators on prey, such as induced defensive strategies, are frequently neglected in the analysis of predator-prey interactions. Yet these effects can have demographic impacts as strong as consumption. As a counterpart to NCEs, resource-availability effects (RAEs) can prompt changes in predators as well, e.g., in their foraging behavior. We studied NCEs and RAEs in the ciliate predator-prey pairDidinium nasutumandParamecium caudatum. We examined the dependence of prey/predator swimming speed and body size on predator/prey presence. We also investigated prey spatial grouping behavior and the dependence of predator movement on local prey abundance. We collected individual movement and morphology data through videography of laboratory-based populations. We compared swimming speeds and body sizes based on their distributions. We used linear models to respectively quantify the effects of local prey abundance on predator displacements and of predator presence on prey grouping behavior. In the presence of prey, predator individuals swam more slowly, were bigger and made smaller displacements. Further, their displacements decreased with increasing local prey abundance. In contrast, in the presence of predators, proportionally more prey individuals showed a fast-swimming behavior and there was weak evidence for increased prey grouping. Trait changes entail energy expenditure shifts, which likely affect interspecific interactions and populations, as has been shown for NCEs. Less is known about the link between RAEs and demography, but it seems likely that the observed effects scale up to influence community and ecosystem stability, yet this remains largely unexplored.Significance StatementTo maximize their fitness, organisms balance investment in foraging and avoiding being eaten. The behaviors of prey and predators are thus expected to depend on the presence and absence of each other and serve either to boost the chances of predation evasion or to increase predation success. Here we provide an example of the co-dependence of behaviors in the predator-prey pairDidinium nasutumandParamecium caudatum. We show that the predator slows down and searches in smaller areas when prey are present, while the prey speeds up and possibly groups more as a response to the presence of predators. Such behavioral changes are likely to have a demographic and community impact that is not accounted for with common measures of predators-prey interactions.
Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain
Authors: Sherman Shachar , Kawakami Koichi , Baier Herwig 
Published: November 2021

SummaryThe brain is assembled during development by both innate and experience-dependent mechanisms1–7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7–9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11–16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.
Multivalent peptide ligands to probe the chromocenter microenvironment in living cells
Authors: Guidotti Nora , Eördögh Ádám , Mivelaz Maxime , Rivera-Fuentes Pablo , Fierz Beat 
Published: November 2021

AbstractChromatin is spatially organized into functional states that are defined by both the presence of specific histone post-translational modifications (PTMs) and a defined set of chromatin-associated ‘reader’ proteins. Different models for the underlying mechanism of such compartmentalization have been proposed, including liquid-liquid phase separation (LLPS) of chromatin-associated proteins to drive spatial organization. Heterochromatin, characterized by lysine 9 methylation on histone H3 (H3K9me3) and the presence of heterochromatin protein 1 (HP1) as a multivalent reader, represents a prime example of a spatially defined chromatin state. Heterochromatin foci exhibit features of protein condensates driven by LLPS; however, the exact nature of the physicochemical environment within heterochromatin in different cell types is not completely understood. Here, we present tools to interrogate the environment of chromatin sub-compartments in the form of modular, cell-permeable, multivalent and fluorescent peptide probes. These probes can be tuned to target specific chromatin states by providing binding sites to reader proteins and can thereby integrate into the PTM-reader interaction network. As a target, here we generate probes specific to HP1, directing them to heterochromatin at chromocenters in mouse fibroblasts. Moreover, we use a polarity-sensing photoactivatable probe that photoconverts to a fluorescent state in phase-separated protein droplets and thereby reports on the local microenvironment. Equipped with this dye, our probes indeed turn fluorescent in murine chromocenters. However, image analysis and single-molecule tracking experiments reveal that the compartments are less dense and more dynamic than HP1 condensates obtained in vitro. Our results thus demonstrate that the local organization of heterochromatin in chromocenters is internally more complex than an HP1 condensate.
Efficient inhibition of cell proliferation and promotion of apoptosis requires continuous treatment with abemaciclib
Authors: Raquel Torres-Guzmán , Patricia Ganado Maria , Cecilia Mur , Carlos Marugán , Carmen Baquero , Yanzhu Yang , Zeng Yi , Huimin Bian , Jian Du , Alfonso de Dios , Oscar Puig , Jose Lallena Maria 
Published: November 2021

AbstractAbemaciclib is an oral, selective cyclin-dependent kinase 4 & 6 inhibitor (CDK4 & 6i), approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) as monotherapy for endocrine refractory disease, and with endocrine therapy (ET) for initial treatment and after progression on ET. Abemaciclib has also shown clinical activity in combination with ET in patients with high risk early BC (EBC). Here, we examined the preclinical attributes of abemaciclib and other CDK4 & 6i using biochemical and cell-based assays. In vitro, abemaciclib preferentially inhibited CDK4 kinase activity versus CDK6, resulting in inhibition of cell proliferation in a panel of BC cell lines with higher average potency than palbociclib or ribociclib. Abemaciclib showed activity regardless of HER2 amplification and phosphatidylinositol 3-kinase (PI3KCA) gene mutation status. In human bone marrow progenitor cells, abemaciclib showed lower impact on myeloid maturation than other CDK4 & 6i when tested at unbound concentrations similar to those observed in clinical trials. Continuous abemaciclib treatment provided profound inhibition of cell proliferation, and triggered senescence and apoptosis. These preclinical results support the unique efficacy and safety profile of abemaciclib observed in clinical trials.
Deep embedding and alignment of protein sequences
Authors: Llinares-López Felipe , Berthet Quentin , Blondel Mathieu , Teboul Olivier , Vert Jean-Philippe 
Published: November 2021

AbstractProtein sequence alignment is a key component of most bioinformatics pipelines to study the structures and functions of proteins. Aligning highly divergent sequences remains, however, a difficult task that current algorithms often fail to perform accurately, leaving many proteins or open reading frames poorly annotated. Here, we leverage recent advances in deep learning for language modelling and differentiable programming to propose DEDAL, a flexible model to align protein sequences and detect homologs. DEDAL is a machine learning-based model that learns to align sequences by observing large datasets of raw protein sequences and of correct alignments. Once trained, we show that DEDAL improves by up to two- or three-fold the alignment correctness over existing methods on remote homologs, and better discriminates remote homologs from evolutionarily unrelated sequences, paving the way to improvements on many downstream tasks relying on sequence alignment in structural and functional genomics.
NucleoMap: a computational tool for identifying nucleosomes in ultra-high resolution contact maps
Authors: Huang Yuanhao , Wang Bingjiang , Liu Jie 
Published: November 2021

1ABSTRACTAlthough poorly positioned nucleosomes are ubiquitous in the prokaryote genome, they are difficult to identify with existing nucleosome identification methods. Recently available enhanced high-throughput chromatin conformation capture techniques such as Micro-C, DNase Hi-C, and Hi-CO characterize nucleosome-level chromatin proximity, probing the positions of mono-nucleosomes and the spacing between nucleosome pairs at the same time, enabling profiling of nucleosomes in poorly positioned regions. Here we develop a novel computational approach, NucleoMap, to identify nucleosome positioning from ultra-high resolution chromatin contact maps. By integrating nucleosome binding preferences, read density, and pairing information, NucleoMap precisely locates nucleosomes in both eukaryotic and prokaryotic genomes and outperforms existing nucleosome identification methods in precision and recall. We rigorously characterize genome-wide association in eukaryotes between the spatial organization of mono-nucleosomes and their corresponding histone modifications, protein binding activities, and higher-order chromatin functions. We also predict two tetra-nucleosome folding structures in human embryonic stem cells using machine learning methods and analysis their distribution at different structural and functional regions. Based on the identified nucleosomes, nucleosome contact maps are constructed, reflecting the inter-nucleosome distances and preserving the original data’s contact distance profile.
Random attention can explain apparent object choice behavior in free-walking blowflies
Authors: Monteagudo José , Egelhaaf Martin , Lindemann Jens Peter 
Published: November 2021

AbstractFlies are often observed to approach dark objects. To a naïve observer they seem to pay selective attention to one out of several objects although previous research identified a reflex-like fixation behavior integrating responses to all objects as possible underlying mechanism. In a combination of behavioral experiments and computational modelling, we investigate the choice behavior of flies freely walking towards an arrangement of two objects placed at a variable distance from each other. The walking trajectories are oriented towards one of the objects much earlier than predicted by a simple reactive model. We show that object choice can be explained by a continuous control scheme in combination with a mechanism randomly responding to the position of each object according to a stochastic process. Although this may be viewed as a special form of an attention-like mechanism, the model does not require an explicit decision mechanism or a memory for the drawn decision.Summary StatementWalking blowflies apparently choose one of two objects to approach. In model simulations, a fixation scheme combined with random attention replicates this behavior without an explicit decision mechanism.
Polo-like kinase 4 homodimerization is not required for catalytic activation, autodestruction, or centriole assembly
Authors: Ryniawec John M. , Buster Daniel W. , Slevin Lauren K. , Boese Cody J. , Amoiroglou Anastasia , Dean Spencer M. , Slep Kevin C. , Rogers Gregory C. 
Published: November 2021

AbstractPolo-like kinase 4 (Plk4) is the master-regulator of centriole assembly and cell cycle-dependent regulation of its activity maintains proper centrosome number. During most of the cell cycle, Plk4 levels are nearly undetectable due to its ability to autophosphorylate and trigger its own ubiquitin-mediated degradation. However, during mitotic exit, Plk4 forms a single aggregate on the centriole surface to stimulate centriole duplication. Whereas most Polo-like kinase family members are monomeric, Plk4 is unique because it forms homodimers. Notably, Plk4 trans-autophosphorylates a degron near its kinase domain, a critical step in autodestruction. While it is thought that the purpose of homodimerization is to promote trans-autophosphorylation, this has not been tested. Here, we generate separation-of-function Plk4 mutants that fail to dimerize, and we show that homodimerization is required to create a binding site for the Plk4 activator, Asterless. Surprisingly, Plk4 dimer mutants are catalytically active in cells, promote centriole assembly, and can trans-autophosphorylate by a process based its on concentration-dependent aggregation. Our findings implicate a concentration-dependent pathway of Plk4 activation that does not require Asterless binding or homodimerization. Lastly, we propose a model of Plk4 cell cycle regulation that utilizes both activation pathways – Asterless-dependent and aggregation-driven – to restrict centriole assembly to mother centrioles.
Structure and functionality of a multimeric human COQ7:COQ9 complex
Authors: Manicki Mateusz , Aydin Halil , Abriata Luciano A. , Overmyer Katherine A. , Guerra Rachel M. , Coon Joshua J. , Peraro Matteo Dal , Frost Adam , Pagliarini David J. 
Published: November 2021

AbstractCoenzyme Q (CoQ, ubiquinone) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined ‘complex Q’ metabolon. Here we present a structure and functional analyses of a substrate- and NADH-bound oligomeric complex comprised of two complex Q subunits: the hydroxylase COQ7, which performs the penultimate step in CoQ biosynthesis, and the prenyl lipid-binding protein COQ9. We reveal that COQ7 adopts a modified ferritin-like fold with an extended hydrophobic access channel whose substrate binding capacity is enhanced by COQ9. Using molecular dynamics simulations, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for CoQ intermediates to translocate from within the bilayer to the proteins’ lipid-binding sites. Two such tetramers assemble into a soluble octamer, closed like a capsid, with lipids captured within. Together, these observations indicate that COQ7 and COQ9 cooperate to access hydrophobic precursors and coordinate subsequent synthesis steps toward producing mature CoQ.
The evolution of widespread recombination suppression on the Dwarf Hamster (Phodopus) X chromosome
Authors: Moore Emily C. , Thomas Gregg W. C. , Mortimer Sebastian , Kopania Emily E. K. , Hunnicutt Kelsie E. , Clare-Salzler Zachary J. , Larson Erica L. , Good Jeffrey M. 
Published: November 2021

The mammalian X chromosome shows strong conservation among distantly related species, limiting insights into the distinct selective processes that have shaped sex chromosome evolution. We constructed a chromosome-scale de novo genome assembly for the Siberian dwarf hamster (Phodopus sungorus), a species reported to show extensive recombination suppression across an entire arm of the X chromosome. Combining a physical genome assembly based on shotgun and long-range proximity ligation sequencing with a dense genetic map, we detected widespread suppression of female recombination across ∼65% of the Phodopus X chromosome. This region of suppressed recombination likely corresponds to the Xp arm, which has previously been shown to be highly heterochromatic. Using additional sequencing data from two closely-related species (P. campbelli and P. roborovskii), we show that recombination suppression on Xp appears to be independent of major structural rearrangements. The suppressed Xp arm was enriched for several transposable element families and de-enriched for genes primarily expressed in the placenta, but otherwise showed similar gene densities, expression patterns, and rates of molecular evolution when compared to the recombinant Xq arm. Phodopus Xp gene content and order was also broadly conserved relative to the more distantly related rat X chromosome. Collectively, these data suggest that widespread suppression of recombination has likely evolved through the transient induction of facultative heterochromatin on the Phodopus Xp arm without major changes in chromosome structure or genetic content. Thus, dramatic changes in the recombination landscape have so far had relatively subtle influences on overall patterns of X-linked molecular evolution.Significance StatementSex chromosome evolution represents a dynamic process of genomic specialization that is thought to be dependent on evolution of recombination. Here we use genome sequencing and genetic mapping to show that one arm comprising the majority of the X chromosome in a species of dwarf hamster has largely lost the ability to recombine in males and females. Although these dramatic shifts in recombination frequencies might eventually lead to sex chromosome degeneration, loss of recombination on this arm is associated with relatively minor changes in chromosome structure and gene contents in this species. These results underscore the conservation of the X chromosome across mammals, and allow us to test predictions about how genetic recombination influences sex chromosome evolution.
Structures of the Cyanobacterial Phycobilisome
Authors: Sauer Paul V. , Dominguez-Martin Maria Agustina , Kirst Henning , Sutter Markus , Bina David , Greber Basil J. , Nogales Eva , Polívka Tomáš , Kerfeld Cheryl A. 
Published: November 2021

AbstractThe phycobilisome is an elaborate antenna that is responsible for light-harvesting in cyanobacteria and red-algae. This large macromolecular complex captures incident sunlight and transfers the energy via a network of pigment molecules called bilins to the photosynthetic reaction centers. The phycobilisome of the model organism Synechocystis PCC 6803 consists of a core to which six rods are attached but its detailed molecular architecture and regulation in response to environmental conditions is not well understood. Here we present cryo-electron microscopy structures of the 6.2 MDa phycobilisome from Synechocystis PCC 6803 resolved at 2.1 Å (rods) to 2.7 Å (core), revealing three distinct conformations, two previously unknown. We found that two of the rods are mobile and can switch conformation within the complex, revealing a layer of regulation not described previously. In addition, we found a novel linker protein in the structure, that may represent a long-sought subunit that tethers the phycobilisome to the thylakoid membrane. Finally, we show how excitation energy is transferred within the phycobilisome and correlate our structures with known spectroscopic properties. Together, our results provide detailed insights into the biophysical underpinnings of cyanobacterial light harvesting and lay the foundation for bioengineering of future phycobilisome variants and artificial light harvesting systems.
River network rearrangements promote speciation in lowland Amazonian birds
Authors: Musher Lukas J. , Giakoumis Melina , Albert James , Del-Rio Glaucia , Rego Marco , Thom Gregory , Aleixo Alexandre , Ribas Camila C. , Brumfield Robb T. , Smith Brian Tilston , Cracraft Joel 
Published: November 2021

AbstractLarge Amazonian rivers impede dispersal for many species, but lowland river networks frequently rearrange, thereby altering the location and effectiveness of river-barriers through time. These rearrangements may promote biotic diversification by facilitating episodic allopatry and secondary contact among populations. We sequenced genome-wide markers to evaluate histories of divergence and introgression in six Amazonian avian species-complexes. We first tested the assumption that rivers are barriers for these taxa and found that even relatively small rivers facilitate divergence. We then tested whether species diverged with gene flow and recovered reticulate histories for all species, including one potential case of hybrid speciation. Our results support the hypothesis that river dynamics promote speciation and reveal that many rainforest taxa are micro-endemic, unrecognized and thus threatened with imminent extinction. We propose that Amazonian hyper-diversity originates in part from fine-scale barrier displacement processes –including river dynamics– which allow small populations to differentiate and disperse into secondary contact.
Cbln1 regulates axon growth and guidance in multiple neural regions
Authors: Han Peng , She Yuanchu , Yang Zhuoxuan , Zhuang Mengru , Wang Qingjun , Luo Xiaopeng , Yin Chaoqun , Zhu Junda , Jaffrey Samie R. , Ji Sheng-Jian 
Published: November 2021

AbstractThe accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon guidance have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS). Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.Impact statementDespite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.