bluuebunny/crossref_metadata_2025 huggingface dataset:
Honey bee symbiont buffers larvae against nutritional stress and supplements lysine
Authors: Parish Audrey J , Rice Danny W , Tanquary Vicki M , Tennessen Jason M , Newton Irene L G
Published: June 2022

Honey bees have suffered dramatic losses in recent years, largely due to multiple stressors underpinned by poor nutrition [1]. Nutritional stress especially harms larvae, who mature into workers unable to meet the needs of their colony [2]. In this study, we characterize the metabolic capabilities of a honey bee larvae-associated bacterium, Bombella apis (formerly Parasaccharibacter apium), and its effects on the nutritional resilience of larvae. We found that B. apis is the only bacterium associated with larvae that can withstand the antimicrobial larval diet. Further, we found that B. apis can synthesize all essential amino acids and significantly alters the amino acid content of synthetic larval diet, largely by supplying the essential amino acid lysine. Analyses of gene gain/loss across the phylogeny suggest that four amino acid transporters were gained in recent B. apis ancestors. In addition, the transporter LysE is conserved across all sequenced strains of B. apis. Finally, we tested the impact of B. apis on developing honey bee larvae subjected to nutritional stress and found that larvae supplemented with B. apis are bolstered against mass reduction despite limited nutrition. Together, these data suggest a novel role of B. apis as a nutritional mutualist of honey bee larvae.
Dentists´ and Dental Hygienists´ experiences of the Capitation Contract System—the dilemma of conflicting loyalties
Authors: Boberg Emelie , Franzon Bengt , Johannsen Annsofi
Published: June 2022

Objective

The Capitation Contract system (CCS) is a payment model adopted by the Swedish Public Dental Health Service (PDHS). Patients enrolled in the CCS are usually assessed as being at lower risk of dental disease and are more regular dental attenders than those treated by Fee for Service (FFS). With increasing numbers of patients and CCS enrolments, Sweden faces a shortage of dental personnel. Our aim was to analyse dentists´ and dental hygienists´ perceptions and experiences of the capitation contact system.

Material and methods

Eleven dentists and dental hygienists from three Swedish regions participated in online qualitative interviews conducted according to the Grounded Theory methodology.

Results

When working with CCS the informants tried hard ´to find a balance between attitudes, compliance with guidelines and clinical resources´. Not all patients were offered CCS, even though they qualified: among other determinants were the informants’ interpretations of guidelines and regulations, clinical resources, and patient interest.

Conclusions

When dental resources are in balance, the informants appreciate the CCS and consider it to be favourable to patient health but are aware of conflicting loyalties of their dual roles of insurance sales agent and care provider. The informants´ individual mindset affects which patients are offered CCS enrolment.
Enantioselective Cu-catalyzed double hydroboration of alkynes to access chiral gem-diborylalkanes
Authors: Jin Shengnan , Li Jinxia , Liu Kang , Ding Wei-Yi , Wang Shuai , Huang Xiujuan , Li Xue , Yu Peiyuan , Song Qiuling
Published: June 2022

Chiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially optically enriched 1,1-diboron compounds, has been greatly inhibited by the lack of direct synthetic protocols. Therefore, it is very challenging to develop a simple and effective strategy to obtain chiral 1,1-diborylalkanes. Herein, we develop an enantioselective copper-catalyzed cascade double hydroboration of terminal alkynes and highly enantioenriched gem-diborylalkanes were readily obtained. Our strategy uses simple terminal alkynes and two different boranes to construct valuable chiral gem-bis(boryl) alkanes with one catalytic and one ligand pattern, which represents the simplest and most straightforward strategy for constructing such chiral gem-diborons.
Closed-loop optimization of fast trapped-ion shuttling with sub-quanta excitation
Authors: Sterk Jonathan D. , Coakley Henry , Goldberg Joshua , Hietala Vincent , Lechtenberg Jason , McGuinness Hayden , McMurtrey Daniel , Parazzoli L. Paul , Van Der Wall Jay , Stick Daniel
Published: June 2022

Shuttling ions at high speed and with low motional excitation is essential for realizing fast and high-fidelity algorithms in many trapped-ion-based quantum computing architectures. Achieving such performance is challenging due to the sensitivity of an ion to electric fields and the unknown and imperfect environmental and control variables that create them. Here we implement a closed-loop optimization of the voltage waveforms that control the trajectory and axial frequency of an ion during transport in order to minimize the final motional excitation. The resulting waveforms realize fast round-trip transport of a trapped ion across multiple electrodes at speeds of 0.5 electrodes per microsecond (35 m﻿·s−1 for a one-way transport of 210 μm in 6 μs) with a maximum of 0.36 ± 0.08 mean quanta gain. This sub-quanta gain is independent of the phase of the secular motion at the distal location, obviating the need for an electric field impulse or time delay to eliminate the coherent motion.
NETISCE: a network-based tool for cell fate reprogramming
Authors: Marazzi Lauren , Shah Milan , Balakrishnan Shreedula , Patil Ananya , Vera-Licona Paola
Published: June 2022

The search for effective therapeutic targets in fields like regenerative medicine and cancer research has generated interest in cell fate reprogramming. This cellular reprogramming paradigm can drive cells to a desired target state from any initial state. However, methods for identifying reprogramming targets remain limited for biological systems that lack large sets of experimental data or a dynamical characterization. We present NETISCE, a novel computational tool for identifying cell fate reprogramming targets in static networks. In combination with machine learning algorithms, NETISCE estimates the attractor landscape and predicts reprogramming targets using signal flow analysis and feedback vertex set control, respectively. Through validations in studies of cell fate reprogramming from developmental, stem cell, and cancer biology, we show that NETISCE can predict previously identified cell fate reprogramming targets and identify potentially novel combinations of targets. NETISCE extends cell fate reprogramming studies to larger-scale biological networks without the need for full model parameterization and can be implemented by experimental and computational biologists to identify parts of a biological system relevant to the desired reprogramming task.
Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer
Authors: Becker Winston R. , Nevins Stephanie A. , Chen Derek C. , Chiu Roxanne , Horning Aaron M. , Guha Tuhin K. , Laquindanum Rozelle , Mills Meredith , Chaib Hassan , Ladabaum Uri , Longacre Teri , Shen Jeanne , Esplin Edward D. , Kundaje Anshul , Ford James M. , Curtis Christina , Snyder Michael P. , Greenleaf William J.
Published: June 2022

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.
Pseudomonas response regulators produced in an E. coli heterologous expression host exhibit host-derived post-translational phosphorylation
Authors: Garber Megan E. , Fregoso Rodrigo , Lake Julie , Kakouridis Anne , Mukhopadhyay Aindrila
Published: June 2022

In this report, we systematically characterize 32 response regulators (RRs) from a metal tolerant groundwater isolate, Pseudomonas stutzeri RCH2 to assess the impact of host-derived post-translational phosphorylation. As observed by distinct shifted bands in a phos-tag gel, 12 of the 24 detected RRs show homogenous mixtures of phosphorylated proteins or heterogenous mixtures of unphosphorylated and phosphorylated proteins. By evaluating the phosphorylation state of CzcR and CopR II under varying assay parameters, we found that changes to pH and exogenous addition of phospho-donors (e.g. acetyl phosphate) have little to no effect on phosphorylation state. By applying protein production conditions that decrease the pool of intracellular acetyl-phosphate in E. coli, we found a reduction in the phosphorylated population of CopR II when magnesium was added to the medium, but observed no change in phosphorylated population when CopR II is expressed in E. coli BL21 (DE3) ∆pta, a mutant with a metabolic disruption to the acetyl-phosphate pathway. Therefore, the specific mechanism of post-translational phosphorylation of RRs in E. coli remains obscure. These findings show the importance of characterizing the phosphorylation state of proteins when heterologously expressed, since their biochemical and physiological properties can be dependent on post-translational modification.
GABAergic CA1 neurons are more stable following context changes than glutamatergic cells
Authors: Schuette Peter J. , Ikebara Juliane M. , Maesta-Pereira Sandra , Torossian Anita , Sethi Ekayana , Kihara Alexandre H. , Kao Jonathan C. , Reis Fernando M. C. V. , Adhikari Avishek
Published: June 2022

The CA1 region of the hippocampus contains both glutamatergic pyramidal cells and GABAergic interneurons. Numerous reports have characterized glutamatergic CAMK2A cell activity, showing how these cells respond to environmental changes such as local cue rotation and context re-sizing. Additionally, the long-term stability of spatial encoding and turnover of these cells across days is also well-characterized. In contrast, these classic hippocampal experiments have never been conducted with CA1 GABAergic cells. Here, we use chronic calcium imaging of male and female mice to compare the neural activity of VGAT and CAMK2A cells during exploration of unaltered environments and also during exposure to contexts before and after rotating and changing the length of the context across multiple recording days. Intriguingly, compared to CAMK2A cells, VGAT cells showed decreased remapping induced by environmental changes, such as context rotations and contextual length resizing. However, GABAergic neurons were also less likely than glutamatergic neurons to remain active and exhibit consistent place coding across recording days. Interestingly, despite showing significant spatial remapping across days, GABAergic cells had stable speed encoding between days. Thus, compared to glutamatergic cells, spatial encoding of GABAergic cells is more stable during within-session environmental perturbations, but is less stable across days. These insights may be crucial in accurately modeling the features and constraints of hippocampal dynamics in spatial coding.
The double-edged sword of inducible defences: costs and benefits of maladaptive switching from the individual to the community level
Authors: Kath Nadja J. , Gaedke Ursula , van Velzen Ellen
Published: June 2022

Phenotypic plasticity can increase individual fitness when environmental conditions change over time. Inducible defences are a striking example, allowing species to react to fluctuating predation pressure by only expressing their costly defended phenotype under high predation risk. Previous theoretical investigations have focused on how this affects predator–prey dynamics, but the impact on competitive outcomes and broader community dynamics has received less attention. Here we use a small food web model, consisting of two competing plastic autotrophic species exploited by a shared consumer, to study how the speed of inducible defences across three trade-off constellations affects autotroph coexistence, biomasses across trophic levels, and temporal variability. Contrary to the intuitive idea that faster adaptation increases autotroph fitness, we found that higher switching rates reduced individual fitness as it consistently provoked more maladaptive switching towards undefended phenotypes under high predation pressure. This had an unexpected positive impact on the consumer, increasing consumer biomass and lowering total autotroph biomass. Additionally, maladaptive switching strongly reduced autotroph coexistence through an emerging source-sink dynamic between defended and undefended phenotypes. The striking impact of maladaptive switching on species and food web dynamics indicates that this mechanism may be of more critical importance than previously recognized.
Deep embeddings to comprehend and visualize microbiome protein space
Authors: Odrzywolek Krzysztof , Karwowska Zuzanna , Majta Jan , Byrski Aleksander , Milanowska-Zabel Kaja , Kosciolek Tomasz
Published: June 2022

Understanding the function of microbial proteins is essential to reveal the clinical potential of the microbiome. The application of high-throughput sequencing technologies allows for fast and increasingly cheaper acquisition of data from microbial communities. However, many of the inferred protein sequences are novel and not catalogued, hence the possibility of predicting their function through conventional homology-based approaches is limited, which indicates the need for further research on alignment-free methods. Here, we leverage a deep-learning-based representation of proteins to assess its utility in alignment-free analysis of microbial proteins. We trained a language model on the Unified Human Gastrointestinal Protein catalogue and validated the resulting protein representation on the bacterial part of the SwissProt database. Finally, we present a use case on proteins involved in SCFA metabolism. Results indicate that the deep learning model manages to accurately represent features related to protein structure and function, allowing for alignment-free protein analyses. Technologies that contextualize metagenomic data are a promising direction to deeply understand the microbiome.
Origin and significance of the human DNase repertoire
Authors: Mori Giulia , Delfino Danila , Pibiri Paola , Rivetti Claudio , Percudani Riccardo
Published: June 2022

The human genome contains four DNase1 and two DNase2 genes. The origin and functional specialization of this repertoire are not fully understood. Here we use genomics and transcriptomics data to infer the evolutionary history of DNases and investigate their biological significance. Both DNase1 and DNase2 families have expanded in vertebrates since ~ 650 million years ago before the divergence of jawless and jawed vertebrates. DNase1, DNase1L1, and DNase1L3 co-existed in jawless fish, whereas DNase1L2 originated in amniotes by tandem duplication of DNase1. Among the non-human DNases, DNase1L4 and newly identified DNase1L5 derived from early duplications that were lost in terrestrial vertebrates. The ancestral gene of the DNase2 family, DNase2b, has been conserved in synteny with the Uox gene across 700 million years of animal evolution,while DNase2 originated in jawless fish. DNase1L1 acquired a GPI-anchor for plasma membrane attachment in bony fishes, and DNase1L3 acquired a C-terminal basic peptide for the degradation of microparticle DNA in jawed vertebrates. The appearance of DNase1L2, with a distinct low pH optimum and skin localization, is among the amniote adaptations to life on land. The expansion of the DNase repertoire in vertebrates meets the diversified demand for DNA debris removal in complex multicellular organisms.
Detection of HOCl-driven degradation of the pericardium scaffolds by label-free multiphoton fluorescence lifetime imaging
Authors: Yakimov B. P. , Vlasova I. I. , Efremov Y. M. , Maksimov E. G. , Shirshin E. A. , Kagan V. E. , Timashev P. S.
Published: June 2022

Artificial biomaterials can significantly increase the rate of tissue regeneration. However, implantation of scaffolds leads not only to accelerated tissue healing but also to an immune response of the organism, which results in the degradation of the biomaterial. The synergy of the immune response and scaffold degradation processes largely determines the efficiency of tissue regeneration. Still, methods suitable for fast, accurate and non-invasive characterization of the degradation degree of biomaterial are highly demandable. Here we show the possibility of monitoring the degradation of decellularized bovine pericardium scaffolds under conditions mimicking the immune response and oxidation processes using multiphoton tomography combined with fluorescence lifetime imaging (MPT-FLIM). We found that the fluorescence lifetimes of genipin-induced cross-links in collagen and oxidation products of collagen are prominent markers of oxidative degradation of scaffolds. This was verified in model experiments, where the oxidation was induced with hypochlorous acid or by exposure to activated neutrophils. The fluorescence decay parameters also correlated with the changes of micromechanical properties of the scaffolds as assessed using atomic force microscopy (AFM). Our results suggest that FLIM can be used for quantitative assessments of the properties and degradation of the scaffolds essential for the wound healing processes in vivo.
Evaluation of root lodging resistance during whole growth stage at the plant level in maize
Authors: Wang Xiaohu , Li Yinchang , Han Wei , Song Zhaoyu , Wang Shengjian , Yang Jinzhong
Published: June 2022

Root lodging due to strong storm wind is a common problem in maize (Zea mays) production, leading to reduced crop yield and quality and harvest efficiency. Little information is available on quantifying effects of vertical leaf area distribution on root lodging in crops such as maize. Anti-lodging index of root was computed by the formula: ALroot = Mroot / Mwind, where AL denotes anti-lodging index, and M moment of force. Mroot, root failure moment of force equals to moment arm times max root side-pulling force measured in situ by means of the digital pole dynamometer, and Mwind, wind resultant moment of force is estimated with vertical leaf area distribution and wind speed. Two maize cultivars were examined at 5 different growth stages from V8 to physiological maturity in 2019 and 2020, in Qingdao, China. Root anti-lodging index in tested cultivars fluctuated to a small extent within any year during whole growth period excluding at V8, while there was an inter-annual shift in index means (1.23 vs 0.84). Both root failure moment and wind resultant moment increased first and then decreased with the growth stage, and their influences on root anti-lodging index varied with the year. At wind grade 6, effect sizes, as contribution to root anti-lodging index, of root moment and wind moment were respectively 0.88 and 0.98. The difference in anti-lodging index between cultivars seemed to be disappearing as wind grade goes up. Root failure moment of force positively related to single root tensile resistance, root-soil ball volume, root number and total root length, whose correlation coefficient was the maximum of 0.94. Root anti-lodging index of maize proved stable from V8 on during whole growth period, and vertical leaf area distribution played a substantial role in maize root lodging in terms of wind resultant moment. Our findings provide the insights into root lodging events in crops such as maize, and would serve an approach to assessing crop root lodging resistance in breeding and cultivation programs.
Impact of Plasmodium vivax malaria on executive and cognitive functions in elderlies in the Brazilian Amazon
Authors: Pessoa Rockson C. , Oliveira-Pessoa Gabriela F. , Souza Brenda K. A. , Sampaio Vanderson S. , Pinto André Luiz C. B. , Barboza Larissa L. , Mouta Gabriel S. , Silva Emanuelle Lira , Melo Gisely C. , Monteiro Wuelton M. , Silva-Filho José H. , Lacerda Marcus V. G. , Baía-da-Silva Djane Clarys
Published: June 2022

The exact path leading to cognitive impairment that goes beyond malaria is unclear, but it appears to be the result of interactive factors. Time of exposure to disease and recurrences are potentially major determinant variables. Cognitive impairment is described mainly in children, rarely in adults. The disease in high endemic areas usually does not affect elderlies, because of acquired immunity over time. However, this population is relatively more frequently sick in lower endemic areas, such as in the Amazon. This study assessed the effect of Plasmodium vivax malaria on the executive and cognitive functions of elderlies, in the Brazilian Amazon. A cohort study was conducted to evaluate executive and cognitive functions one week (T0), two months (T2) and eight months (T8) after the malaria episode. Mini-Mental State Examination (MMSE), Beck Depression Inventory II (BDI-II), Clock Drawing Test (CDT), Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were used to assess executive and cognitive functions. One hundred-forty elderlies were enrolled (70 with P. vivax malaria and 70 without malaria). P. vivax malaria was associated with impairment of the executive and cognitive functions in elderlies for up to 8 months after acute P. vivax malaria. Prior history of malaria, recurrences and higher parasitemia were independently associated with various surrogates of executive and cognitive impairment. With the increase in life expectancy, elderlies living in malaria endemic areas will deserve more attention from health authorities, to guarantee improvement of their quality of life in the tropics.
210Po and 210Pb content in the smoke of Heated Tobacco Products versus Conventional Cigarette smoking
Authors: Berthet Aurélie , Butty Audrey , Rossier Jérémie , Sadowski Isabelle Jacot , Froidevaux Pascal
Published: June 2022

210Po is a radioactive component of conventional cigarette tobacco smoke and is a recognized carcinogen. Despite the expanding market of heated tobacco products, no data are available on the activity of 210Po in the smoke of IQOS Heets cigarette. We determined the 210Po activity in the mainstream smoke of thirteen cigarette brands available on the Swiss market using a smoking machine and compared the results to the 210Po activity measured in the mainstream smoke of the IQOS system. In addition, we measured the 210Po and 210Pb loss on heating after uniform heating from 50 to 600 °C for several cigarette brands and the Heets cigarettes. 13.6 ± 4.1% of 210Po activity was found in the mainstream smoke in conventional cigarette smoking (7% for 210Pb). This dropped to 1.8 ± 0.3% in the mainstream smoke of IQOS Heets. Conversely, when the tobacco was heated uniformly at 330 °C, a loss of 210Po of more than 80% was observed for all type of cigarettes. Apparently, IQOS significantly reduced the 210Po and 210Pb activities in the mainstream smoke. However, our results show that only 15% of the Heets tobacco reaches 330 °C with IQOS. While IQOS reduces the 210Po and 210Pb activities in the mainstream smoke compared to conventional cigarettes, it only heats a marginal fraction of the tobacco present in the Heets cigarette. Because smoking is an addiction (mostly due to nicotine), IQOS could possibly deliver an unsatisfactory dose of nicotine to a Heets cigarette smoker, as most of the tobacco is left unaltered.
Effect of different types of exercise in adult subjects with fibromyalgia: a systematic review and meta-analysis of randomised clinical trials
Authors: Couto Nuno , Monteiro Diogo , Cid Luís , Bento Teresa
Published: June 2022

Exercise has been recommended for fibromyalgia treatment. However, doubts related to exercise benefits remain unclear. The objective of this study was to summarise, through a systematic review with meta-analysis, the available evidence on the effects of aerobic, resistance and stretching exercise on pain, depression, and quality of life. Search was performed using electronic databases Pubmed and Cochrane Library. Studies with interventions based on aerobic exercise, resistance exercise and stretching exercise published until July 2020 and updated in December 2021, were identified. Randomized controlled trials and meta-analyses involving adults with fibromyalgia were also included. Eighteen studies were selected, including a total of 1184 subjects. The effects were summarised using standardised mean differences (95% confidence intervals) by random effect models. In general, aerobic exercise seems to reduce pain perception, depression and improves quality of life; it also improves mental and physical health-related quality of life. Resistance exercise decreases pain perception and improves quality of life and moreover improves the physical dimension of health-related quality of life. It was also observed that resistance exercise appears to have a non-significant positive effect on depression and the mental dimension of health-related quality of life. Studies revealed that stretching exercise reduces the perception and additionally improves quality of life and health-related quality of life. However, a non-significant effect was observed on depression. We conclude that exercise may be a way to reduce depression, and pain and improve the quality of life in adult subjects with fibromyalgia and should be part of the treatment for this pathology.
Development and internal validation of a model to predict type 2 diabetic complications after gestational diabetes
Authors: Ukah Ugochinyere Vivian , Platt Robert W. , Auger Nathalie , Dasgupta Kaberi , Dayan Natalie
Published: June 2022

Gestational diabetes mellitus (GDM) increases the risk of early-onset type 2 diabetes, which further exacerbates the risk of developing diabetic complications such as kidney, circulatory, and neurological complications. Yet, existing models have solely focused on the prediction of type 2 diabetes, and not of its complications, which are arguably the most clinically relevant outcomes. Our aim was to develop a prediction model for type 2 diabetic complications in patients with GDM. Using provincial administrative data from Quebec, Canada, we developed a model to predict type 2 diabetic complications within 10 years among 90,143 women with GDM. The model was internally validated and assessed for discrimination, calibration, and risk stratification accuracy. The incidence of diabetic complications was 3.8 (95% confidence interval (CI) 3.4–4.3) per 10,000 person-years. The final prediction model included maternal age, socioeconomic deprivation, substance use disorder, gestational age at delivery, severe maternal morbidity, previous pregnancy complications, and hypertensive disorders of pregnancy. The model had good discrimination [area under the curve (AUROC) 0.72 (95% CI 0.69–0.74)] and calibration (slope ≥ 0.9) to predict diabetic complications. In the highest category of the risk stratification table, the positive likelihood ratio was 8.68 (95% CI 4.14–18.23), thereby showing a moderate ability to identify women at highest risk of developing type 2 diabetic complications. Our model predicts the risk of type 2 diabetic complications with moderate accuracy and, once externally validated, may prove to be a useful tool in the management of women after GDM.
Open-source, low-cost, in-situ turbidity sensor for river network monitoring
Authors: Droujko Jessica , Molnar Peter
Published: June 2022

Fine sediment transport in rivers is important for catchment nutrient fluxes, global biogeochemical cycles, water quality and pollution in riverine, coastal and marine ecosystems. Monitoring of suspended sediment in rivers with current sensors is challenging and expensive and most monitoring setups are restricted to few single site measurements. To better understand the spatial heterogeneity of fine sediment sources and transport in river networks there is a need for new smart water turbidity sensing that is multi-site, accurate and affordable. In this work, we have created such a sensor, which detects scattered light from an LED source using two detectors in a control volume, and can be placed in a river. We compare several replicates of our sensor to different commercial turbidity probes in a mixing tank experiment using two sediment types over a wide range of typical concentrations observed in rivers. Our results show that we can achieve precise and reproducible turbidity measurements in the 0–4000 NTU or 0–16g/L range. Our sensor can also be used directly as a suspended sediment sensor and bypass an unnecessary calibration to Formazin. The developed turbidity sensor is much cheaper than existing options of comparable quality and is especially intended for distributed sensing across river networks.
On the caveats of a multiplex test for SARS-CoV-2 to detect seroconversion after infection or vaccination
Authors: Fernandes-Siqueira Lorena O. , Ferreira Fabiana A. P. , Sousa Bruna G. , Mebus-Antunes Nathane C. , Neves-Martins Thais C. , Almeida Fabio C. L. , Ferreira Gustavo C. , Salmon Didier , Wermelinger Luciana S. , Da Poian Andrea T.
Published: June 2022

The Covid-19 pandemic, caused by SARS-CoV-2, has resulted in over 6 million reported deaths worldwide being one of the biggest challenges the world faces today. Here we present optimizations of all steps of an enzyme-linked immunosorbent assay (ELISA)-based test to detect IgG, IgA and IgM against the trimeric spike (S) protein, receptor binding domain (RBD), and N terminal domain of the nucleocapsid (N-NTD) protein of SARS-CoV-2. We discuss how to determine specific thresholds for antibody positivity and its limitations according to the antigen used. We applied the assay to a cohort of 126 individuals from Rio de Janeiro, Brazil, consisting of 23 PCR-positive individuals and 103 individuals without a confirmed diagnosis for SARS-CoV-2 infection. To illustrate the differences in serological responses to vaccinal immunization, we applied the test in 18 individuals from our cohort before and after receiving ChAdOx-1 nCoV-19 or CoronaVac vaccines. Taken together, our results show that the test can be customized at different stages depending on its application, enabling the user to analyze different cohorts, saving time, reagents, or samples. It is also a valuable tool for elucidating the immunological consequences of new viral strains and monitoring vaccination coverage and duration of response to different immunization regimens.
Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT1-fragment domains in cardiomyocytes
Authors: Weninger Gunnar , Pochechueva Tatiana , El Chami Dana , Luo Xiaojing , Kohl Tobias , Brandenburg Sören , Urlaub Henning , Guan Kaomei , Lenz Christof , Lehnart Stephan E.
Published: June 2022

Calpains are calcium-activated neutral proteases involved in the regulation of key signaling pathways. Junctophilin-2 (JP2) is a Calpain-specific proteolytic target and essential structural protein inside Ca2+ release units required for excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in heart failure has been reported, the precise molecular identity of the Calpain cleavage sites and the (patho-)physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565, but subsequently at three additional secondary Calpain cleavage sites. Moreover, we identified the Calpain-specific primary cleavage products for the first time in human iPSC-derived cardiomyocytes. Knockout of RyR2 in hiPSC-cardiomyocytes destabilized JP2 resulting in an increase of the Calpain-specific cleavage fragments. The primary N-terminal cleavage product NT1 accumulated in the nucleus of mouse and human cardiomyocytes in a Ca2+-dependent manner, closely associated with euchromatic chromosomal regions, where NT1 is proposed to function as a cardio-protective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies.
High precision robust control design of piezoelectric nanopositioning platform
Authors: Feng Huan , Pang Aiping , Zhou Hongbo
Published: June 2022

The piezoelectric nanopositioning platform requires extremely accurate tracking during the task, while the model uncertainty caused by load variations requires strong robustness of the system. The high accuracy and robustness in the control design are coupled to each other, making it difficult to achieve both optimally at the same time. In addition, the system itself has a weakly damped resonant mode, which makes it extremely difficult to control the piezoelectric nanopositioning platform while suppressing the inherent resonance of the system as well as meeting the requirements for robustness and high accuracy. For the multi-performance integrated control problem of piezoelectric nanopositioning platform, this paper gives two kinds of control designs (integral resonance control (IRC) and H∞ control) satisfying accuracy requirements and robustness, and carries out simulation study and comparative analysis with positive position feedback control (PPF). Simulation results show that the H∞ control strategy given in this paper has the smallest tracking error compared to PPF and IRC under 5, 10 and 20 Hz input grating scan signals, though it has a higher order, with better robustness to mechanical load variations and high frequency signal perturbations in the 0–1000 g load range.
Efficient biodiesel production from oleic and palmitic acid using a novel molybdenum metal–organic framework as efficient and reusable catalyst
Authors: Ghorbani-Choghamarani Arash , Taherinia Zahra , Tyula Yunes Abbasi
Published: June 2022

In this study, metal–organic framework based on molybdenum and piperidine-4-carboxylic acid, was synthesized through a simple solvothermal method and employed as an effective catalyst for biodiesel production from oleic acid and palmitic acid via esterification reaction. The prepared catalyst was characterized by XRD, FTIR, TGA, DSC, BET, SEM, TEM, ICP-OES, X-ray mapping and EDX analysis. The resulting Mo–MOF catalyst exhibit a rod-like morphology, specific surface area of 56 m2/g, and thermal stability up to 300 °C. The solid catalyst exhibited high activities for esterification of oleic acid and palmitic acid. Moreover, the catalyst could be simply recovered and efficiently reutilized for several times without significant loss in its activity, also obtained results revealed that metal–organic framework could be used for the appropriate and rapid biodiesel production.
Numerical modeling of dielectric barrier discharge actuators based on the properties of low-frequency plasmons
Authors: Tehrani D. Soltani , Abdizadeh G. R. , Noori S.
Published: June 2022

Electrohydrodynamic flow control systems have proven to be among the most promising flow control strategies within previous decades. Several methods for efficient evaluation and description of the effect of such systems are indeed available. Yet, due to these systems’ critical role in various applications, possible improvements are still investigated. A new phenomenological model is presented for the simulation of the plasma actuators based on the electrodynamic properties of low-frequency plasmons. The model simulates the plasmonic region as a dispersive medium. This dissipated energy is added to the flow by introducing a high-pressure region, calculated in terms of local body force vectors, requiring the distribution of the electric field and the polarization field. The model determines the electric field for the computation of the body force vector based on the Poisson equation and implements the simplified Lorentz model for the polarization field. To fully explore the performance of the presented model, an experiment has been conducted providing a comparison between the observed effect of plasma actuators on the fluid flow with the results predicted by the model. The model is then validated based on the results of other distinct experiments and exempted numerical models, based on the exchanging momentum with the ambient neutrally charged fluid, demonstrating that the model has improved adaptability and self-adjusting capability compared to the available models.
Daisaikoto improves fatty liver and obesity in melanocortin-4 receptor gene-deficient mice via the activation of brown adipose tissue
Authors: Morita Shinichi , Sakamaki Akira , Koyama Kyutaro , Shibata Osamu , Owaki Takashi , Oda Chiyumi , Kimura Atsushi , Nakaya Taiki , Ohbuchi Katsuya , Nahata Miwa , Fujitsuka Naoki , Sakai Norihiro , Abe Hiroyuki , Kamimura Kenya , Terai Shuji
Published: June 2022

Melanocortin 4 receptor gene-knockout (MC4R-KO) mice are known to develop obesity with a high-fat diet. Meanwhile, daisaikoto, one of Kampo medicines, is a drug that is expected to have therapeutic effects on obesity. Here, we report the efficacy of daisaikoto in MC4R-KO mice. Eight-week-old MC4R-KO male mice (n = 12) were divided into three groups as follows: the SD group, which is fed with a standard diet; the HFD group, fed a high-fat diet; and the DSK group, fed with a high-fat diet containing 10% of daisaikoto. After the four-week observation period, mice in each group were sacrificed and samples were collected. The body weights at 12 weeks were significantly higher in the HFD group than in the other groups, indicating that daisaikoto significantly reduced body weight gain and fat deposition of the liver. The metabolome analysis indicated that degradation of triglycerides and fatty acid oxidation in the liver were enhanced by daisaikoto administration. In MC4R-KO mice, the cytoplasm and uncoupling protein 1 expression of brown adipose tissue was decreased; however, it was reversed in the DSK group. In conclusion, daisaikoto has potentially improved fatty liver and obesity, making it a useful therapeutic agent for obesity and fatty liver.
Prehospital stroke notification and endovascular therapy for large vessel occlusion: a retrospective cohort study
Authors: Fujiwara Satoru , Kuroda Takehito , Matsuoka Yoshinori , Ohara Nobuyuki , Imamura Hirotoshi , Yamamoto Yosuke , Ariyoshi Koichi , Kohara Nobuo , Kawamoto Michi , Sakai Nobuyuki
Published: June 2022

The impact of prehospital notification by emergency medical services (EMS) on outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) remains unclear. We therefore explored the association between prehospital notification and clinical outcomes after EVT. In this single-center retrospective study from 2016 through 2020, we identified all LVO patients who received EVT. Based on the EMS’s usage of a prehospital stroke notification system, we categorized patients into two groups, Hotline and Non-hotline. The primary outcome was good neurological outcome at 90 days; other time metrics were also evaluated. Of all 312 LVO patients, the proportion of good neurological outcomes was 94/218 (43.1%) in the Hotline group and 8/34 (23.5%) in the Non-hotline group (adjusted odds ratio 2.86; 95% confidence interval 1.12 to 7.33). Time from hospital arrival to both tissue plasminogen activator and to groin puncture were shorter in the Hotline group (30 (24 to 38) min vs 48(37 to 65) min, p < 0.001; 40 (32 to 54) min vs 76 (50 to 97) min, p < 0.001), respectively. In conclusion, prehospital notification was associated with a reduction in time from hospital arrival to intervention and improved clinical outcomes in LVO patients treated with EVT.
Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma
Authors: Takehana Keiichi , Sakamoto Ryo , Fujimoto Koji , Matsuo Yukinori , Nakajima Naoki , Yoshizawa Akihiko , Menju Toshi , Nakamura Mitsuhiro , Yamada Ryo , Mizowaki Takashi , Nakamoto Yuji
Published: June 2022

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model.
Super-resolution generative adversarial networks with static T2*WI-based subject-specific learning to improve spatial difference sensitivity in fMRI activation
Authors: Ota Junko , Umehara Kensuke , Kershaw Jeff , Kishimoto Riwa , Hirano Yoshiyuki , Tachibana Yasuhiko , Ohba Hisateru , Obata Takayuki
Published: June 2022

The spatial resolution of fMRI is relatively poor and improvements are needed to indicate more specific locations for functional activities. Here, we propose a novel scheme, called Static T2*WI-based Subject-Specific Super Resolution fMRI (STSS-SRfMRI), to enhance the functional resolution, or ability to discriminate spatially adjacent but functionally different responses, of fMRI. The scheme is based on super-resolution generative adversarial networks (SRGAN) that utilize a T2*-weighted image (T2*WI) dataset as a training reference. The efficacy of the scheme was evaluated through comparison with the activation maps obtained from the raw unpreprocessed functional data (raw fMRI). MRI images were acquired from 30 healthy volunteers using a 3 Tesla scanner. The modified SRGAN reconstructs a high-resolution image series from the original low-resolution fMRI data. For quantitative comparison, several metrics were calculated for both the STSS-SRfMRI and the raw fMRI activation maps. The ability to distinguish between two different finger-tapping tasks was significantly higher [p = 0.00466] for the reconstructed STSS-SRfMRI images than for the raw fMRI images. The results indicate that the functional resolution of the STSS-SRfMRI scheme is superior, which suggests that the scheme is a potential solution to realizing higher functional resolution in fMRI images obtained using 3T MRI.
Probing Notch1-Dll4 signaling in regulating osteogenic differentiation of human mesenchymal stem cells using single cell nanobiosensor
Authors: Zhao Yuwen , Yang Rui , Bousraou Zoe , Richardson Kiarra , Wang Shue
Published: June 2022

Human mesenchymal stem cells (hMSCs) have great potential in cell-based therapies for tissue engineering and regenerative medicine due to their self-renewal and multipotent properties. Recent studies indicate that Notch1-Dll4 signaling is an important pathway in regulating osteogenic differentiation of hMSCs. However, the fundamental mechanisms that govern osteogenic differentiation are poorly understood due to a lack of effective tools to detect gene expression at single cell level. Here, we established a double-stranded locked nucleic acid (LNA)/DNA (LNA/DNA) nanobiosensor for gene expression analysis in single hMSC in both 2D and 3D microenvironments. We first characterized this LNA/DNA nanobiosensor and demonstrated the Dll4 mRNA expression dynamics in hMSCs during osteogenic differentiation. By incorporating this nanobiosensor with live hMSCs imaging during osteogenic induction, we performed dynamic tracking of hMSCs differentiation and Dll4 mRNA gene expression profiles of individual hMSC during osteogenic induction. Our results showed the dynamic expression profile of Dll4 during osteogenesis, indicating the heterogeneity of hMSCs during this dynamic process. We further investigated the role of Notch1-Dll4 signaling in regulating hMSCs during osteogenic differentiation. Pharmacological perturbation is applied to disrupt Notch1-Dll4 signaling to investigate the molecular mechanisms that govern osteogenic differentiation. In addition, the effects of Notch1-Dll4 signaling on hMSCs spheroids differentiation were also investigated. Our results provide convincing evidence supporting that Notch1-Dll4 signaling is involved in regulating hMSCs osteogenic differentiation. Specifically, Notch1-Dll4 signaling is active during osteogenic differentiation. Our results also showed that Dll4 is a molecular signature of differentiated hMSCs during osteogenic induction. Notch inhibition mediated osteogenic differentiation with reduced Alkaline Phosphatase (ALP) activity. Lastly, we elucidated the role of Notch1-Dll4 signaling during osteogenic differentiation in a 3D spheroid model. Our results showed that Notch1-Dll4 signaling is required and activated during osteogenic differentiation in hMSCs spheroids. Inhibition of Notch1-Dll4 signaling mediated osteogenic differentiation and enhanced hMSCs proliferation, with increased spheroid sizes. Taken together, the capability of LNA/DNA nanobiosensor to probe gene expression dynamics during osteogenesis, combined with the engineered 2D/3D microenvironment, enables us to study in detail the role of Notch1-Dll4 signaling in regulating osteogenesis in 2D and 3D microenvironment. These findings will provide new insights to improve cell-based therapies and organ repair techniques.