Search

The phosphorylated 43-kDa transactive response DNA-binding protein (TDP-43) was identified as a major disease protein in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We present a case with progressive muscle weakness who was diagnosed with sporadic ALS. On postmortem examination, TDP-43 immunoreactive neuronal cytoplasmic inclusions were noted in motor cortex, hippocampus and anterior horns of spinal cord, which was compatible with ALS-TDP, stage 4. This is the first documented autopsy-confirmed ALS case with ALS-TDP pathology in Korea.

Background The prevalence of anxiety in patients undergoing total knee arthroplasty (TKA) and its association with postoperative functions are well known; however, the levels of anxiety or anxiety-related characteristics are unknown. This study aimed to investigate the prevalence of clinically significant state anxiety in geriatric patients undergoing TKA for osteoarthritis (OA) of the knee and to evaluate the anxiety-related characteristics experienced by these patients pre- and post-operatively. Methods This retrospective observational study recruited patients who had undergone TKA for knee OA using general anesthesia between February 2020 and August 2021. The study participants were geriatric patients older than 65 years who had moderate or severe OA. We evaluated patient characteristics including age, sex, body mass index, smoking status, hypertension, diabetes, and cancer. We assessed their levels of anxiety status using the STAI-X which comprises 20-item scales. Clinically meaningful state anxiety was defined as a total score of 52 or higher. An independent Student’s t-test was used to determine differences of STAI score between subgroups in terms of patient characteristics. And patients were asked to complete questionnaires, which assessed four areas: (1) the main cause of anxiety; (2) the most helpful factor in overcoming anxiety before surgery; (3) the most helpful factor in reducing anxiety after surgery; and (4) the most anxious moment during the entire process. Results The mean STAI score of patients who underwent TKA was 43.0 points and 16.4% of patients experienced clinically significant state anxiety. The current smoking status affect STAI score and the proportion of patients with clinically meaningful state anxiety. The most common cause of preoperative anxiety was the surgery itself. Overall, 38% of patients reported that they experienced the greatest level of anxiety when the surgeon had recommended TKA in the outpatient clinic. The trust in the medical staff before surgery and the surgeon’s explanations after surgery helped the most in reducing anxiety. Conclusions One in six patients before TKA experience clinically meaningful state anxiety, and about 40% of patients experience anxiety from the time they are recommended for surgery. Patients tended to overcome anxiety before TKA through trust in the medical staff, and the surgeon’s explanations after surgery was found to be helpful in reducing anxiety.

Bipolar electrodialysis was used in a process of desalting a lithium sulfate solution, converting it to lithium hydroxide and sulfuric acid, and concentrating and recovering them. The effects of the experimental variables such as applied voltage, the concentration of electrode solution, the concentration of raw material solution, volume ratio, and impurity were confirmed. The optimum conditions were investigated by comparing the conversion(%) of lithium hydroxide and sulfuric acid, the process time, and energy consumption. As the applied voltage was increased, the energy consumption tended to increase, but the processing time decreased significantly. As the concentration of lithium sulfate in the raw material solution increased, the conversion(%) of lithium hydroxide decreased. As the concentration of lithium sulfate increased, the energy consumption did not increase linearly, and energy consumption increased significantly. When a raw material solution of 0.5 M Li2SO4 or more is used in the bipolar electrodialysis process, an applied voltage of 25 V is preferable. As the applied voltage increased at a constant process time, the conversion(%) of LiOH and H2SO4 increased. Regarding the effect of the electrode solution concentration, when a 5.0 wt% electrode solution was used rather than a 3.0 wt% electrode solution, energy consumption decreased by more than 10%. When the volume of the raw material solution was increased, the processing time required for desalting increased. By using a low concentration raw material solution, it was confirmed that it was simultaneously possible to recover and concentrate lithium hydroxide and sulfuric acid through volume ratio control. When the raw material solution contained Na as an impurity, it was converted to NaOH with a surface LiOH, and it was not possible to separate the lithium and sodium.

Precision medicine refers to the tailoring of individual therapeutics based on each patient’s genetic, phenotypic, and clinical characteristics, therefore seeking the most effective treatment for the patient. With recent advances in genome sequencing technology, it was anticipated that identifying specific genetic alterations would contribute greatly to the realization of precision medicine. However, most cancer patients do not benefit from genomic precision medicine, as shown in recent Next Generation Sequencing (NGS)-driven clinical trials. Functional precision medicine directly uses patient tumor cells to test their ex vivo responses to diverse drugs to predict the most effective drugs. Functional precision medicine is emerging because it provides immediate translatable information to select drugs among clinically available therapeutics. AVATASCAN®, developed by Samsung Medical Center and AimedBio Inc., is a robust and accurate high throughput functional precision medicine platform with more than 1,500 historical sample data. AVATASCAN® has tested more than 1,500 cancer patient samples across 14 different tumor types, including glioblastoma, lung, colorectal, stomach and breast cancers. We achieved a tissue culture success rate and a drug screening success rate of more than 90% in most tumor types. A retrospective analysis of the clinical outcomes of patients given matched drugs demonstrated actual complete/partial response in 85% of AVATASCAN® screening responders. Recognizing its potential for clinical application, AVATASCAN® was selected as one of the datasets referenced by the pediatric tumor board at Seoul National University Hospital for clinical decision-making. Furthermore, AVATASCAN® is now available in Singapore and Thailand as an early-access, premium precision medicine service. Overall, we present compelling evidence that AVATASCAN® is a valuable platform for personalized cancer therapy. Therefore, we are moving forward to adopt and expand this platform in clinical applications. Citation Format: Nam-Gu Her, Gi Ju Lee, Seung Yoon Hyun, San Ha Park, Jae Woo Ahn, Ji Soo Kang, Hong Boon Toh, Do-Hyun Nam. AVATASCAN®, a pioneer of functional precision medicine in guiding clinical decision-making [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3410.

Polymeric porous membranes are important in the protective textile industry because of their high breathability balanced with water resistivity. Developing the membranes which display balanced and optimized properties has proven to be a great challenge. Final membrane performance is dependent on fundamental parameters including membrane thickness, aging temperature, and adhesive aging temperature and time. The aim of this study is to investigate the influence of these parameters on porous membrane morphology and performance. Using a scanning electron microscope, we analyzed membrane thickness impacts on morphology and pore size. We also investigated physical performance such as water pressure, water vapor permeability, and resistance to evaporating heat transfer (RET). We used the Kawabata evaluation system to evaluate the hand values based on quality according to customer choice. However, good mechanical, physical, and aesthetic performance of laminated textile suggest it as a promising substitute for numerous potential applications, especially as outdoor functional protective clothing.

Cupriavidus necator H16 is a gram-negative chemolithoautotrophic bacterium that has been extensively studied for biosynthesis and biodegradation of polyhydroxyalkanoate (PHA) plastics. To improve our understanding of fatty acid metabolism for PHA production, we determined the crystal structure of multi-functional enoyl-CoA hydratase from Cupriavidus necator H16 (CnFadB). The predicted model of CnFadB created by AlphaFold was used to solve the phase problem during determination of the crystal structure of the protein. The CnFadB structure consists of two distinctive domains, an N-terminal enol-CoA hydratase (ECH) domain and a C-terminal 3-hydroxyacyl-CoA dehydrogenase (HAD) domain, and the substrate- and cofactor-binding modes of these two functional domains were identified. Unlike other known FadB enzymes that exist as dimers complexed with FadA, CnFadB functions as a monomer without forming a complex with CnFadA. Small angle X-ray scattering (SAXS) measurement further proved that CnFadB exists as a monomer in solution. The non-sequential action of FadA and FadB in C. necator appears to affect β-oxidation and PHA synthesis/degradation.

Background: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by various combinations of parkinsonism, cerebellar ataxia, autonomic dysfunction and pyramidal signs. Two clinical subtypes are recognized: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The aim of this study was to compare pathological features between MSA-C and MSA-P.Methods: Two autopsy confirmed cases with MSA were included from the Pusan National University Hospital Brain Bank. Case 1 had been clinically diagnosed as MSA-C and case 2 as MSA-P. The severity of neuronal loss and gliosis as well as the glial and neuronal cytoplasmic inclusions were semiquantitatively assessed in both striatonigral and olivopontocerebellar regions. Based on the grading system, pathological phenotypes of MSA were classified as striatonigral degeneration (SND) predominant (SND type), olivopontocerebellar degeneration (OPC) predominant (OPC type), or equivalent SND and OPC pathology (SND=OPC type).Results: Both cases showed widespread and abundant α-synuclein positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures, leading to the primary pathological diagnosis of MSA. Primary age-related tauopathy was incidentally found but Lewy bodies were not in both cases. The pathological phenotypes of MSA were MSA-OPC type in case 1 and MSA-SND=OPC type in case 2.Conclusions: Our data suggest that clinical phenotypes of MSA reflect the pathological characteristics.

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aβ1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aβ biomarkers. We conducted a comparison of CSF Aβ1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Our case with antemortem CSF Aβ1-42 (+)/amyloid PET (-) who was pathologically confirmed with Aβ pathology in the cerebral cortex may indicate CSF Aβ1-42 is more sensitive for assessing in vivo Aβ than amyloid PET.

The demand for functional membranes with balanced waterproofness and with good water vapor transmission in wearable applications is increasing by the day. However, their low wear resistance, low moisture tolerance, complicated fabrication procedures, and high health risk limit their outdoor use. In this study, we fabricated a waterproof and breathable polyurethane porous membrane for a membrane outside/fabric inside wearable fabric through an effective and facile dry process called evaporation induced phase separation. The matrix of the polyurethane membrane was mainly modified by water droplets and diisocyanate crosslinking agents, which allow the resultant membrane to be porous and durable. The water vapor transmission of the polyurethane water in oil emulsion was efficiently enhanced by introducing a porous network incorporated with tiny water droplets in the polyurethane emulsion. The optimization method for the emulsion allowed the waterproof, breathable porous membrane to sustain a tensile load of 35 MPa with an abrasion resistance of 15,000 cycles. Notably, the optimized porous membrane tended to exhibit a high hydrostatic pressure of 3500 mmH2O, good breathability of 3000 g/m2 day, and excellent porosity of 65%, which suggests that evaporation induced phase separation is a facile method for designing the membrane. These promising results show that the waterproof and breathable porous membrane can compete with commercially available protective membranes and coatings because of its porosity, facile synthesis, low cost, non-swelling behavior, high stability, and commercial scale production.

In order to manufacture lithium carbonate to be used as a raw material for a secondary lithium battery, lithium sulfate solution is used as a precursor, and the concentration of lithium is required to be 10 g/L or more. Electrodialysis (ED) was used as a method of concentrating lithium in a low-concentration lithium sulfate solution, and multistage concentration (MSC) electrodialysis was used to increase the concentration ratio (%). When MSC was performed using a raw material solution containing a large amount of sodium sulfate, the process lead time was increased by 60 min. And the concentration ratio (%) of lithium decreased as the number of concentration stages increased. In order to remove sodium sulfate, methanol was added to the raw material solution to precipitate sodium sulfate, and when it was added in a volume ratio of 0.4, lithium was not lost. Using a solution in which sodium sulfate was partially removed, fourth-stage concentration ED was performed to obtain a lithium sulfate solution with a lithium concentration of 10 g/L.

In metabolic engineering and synthetic biology fields, there have been efforts to produce variable bioalcohol fuels, such as isobutanol and 2-phenylethanol, in order to meet industrial demands. YjgB is an aldehyde dehydrogenase from Escherichia coli that shows nicotinamide adenine dinucleotide phosphate (NADP)-dependent broad selectivity for aldehyde derivatives with an aromatic ring or small aliphatic chain. This could contribute to the design of industrial synthetic pathways. We determined the crystal structures of YjgB for both its apo-form and NADP-complexed form at resolutions of 1.55 and 2.00 &Aring, respectively, in order to understand the mechanism of broad substrate selectivity. The hydrophobic pocket of the active site and the nicotinamide ring of NADP(H) are both involved in conferring its broad specificity toward aldehyde substrates. In addition, based on docking-simulation data, we inferred that &pi, &ndash, &pi, stacking between substrates and aromatic side chains might play a crucial role in recognizing substrates. Our structural analysis of YjgB might provide insights into establishing frameworks to understand its broad substrate specificity and develop engineered enzymes for industrial biofuel synthesis.

Objective The Korean patient with Perry syndrome (PS) was the first to come to autopsy. We report a pathologically confirmed patient with PS, and compare to pathological findings of previous literatures. Materials and methods The patient had a family history of parkinsonism and had a mutation in the DCTN1 gene. After death an autopsy was performed. We analyzed macroscopic and microscopic findings of the patient. Results There was no prominent cortical atrophy, but microscopy showed severe neuronal loss, microvacuolation, and gliosis in the substantia nigra (SN). We identified transactive response DNA-binding protein 43 (TDP-43)-positive neuronal cytoplasmic inclusions, dystrophic neurites, and glial cytoplasmic inclusions in surviving SN neurons. In addition, some neurofibrillary tangles (NFTs) were also seen in the parahippocampal gyrus. Conclusion The neuropathology, including TDP-43 proteinopathy, is comparable to that reported previously in Caucasian populations. In addition to the stereotypic features of PS, our patient had NFTs in the parahippocampal gyrus, the pathology similar to that is described as primary age-related tauopathy (PART). These observations suggest that comorbid age-related neuropathologic change may also contribute to cognitive impairment in PS.

Autophagic receptor p62 is a critical mediator of cell detoxification, stress response, and metabolic programs and is commonly deregulated in human diseases. The diverse functions of p62 arise from its ability to interact with a large set of ligands, such as arginylated (Nt-R) substrates. Here, we describe the structural mechanism for selective recognition of Nt-R by the ZZ domain of p62 (p62ZZ). We show that binding of p62ZZ to Nt-R substrates stimulates p62 aggregation and macroautophagy and is required for autophagic targeting of p62. p62 is essential for mTORC1 activation in response to arginine, but it is not a direct sensor of free arginine in the mTORC1 pathway. We identified a regulatory linker (RL) region in p62 that binds p62ZZ in vitro and may modulate p62 function. Our findings shed new light on the mechanistic and functional significance of the major cytosolic adaptor protein p62 in two fundamental signaling pathways.

Human p300 is a transcriptional co-activator and a major acetyltransferase that acetylates histones and other proteins facilitating gene transcription. The activity of p300 relies on the fine-tuned interactome that involves a dozen p300 domains and hundreds of binding partners and links p300 to a wide range of vital signaling events. Here, we report a novel function of the ZZ-type zinc finger (ZZ) of p300 as a reader of histone H3. We show that the ZZ domain and acetyllysine-recognizing bromodomain of p300 play critical roles in modulating p300 enzymatic activity and its association with chromatin. The acetyllysine binding function of bromodomain is essential for acetylation of histones H3 and H4, whereas interaction of the ZZ domain with H3 promotes selective acetylation of the histone H3K27 and H3K18 sites.

Corticobasal syndrome (CBS) is a typical phenotype of corticobasal degeneration (CBD). However, autopsy series have shown that many CBS cases emerge from various types of non-CBD pathology. We report a 73-year-old Korean man who was clinically diagnosed with CBS whose underlying pathology was Alzheimer's disease (AD) at autopsy (CBS-AD). This case suggests that early developing memory impairment and myoclonus, severe temporoparietal atrophy, and visual hallucinations may support a more specific prediction of CBS-AD.

It has been proposed that susceptibility-weighted imaging is a sensitive magnetic resonance imaging (MRI) technique for identifying white matter (WM) pathologic changes involving demyelination and iron accumulation. We identified the tree silhouette-like configuration with a paramagnetic phase shift in the frontal subcortical WM lesions of 4 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia who underwent 3T MRI. According to our postmortem 7T MRI and histologic correlation study to investigate the origin of the susceptibility-related phase contrast, changes in the subcortical WM architecture and central WM loss with the relative preservation of iron-rich U-fibers may contribute to the paramagnetic susceptibility.

Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as a selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings reveal a previously uncharacterized acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation., Histone methyltransferase MLL4 is a transcriptional regulator. Here the authors identify the PHD6 finger of MLL4 as a selective reader of the epigenetic modification H4K16ac and show that a subset of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions, which depends on MOF activity.

This paper presents the technology and implementation results of manipulating the MAC and IP Address of the transmitting side in MCU(Microcontroller Unit), when data communication with remote APs is performed on CC3220 Wi-Fi module associated with STM32 MCU. Because the existing packet sending and receiving process also changes in the CRC as MAC and IP change, CRC checksum errors occur when MAC and IP are manipulated. The method presented in this paper reduces the resources required for computations to match the CRC checksum in the transmission and reception environment between MCU and external AP, and it also allows the sending-receiving and exchanging data with minimal manipulation.

Summary Microrchidia 3 (MORC3), a human ATPase linked to several autoimmune disorders, has been characterized both as a negative and positive regulator of influenza A virus. Here, we report that the CW domain of MORC3 (MORC3-CW) is targeted by the C-terminal tail of the influenza H3N2 protein NS1. The crystal structure of the MORC3-CW:NS1 complex shows that NS1 occupies the same binding site in CW that is normally occupied by histone H3, a physiological ligand of MORC3-CW. Comparable binding affinities of MORC3-CW to H3 and NS1 peptides and to the adjacent catalytic ATPase domain suggest that the viral protein can compete with the host histone for the association with CW, releasing MORC3 autoinhibition and activating the catalytic function of MORC3. Our structural, biochemical, and cellular analyses suggest that MORC3 might affect the infectivity of influenza virus and therefore has a role in cell immune response.