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Biomedical subjects

Jiho Park

Publications and source records attributed to Jiho Park.

10 recordsLinked to original sources

Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.

Glioblastoma (GBM) remains lethal despite maximal therapy. The adult subventricular zone (SVZ), a neural stem-cell niche, has been implicated as a potential site of origin, yet the identity and functional properties of putative GBM origin-like cells (GBM-OCs) within the SVZ remain unclear. An SVZ-restricted somatic mutation mouse model (Cre-induced EGFRvIII expression with Trp53 and Pten disruption) was established and mouse SVZ-derived cells were prospectively isolated for functional and molecular profiling. Self-renewal, multipotency, invasive potential and tumour-initiating capacity were assessed relative to control SVZ cells and matched tumour-derived tumourspheres. Whole-genome and RNA sequencing defined genomic and transcriptional alterations during early progression. Mouse GBM-OCs exhibited self-renewal and multilineage differentiation and initiated tumours only after re-implantation into the SVZ (11/29, 38%), whereas direct striatal implantation failed (0/25, 0%), indicating context-dependent tumorigenic potential associated with the SVZ microenvironment. In contrast, tumour-derived tumourspheres retained tumorigenic capacity upon implantation into both the SVZ and the striatum. During progression from mouse GBM-OCs to tumours, whole-chromosome and arm-level aneuploidies accumulated. In patients with GBM, multi-region single-nucleus RNA sequencing of tumour-free SVZ, matched tumours and tumour-free cortex identified rare neural stem cell-like, astrocyte-like and oligodendrocyte precursor-like SVZ populations transcriptionally aligned with GBM programmes. These cells showed single-nucleus RNA-inferred chromosome 7 gain and/or chromosome 10 loss signals, with concordant low-frequency copy-number alterations in the SVZ detected by exome sequencing and enriched in matched tumours. Together, these findings support the presence of SVZ-resident stem or progenitor-like populations with early GBM-associated features, consistent with putative GBM-OCs, and highlight the SVZ niche as a potential target for early detection and niche-informed therapeutic strategies.

Animals↗

Expanding the druggable zinc-finger proteome defines properties of drug-induced degradation.

Glutarimide analogs, such as thalidomide, redirect the E3 ubiquitin ligase CRL4CRBN to induce degradation of certain zinc finger (ZF) proteins. Although the core structural motif recognized by CRBN has been characterized, it does not fully explain substrate specificity. To explore the role of residues adjacent to this core motif, we constructed a comprehensive ZF reporter library of 9,097 reporters derived from 1,655 human ZF proteins and conducted a library-on-library screen with 29 glutarimide analogs to identify compounds that collectively degrade 38 ZF reporters. Cryo-electron microscopy and crystal structures of ZFs in complex with CRBN revealed the importance of interactions beyond the core ZF degron. We used systematic mutagenesis of ZFs and CRBN to identify modes of neosubstrate recruitment requiring distinct amino acids. Finally, we found subtle chemical variations in glutarimide analogs that alter target scope and selectivity, thus providing a roadmap for their rational design.

Humans↗

Ozonolysis and photolysis of alkene-terminated self-assembled monolayers on quartz nanoparticles: implications for photochemical aging of organic aerosol particles.

Photolysis of alkene-terminated self assembled monolayers (SAM) deposited on Degussa SiO(2) nanoparticles is studied following oxidation of SAM with a gaseous ozone/oxygen mixture. Infrared cavity ring-down spectroscopy is used to observe gas-phase products generated during ozonolysis and subsequent photolysis of SAM in real time. Reactions taking place during ozonolysis transform alkene-terminated SAM into a photochemically active state capable of photolysis in the tropospheric actinic window (lambda > 295 nm). Formaldehyde and formic acid are the observed photolysis products. Photodissociation action spectra of oxidized SAM and the observed pattern of gas-phase products are consistent with the well-established Criegee mechanism of ozonolysis of terminal alkenes. There is strong evidence for the presence of secondary ozonides (1,3,4-trioxalones) and other peroxides on the oxidized SAM surface. The data imply that photolysis plays a role in atmospheric aging of primary and secondary organic aerosol particles.

Journal Article↗

UV photodissociation spectroscopy of oxidized undecylenic acid films.

Oxidation of thin multilayered films of undecylenic (10-undecenoic) acid by gaseous ozone was investigated using a combination of spectroscopic and mass spectrometric techniques. The UV absorption spectrum of the oxidized undecylenic acid film is significantly red-shifted compared to that of the initial film. Photolysis of the oxidized film in the tropospheric actinic region (lambda > 295 nm) readily produces formaldehyde and formic acid as gas-phase products. Photodissociation action spectra of the oxidized film suggest that organic peroxides are responsible for the observed photochemical activity. The presence of peroxides is confirmed by mass-spectrometric analysis of the oxidized sample and an iodometric test. Significant polymerization resulting from secondary reactions of Criegee radicals during ozonolysis of the film is observed. The data strongly imply the importance of photochemistry in aging of atmospheric organic aerosol particles.

Journal Article↗

The UV photodissociation dynamics of ClO radical using velocity map ion imaging.

We have studied the wavelength-dependent photodissociation dynamics of jet-cooled ClO radical from 235 to 291 nm using velocity map ion imaging. We find that Cl(2P(3/2))+O(1D(2)) is the dominant channel above the O(1D(2)) threshold with minor contributions from the Cl(2P(J))+O(3P(J)) and Cl(2P(1/2))+O(1D(2)) channels. We have measured the photofragment angular distributions for each dissociation channel and find that the A 2pi state reached via a parallel transition carries most of the oscillator strength above the O(1D(2)) threshold. The formation of O(3P(J)) fragments with positive anisotropy is evidence of curve crossing from the A 2pi state to one of several dissociative states. The curve crossing probability increases with wavelength in good agreement with previous theoretical calculations. We have directly determined the O(1D(2)) threshold to be 38,050+/-20 cm(-1) by measuring O(1D(2)) quantum yield in the wavelength range of 260-270 nm. We also report on the predissociation dynamics of ClO below the O(1D(2)) threshold. We find that the branching ratio of Cl(2P(3/2))/Cl(2P(1/2)) is 1.5+/-0.1 at both 266 and 291 nm. The rotational depolarization of the anisotropy parameters of the Cl(2P(3/2)) fragments provides predissociation lifetimes of 1.5+/-0.2 ps for the 9-0 band and 1.0+/-0.4 ps for the 8-0 band, in reasonable agreement with previous spectroscopic and theoretical studies.

Journal Article↗

The OH-initiated oxidation of 1,3-butadiene in the presence of O2 and NO: a photolytic route to study isomeric selective reactivity.

We report the study of the isomeric selective OH-initiated oxidation of 1,3-butadiene in the presence of O2 and NO using the LP/LIF technique. The photolysis of monodeuterated 1-iodo-3-buten-2-ol provides only one of the possible OD-butadiene adducts, the minor addition channel product, simplifying the oxidation mechanism. We find, based on analysis of OD time-dependent traces that prompt rearrangement of initial beta-hydroxyalkyl radicals to alpha-hydroxyalkyl radicals occurs in agreement with RRKM/ME theoretical predictions. We report a rate constant of (3.3+/-1.0) x 10(-11) cm3 molecules(-1) s(-1) for deuterium abstraction from the alpha-hydroxyalkyl radical at 298 +/-2 K. Our approach demonstrates the feasibility of isomeric selective kinetic studies of the OH-initiated oxidation of unsaturated hydrocarbons.

Journal Article↗

Recovery of image blocks using the method of alternating projections.

A technique for block-loss restoration in block-based image and video coding, dubbed recovery of image blocks using the method of alternating projections (RIBMAP), is developed. The algorithm is based on orthogonal projections onto constraint sets in a Hilbert space. For the recovery of a linear dimension N size block, a total of 8N vectors are extracted from the surrounding area of an N x N missing block. These vectors form a library from which the best matching spatial information for the missing block is extracted. Recovery vectors, including both undamaged and restored damaged pixels, are introduced. The vectors are used to find highly correlated information relating to the lost pixels. To assure continuity with the surrounding undamaged area, three additional convex constraints are formulated. Adherance to these sets is imposed using alternating projections. Simulation results using orthogonal projections demonstrate that RIBMAP recovers spatial structure faithfully. Simulation comparisons with other procedures are presented: Ancis and Giusto's hybrid edge-based average-median interpolation technique, Sun and Kwok's projections onto convex sets-based method, Hemami and Meng's interblock correlation interpolation approach, Shirani et al.'s modified interblock correlation interpolation scheme, and Alkachouh and Bellanger's fast discrete cosine transformation-based spatial domain interpolation algorithm. Characteristic of the results are those of the "Lena" JPEG image when one fourth of periodically spaced blocks in the image have errors. The peak signal-to-noise ratio of the restored image is 28.68, 29.99, 31.86, 31.69, 31.57, and 34.65 dB using that of Ancis and Giusto, Sun and Kwok, Hemami and Meng, Shirani et al., Alkachouh and Bellanger, and RIPMAP, respectively.

Algorithms↗

Content-based adaptive spatio-temporal methods for MPEG repair.

Block loss and propagation error due to cell loss or missing packet information during the transmission over lossy networks can cause severe degradation of block and predictive-based video coding. Herein, new fast spatial and temporal methods are presented for block loss recovery. In the spatial algorithm, missing block recovery and edge extention are performed by pixel replacement based on range constraints imposed by surrounding neighborhood edge information and structure. In the temporal algorithm, an adaptive temporal correlation method is proposed for motion vector (MV) recovery. Parameters for the temporal correlation measurement are adaptively changed in accordance to surrounding edge information of a missing macroblock (MB). The temporal technique utilizes pixels in the reference frame as well as surrounding pixels of the lost block. Spatial motion compensation is applied after MV recovery when the reference frame does not have sufficient information for lost MB restoration. Simulations demonstrate that the proposed algorithms recover image information reliably using both spatial and temporal restoration. We compare the proposed algorithm with other procedures with consistently favorable results.

Algorithms↗

Induction of TGF-beta-inducible gene-h3 (betaig-h3) by TGF-beta1 in astrocytes: implications for astrocyte response to brain injury.

Transforming growth factor (TGF)-beta-inducible gene-h3 (betaig-h3) product is a secreted protein that is induced by TGF-beta in several cell types and implicated in various tissue pathologies. The aims of this study were to determine the effect of TGF-beta1 on betaig-h3 expression in cultured astrocytes and to examine whether betaig-h3 is expressed in the brain after traumatic injury. The results showed that betaig-h3 mRNA and protein increased in response to TGF-beta1 in U87 human astrocytoma cells and mouse cortical astrocytes. Treatment with other cytokines, including tumor necrosis factor-alpha and fibroblast growth factor-2, did not enhance the expression of betaig-h3 in astrocytes. betaig-h3 was significantly expressed in reactive astrocytes at the site of a stab wound in the cerebral cortex of adult rats. These results provide an insight into understanding a novel role for betaig-h3 protein in the response of astrocytes to brain injury.

Animals↗

Hydroxy peroxy nitrites and nitrates from OH initiated reactions of isoprene.

The reaction of hydroxy peroxy radicals (RO(2)) with NO represents one of the most crucial tropospheric processes, leading to terrestrial ozone formation or NO(x)() removal and chain termination. We investigate the formation of hydroxy peroxy nitrites (ROONO) and nitrates (RONO(2)) from the OH-isoprene reactions using DFT and ab initio theories and variational RRKM/master equation (vRRKM/ME) formalism. The binding energies of ROONO from NO addition to RO(2) are determined to be in the range of 20-22 kcal mol(-)(1), and the bond dissociation energies of ROONO to form an alkoxy radical (RO) and NO(2) range from 6 to 9 kcal mol(-)(1). Isomerization of ROONO to RONO(2) is exothermic by 22-28 kcal mol(-)(1). The entrance and exit channels of the RO(2)-NO reaction are found to be barrierless, and the rate constants to form ROONO are calculated to be 3 x 10(-)(12) to 2 x 10(-)(11) cm(3) molecule(-)(1) s(-)(1) using the canonical variational transition state theory. The vRRKM/ME analysis reveals negligible stabilization of excited ROONO and provides an assessment of ROONO isomerization to RONO(2).

Journal Article↗