bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially resolved gene regulatory and disease vulnerability map of the adult Macaque cortex
Authors: Lei Ying , Cheng Mengnan , Li Zihao , Zhuang Zhenkun , Wu Liang , Sun Yunong , Han Lei , Huang Zhihao , Wang Yuzhou , Wang Zifei , Xu Liqin , Yuan Yue , Liu Shang , Pan Taotao , Xie Jiarui , Liu Chuanyu , Volpe Giacomo , Ward Carl , Lai Yiwei , Xu Jiangshan , Wang Mingyue , Yu Hao , Sun Haixi , Yu Qichao , Wu Liang , Wang Chunqing , Wong Chi Wai , Liu Wei , Xu Liangzhi , Wei Jingkuan , Chen Dandan , Shang Zhouchun , Li Guibo , Ma Kun , Cheng Le , Ling Fei , Tan Tao , Chen Kai , Tasic Bosiljka , Dean Michael , Ji Weizhi , Yang Huanming , Gu Ying , Esteban Miguel A. , Li Yuxiang , Chen Ao , Niu Yuyu , Zeng Hongkui , Hou Yong , Liu Longqi , Liu Shiping , Xu Xun 
Published: May 2020

AbstractSingle cell approaches have increased our knowledge about the cell type composition of the non-human primate (NHP), but a detailed characterization of area-specific regulatory features remains outstanding. We generated single-cell chromatin accessibility (single-cell ATAC) and transcriptomic data of 358,237 cells from prefrontal cortex (PFC), primary motor cortex (M1) and primary visual cortex (V1) of adult cynomolgus monkey brain, and integrated this dataset with Stereo-seq (Spatio-Temporal Enhanced REsolution Omics-sequencing) of the corresponding cortical areas to assign topographic information to molecular states. We identified area-specific chromatin accessible sites and their targeted genes, including the cell type-specific transcriptional regulatory network associated with excitatory neurons heterogeneity. We reveal calcium ion transport and axon guidance genes related to specialized functions of PFC and M1, identified the similarities and differences between adult macaque and human oligodendrocyte trajectories, and mapped the genetic variants and gene perturbations of human diseases to NHP cortical cells. This resource establishes a transcriptomic and chromatin accessibility combinatory regulatory landscape at a single-cell and spatially resolved resolution in NHP cortex.
Superior Colliculus-Projecting GABAergic Retinal Ganglion Cells Mediate Looming-Evoked Flight Response
Authors: Luo Xue , Cai Danrui , Shen Kejiong , Deng Qinqin , Lei Xinlan , Jin Sen , Zeng Wen-Bo , Li Hua , Xu Fuqiang , Huang Lu , Ren Chaoran , Luo Min-Hua , Xie Ting , Shen Yin 
Published: May 2020

AbstractThe looming stimulus-evoked flight response is an experimental paradigm for studying innate defensive behaviors. However, how the visual looming stimulus is transmitted from the retina to the brain remains poorly understood. Here, we report that superior colliculus (SC)-projecting RGCs transmit the looming signal from the retina to the brain to mediate the looming-evoked flight behavior by releasing GABA. In the mouse retina, GABAergic RGCs are capable of projecting to many brain areas, including the SC. Superior colliculus (SC)-projecting GABAergic RGCs (spgRGCs) are mono-synaptically connected to the parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of spgRGCs triggers GABA-mediated inhibition in SC neurons. The ablation or silence of spgRGCs compromises looming-evoked flight response but not image-forming functions. Therefore, this study shows that spgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex
Authors: Andrews Madeline G. , Subramanian Lakshmi , Kriegstein Arnold R. 
Published: May 2020

AbstractOuter radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease.
Functional redundancy in natural pico-phytoplankton communities depends on temperature and biogeography
Authors: Zhong Duyi , Listmann Luisa , Santelia Maria-Elisabetta , Schaum C-Elisa 
Published: May 2020

AbstractBiodiversity affects ecosystem function, but how this relationship will pan out in a changing world is still a major question in ecology. It remains especially understudied for pico-phytoplankton communities, which contribute to carbon cycles and aquatic food webs year-round. Observational studies show a link between phytoplankton community diversity and ecosystem stability, but there is only scarce causal or empirical evidence. Here, we sampled phytoplankton communities from two biogeographically distinct (but close enough to not be confounded by differences in day length and precipitation) regions in the Southern Baltic Sea, and carried out a series of dilution/regrowth experiments across three assay temperatures. This allowed us to investigate the effects of loss of rare taxa and establish causal links in natural communities between species richness and several ecologically relevant traits (e.g. size, biomass production, and oxygen production), depending on sampling location and assay temperature. We found that the samples’ bio-geographical origin determined whether and how functional redundancy changed as a function of temperature for all traits under investigation. Samples obtained from the slightly warmer and more thermally variable regions showed overall high functional redundancy. Samples from the slightly cooler, less variable, stations showed little functional redundancy, i.e. function decreased the more species were lost from the community. The differences between regions were more pronounced at elevated assay temperatures. Our results imply that the importance of rare species and the amount of species required to maintain ecosystem function even under short-term warming (e.g. during heat waves) may differ drastically even within geographically closely related regions of the same ecosystem.
Correlates of auditory decision making in prefrontal, auditory, and basal lateral amygdala cortical areas
Authors: Napoli Julia L. , Camalier Corrie R. , Brown Anna Leigh , Jacobs Jessica , Mishkin Mortimer M. , Averbeck Bruno B. 
Published: May 2020

AbstractAuditory selective listening and decision making underlies important processes, including attending to a single speaker in a crowded room, often referred to as the cocktail party problem. To examine the neural mechanisms underlying these behaviors, we developed a novel auditory selective listening paradigm for monkeys. In this task, monkeys had to detect a difficult to discriminate target embedded in noise when presented in a pre-cued location (either left or right) and ignore it if it was in the opposite location. While the animals carried out the task we recorded neural activity in primary auditory cortex (AC), dorsal lateral prefrontal cortex (dlPFC) and the basal lateral amygdala (BLA), given that these areas have been implicated in auditory decision making, selective listing, and/or reward-guided decision making. There were two main findings in the neural data. First, primary AC encoded the side of the cue and target, and the monkey’s choice, before either dlPFC or the amygdala. The BLA encoded cue and target variables negligibly, but was engaged at the time of the monkey’s choice. Second, decoding analyses suggested that errors followed primarily from a failure to encode the target stimulus in both AC and PFC, but earlier in AC. Thus, AC neural activity is poised to represent the sensory volley and decision making during selective listening before dlPFC, and they both precede activity in BLA.
Topography of Hippocampal Connectivity with Sensorimotor Cortex Revealed by Optimizing Smoothing Kernel and Voxel Size
Authors: Burman Douglas D. 
Published: May 2020

AbstractStudies of the hippocampus use smaller voxel sizes and smoothing kernels than cortical activation studies, typically using a multivoxel seed with specified radius for connectivity analysis. This study identified optimal processing parameters for evaluating hippocampal connectivity with sensorimotor cortex (SMC), comparing effectiveness by varying parameters during both activation and connectivity analysis. Using both 3mm and 4mm isovoxels, smoothing kernels of 6-10mm were evaluated on the amplitude and extent of motor activation and hippocampal connectivity with SMC. Psychophysiological interactions identified hippocampal connectivity with SMC during volitional movements, and connectivity effects from multivoxel seeds were compared with alternate methods; a structural seed represented the mean connectivity map from all voxels within a region, whereas a functional seed represented the regional voxel with maximal SMC connectivity. With few exceptions, the same parameters were optimal for activation and connectivity. Larger isovoxels showed larger activation volumes in both SMC and the hippocampus; connectivity volumes from structural seeds were also larger, except from the posterior hippocampus. Regardless of voxel size, the 10mm smoothing kernel generated larger activation and connectivity volumes from structural seeds, as well as larger beta estimates at connectivity maxima; structural seeds also produced larger connectivity volumes than multivoxel seeds. Functional seeds showed lesser effects from voxel size and smoothing kernels. Optimal parameters revealed topography in structural seed connectivity along both the longitudinal axis and mediolateral axis of the hippocampus. These results indicate larger voxels and smoothing kernels improve sensitivity for detecting both cortical activation and hippocampal connectivity.
Identification of amyloid beta oligomers in locus coeruleus (LC) neurons of Alzheimer’s patients and their impact on LC oxidative stress, inhibitory neurotransmitter receptors and neuronal excitability
Authors: Kelly Louise , Seifi Mohsen , Ma Ruolin , Mitchell Scott , Rudolph Uwe , Viola Kirsten L. , Klein William L. , Lambert Jeremy J. , Swinny Jerome D. 
Published: May 2020

AbstractAmyloid β oligomers (AβO) are potent modulators of two key Alzheimer’s pathological processes, namely synaptic dysfunction and tau tangle formation in various brain regions. Remarkably, the impact of AβO in one of the earliest brain regions to exhibit Alzheimer’s pathology, the locus coeruleus (LC), remains to be determined. Of particular importance is the effect of AβO on the excitability of individual LC neurons. This parameter determines brain-wide noradrenaline (NA) release, and thus NA-mediated brain functions, including cognition, emotion and immune function, which are all severely compromised in Alzheimer’s. Using a mouse model of increased Aβ production (APP-PSEN1), together with correlative histopathological analyses in post mortem Alzheimer’s patient samples, we determined the impact of Aβ pathology on various correlates of LC neuronal integrity. AβO immunoreactivity in the LC of APP-PSEN1 mice was replicated in patient samples, presenting as individual clusters located both intraneuronally, in mitochondrial compartments, as well as extracellularly in association with inhibitory synapses. No specific signal was detected in either patient control or wild type mouse samples. Accompanying this AβO expression profile was LC neuronal hyperexcitability and indicators of oxidative stress in APP-PSEN1 mice. LC hyperexcitability arose from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA-A receptor (GABAAR) α3 subunit. Importantly, this altered LC α3-GABAAR expression profile overlapped with AβO expression in both APP-PSEN1 mice and Alzheimer’s patient samples. Finally, strychnine-sensitive glycine receptors (GlyRs) remained resilient to AβO-induced changes and their activation reversed LC hyperexcitability. Alongside this first demonstration of AβO expression in the LC of Alzheimer’s patients, the study is also first to reveal a direct association between AβO and LC neuronal excitability. GlyR-α3-GABAAR modulation of AβO-dependent LC hyperexcitability could delay the onset of cognitive and psychiatric symptoms arising from LC-NA deficits, thereby significantly diminishing the disease burden for Alzheimer’s patients.
Replicating infant astrocyte behavior in the adult after brain injury improves outcomes
Authors: Teo Leon , Boghdadi Anthony G. , Homman-Ludiye Jihane , Carril-Mundiñano Iñaki , Kwan William C. , Bourne James A. 
Published: May 2020

AbstractInfants and adults respond differently to brain injuries. Specifically, improved neuronal sparing along with reduced astrogliosis and glial scarring often observed earlier in life, likely contributes to improved long-term outcomes. Understanding the underlying mechanisms could enable the recapitulation of neuroprotective effects, observed in infants, to benefit adult patients after brain injuries. We reveal that in primates, Eph/ ephrin signaling contributes to age-dependent reactive astrocyte behavior. Ephrin-A5 expression on astrocytes was more protracted in adults, whereas ephrin-A1 was associated only with infant astrocytes. Furthermore, ephrin-A5 exacerbated major hallmarks of astrocyte reactivity via EphA2 and EphA4 receptors, which was subsequently alleviated by ephrin-A1. Rather than suppressing reactivity, ephrin-A1 signaling shifted astrocytes towards GAP43+ neuroprotection, accounting for improved neuronal sparing in infants. Reintroducing ephrin-A1 after middle-aged ischemic stroke significantly attenuated glial scarring, improved neuronal sparing and preserved circuitry. Therefore, beneficial infant mechanisms can be recapitulated in adults to improve outcomes after CNS injuries.
Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue
Authors: Huang Zan , Zhang Zengdi , Heck Ryan , Hu Ping , Nanda Hezkiel , Ren Kaiqun , Sun Zequn , Bartolomucci Alessandro , Gao Yan , Chung Dongjun , Zhu Weiyun , Shen Steven , Ruan Hai-Bin 
Published: May 2020

SUMMARYIn humans, brown adipose tissue (BAT) undergoes progressive involution or atrophy with increasing age, as manifested by decreased prevalence and mass, transformation to white adipose tissue (WAT), and reduction in thermogenic activity. This involution process cannot be fully recapitulated in rodent models and thus underlying cellular mechanisms are poorly understood. Here, we show that the interscapular BAT (iBAT) in rabbits involutes rapidly in early life, similarly to that in humans. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied with the loss of brown adipogenic competence of their precursor cells. Through single-cell RNA sequencing, we surveyed the heterogenous populations of mesenchymal cells within the stromal vascular fraction of rabbit and human iBAT. An analogousFSTL1highpopulation of brown adipocyte progenitors exists in both species while gradually disappear during iBAT involution in rabbits. In mice, FSTL1 is highly expressed by adipocyte progenitors in iBAT and genetic deletion of FSTL1 causes defective WNT signaling and iBAT atrophy in neonates. Our results underscore the BAT-intrinsic contribution fromFSTL1highprogenitors to age-related tissue involution and point to a potential therapeutic approach for obesity and its comorbidities.HIGHLIGHTSRabbit BAT irreversibly transforms to WAT before puberty.iBAT adipocyte progenitors reprogram transcriptome and lose brown adipogenic ability.ComparableFSTL1highbrown adipocyte progenitors exist in rabbit and human iBAT.Loss of FSTL1 in brown adipocyte progenitors causes iBAT atrophy in mice.
Pattern- based Contractility Screening (PaCS), a reference-free traction force microscopy methodology, reveals contractile differences in breast cancer cells
Authors: Ghagre Ajinkya , Amini Ali , Srivastava Luv Kishore , Tirgar Pouria , Khavari Adele , Koushki Newsha , Ehrlicher Allen 
Published: May 2020

AbstractThe sensing and generation of cellular forces are essential aspects of life. Traction Force Microscopy (TFM) has emerged as a standard broadly applicable methodology to measure cell contractility and its role in cell behavior. While TFM platforms have enabled diverse discoveries, their implementation remains limited in part due to various constraints, such as time-consuming substrate fabrication techniques, the need to detach cells to measure null force images, followed by complex imaging and analysis, and the unavailability of cells for post-processing. Here we introduce a reference-free technique to measure cell contractile work in real-time, with basic substrate fabrication methodologies, simple imaging, and analysis with the availability of the cells for post-processing. In this technique, we confine the cells on fluorescent adhesive protein micropatterns of a known area on compliant silicone substrates and use the cell deformed pattern area to calculate cell contractile work. We validated this approach by comparing this Pattern-based Contractility Screening (PaCS) to conventional bead-displacement TFM and show quantitative agreement between the methodologies. Using this platform, we measure the contractile work of highly metastatic MDA-MB-231 breast cancer cells is significantly higher than non-invasive MCF-7 cells. PaCS enables the broader implementation of contractile work measurements in diverse quantitative biology and biomedical applications.
Mapping Cognitive Brain Functions at Scale
Authors: Balasubramani Pragathi Priyadharsini , Ojeda Alejandro , Grennan Gillian , Maric Vojislav , Le Hortense , Alim Fahad , Zafar-Khan Mariam , Diaz-Delgado Juan , Silveira Sarita , Ramanathan Dhakshin , Mishra Jyoti 
Published: May 2020

AbstractA fundamental set of cognitive abilities enable humans to efficiently process goal-relevant information, suppress irrelevant distractions, maintain information in working memory, and act flexibly in different behavioral contexts. Yet, studies of human cognition and their underlying neural mechanisms usually evaluate these cognitive constructs in silos, instead of comprehensively in-tandem within the same individual. Here, we developed a scalable, mobile platform, “BrainE” (short for Brain Engagement), to rapidly assay several essential aspects of cognition simultaneous with wireless electroencephalography (EEG) recordings. UsingBrainE, we rapidly assessed five aspects of cognition including (1) selective attention, (2) response inhibition, (3) working memory, (4) flanker interference and (5) emotion interference processing, in 102 healthy young adults. We evaluated stimulus encoding in all tasks using the EEG neural recordings, and isolated the cortical sources of the spectrotemporal EEG dynamics. Additionally, we usedBrainEin a two-visit study in 24 young adults to investigate the reliability of the neuro-cognitive data as well as its plasticity to transcranial magnetic stimulation (TMS). We found that stimulus encoding on multiple cognitive tasks could be rapidly assessed, identifying common as well as distinct task processes in both sensory and cognitive control brain regions. Event related synchronization (ERS) in the theta (3-7 Hz) and alpha (8-12 Hz) frequencies as well as event related desynchronization (ERD) in the beta frequencies (13-30 Hz) were distinctly observed in each task. The observed ERS/ERD effects were overall anticorrelated. The two-visit study confirmed high test-retest reliability for both cognitive and neural data, and neural responses showed specific TMS protocol driven modulation. We also show that the global cognitive neural responses are sensitive to mental health symptom self-reports. This first study with theBrainEplatform showcases its utility in studying neuro-cognitive dynamics in a rapid and scalable fashion.HighlightsRapid and scalable EEG recordings reveal common and distinct cortical activations across five core cognitive tasks.Data acquired across visits one-week-apart show high test-retest reliability for both cognitive and neural measurements.Evoked neural responses during emotion interference processing demonstrate specific short-term plasticity driven by type of neurostimulation.Cognitively evoked neural responses are sensitive to variations in mental health symptoms.
The legacy of C4evolution in the hydraulics of C3and C4grasses
Authors: Zhou Haoran , Akçay Erol , Edwards Erika , Helliker Brent 
Published: May 2020

AbstractThe anatomical reorganization required for optimal C4photosynthesis should also impact plant hydraulics. Most C4plants possess large bundle-sheath cells and high vein density, which should also lead to higher leaf hydraulic conductance (Kleaf) and capacitance. Paradoxically, the C4pathway reduces water demand and increases water-use-efficiency, creating a potential mis-match between supply capacity and demand in C4plant water relations. We use phylogenetic analyses, physiological measurements, and models to examine the reorganization of hydraulics in closely-related C4and C3grasses. Evolutionarily young C4lineages have higher Kleaf, capacitance, turgor-loss-point, and lower stomatal conductance than their C3relatives. In contrast, species from older C4lineages show decreased Kleafand capacitance, indicating that over time, C4plants have evolved to optimize hydraulic investments while maintaining C4anatomical requirements. The initial “over-plumbing” of C4plants disrupts the positive correlation between maximal assimilation rate and Kleaf, decoupling a key relationship between hydraulics and photosynthesis generally observed in vascular plants.
Preferential synthesis of very long chain polyunsaturated fatty acids ineutreptiellasp. (eugelnozoa) revealed by chromatographic and transcriptomic analyses
Authors: Kuo Rita C. , Zhang Huan , Stuart James D. , Provatas Anthony A. , Hannick Linda , Lin Senjie 
Published: May 2020

AbstractAlgal lipids are important fuel storage molecules in algae and a currency for energy transfer in the marine food chain as well as materials for biofuel production, but their production and regulation are not well understood in many species including the common coastal phytoplanktonEutreptiellaspp. Here, using gas chromatography-tandem mass spectrometry (GC/MS/MS), we discovered 24 types of fatty acids (FAs) inEutreptiellasp. with a relatively high proportion of long chain unsaturated FAs. The abundances of C16, C18 and saturated FAs decreased when phosphate in the culture medium was depleted. Among the 24 FAs, docosahexaenoic acid (22:6) and eicosapentaenoic acid (20:5) were the most abundant, suggesting thatEutreptiellasp. preferentially invests in the synthesis of very long chain polyunsaturated fatty acids (VLCPFA). Further transcriptomic analysis revealed thatEutreptiellasp. likely synthesizes VLCPFA via Δ8 pathway and uses type I and II fatty acid synthases. Using RT-qPCR, we found that some of the lipid production genes, such as β-ketoacyl-ACP reductase, fatty acid desaturase, acetyl-CoA carboxylase, acyl carrier protein, Δ8 desaturase, and Acyl-ACP thioesterase, were more actively expressed during light period. Besides, two carbon-fixation genes were more highly expressed in the high lipid illuminated cultures, suggesting a linkage between photosynthesis and lipid production.