Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.

Type 2 diabetes (T2D) and obesity are prevalent metabolic disorders affecting millions of individuals worldwide. A new effective therapeutic drug called tirzepatide for the treatment of obesity and T2D is a dual agonist of the GIP receptor and GLP-1 receptor. Tirzepatide is clinically more effective than GLP-1 receptor agonists but the reasons why are not well understood. Tirzepatide reportedly stimulates the GIP receptor more potently than the GLP-1 receptor. However, tirzepatide signaling has not been thoroughly investigated at the E354 (wildtype) or Q354 (E354Q) GIP receptor variants. The E354Q variant is associated increased risk of T2D and lower body mass index. To better understand GIP receptor signaling we characterized the activity of endogenous agonists and tirzepatide at both GIP receptor variants. Using Cos7 cells we examined wildtype and E354Q GIP receptor signaling, analyzing cAMP and IP1 accumulation as well as AKT, ERK1/2 and CREB phosphorylation. GIP(1-42) and GIP(1-30)NH2 displayed equipotent effects on these pathways excluding CREB phosphorylation where GIP(1-30)NH2 was more potent than GIP(1-42) at the E354Q GIP receptor. Tirzepatide favored cAMP signaling at both variants. These findings indicate that tirzepatide is a biased agonist towards Gαs signaling and suggests it equally activates the wildtype and E354Q GIP receptor variants. We also observed differences between the pharmacology of the GIP receptor variants with endogenous peptides, which may help to explain differences in phenotype. These findings contribute to a comprehensive understanding of GIP receptor signaling, and will aid development of therapies combating T2D and obesity.

Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

Flavivirga spongiicola sp. nov. and Flavivirga abyssicola sp. nov., Isolated from Marine Environments.

Two novel Gram-stain-negative, strictly-aerobic, rod-shaped (1.2 ± 3.4 µm × 0.3 ± 0.7 µm), and non-motile marine bacterial species, designated MEBiC05379T and MEBiC07777T, were isolated from a marine sponge Pseudaxinella sp. in Gangneung City and deep-sea sediments of the Ulleung basin in the East Sea of Korea, respectively. The 16S rRNA gene sequence analysis revealed high levels of similarities between these strains and members of the genus Flavivirga (97.0-98.4% sequence identities). Both novel strains revealed as mesophilic, neutrophilic in pH and slightly halophilic. Similar to those of other Flavivirga members, the primary cellular fatty acids of both strains were iso-C15:0, iso-C15:1 G, iso-C15:03-OH, and iso-C17:0 3-OH, with MEBiC05379T and MEBiC07777T containing relatively higher proportions of C12:0 and summed feature 3 (C16:1ω7c and/or C16:1ω6c). In both taxa, the major isoprenoid quinone was MK-6. The DNA G + C contents of MEBiC05379T and MEBiC07777T genomes were 32.62 and 32.46 mol%, respectively. Compared to other members of Flavivirga, both strains exhibited similar DNA G + C ratio and fatty acids pattern, yet enzyme expression and carbon sources utilization pattern were different. Genomes of the genus Flavivirga showed enzyme preferences to fucoidan and sulfated galactans. Considering the monophyly rule, AAI values delineate the genus Flavivirga from adjacent genera calculated to be 76.0-78.7%. Based on the phenotypic, genomic and biochemical data, strains for MEBiC05379T and MEBiC07777T thus represent two novel species in the genus Flavivirga, for which the names Flavivirga spongiicola sp. nov. (MEBiC05379T [= KCTC 92527 T = JCM 16662 T]), and Flavivirga abyssicola sp. nov. (MEBiC07777T [= KCTC 92563 T = JCM 36477 T]) are proposed.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

NMR Shows Why a Small Chemical Change Almost Abolishes the Antimicrobial Activity of Glycocin F.

Glycocin F (GccF), a ribosomally synthesized, post-translationally modified peptide secreted by Lactobacillus plantarum KW30, rapidly inhibits the growth of susceptible bacteria at nanomolar concentrations. Previous studies have highlighted structural features important for its activity and have shown the absolute requirement for the Ser18 O-linked GlcNAc on the eight-residue loop linking the two short helices of the (C-X6-C)2 structure. Here, we show that an ostensibly very small chemical modification to Ser18, the substitution of the Cα proton with a methyl group, reduces the antimicrobial activity of GccF 1000-fold (IC50 1.5 µM cf. 1.5 nM). A comparison of the GccFα-methylSer18 NMR structure (PDB 8DFZ) with that of the native protein (PDB 2KUY) showed a marked difference in the orientation and mobility of the loop, as well as a markedly different positioning of the GlcNAc, suggesting that loop conformation, dynamics, and glycan presentation play an important role in the interaction of GccF with as yet unknown but essential physiological target molecules.

P1 Glutamine isosteres in the design of inhibitors of 3C/3CL protease of human viruses of the Pisoniviricetes class.

Viral infections are one of the leading causes of acute morbidity in humans and much endeavour has been made by the synthetic community for the development of drugs to treat associated diseases. Peptide-based enzyme inhibitors, usually short sequences of three or four residues, are one of the classes of compounds currently under development for enhancement of their activity and pharmaceutical properties. This review reports the advances made in the design of inhibitors targeting the family of highly conserved viral proteases 3C/3CLpro, which play a key role in viral replication and present minimal homology with mammalian proteases. Particular focus is put on the reported development of P1 glutamine isosteres to generate potent inhibitors mimicking the natural substrate sequence at the site of recognition.'

Thermococcus argininiproducens sp. nov., an arginine biosynthesis archaeal species isolated from the Central Indian Ocean ridge.

A strictly anaerobic hyperthermophilic archaeon, designated strain IOH2T, was isolated from a deep-sea hydrothermal vent (Onnuri vent field) area on the Central Indian Ocean Ridge. Strain IOH2T showed high 16S rRNA gene sequence similarity to Thermococcus sibiricus MM 739T (99.42 %), Thermococcus alcaliphilus DSM 10322T (99.28 %), Thermococcus aegaeus P5T (99.21 %), Thermococcus litoralis DSM 5473T (99.13 %), 'Thermococcus bergensis' T7324T (99.13 %), Thermococcus aggregans TYT (98.92 %) and Thermococcus prieurii Bio-pl-0405IT2T (98.01 %), with all other strains showing lower than 98 % similarity. The average nucleotide identity and in silico DNA-DNA hybridization values were highest between strain IOH2T and T. sibiricus MM 739T (79.33 and 15.00 %, respectively); these values are much lower than the species delineation cut-offs. Cells of strain IOH2T were coccoid, 1.0-1.2 µm in diameter and had no flagella. Growth ranges were 60-85 °C (optimum at 80 °C), pH 4.5-8.5 (optimum at pH 6.3) and 2.0-6.0 % (optimum at 4.0 %) NaCl. Growth of strain IOH2T was enhanced by starch, glucose, maltodextrin and pyruvate as a carbon source, and elemental sulphur as an electron acceptor. Through genome analysis of strain IOH2T, arginine biosynthesis related genes were predicted, and growth of strain IOH2T without arginine was confirmed. The genome of strain IOH2T was assembled as a circular chromosome of 1 946 249 bp and predicted 2096 genes. The DNA G+C content was 39.44 mol%. Based on the results of physiological and phylogenetic analyses, Thermococcus argininiproducens sp. nov. is proposed with type strain IOH2T (=MCCC 4K00089T=KCTC 25190T).

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

Description of Fervidibacillus gen. nov. with Two Species, Fervidibacillus albus sp. nov., and Fervidibacillus halotolerans sp. nov., Isolated from Tidal Flat Sediments and Emendation of Misclassificed Taxa in the Genus Caldibacillus.

Two Gram-stain-positive, motile, endospore-forming, facultatively anaerobic strains, designated MEBiC13591T and MEBiC13594T, were isolated from tidal flat sediment of the Incheon City on the west coast of Korea. Growth of both novel strains was observed at pH 5-9 (optimum, pH 7-7.5), and in 0-8% NaCl (optimum, 2% for MEBiC13591T and 3% for MEBiC13594T). Strains MEBiC13591T and MEBiC13594T grew optimally at 50 °C, (37.5-56.1 °C) and 44 °C (20.7-50.7 °C), respectively. The main cellular fatty acids of strain MEBiC13591T were iso-C15: 0, anteiso-C15: 0, iso-C16: 0, iso-C17: 0 and anteiso-C17: 0, while those for strain MEBiC13594T were C14: 0, iso-C14: 0, iso-C15: 0, anteiso-C15: 0 and C16: 0. In both taxa, the major isoprenoid was MK-7. The genomic DNA G + C contents were 34.1 and 37.0 mol% for MEBiC13591T and MEBiC13594T, respectively. A 16S rRNA gene sequence analysis revealed that the novel strains showed high similarity with members of the genera Aeribacillus (95.0%) and Caldibacillus (93.5-94.5%); however, showed lower than 90% with Caldibacillus debilis TfT. Phylogenetic and Phylogenomic analysis revealed that two novel strains comprised distinct phyletic line with members formerly assigned to Caldibacillus. Based on genomic indices, such as AAI and ANI, members formerly affiliated with Caldibacillus and Bacillus as well as the novel strains should be classified into five independent genera. Based on the phenotypic, genomic and biochemical data, strains MEBiC13591T and MEBiC13594T represent two novel species in the novel genus, for which the names Fervidibacillus albus gen. nov., sp. nov. (MEBiC13591T [= KCCM 43317T = KCTC 43181T = JCM 33662T = MCCC 1K04565T]), and Fervidibacillus halotolerans sp. nov. (MEBiC13594T [= KCTC 43182T = JCM 34001T]) are proposed. Three additional genera Caldifermentibacillus, Palidibacillus, and Perspicuibacillus are also proposed by reclassification of the several species with valid names that formerly affiliated with the genera Caldibacillus.

Semi-Supervised Adversarial Auto-Encoder to Expedite Human Activity Recognition.

The study of human activity recognition concentrates on classifying human activities and the inference of human behavior using modern sensing technology. However, the issue of domain adaptation for inertial sensing-based human activity recognition (HAR) is still burdensome. The existing requirement of labeled training data for adapting such classifiers to every new person, device, or on-body location is a significant barrier to the widespread adoption of HAR-based applications, making this a challenge of high practical importance. We propose the semi-supervised HAR method to improve reconstruction and generation. It executes proper adaptation with unlabeled data without changes to a pre-trained HAR classifier. Our approach decouples VAE with adversarial learning to ensure robust classifier operation, without newly labeled training data, under changes to the individual activity and the on-body sensor position. Our proposed framework shows the empirical results using the publicly available benchmark dataset compared to state-of-art baselines, achieving competitive improvement for handling new and unlabeled activity. The result demonstrates SAA has achieved a 5% improvement in classification score compared to the existing HAR platform.

Randomized phase II study of capecitabine plus cisplatin with or without sorafenib in patients with metastatic gastric cancer (STARGATE).

BACKGROUND: In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first-line chemotherapy in advanced gastric cancer. PATIENTS AND METHODS: Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm. RESULTS: Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow-up of 12.6 months (range, 0.1-29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67-1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand-foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2-1.7). CONCLUSION: The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first-line treatment of metastatic gastric cancer.

Detection of Image Level Forgery with Various Constraints Using DFDC Full and Sample Datasets.

The emergence of advanced machine learning or deep learning techniques such as autoencoders and generative adversarial networks, can generate images known as deepfakes, which astonishingly resemble the realistic images. These deepfake images are hard to distinguish from the real images and are being used unethically against famous personalities such as politicians, celebrities, and social workers. Hence, we propose a method to detect these deepfake images using a light weighted convolutional neural network (CNN). Our research is conducted with Deep Fake Detection Challenge (DFDC) full and sample datasets, where we compare the performance of our proposed model with various state-of-the-art pretrained models such as VGG-19, Xception and Inception-ResNet-v2. Furthermore, we perform the experiments with various resolutions maintaining 1:1 and 9:16 aspect ratios, which have not been explored for DFDC datasets by any other groups to date. Thus, the proposed model can flexibly accommodate various resolutions and aspect ratios, without being constrained to a specific resolution or aspect ratio for any type of image classification problem. While most of the reported research is limited to sample or preview DFDC datasets only, we have also attempted the testing on full DFDC datasets and presented the results. Contemplating the fact that the detailed results and resource analysis for various scenarios are provided in this research, the proposed deepfake detection method is anticipated to pave new avenues for deepfake detection research, that engages with DFDC datasets.

Synthesis, Antibacterial Activity, and Nephrotoxicity of Polymyxin B Analogues Modified at Leu-7, d-Phe-6, and the N-Terminus Enabled by S-Lipidation.

With the post-antibiotic era rapidly approaching, many have turned their attention to developing new treatments, often by structural modification of existing antibiotics. Polymyxins, a family of lipopeptide antibiotics that are used as a last line of defense in the clinic, have recently developed resistance and exhibit significant nephrotoxicity issues. Using thiol-ene chemistry, the facile preparation of six unique S-lipidated building blocks was demonstrated and used to generate lipopeptide mimetics upon incorporation into solid-phase peptide synthesis (SPPS). We then designed and synthesized 38 polymyxin analogues, incorporating these unique building blocks at the N-terminus, or to replace hydrophobic residues at positions 6 and 7 of the native lipopeptides. Several polymyxin analogues bearing one or more S-linked lipids were found to be equipotent to polymyxin, showed minimal kidney nephrotoxicity, and demonstrated activity against several World Health Organisation (WHO) priority pathogens. The S-lipidation strategy has demonstrated potential as a novel approach to prepare innovative new lipopeptide antibiotics.

HHI-AttentionNet: An Enhanced Human-Human Interaction Recognition Method Based on a Lightweight Deep Learning Model with Attention Network from CSI.

Nowadays WiFi based human activity recognition (WiFi-HAR) has gained much attraction in an indoor environment due to its various benefits, including privacy and security, device free sensing, and cost-effectiveness. Recognition of human-human interactions (HHIs) using channel state information (CSI) signals is still challenging. Although some deep learning (DL) based architectures have been proposed in this regard, most of them suffer from limited recognition accuracy and are unable to support low computation resource devices due to having a large number of model parameters. To address these issues, we propose a dynamic method using a lightweight DL model (HHI-AttentionNet) to automatically recognize HHIs, which significantly reduces the parameters with increased recognition accuracy. In addition, we present an Antenna-Frame-Subcarrier Attention Mechanism (AFSAM) in our model that enhances the representational capability to recognize HHIs correctly. As a result, the HHI-AttentionNet model focuses on the most significant features, ignoring the irrelevant features, and reduces the impact of the complexity on the CSI signal. We evaluated the performance of the proposed HHI-AttentionNet model on a publicly available CSI-based HHI dataset collected from 40 individual pairs of subjects who performed 13 different HHIs. Its performance is also compared with other existing methods. These proved that the HHI-AttentionNet is the best model providing an average accuracy, F1 score, Cohen's Kappa, and Matthews correlation coefficient of 95.47%, 95.45%, 0.951%, and 0.950%, respectively, for recognition of 13 HHIs. It outperforms the best existing model's accuracy by more than 4%.

Alkalibacter rhizosphaerae sp. nov., a CO-utilizing bacterium isolated from tidal flat sediment, and emended description of the genus Alkalibacter.

A novel anaerobic, rod-shaped, non-motile bacterium, designated strain ES005T, was isolated from tidal flat sediments near the rhizosphere of Phragmites australis at Eulsukdo Island, Republic of Korea. A polyphasic approach revealed that cells of the strain were Gram-stain-positive, catalase- and oxidase-negative, non-spore-forming rods. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain ES005T belonged to the family Eubacteriaceae, class Clostridia and showed the highest sequence similarity to Alkalibacter mobilis (97.52 %) and followed by Alkalibacter saccharofermentans Z-79820T (96.72%). The OrthoANI value between strain ES005T and A. mobilis was 69.67 %. Strain ES005T grew optimally at 33-37 °C, at pH 6.0-7.0 and in the presence of 1-2 % (w/v) NaCl. Growth in 12.5 % CO atmosphere was observed. Acetate and formate were end products of fructose fermentation and growth on CO. The major cellular fatty acids of strain ES005T were C14 : 0 (39.1 %) and C16 : 0 (26.6 %). The major polar lipids were diphoshatidylgycerol, phosphatidylglycerol and three unidentified phospholipids. The DNA G+C content of strain ES005T was 46.9 mol%. Based on the phenotypic, phylogenetic, genomic and chemotaxonomic features of the isloate, strain ES005T represents a novel species, for which the name Alkalibacter rhizosphaerae sp. nov. is proposed. The type strain is ES005T (=KCTC 25246T=JCM 34530T).

Semi-Supervised Adversarial Learning Using LSTM for Human Activity Recognition.

The training of Human Activity Recognition (HAR) models requires a substantial amount of labeled data. Unfortunately, despite being trained on enormous datasets, most current models have poor performance rates when evaluated against anonymous data from new users. Furthermore, due to the limits and problems of working with human users, capturing adequate data for each new user is not feasible. This paper presents semi-supervised adversarial learning using the LSTM (Long-short term memory) approach for human activity recognition. This proposed method trains annotated and unannotated data (anonymous data) by adapting the semi-supervised learning paradigms on which adversarial learning capitalizes to improve the learning capabilities in dealing with errors that appear in the process. Moreover, it adapts to the change in human activity routine and new activities, i.e., it does not require prior understanding and historical information. Simultaneously, this method is designed as a temporal interactive model instantiation and shows the capacity to estimate heteroscedastic uncertainty owing to inherent data ambiguity. Our methodology also benefits from multiple parallel input sequential data predicting an output exploiting the synchronized LSTM. The proposed method proved to be the best state-of-the-art method with more than 98% accuracy in implementation utilizing the publicly available datasets collected from the smart home environment facilitated with heterogeneous sensors. This technique is a novel approach for high-level human activity recognition and is likely to be a broad application prospect for HAR.

Proteiniclasticum aestuarii sp. nov., isolated from tidal flat sediment, and emended descriptions of the genus Proteiniclasticum and Proteiniclasticum ruminis.

A novel bacterium, designated SCR006T, was isolated from tidal flat sediment from Suncheon Bay, Republic of Korea. Cells of strain SCR006T were strictly anaerobic, motile cocci, Gram-reaction-negative, and catalase- and oxidase-negative. Growth was observed at 4-41 °C (optimum, 34-37 °C), at pH 6.5-10.0 (optimum, pH 7.0-7.5) and in presence of 0-8 % NaCl (optimum, 0-2 %). Fermentation products of peptone-yeast-glucose medium were acetate and ethanol. Results of phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SCR006T had high sequence similarity to Proteiniclasticum ruminis D3RC-2T (97.9 %), followed by Youngiibacter multivorans DSM 6139T (95.9 %) and Youngiibacter fragilis 232.1T (95.0 %). The average nucleotide identity value between strain SCR006T and P. ruminis DSM 24773T was 72.7 %, which strongly supported that strain SCR006T reresents a novel species within the genus Proteiniclasticum. The major cellular fatty acids are iso-C15 : 0 (27.2 %) and anteiso-C15 : 0 (16.9 %). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. The genomic size was 3.2 Mb with genomic DNA G+C content of 45.6 mol%. The results of 16S rRNA-based and genome-based phylogenetic tree analyses indicated that SCR006T should be assigned to the genus Proteiniclasticum. Strain SCR006T could be distinguished from P. ruminis D3RC-2T by its growth conditions, cell morphology and genomic characteristics. Based on the phenotypic, phylogenetic, genomic and chemotaxonomic features, strain SCR006T represents a novel species, for which the name Proteiniclasticum aestuarii sp. nov. is proposed, with the type strain SCR006T (=KCTC 25245T= JCM 34531T).

Lipidated Calcitonin Gene-Related Peptide (CGRP) Peptide Antagonists Retain CGRP Receptor Activity and Attenuate CGRP Action In Vivo.

Signaling through calcitonin gene-related peptide (CGRP) receptors is associated with pain, migraine, and energy expenditure. Small molecule and monoclonal antibody CGRP receptor antagonists that block endogenous CGRP action are in clinical use as anti-migraine therapies. By comparison, the potential utility of peptide antagonists has received less attention due to suboptimal pharmacokinetic properties. Lipidation is an established strategy to increase peptide half-life in vivo. This study aimed to explore the feasibility of developing lipidated CGRP peptide antagonists that retain receptor antagonist activity in vitro and attenuate endogenous CGRP action in vivo. CGRP peptide analogues based on the archetypal CGRP receptor antagonist, CGRP8-37, were palmitoylated at the N-terminus, position 24, and near the C-terminus at position 35. The antagonist activities of the lipidated peptide analogues were tested in vitro using transfected Cos-7 cells expressing either the human or mouse CGRP receptor, amylin subtype 1 (AMY1) receptor, adrenomedullin (AM) receptors, or calcitonin receptor. Antagonist activities were also evaluated in SK-N-MC cells that endogenously express the human CGRP receptor. Lipidated peptides were then tested for their ability to antagonize endogenous CGRP action in vivo using a capsaicin-induced dermal vasodilation (CIDV) model in C57/BL6J mice. All lipidated peptides except for the C-terminally modified analogue retained potent antagonist activity compared to CGRP8-37 towards the CGRP receptor. The lipidated peptides also retained, and sometimes gained, antagonist activities at AMY1, AM1 and AM2 receptors. Several lipidated peptides produced robust inhibition of CIDV in mice. This study demonstrates that selected lipidated peptide antagonists based on αCGRP8-37 retain potent antagonist activity at the CGRP receptor and are capable of inhibition of endogenous CGRP action in vivo. These findings suggest that lipidation can be applied to peptide antagonists, such as αCGRP8-37 and are a potential strategy for antagonizing CGRP action.

Epileptic-Net: An Improved Epileptic Seizure Detection System Using Dense Convolutional Block with Attention Network from EEG.

Epilepsy is a complex neurological condition that affects a large number of people worldwide. Electroencephalography (EEG) measures the electrical activity of the brain and is widely used in epilepsy diagnosis, but it usually requires manual inspection, which can be hours long, by a neurologist. Several automatic systems have been proposed to detect epilepsy but still have some unsolved issues. In this study, we proposed a dynamic method using a deep learning model (Epileptic-Net) to detect an epileptic seizure. The proposed method is largely heterogeneous and comprised of the dense convolutional blocks (DCB), feature attention modules (FAM), residual blocks (RB), and hypercolumn technique (HT). Firstly, DCB is used to get the discriminative features from the EEG samples. Then, FAM extracts the essential features from the samples. After that, RB learns more vital parts as it entirely uses information in the convolutional layer. Finally, HT retains the efficient local features extracted from the layers situated at the different levels of the model. Its performance has been evaluated on the University of Bonn EEG dataset, divided into five distinct classes. The proposed Epileptic-Net achieves the average accuracy of 99.95% in the two-class classification, 99.98% in the three-class classification, 99.96% in the four-class classification, and 99.96% in classifying the complicated five-class problem. Thus the proposed approach shows more competitive results than the existing model to detect epileptic seizures. We also hope that this method can support experts in achieving objective and reliable results, lowering the misdiagnosis rate, and assisting in decision-making.

Constantimarinum furrinae gen. nov., sp. nov., a marine bacterium isolated from saline volcanic rock aquifer (lava seawater) at Jeju Island, Republic of Korea.

A Gram-stain-negative, aerobic, rod-shaped (0.3-0.5 × 1.0-1.9 µm), non-motile marine bacterium designated as ALE3EIT was isolated from a saline volcanic rock aquifer (lava sea-water) on Jeju Island, Republic of Korea. The 16S rRNA gene sequence analysis revealed that strain ALE3EIT showed high similarity to 'Altibacter lentus' JLT2010T (97.2%), followed by Marixanthomonas ophiurae KMM 3046T (94.5%). Growth was observed at 10-41°C (optimum, 30°C), at pH 6.0-8.5 (optimum, pH 7.5) and at 0.5-8% (optimum, 4.0%) NaCl. The predominant cellular fatty acids were iso-C15:0 (23.5%), iso-C16:0 (10.2%), iso-C16:0 3OH (10.5%), and iso-C17:0 3OH (16.8%). The DNA G + C contents was 40.4 mol%. The major respiratory quinone was MK-6. The major polar lipids were determined to be phosphatidylethanolamine, two unidentified glycolipids, and two unidentified aminolipids. Several phenotypic characteristics such as production of acetoin, activities of arginine dihydrolase and acid phosphatase, and utilization pattern of carbon sources differentiate strain ALE3EIT from 'A. lentus' JLT2010T. Activities of the lipase, trypsin, α-chymotrypsin and gelatinase and utilization pattern of carbon sources differentiate strain ALE3EIT from M. ophiurae KMM 3046T. The genome of strain ALE3EIT is 3.0 Mbp long and its ANI and AAI values against 'A. lentus' JLT2010T were 76.58 and 72.76, respectively, however, AAI values against members in other genera were lower than 72%. The phylogenomic tree inferred by PhyloPhlAn clearly differentiated the strain ALE3EIT together with strain JLT2010T from other genera in the Falvobacteriaceae. This polyphasic taxonomic data indicates that strain ALE3EIT should be identified as a novel species in the genus 'Altibacter', however, the name has not been validated. Therefore, the strain is classified as a novel genus and is proposed as Constantimarinum furrinae gen. nov., sp. nov. The type strain is ALE3EIT (= KCCM 43303T = JCM 33022T).