bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenergic modulation of melanocortin pathway by hunger signals
Authors: Sayar-Atasoy Nilufer , Laule Connor , Aklan Iltan , Kim Hyojin , Yavuz Yavuz , Ates Tayfun , Coban Ilknur , Koksalar-Alkan Fulya , Rysted Jacob , Davis Debbie , Singh Uday , Alp Muhammed Ikbal , Yilmaz Bayram , Cui Huxing , Atasoy Deniz
Published: October 2023

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway.
Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer
Authors: Dong Shiyan , Liu Xuan , Bi Ye , Wang Yifan , Antony Abin , Lee DaeYong , Huntoon Kristin , Jeong Seongdong , Ma Yifan , Li Xuefeng , Deng Weiye , Schrank Benjamin R. , Grippin Adam J. , Ha JongHoon , Kang Minjeong , Chang Mengyu , Zhao Yarong , Sun Rongze , Sun Xiangshi , Yang Jie , Chen Jiayi , Tang Sarah K. , Lee L. James , Lee Andrew S. , Teng Lirong , Wang Shengnian , Teng Lesheng , Kim Betty Y. S. , Yang Zhaogang , Jiang Wen
Published: October 2023

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.
Biosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine
Authors: Chen Hanna , Zhong Lin , Zhou Haibo , Bai Xianping , Sun Tao , Wang Xingyan , Zhao Yiming , Ji Xiaoqi , Tu Qiang , Zhang Youming , Bian Xiaoying
Published: October 2023

The broad bioactivities of nonribosomal peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029 leads to the identification of a class of dodecapeptides, glidonins, that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus. The N-terminal diversity originates from the wide substrate selectivity of the initiation module. The C-terminal putrescine moiety is introduced by the unusual termination module 13, the condensation domain directly catalyzes the assembly of putrescine into the peptidyl backbone, and other domains are essential for stabilizing the protein structure. Swapping of this module to another two nonribosomal peptide synthetases leads to the addition of a putrescine to the C-terminus of related nonribosomal peptides, improving their hydrophilicity and bioactivity. This study elucidates the mechanism for putrescine addition and provides further insights to generate diverse and improved nonribosomal peptides by introducing a C-terminal putrescine.
Automatic correction of performance drift under acquisition shift in medical image classification
Authors: Roschewitz Mélanie , Khara Galvin , Yearsley Joe , Sharma Nisha , James Jonathan J. , Ambrózay Éva , Heroux Adam , Kecskemethy Peter , Rijken Tobias , Glocker Ben
Published: October 2023

Image-based prediction models for disease detection are sensitive to changes in data acquisition such as the replacement of scanner hardware or updates to the image processing software. The resulting differences in image characteristics may lead to drifts in clinically relevant performance metrics which could cause harm in clinical decision making, even for models that generalise in terms of area under the receiver-operating characteristic curve. We propose Unsupervised Prediction Alignment, a generic automatic recalibration method that requires no ground truth annotations and only limited amounts of unlabelled example images from the shifted data distribution. We illustrate the effectiveness of the proposed method to detect and correct performance drift in mammography-based breast cancer screening and on publicly available histopathology data. We show that the proposed method can preserve the expected performance in terms of sensitivity/specificity under various realistic scenarios of image acquisition shift, thus offering an important safeguard for clinical deployment.
Deterministic full-scenario analysis for maximum credible earthquake hazards
Authors: Wang Xiang-Chao , Wang Jin-Ting , Zhang Chu-Han
Published: October 2023

Great earthquakes are one of the major threats to modern society due to their great destructive power and unpredictability. The maximum credible earthquake (MCE) for a specific fault, i.e., the largest magnitude earthquake that may occur there, has numerous potential scenarios with different source processes, making the future seismic hazard highly uncertain. We propose a full-scenario analysis method to evaluate the MCE hazards with deterministic broadband simulations of numerous scenarios. The full-scenario analysis is achieved by considering all uncertainties of potential future earthquakes with sufficient scenarios. Here we show an application of this method in the seismic hazard analysis for the Xiluodu dam in China by simulating 22,000,000 MCE scenarios in 0–10 Hz. The proposed method can provide arbitrary intensity measures, ground-motion time series, and spatial ground-motion fields for all hazard levels, which enables more realistic and accurate MCE hazard evaluations, and thus has great application potential in earthquake engineering.
Ligand activation mechanisms of human KCNQ2 channel
Authors: Ma Demin , Zheng Yueming , Li Xiaoxiao , Zhou Xiaoyu , Yang Zhenni , Zhang Yan , Wang Long , Zhang Wenbo , Fang Jiajia , Zhao Guohua , Hou Panpan , Nan Fajun , Yang Wei , Su Nannan , Gao Zhaobing , Guo Jiangtao
Published: October 2023

The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP2), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP2, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2.
Obesity dysregulates the pulmonary antiviral immune response
Authors: Almond Mark , Farne Hugo A. , Jackson Millie M. , Jha Akhilesh , Katsoulis Orestis , Pitts Oliver , Tunstall Tanushree , Regis Eteri , Dunning Jake , Byrne Adam J. , Mallia Patrick , Kon Onn Min , Saunders Ken A. , Simpson Karen D. , Snelgrove Robert J. , Openshaw Peter J. M. , Edwards Michael R. , Barclay Wendy S. , Heaney Liam M. , Johnston Sebastian L. , Singanayagam Aran
Published: October 2023

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.
Selective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite
Authors: Cordisco Estefanía , Zanor María Inés , Moreno Diego Martín , Serra Diego Omar
Published: October 2023

The propensity of bacteria to grow collectively in communities known as biofilms and their ability to overcome clinical treatments in this condition has become a major medical problem, emphasizing the need for anti-biofilm strategies. Antagonistic microbial interactions have extensively served as searching platforms for antibiotics, but their potential as sources for anti-biofilm compounds has barely been exploited. By screening for microorganisms that in agar-set pairwise interactions could antagonize Escherichia coli’s ability to form macrocolony biofilms, we found that the soil bacterium Bacillus subtilis strongly inhibits the synthesis of amyloid fibers –known as curli-, which are the primary extracellular matrix (ECM) components of E. coli biofilms. We identified bacillaene, a B. subtilis hybrid non-ribosomal peptide/polyketide metabolite, previously described as a bacteriostatic antibiotic, as the effector molecule. We found that bacillaene combines both antibiotic and anti-curli functions in a concentration-dependent order that potentiates the ecological competitiveness of B. subtilis, highlighting bacillaene as a metabolite naturally optimized for microbial inhibition. Our studies revealed that bacillaene inhibits curli by directly impeding the assembly of the CsgB and CsgA curli subunits into amyloid fibers. Moreover, we found that curli inhibition occurs despite E. coli attempts to reinforce its protective ECM by inducing curli genes via a RpoS-mediated competition sensing response trigged by the threatening presence of B. subtilis. Overall, our findings illustrate the relevance of exploring microbial interactions not only for finding compounds with unknown and unique activities, but for uncovering additional functions of compounds previously categorized as antibiotics.
Extracting quantum dynamical resources: consumption of non-Markovianity for noise reduction
Authors: Berk Graeme D. , Milz Simon , Pollock Felix A. , Modi Kavan
Published: October 2023

A great many efforts are dedicated to developing noise reduction and mitigation methods. One remarkable achievement in this direction is dynamical decoupling (DD), although its applicability remains limited because fast control is required. Using resource theoretic tools, we show that non-Markovianity is a resource for noise reduction, raising the possibility that it can be leveraged for noise reduction where traditional DD methods fail. We propose a non-Markovian optimisation technique for finding DD pulses. Using a prototypical noise model, we numerically demonstrate that our optimisation-based methods are capable of drastically improving the exploitation of temporal correlations, extending the timescales at which noise suppression is viable by at least two orders of magnitude, compared to traditional DD which does not use any knowledge of the non-Markovian environment. Importantly, the corresponding tools are built on operational grounds and can be easily implemented to reduce noise in the current generation of quantum devices.
An intense narrow equatorial jet in Jupiter’s lower stratosphere observed by JWST
Authors: Hueso Ricardo , Sánchez-Lavega Agustín , Fouchet Thierry , de Pater Imke , Antuñano Arrate , Fletcher Leigh N. , Wong Michael H. , Rodríguez-Ovalle Pablo , Sromovsky Lawrence A. , Fry Patrick M. , Orton Glenn S. , Guerlet Sandrine , Irwin Patrick G. J. , Lellouch Emmanuel , Harkett Jake , de Kleer Katherine , Melin Henrik , Hue Vincent , Simon Amy A. , Luszcz-Cook Statia , Sayanagi Kunio M.
Published: October 2023

The atmosphere of Jupiter has east–west zonal jets that alternate as a function of latitude as tracked by cloud motions at tropospheric levels. Above and below the cold tropopause at ~100 mbar, the equatorial atmosphere is covered by hazes at levels where thermal infrared observations used to characterize the dynamics of the stratosphere lose part of their sensitivity. James Webb Space Telescope observations of Jupiter in July 2022 show these hazes in higher detail than ever before and reveal the presence of an intense (140 m s−1) equatorial jet at 100–200 mbar (70 m s−1 faster than the zonal winds at the cloud level) that is confined to ±3° of the equator and is located below stratospheric thermal oscillations that extend at least from 0.1 to 40 mbar and repeat in multiyear cycles. This suggests that the new jet is a deep part of Jupiter’s Equatorial Stratospheric Oscillation and may therefore vary in strength over time.
Freshwater fish diversity in the western Amazon basin shaped by Andean uplift since the Late Cretaceous
Authors: Boschman Lydian M. , Carraro Luca , Cassemiro Fernanda A. S. , de Vries Jorad , Altermatt Florian , Hagen Oskar , Hoorn Carina , Pellissier Loïc
Published: October 2023

South America is home to the highest freshwater fish biodiversity on Earth, and the hotspot of species richness is located in the western Amazon basin. The location of this hotspot is enigmatic, as it is inconsistent with the pattern observed in river systems across the world of increasing species richness towards a river’s mouth. Here we investigate the role of river capture events caused by Andean mountain building and repeated episodes of flooding in western Amazonia in shaping the modern-day richness pattern of freshwater fishes in South America, and in Amazonia in particular. To this end, we combine a reconstruction of river networks since 80 Ma with a mechanistic model simulating dispersal, allopatric speciation and extinction over the dynamic landscape of rivers and lakes. We show that Andean mountain building and consequent numerous small river capture events in western Amazonia caused freshwater habitats to be highly dynamic, leading to high diversification rates and exceptional richness. The history of marine incursions and lakes, including the Miocene Pebas mega-wetland system in western Amazonia, played a secondary role.
A comparison of neuroelectrophysiology databases
Authors: Subash Priyanka , Gray Alex , Boswell Misque , Cohen Samantha L. , Garner Rachael , Salehi Sana , Fisher Calvary , Hobel Samuel , Ghosh Satrajit , Halchenko Yaroslav , Dichter Benjamin , Poldrack Russell A. , Markiewicz Chris , Hermes Dora , Delorme Arnaud , Makeig Scott , Behan Brendan , Sparks Alana , Arnott Stephen R , Wang Zhengjia , Magnotti John , Beauchamp Michael S. , Pouratian Nader , Toga Arthur W. , Duncan Dominique
Published: October 2023

As data sharing has become more prevalent, three pillars - archives, standards, and analysis tools - have emerged as critical components in facilitating effective data sharing and collaboration. This paper compares four freely available intracranial neuroelectrophysiology data repositories: Data Archive for the BRAIN Initiative (DABI), Distributed Archives for Neurophysiology Data Integration (DANDI), OpenNeuro, and Brain-CODE. The aim of this review is to describe archives that provide researchers with tools to store, share, and reanalyze both human and non-human neurophysiology data based on criteria that are of interest to the neuroscientific community. The Brain Imaging Data Structure (BIDS) and Neurodata Without Borders (NWB) are utilized by these archives to make data more accessible to researchers by implementing a common standard. As the necessity for integrating large-scale analysis into data repository platforms continues to grow within the neuroscientific community, this article will highlight the various analytical and customizable tools developed within the chosen archives that may advance the field of neuroinformatics.
Europe PMC annotated full-text corpus for gene/proteins, diseases and organisms
Authors: Yang Xiao , Saha Shyamasree , Venkatesan Aravind , Tirunagari Santosh , Vartak Vid , McEntyre Johanna
Published: October 2023

Named entity recognition (NER) is a widely used text-mining and natural language processing (NLP) subtask. In recent years, deep learning methods have superseded traditional dictionary- and rule-based NER approaches. A high-quality dataset is essential to fully leverage recent deep learning advancements. While several gold-standard corpora for biomedical entities in abstracts exist, only a few are based on full-text research articles. The Europe PMC literature database routinely annotates Gene/Proteins, Diseases, and Organisms entities. To transition this pipeline from a dictionary-based to a machine learning-based approach, we have developed a human-annotated full-text corpus for these entities, comprising 300 full-text open-access research articles. Over 72,000 mentions of biomedical concepts have been identified within approximately 114,000 sentences. This article describes the corpus and details how to access and reuse this open community resource.
Observed increases in North Atlantic tropical cyclone peak intensification rates
Authors: Garner Andra J.
Published: October 2023

Quickly intensifying tropical cyclones (TCs) are exceptionally hazardous for Atlantic coastlines. An analysis of observed maximum changes in wind speed for Atlantic TCs from 1971 to 2020 indicates that TC intensification rates have already changed as anthropogenic greenhouse gas emissions have warmed the planet and oceans. Mean maximum TC intensification rates are up to 28.7% greater in a modern era (2001–2020) compared to a historical era (1971–1990). In the modern era, it is about as likely for TCs to intensify by at least 50 kts in 24 h, and more likely for TCs to intensify by at least 20 kts within 24 h than it was for TCs to intensify by these amounts in 36 h in the historical era. Finally, the number of TCs that intensify from a Category 1 hurricane (or weaker) into a major hurricane within 36 h has more than doubled in the modern era relative to the historical era. Significance tests suggest that it would have been statistically impossible to observe the number of TCs that intensified in this way during the modern era if rates of intensification had not changed from the historical era.
Privately vertically mining of sequential patterns based on differential privacy with high efficiency and utility
Authors: Liang Wenjuan , Zhang Wenke , Liang Songtao , Yuan Caihong
Published: October 2023

Sequential pattern mining is one of the fundamental tools for many important data analysis tasks, such as web browsing behavior analysis. Based on frequent patterns, decision-makers can obtain both economic gains and social values. Sequential data, on the other hand, frequently contain sensitive information, and directly analyzing these data will raise user concerns from a privacy perspective. Differential privacy (DP), as the most popular privacy model, has been employed to address this privacy concern. Most existing DP-Solutions are designed to combine horizontal sequence pattern mining algorithms with differential privacy. Due to the inefficiency of horizontal algorithms, their DP-Solutions cannot ensure high efficiency and accuracy while offering a high privacy guarantee. Therefore, we proposed privVertical, a new private sequence pattern mining scheme combining the vertical mining algorithm with differential privacy to achieve the above objective. Unlike DP-solutions based on horizontal algorithms, privVertical can promote efficiency by avoiding performing costly database scans or costly projection database constructions. Moreover, to promote accuracy, a differentially private hash MapList (called privHashMap) is designed to record frequent concurrency items and their noisy support based on the Sparse Vector Technique. PrivHashMap is used to pre-pruning excessive infrequent candidate sequences in private mining, and Sparse Vector Technique is used to promote the accuracy of PrivHashMap. After pruning these invalid candidate sequences, less noise is required to achieve the same level of privacy, increasing the accuracy of private mining. Theoretical privacy analysis proves privVertical satisfies $$\varepsilon$$
ε
-differential privacy. Experiments show that privVertical achieves higher accuracy and efficiency while achieving the same privacy level.
Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas
Authors: Hoppner Jorge , van Genabith Levin , Hielscher Thomas , Heger Ulrike , Sperling Lucas , Colbatzky Teresa , Gutjahr Ewgenija , Lang Matthias , Pausch Thomas , Spektor Anna-Maria , Glatting Frederik M. , Liermann Jakob , Hackert Thilo , Kratochwil Clemens , Giesel Frederik L. , Haberkorn Uwe , Röhrich Manuel
Published: October 2023

Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses.
Tuning aminopolycarboxylate chelators for efficient complexation of trivalent actinides
Authors: Pilgrim Corey D. , Grimes Travis S. , Smith Clayn , Heathman Colt R. , Mathew Jopaul , Jansone-Popova Santa , Roy Santanu , Ray Debmalya , Bryantsev Vyacheslav S. , Zalupski Peter R.
Published: October 2023

The complexation of trivalent lanthanides and minor actinides (Am3+, Cm3+, and Cf3+) by the acyclic aminopolycarboxylate chelators 6,6′-((ethane-1,2-diylbis–((carboxymethyl)azanediyl))bis–(methylene))dipicolinic acid (H4octapa) and 6,6'-((((4-(1-(2-(2-(2-hydroxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)pyridine-2,6-diyl)bis–(methylene))bis–((carboxymethyl)azanediyl))bis–(methylene)) dipicolinic acid (H4pypa-peg) were studied using potentiometry, spectroscopy, competitive complexation liquid–liquid extraction, and ab initio molecular dynamics simulations. Two studied reagents are strong multidentate chelators, well-suited for applications seeking radiometal coordination for in-vivo delivery and f-element isolation. The previously reported H4octapa forms a compact coordination packet, while H4pypa-peg is less sterically constrained due to the presence of central pyridine ring. The solubility of H4octapa is limited in a non-complexing high ionic strength perchlorate media. However, the introduction of a polyethylene glycol group in H4pypa-peg increased the solubility without influencing its ability to complex the lanthanides and minor actinides in solution.
Novel approach toward the understanding of genetic diversity based on the two types of amino acid repeats in Erwinia amylovora
Authors: Ham Hyeonheui , Park Dong Suk
Published: October 2023

Erwinia amylovora is a notorious plant pathogenic bacterium of global concern that has devastated the apple and pear production industry worldwide. Nevertheless, the approaches available currently to understand the genetic diversity of E. amylovora remain unsatisfactory because of the lack of a trustworthy index and data covering the globally occurring E. amylovora strains; thus, their origin and distribution pattern remains ambiguous. Therefore, there is a growing need for robust approaches for obtaining this information via the comparison of the genomic structure of Amygdaloideae-infecting strains to understand their genetic diversity and distribution. Here, the whole-genome sequences of 245 E. amylovora strains available from the NCBI database were compared to identify intraspecific genes for use as an improved index for the simple classification of E. amylovora strains regarding their distribution. Finally, we discovered two kinds of strain-typing protein-encoding genes, i.e., the SAM-dependent methyltransferase and electron transport complex subunit RsxC. Interestingly, both of these proteins carried an amino acid repeat in these strains: SAM-dependent methyltransferase comprised a single-amino-acid repeat (asparagine), whereas RsxC carried a 40-amino-acid repeat, which was differentially distributed among the strains. These noteworthy findings and approaches may enable the exploration of the genetic diversity of E. amylovora from a global perspective.
Tamm–Horsfall protein in humane urine: sex-dependent differences in the excretion and N-glycosylation pattern
Authors: Mo Boris , Scharf Birte , Gutheil Christian , Letzel Matthias C. , Hensel Andreas
Published: October 2023

Tamm–Horsfall protein (THP) is a highly N-glycosylated protein from epithelial cells of the ascending limb of Henle loop. It is secreted into the urine as part of the innate immune response against uropathogenic pathogens. As women are more likely to suffer from urinary tract infections, biomedical studies were conducted to investigate sex-differences in THP excretion, as well as differences in the THP N-glycosylation pattern. A total of 238 volunteers (92 men, 146 women, 69 with hormonal contraceptives) participated in this study, providing urine samples. Women showed a clear tendency to have higher THP concentration and excretion rates than men (p < 0.16). Regular intake of hormonal contraceptives had no significant influence on urinary THP concentration compared to no regular intake. The individual N-glycosylation pattern of THP in urine samples from randomly selected individuals (10 female, 10 male) was investigated after enzymatic release and MS analysis of the oligosaccharides. Female subjects tended to have an increased proportion of oligomannose type N-glycans and non-fucosylated glycans, whereas men had an increased proportion of fucosylated complex-type glycans. The higher level of oligomannose-type glycans in THP from women might be explained by a self-defence mechanism to overcome the higher infections pressure by the female anatomical properties.
Nucleus-forming vibriophage cocktail reduces shrimp mortality in the presence of pathogenic bacteria
Authors: Thammatinna Khrongkhwan , Sinprasertporn Ammara , Naknaen Ampapan , Samernate Thanadon , Nuanpirom Jiratchaya , Chanwong Parinda , Somboonwiwat Kunlaya , Pogliano Joe , Sathapondecha Ponsit , Thawonsuwan Jumroensri , Nonejuie Poochit , Chaikeeratisak Vorrapon
Published: October 2023

The global aquaculture industry has suffered significant losses due to the outbreak of Acute Hepatopancreatic Necrosis Disease (AHPND) caused byVibrio parahaemolyticus. Since the use of antibiotics as control agents has not been shown to be effective, an alternative anti-infective regimen, such as phage therapy, has been proposed. Here, we employed high-throughput screening for potential phages from 98 seawater samples and obtained 14 phages exhibiting diverse host specificity patterns against pathogenic VPAHPNDstrains. Among others, twoChimallinviridaephages, designated Eric and Ariel, exhibited the widest host spectrum against vibrios. In vitro and in vivo studies revealed that a cocktail derived from these two nucleus-forming vibriophages prolonged the bacterial regrowth of various pathogenic VPAHPNDstrains and reduced shrimp mortality from VPAHPNDinfection. This research highlights the use of high-throughput phage screening that leads to the formulation of a nucleus-forming phage cocktail applicable for bacterial infection treatment in aquaculture.
Magnetically retrievable nanocatalyst Fe3O4@CPTMO@dithizone-Ni for the fabrication of 4H-benzo[h]chromenes under green medium
Authors: Bibak Sepideh , Poursattar Marjani Ahmad
Published: October 2023

In the research, the core–shell procedure synthesized a novel magnetically separable heterogeneous nanocatalyst with high stability named Fe3O4@CPTMO@dithizone-Ni. In this method, Fe3O4 was modified as a magnetic core using surfactant (SDS) and polyethylene glycol (PEG) coating; after functionalizing the magnetic nanoparticles with 3-chloropropyl-tri-methoxysilane and dithizone, Ni metal was immobilized. The prepared catalyst was identified and specified utilizing diverse physicochemical techniques involving FT-IR, XRD, SEM, EMA, BET, ICP, EDS, TGA, Raman, and TEM. In the following, to vouch for the efficiency of the obtaining catalyst for the green synthesis of 4H-benzo[h]chromenes utilizing the three-component, one-pot condensation reaction of α-naphthol, aryl glyoxal, and malononitrile as precursors were evaluated. The catalyst exhibited high recyclability with a slight reduction in activity at least eight series without a substantial decrease in stability and efficiency. The synthesized nanocatalyst was evaluated in various conditions such as different solvents, etc. the best of these conditions is the initial concentration of 30 mg of nanocatalyst with water as a solvent in 3 min with 98% yield. The prominent merits of the present research include easy separation of the catalyst without centrifugation, high-accessible raw precursors, cost-effectiveness, environmental friendliness, green reaction status, quick reaction, and excellent product yields.
New design of high-power in-motion inductive charger for low power pulsation
Authors: Shaier Ahmed A. , Mohamed Ahmed A. S. , Metwally Hamid , Selem Sameh I.
Published: October 2023

The magnetic coupler is the most vital component for charging EV wirelessly. Through it, the output power can be transported from the transmitter to the receiver by means of electromagnetic fields. Therefore, this manuscript presents a proposed design of a magnetic coupler in the form of Double-D (DD) on both sides, which is suitable for in-motion inductive charging. This charger is capable of transferring power of 200-kW through an airgap of 250 mm with an efficiency of 91.88% and an operating frequency of 85 kHz. Computational modeling is conducted to obtain the magnetic coupler and the compensation parameters of the proposed system. The appropriate dimensions of the coils, magnetic and metallic shielding are obtained by using the finite element model (FEM). The effect of misalignments on the self and mutual inductances of the two coils (Lp, Ls, M), the output power (Po), and the transmission efficiency (η) is studied in case of one and two coils at transmitter side. The output power in the distance between the two transmitter coils (d) is improved by controlling the operating frequency, adding magnetizable concrete (MC), or both together. These techniques have proven effectiveness in improving the output power by 45.15% for small d and 72.51% for large d. In addition, the efficiency improved by 15.95% for small d and 60.76% for large d. Moreover, these improvement cases were compared in terms of size, weight and cost for a 100-m driving track.
Biochemical and structural basis of mercuric reductase, GbsMerA, from Gelidibacter salicanalis PAMC21136
Authors: Pardhe Bashu Dev , Lee Min Ju , Lee Jun Hyuck , Do Hackwon , Oh Tae-Jin
Published: October 2023

Heavy metals, including mercury, are non-biodegradable and highly toxic to microorganisms even at low concentrations. Understanding the mechanisms underlying the environmental adaptability of microorganisms with Hg resistance holds promise for their use in Hg bioremediation. We characterizedGbsMerA, a mercury reductase belonging to the mercury-resistant operon ofGelidibacter salicanalisPAMC21136, and found its maximum activity of 474.7 µmol/min/mg in reducing Hg+2. In the presence of Ag and Mn, the enzyme exhibited moderate activity as 236.5 µmol/min/mg and 69 µmol/min/mg, respectively.GbsMerA exhibited optimal activity at pH 7.0 and a temperature of 60 °C. Moreover, the crystal structure ofGbsMerA and structural comparison with homologues indicated thatGbsMerA contains residues, Tyr437´ and Asp47, which may be responsible for metal transfer at thesi-face by providing a hydroxyl group (−OH) to abstract a proton from the thiol group of cysteine. The complex structure with NADPH indicated that Y174 in there-face can change its side chain direction upon NADPH binding, indicating that Y174 may have a role as a gate for NADPH binding. Moreover, the heterologous host expressingGbsMerA (pGbsMerA) is more resistant to Hg toxicity when compared to the host lackingGbsMerA. Overall, this study provides a background for understanding the catalytic mechanism and Hg detoxification byGbsMerA and suggests the application of genetically engineeredE. colistrains for environmental Hg removal.
Cladophora glomerata extracts produced by Ultrasound-Assisted Extraction support early growth and development of lupin (Lupinus angustifolius L.)
Authors: Lewandowska Sylwia , Dziergowska Katarzyna , Galek Renata , Michalak Izabela
Published: October 2023

The effect of the extract obtained by Ultrasound-Assisted Extraction (UAE) from green macroalga Cladophora glomerata on the germination and early growth of three narrow-leaved lupin varieties (cv. Homer, Jowisz, and Tytan) was examined. The seeds of these varieties came from five growing seasons (2015–2019) and this was their successive propagation stage. In total, 45 groups were tested. Narrow-leaved lupin like other legumes have a beneficial effect on the physical properties and fertility of the soil. Its high nutritive value makes it suitable for the production of valuable fodder. The algal extract, which was screened for the content of active compounds responsible for their biostimulant effect was applied in two concentrations: 10 and 20%. The germination percentage, root, hypocotyl, epicotyl length and chlorophyll content in cotyledons were evaluated at the end of the experiment. The 20% extract stimulated the growth of seedlings of all lupin cultivars better than the 10% application. The Jowisz variety deserves special attention, as it has the longest root system of seedlings.
General, open-source vertex modeling in biological applications using Tissue Forge
Authors: Sego T. J. , Comlekoglu Tien , Peirce Shayn M. , Desimone Douglas W. , Glazier James A.
Published: October 2023

Vertex models are a widespread approach for describing the biophysics and behaviors of multicellular systems, especially of epithelial tissues. Vertex models describe a wide variety of developmental scenarios and behaviors like cell rearrangement and tissue folding. Often, these models are implemented as single-use or closed-source software, which inhibits reproducibility and decreases accessibility for researchers with limited proficiency in software development and numerical methods. We developed a physics-based vertex model methodology in Tissue Forge, an open-source, particle-based modeling and simulation environment. Our methodology describes the properties and processes of vertex model objects on the basis of vertices, which allows integration of vertex modeling with the particle-based formalism of Tissue Forge, enabling an environment for developing mixed-method models of multicellular systems. Our methodology in Tissue Forge inherits all features provided by Tissue Forge, delivering open-source, extensible vertex modeling with interactive simulation, real-time simulation visualization and model sharing in the C, C++ and Python programming languages and a Jupyter Notebook. Demonstrations show a vertex model of cell sorting and a mixed-method model of cell migration combining vertex- and particle-based models. Our methodology provides accessible vertex modeling for a broad range of scientific disciplines, and we welcome community-developed contributions to our open-source software implementation.
Structural equation modeling of female gait attractiveness using gait kinematics
Authors: Tanabe Hiroko , Yamamoto Kota
Published: October 2023

In our social lives, movement’s attractiveness greatly affects interpersonal cognition, and gait kinematics mediates walkers’ attractiveness. However, no model using gait kinematics has so far predicted gait attractiveness. Thus, this study constructed models of female gait attractiveness with gait kinematics and physique factors as explanatory variables for both barefoot and high-heel walking. First, using motion capture data from 17 women walking, including seven professional runway models, we created gait animations. We also calculated the following gait kinematics as candidate variables to explain walking’s attractiveness: four body-silhouette-related variables and six health-related variables. Then, 60 observers evaluated each gait animation’s attractiveness and femininity. We performed correlation analysis between these variables and evaluation scores to obtain explanatory variables. Structural equation modeling suggested two models for gait attractiveness, one composed of trunk and head silhouette factors and the other of physique, trunk silhouette, and health-related gait factors. The study’s results deepened our understanding of mechanisms behind nonverbal interpersonal cognition through physical movement and brought us closer to realization of artificial generation of attractive gait motions.
Early cochlear implantation supports narrative skills of children with prelingual single-sided deafness
Authors: Arras Tine , Boudewyns An , Dhooge Ingeborg , Zarowski Andrzej , Philips Birgit , Desloovere Christian , Wouters Jan , van Wieringen Astrid
Published: October 2023

Prelingual single-sided deafness (SSD) not only affects children’s hearing skills, but can also lead to speech-language delays and academic underachievement. Early cochlear implantation leads to improved spatial hearing, but the impact on language development is less studied. In our longitudinal study, we assessed the language skills of young children with SSD and a cochlear implant (CI). In particular, we investigated their narrative skills in comparison to two control groups: children with SSD without a CI, and children with bilateral normal hearing. We found that children with SSD and a CI performed in line with their normal-hearing peers with regard to narrative and verbal short-term memory skills. Children with SSD without a CI had worse narrative (group difference = − 0.67, p = 0.02) and verbal short-term memory (group difference = − 0.68, p = 0.03) scores than the implanted group. Verbal short-term memory scores and grammar scores each correlated positively with narrative scores across all groups. Early grammar scores (at 2–3 years of age) could partially predict later narrative scores (at 4–6 years of age). These results show that young children with prelingual SSD can benefit from early cochlear implantation to achieve age-appropriate language skills. They support the provision of a CI to children with prelingual SSD.
Acamprosate reduces ethanol intake in the rat by a combined action of different drug components
Authors: Ademar Karin , Loftén Anna , Nilsson Mathilda , Domi Ana , Adermark Louise , Söderpalm Bo , Ericson Mia
Published: October 2023

Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral® (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as relapse prevention therapy. The mechanism underlying its effect has in some studies been attributed to the calcium moiety and not to the N-acetylhomotaurine part of the compound. We recently suggested that the dopamine elevating effect of acamprosate is mediated both by N-acetylhomotaurine and calcium in a glycine receptor dependent manner. Here we aimed to explore, by means of in vivo microdialysis, if our previous study using local administration was functionally relevant and if systemic administration of the sodium salt of N-acetylhomotaurine (sodium acamprosate; 200 mg/kg, i.p.) enhanced the effects of calcium chloride (CaCl2; 73.5 mg/kg, i.p.) on nucleus accumbens (nAc) dopamine and/or taurine levels in male Wistar rats. In addition, we investigated the impact of regular acamprosate and the combination of CaCl2 and N-acetylhomotaurine on the alcohol deprivation effect (ADE). Finally, we assessed if N-acetylhomotaurine potentiates the ethanol-intake reducing effect of CaCl2 in a two-bottle choice voluntary ethanol consumption model followed by an ADE paradigm. Systemic administration of regular acamprosate, sodium acamprosate and CaCl2 all trended to increase nAc dopamine whereas the combination of CaCl2 and sodium acamprosate produced a significant increase. Sodium acamprosate elevated extracellular taurine levels without additional effects of CaCl2. Ethanol intake was significantly reduced by systemic administration of CaCl2 without additional effects of the combination of CaCl2 and sodium acamprosate. Both acamprosate and CaCl2 combined with sodium acamprosate blocked the ADE following acute treatment. The data presented suggest that CaCl2 and N-acetylhomotaurine act in concert on a neurochemical level, but calcium appears to have the predominant effect on ethanol intake.
The role of melatonin in amyloid beta-induced inflammation mediated by inflammasome signaling in neuronal cell lines
Authors: Nopparat Chutikorn , Boontor Anuttree , Kutpruek Suchanoot , Govitrapong Piyarat
Published: October 2023

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. In addition to amyloid beta (Aβ) and tau, neuroinflammation is a crucial element in the etiology of this disease. However, the relevance of inflammasome-induced pyroptosis to AD is unknown. We aimed to clarify whether the anti-inflammatory effects of melatonin could prevent Aβ-mediated activation of the inflammasome. We demonstrated that Aβ upregulated NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, and cysteinyl aspartate-specific proteinase caspase (caspase 1) expression in SH-SY5Y neuroblastoma cells, resulting in the release of proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor (TNF-α). Melatonin prevented inflammasome signaling and excessive cytokine release caused by Aβ. We found that ethyl 2[(2-chlorophenyl)(hydroxy) methyl]acrylate (INF-4E, NLRP3 and caspase 1 inhibitor) significantly abolished Aβ-induced proinflammatory cytokine expression. The increase in cleaved-caspase 1, pro-IL18, and cleaved-IL18 caused by Aβ suggested the occurrence of pyroptosis, which was further confirmed by the increased expression of N-terminal gasdermin D (N-GSDMD). Melatonin plays a protective role against Aβ-induced inflammation via an inflammasome-associated mechanism that is essential in inducing the active forms of cytokines and pyroptosis. The ability of melatonin to inhibit inflammasome may represent a turning point in the treatment of AD progression.
A vignette-based evaluation of ChatGPT’s ability to provide appropriate and equitable medical advice across care contexts
Authors: Nastasi Anthony J. , Courtright Katherine R. , Halpern Scott D. , Weissman Gary E.
Published: October 2023

ChatGPT is a large language model trained on text corpora and reinforced with human supervision. Because ChatGPT can provide human-like responses to complex questions, it could become an easily accessible source of medical advice for patients. However, its ability to answer medical questions appropriately and equitably remains unknown. We presented ChatGPT with 96 advice-seeking vignettes that varied across clinical contexts, medical histories, and social characteristics. We analyzed responses for clinical appropriateness by concordance with guidelines, recommendation type, and consideration of social factors. Ninety-three (97%) responses were appropriate and did not explicitly violate clinical guidelines. Recommendations in response to advice-seeking questions were completely absent (N = 34, 35%), general (N = 18, 18%), or specific (N = 44, 46%). 53 (55%) explicitly considered social factors like race or insurance status, which in some cases changed clinical recommendations. ChatGPT consistently provided background information in response to medical questions but did not reliably offer appropriate and personalized medical advice.