Biology subjects

Park, K.

Publications and source records attributed to Park, K..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Reciprocal discoidin domain receptor signaling strengthens integrin adhesion to connect adjacent tissues

Separate tissues connect through adjoining basement membranes to carry out molecular barrier, exchange, and organ support functions. Cell adhesion at these connections must be robust and balanced to withstand independent tissue movement. Yet, how cells achieve synchronized adhesion to connect tissues is unknown. Here, we have investigated this question using the C. elegans utse-seam tissue connection that supports the uterus during egg-laying. Through genetics, quantitative fluorescence, and cell specific molecular disruption, we show that type IV collagen, which fastens the linkage, also activates the collagen receptor discoidin domain receptor 2 (DDR-2) in both the utse and seam. RNAi depletion, genome editing, and photobleaching experiments revealed that DDR-2 signals through LET-60/Ras to coordinately strengthen an integrin adhesion in the utse and seam that stabilizes their connection. These results uncover a synchronizing mechanism for robust adhesion during tissue connection, where collagen both affixes the linkage and signals to both tissues to bolster their adhesion.

developmental biology↗

bioRxiv2023

Melanotransferrin Functions as a Pro-Oncogenic WNT Agonist: A Yin-Yang Relationship in Melanoma with the WNT Antagonist and Metastasis Suppressor, NDRG1

A persistent mystery in the melanoma field has been the function of one of the first melanoma tumor antigens characterized, namely p97 (melanotransferrin; MTf). While MTf expression increases melanoma cell proliferation, migration, and tumorigenesis, the molecular mechanism responsible is unknown. On the other hand, N-myc down-stream regulated gene 1 (NDRG1) is a potent metastasis suppressor and WNT antagonist. Expression of NDRG1 in melanoma cells suggests a role in inhibiting metastasis, with this study investigating MTfs role in oncogenic signaling. We demonstrate MTf acts as a pro-oncogenic WNT agonist, which down-regulates NDRG1, while silencing MTf increases NDRG1 expression. In contrast, silencing NDRG1 increases MTf expression. These observations demonstrate a bidirectional negative feedback loop and "Yin-Yang" relationship between MTf and NDRG1. Mechanistically, MTf was directly associated with the WNT co-receptor, lipoprotein-receptor 6 (LRP6), and increased total LRP6 expression, activated p-LRP6 (Ser1490), {beta}-catenin, and activated {beta}-catenin (Ser552) levels, with MTf expression inducing their nuclear accumulation. Additionally, MTf expression increased downstream WNT targets, namely cyclin D1 and c-Myc, with c-Myc down-regulating NDRG1 expression. Silencing c-Myc prevented the Yin-Yang relationship between NDRG1 and MTf, indicating c-Myc played a key role in their inverse regulation. Melanoma patient specimens demonstrated that a low NDRG1/MTf ratio was significantly (p = 0.008) associated with lower survival and metastasis. Chemotherapeutic agents that up-regulated NDRG1 depressed MTf and nuclear LRP6 and potently inhibited melanoma xenograft growth in vivo. This study demonstrates MTf acts as a WNT agonist, with a Yin-Yang relationship being observed with the WNT antagonist, NDRG1.

cancer biology↗

bioRxiv2023

Joint tensor modeling of single cell 3D genome and epigenetic data with Muscle

Emerging single cell technologies that simultaneously capture long-range interactions of genomic loci together with their DNA methylation levels are advancing our understanding of three-dimensional genome structure and its interplay with the epigenome at the single cell level. While methods to analyze data from single cell high throughput chromatin conformation capture (scHi-C) experiments are maturing, methods that can jointly analyze multiple single cell modalities with scHi-C data are lacking. Here, we introduce Muscle, a semi-nonnegative joint decomposition of Multiple single cell tensors, to jointly analyze 3D conformation and DNA methylation data at the single cell level. Muscle takes advantage of the inherent tensor structure of the scHi-C data, and integrates this modality with DNA methylation. We developed an alternating least squares algorithm for estimating Muscle parameters and established its optimality properties. Parameters estimated by Muscle directly align with the key components of the downstream analysis of scHi-C data in a cell type specific manner. Evaluations with data-driven experiments and simulations demonstrate the advantages of the joint modeling framework of Muscle over single modality modeling or a baseline multi modality modeling for cell type delineation and elucidating associations between modalities. Muscle is publicly available at https://github.com/keleslab/muscle.

genomics↗

bioRxiv2022

The C. elegans Anchor Cell Transcriptome: Ribosome Biogenesis Drives Cell Invasion through Basement Membrane

Cell invasion through basement membrane (BM) barriers is important in development, immune function, and cancer progression. As invasion through BM is often stochastic, capturing gene expression profiles of cells actively transmigrating BM in vivo remains elusive. Using the stereotyped timing of C. elegans anchor cell (AC) invasion, we generated an AC transcriptome during BM breaching. Through a focused RNAi screen of transcriptionally enriched genes, we identified new invasion regulators, including TCTP (Translationally Controlled Tumor Protein). We also discovered gene enrichment of ribosomal proteins. AC-specific RNAi, endogenous ribosome labeling, and ribosome biogenesis analysis revealed a burst of ribosome production occurs shortly after AC specification, which drives the translation of proteins mediating BM removal. Ribosomes also strongly localize to the ACs endoplasmic reticulum (ER) and the endomembrane system expands prior to invasion. We show that AC invasion is sensitive to ER stress, indicating a heightened requirement for translation of ER trafficked proteins. These studies reveal key roles for ribosome biogenesis and endomembrane expansion in cell invasion through BM and establish the AC transcriptome as a resource to identify mechanisms underlying BM transmigration.

cell biology↗

bioRxiv2022

Cotranslational formation of disulfides guides folding of the SARS CoV-2 receptor binding domain

Many secreted proteins contain multiple disulfide bonds. How disulfide formation is coupled to protein folding in the cell remains poorly understood at the molecular level. Here, we combine experiment and simulation to address this question as it pertains to the SARS-CoV-2 receptor binding domain (RBD). We show that, whereas RBD can refold reversibly when its disulfides are intact, their disruption causes misfolding into a nonnative molten-globule state that is highly prone to aggregation and disulfide scrambling. Thus, non-equilibrium mechanisms are needed to ensure disulfides form prior to folding in vivo. Our simulations suggest that co-translational folding may accomplish this, as native disulfide pairs are predicted to form with high probability at intermediate lengths, ultimately committing the RBD to its metastable native state and circumventing nonnative intermediates. This detailed molecular picture of the RBD folding landscape may shed light on SARS-CoV-2 pathology and molecular constraints governing SARS-CoV-2 evolution.

biophysics↗

bioRxiv2022

Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice

After severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) made the world tremble with a global pandemic, SARS-CoV2 vaccines were developed. However, due to the coronaviruss intrinsic nature, new variants emerged, such as Delta and Omicron, refractory to the vaccines derived using the original Wuhan strain. We developed an HERV-enveloped recombinant baculoviral DNA vaccine against SARS-CoV2 (AcHERV-COVID19S). A non-replicating recombinant baculovirus that delivers the SARS-CoV2 spike gene showed a protective effect against the homologous challenge in a K18-hACE2 Tg mice model; however, it offered only a 50% survival rate against the SARS-CoV2 Delta variant. Therefore, we further developed the AcHERV-COVID19 Delta vaccine (AcHERV-COVID19D). Cross-protection experiments revealed that mice vaccinated with the AcHERV-COVID19D showed 100% survival upon challenge with Delta and Omicron variants and 71.4% survival against prototype SARS-CoV2. These results support the potential of the viral vector vaccine, AcHERV-COVID19D, in preventing the spread of coronavirus variants such as Omicron and SARS-CoV2 variants. Author SummaryAfter the SARS-CoV2 pandemic, it is known that the existing vaccine has diminished efficacy against the emerging variants. We developed a baculoviral COVID19 DNA vaccine for the Delta variant (AcHERV-COVIS19D). Compared to AcHERV-COVID19S, designed to protect from the prototype of SARS-CoV2, AcHERV-COVID19D elicited higher humoral and cellular immunity and showed perfect protection against SARS-CoV2 delta strain and Omicron challenge. The broad and robust cellular immunity of the AcHERV-COVID19D vaccine appears to have played a significant role in the cross-protection of the Omicron variant. Our AcHERV-COVID19D can be a potential vaccine against emerging SARS-CoV2 variants.

immunology↗

bioRxiv2022

Design of a highly specific glutamine sensor by splitting the glutamine-binding protein

Studies on glutamine (Gln) metabolism have illuminated the vital role of Gln in cellular functions and its potential as a biomarker for disease detection. Despite the increasing interest in Gln metabolism, in-depth evaluations are challenging owing to limitations of conventional Gln-measuring methods. Thus, we developed a ligand-induced dimerization-based sensor for Gln, termed Q-SHINE, by splitting a glutamine binding protein into two separate domains. Q-SHINE enables highly accurate and convenient measurement of Gln concentration in bio-fluid samples, and the detection range is optimal for physiological Gln levels. Genetically encoded Q-SHINE sensors could also visualize intracellular Gln levels and quantify cytoplasmic and mitochondrial Gln change in living cells, which enabled detection of various cell responses to extracellular Gln supplement.

bioengineering↗

bioRxiv2022

McaA and McaB control the dynamic positioning of a bacterial magnetic organelle

Magnetotactic bacteria (MTB) are a diverse group of microorganisms that use intracellular chains of ferrimagnetic nanocrystals, produced within their magnetosome organelles, to align and navigate along the geomagnetic field. The cell biological and biochemical properties of magnetosomes make them a powerful model for studying the molecular mechanisms of biomineralization and compartmentalization in bacteria. While several conserved magnetosome formation genes have been described, the evolutionary strategies for their species-specific diversification remain unknown. Here, we demonstrate that the fragmented nature of magnetosome chains in Magnetospirillum magneticum AMB-1 is controlled by two genes named mcaA and mcaB. McaA recognizes the positive curvature of the inner cell membrane while McaB localises to magnetosomes. Along with the MamK actin-like cytoskeleton, they create space for addition of new magnetosomes in between pre-existing magnetosomes. Phylogenetic analyses suggest that McaAB homologs are widespread and may represent an ancient strategy for organelle positioning in MTB.

microbiology↗

bioRxiv2022

Systematic conformation-to-phenotype mapping via limited deep-sequencing of proteins

Non-native conformations drive protein misfolding diseases, complicate bioengineering efforts, and fuel molecular evolution. No current experimental technique is well-suited for elucidating them and their phenotypic effects. Especially intractable are the transient conformations populated by intrinsically disordered proteins. We describe an approach to systematically discover, stabilize, and purify native and non-native conformations, generated in vitro or in vivo, and directly link conformations to molecular, organismal, or evolutionary phenotypes. This approach involves high-throughput disulfide scanning (HTDS) of the entire protein. To reveal which disulfides trap which chromatographically resolvable conformers, we devised a deep-sequencing method for double-Cys variant libraries of proteins that precisely and simultaneously locates both Cys residues within each polypeptide. HTDS of the abundant E. coli periplasmic chaperone HdeA revealed distinct classes of disordered hydrophobic conformers with variable cytotoxicity depending on where the backbone was cross-linked. HTDS can bridge conformational and phenotypic landscapes for many proteins that function in disulfide-permissive environments.

biophysics↗

bioRxiv2022

Bicarbonate Activation of Monomeric Photosystem II-PsbS/Psb27 Complex

In thylakoid membranes, Photosystem II monomers from the stromal lamellae contain the subunits PsbS and Psb27 (PSIIm-S/27), while Photosystem II monomers from granal regions (PSIIm) lack these subunits. Here, we have isolated and characterised these two types of Photosystem II complexes. The PSIIm-S/27 showed enhanced fluorescence, the near-absence of oxygen evolution, as well as limited and slow electron transfer from QA to QB compared to the near-normal activities in the granal PSIIm. However, when bicarbonate was added to the PSIIm-S/27, water splitting and QA to QB electron transfer rates were comparable to those in granal PSIIm. The findings suggest that the binding of PsbS and/or Psb27 inhibits forward electron transfer and lowers the binding affinity for the bicarbonate. This can be rationalized in terms of the recently discovered photoprotection role played by bicarbonate binding via the redox tuning of the QA/QA*- couple, which controls the charge recombination route, and this limits chlorophyll triplet mediated 1O2 formation (Brinkert K et al. (2016) Proc Natl Acad Sci U S A. 113(43):12144-12149). These findings suggest that PSIIm-S/27 is an intermediate in the assembly of PSII in which PsbS and/or Psb27 restrict PSII activity while in transit, by using a bicarbonate-mediated switch and protective mechanism. One sentence summaryA photosystem II monomer with PsbS and Psb27 as additional subunits, is inactive as isolated but activated by bicarbonate, and is attributed to be a late-stage intermediate in photoassembly.

plant biology↗

bioRxiv2021

Hemicentin mediated type IV collagen assembly strengthens juxtaposed basement membrane linkage

Basement membrane (BM) matrices surround and separate most tissues. However, through poorly understood mechanisms, BMs of adjacent tissues can also stably link to support organ structure and function. Using endogenous knock-in fluorescent proteins, conditional RNAi, optogenetics, and quantitative live imaging, we identified matrix proteins mediating a BM linkage (B-LINK) between the uterine utse and epidermal seam cell BMs in Caenorhabditis elegans that supports the uterus during egg-laying. We found that hemicentin is secreted by the utse and promotes fibulin-1 assembly to jointly initiate the B-LINK. During egg-laying, however, both proteins decline in levels and are not required for B-LINK maintenance. Instead, we discovered that hemicentin also promotes type IV collagen assembly, which accumulates to high levels during egg-laying and sustains the B-LINK during the mechanically active egg-laying period. This work reveals mechanisms underlying BM-BM connection maturation and identifies a crucial function for hemicentin and fibulin-1 in initiating attachment and type IV collagen in strengthening this specialized form of tissue linkage. SummaryTissue attachment through linking juxtaposed basement membranes (BMs) is crucial for the structure and function of many organs. Gianakas et al. identify a key role for hemicentin and fibulin-1 in initiating BM-BM attachment and type IV collagen in stabilizing this linkage and allowing it to resist high mechanical loads.

developmental biology↗

bioRxiv2021

Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

While health effects of conventional tobacco are well defined, data on vaping devices, including the most popular e-cigarette JUUL, are less established. Prior acute e-cigarette studies demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated effects of chronic flavored JUUL aerosol inhalation on inflammatory markers in brain, lung, heart, and colon. JUUL induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens. Inflammatory gene expression increased in colon, and cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-dependent changes in several responses were also observed. Our findings raise concerns regarding long-term risks of e-cigarette use as neuroinflammation may contribute to behavioral changes and mood disorders, while gut inflammation has been tied to poor systemic health and cardiac inflammation to development of heart disease. One Sentence SummaryChronic, daily inhalation of pod-based e-cigarette aerosols alters the inflammatory state across multiple organ systems in mice.

immunology↗

bioRxiv2021

Novel Paju Apodemus Paramyxovirus 1 and 2, Harbored by Apodemus agrarius in The Republic of Korea

Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a potential threat to public health. Currently, 78 species and 17 genera of paramyxoviruses are classified and harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Jeilongvirus has been proposed as a novel paramyxovirus genus containing J-, Beilong, and Tailam viruses, found in wild rodents. Using RT-PCR, 824 Apodemus agrarius individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was detected in 108 (13.1%) rodents captured at 14 trapping sites in Korea. We first present two genetically distinct novel paramyxoviruses (genus Jeilongvirus), Paju Apodemus paramyxoviruses 1 (PAPV-1) and 2 (PAPV-2), from A. agrarius. Six PAPV strains were completely sequenced using next-generation and Sanger sequencing. PAPV-1 genome comprised 19,716 nucleotides, with eight genes (3'-N-P/V/C-M-F-SH-TM-G-L-5'), whereas PAPV-2 genome contained 17,475 nucleotides, with seven genes (3'-N-P/V/C-M-F-TM-G-L-5'). The disparity between PAPV-1 and -2 revealed the presence of the SH gene and length of the G gene in the genome organization. The phylogenies of PAPV-1 and -2 belong to distinct genetic lineages of Jeilongvirus despite being from the same natural host. PAPV-1 clustered with Beilong and Tailam viruses, while PAPV-2 formed a genetic lineage with Mount Mabu Lophuromys virus-1. PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. Therefore, this study provides profound insights into the molecular epidemiology, virus-host interactions, and zoonotic potential of novel rodent-borne paramyxoviruses. ImportanceParamyxoviruses are a critical public health and socio-economic burden to humans. Rodents play a crucial role in transmitting pathogens to humans. In the last decade, novel paramyxoviruses have been discovered in different rodents. Here, we found that Apodemus agrarius harbored two distinct genotypes of the novel paramyxoviruses, Paju Apodemus paramyxovirues 1 (PAPV-1) and 2 (PAPV-2), possessing unique genome structures that are responsible for encoding TM and G proteins of different sizes. In addition, PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III IFNs, ISGs, and proinflammatory cytokines. Thus, this study provides significant insights into molecular prevalence, virus-host interactions of paramyxoviruses. These observations raise the awareness of physicians and scientists about the emergence of new rodent-borne paramyxoviruses.

microbiology↗

bioRxiv2020

Altering CLC stoichiometry by reducing non-polar side-chains at the dimerization interface

CLC-ec1 is a Cl-/H+ antiporter that forms stable homodimers in lipid bilayers, with a free energy of -10.9 kcal/mole relative to the 1 subunit/lipid standard state in 2:1 POPE/POPG lipid bilayers. The dimerization interface is formed by four transmembrane helices: H, I, P and Q, that are lined by non-polar side-chains that come in close contact, yet it is unclear as to whether their interactions drive dimerization. To investigate whether non-polar side-chains are required for dimer assembly, we designed a series of constructs where side-chain packing in the dimer state is significantly reduced by making 4-5 alanine substitutions along each helix (H-ala, I-ala, P-ala, Q-ala). All constructs are functional and three purify as stable dimers in detergent micelles despite the removal of significant side-chain interactions. On the other hand, H-ala shows the unique behavior of purifying as a mixture of monomers and dimers, followed by a rapid and complete conversion to monomers. In lipid bilayers, all four constructs are monomeric as examined by single-molecule photobleaching analysis. Further study of the H-helix shows that the single mutation L194A is sufficient to yield monomeric CLC-ec1 in detergent micelles and lipid bilayers. X-ray crystal structures of L194A reveal the protein re-assembles to form dimers, with a structure that is identical to wild-type. Altogether, these results demonstrate that non-polar membrane embedded side-chains play an important role in defining dimer stability, but the stoichiometry is highly contextual to the solvent environment. Furthermore, we discovered that L194 is a molecular hot-spot for defining dimerization of CLC-ec1.

biophysics↗

bioRxiv2020

Fibroblasts close a void in free space by a purse-string mechanism

How stromal cells fill voids in wounded tissue remains one of the most fundamental questions in regenerative medicine. Fibroblasts are known to fill voids by depositing extracellular matrix (ECM) proteins while migrating towards the wound site; however, their ability to adopt an epithelial-like purse-string behaviour remains unexplored. Here, we fabricated an artificial wound with a deep void space to investigate fibroblasts behaviour during gap closure. We found that fibroblasts can form a free-standing bridge on deep microvoids and consequently close the void through the purse-string contraction, which was previously believed to be exclusively an epithelial wound closure mechanism. The results also revealed that the fibroblast gap closure in our fabricated 3D artificial wound depends on myosin II-mediated contractility and intercellular adherent junctions. Our study reveals that stromal cells can gain the structural features of epithelial cells, namely, intercellular contractile rings, to fulfil their functions under the specific microenvironmental conditions of tissue repair. Furthermore, fibroblasts can close artificial wounds with gap widths up to 300 m, approximately twice as large as the critical epithelial gap closure size on non-adherent substrates. Fibroblasts exhibited a zip-up gap closure mechanism with a geometrical size effect. These findings reveal a new mechanism for gap closure by stromal cells during wound healing and pave a way to groundbreaking therapeutic strategies for tissue repair.

biophysics↗

bioRxiv2020

T cell subset-selective IL2RA enhancers shape autoimmune diabetes risk

The majority of genetic variants associated with complex human autoimmune diseases reside in enhancers1-3, non-coding regulatory elements that control gene expression. In contrast with variants that directly alter protein-coding sequences, enhancer variants are predicted to tune gene expression modestly and function in specific cellular contexts4, suggesting that small alterations in the functions of key immune cell populations are sufficient to shape disease risk. Here we tested this concept by experimentally perturbing distinct enhancers governing the high affinity IL-2 receptor alpha chain (IL2RA; also known as CD25). IL2RA is an immune regulator that promotes the pro- and anti-inflammatory functions of conventional T cells (Tconvs) and regulatory T cells (Tregs), respectively, and non-coding genetic variants in IL2RA have been linked to multiple autoimmune disorders4. We previously tiled across the IL2RA locus using CRISPR-activation and identified a stimulation-responsive element (CaRE4) with an enhancer that modestly affects the kinetics of IL2RA expression in Tconvs5. This enhancer is conserved across species and harbors a common human SNP associated with protection from Type 1 Diabetes (T1D)5,6. We now identified an additional conserved enhancer, termed CaRE3 enhancer, which modestly affected steady state IL2RA expression in regulatory T cells (Tregs). Despite their seemingly subtle impact on gene expression, the CaRE3 and CaRE4 enhancers had pronounced yet divergent effects on the incidence of diabetes in autoimmune prone animals. Deletion of the conserved CaRE4 enhancer completely protected against autoimmune diabetes even in animals treated with an immunostimulating anti-PD1 checkpoint inhibitor, whereas deletion of the CaRE3 enhancer accelerated spontaneous disease progression. Quantitative multiplexed imaging of the pancreatic lymph nodes (panLNs) revealed that each enhancer deletion preferentially affected the protein expression levels of IL2RA in activated Tconvs or Tregs, reciprocally tuning local competition for IL-2 input signals. In animals lacking the CaRE4 enhancer, skewed IL-2 signaling favored Tregs, increasing their local density around activated Tconvs to strongly suppress emergence of autoimmune effectors. By contrast, in animals lacking the CaRE3 enhancer, IL-2 signals were skewed towards activated Tconvs, promoting their escape from Treg control. Collectively, this work illustrates how subtle changes in gene regulation due to non-coding variation can significantly alter disease progression and how distinct enhancers controlling the same gene can have opposing effects on disease outcomes through cell type-selective activity.

immunology↗

bioRxiv2020

Astroglial Calcium Signaling Encodes Sleep Need in Drosophila

Sleep is under homeostatic control, whereby increasing wakefulness generates sleep need and triggers sleep drive. However, the molecular and cellular pathways by which sleep need is encoded are poorly understood. In addition, the mechanisms underlying both how and when sleep need is transformed to sleep drive are unknown. Here, using ex vivo and in vivo imaging, we show in Drosophila that astroglial Ca2+ signaling increases with sleep need. We demonstrate that this signaling is dependent on a specific L-type Ca2+ channel and is required for homeostatic sleep rebound. Thermogenetically increasing Ca2+ in astrocytes induces persistent sleep behavior, and we exploit this phenotype to conduct a genetic screen for genes required for the homeostatic regulation of sleep. From this large-scale screen, we identify TyrRII, a monoaminergic receptor required in astrocytes for sleep homeostasis. TyrRII levels rise following sleep deprivation in a Ca2+-dependent manner, promoting further increases in astrocytic Ca2+ and resulting in a positive-feedback loop. These data suggest that TyrRII acts as a gate to enable the transformation of sleep need to sleep drive at the appropriate time. Moreover, our findings suggest that astrocytes then transmit this sleep need to the R5 sleep drive circuit, by upregulation and release of the interleukin-1 analog Spatzle. These findings define astroglial Ca2+ signaling mechanisms encoding sleep need and reveal dynamic properties of the sleep homeostatic control system.

neuroscience↗

bioRxiv2020

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↗