julilili42/papers huggingface dataset:
Ciliopathy-associated missense mutations in IFT140 are hypomorphic and have edgetic effects on protein interaction networks
2023-01-19

Abstract The mechanisms underlying recessive Mendelian diseases and the interplay between genotype and phenotype still need to be better understood. It is therefore necessary to characterise the functional effects of missense mutations at the protein level. Here we focus on missense mutations in the intraflagellar transport protein IFT140, which forms part of the IFT complex A (IFT-A), a crucial component of the ciliary machinery. Mutations in IFT140 can cause a vast spectrum of diseases belonging to the group of ciliopathies, reaching from isolated retinal dystrophy to severe skeletal abnormalities and multi-organ diseases such as Mainzer-Saldino and Jeune syndrome. We hypothesise that missense mutations in IFT140 are hypomorphic leading to quantitative effects on a subset of protein-protein interactions. This may affect complex stability as well as perturbations of protein interaction networks. In this work we assessed how 24 missense mutations in IFT140 affect interactions with other IFT and effector proteins using affinity purification coupled to mass spectrometry. Our data reveals that several mutations in IFT140 are hypomorphic and disrupt the stability of the IFT-A complex to varying degrees in a quantitative way. Allelic combination and the degree of IFT-A complex disruption in analysed missense mutations correlates with the severity of the observed phenotype in a subset of patients. In addition, we show that a distinct subset of mutations in IFT140 shows edgetic effects by disrupting specific PPIs rather than causing a total loss of IFT-A binding. This is the case e.g. with the disease-associated protein TULP3 which is involved in cilia-dependent sonic hedgehog signalling.
nf-root: a best-practice pipeline for deep learning-based analysis of apoplastic pH in microscopy images of developmental zones in plant root tissue
2023-01-19

Abstract Here we report nextflow-root ( nf-root ), a novel best-practice pipeline for deep learning-based analysis of fluorescence microscopy images of plant root tissue, aimed at studying hormonal mechanisms associated with cell elongation, given the vital role that plant hormones play in the development and growth of plants. This bioinformatics pipeline performs automatic identification of developmental zones in root tissue images, and analysis of apoplastic pH measurements of tissue zones, which is useful for modeling plant hormone signaling and cell physiological responses. Mathematical models of physiological responses of plant hormones, such as brassinolide, have been successfully established for certain root tissue types, by evaluating apoplastic pH via fluorescence imaging. However, the generation of data for this modeling is time-consuming, as it requires the manual segmentation of tissue zones and evaluation of large amounts of microscopy data. We introduce a high-throughput, highly reproducible Nextflow pipeline based on nf-core standards that automates tissue zone segmentation by implementing a deep-learning module, which deploys deterministically trained (i.e. bit-exact reproducible) convolutional neural network models, and augments the segmentation predictions with measures of prediction uncertainty and model interpretability , aiming to facilitate result interpretation and verification by experienced plant biologists. To train our segmentation prediction models, we created a publicly available dataset composed of confocal microscopy images of A. thaliana root tissue using the pH-sensitive fluorescence indicator, and manually annotated segmentation masks that identify relevant tissue zones. We applied this pipeline to analyze exemplary data, and observed a high statistical similarity between the manually generated results and the output of nf-root . Our results indicate that this approach achieves near human-level performance, and significantly reduces the time required to analyze large volumes of data, from several days to hours.
The Global Influence of Sodium on Cyanobacteria in Resuscitation from Nitrogen Starvation
2023-01-19

Dormancy and resuscitation are key to bacterial survival under fluctuating environmental conditions. In the absence of combined nitrogen sources, the non-diazotrophic model cyanobacterium Synechocystis sp. PCC 6803 enters into a metabolically quiescent state during a process termed chlorosis. This state enables the cells to survive until nitrogen sources reappear, whereupon the cells resuscitate in a process that follows a highly orchestrated program. This coincides with a metabolic switch into a heterotrophic-like mode where glycogen catabolism provides the cells with reductant and carbon skeletons for the anabolic reactions that serve to re-establish a photosynthetically active cell. Here we show that the entire resuscitation process requires the presence of sodium, a ubiquitous cation that has a broad impact on bacterial physiology. The requirement for sodium in resuscitating cells persists even at elevated CO2 levels, a condition that, by contrast, relieves the requirement for sodium ions in vegetative cells. Using a multi-pronged approach, including the first metabolome analysis of Synechocystis cells resuscitating from chlorosis, we reveal the involvement of sodium at multiple levels. Not only does sodium play a role in the bioenergetics of chlorotic cells, as previously shown, but it is also involved in nitrogen compound assimilation, pH regulation, and synthesis of key metabolites.
Impact of different immunosuppressive protocols on clinical outcomes in obese kidney transplant recipients: a propensity score–matched analysis
2023-01-19

ABSTRACT Background Although obesity has become a significant problem in transplantation medicine, the impact of different immunosuppressive protocols on clinical outcomes in obese transplant recipients remains unclear. Methods We performed an analysis of the Scientific Registry of Transplant Recipients database. Kidney transplant recipients were categorized according to body mass index (BMI) categories and immunosuppressive protocols: (i) tacrolimus/mycophenolate mofetil (Tac-MMF), (ii) mTOR-inhibitor/Tac (mTORi-Tac), (iii) mTORi/cyclosporin (mTORi-Cyc) and (iv) mTORi-MMF. Results Graft recipients with advanced obesity (BMI ≥35 kg/m2) exhibited significantly lower rates of acute rejection during the first year after transplantation in the mTORi-Tac (6.4%) group compared with Tac-MMF (11.2%). Obesity class 1 (30 &amp;lt; BMI &amp;lt; 35 kg/m2) was associated with a significant risk of acute rejection for the mTORi-Tac group [obesity class 1 hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.21–2.62, P = .003]. A similar trend was observed in the Tac-MMF group for advanced obesity HR 1.29; 95% CI 0.96–1.73, P = .087). For the Tac-MMF group, recipients with both overweight and obesity had significantly impaired survival due to cardiovascular events and also increased mortality due to infection in advanced obesity. Combination of mTORi and calcineurin inhibitor was associated with lower rejection rates and stable long-term kidney function while reducing cardiovascular side effects linked to calcineurin inhibitors in obese kidney graft recipients. Conclusion These results are critical for the growing number of obese graft recipients and warrant prospective evaluation.
Thermodynamics of quantum trajectories on a quantum computer
2023-01-19

Quantum computers have recently become available as noisy intermediate-scale quantum devices. Already these machines yield a useful environment for research on quantum systems and dynamics. Building on this opportunity, we investigate open-system dynamics that are simulated on a quantum computer by coupling a system of interest to an ancilla. After each interaction the ancilla is measured and the sequence of measurements defines a quantum trajectory. Using a thermodynamic analogy, which identifies trajectories as microstates, we show how to control the dynamics of the open system in order to enhance the probability of quantum trajectories with desired properties, e.g., particular patterns or temporal correlations. We discuss how such biased -- generally non-Markovian -- dynamics can be implemented on a unitary, gate-based quantum computer and show proof-of-principle results on the publicly accessible \\texttt{ibm\\_jakarta} machine. While our study is solely conducted on small systems, it highlights the challenges in controlling complex aspects of open-system dynamics on digital quantum computers.
PlasmoFAB
2023-01-19

&lt;p&gt;PlasmoFAB is a curated dataset containing amino acid sequences of proteins expressed by Plasmodium falciparum (Pf). Sequences are separated into antigen candidates and intracellular proteins. PlasmoFAB is created to provide a high-quality trainings set for machine learning models that will be used for Pf antigen exploration.&lt;/p&gt; &lt;p&gt;We provide PlasmoFAB in form of two separate csv files. One file, named &lt;em&gt;PlasmoFAB_pos.csv&lt;/em&gt;, contains the positive set, i.e., all protein sequences that are antigen candidates. The other file, named &lt;em&gt;PlasmoFAB_neg.csv&lt;/em&gt;, contains the negative set, i.e., all protein sequences that are intracellular proteins. Each sequence has a flag in the datafield &quot;test&quot; that indicates whether or not the sequence was used in the test set of machine learning experiments performed in the corresponding manuscript.&lt;/p&gt; &lt;p&gt;Additionally, the file &lt;em&gt;PlasmoFAB_datasheet.md&lt;/em&gt; contains a datasheet for PlasmoFAB as introduced in Gebru, Timnit, et al. &quot;Datasheets for datasets.&quot; &lt;em&gt;Communications of the ACM&lt;/em&gt; 64.12 (2021): 86-92.&lt;/p&gt;
PlasmoFAB
2023-01-19

PlasmoFAB is a curated dataset containing amino acid sequences of proteins expressed by Plasmodium falciparum (Pf). Sequences are separated into antigen candidates and intracellular proteins. PlasmoFAB is created to provide a high-quality trainings set for machine learning models that will be used for Pf antigen exploration. We provide PlasmoFAB in form of two separate csv files. One file, named <em>PlasmoFAB_pos.csv</em>, contains the positive set, i.e., all protein sequences that are antigen candidates. The other file, named <em>PlasmoFAB_neg.csv</em>, contains the negative set, i.e., all protein sequences that are intracellular proteins. Each sequence has a flag in the datafield "test" that indicates whether or not the sequence was used in the test set of machine learning experiments performed in the corresponding manuscript. Additionally, the file <em>PlasmoFAB_datasheet.md</em> contains a datasheet for PlasmoFAB as introduced in Gebru, Timnit, et al. "Datasheets for datasets." <em>Communications of the ACM</em> 64.12 (2021): 86-92.
Development of tailored splice-switching oligonucleotides for progressive brain disorders in Europe: development, regulation, and implementation considerations
2023-01-20

Splice-modulating antisense oligonucleotides (ASOs) offer treatment options for rare neurological diseases, including those with very rare mutations, where patient-specific, individualized ASOs have to be developed. Inspired by the development of milasen, the 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop patient-specific ASOs and treat eligible patients within Europe and the Netherlands, respectively. Treatment will be provided under a named patient setting. Our initiatives benefited from regulatory advice from the European Medicines Agency (EMA) with regard to preclinical proof-of-concept studies, safety studies, compounding and measuring benefit and safety in treated patients. We here outline the most important considerations from these interactions and how we implemented this advice into our plan to develop and treat eligible patients within Europe.
Tools to compare antibody gold nanoparticle conjugates for a small molecule immunoassay
2023-01-20

Abstract Antibody gold nanoparticle conjugates as recognition elements are essential for the overall performance of lateral flow assays. When immobilizing antibodies on gold nanoparticles, the challenge is to prevent aggregation and to ensure that the antibodies are correctly oriented so that they remain functional and their paratopes remain accessible. There are many methods available, and it is difficult to decide which one to use. To help selecting the most appropriate conjugate production method, different synthetic routes of binding antibodies to gold nanoparticles are systematically investigated for the purpose of a quantitative lateral flow test for small molecules. The direct comparison of different conjugate syntheses shows how to select a suitable conjugate for a lateral flow assay. The syntheses examined are direct adsorption of antibody, direct adsorption of reduced antibody, covalent binding to polyethylene glycol linker, and binding via biotin-streptavidin interaction. The conjugates are characterized using UV-Vis spectroscopy and dynamic light scattering to determine their stability. Their performance on structured lateral flow test strips is examined using calibrations for different amitriptyline concentrations. It was shown that the best conjugate for quantification of amitriptyline was realized by direct adsorption of an UV-light irradiated antibody to gold nanoparticles. The methods employed can serve as a guide for selecting the most appropriate conjugate for an application and enhance the performance of lateral flow assays. Graphical abstract
Analytical performance of 17 commercially available point-of-care tests for CRP to support patient management at lower levels of the health system
2023-01-20

Accurate and precise point-of-care (POC) testing for C-reactive protein (CRP) can help support healthcare providers in the clinical management of patients. Here, we compared the analytical performance of 17 commercially available POC CRP tests to enable more decentralized use of the tool. The following CRP tests were evaluated. Eight quantitative tests: QuikRead go (Aidian), INCLIX (Sugentech), Spinit (Biosurfit), LS4000 (Lansionbio), GS 1200 (Gensure Biotech), Standard F200 (SD Biosensor), Epithod 616 (DxGen), IFP-3000 (Xincheng Biological); and nine semi-quantitative tests: Actim CRP (ACTIM), NADAL Dipstick (nal von minden), NADAL cassette (nal von minden), ALLTEST Dipstick (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-40-80 (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10–30 (Hangzhou Alltest Biotech), Biotest (Hangzhou Biotest Biotech), BTNX Quad Line (BTNX), BTNX Tri Line (BTNX). Stored samples (n = 660) had previously been tested for CRP using Cobas 8000 Modular analyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland (reference standards). CRP values represented the clinically relevant range (10–100 mg/L) and were grouped into four categories (&lt;10 mg/L, 10–40 mg/L or 10–30 mg/L, 40–80 mg/L or 30–80 mg/L, and &gt; 80mg/L) for majority of the semi-quantitative tests. Among the eight quantitative POC tests evaluated, QuikRead go and Spinit exhibited better agreement with the reference method, showing slopes of 0.963 and 0.921, respectively. Semi-quantitative tests with the four categories showed a poor percentage agreement for the intermediate categories and higher percentage agreement for the lower and upper limit categories. Analytical performance varied considerably for the semi-quantitative tests, especially among the different categories of CRP values. Our findings suggest that quantitative tests might represent the best choice for a variety of use cases, as they can be used across a broad range of CRP categories.
Tuning Molecular Electron Affinities against Atomic Electronegativities by Spatial Expansion of a π‐System
2023-01-20

Abstract 2,1,3‐Benzochalcogenadiazoles C 6 R 4 N 2 E ( E / R ; E=S, Se, Te; R=H, F, Cl, Br, I) and C 6 H 2 R 2 N 2 E ( E / R’ ; E=S, Se, Te; R=Br, I) are 10π‐electron hetarenes. By CV/EPR measurements, DFT calculations, and QTAIM and ELI‐D analyses, it is shown that their molecular electron affinities (EAs) increase with decreasing Allen electronegativities and electron affinities of the E and non‐hydrogen R (except Cl) atoms. DFT calculations for E / R +e⋅ − →[E/R]⋅ − electron capture reveal negative ΔG values numerically increasing with increasing atomic numbers of the E and R atoms; positive ΔS has a minor influence. It is suggested that the EA increase is caused by more effective charge/spin delocalization in the radical anions of heavier derivatives due to contributions from diffuse (a real‐space expanded) p‐AOs of the heavier E and R atoms; and that this counterintuitive effect might be of the general character.
How can signaling in authentic classroom videos support reasoning on how to induce learning strategies?
2023-01-20

Classroom videos are a viable means to implement evidence-informed reasoning in teacher education in order to establish an evidence-informed teaching practice. Although learning with videos relieves pre-service teachers from acting in parallel and might reduce complexity, the material still poses higher cognitive load than written text vignettes or other traditionally used static material. In particular, the information they deliver is transient and can, therefore, easily be missed. Signaling can guide learners’ attention to central aspects of a video, thereby reducing cognitive load and enhancing learning outcomes. In the current project, pre-service teachers acquired scientific knowledge about learning strategies and their promotion in a computer-based learning environment. We explored the effect of different arrangements of signaling in classroom video-examples on conceptual knowledge and the reasoning-component of professional vision. Therefore, we conducted a set of two studies with 100 student teachers including two signal arrangements in order to investigate how signaling can help learning to reason about classroom videos. In addition, we varied if participants received information on the use of signals in advance (informed) or not (uninformed). We measured conceptual knowledge by asking participants what they knew about self-regulation strategies. Additionally, we assessed reasoning by asking participants to notice sequences in a video where teachers induced learning strategies, and to reason in what respect the observed behavior was useful to induce the strategy. Uninformed signaling did not affect the acquisition of conceptual knowledge and reasoning. Informed signaling led to significantly better conceptual knowledge than uninformed signaling. It is argued that the signal-induced extraneous load exceeded the load reduction due to the signal’s selection advantage in the uninformed conditions. In a third, exploratory study, nine participants were interviewed on the perception of different signals and indicated that spotlight and zoom-in signals foster processing of classroom videos.
Nickel Catalyzed Cross Coupling of Aryl and Alkenyl Triflates with Alkyl Thiols
2023-01-20

We report a nickel catalyzed C-S cross-coupling of aryl and alkenyl triflates with alkyl thiols. A variety of the corresponding thioethers were synthesized using an air-stable nickel precatalyst under mild reaction conditions with short reaction times. A broad substrate scope, including pharmaceutically relevant compounds, could be demonstrated.
Short-Term Outcomes and Risk Factors of In-Hospital Mortality in Patients Suffering Acute Mesenteric Ischemia after Cardiac Surgery: Role of Opioids and Lactic Acid
2023-01-20

Acute mesenteric ischemia (AMI) is associated with poor clinical results after cardiac surgery. The aim of this study was to analyse the influence of AMI on short-term outcomes and all relevant risk factors of in-hospital mortality after cardiac surgery. Moreover, we aimed to investigate the role of opioids and lactic acid in the detection and prevention of AMI. Between August 2011 and September 2015, 176 consecutive patients with gastrointestinal complications after undergoing open-heart surgery were identified and included in this study. All patients were divided into two groups: AMI group (n = 39) and non-AMI group (n = 137). In terms of comorbidities, the groups were fairly equal and showed no significant differences. Dialysis was significantly higher (p &lt; 0.001) in patients that suffered from AMI. Moreover, gastro-intestinal symptoms such as muscular defense (p = 0.004) and the laparotomy rate (p &lt; 0.001) were significantly higher in the AMI group. Likewise, in-hospital mortality (p &lt; 0.001) was significantly higher in patients with detected AMI. Univariate (p &lt; 0.001) and multivariate analysis (p = 0.025) of both groups revealed that lactic acid value &gt;2 mmol/L and present treatment with opioids are independent combined predictors of mesenteric ischemia in patients after undergoing cardiac surgery. Moreover, multivariate analysis showed peripheral vascular disease (p = 0.004), dialysis (p = 0.010), and septic shock (p = 0.003) as relevant predictors of in-hospital mortality. Prolonged analgetic treatment with opioids and sudden increase of lactic acid levels are independent combined predictors of mesenteric ischemia in patients after undergoing cardiac surgery. Furthermore, peripheral vascular disease, dialysis, and septic shock are relevant predictors for in-hospital mortality.
Concurrent intrinsic optical imaging and fMRI at ultra‐high field using magnetic field proof optical components
2023-01-20

Intrinsic optical imaging (IOI) is a well established technique to quantify activation‐related hemodynamical changes at the surface of the brain, which can be used to investigate the underlying processes of BOLD signal formation. To directly and quantitatively relate IOI and fMRI, simultaneous measurements with the two modalities are necessary. Here, a novel technical solution for a completely in‐bore setup is presented, which uses only magnetic field proof components and thus allows concurrent recordings with a quality similar to that obtained in separate experiments. Measurements of the somatosensory cortex of rats with electrical forepaw stimulation were used to verify this approach. The high spatial and temporal resolution of the fMRI data, which is possible due to the high magnetic field of 14.1 T, the use of a point‐spread function‐based distortion correction and optimized additional anatomical images, allowed accurate colocalization of the images of the two modalities. Accordingly, detailed investigations of the temporal and spatial relationships between the hemodynamic parameters and the fMRI signal, which demonstrate the linear dependence of the BOLD effect on changes in the concentrations of oxygenated and deoxygenated hemoglobin, are possible. Comparisons between the signals emerging from arterial, venous and parenchymal areas are possible and show clearly distinct characteristics. The presented setup allows combining MRI measurements and optical recordings without serious losses in the data quality of either modality. While the proposed combination of fMRI and IOI can help to gain valuable insight into the generation of the BOLD effect, the setup can be easily modified to include different types of optical or MRI measurements.