Biology subjects

Kim, G.

Publications and source records attributed to Kim, G..

14 recordsLinked to original sources

bioRxiv2018

Effects of individuation and grouping on face representations in the visual cortex

Top-down signals can influence our visual perception by providing guidance on information processing. Especially, top-down control between two basic frameworks, \"Individuation\" and \"grouping\", is critical for information processing during face perception. Individuation of faces supports identity recognition while grouping subserves higher category level face perception such as race or gender. However, it still remains elusive how top-down dependent control between individuation and grouping affects cortical representations during face perception. Here we performed an fMRI experiment to investigate whether representations across early and high-level visual areas can be altered by top-down control between individuation and grouping process during face perception. Focusing on neural response patterns across the early visual cortex (EVC) and the face-selective area (the fusiform face area (FFA)), we found that the discriminability of individual faces from the response patterns was strong in the FFA but weak in the EVC during the individuation task whereas the EVC but not the FFA showed significant face discrimination during the grouping tasks. Thus, these findings suggest that the representation of face information across the early and high-level visual cortex is flexible depending on the top-down control of the perceptual framework between individuation and grouping.

neuroscience↗

bioRxiv2018

Learning-based screening of hematologic disorders using quantitative phase imaging of individual red blood cells

We present a rapid and label-free method for hematologic screening for diseases and syndromes, utilizing quantitative phase imaging (QPI) and machine learning. We aim to establish an efficient blood examination framework that does not suffer from the drawbacks of conventional blood assays, which are incapable of profiling single cells or using labeling procedures. Our method involves the synergistic employment of QPI and machine learning. The high-dimensional refractive index information arising from the QPI-based profiling of single red blood cells is processed to screen for diseases and syndromes using machine learning, which can utilize high-dimensional data beyond the human level. Accurate screening for iron-deficiency anemia, reticulocytosis, hereditary spherocytosis, and diabetes mellitus is demonstrated (>99% accuracy) using the proposed method. Furthermore, we highlight the synergy between QPI and machine learning in the proposed method by analyzing the performance of the method.

biophysics↗

bioRxiv2018

The Miniature-chemostat Aging Device: A new experimental platform facilitates assessment of the transcriptional and chromatin landscapes of replicatively aging yeast

Replicative aging of Saccharomyces cerevisiae is an established model system for eukaryotic cellular aging. A major limitation in yeast lifespan studies has been the difficulty of separating old cells from young cells in large quantities for in-depth comparative analyses. We engineered a new platform, the Miniature-chemostat Aging Device (MAD), that enables purification of aged cells at sufficient quantities to enable genomic and biochemical characterization of aging yeast populations. Using the MAD platform, we measured DNA accessibility (ATAC-Seq) and gene expression (RNA-Seq) changes in aging cells. Our data highlight an intimate connection between aging, growth rate, and stress, as many (but not all) genes that change with age have altered expression in cells that are subjected to stress. Stress-independent genes that change with age are highly enriched for targets of the signal recognition particle (SRP). By obtaining pure populations of old cells, we find that nucleosome occupancy does not change significantly with age; however, significant age-dependent changes in accessibility at ~12% of genomic loci reflect decreased replication and changing activities of cell cycle and metabolic regulators. Finally, ATAC-seq revealed that upregulating the proteasome by deleting UBR2 reduces rDNA instability usually observed in aging cells, demonstrating a connection between proteasome activity and genomic stability.

systems biology↗

bioRxiv2018

Universality of the developmental origins of diverse functional maps in the visual cortex

The primary visual cortex of higher mammals is organized into diverse functional maps of correlated topography, implying an efficient tiling of functional domains. However, no fundamental principle is available on how systematic organization of the maps could develop initially in various species. Here, we propose that diverse functional maps are seeded from a common framework of retinal afferents, and that this universality of development explains the observed topographical correlations among the maps. From the simulation of retinal ganglion cell mosaics, we successfully developed all four cortical maps observed so far. We validated our model prediction of inter-map relationships from analysis of map data in evolutionarily divergent mammalian species. Our key prediction, the hexagonal periodicity of every functional map, was validated from analysis of the map data in diverse mammalian species. Our results provide new insight into a universal mechanism for the development and evolution of the visual cortex.

neuroscience↗

bioRxiv2018

Three-dimensional refractive index distributions of individual angiosperm pollen grains

Three-dimensional (3D) refractive index (RI) imaging and quantitative analyses of angiosperm pollen grains are presented. Using optical diffraction tomography, the 3D RI structures of individual angiosperm pollen grains were measured without using labeling or other preparation techniques. Various physical quantities, including volume, surface area, exine volume, and sphericity, were determined from the measured RI tomograms of pollen grains. Exine skeletons, the distinct internal structures of angiosperm pollen grains, were identified and systematically analyzed.

plant biology↗

bioRxiv2018

Two distinct proprioceptive representations of voluntary movements in primate spinal neurons

When willingly setting our body in motion, we simultaneously know where and how our limbs are moving. While this indicates that proprioceptive information is readily represented in the neurons of the central nervous system, it is still unclear how. We recorded the activity of spinal neurons with direct projections from muscle spindle afferents in four monkeys, while they performed simple wrist movements. Against the assumption that these spinal neurons act as a simple relay of afferent input, we found the majority (56%) of neurons had firing patterns incongruent with a simple representation of spindle activity, and the minority had congruent patterns. Two groups of neurons showed distinct intrinsic characteristics (spike width, base firing rate and firing irregularity), and distinct control of their input-output gain. These results are the first demonstration that proprioceptive representation is achieved by the coordinated activity of distinct groups of neurons during volitional movement.

neuroscience↗

bioRxiv2017

Label-free non-invasive quantitative measurement of lipid contents in individual microalgal cells using refractive index tomography

Microalgae are promising candidates for biofuel production due to their high lipid content. To facilitate utilization of the microalgae for biofuel, rapid quantification of the lipid contents in microalgae is necessary. However, conventional methods based on the chemical extraction of lipids require a time-consuming destructive extraction process. Here, we demonstrate label-free, non-invasive, rapid quantification of the lipid contents in individual micro-algal cells measuring the three-dimensional refractive index tomograms. We measure three-dimensional refractive index distributions within Nannochloropsis oculata cells and find that lipid droplets are identifiable in tomograms by their high refractive index. In addition, we alter N. oculata under nitrogen deficiency by measuring the volume, lipid weight, and dry cell weight of individual cells. Characterization of individual cells allows correlative analysis between the lipid content and size of individual cells.

bioengineering↗

bioRxiv2017

3D label-free imaging and analysis of Pinus pollen grains using optical diffraction tomography

O_LIThe structure of pollen grains is related to the reproductive function of the plants. Here, three-dimensional (3D) refractive index maps were obtained for individual conifer pollen grains using optical diffraction tomography (ODT).\nC_LIO_LIThe 3D morphological features of pollen grains from pine trees were investigated using measured refractive index maps, in which distinct substructures were clearly distinguished and analyzed.\nC_LIO_LIMorphological and physiochemical parameters of the pollen grains were quantified from the obtained refractive index (RI) maps and used to quantitatively study the interspecific differences of pollen grains from different strains.\nC_LIO_LIOur results demonstrate that ODT can assess the structure of pollen grains. This label-free and rapid 3D imaging approach may provide a new platform for understanding the physiology of pollen grains.\nC_LI

plant biology↗

bioRxiv2017

Measurements of three-dimensional refractive index tomography and membrane deformability of live erythrocytes from Pelophylax nigromaculatus

Unlike mammalian erythrocytes, amphibian erythrocytes have distinct morphological features including large cell sizes and the presence of nuclei. The sizes of the cytoplasm and nuclei of erythrocytes vary significantly over different species, their environments, or pathophysiology, which makes hematological studies important for investigating amphibian species. Here, we present a label-free three-dimensional optical quantification of individual amphibian erythrocytes from frogs Pelophylax nigromaculatus (Rana nigromaculata). Using optical diffraction tomography, we measured three-dimensional refractive index (RI) tomograms of the cells, which clearly distinguished the cytoplasm and nuclei inside the erythrocytes. From the measured RI tomograms, we extracted the relevant biochemical parameters of the cells, including hemoglobin contents and hemoglobin concentrations. Furthermore, we measured dynamic membrane fluctuations and investigated the mechanical properties of the cell membrane. From the statistical and correlative analysis of these retrieved parameters, we investigated interspecific differences between frogs and previously studied mammals.

biophysics↗

bioRxiv2017

MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs

First paragraphDodders (Cuscuta spp.) are obligate parasitic plants that obtain water and nutrients from the stems of host plants via specialized feeding structures called haustoria. Dodder haustoria facilitate bi-directional movement of viruses, proteins, and mRNAs between host and parasite1, but the functional effects of these movements are not clear. Here we show that C. campestris haustoria accumulate high levels of many novel microRNAs (miRNAs) while parasitizing Arabidopsis thaliana hosts. Many of these miRNAs are 22 nts long, a usually rare size of plant miRNA associated with amplification of target silencing through secondary small interfering RNA (siRNA) production2. Several A. thaliana mRNAs are targeted by C. campestris 22 nt miRNAs during parasitism, resulting in mRNA cleavage, secondary siRNA production, and decreased mRNA accumulation levels. Hosts with mutations in two of the targets supported significantly higher growth of C. campestris. Homologs of target mRNAs from diverse plants also have predicted target sites to induced C. campestris miRNAs, and the same miRNAs are expressed and active against host targets when C. campestris parasitizes a different host, Nicotiana benthamiana. These data show that C. campestris miRNAs act as trans-species regulators of host gene expression, and suggest that they may act as virulence factors during parasitism.

plant biology↗

bioRxiv2017

HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo

Alternative pre-mRNA splicing plays a major role in expanding the transcript output of human genes. This process is regulated, in part, by the interplay of trans-acting RNA binding proteins (RBPs) with myriad cis-regulatory elements scattered throughout pre-mRNAs. These molecular recognition events are critical for defining the protein coding sequences (exons) within pre-mRNAs and directing spliceosome assembly on non-coding regions (introns). One of the earliest events in this process is recognition of the 3 splice site by U2 small nuclear RNA auxiliary factor 2 (U2AF2). Splicing regulators, such as the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), influence spliceosome assembly both in vitro and in vivo, but their mechanisms of action remain poorly described on a global scale. HNRNPA1 also promotes proof reading of 3ss sequences though a direct interaction with the U2AF heterodimer. To determine how HNRNPA1 regulates U2AF-RNA interactions in vivo, we analyzed U2AF2 RNA binding specificity using individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) in control- and HNRNPA1 over-expression cells. We observed changes in the distribution of U2AF2 crosslinking sites relative to the 3 splice sites of alternative cassette exons but not constitutive exons upon HNRNPA1 over-expression. A subset of these events shows a concomitant increase of U2AF2 crosslinking at distal intronic regions, suggesting a shift of U2AF2 to \"decoy\" binding sites. Of the many non-canonical U2AF2 binding sites, Alu-derived RNA sequences represented one of the most abundant classes of HNRNPA1-dependent decoys. Splicing reporter assays demonstrated that mutation of U2AF2 decoy sites inhibited HNRNPA1-dependent exon skipping in vivo. We propose that HNRNPA1 regulates exon definition by modulating the interaction of U2AF2 with decoy or bona fide 3 splice sites.

molecular biology↗

bioRxiv2017

Visualization And Label-Free Quantification Of Microfluidic Mixing Using Quantitative Phase Imaging

Microfluidic mixing plays a key role in various fields, including biomedicine and chemical engineering. To date, although various approaches for imaging microfluidic mixing have been proposed, they provide only quantitative imaging capability and require for exogenous labeling agents. Quantitative phase imaging techniques, however, circumvent these problems and offer label-free quantitative information about concentration maps of microfluidic mixing. We present the quantitative phase imaging of microfluidic mixing in various types of PDMS microfluidic channels with different geometries; the feasibility of the present method was validated by comparing it with the results obtained by theoretical calculation based on Ficks law.

bioengineering↗

bioRxiv2017

Neural Overlap In Item Representations Across Episodes Impairs Context Memory

We frequently encounter the same item in different contexts, and when that happens, memories of earlier encounters can get reactivated in the brain. Here we examined how these existing memories are changed as a result of such reactivation. We hypothesized that when an items initial and subsequent neural representations overlap, this allows the initial item to become associated with novel contextual information, interfering with later retrieval of the initial context. That is, we predicted a negative relationship between representational similarity across repeated experiences of an item and subsequent source memory for the initial context. We tested this hypothesis in an fMRI study, in which objects were presented multiple times during different tasks. We measured the similarity of the neural patterns in lateral occipital cortex that were elicited by the first and second presentations of objects, and related this neural overlap score to source memory in a subsequent test. Consistent with our hypothesis, greater item-specific pattern similarity was linked to worse source memory for the initial task. Our findings suggest that the influence of novel experiences on an existing context memory depends on how reliably a shared component (i.e., same item) is represented across these episodes.

neuroscience↗

bioRxiv2016

Neural differentiation of incorrectly predicted memories

When an item is predicted in a particular context but the prediction is violated, memory for that item is weakened (Kim et al., 2014). Here we explore what happens when such previously mispredicted items are later re-encountered. According to prior neural network simulations, this sequence of events - misprediction and subsequent restudy - should lead to differentiation of the item's neural representation from the previous context (on which the misprediction was based). Specifically, misprediction weakens connections in the representation to features shared with the previous context, and restudy allows new features to be incorporated into the representation that are not shared with the previous context. This cycle of misprediction and restudy should have the net effect of moving the item s neural representation away from the neural representation of the previous context. We tested this hypothesis using fMRI, by tracking changes in item-specific BOLD activity patterns in the hippocampus, a key structure for representing memories and generating predictions. In left CA2/3/DG, we found greater neural differentiation for items that were repeatedly mispredicted and restudied compared to items from a control condition that was identical except without misprediction. We also measured prediction strength in a trial-by-trial fashion and found that greater misprediction for an item led to more differentiation, further supporting our hypothesis. Thus, the consequences of prediction error go beyond memory weakening: If the mispredicted item is restudied, the brain adaptively differentiates its memory representation to improve the accuracy of subsequent predictions and to shield it from further weakening.\n\nSignificanceCompetition between overlapping memories leads to weakening of non-target memories over time, making it easier to access target memories. However, a non-target memory in one context might become a target memory in another context. How do such memories get re-strengthened without increasing competition again? Computational models suggest that the brain handles this by reducing neural connections to the previous context and adding connections to new features that were not part of the previous context. The result is neural differentiation away from the previous context. Here provide support for this theory, using fMRI to track neural representations of individual memories in the hippocampus and how they change based on learning.

neuroscience↗