bluuebunny/crossref_metadata_2025_split huggingface dataset:
The overlapping modular organization of human brain functional networks across the adult lifespan
Authors: Gu Yue , Li Liangfang , Zhang Yining , Ma Junji , Yang Chenfan , Xiao Yu , Shu Ni ,   Cam-CAN, Lin Ying , Dai Zhengjia 
Published: November 2021

AbstractPrevious lifespan studies have demonstrated that the brain functional modular organization would change along with the adult lifespan. Yet, they assumed mutual exclusion among functional modules, ignoring convergent evidence for the existence of modular overlap. To reveal how age affects the overlapping functional modular organization, this study applied a detection algorithm requiring no prior knowledge of the resting-state fMRI data of a healthy cohort (N = 570, 18-88 years). Age-related regression analyses found a linear decrease in the overlapping modularity and the similarity of modular structure and overlapping node (i.e., region involved in multiple modules) distribution. The number of overlapping nodes increased with age, but the increment was distributed unevenly. In addition, across the adult lifespan and within each age group, the nodal overlapping probability consistently exhibited positive correlations with both functional gradient and flexibility. Further, we showed that the influence of age on memory-related cognitive performance might be explained by the change in the overlapping functional modular organization. Together, our results revealed age-related decreased segregation from the perspective of brain functional overlapping modular organization, providing new insight into the adult lifespan change in brain function and its influence on cognitive performance.
Synaptic Self-Organization of Spatio-Temporal Pattern Selectivity
Authors: Dehghani-Habibabadi Mohammad , Pawelzik Klaus Richard 
Published: November 2021

ABSTRACTSpiking model neurons can be set up to respond selectively to specific spatio-temporal spike patterns by optimization of their input weights. It is unknown, however, if existing synaptic plasticity mechanisms can achieve this temporal mode of neuronal coding and computation. Here it is shown that changes of synaptic efficacies which tend to balance excitatory and inhibitory synaptic inputs can make neurons sensitive to particular input spike patterns. Simulations demonstrate that a combination of Hebbian mechanisms, hetero-synaptic plasticity and synaptic scaling is sufficient for self-organizing sensitivity for spatio-temporal spike patterns that repeat in the input. In networks inclusion of hetero-synaptic plasticity leads to specialization and faithful representation of pattern sequences by a group of target neurons. Pattern detection is robust against a range of distortions and noise. The proposed combination of Hebbian mechanisms, hetero-synaptic plasticity and synaptic scaling is found to protect the memories for specific patterns from being overwritten by ongoing learning during extended periods when the patterns are not present. This suggests a novel explanation for the long term robustness of memory traces despite ongoing activity with substantial synaptic plasticity. Taken together, our result promote the plausibility of precise temporal coding in the brain.Author summaryNeurons communicate using action potentials, that are pulses localized in time. There is evidence that the exact timing of these so called spikes carries information. The hypothesis, however, that computations in brains are indeed based on precise patterns of spikes is debated, particularly because this would require the existence of suitable detectors. While theoretically, individual neurons can perform spike pattern detection when their input synapses are carefully adjusted, it is not known if existing synaptic plasticity mechanisms indeed support this coding principle. Here, a combination of basic but realistic mechanisms is demonstrated to self-organize the synaptic input efficacies such that individual neurons become detectors of patterns repeating in the input. The proposed combination of learning mechanisms yields a balance of excitation and inhibition similar to observations in cortex, robustness of detection against perturbations and noise, and persistence of memory against plasticity during ongoing activity without the learned patterns. The proposed learning mechanism enables groups of neurons to incrementally acquire sets of patterns thereby faithfully representing their ’which’ and ’when’ in sequences. These results suggest that computations based on spatio-temporal spike patterns might emerge without any supervision from the synaptic plasticity mechanisms present in the brain.
Multiplexed detection of bacterial nucleic acids using Cas13 in droplet microarrays
Authors: Thakku Sri Gowtham , Ackerman Cheri M. , Myhrvold Cameron , Bhattacharyya Roby P. , Livny Jonathan , Ma Peijun , Gomez Giselle Isabella , Sabeti Pardis C. , Blainey Paul C. , Hung Deborah T. 
Published: November 2021

AbstractRapid and accurate diagnosis of infections is fundamental to individual patient care and public health management. Nucleic acid detection methods are critical to this effort, but are limited either in the breadth of pathogens targeted or by the expertise and infrastructure required. We present here a high-throughput system that enables rapid identification of bacterial pathogens, bCARMEN, which utilizes: (1) modular CRISPR-Cas13-based nucleic acid detection with enhanced sensitivity and specificity; and (2) a droplet microfluidic system that enables thousands of simultaneous, spatially multiplexed detection reactions at nanoliter volumes; and (3) a novel pre-amplification strategy that further enhances sensitivity and specificity. We demonstrate bCARMEN is capable of detecting and discriminating 52 clinically relevant bacterial species and several key antibiotic resistance genes. We further develop a proof of principle system for use with stabilized reagents and a simple workflow with optical readout using a cell phone camera, opening up the possibility of a rapid point-of-care multiplexed bacterial pathogen identification and antibiotic susceptibility testing.Significance StatementIn this paper, we use a novel primer design method combined with droplet-based CRISPR Cas13 detection to distinguish 52 clinically relevant bacterial pathogens in a single assay. We also apply the method to detect and distinguish a panel of major antibiotic resistance genes, which is of critical importance in this era of rising antibiotic resistance. Finally, we make key advances towards making our diagnostic assay deployable at the point-of-care, with a simplified emulsion-free assay process that uses mobile phone camera for detection and reduces infrastructure/skilled labor requirements.
An integrated resource for functional and structural connectivity of the marmoset brain
Authors: Tian Xiaoguang , Chen Yuyan , Majka Piotr , Szczupak Diego , Perl Yonatan Sanz , Yen Cecil Chern-Chyi , Tong Chuanjun , Feng Furui , Jiang Haiteng , Glen Daniel , Deco Gustavo , Rosa Marcello G. P. , Silva Afonso C. , Liang Zhifeng , Liu Cirong 
Published: November 2021

AbstractComprehensive integration of structural and functional connectivity data is required to model brain functions accurately. While resources for studying the structural connectivity of non-human primate brains already exist, their integration with functional connectivity data has remained unavailable. Here we present a comprehensive resource that integrates the most extensive awake marmoset resting-state fMRI data available to date (39 marmoset monkeys, 710 runs, 12117 mins) with previously published cellular-level neuronal tracing (52 marmoset monkeys, 143 injections) and multi-resolution diffusion MRI datasets. The combination of these data allowed us to (1) map the fine-detailed functional brain networks and cortical parcellations; (2) develop a deep-learning-based parcellation generator that preserves the topographical organization of functional connectivity and reflects individual variabilities, and (3) investigate the structural basis underlying functional connectivity by computational modeling. This resource will enable modeling structure-function relationships and facilitate future comparative and translational studies of primate brains.
Systematic assessment of lipid profiles for the discovery of tissue contributors to the circulating lipid pool in cold exposure
Authors: Jain Raghav , Wade Gina , Ong Irene , Chaurasia Bhagirath , Simcox Judith 
Published: November 2021

AbstractPlasma lipid levels are altered in chronic conditions such as type 2 diabetes and cardiovascular disease as well as acute stresses such as fasting and cold exposure. Advances in mass spectrometry based lipidomics have uncovered the complexity of the plasma lipidome which includes over 500 lipids that serve functional roles including energy substrate and signaling molecule. The plasma lipid pool is maintained through regulation of tissue production, secretion, and uptake. A major challenge is establishing the tissues of origin and uptake for various plasma lipids, which is necessary to determine the lipid function. Using cold exposure as an acute stress, we performed global lipidomics on the plasma and nine tissues that may contribute to the circulating pool. We found that numerous species of plasma acylcarnitines (ACars) and ceramides were significantly changed with cold exposure. Through computational assessment, we identified the liver and brown adipose tissue (BAT) as major contributors and consumers of circulating ACars, in agreement with our previous work. We further identified the kidney and intestine as novel contributors to the circulating ACar pool and validated these findings with gene expression analysis. Regression analysis also identified that the BAT and kidney as regulators of the plasma ceramide pool. These studies provide an adaptable computational tool to assess tissue contribution to the plasma lipid pool. Our findings have implications in understanding the function of plasma ACars and ceramides, which are elevated in metabolic diseases.SummaryThere are over 500 identified lipids in circulating plasma, many without known origin or function. Using untargeted lipidomics on plasma and nine other tissues of cold exposed mice, we identified novel regulation of circulating acylcarnitines through the kidney and intestine, and a multiorgan system that regulates plasma ceramides. Our findings offer new targets for the study and functional characterization of circulating lipids in acute cold exposure and a computational resource for other investigators to explore multi-tissue lipidome remodeling during cold exposure.HighlightsGlobal lipidomics atlas of 9 tissues and plasma demonstrate dynamic shift with cold exposure.Adaptive resource for the selection of extraction method, data processing, and data analysis of multi-tissue global lipidomics data.Regression analysis identified the liver, BAT, intestine, and kidney as regulators of the plasma acylcarnitine pool that are not apparent by lipid levels alone.Acute cold exposure increases plasma ceramide levels, with the BAT and kidney as major contributors
Fingerprinting of skin cells by live cell Raman spectroscopy reveals melanoma cell heterogeneity and cell-type specific responses to UVR
Authors: Wilkinson Emma L. , Ashton Lorna , Kerns Jemma G. , Allinson Sarah L. , Mort Richard L. 
Published: November 2021

ABSTRACTRaman spectroscopy is an emerging dermatological technique with the potential to discriminate biochemically between cell types in a label free and non-invasive manner. Here we use live single cell Raman spectroscopy and principal component analysis (PCA) to fingerprint mouse melanoblasts, melanocytes, keratinocytes and melanoma cells. We show the differences in their spectra are attributable to biomarkers in the melanin biosynthesis pathway and that melanoma cells are a heterogeneous population that sit on a trajectory between undifferentiated melanoblasts and differentiated melanocytes. We demonstrate the utility of Raman spectroscopy as a highly sensitive tool to probe the melanin biosynthesis pathway and its immediate response to UV irradiation revealing previously undescribed opposing responses to UVA and UVB irradiation in melanocytes. Finally, we identify melanocyte specific accumulation of β-carotene correlated with a stabilisation of the UVR response in lipids and proteins consistent with a β-carotene mediated photoprotective mechanism. In summary our data show that Raman spectroscopy can be used to determine the differentiation status of cells of the melanocyte lineage and describe the immediate and temporal biochemical changes associated with UV exposure which differ depending on cell type, differentiation status and competence to synthesise melanin.
smBEVO: A computer vision approach to rapid baseline correction of single-molecule time series
Authors: Tran Khue , Bandyopadhyay Argha , Goldschen-Ohm Marcel P. 
Published: November 2021

AbstractSingle-molecule time series inform on the dynamics of molecular mechanisms that are occluded in ensemble-averaged measures. Amplitude-based methods and hidden Markov models (HMMs) frequently used for interpreting these time series require removal of low frequency drift that can be difficult to completely avoid in real world experiments. Current approaches for drift correction primarily involve either tedious manual assignment of the baseline or unsupervised frameworks such as infinite HMMs coupled with baseline nodes that are computationally expensive and unreliable. Here, we develop an image-based method for baseline correction using techniques from computer vision such as lane detection and active contours. The approach is remarkably accurate and efficient, allowing for rapid analysis of single-molecule time series contaminated with nearly any type of slow baseline drift.
Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice
Authors: Schor Jonathan S , Montalvo Isabelle Gonzalez , Spratt Perry W E , Brakaj Rea J , Stansil Jasmine A , Bender Kevin J , Nelson Alexandra B 
Published: November 2021

AbstractSubthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson’s Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free calcium imaging to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.
Pathways to polar adaptation in fishes revealed by long-read sequencing
Authors: Hotaling Scott , Desvignes Thomas , Sproul John S. , Lins Luana S.F. , Kelley Joanna L. 
Published: November 2021

AbstractLong-read sequencing is driving a new reality for genome science where highly contiguous assemblies can be produced efficiently with modest resources. Genome assemblies from long-read sequences are particularly exciting for understanding the evolution of complex genomic regions that are often difficult to assemble. In this study, we leveraged long-read sequencing data to generate a high-quality genome assembly for an Antarctic eelpout, Opthalmolycus amberensis, the first for the globally distributed family Zoarcidae. We used this assembly to understand how O. amberensis has adapted to the harsh Southern Ocean and compared it to another group of Antarctic fishes: the notothenioids. We showed that selection has largely acted on different targets in eelpouts relative to notothenioids. However, we did find some overlap; in both groups, genes involved in membrane structure, thermal tolerance, and vision have evidence of selection. We found evidence for historical shifts of transposable element activity in O. amberensis and other polar fishes, perhaps reflecting a response to environmental change. We were specifically interested in the evolution of two complex genomic loci known to underlie key adaptations to polar seas: hemoglobin and antifreeze proteins (AFPs). We observed unique evolution of the hemoglobin MN cluster in eelpouts and related fishes in the suborder Zoarcoidei relative to other Perciformes. For AFPs, we identified the first species in the suborder with no evidence of afpIII sequences (Cebidichthys violaceus) in the genomic region where they are found in all other Zoarcoidei, potentially reflecting a lineage-specific loss of this cluster. Beyond polar fishes, our results highlight the power of long-read sequencing to understand genome evolution.
The dorsal visual pathway represents object-centered spatial relations for object recognition
Authors: Ayzenberg Vladislav , Behrmann Marlene 
Published: November 2021

AbstractAlthough there is mounting evidence that input from the dorsal visual pathway is crucial for object processes in the ventral pathway, the specific functional contributions of dorsal cortex to these processes remain poorly understood. Here, we hypothesized that dorsal cortex computes the spatial relations among an object’s parts – a processes crucial for forming global shape percepts – and transmits this information to the ventral pathway to support object categorization. Using fMRI with human participants (females and males), we discovered regions in the intraparietal sulcus (IPS) that were selectively involved in computing object-centered part relations. These regions exhibited task-dependent functional and effective connectivity with ventral cortex, and were distinct from other dorsal regions, such as those representing allocentric relations, 3D shape, and tools. In a subsequent experiment, we found that the multivariate response of posterior IPS, defined on the basis of part-relations, could be used to decode object category at levels comparable to ventral object regions. Moreover, mediation and multivariate effective connectivity analyses further suggested that IPS may account for representations of part relations in the ventral pathway. Together, our results highlight specific contributions of the dorsal visual pathway to object recognition. We suggest that dorsal cortex is a crucial source of input to the ventral pathway and may support the ability to categorize objects on the basis of global shape.Significance StatementHumans categorize novel objects rapidly and effortlessly. Such categorization is achieved by representing an object’s global shape structure, that is, the relations among object parts. Yet, despite their importance, it is unclear how part relations are represented neurally. Here, we hypothesized that object-centered part relations may be computed by the dorsal visual pathway, which is typically implicated in visuospatial processing. Using fMRI, we identified regions selective for the part relations in dorsal cortex. We found that these regions can support object categorization, and even mediate representations of part relations in the ventral pathway, the region typically thought to support object categorization. Together, these findings shed light on the broader network of brain regions that support object categorization.
A two-phase plant-soil feedback experiment to explore biotic influences on Phragmites australis invasion in North American wetlands
Authors: Lee Sean F.H. , Mozdzer Thomas J. , Chapman Samantha K. , Mateu M. Gonzalez , Baldwin A. H. , Langley J. Adam 
Published: November 2021

ABSTRACTPlants can cultivate soil microbial communities that affect subsequent plant growth through a plant-soil feedback (PSF). Strong evidence indicates that PSFs can mediate the invasive success of exotic upland plants, but many of the most invasive plants occur in wetlands. In North America, the rapid spread of European Phragmites australis cannot be attributed to innate physiological advantages, thus PSFs may mediate invasion. Here we apply a two-phase fully-factorial plant-soil feedback design in which field-derived soil inocula were conditioned using saltmarsh plants and then were added to sterile soil mesocosms and planted with each plant type. This design allowed us to assess complete soil biota effects on intraspecific PSFs between native and introduced P. australis as well as heterospecific feedbacks between P. australis and the native wetland grass, Spartina patens. Our results demonstrate that native P. australis experienced negative conspecific feedbacks while introduced P. australis experienced neutral conspecific feedbacks. Interestingly, S. patens soil inocula inhibited growth in both lineages of P. australis while introduced and native P. australis inocula promoted the growth of S. patens suggestive of biotic resistance against P. australis invasion by S. patens. Our findings suggest that PSFs are not directly promoting the invasion of introduced P. australis in North America. Furthermore, native plants like S. patens seem to exhibit soil microbe mediated biotic resistance to invasion which highlights the importance of disturbance in mediating introduced P. australis invasion.
The mediating role of cost of capital in the relationship between capital structure and loan portfolio quality
Authors: Agasha Ester , Kamukama Nixon , Sserwanga Arthur 
Published: November 2021

PurposeThe purpose of this paper is to establish the mediating role of cost of capital in the relationship between capital structure and loan portfolio quality in Uganda's microfinance institutions (MFIs).Design/methodology/approachA cross-sectional research design was adopted to collect data and partial least squares structural equation modelling was used to test the study hypotheses.FindingsCost of capital partially mediates the relationship between capital structure and loan portfolio quality. Hence, cost of capital acts as a conduit through which capital structure affects loan portfolio quality.Research limitations/implicationsCost of capital was generalized as financial and administrative costs. The impact of costs like dividend pay-outs, interest rates and/or loan covenants on loan portfolio quality could be investigated individually.Practical implicationsMFIs should be vigilant about loan recovery by using strategies like credit rationing to ensure timely repayments.Originality/valueThe study contributes to the ongoing academic debate by identifying the significant indirect role of cost of capital in explaining loan portfolio quality.