Biology subjects

Kim, C.

Publications and source records attributed to Kim, C..

8 recordsLinked to original sources

bioRxiv2018

Implantable electrical stimulation bioreactor with liquid crystal polymer based electrodes for enhanced bone regeneration at mandibular large defects in rabbit

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Our previous studies demonstrated that electrical stimulation (ES) with biphasic current pulse showed proliferative effects on bone cells and enhanced secretion of bone-forming growth factors. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which has excellent bone-binding property. The bioreactor was implanted into a critical sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via bioreactor was compared with a sham control group and positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20 g). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 171% (p < 0.001) and 210% (p < 0.001), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within bone defects and adjacent to LCP in all groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation.

bioengineering↗

bioRxiv2018

Dynamics of multiple interacting excitatory and inhibitory populations with delays

A network consisting of excitatory and inhibitory (EI) neurons is a canonical model for understanding cortical network activity. In this study, we extend the EI network model and investigate how its dynamical landscape can be enriched when it interacts with another excitatory (E) population with transmission delays. Through analysis and simulations of a rate model and a spiking network model, we study the transition from stationary to oscillatory states by analyzing the Hopf bifurcation structure in terms of two network parameters: 1) transmission delay between the EI subnetwork and the E population and 2) inhibitory couplings that induce oscillatory activity in the EI subnetwork. We find that the critical coupling strength can strongly modulate as a function of transmission delay, and consequently the stationary state is interwoven intricately with oscillatory states generating different frequency modes. This leads to the emergence of an isolated stationary state surrounded by multiple oscillatory states and cross-frequency coupling develops at the bifurcation points. We identify the possible network motifs that induce oscillations and examine how multiple oscillatory states come together to enrich the dynamical landscape.

neuroscience↗

bioRxiv2018

The Effect of Aldehyde Dehydrogenase Activator, Alda-1(R), on the Ethanol-induced Brain Damage in a Rat of Binge Ethanol Intoxication.

AimsThis study aimed to investigate whether an aldehyde dehydrogenase (ALDH) activator (Alda-1(R)) reduces neuronal damage in a rat model of binge ethanol exposure.\n\nMethodsThirty-six adolescent male rats (130-150 g) were randomly assigned into three groups: sham, ethanol-only group (25% ethanol intragastrically thrice daily for four days, approximately 10 g/kg/day) and ethanol with Alda-1(R) group (10 mg/kg thrice daily for four days). The ALDH activity at baseline and 90 min after the last infusion in each group was measured. Brain damage was investigated using Luxol fast blue-Cresyl violet staining in the hippocampus, CA1 and CA2/3. The activation of astrocytes and microglia was examined using immunohistochemistry for antiglial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1).\n\nResultsAfter a four-day binge, the ALDH activity level was doubled in the ethanol with Alda-1(R) group (mean: 7.87, SD: 0.67), whereas the levels in the sham group (mean: 4.07, SD: 0.53) and ethanol-only group (mean: 3.77, SD: 0.36) were slightly decreased. More significant neuronal shrinkage, fewer neurons, and loss of Nissl in the hippocampus were observed in the ethanol-only group compared to the ethanol with Alda-1(R) group. Astrocytosis and microgliosis of the hippocampus also showed increased activation in the ethanol only group compared with the ethanol with Alda-1(R) group.\n\nConclusionAlda-1(R) administration reduces cytotoxic damage to the hippocampus in adolescent rats with binge ethanol exposure.

neuroscience↗

bioRxiv2018

Association between Parkinson’s Disease subtypes and tests of physical function: the 360-degree turn test is most predictive

BACKGROUND AND PURPOSEPeople with Parkinsons disease (PD) present phenotypes that can be characterized as tremor-dominant (TD) or postural instability / gait difficulty (PIGD) subtypes. Differentiation of subtypes allows clinicians to predict the disease course and adjust treatment accordingly. We examined whether brief mobility and balance measures can discriminate PIGD from TD phenotypes.\n\nMETHODSWe performed a cross-sectional study with individuals with PD (N=104). Blinded raters assessed participants with the UPDRS or MDS-UPDRS, and potential predictor variables: 360-degree turn test, one-leg stance, backward perturbation test and tandem walk. Participant were classified as PIGD or TD based on the Unified Parkinsons Disease Rating Scale or the Movement Disorder Society revision (UPDRS or MDS-UPDRS) assessment results. Differences in study variables between subtype groups were assessed with univariate analyses. Receiver operating characteristic (ROC) curve analyses were performed to investigate the ability of candidate predictor variables to differentiate PD subtypes.\n\nRESULTSMean age and disease duration were 68{+/-}9 and 7{+/-}5 years, respectively, and Hoehn & Yahr Stages I-IV median (1st,3rd quartile) = II (II, III). No differences between subtypes were observed for tandem walk or reactive postural control. PIGD participants performed worse on number of steps (p<0.001) and time to complete (p=0.003) the 360-degree turn test and one-leg stance (p=0.006). ROC curves showed only the 360-degree turn test could discriminate PIGD from TD with high sensitivity.\n\nCONCLUSIONSThe 360-degree turn test requires minimal time to administer and may be useful in mild-moderate PD for distinguishing PIGD from TD subtypes.

neuroscience↗

bioRxiv2018

Genotyping by sequencing of 393 Sorghum bicolor BTx623 x IS3620C recombinant inbred lines improves sensitivity and resolution of QTL detection

We describe a genetic map with a total of 381 bins of 616 genotyping by sequencing (GBS)-based SNP markers in a F6-F8 recombinant inbred line (RIL) population of 393 individuals derived from crossing S. bicolor BTx623 to S. bicolor IS3620C, a guinea line substantially diverged from BTx623. Five segregation distorted regions were found with four showing enrichment for S. bicolor alleles, suggesting possible selection during formation of this RIL population. A quantitative trait locus (QTL) study with this number of individuals, tripled relative to prior studies of this cross, provided resources, validated previous findings, and demonstrated improved power to detect plant height and flowering time related QTLs relative to other published studies. An unexpected low correlation between flowering time and plant height permitted us to separate QTLs for each trait and provide evidence against pleiotropy. Ten non-random syntenic regions conferring QTLs for the same trait suggest that those QTLs may represent alleles at genes functioning in the same manner since the 96 million year ago genome duplication that created these syntenic relationships, while syntenic regions conferring QTLs for different trait may suggest sub-functionalization after duplication. Collectively, this study provides resources for marker-assisted breeding, as well as a framework for fine mapping and subsequent cloning of major genes for important traits such as plant height and flowering time in sorghum.

genetics↗

bioRxiv2018

Hedgehog signaling controls progenitor differentiation timing during heart development

Heterochrony, defined as differences in the timing of developmental processes, impacts organ development, homeostasis, and regeneration. The molecular basis of heterochrony in mammalian tissues is poorly understood. We report that Hedgehog signaling activates a heterochronic pathway that controls differentiation timing in multiple lineages. A differentiation trajectory from second heart field cardiac progenitors to first heart field cardiomyocytes was identified by single-cell transcriptional profiling in mouse embryos. A survey of developmental signaling pathways revealed specific enrichment for Hedgehog signaling targets in cardiac progenitors. Removal of Hh signaling caused loss of progenitor and precocious cardiomyocyte differentiation gene expression in the second heart field in vivo. Introduction of active Hh signaling to mESC-derived progenitors, modelled by transient expression of the Hh-dependent transcription factor GLI1, delayed differentiation in cardiac and neural lineages in vitro. A shared GLI1-dependent network in both cardiac and neural progenitors was enriched with FOX family transcription factors. FOXF1, a GLI1 target, was sufficient to delay onset of the cardiomyocyte differentiation program in progenitors, by epigenetic repression of cardiomyocyte-specific enhancers. Removal of active Hh signaling or Foxf1 expression from second heart field progenitors caused precocious cardiac differentiation in vivo, establishing a mechanism for resultant Congenital Heart Disease. Together, these studies suggest that Hedgehog signaling directly activates a gene regulatory network that functions as a heterochronic switch to control differentiation timing across developmental lineages.

developmental biology↗

bioRxiv2017

Effects of gamification and active listening on short-term sound localization training in virtual reality

Head-related transfer functions (HRTFs) capture the direction-dependant way that sound interacts with the head and torso. In virtual audio systems, which aim to emulate these effects, non-individualized, generic HRTFs are typically used leading to an inaccurate perception of virtual sound location. Training has the potential to exploit the brains ability to adapt to these unfamiliar cues. In this study, three virtual sound localization training paradigms were evaluated; one provided simple visual positional confirmation of sound source location, a second introduced game design elements ("gamification") and a final version additionally utilized head-tracking to provide listeners with experience of relative sound source motion ("active listening"). The results demonstrate a significant effect of training after a small number of short (12-minute) training sessions, which is retained across multiple days. Gamification alone had no significant effect on the efficacy of the training, but active listening resulted in a significantly greater improvements in localization accuracy. In general, improvements in virtual sound localization following training generalized to a second set of non-individualized HRTFs, although some HRTF-specific changes were observed in polar angle judgement for the active listening group. The implications of this on the putative mechanisms of the adaptation process are discussed.

animal behavior and cognition↗

bioRxiv2017

High-throughput live-imaging of embryos in microwell arrays using a modular, inexpensive specimen mounting system

Live-imaging embryos in a high-throughput manner is essential for shedding light on a wide range of questions in developmental biology, but it is difficult and costly to mount and image embryos in consistent conditions. Here, we present OMMAwell, a simple, reusable device that makes it easy to mount up to hundreds of embryos in arrays of agarose microwells with customizable dimensions and spacing. OMMAwell can be configured to mount specimens for upright or inverted microscopes, and includes a reservoir to hold live-imaging medium to maintain constant moisture and osmolarity of specimens during time-lapse imaging. All device components can be cut from a sheet of acrylic using a laser cutter. Even a novice user will be able to cut the pieces and assemble the device in less than an hour. At the time of writing, the total materials cost is less than five US dollars. We include all device design files in a commonly used format, as well as complete instructions for its fabrication and use. We demonstrate a detailed workflow for designing a custom mold and employing it to simultaneously live-image dozens of embryos at a time for more than five days, using embryos of the cricket Gryllus bimaculatus as an example. Further, we include descriptions, schematics, and design files for molds that can be used with 14 additional vertebrate and invertebrate species, including most major traditional laboratory models and a number of emerging model systems. Molds have been user-tested for embryos including zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), coqui frog (Eleutherodactylus coqui), annelid worm (Capitella teleta), amphipod crustacean (Parhyale hawaiensis), red flour beetle (Tribolium castaneum), and three-banded panther worm (Hofstenia miamia), as well mouse organoids (Mus musculus). Finally, we provide instructions for researchers to customize OMMAwell inserts for embryos or tissues not described herein.\n\nSummary StatementThis Techniques and Resources article describes an inexpensive, customizable device for mounting and live-imaging a wide range of tissues and species; complete design files and instructions for assembly are included.

developmental biology↗