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Kim, M.-J.

Publications and source records attributed to Kim, M.-J..

13 recordsLinked to original sources

Skin-Related Effects of Corynebacterium amycolatum SB-1 Ferment Filtrate and Functional Characterization of Ellagic Acid

Previous research has established a link between the genus Corynebacterium in the skin microbiota and skin health; however, studies investigating the specific effects of Corynebacterium-derived substances on skin cells remain limited. In this study, we isolated eight strains of Corynebacterium from the facial skin of female participant. To investigate the potential skin improvement effects of these isolates, three cultured skin cell lines (Hs68, HaCaT, and B16-F10) were treated with the supernatants of each strain. We then evaluated and compared the gene expression levels (ELN, COL1A1, IL-1{beta}, and HAS3) alongside their inhibitory effects on melanin biosynthesis. Corynebacterium amycolatum SB-1 was selected as the final candidate for subsequent analysis, primarily based on its rapid growth rate and high cell yield. Using LC-TOF/MS, we screened the postbiotic candidates from the SB-1 strain and identified ellagic acid as a known polyphenolic antioxidant with potent anti-melanogenic effects beneficial for skin improvement. To validate the effects of ellagic acid on skin cells, we assessed FLG gene expression and its inhibition of melanin biosynthesis. Additionally, RNA sequencing was performed to elucidate the underlying molecular mechanisms, revealing that ellagic acid is significantly involved in inhibiting melanogenesis and promoting collagen synthesis. Taken together, our results highlight ellagic acid derived from strain SB-1 as a highly effective bioactive compound for improving skin health, specifically targeting hyperpigmentation and skin aging.

genomics↗

cDNA-guided functional selection uncovers selective defense systems against RNA phages

Bacteria encode diverse antiphage defense systems, yet mechanisms that target RNA phages remain comparatively underexplored. Here, we used a cDNA-based functional selection strategy to systematically identify genes that confer resistance to RNA phage infection independently of receptor variation in Pseudomonas aeruginosa. This approach uncovered previously uncharacterized antiphage defense systems, most of which are located within genomic islands, consistent with their being bona fide components of bacterial immune systems. Several systems conferred selective resistance to RNA phages and their carriage was associated with pilin variability, suggesting layered anti-phage immunity. Among these systems, Zws is the most prevalent RNA phage defense system and functions as a multidomain effector. Structural modeling and in vitro cleavage assays showed that ZwsA is an RNA endonuclease that selectively cleaves RNA phage genomes through a predicted NERD domain. Together, these findings expand the current framework of bacterial antiphage immunity and highlight the power of functional genomics to uncover cryptic components of the bacterial antiviral arsenal. IMPORTANCEBacteria harbor a broad repertoire of antiphage defense systems, but our understanding of mechanisms that target RNA phages remains limited, being heavily biased toward defenses against DNA phages. By applying a cDNA-based functional selection strategy, this study overcomes a major obstacle in defense-gene discovery and uncovers previously uncharacterized genes that represent bona fide components of the bacterial immune arsenal against RNA phages. The identification and characterization of Zowangsin (ZwsA), a NERD-domain RNA endonuclease that selectively cleaves specific signatures within RNA phage genomes, establish targeted RNA degradation as a central principle of bacterial defense against RNA phages. More broadly, this work expands the conceptual framework of bacterial antiviral immunity and illustrates the utility of functional selection for uncovering cryptic immune systems with implications for phage biology, RNA biology, and biotechnology. HIGHLIGTHSO_LIcDNA-based functional screen identifies six defense systems that restrict RNA phages C_LIO_LIThese defense systems are enriched within genomic islands of Pseudomonas aeruginosa C_LIO_LIZws, Szs, and Mws systems confer selective defense against RNA phages C_LIO_LIZwsA is a signature-selective RNA endonuclease that targets phage genomic RNA C_LI

microbiology↗

Characterization of ORF19.7608 (PPP1), a Biofilm-induced Gene of Candida albicans

The opportunistic human pathogen Candida albicans is an important cause of nosocomial infections, in large part because of its propensity to form biofilms on indwelling medical devices such as catheters. The formation of these biofilms is controlled by a complex transcriptional network and involves over a thousand genes, many of which are uncharacterized. We have investigated three genes (ORF19.4654, ORF19.7608, and PBR1), found only in C. albicans and closely related species, that are highly induced under biofilm conditions and encode small proteins with N-terminal signal sequences. Through the construction of fluorescent protein fusions, we have examined the location of the encoded proteins in both planktonic and biofilm cells. Orf19.4654-Scarlet and Pbr1-Scarlet were localized to the vacuole under both conditions. In contrast, the Orf19.7608-GFP fusion generated a punctate pattern only under biofilm conditions and was designated Ppp1 (Punctate Pattern Protein 1). The Ppp1-GFP puncta were similar in location, stability, and size to those formed by the eisosome subunit Sur7, but co-localization studies suggest that Ppp1 and Sur7 define separate elements. The PPP1 mutation does not cause a distinct phenotype under various stress conditions or in the presence of antifungals and does not impact biofilm formation and biomass. These data suggest that while the expression and cellular localization of Ppp1 appear controlled by conditions generating biofilms, and define a unique subcellular localization pattern, Ppp1 protein function is not essential for biofilm formation. IMPORTANCEBiofilm formation is a virulence factor of medical importance in C. albicans. Identifying the biological function and cellular localization of biofilm-related proteins can help in their characterization and understanding of the biofilm network. Microscopy was employed to identify the subcellular localization of putative biofilm proteins, aiming to provide insight into their possible functions. Prb1 and Orf19.4654 localized to the vacuole, while Orf19.7608 (Ppp1) formed puncta. Phenotypic assays to investigate the uniqueness of PPP1 revealed that it does not play a major role in the stress response pathways or antifungal activity. Overall, our study provides insight into the localization of the products of Candida-specific biofilm genes.

microbiology↗

A Myosin Nanomotor Essential for Stereocilia Maintenance Expands the Etiology of Hereditary Hearing Loss DFNB3

Cochlear hair cells transduce sound using stereocilia, and disruption to these delicate mechanosensors is a significant cause of hearing loss. Stereocilia architecture is dependent upon the nanomotor myosin 15. A short isoform (MYO15A-2) drives stereocilia development by delivering an elongation-promoting complex (EC) to stereocilia tips, and an alternatively spliced long isoform (MYO15A-1) tunes postnatal size in shorter stereocilia, which possess mechanosensitive ion channels. Disruption of these functions causes two distinct stereocilia pathologies, which underly human autosomal recessive non-syndromic hearing loss DFNB3. Here, we characterize a new isoform, MYO15A-3, that increases expression in postnatal hair cells as the developmental MYO15A-2 isoform wanes reciprocally. We show the critical EC complex is initially delivered by MYO15A-2, followed by a postnatal handover to MYO15A-3, which continues to deliver the EC. In a Myo15a-3 mutant mouse, stereocilia develop normally with correct EC targeting, but lack the EC postnatally and do not maintain their adult architecture, leading to progressive hearing loss. We conclude MYO15A-3 delivers the EC in postnatal hair cells and that the EC and MYO15A-3 are both required to maintain stereocilia integrity. Our results add to the spectrum of stereocilia pathology underlying DFNB3 hearing loss and reveal new molecular mechanisms necessary for resilient hearing during adult life.

neuroscience↗

Linking Expression and Function of Drosophila Type-I TGF-b Receptor Baboon Isoforms: Multiple Roles of BaboA Isoform in Shaping of the Adult Central Nervous System

Evolutionarily conserved transforming growth factor {beta} (TGF-{beta}) signaling is used in both vertebrates and invertebrates to regulate a variety of developmental and cellular processes. The baboon (babo) gene encoding a Drosophila type-I TGF-{beta} receptor produces three isoforms via alternative splicing: BaboA, BaboB, and BaboC. In this study, we generated three fly lines, each carrying an isoform-specific GFP tag, and another line with a GFP conjugated at the C-terminus common to all isoforms. Using these lines, we assessed (1) whether the tagged proteins function properly in rescue assays and (2) how the isoform expression is regulated in various tissues including the central nervous system (CNS). A Gal4 knock-in line in the babo locus was also characterized for reporter expression, mutant phenotypes, and isoform-specific knockdown phenotypes. We found that the C-terminal tag does not interrupt the subcellular targeting and functions of the tagged isoforms, but the internal isoform tags do so in a cell- and isoform-specific fashion. Nevertheless, our results demonstrated that these tags faithfully reflect endogenous expression of individual isoforms. Certain cell types express single or multiple isoforms at different levels, suggesting that alternative splicing could determine the isoform types and their levels depending on cell (or tissue) type. The larval CNS displays distinct patterns of two isoforms, BaboA and BaboC. BaboC is mostly expressed in neural cells originating during embryogenesis, while BaboA is broadly expressed in neural cells produced from both embryonic and postembryonic stages. Assays of both isoform-specific mutants and cell-specific knockdown of individual isoforms revealed broad roles played by BaboA in postembryonic neurogenesis and differentiation of precursor neurons, remodeling processes of persisting larval neurons, and metamorphic CNS reorganization, which are essential for establishing of the adult CNS. Taken together, this study demonstrates that the GFP-tagged lines permit visualization of endogenous expression of individual isoforms, which further provides clues about cell- and stage-specific functions played by each isoform.

developmental biology↗

A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135FUN025/FUN025 (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

neuroscience↗

Multiple Isoforms of the Activin-like receptor Baboon differentially regulate proliferation and conversion behaviors of neuroblasts and neuroepithelial cells in the Drosophila larval brain

In Drosophila coordinated proliferation of two neural stem cells, neuroblasts (NB) and neuroepithelial (NE) cells, is pivotal for proper larval brain growth that ultimately determines the final size and performance of an adult brain. The larval brain growth displays two phases based on behaviors of NB and NEs: the first one in early larval stages, influenced by nutritional status and the second one in the last larval stage, promoted by ecdysone signaling after critical weight checkpoint. Mutations of the baboon (babo) gene that produces three isoforms (BaboA-C), all acting as type-I receptors of Activin-type transforming growth factor {beta} (TGF-{beta}) signaling, cause a small brain phenotype due to severely reduced proliferation of the neural stem cells. In this study we show that loss of babo function severely affects proliferation of NBs and NEs as well as conversion of NEs from both phases. By analyzing babo-null and newly generated isoform-specific mutants by CRISPR mutagenesis as well as isoform-specific RNAi knockdowns in a cell- and stage-specific manner, we further demonstrate differential contributions of the isoforms for these cellular events with BaboA playing the major role. Our data show that stage-specific expression of EcR-B1 in the brain is also regulated primarily by BaboA along with function of the other isoforms. Blocking EcR function in both neural stem cells results in a small brain phenotype that is more severe than baboA-knockdown alone. In summary, our study proposes that the Babo-mediated signaling promotes proper behaviors of the neural stem cells in both phases and achieves this by acting upstream of EcR-B1 expression in the second phase. Author SummaryEvolutionarily conserved TGF-{beta} signaling pathway is widely utilized as a regulator of diverse processes of brain development in both vertebrates and invertebrates. A key element in Drosophila Activin type TGF-{beta} signaling pathway is the type-I receptor Babo. The babo gene produces three isoforms, each with a unique ligand preference. Our study uncovers that Babo-mediated signaling promotes proper proliferation of NBs and NEs and conversion of NEs, together responsible for the magnitude of larval brain size growth. Three isoforms act individually or together to regulate these cellular events in coordination with developmental status. Our findings emphasize that Babo-mediated signaling is a crucial regulator of postembryonic neurogenesis that generates 90% of neuronal population for the adult brain.

developmental biology↗

Loss of Esr1 Does Not Affect Hearing and Balance

Although estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) and Esr1 knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight of Esr1 KO females was lower than that of Esr1 KO males. Body weight of Esr1 KO females was higher than that of WT females, while there was no difference in body weight between WT and Esr1 KO males. Similarly, head diameter was higher in Esr1 KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT and Esr1 KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance in Esr1 KO mice. Taken together, our findings show that Esr1 deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss of Esr1 is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions. HighlightsO_LIHead diameter of female Esr1 KO mice was higher than that of female WT mice. C_LIO_LIABRs and DPOAEs were not different in WT and Esr1 KO mice. C_LIO_LIThere were no sex differences in ABRs and DPOAEs in Esr1 KO mice. C_LIO_LIRotarod balance performance was not different in WT and Esr1 KO mice. C_LIO_LIThere were no sex differences in rotarod balance performance in Esr1 KO mice. C_LIO_LILoss of Esr1 does not affect auditory function or balance performance under normal physiological conditions. C_LI

neuroscience↗

Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1

Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, Metastasis Suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.

developmental biology↗

Sensitivity of radio-photoluminescence glass dosimeters to accumulated doses

BackgroundThis study investigated the effect of accumulated doses on radio-photoluminescence glass dosimeters (RPLGDs) from measurements involving mega-voltage photons. MethodsForty-five commercially available RPLGDs were irradiated to estimate their dose responses. Photon beams of 6, 10, and 15 MV were irradiated onto the RPLGDs inside a phantom, which were divided into five groups with different doses and energies. Groups 1 and 2 were irradiated at 1, 5, 10, 50, and 100 Gy in a sequential manner; Group 3 was irradiated 10 times with a dose of 10 Gy; and Groups 4 and 5 followed the same method as that of Group 3, but with doses of 50 Gy and 100 Gy, respectively. ResultsFor the annealed Group 1, RPLGD exhibited a linearity response with variance within 5%. For the non-annealed Group 2, readings demonstrated hyperlinearity at 6 MV and 10 MV, and linearity at 15 MV. Following the 100 Gy irradiation, the readings for Group 2 were 118.7 {+/-} 1.9%, 112.2 {+/-} 2.7%, and 101.5 {+/-} 2.3% at 6, 10, and 15 MV, respectively. For Groups 3, 4, and 5, the responsiveness of the RPLGDs gradually decreased as the number of repeated irradiations increased. The percentage readings for the 10th beam irradiation with respect to the readings for the primary beam irradiation were 84.6 {+/-} 1.9%, 87.5 {+/-} 2.4%, and 93.0 {+/-} 3.0% at 6 MV, 10 MV, and 15 MV, respectively. ConclusionsThe non-annealed RPLGD response to dose was hyperlinear for the 6 MV and 10 MV photon beams but not for the 15 MV photon beam. Additionally, the annealed RPLGD exhibited a fading phenomenon when the measurement was repeated several times and demonstrated a relatively large fading effect at low energies than at high energies.

cancer biology↗

Drosophila Activin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes

The Myostatin/Activin branch of the TGF{beta} superfamily acts as a negative regulator of mammalian skeletal muscle size, in part, through downregulation of insulin/IGF-1 signaling. Surprisingly, recent studies in Drosophila indicate that Activin signaling acts as a positive regulator of muscle size. Here we demonstrate that Drosophila Activin signaling promotes growth of the muscle cells along all three axes; width, length and thickness. In addition, Activin signaling positively regulates the InR/dTORC1 pathway and the level of MHC, an essential sarcomeric protein, via promoting the transcription of Pdk1 and Akt1. Enhancing InR/dTORC1 signaling in the muscle of Activin pathway mutants restores MHC levels close to wild-type, but only increased the width of muscle cells. In contrast, hyperactivation of the Activin pathway increases the length of muscle cells even when MHC levels were lowered by suppression of dTORC1. Together, these results indicate that Drosophila Activin pathway regulates larval muscle geometry via promoting InR/dTORC1-dependent MHC production and the differential assembly of sarcomeric components into either pre-existing (width) or new (length) sarcomeric units depending on the balance of InR/dTORC1 and Activin signals.

developmental biology↗

Motoneuron-derived Activinβ regulates Drosophila body size and tissue-scaling during larval growth and adult development

Correct scaling of body and organ size is crucial for proper development and survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. The identity of additional factors that might contribute to scaling of organs and appendages with body size is unknown. Here we report that loss-of-function mutations in Drosophila Activin{beta} (Act{beta}), a member of the TGF-{beta} superfamily, lead to production of small larvae/pupae and undersized rare adult escapers. Morphometric measurements of escaper adult appendage size (wings, legs), as well as heads, thoraxes, and abdomens, reveal a disproportional reduction in abdominal size compared to other tissues. Similar size measurements of selected Act{beta} mutant larval tissues demonstrate that somatic muscle size is disproportionately smaller when compared to fat body, salivary glands, prothoracic glands, imaginal discs and brain. We also show that Act{beta} control of body size is dependent on canonical signaling through the transcription-factor dSmad2 and that it modulates the growth rate, but not feeding behavior, during the third instar period. Tissue and cell-specific knockdown and overexpression studies reveal that motoneuron derived Act{beta} is essential for regulating proper body size and tissue scaling. These studies suggest that, unlike in vertebrates where Myostatin, and certain other Activin-like factors act as systemic negative regulators of muscle mass, in Drosophila Act{beta} is a positive regulator of muscle mass that is directly delivered to muscles by motoneurons. We discuss the importance of these findings in coordinating proportional scaling of insect muscle mass to appendage size.

developmental biology↗

Predicting potential current distribution of Lycorma delicatula (Hemiptera: Fulgoridae) using MaxEnt model in South Korea

Lycorma delicatula (Hemiptera: Fulgoridae) is invasive insect in Korea which causes plant damages by sucking and sooty molds. Lycorma delicatula was first detected in South Korea in 2004, where its introduction and spreading possibly were affected by human activity-related factors. Here, we used MaxEnt to describe current distribution of L. delicatula in Korea and tried to find out the impact of human influences for distribution. We used 143 sites of occurrence data, 19 bioclimatic variables, duration of temperature below -11{degrees}C, average daily minimum temperature in January, cumulative thermal unit variable, the distribution of grape orchard variable and human footprint to create models. These models were estimated by two sets of 24 candidates with feature combinations and regularization multipliers. In addition, these two sets were created as models with and without footprint for how human influence affect to distribution. Model selection for optimal model was performed by selecting a model with a lowest sum of each rank in small sample-size corrected Akaikes information criterion and difference between training and test AUC. Model of LQ10 parameter combinations was selected as optimal models for both model sets. Consequently, both of distribution maps from these models showed similar patterns of presence probability for L. delicatula. Both models expected that low altitude regions were relatively more suitable than mountain areas in Korea. Footprint might be limited for the distribution and L. delicatula might already occupy most of available habitats. Human-related factors might contribute to spread of L. delicatula to uninfected areas.

ecology↗