bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Authors: Amiri Sorosh , Muresan Camelia , Shang Xingbo , Huet-Calderwood Clotilde , Schwartz Martin A. , Calderwood David A. , Murrell Michael
Published: December 2023

The filamentous actin (F-actin) cytoskeleton is a composite material consisting of cortical actin and bundled F-actin stress fibers, which together mediate the mechanical behaviors of the cell, from cell division to cell migration. However, as mechanical forces are typically measured upon transmission to the extracellular matrix, the internal distribution of forces within the cytoskeleton is unknown. Likewise, how distinct F-actin architectures contribute to the generation and transmission of mechanical forces is unclear. Therefore, we have developed a molecular tension sensor that embeds into the F-actin cytoskeleton. Using this sensor, we measure tension within stress fibers and cortical actin, as the cell is subject to uniaxial stretch. We find that the mechanical response, as measured by FRET, depends on the direction of applied stretch relative to the cell’s axis of alignment. When the cell is aligned parallel to the direction of the stretch, stress fibers and cortical actin both accumulate tension. By contrast, when aligned perpendicular to the direction of stretch, stress fibers relax tension while the cortex accumulates tension, indicating mechanical anisotropy within the cytoskeleton. We further show that myosin inhibition regulates this anisotropy. Thus, the mechanical anisotropy of the cell and the coordination between distinct F-actin architectures vary and depend upon applied load.
Nitric oxide controls shoot meristem activity via regulation of DNA methylation
Authors: Zeng Jian , Zhao Xin’Ai , Liang Zhe , Hidalgo Inés , Gebert Michael , Fan Pengfei , Wenzl Christian , Gornik Sebastian G. , Lohmann Jan U.
Published: December 2023

Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA-directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling. Importantly, we find that the stem cell inducing WUSCHEL transcription factor directly interacts with AGO4 in a NO dependent manner, explaining how these two signaling systems may converge to modify DNA methylation patterns. Taken together, our results reveal that NO signaling plays an important role in controlling plant stem cell homeostasis via the regulation of de novo DNA methylation.
Regulation of the cell division hydrolase RipC by the FtsEX system in Mycobacterium tuberculosis
Authors: Li Jianwei , Xu Xin , Shi Jian , Hermoso Juan A. , Sham Lok-To , Luo Min
Published: December 2023

The FtsEX complex regulates, directly or via a protein mediator depending on bacterial genera, peptidoglycan degradation for cell division. In mycobacteria and Gram-positive bacteria, the FtsEX system directly activates peptidoglycan-hydrolases by a mechanism that remains unclear. Here we report our investigation of Mycobacterium tuberculosis FtsEX as a non-canonical regulator with high basal ATPase activity. The cryo-EM structures of the FtsEX system alone and in complex with RipC, as well as the ATP-activated state, unveil detailed information on the signal transduction mechanism, leading to the activation of RipC. Our findings indicate that RipC is recognized through a “Match and Fit” mechanism, resulting in an asymmetric rearrangement of the extracellular domains of FtsX and a unique inclined binding mode of RipC. This study provides insights into the molecular mechanisms of FtsEX and RipC regulation in the context of a critical human pathogen, guiding the design of drugs targeting peptidoglycan remodeling.
Microplastic burden in marine benthic invertebrates depends on species traits and feeding ecology within biogeographical provinces
Authors: Porter Adam , Godbold Jasmin A. , Lewis Ceri N. , Savage Georgie , Solan Martin , Galloway Tamara S.
Published: December 2023

The microplastic body burden of marine animals is often assumed to reflect levels of environmental contamination, yet variations in feeding ecology and regional trait expression could also affect a species’ risk of contaminant uptake. Here, we explore the global inventory of individual microplastic body burden for invertebrate species inhabiting marine sediments across 16 biogeographic provinces. We show that individual microplastic body burden in benthic invertebrates cannot be fully explained by absolute levels of microplastic contamination in the environment, because interspecific differences in behaviour and feeding ecology strongly determine microplastic uptake. Our analyses also indicate a degree of species-specific particle selectivity; likely associated with feeding biology. Highest microplastic burden occurs in the Yellow and Mediterranean Seas and, contrary to expectation, amongst omnivores, predators, and deposit feeders rather than suspension feeding species. Our findings highlight the inadequacy of microplastic uptake risk assessments based on inventories of environmental contamination alone, and the need to understand how species behaviour and trait expression covary with microplastic contamination.
Cooperative supramolecular polymerization of styrylpyrenes for color-dependent circularly polarized luminescence and photocycloaddition
Authors: Yuan Wei , Chen Letian , Yuan Chuting , Zhang Zidan , Chen Xiaokai , Zhang Xiaodong , Guo Jingjing , Qian Cheng , Zhao Zujin , Zhao Yanli
Published: December 2023

Developing facile and efficient methods to obtain circularly polarized luminescence (CPL) materials with a large luminescence dissymmetry factor (glum) and fluorescence quantum yield (ΦY) is attractive but still challenging. Herein, supramolecular polymerization of styrylpyrenes (R/S-PEB) is utilized to attain this aim, which can self-assemble into helical nanoribbons. Benefiting from the dominant CH-π interactions between the chromophores, the supramolecular solution of S-PEB shows remarkable blue-color CPL property (glum: 0.011, ΦY: 69%). From supramolecular solution to gel, the emission color (blue to yellow-green) and handedness of CPL (glum: –0.011 to +0.005) are concurrently manipulated, while the corresponding supramolecular chirality maintains unchanged, representing the rare example of color-dependent CPL materials. Thanks to the supramolecular confine effect, the [2 + 2] cycloaddition reaction rate of the supramolecular solution is 10.5 times higher than that of the monomeric solution. In contrast, no cycloaddition reaction occurs for the gel and assembled solid samples. Our findings provide a vision for fabricating multi-modal and high-performance CPL-active materials, paving the way for the development of advanced photo-responsive chiral systems.
Fluorescence lifetime Hong-Ou-Mandel sensing
Authors: Lyons Ashley , Zickus Vytautas , Álvarez-Mendoza Raúl , Triggiani Danilo , Tamma Vincenzo , Westerberg Niclas , Tassieri Manlio , Faccio Daniele
Published: December 2023

Fluorescence Lifetime Imaging Microscopy in the time domain is typically performed by recording the arrival time of photons either by using electronic time tagging or a gated detector. As such the temporal resolution is limited by the performance of the electronics to 100’s of picoseconds. Here, we demonstrate a fluorescence lifetime measurement technique based on photon-bunching statistics with a resolution that is only dependent on the duration of the reference photon or laser pulse, which can readily reach the 1–0.1 picosecond timescale. A range of fluorescent dyes having lifetimes spanning from 1.6 to 7 picoseconds have been here measured with only ~1 s measurement duration. We corroborate the effectiveness of the technique by measuring the Newtonian viscosity of glycerol/water mixtures by means of a molecular rotor having over an order of magnitude variability in lifetime, thus introducing a new method for contact-free nanorheology. Accessing fluorescence lifetime information at such high temporal resolution opens a doorway for a wide range of fluorescent markers to be adopted for studying yet unexplored fast biological processes, as well as fundamental interactions such as lifetime shortening in resonant plasmonic devices.
Automated classification of big X-ray diffraction data using deep learning models
Authors: Salgado Jerardo E. , Lerman Samuel , Du Zhaotong , Xu Chenliang , Abdolrahim Niaz
Published: December 2023

In current in situ X-ray diffraction (XRD) techniques, data generation surpasses human analytical capabilities, potentially leading to the loss of insights. Automated techniques require human intervention, and lack the performance and adaptability required for material exploration. Given the critical need for high-throughput automated XRD pattern analysis, we present a generalized deep learning model to classify a diverse set of materials’ crystal systems and space groups. In our approach, we generate training data with a holistic representation of patterns that emerge from varying experimental conditions and crystal properties. We also employ an expedited learning technique to refine our model’s expertise to experimental conditions. In addition, we optimize model architecture to elicit classification based on Bragg’s Law and use evaluation data to interpret our model’s decision-making. We evaluate our models using experimental data, materials unseen in training, and altered cubic crystals, where we observe state-of-the-art performance and even greater advances in space group classification.
The evolution of human altriciality and brain development in comparative context
Authors: Gómez-Robles Aida , Nicolaou Christos , Smaers Jeroen B. , Sherwood Chet C.
Published: December 2023

Human newborns are considered altricial compared with other primates because they are relatively underdeveloped at birth. However, in a broader comparative context, other mammals are more altricial than humans. It has been proposed that altricial development evolved secondarily in humans due to obstetrical or metabolic constraints, and in association with increased brain plasticity. To explore this association, we used comparative data from 140 placental mammals to measure how altriciality evolved in humans and other species. We also estimated how changes in brain size and gestation length influenced the timing of neurodevelopment during hominin evolution. Based on our data, humans show the highest evolutionary rate to become more altricial (measured as the proportion of adult brain size at birth) across all placental mammals, but this results primarily from the pronounced postnatal enlargement of brain size rather than neonatal changes. In addition, we show that only a small number of neurodevelopmental events were shifted to the postnatal period during hominin evolution, and that they were primarily related to the myelination of certain brain pathways. These results indicate that the perception of human altriciality is mostly driven by postnatal changes, and they point to a possible association between the timing of myelination and human neuroplasticity.
The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
Authors: Caswell Deborah R. , Gui Philippe , Mayekar Manasi K. , Law Emily K. , Pich Oriol , Bailey Chris , Boumelha Jesse , Kerr D. Lucas , Blakely Collin M. , Manabe Tadashi , Martinez-Ruiz Carlos , Bakker Bjorn , De Dios Palomino Villcas Juan , I. Vokes Natalie , Dietzen Michelle , Angelova Mihaela , Gini Beatrice , Tamaki Whitney , Allegakoen Paul , Wu Wei , Humpton Timothy J. , Hill William , Tomaschko Mona , Lu Wei-Ting , Haderk Franziska , Al Bakir Maise , Nagano Ai , Gimeno-Valiente Francisco , de Carné Trécesson Sophie , Vendramin Roberto , Barbè Vittorio , Mugabo Miriam , Weeden Clare E. , Rowan Andrew , McCoach Caroline E. , Almeida Bruna , Green Mary , Gomez Carlos , Nanjo Shigeki , Barbosa Dora , Moore Chris , Przewrocka Joanna , Black James R. M. , Grönroos Eva , Suarez-Bonnet Alejandro , Priestnall Simon L. , Zverev Caroline , Lighterness Scott , Cormack James , Olivas Victor , Cech Lauren , Andrews Trisha , Rule Brandon , Jiao Yuwei , Zhang Xinzhu , Ashford Paul , Durfee Cameron , Venkatesan Subramanian , Temiz Nuri Alpay , Tan Lisa , Larson Lindsay K. , Argyris Prokopios P. , Brown William L. , Yu Elizabeth A. , Rotow Julia K. , Guha Udayan , Roper Nitin , Yu Johnny , Vogel Rachel I. , Thomas Nicholas J. , Marra Antonio , Selenica Pier , Yu Helena , Bakhoum Samuel F. , Chew Su Kit , Reis-Filho Jorge S. , Jamal-Hanjani Mariam , Vousden Karen H. , McGranahan Nicholas , Van Allen Eliezer M. , Kanu Nnennaya , Harris Reuben S. , Downward Julian , Bivona Trever G. , Swanton Charles
Published: December 2023

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.
Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
Authors: Liu Dan , Winer Benjamin Y. , Chou Marissa Y. , Tam Hanson , Xu Ying , An Jinping , Gardner James M. , Cyster Jason G.
Published: December 2023

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.
A Satellite Imagery Dataset for Long-Term Sustainable Development in United States Cities
Authors: Xi Yanxin , Liu Yu , Li Tong , Ding Jingtao , Zhang Yunke , Tarkoma Sasu , Li Yong , Hui Pan
Published: December 2023

Cities play an important role in achieving sustainable development goals (SDGs) to promote economic growth and meet social needs. Especially satellite imagery is a potential data source for studying sustainable urban development. However, a comprehensive dataset in the United States (U.S.) covering multiple cities, multiple years, multiple scales, and multiple indicators for SDG monitoring is lacking. To support the research on SDGs in U.S. cities, we develop a satellite imagery dataset using deep learning models for five SDGs containing 25 sustainable development indicators. The proposed dataset covers the 100 most populated U.S. cities and corresponding Census Block Groups from 2014 to 2023. Specifically, we collect satellite imagery and identify objects with state-of-the-art object detection and semantic segmentation models to observe cities’ bird’s-eye view. We further gather population, nighttime light, survey, and built environment data to depict SDGs regarding poverty, health, education, inequality, and living environment. We anticipate the dataset to help urban policymakers and researchers to advance SDGs-related studies, especially applying satellite imagery to monitor long-term and multi-scale SDGs in cities.
Introducing MEG-MASC a high-quality magneto-encephalography dataset for evaluating natural speech processing
Authors: Gwilliams Laura , Flick Graham , Marantz Alec , Pylkkänen Liina , Poeppel David , King Jean-Rémi
Published: December 2023

The “MEG-MASC” dataset provides a curated set of raw magnetoencephalography (MEG) recordings of 27 English speakers who listened to two hours of naturalistic stories. Each participant performed two identical sessions, involving listening to four fictional stories from the Manually Annotated Sub-Corpus (MASC) intermixed with random word lists and comprehension questions. We time-stamp the onset and offset of each word and phoneme in the metadata of the recording, and organize the dataset according to the ‘Brain Imaging Data Structure’ (BIDS). This data collection provides a suitable benchmark to large-scale encoding and decoding analyses of temporally-resolved brain responses to speech. We provide the Python code to replicate several validations analyses of the MEG evoked responses such as the temporal decoding of phonetic features and word frequency. All code and MEG, audio and text data are publicly available to keep with best practices in transparent and reproducible research.
Unveiling Hypothalamic Molecular Signatures via Retrograde Viral Tracing and Single-Cell Transcriptomics
Authors: Junaid Muhammad , Choe Han Kyoung , Kondoh Kunio , Lee Eun Jeong , Lim Su Bin
Published: December 2023

Despite the importance of hypothalamic neurocircuits in regulating homeostatic and survival-related behaviors, our understanding of the intrinsic molecular identities of neural components involved in these complex multi-synaptic interactions remains limited. In this study, we constructed a Cre recombinase-dependent pseudorabies virus (PRVs) capable of crossing synapses, coupled with transcriptome analysis of single upstream neurons post-infection. By utilizing this retrograde nuclear Connect-seq (nuConnect-seq) approach, we generated a single nuclei RNA-seq (snRNA-seq) dataset of 1,533 cells derived from the hypothalamus of CRH-IRES-Cre (CRH-Cre) mice. To ensure the technical validity of our nuConnect-seq dataset, we employed a label transfer technique against an integrated reference dataset of postnatal mouse hypothalamus comprising 152,524 QC-passed cells. The uniqueness of our approach lies in the integration of diverse datasets for validation, providing a more nuanced diversity of hypothalamic cell types. The presented validated dataset may deepen our understanding of hypothalamic neurocircuits and underscore the essential role of comprehensive integrated transcriptomic data for technical validity.
Correlation between birefringence and absorption mapping in large-size Sapphire substrates for gravitational-wave interferometry
Authors: Zeidler Simon , Eisenmann Marc , Bazzan Marco , Li Pengbo , Leonardi Matteo
Published: December 2023

In high-sensitive laser interferometers, such as the gravitational-wave detector KAGRA, ultra-high-quality mirrors are essential. In the case of KAGRA, where cavity mirrors are cooled down to 20 K, large-size Sapphire crystals are used as the substrate for the main mirrors to achieve both a good optical quality (i.e., low absorption and uniform refractive index) and optimized thermal behavior under cryogenic temperatures. To implement the very tight optical specifications required by this demanding application, it is mandatory to test the optical homogeneity of different substrates. In order to characterize refractive-index inhomogeneities of large-size uniaxial samples such as the KAGRA Sapphire test masses, we developed a dedicated setup, allowing to resolve birefringence changes with a sensitivity in the order of $$\Delta n\approx 2 \times 10^{-10}$$

Δ
n
≈
2
×

10

-
10

and a spatial resolution of $$1\,{{{\hbox {mm}}}}^{2}$$

1

mm

2

. Moreover, the same setup allows us to simultaneously record residual absorption maps, thus allowing for a comparison between birefringence and absorption features. In this paper, we will present for the first time measurements on a KAGRA-sized Sapphire substrate which has been characterized in terms of absorption already in an earlier work. Both birefringence inhomogeneities and absorption distributions will be compared and correlations discussed.
A computational spatial whole-Cell model for hepatitis B viral infection and drug interactions
Authors: Ghaemi Zhaleh , Nafiu Oluwadara , Tajkhorshid Emad , Gruebele Martin , Hu Jianming
Published: December 2023

Despite a vaccine, hepatitis B virus (HBV) remains a world-wide source of infections and deaths. We develop a whole-cell computational platform combining spatial and kinetic models describing the infection cycle of HBV in a hepatocyte host. We simulate key parts of the infection cycle with this whole-cell platform for 10 min of biological time, to predict infection progression, map out virus-host and virus-drug interactions. We find that starting from an established infection, decreasing the copy number of the viral envelope proteins shifts the dominant infection pathway from capsid secretion to re-importing the capsids into the nucleus, resulting in more nuclear-localized viral covalently closed circular DNA (cccDNA) and boosting transcription. This scenario can mimic the consequence of drugs designed to manipulate viral gene expression. Mutating capsid proteins facilitates capsid destabilization and disassembly at nuclear pore complexes, resulting in an increase in cccDNA copy number. However, excessive destabilization leads to premature cytoplasmic disassembly and does not increase the cccDNA counts. Finally, our simulations can predict the best drug dosage and its administration timing to reduce the cccDNA counts. Our adaptable computational platform can be parameterized to study other viruses and identify the most central viral pathways that can be targeted by drugs.
African dust transport and deposition modelling verified through a citizen science campaign in Finland
Authors: Meinander Outi , Kouznetsov Rostislav , Uppstu Andreas , Sofiev Mikhail , Kaakinen Anu , Salminen Johanna , Rontu Laura , Welti André , Francis Diana , Piedehierro Ana A. , Heikkilä Pasi , Heikkinen Enna , Laaksonen Ari
Published: December 2023

African desert dust is emitted and long-range transported with multiple effects on climate, air quality, cryosphere, and ecosystems. On 21–23 February 2021, dust from a sand and dust storm in northern Africa was transported to Finland, north of 60°N. The episode was predicted 5 days in advance by the global operational SILAM forecast, and its key features were confirmed and detailed by a retrospective analysis. The scavenging of dust by snowfall and freezing rain in Finland resulted in a rare case of substantial mineral dust contamination of snow surfaces over a large area in the southern part of the country. A citizen science campaign was set up to collect contaminated snow samples prepared according to the scientists’ instructions. The campaign gained wide national interest in television, radio, newspapers and social media, and dust samples were received from 525 locations in Finland, up to 64.3°N. The samples were utilised in investigating the ability of an atmospheric dispersion model to simulate the dust episode. The analysis confirmed that dust came from a wide Sahara and Sahel area from 5000 km away. Our results reveal the features of this rare event and demonstrate how deposition samples can be used to evaluate the skills and limitations of current atmospheric models in simulating transport of African dust towards northern Europe.
Sustainable utilization of the vegetable oil manufacturing waste product in the formulation of eco-friendly emulsifiable cutting fluids
Authors: Hassan Toka , Kandeel Eman M. , Taher M. S. , Badr Entsar E. , El-Tabei A. S.
Published: December 2023

The conventional Metal cutting fluids (MCFs) used are mineral-based petroleum oils that perform well but are toxic and difficult to dispose of; therefore, these are hazardous to human health as well as the environment. This issue can be solved by using natural vegetable oil-based MCF, which are readily available, environment and human-friendly, and renewable. Therefore, we synthesized various types of emulsifiers (anionic, and nonionic with different ethylene oxide units as well as mono and gemini cationic surfactants as corrosion inhibitors and biocides) based on recycled vegetable oil (RO) from spent bleaching earth (SBE), and elucidated their chemical structures by different spectroscopic techniques. The individually synthesized emulsifiers (anionic, and nonionic with different ethylene oxide units) at different ratios (8–15 by wt.%) and mixed emulsifiers (anionic/nonionic, nonionic/nonionic with different degrees of ethylene oxide) at different ratios (8–12 by wt.%) were utilized as additives in the preparation of different vegetable residual oil-based MCF formulations. The mixed emulsifiers at different ratios of nonionic/nonionic with hydrophilic-lipophilic balance (HLB) value 10 (Formulas I, II, III, and IV), and anionic/nonionic (Formula V, and VI) exhibited stable emulsions compared to individual emulsifiers. Formulas (I and VI) displayed good protection effectiveness in corrosion tests. Formula VI had better wettability (25.22 on CS, 23.68 on Al, and 22.28 on WC) and a smaller particle size (63.97 nm). Tribological properties of Formula VI were also performed. The results exhibit that Formula VI is consistent with the commercial sample. As a result, this study contributed to the resolution of one of the industry's problems
Startup process, safety and risk assessment of biomass gasification for off-grid rural electrification
Authors: Rahman Md Mashiur , Henriksen Ulrik Birk , Ciolkosz Daniel
Published: December 2023

Biomass gasification has significantly advanced in terms of performance and is increasingly used in rural off-grid electricity applications. The downdraft gasifier is primarily used in biomass gasification applications, in which it functions as a reactor into which biomass and gasifying air are introduced to generate producer gas that is then used in an engine generator to produce electricity. However, the safety and stability of biomass gasification remain challenging and depend on several factors, such as the startup heating process, which can affect risks of fire, explosion, and toxic gas emissions. As the biomass gasification is associated with high temperatures and demands safety measures, its startup process should follow a rigorous procedure that ensures reliable operation and minimizes the risk of hazard issues. This study presents a gasifier startup heating process based on a proposed safety protocols hazard analysis. The study indicates that the heating temperature in startup processes has been identified as a critical factor due to its role in impacting safety. The findings indicate that the biomass gasification process has significant risks, including the potential for fire, explosion, and release of environmental emissions via multiple pathways. The methods proposed here could lead to reduced risk from the abovementioned issues.
Hydrogen sulfide production in the medullary respiratory center modulates the neural circuit for respiratory pattern and rhythm generations
Authors: Okazaki Minako , Matsumoto Masayuki , Koganezawa Tadachika
Published: December 2023

Hydrogen sulfide (H2S), which is synthesized in the brain, modulates the neural network. Recently, the importance of H2S in respiratory central pattern generation has been recognized, yet the function of H2S in the medullary respiratory network remains poorly understood. Here, to evaluate the functional roles of H2S in the medullary respiratory network, the Bötzinger complex (BötC), the pre-Bötzinger complex (preBötC), and the rostral ventral respiratory group (rVRG), we observed the effects of inhibition of H2S synthesis at each region on the respiratory pattern by using an in situ arterially perfused preparation of decerebrated male rats. After microinjection of an H2S synthase inhibitor, cystathionine β-synthase, into the BötC or preBötC, the amplitude of the inspiratory burst decreased and the respiratory frequency increased according to shorter expiration and inspiration, respectively. These alterations were abolished or attenuated in the presence of a blocker of excitatory synaptic transmission. On the other hand, after microinjection of the H2S synthase inhibitor into the rVRG, the amplitude of the inspiratory burst was attenuated, and the respiratory frequency decreased, which was the opposite effect to those obtained by blockade of inhibitory synaptic transmission at the rVRG. These results suggest that H2S synthesized in the BötC and preBötC functions to limit respiratory frequency by sustaining the respiratory phase and to maintain the power of inspiration. In contrast, H2S synthesized in the rVRG functions to promote respiratory frequency by modulating the interval of inspiration and to maintain the power of inspiration. The underlying mechanism might facilitate excitatory synaptic transmission and/or attenuate inhibitory synaptic transmission.
Pulse-controlled qubit in semiconductor double quantum dots
Authors: Lasek Aleksander , Lepage Hugo V. , Zhang Kexin , Ferrus Thierry , Barnes Crispin H. W.
Published: December 2023

We present a numerically-optimized multipulse framework for the quantum control of a single-electron double quantum dot qubit. Our framework defines a set of pulse sequences, necessary for the manipulation of the ideal qubit basis, that avoids errors associated with excitations outside the computational subspace. A novel control scheme manipulates the qubit adiabatically, while also retaining high speed and ability to perform a general single-qubit rotation. This basis generates spatially localized logical qubit states, making readout straightforward. We consider experimentally realistic semiconductor qubits with finite pulse rise and fall times and determine the fastest pulse sequence yielding the highest fidelity. We show that our protocol leads to improved control of a qubit. We present simulations of a double quantum dot in a semiconductor device to visualize and verify our protocol. These results can be generalized to other physical systems since they depend only on pulse rise and fall times and the energy gap between the two lowest eigenstates.
Neural networks memorise personal information from one sample
Authors: Hartley John , Sanchez Pedro P. , Haider Fasih , Tsaftaris Sotirios A.
Published: December 2023

Deep neural networks (DNNs) have achieved high accuracy in diagnosing multiple diseases/conditions at a large scale. However, a number of concerns have been raised about safeguarding data privacy and algorithmic bias of the neural network models. We demonstrate that unique features (UFs), such as names, IDs, or other patient information can be memorised (and eventually leaked) by neural networks even when it occurs on a single training data sample within the dataset. We explain this memorisation phenomenon by showing that it is more likely to occur when UFs are an instance of a rare concept. We propose methods to identify whether a given model does or does not memorise a given (known) feature. Importantly, our method does not require access to the training data and therefore can be deployed by an external entity. We conclude that memorisation does have implications on model robustness, but it can also pose a risk to the privacy of patients who consent to the use of their data for training models.
Effectiveness of VSV vectored SARS-CoV-2 spike when administered through intranasal, intramuscular or a combination of both
Authors: Beitari Saina , Agbayani Gerard , Hewitt Melissa , Duque Diana , Bavananthasivam Jegarubee , Sandhu Jagdeep K. , Akache Bassel , Hadžisejdić Ita , Tran Anh
Published: December 2023

A critical feature of the VSV vector platform is the ability to pseudotype the virus with different glycoproteins from other viruses, thus altering cellular tropism of the recombinant virus. The route of administration is critical in triggering local and systemic immune response and protection. Most of the vaccine platforms used at the forefront are administered by intramuscular injection. However, it is not known at what level ACE2 is expressed on the surface of skeletal muscle cells, which will have a significant impact on the efficiency of a VSV-SARS-CoV-2 spike vaccine to mount a protective immune response when administered intramuscularly. In this study, we investigate the immunogenicity and efficacy of a prime-boost immunization regimen administered intranasally (IN), intramuscularly (IM), or combinations of the two. We determined that the prime-boost combinations of IM followed by IN immunization (IM + IN) or IN followed by IN immunization (IN + IN) exhibited strong spike-specific IgG, IgA and T cell response in vaccinated K18 knock-in mice. Hamsters vaccinated with two doses of VSV expressing SARS-CoV-2 spike, both delivered by IN or IM + IN, showed strong protection against SARS-CoV-2 variants of concern Alpha and Delta. This protection was also observed in aged hamsters. Our study underscores the highly crucial role immunization routes have with the VSV vector platform to elicit a strong and protective immune response.
In silico drug repurposing carvedilol and its metabolites against SARS-CoV-2 infection using molecular docking and molecular dynamic simulation approaches
Authors: Zhang Chunye , Liu Jiazheng , Sui Yuxiang , Liu Shuai , Yang Ming
Published: December 2023

The pandemic of coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a significant impact on the economy and public health worldwide. Therapeutic options such as drugs and vaccines for this newly emerged disease are eagerly desired due to the high mortality. Using the U.S. Food and Drug Administration (FDA) approved drugs to treat a new disease or entirely different diseases, in terms of drug repurposing, minimizes the time and cost of drug development compared to the de novo design of a new drug. Drug repurposing also has some other advantages such as reducing safety evaluation to accelerate drug application on time. Carvedilol, a non-selective beta-adrenergic blocker originally designed to treat high blood pressure and manage heart disease, has been shown to impact SARS-CoV-2 infection in clinical observation and basic studies. Here, we applied computer-aided approaches to investigate the possibility of repurposing carvedilol to combat SARS-CoV-2 infection. The molecular mechanisms and potential molecular targets of carvedilol were identified by evaluating the interactions of carvedilol with viral proteins. Additionally, the binding affinities of in vivo metabolites of carvedilol with selected targets were evaluated. The docking scores for carvedilol and its metabolites with RdRp were − 10.0 kcal/mol, − 9.8 kcal/mol (1-hydroxyl carvedilol), − 9.7 kcal/mol (3-hydroxyl carvedilol), − 9.8 kcal/mol (4-hydroxyl carvedilol), − 9.7 kcal/mol (5-hydroxyl carvedilol), − 10.0 kcal/mol (8-hydroxyl carvedilol), and − 10.1 kcal/mol (O-desmethyl carvedilol), respectively. Using the molecular dynamics simulation (100 ns) method, we further confirmed the stability of formed complexes of RNA-dependent RNA polymerase (RdRp) and carvedilol or its metabolites. Finally, the drug-target interaction mechanisms that contribute to the complex were investigated. Overall, this study provides the molecular targets and mechanisms of carvedilol and its metabolites as repurposed drugs to fight against SARS-CoV-2 infection.
Impact of chemical reaction on Eyring–Powell fluid flow over a thin needle with nonlinear thermal radiation
Authors: Nadeem Muhammad , Siddique Imran , Saif Ud Din Irfan , Awwad Fuad A. , Ismail Emad A. A. , Ahmad Hijaz
Published: December 2023

The thin needle is viewed as a revolutionary object since it has a thinner thickness than a boundary layer. As a consequence, scientific and engineering applications for instance electrical equipment, hot wire anemometers and geothermal power generation are significantly impacted by the flow deformed by a thin moving needle. MHD Eyring–Powell fluid flow over a thin needle perceiving heat source, chemical reaction and nonlinear thermal radiation is the subject of the current investigation. In addition, the present study utilizes the Buongiorno model to examine the special effects of the fluid's Brownian and thermophoretic forces. The solution of the dimensionless form of ODEs is produced by applying exact renovations to the given problem, which is determined by the structure of PDEs. The bvp4c algorithm, based on the finite difference approach is utilized to numerically solve such modified ODEs. For validation, the results obtained indicate good agreement when compared to the literature. Finally, a detailed graphical analysis of key parameters is shown and explained while keeping in mind the physical significance of flow parameters. The results show that as magnetic and fluid parameter values improve, the velocity gradient falls. Increasing heat source and radiation parameters optimises heat transfer rate. The augmentation of the Lewis number and chemical reaction accelerates the rate of mass transfer on the surface. Brownian motion and thermophoresis provide enhanced thermal performance for the fluid temperature. Growing the thermophoresis parameter from 0.1 to 0.3 upsurges the Nusselt number by 5.47% and the Sherwood number by 12.26%.
Molecular epidemiology and drug sensitivity of Mycobacterium tuberculosis in homeless individuals in the Addis Ababa city, Ethiopia
Authors: Shamebo Tsegaye , Gumi Balako , Zewude Aboma , Gashaw Fikru , Mohammed Temesgen , Girma Muse , Zerihun Betselot , Getu Melak , Mekasha Sindew , Getahun Muluwork , Wondale Biniam , Petros Beyene , Ameni Gobena
Published: December 2023

Although homeless segment of the society could be the hotspots for tuberculosis (TB) transmission, there is little data on TB in homeless individuals in Ethiopia. The objective of this study was to investigate the molecular epidemiology and drug sensitivity of Mycobacterium tuberculosis (M. tuberculosis) isolated from homeless individuals in Addis Ababa, Ethiopia. The study was conducted on 59 M. tuberculosis isolates, which were recovered by the clinical screening of 5600 homeless individuals and bacteriological examination of 641 individuals with symptoms of pulmonary tuberculosis (PTB). Region of difference-9 (RD9) based polymerase-chain reaction (PCR), Spoligotyping and 24-loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing were used for genotyping of the isolates. In addition, drug sensitivity test was performed on the isolates using BD Bactec Mycobacterial Growth Inhibition Tube (MGIT) 960. Fifty-eight of the 59 isolates were positive by spoligotyping and spoligotyping International type (SIT) 53, SIT 37, and SIT 149 were the dominant spoligotypes; each consisting of 19%, 15.5%, and10.3% of the isolates, respectively. The majority of the isolates (89.7%) were members of the Euro-American (EA) major lineage. MIRU-VNTR identified Ethiopia_3, Delhi/CAS, Ethiopia_2, TUR, X-type, Ethiopia_H37Rv-like strain, Haarlem and Latin-American Mediterranean (LAM) sub lineages. The proportion of clustering was 77.6% (45/58) in spoligotyping while it was 39.7% (23/58) in 24-loci MIRU-VNTR typing. Furthermore, the proportion of clustering was significantly lowered to 10.3% (6/58) when a combination of spoligotyping and 24-loci MIRU-VNTRplus was used. The recent transmission index (RTI) recorded by spoligotyping, 24-loci MIRU-VNTR typing, and a combination of the two genotyping methods were 58.6%, 27.6% and 5.2%, respectively. Young age and living in groups were significantly associated with strain clustering (P < 0.05). The drug sensitivity test (DST) result showed 8.9% (4/58) of the isolates were resistant to one or more first line ant-TB drugs; but multidrug resistant isolate was not detected. Clustering and RTI could suggest the transmission of TB in the homeless individuals, which could suggest a similar pattern of transmission between homeless individuals and the general population. Hence, the TB control program should consider homeless individuals during the implementation of TB control program.
High levels of alpha-gal with large variation in the salivary glands of lone star ticks fed on human blood
Authors: Maldonado-Ruiz L. Paulina , Reif Kathryn E. , Ghosh Anuradha , Foré Stephanie , Johnson Rachel L. , Park Yoonseong
Published: December 2023

Tick bites, associated with the secretion of tick saliva containing the xenoglycan galactose-alpha-1, 3-galactose (alpha-gal or aGal), are recognized as the causal factors of alpha-Gal syndrome (AGS; or red meat allergy) in humans. AGS occurs after the increased production of IgE antibodies against aGal, which is found in most mammalian cells, except for the Old World monkey and humans. The aGal sensitization event has been linked to an initial tick bite, followed by consumption of red meat containing the aGal glycan, which triggers the onset of the allergic response resulting in urticaria, anaphylaxis, or even death. In North America, the lone star tick, Amblyomma americanum, has been identified as the main culprit for AGS. However, only a subset of the human population exposed to lone star tick bites develops AGS. This suggests the presence of unidentified variables associated with the sensitization event. To evaluate the quantitative variations of the aGal in ticks, we evaluated the differences in aGal levels in different strains of A. americanum ticks partially fed on different blood sources using an artificial feeding system and animal hosts. We found significantly higher aGal levels in the female ticks fed on human blood than those fed on the blood of other mammals with large variations among different tick populations and individuals. We propose that host-specific genetic components in the A. americanum ticks are involved in the production of high aGal epitope in the tick saliva, which provides a part of the explanation for the variables associated with the AGS sensitization event of the tick bite.
Social information modifies the associations between forest fragmentation and the abundance of a passerine bird
Authors: Bełcik Michał , Lenda Magdalena Lidia , Pustkowiak Sylwia , Woźniak Bartłomiej , Skórka Piotr
Published: December 2023

Habitat loss and fragmentation are the main factors driving the occurrence and abundance of species in the landscape. However, the local occurrence and abundance of species may also depend on conspecific and heterospecific social information e.g. clues of animals’ presence or their voices. We investigated the impact of the interaction between different types of social information and forest fragmentation on the abundance of the song thrush, Turdus philomelos, in Central Europe. Three types of social information (attractive, repulsive, and mixed) and procedural control were broadcasted via loudspeakers in 150 forest patches that varied in size and isolation metrics. Repulsive social information (cues of presence of predator) decreased abundance of song thrush. Also, the repulsive social information changed the association between forest patch isolation, size and the abundance. Attractive social information (songs of the studied thrush) had no effect on song thrush abundance. However, the attractive social information reversed the positive correlation between habitat patch size and the abundance. Mixed social information (both repulsive and attractive) had no impact on the abundance nor interacted with habitat fragmentation. The observed effects mostly did not last to the next breeding season. Overall, our findings indicate that lands of fear and social attraction could modify the effect of habitat fragmentation on the species abundance but these effects probably are not long-lasting.
Analog monolayer SWCNTs-based memristive 2D structure for energy-efficient deep learning in spiking neural networks
Authors: Abunahla Heba , Abbas Yawar , Gebregiorgis Anteneh , Waheed Waqas , Mohammad Baker , Hamdioui Said , Alazzam Anas , Rezeq Moh’d
Published: December 2023

Advances in materials science and memory devices work in tandem for the evolution of Artificial Intelligence systems. Energy-efficient computation is the ultimate goal of emerging memristor technology, in which the storage and computation can be done in the same memory crossbar. In this work, an analog memristor device is fabricated utilizing the unique characteristics of single-wall carbon nanotubes (SWCNTs) to act as the switching medium of the device. Via the planar structure, the memristor device exhibits analog switching ability with high state stability. The device’s conductance and capacitance can be tuned simultaneously, increasing the device's potential and broadening its applications' horizons. The multi-state storage capability and long-term memory are the key factors that make the device a promising candidate for bio-inspired computing applications. As a demonstrator, the fabricated memristor is deployed in spiking neural networks (SNN) to exploit its analog switching feature for energy-efficient classification operation. Results reveal that the computation-in-memory implementation performs Vector Matrix Multiplication with 95% inference accuracy and few femtojoules per spike energy efficiency. The memristor device presented in this work opens new insights towards utilizing the outstanding features of SWCNTs for efficient analog computation in deep learning systems.
Development and validation of a blood routine-based extent and severity clinical decision support tool for ulcerative colitis
Authors: Chen Hongliang , Lin Xindi , Pan Xinyue , Xu Hongyu , Zhang Xuemei , Liang Guoying , Qiu Jiawei , Zhang Xueyan , Gao Yang , Tan Xin , Li Ning , Cai Huimin , Cang Xueyu , Qi Jihan , Li Wei , Li Shuang , Zheng Yutong , Zhao Lei , Jin Shizhu
Published: December 2023

Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/. Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.