bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active vision during prey-capture in wild marmoset monkeys
Authors: Ngo Victoria , Gorman Julia C. , De la Fuente María Fernanda , Souto Antonio , Schiel Nicola , Miller Cory T. 
Published: April 2022

AbstractHere, we examined prey-capture in wild common marmosets (Callithrix jacchus) to explicate the active role of primate vision for high-precision, goal-directed motor actions in challenging natural environments. We observed distinct marmoset hunting strategies that each relied on the close integration of visual processes and dynamic biomechanical motor movements, but differed based on several factors including prey size/speed, substrate, and their relative distance to the prey. Marmoset positional behavior in these complex arboreal settings often involves extending the body, including inversions, while relying on vision to guide prey capture. Applying markerless pose estimation technology, analyses revealed details of how primate vision both guides and corrects rapid motor actions in real-time during prey-capture in the wild. These findings illustrate the significance of active vision during primate ethological behaviors in response to the very challenges the visual system evolved to solve.
Principal component analysis- and tensor decomposition-based unsupervised feature extraction to select more suitable differentially methylated cytosines: Optimization of standard deviation versus state-of-the-art methods
Authors: Taguchi Y-H. , Turki Turki 
Published: April 2022

ABSTRACTIn contrast to RNA-seq analysis, which has various standard methods, no standard methods for identifying differentially methylated cytosines (DMCs) exist. To identify DMCs, we tested principal component analysis and tensor decomposition-based unsupervised feature extraction with optimized standard deviation, which has been shown to be effective for differentially expressed gene (DEG) identification. The proposed method outperformed certain conventional methods, including those that assume beta-binomial distribution for methylation as the proposed method does not require this, especially when applied to methylation profiles measured using high throughput sequencing. DMCs identified by the proposed method also significantly overlapped with various functional sites, including known differentially methylated regions, enhancers, and DNase I hypersensitive sites. The proposed method was applied to data sets retrieved from The Cancer Genome Atlas to identify DMCs using American Joint Committee on Cancer staging system edition labels. This suggests that the proposed method is a promising standard method for identifying DMCs.
Evolutionary responses of a reef-building coral to climate change at the end of the last glacial maximum
Authors: Zhang Jia , Richards Zoe T. , Adam Arne A. S. , Chan Cheong Xin , Shinzato Chuya , Gilmour James , Thomas Luke , Strugnell Jan M. , Miller David J. , Cooke Ira 
Published: April 2022

AbstractClimate change threatens the survival of coral reefs on a global scale, primarily through mass bleaching and mortality as a result of marine heatwaves. While these short-term effects are clear, predicting the fate of coral reefs over the coming century is a major challenge. One way to understand the longer-term effects of rapid climate change is to examine the response of coral populations to past climate shifts. Coastal and shallow-water marine ecosystems such as coral reefs have been reshaped many times by sea-level changes during the Pleistocene, yet, few studies have directly linked this with its consequences on population demographics, dispersal, and adaptation. Here we use powerful analytical techniques, afforded by haplotype phased whole-genomes, to establish such links for the reef-building coral,Acropora digitifera. We show that three genetically distinct populations are present in northwestern Australia, and that their rapid divergence since the last glacial maximum (LGM) can be explained by a combination of founder-effects and restricted gene flow. Signatures of selective sweeps, too strong to be explained by demographic history, are present in all three populations and overlap with genes that show different patterns of functional enrichment between inshore and offshore habitats. In contrast to rapid divergence in the host, we find that photosymbiont communities are largely undifferentiated between corals from all three locations, spanning almost 1000 km, indicating that selection on host genes and not acquisition of novel symbionts, has been the primary driver of adaptation for this species in northwestern Australia.
Emergence of distinct neural subspaces in motor cortical dynamics during volitional adjustments of ongoing locomotion
Authors: Xing David , Truccolo Wilson , Borton David A. 
Published: April 2022

3AbstractThe brain is capable of simultaneously carrying out multiple functions, such as making different types of movements at the same time. One example is how we are able to both carry out stereotyped walking or running movements, while concurrently performing precise, target-directed movements such as kicking a ball in a soccer match. Recently, research has shown that different computations within the same population of neurons can be carried out without disrupting each other by confining the processes into separate subspaces. Whether this strategy is used to precisely control our limbs while maintaining locomotion is still an open question. Here, we recorded the activity of primary motor cortex in nonhuman primates during obstacle avoidance on a treadmill. We found that the same neural population was active during both basic unobstructed locomotion and volitional obstacle avoidance movements. Additionally, we identified the neural modes spanning the subspace of the low-dimensional dynamics in M1 using both supervised and unsupervised techniques. We found that motor cortex employs a subspace that consistently maintains the same cyclic activity throughout obstacle stepping, despite large changes in the movement itself. All the variance corresponding to the large change in movement during the obstacle avoidance is confined to its own distinct subspace. Our findings suggest that M1 utilizes different activity subspaces to coordinate the maintenance of ongoing locomotor-related neural dynamics and fast volitional gait adjustments during complex locomotion.4Significance StatementOur ability to modulate our ongoing walking gait with precise, voluntary adjustments is what allows us to navigate complex terrains. Locomotion and precise, goal-directed movements, such as reaching are two distinct movement modalities and have been shown to have differing requirements of motor cortical input. It is unknown how these two movements are represented in M1 low dimensional dynamics when both are carried out at the same time, such as during obstacle avoidance. We developed a novel obstacle avoidance paradigm in freely-moving non-human primates and discovered that the strategy employed by motor cortex is to confine the rhythmic locomotion-related dynamics and the voluntary, gait-adjustment movement into separate subspaces.
Exon Elongation Added Intrinsically Disordered Regions to the Encoded Proteins and Facilitated the Emergence of the Last Eukaryotic Common Ancestor
Authors: Fukuchi Satoshi , Noguchi Tamotsu , Anbo Hiroto , Homma Keiichi 
Published: April 2022

AbstractMost prokaryotic proteins consist of a single structural domain (SD) with little intrinsically disordered regions (IDRs) that by themselves do not adopt stable structures, while the typical eukaryotic protein is comprised of multiple SDs and IDRs. How eukaryotic proteins evolved to differ from prokaryotic proteins has not been fully elucidated. Here, we found that the longer internal exons are, the more frequently they encode IDRs in eight eukaryotes including vertebrates, invertebrates, a fungus, and plants. Based on this observation, we propose the “small bang” model from the proteomic viewpoint: the protoeukaryotic genes had no introns and mostly encoded one SD each, but a majority of them subsequently divided into multiple exons (step 1). Many exons unconstrained by SDs elongated to encode IDRs (step 2). The elongated exons encoding IDRs frequently facilitated the acquisition of multiple SDs to make the last common ancestor of eukaryotes (step 3). One prediction of the model is that long internal exons are mostly unconstrained exons. Analytical results of the eight eukaryotes are consistent with this prediction. In support of the model, we identified cases of internal exons that elongated after the rat-mouse divergence and discovered that the expanded sections are mostly in unconstrained exons and preferentially encode IDRs. The model also predicts that SDs followed by long internal exons tend to have other SDs downstream. This prediction was also verified in all the eukaryotic species analysed. Our model accounts for the dichotomy between prokaryotic and eukaryotic proteins and proposes a selective advantage conferred by IDRs.
Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury
Authors: Fröhlich Albrecht , Heuvel Florian olde , Rehman Rida , Krishnamurthy Sruthi Sankari , Li Shun , Li Zhenghui , Bayer David , Conquest Alison , Hagenston Anna M. , Ludolph Albert , Huber-Lang Markus , Boeckers Tobias , Knöll Bernd , Morganti-Kossmann Maria Cristina , Bading Hilmar , Roselli Francesco 
Published: April 2022

AbstractBackgroundTraumatic Brain Injury (TBI) is characterized by massive changes in neuronal excitation, from acute excitotoxicity to chronic hyper- or hypoexcitability. Nuclear calcium signaling pathways are involved in translating changes in synaptic inputs and neuronal activity into discrete transcriptional programs which not only affect neuronal survival and synaptic integrity, but also the crosstalk between neurons and glial cells. Here we report the effects of blunting neuronal nuclear calcium signals in the context of TBI.MethodsWe used AAV vectors to express the genetically-encoded and nuclear-targeted calcium buffer parvalbumin (PV.NLS.mCherry) or the calcium/calmodulin buffer CaMBP4.mCherry in neurons only. Upon TBI, the extent of neuroinflammation, neuronal death and synaptic loss were assessed by immunohistochemistry and targeted transcriptome analysis. Modulation of the overall level of neuronal activity was achieved by PSAM/PSEM chemogenetics targeted to parvalbumin interneurons. The functional impact of neuronal nuclear Calcium buffering in TBI was assessed by quantification of spontaneous whisking.ResultsBuffering neuronal nuclear calcium unexpectedly resulted in a massive and long-lasting increase in the recruitment of reactive microglia to the injury site, which was characterised by a disease-associated and phagocytic phenotypes. This effect was accompanied by a substantial surge in synaptic loss and significantly reduced whisking activity. Transcriptome analysis revealed a complex effect of TBI in the context of neuronal nuclear calcium buffering, with upregulation of complement factors, chemokines and interferon-response genes, as well as the downregulation of synaptic genes and epigenetic regulators compared to control conditions. Notably, nuclear calcium buffering led to a substantial loss in neuronal osteoprotegerin (OPG). Whereas stimulation of neuronal firing induced OPG expression. Viral re-expression of OPG resulted in decreased microglial recruitment and synaptic loss. OPG upregulation was also observed in the CSF of human TBI patients, underscoring its translational value.ConclusionNeuronal nuclear calcium signals regulate the degree of microglial recruitment and reactivity upon TBI via, among others, osteoprotegerin signals. Our findings support a model whereby neuronal activity altered after TBI exerts a powerful impact on the neuroinflammatory cascade, which in turn contributes to the overall loss of synapses and functional impairment.
T cell-mediated development of stromal fibroblasts with an immune-enhancing chemokine profile
Authors: Yan Ran , Fearon Douglas T. 
Published: April 2022

AbstractStromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or immune activation, but whether these cells adapt to these contrasting microenvironments is not known. Cancer-associated fibroblasts (CAFs) mediate immune quiescence by producing the chemokine CXCL12 that coats cancer cells to suppress T cell infiltration. We examined whether CAFs can adopt an immune-promoting chemokine profile. Single-cell RNA-sequencing of CAFs from mouse pancreatic adenocarcinomas identified a sub-population with decreased expression of CXCL12 and increased expression of the T cell-attracting chemokine, CXCL9, that was expanded when tumors were infiltrated with T cells. Conditioned media from activated CD8+ T cells containing TNFα and IFNγ converted the chemokine profile of stromal fibroblasts from a CXCL12+/CXCL9- immune suppressive phenotype into a CXCL12-/CXCL9+ immune-activating phenotype. Studies with recombinant cytokines showed that TNFα acted synergistically with IFNγ to induce CXCL9 expression, and alone was mainly responsible for suppressing CXCL12 expression. This coordinated chemokine switch demonstrates that stromal fibroblasts have a phenotypic plasticity that allow their adaptation to contrasting immune tissue microenvironments.SummaryIt is unclear whether and how stromal fibroblasts adapt and contribute to varying tissue microenvironments. This study shows immune-suppressive cancer-associated fibroblasts (CAFs) have the capacity to develop an immune-promoting chemokine profile in response to cytokines from infiltrating T cells.
Transcriptional Heterogeneity and Cell Cycle Regulation as Central Determinants of Primitive Endoderm Priming
Authors: Perera Marta , Nissen Silas B. , Proks Martin , Pozzi Sara , Monteiro Rita S. , Trusina Ala , Brickman Joshua M. 
Published: April 2022

AbstractDuring embryonic development cells acquire identity at the same time as they are proliferating, implying that an intrinsic facet of cell fate choice requires coupling lineage decisions to rates of cell division. How is the cell cycle regulated to promote or suppress heterogeneity and differentiation? We explore this question combining time lapse imaging with single cell RNA-seq in the contexts of self-renewal, priming and differentiation of embryonic stem cells (ESCs) towards the Primitive Endoderm lineage (PrE). Since ESCs are derived from the Inner Cell Mass of the mammalian blastocyst, ESCs in standard culture conditions are transcriptionally heterogeneous containing subfractions that are primed for either of the two ICM lineages, Epiblast and PrE. These subfractions represent dynamic states that can readily interconvert in culture, and the PrE subfraction is functionally primed for endoderm differentiation. Here we find that differential regulation of cell cycle can tip the balance between these primed populations, such that naïve ESC culture conditions promote Epiblast-like expansion and PrE differentiation stimulates the selective proliferation of PrE-primed cells. In endoderm differentiation, we find that this change is accompanied by a counter-intuitive increase in G1 length that also appears replicatedin vivo. While FGF/ERK signalling is a known key regulator of ESCs and PrE differentiation, we find it is not just responsible for ESCs heterogeneity, but also cell cycle synchronisation, required for the inheritance of similar cell cycles between sisters and cousins. Taken together, our results point to a tight relationship between transcriptional heterogeneity and cell cycle regulation in the context of lineage priming, with primed cell populations providing a pool of flexible cell types that can be expanded in a lineage-specific fashion while allowing plasticity during early determination.
A sleep-active neuron can promote survival while sleep behavior is disturbed
Authors: Busack Inka , Bringmann Henrik 
Published: April 2022

AbstractSleep is controlled by neurons that induce behavioral quiescence and physiological restoration. It is not known, however, how sleep neurons link sleep behavior and survival. InCaenorhabditis elegans, the sleep-active RIS neuron induces sleep behavior and is required for survival of starvation and wounding. Sleep-active neurons such as RIS might hypothetically promote survival primarily by causing sleep behavior and associated conservation of energy. Alternatively, RIS might provide a survival benefit that does not depend on behavioral sleep. To probe these hypotheses, we tested how activity of the sleep-active RIS neuron inCaenorhabditis eleganscontrols sleep behavior and survival during larval starvation. To manipulate the activity of RIS, we expressed constitutively active potassium channel (twk-18gfandegl-23gf) or sodium channel (unc-58gf) mutant alleles in this neuron. Low levels ofunc-58gfexpression in RIS increased RIS calcium transients and sleep. High levels ofunc-58gfexpression in RIS elevated baseline calcium activity and inhibited calcium activation transients, thus locking RIS activity at a high but constant level. This manipulation caused a nearly complete loss of sleep behavior but increased survival. Long-term optogenetic activation also caused constantly elevated RIS activity and a small trend towards increased survival. Disturbing sleep by lethal blue-light stimulation also overactivated RIS, which again increased survival. FLP-11 neuropeptides were important for both, induction of sleep behavior and starvation survival, suggesting that FLP-11 might have divergent roles downstream of RIS. These results indicate that promotion of sleep behavior and survival are separable functions of RIS. These two functions may normally be coupled but can be uncoupled during conditions of strong RIS activation or when sleep behavior is impaired. Through this uncoupling, RIS can provide survival benefits under conditions when behavioral sleep is disturbed. Promoting survival in the face of impaired sleep might be a general function of sleep neurons.Author SummaryThe sleep neuron RIS inCaenorhabditis elegansis required to induce sleep behavior and to promote survival upon stress. Here we show that RIS can provide survival benefits even when sleep is disturbed.
Microglia Detect Externalized Phosphatidylserine on Synapses for Elimination via TREM2 in Alzheimer’s Disease Models
Authors: Rueda-Carrasco Javier , Sokolova Dimitra , Lee Sang-Eun , Childs Thomas , Jurčáková Natália , De Schepper Sebastiaan , Ge Judy Z. , Lachica Joanne I. , Toomey Christina E. , Freeman Oliver J. , Hardy John , Stevens Beth , Lashley Tammaryn , Chang Sunghoe , Hong Soyon 
Published: April 2022

AbstractGenetic studies implicate phagocytosis pathways in microglia to be a major Alzheimer’s disease (AD)-associated process. Microglia phagocytose synapses in AD mouse models, suggesting a role for microglia in region-specific synapse loss, a pathological hallmark of AD. However, whether specific synapses are targeted for elimination, and if so, how, remains to be elucidated. Here, we show that synapses externalize phosphatidylserine (PtdSer) upon challenge by β-amyloid oligomers, which are then selectively engulfed by microglia. Mechanistically, we find that Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is critical for microglia to sense and preferentially engulf AD synapses. In brains of mice and humans, TREM2 dysfunction leads to exacerbation of apoptotic synapses. Our work altogether suggests a fundamental role for microglia as brain-resident macrophages to remove damaged synapses in AD. We provide mechanistic insight into how TREM2 variants associated with increased risk of developing AD may contribute to defective microglia-synapse function.One-Sentence summaryMicroglia selectively engulf synapses in Alzheimer-like mouse brains via PtdSer-TREM2 signaling.
Cholinergic stimulation modulates the functional composition of CA3 cell types in the hippocampus
Authors: Puhl Christopher Jon , Wefelmeyer Winnie , Burrone Juan 
Published: April 2022

AbstractThe functional heterogeneity of hippocampal CA3 pyramidal neurons has emerged as a key aspect of circuit function. Here, we explored the effects of long-term cholinergic activity on the functional heterogeneity of CA3 pyramidal neurons in organotypic slices. Application of agonists to either acetylcholine receptors (AChRs) generally, or muscarinic AChRs (mAChRs) specifically, induced robust increases in network activity in the low-gamma range. Prolonged AChR stimulation for 48 hrs uncovered a population of hyperadapting CA3 pyramidal neurons that typically fired a single, early action potential in response to current injection. Although these neurons were present in control networks, their proportions were dramatically increased following long-term cholinergic activity. Characterised by the presence of a strong M-current, the hyperadaptation phenotype was abolished by acute application of either M-channel antagonists or the re-application of AChR agonists. We conclude that long-term mAChR activation modulates the intrinsic excitability of a subset of CA3 pyramidal cells, uncovering a highly plastic cohort of neurons that are sensitive to chronic ACh modulation. Our findings provide evidence for the activity-dependent plasticity of functional heterogeneity in the hippocampus.
Detection and molecular characterization of a phytoplasma associated with Cucumber (Cucumis sativus) and its first report from India
Authors: Muttappagol Mantesh , Kumar H. D. Vinay , Hiremath Shridhar , Nandan M. , Basha C. R. Jahir , Shankarappa K. S. , Venkataravanappa V. , Reddy C. N. Lakshminarayana 
Published: April 2022

AbstractCucumber (Cucumis sativus) plants exhibiting typical phyllody symptoms were collected from farmers field of Chintamani, Chickballapur districts of Karnataka (India). Disease incidence of phyllody was 2-3%. The etiology of the cucumber phyllody phytoplasma (CuPP) was confirmed by amplifying 16S rRNA gene from symptomatic plants using PCR followed by nested PCR using universal primers pairs P1/P7 and R16F2n/R16R2. After general detection the non-ribosomal SecY and rp (ribosomal protein) genes was amplified using specific primers. The PCR amplified products 16SrRNA (1.2 kb), SecY (1.6 kb) rp gene (1.2 kb) was cloned and sequenced. Sequence and phylogenetic analyses of 16S rRNA, secY and rp genes revealed that the detected phytoplasma is a member of the 16SrI group (Candidatus Phytoplasma asteris). Further on the basis of computer-simulated RFLP (= in silico RFLP) analysis of amplified F2n/R2 region of 16S rRNA gene indicates that, the detected phytoplasma was belongs to the subgroup X (16SrII-X). This is the first report on phytoplasma associated with phyllody disease of cucumber in India.