bluuebunny/crossref_metadata_2025 huggingface dataset:
A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly
Authors: Lyu Quanxia , Gong Shu , Lees Jarmon G. , Yin Jialiang , Yap Lim Wei , Kong Anne M. , Shi Qianqian , Fu Runfang , Zhu Qiang , Dyer Ash , Dyson Jennifer M. , Lim Shiang Y. , Cheng Wenlong
Published: November 2022

Time-lapse mechanical properties of stem cell derived cardiac organoids are important biological cues for understanding contraction dynamics of human heart tissues, cardiovascular functions and diseases. However, it remains difficult to directly, instantaneously and accurately characterize such mechanical properties in real-time and in situ because cardiac organoids are topologically complex, three-dimensional soft tissues suspended in biological media, which creates a mismatch in mechanics and topology with state-of-the-art force sensors that are typically rigid, planar and bulky. Here, we present a soft resistive force-sensing diaphragm based on ultrasensitive resistive nanocracked platinum film, which can be integrated into an all-soft culture well via an oxygen plasma-enabled bonding process. We show that a reliable organoid-diaphragm contact can be established by an ‘Atomic Force Microscope-like’ engaging process. This allows for instantaneous detection of the organoids’ minute contractile forces and beating patterns during electrical stimulation, resuscitation, drug dosing, tissue culture, and disease modelling.
circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment
Authors: Piras Roberta , Ko Emily Y. , Barrett Connor , De Simone Marco , Lin Xianzhi , Broz Marina T. , Tessaro Fernando H. G. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Goodridge Helen S. , Di Vizio Dolores , Batish Mona , Lawrenson Kate , Chen Y. Grace , Chan Keith Syson , Guarnerio Jlenia
Published: November 2022

Exonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed in soft tissue sarcoma cells and explore how the circRNAs regulate sarcoma growth in vivo. We show that circCsnk1g3 and circAnkib1 promote tumor growth by shaping a pro-tumorigenic microenvironment, possibly due to their capabilities to regulate tumor-promoting elements extrinsic to the tumor cells. Accordingly, circCsnk1g3 and circAnkib1 can control the expression of interferon-related genes and pro-inflammatory factors in the sarcoma cells, thus directing immune cell recruitment into the tumor mass, and hence their activation. Mechanistically, circRNAs may repress pro-inflammatory elements by buffering activation of the pathways mediated by RIG-I, the cytosolic viral RNA sensor. The current findings suggest that the targeting of specific circRNAs could augment the efficacy of tumor and immune response to mainstay therapies.
CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Authors: Pierson Sheila K. , Katz Laura , Williams Reece , Mumau Melanie , Gonzalez Michael , Guzman Stacy , Rubenstein Ayelet , Oromendia Ana B. , Beineke Philip , Fosså Alexander , van Rhee Frits , Fajgenbaum David C.
Published: November 2022

Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD.
Holocene hydroclimatic variability in the tropical Pacific explained by changing ENSO diversity
Authors: Karamperidou Christina , DiNezio Pedro N.
Published: November 2022

Understanding El Niño-Southern Oscillation (ENSO) response to past climate forcings is hindered by conflicting paleoclimate evidence. Records from the eastern Pacific show an intensification of ENSO variability from early to late Holocene, while records from the central Pacific show highly variable ENSO throughout the Holocene without an obvious relation to insolation forcing, which is the main climate driver during this interval. Here, we show via climate model simulations that conflicting Holocene records can be reconciled by considering changes in the relative frequency of the three preferred spatial patterns in which El Niño events occur (Eastern Pacific, Central Pacific, and Coastal) and in the strength of their hydroclimatic impacts. The relationship between ENSO diversity and variance is not only crucial for interpreting paleo-ENSO records and understanding ENSO response to external forcings but can also be used across climate model simulations to help evaluate the realism of ENSO projections in a changing climate.
AlphaPeptDeep: a modular deep learning framework to predict peptide properties for proteomics
Authors: Zeng Wen-Feng , Zhou Xie-Xuan , Willems Sander , Ammar Constantin , Wahle Maria , Bludau Isabell , Voytik Eugenia , Strauss Maximillian T. , Mann Matthias
Published: November 2022

Machine learning and in particular deep learning (DL) are increasingly important in mass spectrometry (MS)-based proteomics. Recent DL models can predict the retention time, ion mobility and fragment intensities of a peptide just from the amino acid sequence with good accuracy. However, DL is a very rapidly developing field with new neural network architectures frequently appearing, which are challenging to incorporate for proteomics researchers. Here we introduce AlphaPeptDeep, a modular Python framework built on the PyTorch DL library that learns and predicts the properties of peptides (https://github.com/MannLabs/alphapeptdeep). It features a model shop that enables non-specialists to create models in just a few lines of code. AlphaPeptDeep represents post-translational modifications in a generic manner, even if only the chemical composition is known. Extensive use of transfer learning obviates the need for large data sets to refine models for particular experimental conditions. The AlphaPeptDeep models for predicting retention time, collisional cross sections and fragment intensities are at least on par with existing tools. Additional sequence-based properties can also be predicted by AlphaPeptDeep, as demonstrated with a HLA peptide prediction model to improve HLA peptide identification for data-independent acquisition (https://github.com/MannLabs/PeptDeep-HLA).
Insights into protein post-translational modification landscapes of individual human cells by trapped ion mobility time-of-flight mass spectrometry
Authors: Orsburn Benjamin C. , Yuan Yuting , Bumpus Namandjé N.
Published: November 2022

Single cell proteomics is a powerful tool with potential for markedly enhancing understanding of cellular processes. Here we report the development and application of multiplexed single cell proteomics using trapped ion mobility time-of-flight mass spectrometry. When employing a carrier channel to improve peptide signal, this method allows over 40,000 tandem mass spectra to be acquired in 30 min. Using a KRASG12C model human-derived cell line, we demonstrate the quantification of over 1200 proteins per cell with high relative sequence coverage permitting the detection of multiple classes of post-translational modifications in single cells. When cells were treated with a KRASG12C covalent inhibitor, this approach revealed cell-to-cell variability in the impact of the drug, providing insight missed by traditional proteomics. We provide multiple resources necessary for the application of single cell proteomics to drug treatment studies including tools to reduce cell cycle linked proteomic effects from masking pharmacological phenotypes.
Global landscape of replicative DNA polymerase usage in the human genome
Authors: Koyanagi Eri , Kakimoto Yoko , Minamisawa Tamiko , Yoshifuji Fumiya , Natsume Toyoaki , Higashitani Atsushi , Ogi Tomoo , Carr Antony M. , Kanemaki Masato T. , Daigaku Yasukazu
Published: November 2022

The division of labour among DNA polymerase underlies the accuracy and efficiency of replication. However, the roles of replicative polymerases have not been directly established in human cells. We developed polymerase usage sequencing (Pu-seq) in HCT116 cells and mapped Polε and Polα usage genome wide. The polymerase usage profiles show Polε synthesises the leading strand and Polα contributes mainly to lagging strand synthesis. Combining the Polε and Polα profiles, we accurately predict the genome-wide pattern of fork directionality plus zones of replication initiation and termination. We confirm that transcriptional activity contributes to the pattern of initiation and termination and, by separately analysing the effect of transcription on co-directional and converging forks, demonstrate that coupled DNA synthesis of leading and lagging strands is compromised by transcription in both co-directional and convergent forks. Polymerase uncoupling is particularly evident in the vicinity of large genes, including the two most unstable common fragile sites, FRA3B and FRA3D, thus linking transcription-induced polymerase uncoupling to chromosomal instability. Together, our result demonstrated that Pu-seq in human cells provides a powerful and straightforward methodology to explore DNA polymerase usage and replication fork dynamics.
Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter
Authors: Yamagata Atsushi , Murata Yoshiko , Namba Kosuke , Terada Tohru , Fukai Shuya , Shirouzu Mikako
Published: November 2022

Calcareous soils cover one-third of all land and cause severe growth defects in plants due to the poor water solubility of iron at high pH. Poaceae species use a unique chelation strategy, whereby plants secrete a high-affinity metal chelator, known as phytosiderophores (mugineic acids), and reabsorb the iron-phytosiderophore complex by the yellow stripe 1/yellow stripe 1-like (YS1/YSL) transporter for efficient uptake of iron from the soil. Here, we present three cryo-electron microscopy structures of barley YS1 (HvYS1) in the apo state, in complex with an iron-phytosiderophore complex, Fe(III)-deoxymugineic acid (Fe(III)–DMA), and in complex with the iron-bound synthetic DMA analog (Fe(III)–PDMA). The structures reveal a homodimeric assembly mediated through an anti-parallel β-sheet interaction with cholesterol hemisuccinate. Each protomer adopts an outward open conformation, and Fe(III)–DMA is bound near the extracellular space in the central cavity. Fe(III)–PDMA occupies the same binding site as Fe(III)–DMA, demonstrating that PDMA can function as a potent fertilizer in an essentially identical manner to DMA. Our results provide a structural framework for iron-phytosiderophore recognition and transport by YS1/YSL transporters, which will enable the rational design of new, high-potency fertilizers.
Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death
Authors: Scur Michal , Mahmoud Ahmad Bakur , Dey Sayanti , Abdalbarri Farah , Stylianides Iona , Medina-Luna Daniel , Gamage Gayani S. , Woblistin Aaron , Wilson Alexa N. M. , Zein Haggag S. , Stueck Ashley , Wight Andrew , Aguilar Oscar A. , Di Cara Francesca , Parsons Brendon D. , Rahim Mir Munir A. , Carlyle James R. , Makrigiannis Andrew P.
Published: November 2022

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming.Nkrp1b−/−mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM ofNkrp1b−/−mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.
The molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane
Authors: Matthaeus Claudia , Sochacki Kem A. , Dickey Andrea M. , Puchkov Dmytro , Haucke Volker , Lehmann Martin , Taraska Justin W.
Published: November 2022

Caveolae are small coated plasma membrane invaginations with diverse functions. Caveolae undergo curvature changes. Yet, it is unclear which proteins regulate this process. To address this gap, we develop a correlative stimulated emission depletion (STED) fluorescence and platinum replica electron microscopy imaging (CLEM) method to image proteins at single caveolae. Caveolins and cavins are found at all caveolae, independent of curvature. EHD2 is detected at both low and highly curved caveolae. Pacsin2 associates with low curved caveolae and EHBP1 with mostly highly curved caveolae. Dynamin is absent from caveolae. Cells lacking dynamin show no substantial changes to caveolae, suggesting that dynamin is not directly involved in caveolae curvature. We propose a model where caveolins, cavins, and EHD2 assemble as a cohesive structural unit regulated by intermittent associations with pacsin2 and EHBP1. These coats can flatten and curve to enable lipid traffic, signaling, and changes to the surface area of the cell.
High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
Authors: Ouyang Ruochen , Costa Ana Rita , Cassidy C. Keith , Otwinowska Aleksandra , Williams Vera C. J. , Latka Agnieszka , Stansfeld Phill J. , Drulis-Kawa Zuzanna , Briers Yves , Pelt Daniël M. , Brouns Stan J. J. , Briegel Ariane
Published: November 2022

The Klebsiella jumbo myophage ϕKp24 displays an unusually complex arrangement of tail fibers interacting with a host cell. In this study, we combine cryo-electron microscopy methods, protein structure prediction methods, molecular simulations, microbiological and machine learning approaches to explore the capsid, tail, and tail fibers of ϕKp24. We determine the structure of the capsid and tail at 4.1 Å and 3.0 Å resolution. We observe the tail fibers are branched and rearranged dramatically upon cell surface attachment. This complex configuration involves fourteen putative tail fibers with depolymerase activity that provide ϕKp24 with the ability to infect a broad panel of capsular polysaccharide (CPS) types of Klebsiella pneumoniae. Our study provides structural and functional insight into how ϕKp24 adapts to the variable surfaces of capsulated bacterial pathogens, which is useful for the development of phage therapy approaches against pan-drug resistant K. pneumoniae strains.
Water induced ultrathin Mo2C nanosheets with high-density grain boundaries for enhanced hydrogen evolution
Authors: Yang Yang , Qian Yumin , Luo Zhaoping , Li Haijing , Chen Lanlan , Cao Xumeng , Wei Shiqiang , Zhou Bo , Zhang Zhenhua , Chen Shuai , Yan Wenjun , Dong Juncai , Song Li , Zhang Wenhua , Feng Renfei , Zhou Jigang , Du Kui , Li Xiuyan , Zhang Xian-Ming , Fan Xiujun
Published: November 2022

Grain boundary controlling is an effective approach for manipulating the electronic structure of electrocatalysts to improve their hydrogen evolution reaction performance. However, probing the direct effect of grain boundaries as highly active catalytic hot spots is very challenging. Herein, we demonstrate a general water-assisted carbothermal reaction strategy for the construction of ultrathin Mo2C nanosheets with high-density grain boundaries supported on N-doped graphene. The polycrystalline Mo2C nanosheets are connected with N-doped graphene through Mo–C bonds, which affords an ultra-high density of active sites, giving excellent hydrogen evolution activity and superior electrocatalytic stability. Theoretical calculations reveal that the dz2 orbital energy level of Mo atoms is controlled by the MoC3 pyramid configuration, which plays a vital role in governing the hydrogen evolution activity. The dz2 orbital energy level of metal atoms exhibits an intrinsic relationship with the catalyst activity and is regarded as a descriptor for predicting the hydrogen evolution activity.
Comparison of antibody responses to SARS-CoV-2 variants in Australian children
Authors: Toh Zheng Quan , Mazarakis Nadia , Nguyen Jill , Higgins Rachel A. , Anderson Jeremy , Do Lien Anh Ha , Burgner David P. , Curtis Nigel , Steer Andrew C. , Mulholland Kim , Crawford Nigel W. , Tosif Shidan , Licciardi Paul V.
Published: November 2022

There is limited understanding of antibody responses in children across different SARS-CoV-2 variants. As part of an ongoing household cohort study, we assessed the antibody response among unvaccinated children infected with Wuhan, Delta, or Omicron variants, as well as vaccinated children with breakthrough Omicron infection, using a SARS-CoV-2 S1-specific IgG assay and surrogate virus neutralization test (% inhibition). Most children infected with Delta (100%, 35/35) or Omicron (81.3%, 13/16) variants seroconverted by one month following infection. In contrast, 37.5% (21/56) children infected with Wuhan seroconverted, as previously reported. However, Omicron-infected children (geometric mean concentration 46.4 binding antibody units/ml; % inhibition = 16.3%) mounted a significantly lower antibody response than Delta (435.5 binding antibody untis/mL, % inhibition = 76.9%) or Wuhan (359.0 binding antibody units/mL, % inhibition = 74.0%). Vaccinated children with breakthrough Omicron infection mounted the highest antibody response (2856 binding antibody units/mL, % inhibition = 96.5%). Our findings suggest that despite a high seropositivity rate, Omicron infection in children results in lower antibody levels and function compared with Wuhan or Delta infection or with vaccinated children with breakthrough Omicron infection. Our data have important implications for public health measures and vaccination strategies to protect children.
Unexpectedly efficient ion desorption of graphene-based materials
Authors: Xia Xinming , Zhou Feng , Xu Jing , Wang Zhongteng , Lan Jian , Fan Yan , Wang Zhikun , Liu Wei , Chen Junlang , Feng Shangshen , Tu Yusong , Yang Yizhou , Chen Liang , Fang Haiping
Published: November 2022

Ion desorption is extremely challenging for adsorbents with superior performance, and widely used conventional desorption methods involve high acid or base concentrations and large consumption of reagents. Here, we experimentally demonstrate the rapid and efficient desorption of ions on magnetite-graphene oxide (M-GO) by adding low amounts of Al3+. The corresponding concentration of Al3+ used is reduced by at least a factor 250 compared to conventional desorption method. The desorption rate reaches ~97.0% for the typical radioactive and bivalent ions Co2+, Mn2+, and Sr2+ within ~1 min. We achieve effective enrichment of radioactive 60Co and reduce the volume of concentrated 60Co solution by approximately 10 times compared to the initial solution. The M-GO can be recycled and reused easily without compromising its adsorption efficiency and magnetic performance, based on the unique hydration anionic species of Al3+ under alkaline conditions. Density functional theory calculations show that the interaction of graphene with Al3+ is stronger than with divalent ions, and that the adsorption probability of Al3+ is superior than that of Co2+, Mn2+, and Sr2+ ions. This suggests that the proposed method could be used to enrich a wider range of ions in the fields of energy, biology, environmental technology, and materials science.
Active matter in space
Authors: Volpe Giorgio , Bechinger Clemens , Cichos Frank , Golestanian Ramin , Löwen Hartmut , Sperl Matthias , Volpe Giovanni
Published: November 2022

In the last 20 years, active matter has been a highly dynamic field of research, bridging fundamental aspects of non-equilibrium thermodynamics with applications to biology, robotics, and nano-medicine. Active matter systems are composed of units that can harvest and harness energy and information from their environment to generate complex collective behaviours and forms of self-organisation. On Earth, gravity-driven phenomena (such as sedimentation and convection) often dominate or conceal the emergence of these dynamics, especially for soft active matter systems where typical interactions are of the order of the thermal energy. In this review, we explore the ongoing and future efforts to study active matter in space, where low-gravity and microgravity conditions can lift some of these limitations. We envision that these studies will help unify our understanding of active matter systems and, more generally, of far-from-equilibrium physics both on Earth and in space. Furthermore, they will also provide guidance on how to use, process and manufacture active materials for space exploration and colonisation.
Estimating the randomness of quantum circuit ensembles up to 50 qubits
Authors: Liu Minzhao , Liu Junyu , Alexeev Yuri , Jiang Liang
Published: November 2022

Random quantum circuits have been utilized in the contexts of quantum supremacy demonstrations, variational quantum algorithms for chemistry and machine learning, and blackhole information. The ability of random circuits to approximate any random unitaries has consequences on their complexity, expressibility, and trainability. To study this property of random circuits, we develop numerical protocols for estimating the frame potential, the distance between a given ensemble and the exact randomness. Our tensor-network-based algorithm has polynomial complexity for shallow circuits and is high-performing using CPU and GPU parallelism. We study 1. local and parallel random circuits to verify the linear growth in complexity as stated by the Brown–Susskind conjecture, and; 2. hardware-efficient ansätze to shed light on its expressibility and the barren plateau problem in the context of variational algorithms. Our work shows that large-scale tensor network simulations could provide important hints toward open problems in quantum information science.
Enviroscore: normalization, weighting, and categorization algorithm to evaluate the relative environmental impact of food and drink products
Authors: Ramos Saioa , Segovia Lucia , Melado-Herreros Angela , Cidad Maite , Zufía Jaime , Vranken Liesbet , Matthys Christophe
Published: November 2022

A 5-scale label that relativizes the environmental impact of a given product referred to the impact of the European food basket is proposed. It was developed based on the Product Environmental Footprint methodology with the following stepwise approach. First, a set of normalization and weighting factors were defined to aggregate all the environmental impact categories into a single dimensionless index referred to as the European food basket, coined the European Food Environmental Footprint Single Index (EFSI). Next, the effectiveness of the EFSI index was evaluated by assessing the distribution of the EFSI results on 149 hypothetical food items and comparing it with the results obtained with EC Single Score. Finally, the thresholds to translate the EFSI index into the 5-scale Enviroscore (A, B, C, D, and E) were established and validated using the Delphi method. Results indicated that both, Enviroscore and EFSI, were able to account for impact variability between and within food products. Differences on the final score were observed due to the type of products (vegetables vs. animal products), the country of origin and the mean of transportation. Regarding country of origin, results indicated that differences in water stress impact category were better captured by the EFSI index (r = 0.624) than by the EC Single Score (r = 0.228). Finally, good agreement achieved with the Delphi method (weighted Kappa 0.642; p = 0.0025), ensures the acceptability of the Enviroscore. In conclusion, this study developed a method to communicate environmental impact assessment in a front-of-packaging label.
Within-job gender pay inequality in 15 countries
Authors: Penner Andrew M. , Petersen Trond , Hermansen Are Skeie , Rainey Anthony , Boza István , Elvira Marta M. , Godechot Olivier , Hällsten Martin , Henriksen Lasse Folke , Hou Feng , Mrčela Aleksandra Kanjuo , King Joe , Kodama Naomi , Kristal Tali , Křížková Alena , Lippényi Zoltán , Melzer Silvia Maja , Mun Eunmi , Apascaritei Paula , Avent-Holt Dustin , Bandelj Nina , Hajdu Gergely , Jung Jiwook , Poje Andreja , Sabanci Halil , Safi Mirna , Soener Matthew , Tomaskovic-Devey Donald , Tufail Zaibu
Published: November 2022

Extant research on the gender pay gap suggests that men and women who do the same work for the same employer receive similar pay, so that processes sorting people into jobs are thought to account for the vast majority of the pay gap. Data that can identify women and men who do the same work for the same employer are rare, and research informing this crucial aspect of gender differences in pay is several decades old and from a limited number of countries. Here, using recent linked employer–employee data from 15 countries, we show that the processes sorting people into different jobs account for substantially less of the gender pay differences than was previously believed and that within-job pay differences remain consequential.
AlphaFill: enriching AlphaFold models with ligands and cofactors
Authors: Hekkelman Maarten L. , de Vries Ida , Joosten Robbie P. , Perrakis Anastassis
Published: November 2022

Artificial intelligence-based protein structure prediction approaches have had a transformative effect on biomolecular sciences. The predicted protein models in the AlphaFold protein structure database, however, all lack coordinates for small molecules, essential for molecular structure or function: hemoglobin lacks bound heme; zinc-finger motifs lack zinc ions essential for structural integrity and metalloproteases lack metal ions needed for catalysis. Ligands important for biological function are absent too; no ADP or ATP is bound to any of the ATPases or kinases. Here we present AlphaFill, an algorithm that uses sequence and structure similarity to ‘transplant’ such ‘missing’ small molecules and ions from experimentally determined structures to predicted protein models. The algorithm was successfully validated against experimental structures. A total of 12,029,789 transplants were performed on 995,411 AlphaFold models and are available together with associated validation metrics in the alphafill.eu databank, a resource to help scientists make new hypotheses and design targeted experiments.
Rhodiola pre-conditioning reduces exhaustive exercise-induced myocardial injury of insulin resistant mice
Authors: You Baiyang , Cheng Jing , Dun Yaoshan , Ripley-Gonzalez Jeffrey W. , Liu Jie , Li Dezhao , Fu Siqian , Hong Chuangxiong , Liu Suixin
Published: November 2022

Myocardial injury reduction and recovery under acute cardiac stress are adversely impacted by insulin resistance (IR). We previously demonstrated that Rhodiola improved cardiac anti-stress capacity in mice. Thus, this study focuses on the preventive efficacy of Rhodiola on exhaustive exercise (EE)-induced myocardial injury of IR mice. An 8-week high-fat diet (HFD) model of IR mice was established. Rhodiola was administrated by garaging. After the 8-week intervention, half of the mice performed EE to simulate acute cardiac stress, and determine myocardial injury; The remaining mice were sacrificed following fasting to assess metabolic disorder. We found myocardial injury induced by EE in IR mice was worse and was alleviated by Rhodiola pre-conditioning. Further, the nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidant system was impaired by HFD, while mitochondrial dynamic fusion and fission were activated by HFD as a physiological protective compensation. The Rhodiola administration rescued Nrf2 impairment and further facilitated mitochondrial fusion and fission. All these results indicate that Rhodiola is a potential treatment for the prevention of cardiac events in type 2 diabetes mellitus and metabolic syndrome patients, and the Nrf2-related antioxidant activity and mitochondrial dynamics are the proposed mechanisms.
Predicting the potential global distribution of an invasive alien pest Trioza erytreae (Del Guercio) (Hemiptera: Triozidae)
Authors: Aidoo Owusu Fordjour , Souza Philipe Guilherme Corcino , da Silva Ricardo Siqueira , Júnior Paulo Antonio Santana , Picanço Marcelo Coutinho , Kyerematen Rosina , Sétamou Mamoudou , Ekesi Sunday , Borgemeister Christian
Published: November 2022

The impact of invasive alien pests on agriculture, food security, and biodiversity conservation has been worsened by climate change caused by the rising earth’s atmospheric greenhouse gases. The African citrus triozid, Trioza erytreae (Del Guercio; Hemiptera: Triozidae), is an invasive pest of all citrus species. It vectors the phloem-limited bacterium “Candidatus Liberibacter africanus”, a causal agent of citrus greening disease or African Huanglongbing (HLB). Understanding the global distribution of T. erytreae is critical for surveillance, monitoring, and eradication programs. Therefore, we combined geospatial and physiological data of T. erytreae to predict its global distribution using the CLIMEX model. The model’s prediction matches T. erytreae present-day distribution and shows that parts of the Mediterranean region have moderate (0 < EI < 30) to high (EI > 30) suitability for the pest. The model predicts habitat suitability in the major citrus-producing countries, such as Mexico, Brazil, China, India, and the USA. In the Special Report on Emissions Scenarios (SRES) A1B and A2 scenarios, the model predicts a reduction in habitat suitability from the current time to 2070. The findings show that global citrus production will continue to be threatened by T. erytreae. However, our study provides relevant information for biosecurity and risk assessment.
Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4+ regulatory T cells
Authors: Mensink Mark , Schrama Ellen , Cuadrado Eloy , Amsen Derk , de Kivit Sander , Borst Jannie
Published: November 2022

The CD4+ regulatory T (Treg) cell lineage, defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. As a model for Treg cells, studies employ TGF-β-induced (i)Treg cells generated from CD4+ conventional T (Tconv) cells in vitro. Here, we describe how human iTreg cells relate to human blood-derived tTreg and Tconv cells according to proteomic analysis. Each of these cell populations had a unique protein expression pattern. iTreg cells had very limited overlap in protein expression with tTreg cells, regardless of cell activation status and instead shared signaling and metabolic proteins with Tconv cells. tTreg cells had a uniquely modest response to CD3/CD28-mediated stimulation. As a benchmark, we used a previously defined proteomic signature that discerns ex vivo naïve and effector Treg cells from Tconv cells and includes conserved Treg cell properties. iTreg cells largely lacked this Treg cell core signature and highly expressed e.g. STAT4 and NFATC2, which may contribute to inflammatory responses. We also used a proteomic signature that distinguishes ex vivo effector Treg cells from Tconv cells and naïve Treg cells. iTreg cells contained part of this effector Treg cell signature, suggesting acquisition of pTreg cell features. In conclusion, iTreg cells are distinct from tTreg cells and share limited features with ex vivo Treg cells at the proteomic level.
Development of a wearable belt with integrated sensors for measuring multiple physiological parameters related to heart failure
Authors: Iqbal Sheikh M. A. , Mahgoub Imadeldin , Du E , Leavitt Mary Ann , Asghar Waseem
Published: November 2022

Heart failure is a chronic disease, the symptoms of which occur due to a lack of cardiac output. It can be better managed with continuous and real time monitoring. Some efforts have been made in the past for the management of heart failure. Most of these efforts were based on a single parameter for example thoracic impedance or heart rate alone. Herein, we report a wearable device that can provide monitoring of multiple physiological parameters related to heart failure. It is based on the sensing of multiple parameters simultaneously including thoracic impedance, heart rate, electrocardiogram and motion activity. These parameters are measured using different sensors which are embedded in a wearable belt for their continuous and real time monitoring. The healthcare wearable device has been tested in different conditions including sitting, standing, laying, and walking. Results demonstrate that the reported wearable device keeps track of the aforementioned parameters in all conditions.
Analysis of serum circulating MicroRNAs level in Malaysian patients with gestational diabetes mellitus
Authors: Jamalpour Sajad , Zain Shamsul Mohd , Vazifehmand Reza , Mohamed Zahurin , Pung Yuh Fen , Kamyab Hesam , Omar Siti Zawiah
Published: November 2022

Gestational diabetes mellitus (GDM) is a severe global issue that requires immediate attention. MicroRNA expression abnormalities are possibly disease-specific and may contribute to GDM pathological processes. To date, there is limited data on miRNA profiling in GDM, especially that involves a longitudinal study. Here, we performed miRNA expression profiling in the entire duration of pregnancy (during pregnancy until parturition and postpartum) using a miRNA- polymerase chain reaction array (miRNA-PCRArray) and in-silico analysis to identify unique miRNAs expression and their anticipated target genes in Malay maternal serum. MiRNA expression levels and their unique potential as biomarkers were explored in this work. In GDM patients, the expression levels of hsa-miR-193a, hsa-miR-21, hsa-miR-23a, and hsa-miR-361 were significantly increased, but miR-130a was significantly downregulated. The area under the curve (AUC) and receiver operating characteristic (ROC) curve study demonstrated that hsa-miR-193a (AUC = 0.89060 ± 04,470, P = 0.0001), hsa-miR-21 (AUC = 0.89500 ± 04,411, P = 0.0001), and miR-130a (AUC = 0.6939 ± 0.05845, P = 0.0025) had potential biomarker features in GDM. In-silico analysis also revealed that KLF (Kruppel-Like family of transcription factor), ZNF25 (Zinc finger protein 25), AFF4 (ALF transcription elongation factor 4), C1orf143 (long intergenic non-protein coding RNA 2869), SRSF2 (serine and arginine rich splicing factor 2), and ZNF655 (Zinc finger protein 655) were prominent genes targeted by the common nodes of miR23a, miR130, miR193a, miR21, and miR361.Our findings suggest that circulating microRNAs in the first trimester has the potential for GDM screening in the Malay population.
Non-destructive analysis of a mixed H2O–CO2 fluid in experimental noble-metal capsule by means of freezing and high-energy synchrotron X-ray diffraction
Authors: Tumiati Simone , Merlini Marco , Amalfa Andrea , Di Michiel Marco , Toffolo Luca
Published: November 2022

High-pressure high-temperature syntheses that involve volatile-bearing aqueous fluids are typically accomplished by enclosing the samples in gas-tight welded shut noble-metal capsules, from which the bulk volatile content must be extracted to be analyzed with mass spectroscopy, hence making the analysis non-replicable. Here we describe a novel non-destructive method that ensures the identification and the quantitative estimate of the volatiles directly in the sealed capsule, focusing on fluid H2O–CO2 mixtures equilibrated with graphite at conditions of geological interest (1 GPa, 800 °C). We used a high-energy (77 keV) synchrotron X-ray radiation combined with a cryostat to produce X-ray diffraction patterns and X-ray diffraction microtomographic cross-sections of the volatile-bearing samples down to –180 °C, thus encompassing the conditions at which crystalline phases-solid CO2 and clathrate (CO2 hydrate)-form. The uncertainty of the method is < 15 mol%, which reflects the difference between the volatile proportion estimated by both Rietveld refinement of the diffraction data and by image analysis of the microtomograms, and the reference value measured by quadrupole mass spectrometry. Therefore, our method can be reliably applied to the analysis of frozen H2O–CO2 mixtures and, moreover, has the potential to be extended to experimental fluids of geological interest containing other volatiles, such as CH4, SO2 and H2S.
In silico and in vitro analysis of microRNAs with therapeutic potential in atherosclerosis
Authors: Mahjoubin-Tehran Maryam , Aghaee-Bakhtiari Seyed Hamid , Sahebkar Amirhossein , Butler Alexandra E. , Oskuee Reza Kazemi , Jalili Amin
Published: November 2022

Atherosclerosis is a chronic inflammatory disease in which aberrant lipid metabolism plays a key role. MicroRNAs (miRNAs), micro-coordinators of gene expression, have been recently proposed as novel clinical biomarkers and potential therapeutic tools for a broad spectrum of diseases. This study aimed to identify miRNAs with therapeutic potential in atherosclerosis. Bioinformatic databases, including experimentally validated and computational prediction tools as well as a novel combination method, were used to identify miRNAs that are able to simultaneously inhibit key genes related to the pathogenesis of atherosclerosis. Further validation of genes and miRNAs was conducted using the STRING online tool, KEGG pathway analysis and DIANA-miRPath. The inhibitory effects of the identified miRNAs in HepG2 and Huh7 cells were verified by real-time PCR. The MTT assay was utilized to evaluate cell cytotoxicity effects of miRNAs. Atherosclerotic drug-targeted genes were selected as key genes. Strong interactions between genes were confirmed using STRING. These genes were shown to be integral to critical pathological processes involved in atherosclerosis. A novel combined method of validated and predicted tools for the identification of effective miRNAs was defined as the combination score (C-Score). Bioinformatic analysis showed that hsa-miR-124-3p and hsa-miR-16-5p possessed the best C-Score (0.68 and 0.62, respectively). KEGG and DIANA-miRPath analysis showed that selected genes and identified miRNAs were involved in atherosclerosis-related pathways. Compared with the controls in both HepG2 and Huh7 cell lines, miR-124 significantly reduced the expression of CETP, PCSK9, MTTP, and APOB, and miR-16 significantly reduced the expression of APOCIII, CETP, HMGCR, PCSK9, MTTP, and APOB, respectively. The cytotoxicity assay showed that miR-124 reduced cell viability, especially after 72 h; however, miR-16 did not show any significant cytotoxicity in either cell line. Our findings indicate that hsa-miR-124 and miR-16 have potential for use as therapeutic candidates in the treatment of atherosclerosis.
Suppressing gain-of-function proteins via CRISPR/Cas9 system in SCA1 cells
Authors: Pappadà Mariangela , Bonuccelli Ottavia , Buratto Mattia , Fontana Riccardo , Sicurella Mariaconcetta , Caproni Anna , Fuselli Silvia , Benazzo Andrea , Bertorelli Roberto , De Sanctis Veronica , Cavallerio Paolo , Simioni Valentina , Tugnoli Valeria , Salvatori Francesca , Marconi Peggy
Published: November 2022

SCAs are autosomal dominant neurodegenerative disorders caused by a gain-of-function protein with toxic activities, containing an expanded polyQ tract in the coding region. There are no treatments available to delay the onset, stop or slow down the progression of these pathologies. In this work we focus our attention on SCA1 which is one of the most common genotypes circulating in Italy. Here, we develop a CRISPR/Cas9-based approach to reduce both forms of the ATXN1 protein, normal and mutated with expanded polyQ. We started with the screening of 10 different sgRNAs able to target Exon 8 of the ATXN1 gene. The two most promising sgRNAs were validated in fibroblasts isolated from SCA1 patients, following the identification of the best transfection method for this type of cell. Our silencing approach significantly downregulated the expression of ataxin1, due to large deletions and the introduction of small changes in the ATXN1 gene, evidenced by NGS analysis, without major effects on cell viability. Furthermore, very few significant guide RNA-dependent off-target effects were observed. These preliminary results not only allowed us to identify the best transfection method for SCA1 fibroblasts, but strongly support CRISPR/Cas9 as a promising approach for the treatment of expanded polyQ diseases. Further investigations will be needed to verify the efficacy of our silencing system in SCA1 neurons and animal models.
Effect of TX-100 pretreatment on carbon paste electrode for selective sensing of dopamine in presence of paracetamol
Authors: Kumara J. K. Shashi , Swamy B. E. Kumara , Jayaprakash G. K. , Sharma S. C. , Flores.-Moreno Roberto , Mohanty Kaustubha , Hariprasad S. A.
Published: November 2022

Dopamine (DA) is one of the chief neurotransmitters present in the central nervous system of mammals. Therefore detection of DA in presence of various analytes like paracetamol has great importance. In the current work, we are proposing that Triton X-100 (TX-100) pretreated carbon paste electrode (CPE) can be useful to detect the DA selectively in presence of PA. After the pretreatment CPE can detect DA in presence of PA effectively. Cyclic voltammetry was employed to observe the amplified electron transfer reaction between the modified CPE and DA. To understand electron transfer regioselectivity at the TX-100 pretreated CPE, a dual descriptor was used. The prepared electrode showed satisfactory stability when kept under ambient conditions. The proposed approach also showed excellent analytical applicability to identify DA and PA in commercial formulations. The scope of the work is limited to detecting DA in presence of PA. We will consider the other interferes for future works.
Dynamic monitoring and analysis of factors influencing ecological environment quality in northern Anhui, China, based on the Google Earth Engine
Authors: Wang Xia , Yao Xiaojie , Jiang Changzheng , Duan Wei
Published: November 2022

Monitoring the ecological environment quality is an important task that is often connected to achieving sustainable development. Timely and accurate monitoring can provide a scientific basis for regional land use planning and environmental protection. Based on the Google Earth Engine platform coupled with the greenness, humidity, heat, and dryness identified in remote sensing imagery, this paper constructed a remote sensing ecological index (RSEI) covering northern Anhui and quantitatively analyzed the characteristics of the spatiotemporal changes in the ecological environment quality from 2001 to 2020. Geodetector software was used to explore the mechanism driving the characteristics of spatial differentiation in the ecological environment quality. The main conclusions were as follows. First, the ecological environment quality in northern Anhui declined rapidly from 2001 to 2005, but the rate of decline slowed from 2005 to 2020 and a trend of improvement gradually emerged. The ecological environment quality of Huainan from 2001 to 2020 was better and more stable compared with other regional cities. Bengbu and Suzhou showed a trend of initially declining and then improving. Huaibei, Fuyang, and Bozhou demonstrated a trend of a fluctuating decline over time. Second, vegetation coverage was the main influencing factor of the RSEI, while rainfall was a secondary factor in northern Anhui from 2001 to 2020. Finally, interactions were observed between the factors, and the explanatory power of these factors increased significantly after the interaction. The most apparent interaction was between vegetation coverage and rainfall (q = 0.404). In addition, we found that vegetation abundance had a positive impact on ecological environment quality, while population density and urbanization had negative impacts, and the ecological environment quality of wetlands was the highest. Our research will provide a theoretical basis for environmental protection and support the high-quality development of northern Anhui.
Improvement of the cell viability of hepatocytes cultured in three-dimensional collagen gels using pump-free perfusion driven by water level difference
Authors: Ishida-Ishihara Sumire , Takada Ryota , Furusawa Kazuya , Ishihara Seiichiro , Haga Hisashi
Published: November 2022

Cell-containing collagen gels are one of the materials employed in tissue engineering and drug testing. A collagen gel is a useful three-dimensional (3D) scaffold that improves various cell functions compared to traditional two-dimensional plastic substrates. However, owing to poor nutrient availability, cells are not viable in thick collagen gels. Perfusion is an effective method for supplying nutrients to the gel. In this study, we maintained hepatocytes embedded in a 3D collagen gel using a simple pump-free perfusion cell culture system with ordinary cell culture products. Flow was generated by the difference in water level in the culture medium. Hepatocytes were found to be viable in a collagen gel of thickness 3.26 (± 0.16 S.E.)-mm for 3 days. In addition, hepatocytes had improved proliferation and gene expression related to liver function in a 3D collagen gel compared to a 2D culture dish. These findings indicate that our perfusion method is useful for investigating the cellular functions of 3D hydrogels.
Development of an insilico model of eccrine sweat using molecular modelling techniques
Authors: Deshpande Parijat , Ravikumar Bharath , Tallur Siddharth , Paul Debjani , Rai Beena
Published: November 2022

Eccrine sweat is an ideal surrogate diagnostic biofluid for physiological and metabolic biomarkers for wearable biosensor design. Its periodic and non-invasive availability for candidate analytes such as glucose and cortisol along with limited correlation with blood plasma is of significant research interest. An insilico model of eccrine sweat can assist in the development of such wearable biosensors. In this regard, molecular modelling can be employed to observe the most fundamental interactions. Here, we determine a suitable molecular model for building eccrine sweat. The basic components of sweat are water and sodium chloride, in which glucose and other analytes are present in trace quantities. Given the wide range of water models available in the molecular dynamics space, in this study, we first validate the water models. We use three compounds to represent the base to build bulk sweat fluid and validate the force fields. We compare the self-diffusivity of water, glucose, sodium, and chloride ions as well as bulk viscosity values and present the results which are > 90% accurate as compared with the available literature. This validated insilico eccrine sweat model can serve as an aid to expedite the development de novo biosensors by addition of other analytes of interest e.g. cortisol, uric acid etc., simulate various temperatures and salt concentrations, expand search space for screening candidate target receptors by their binding affinity and assess the interference between competing species via simulations.