julilili42/papers huggingface dataset:
Dataset (VIII) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-10-15

MD simulation data of compound <strong>1</strong> in MSM <strong>2-<em>S</em><sub>3</sub></strong> conformations of the related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
Dataset (IX) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-10-15

Well-tempered metadynamics simulation data of compounds <strong>1 </strong>and<strong> 2</strong> of the related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
The Role of Alkyl Chain Length and Halide Counter Ion in Layered Dion-Jacobson Perovskites with Aromatic Spacers
2021-10-15

Structural, optoelectronic and supplementary characterization data for “The Role of Alkyl Chain Length and Halide Counter Ion in Layered Dion-Jacobson Perovskites with Aromatic Spacers”, doi.org/10.1021/acs.jpclett.1c02937. Figure 2.zip: 2a and 2b (XRD patterns) in *.csv files. 2c and 2d raw and processed solid state NMR spectra of (PDEA)PbI4 and (PDEA)I2, comprising 207Pb, 207Pb-&gt;1H HETCOR. NMR data is given in the JCAMP-DX 6.0 format including acquisition and processing parameters. The TopSpin software is recommended as this was used to record the NMR data. 2e-h GIWAXS images in *.tiff format Figure 3.zip: 3a and 3c (UV-Vis absorption spectra) in *.csv format 3b and 3d (PL emission) in *.xlsx data Figure 4.zip: Transient absorption spectroscopy data in *.xlsx format Figure 5.zip: 5a-f (XRD patterns) in *.csv data Figure S2.zip: S2a-b (UV-Vis spectra) in *.csv data S2c-d (XRD patterns) in *.csv data Figure S3.zip: GIWAXS images in *.tiff format Figure S4.zip: S4 Raw and processed solid state NMR spectra of 1H-&gt;13C cross polarisation spectra. NMR data is given in the JCAMP-DX 6.0 format including acquisition and processing parameters. The TopSpin software is recommended as this was used to record the NMR data. Figure S5-S6.zip: Raw and processed solution NMR spectra of (PDEA)I2 and (PDEA)Br2 in deuterated DMSO, comprising 1H and 13C 1D and 2D HSQC/HMBC spectra. NMR data is given in the JCAMP-DX 6.0 format including acquisition and processing parameters. The TopSpin software is recommended as this was used to record the NMR data. Figure S7.zip: PL emission data in *.xlsx format Figure S8.zip: Transient absorption spectroscopy data in *.xlsx format Figure S9.zip: S9a-f optical absorption data in *.csv format Figure S10.zip: PL emission data in *.xlsx format Figure S11.zip: *.png image of contact angle measurements
Platelet-Derived PCSK9 Is Associated with LDL Metabolism and Modulates Atherothrombotic Mechanisms in Coronary Artery Disease
2021-10-16

Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in the regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors of this article sought to characterize platelets as a major source of PCSK9 and PCSK9’s role in atherothrombosis. In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity, and platelet-derived PCSK9 release were analyzed. The role of platelet PCSK9 on platelet and monocyte function was investigated in vitro. Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration, and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation. The authors identified platelets as a source of PCSK9 in CAD, which may have an impact on LDL metabolism. Furthermore, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation, which may contribute to the reported beneficial clinical effects.
Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes
2021-10-16

Background Human coenzyme Q4 (COQ4) is essential for coenzyme Q 10 (CoQ 10 ) biosynthesis. Pathogenic variants in COQ4 cause childhood-onset neurodegeneration. We aimed to delineate the clinical spectrum and the cellular consequences of COQ4 deficiency. Methods Clinical course and neuroradiological findings in a large cohort of paediatric patients with COQ4 deficiency were analysed. Functional studies in patient-derived cell lines were performed. Results We characterised 44 individuals from 36 families with COQ4 deficiency (16 newly described). A total of 23 different variants were identified, including four novel variants in COQ4 . Correlation analyses of clinical and neuroimaging findings revealed three disease patterns: type 1: early-onset phenotype with neonatal brain anomalies and epileptic encephalopathy; type 2: intermediate phenotype with distinct stroke-like lesions; and type 3: moderate phenotype with non-specific brain pathology and a stable disease course. The functional relevance of COQ4 variants was supported by in vitro studies using patient-derived fibroblast lines. Experiments revealed significantly decreased COQ4 protein levels, reduced levels of cellular CoQ 10 and elevated levels of the metabolic intermediate 6-demethoxyubiquinone. Conclusion Our study describes the heterogeneous clinical presentation of COQ4 deficiency and identifies phenotypic subtypes. Cell-based studies support the pathogenic characteristics of COQ4 variants. Due to the insufficient clinical response to oral CoQ 10 supplementation, alternative treatment strategies are warranted.
Electronically monitored occlusion therapy in amblyopia with eccentric fixation
2021-10-16

Abstract Purpose Amblyopia with eccentric fixation, especially when not diagnosed early, is a therapeutic challenge, as visual outcome is known to be poorer than in amblyopia with central fixation. Consequently, treatment after late diagnosis is often denied. Electronic monitoring of occlusion provides us the chance to gain first focussed insight into age-dependent dose response and treatment efficiency, as well as the shift of fixation in this rare group of paediatric patients. Methods In our prospective pilot study, we examined amblyopes with eccentric fixation during 12 months of occlusion treatment. We evaluated their visual acuity, recorded patching duration using a TheraMon®-microsensor, and determined their fixation with a direct ophthalmoscope. Dose-response relationship and treatment efficiency were calculated. Results The study included 12 participants with strabismic and combined amblyopia aged 2.9–12.4 years (mean 6.5). Median prescription of occlusion was 7.7 h/day (range 6.6–9.9) and median daily received occlusion was 5.2 h/day (range 0.7–9.7). At study end, median acuity gain was 0.6 log units (range 0–1.6) and residual interocular visual acuity difference (IOVAD) 0.3 log units (range 0–1.8). There was neither significant acuity gain nor reduction in IOVAD after the 6th month of treatment. Children younger than 4 years showed best response with lowest residual IOVAD at study end. Efficiency calculation showed an acuity gain of approximately one line from 100 h of patching in the first 2 months and half a line after 6 months. There was a significant decline of treatment efficiency with age ( p = 0.01). Foveolar fixation was achieved after median 3 months (range 1–6). Three patients (&gt; 6 years) did not gain central fixation. Conclusion Eccentric fixation is a challenge to therapy success. Based on electronic monitoring, our study quantified for the first time the reduction of treatment efficiency with increasing age in amblyopes with eccentric fixation. Despite some improvement in patients up to 8 years, older patients showed significantly lower treatment efficiency. In younger patients with good adherence, despite poor initial acuity, central fixation and low residual IOVAD could be attained after median 3 months. Hence, the necessity of early diagnosis and intensive occlusion should be emphasized.
Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants
2021-10-16

Rhodopsin (RHO) misfolding mutations are a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). The most prevalent mutation, RHOP23H, results in its misfolding and retention in the endoplasmic reticulum (ER). Under homeostatic conditions, misfolded proteins are selectively identified, retained at the ER, and cleared via ER-associated degradation (ERAD). Overload of these degradation processes for a prolonged period leads to imbalanced proteostasis and may eventually result in cell death. ERAD of misfolded proteins, such as RHOP23H, includes the subsequent steps of protein recognition, targeting for ERAD, retrotranslocation, and proteasomal degradation. In the present study, we investigated and compared pharmacological modulation of ERAD at these four different major steps. We show that inhibition of the VCP/proteasome activity favors cell survival and suppresses P23H-mediated retinal degeneration in RHOP23H rat retinal explants. We suggest targeting this activity as a therapeutic approach for patients with currently untreatable adRP.
Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System
2021-10-16

Background: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. Methods: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low- or high-molar mass fluorescent cargo. PPE implants were subsequently coated with these nanocarriers. In control cohorts, the implant was coated with the homologue non-encapsulated cargo substance by dip coating. Implants were consequently analyzed in vivo using repetitive fluorescence microscopy utilizing the dorsal skinfold chamber in mice for ten days post implantation. Results: Implant-modification with MSA nanocarriers significantly prolonged the presence of the encapsulated small molecules while macromolecules were detectable during the investigated timeframe regardless of the form of application. Conclusions: Surface modification of PPE implants with MSA nanocarriers results in the alternation of release kinetics especially when small molecular substances are used and therefore allows a prolonged factor release for the promotion of implant integration.
Temperature sensitivity of anaerobic methane oxidation versus methanogenesis in paddy soil: Implications for the CH4 balance under global warming
2021-10-17

Abstract The global methane (CH 4 ) budget is based on a sensitive balance between methanogenesis and CH 4 oxidation (aerobic and anaerobic). The response of these processes to climate warming, however, is not quantified. This largely reflects our lack of knowledge about the temperature sensitivity ( Q 10 ) of the anaerobic oxidation of CH 4 (AOM)—a ubiquitous process in soils. Based on a 13 CH 4 labeling experiment, we determined the rate, Q 10 and activation energy of AOM and of methanogenesis in a paddy soil at three temperatures (5, 20, 35°C). The rates of AOM and of methanogenesis increased exponentially with temperature, whereby the AOM rate was significantly lower than methanogenesis. Both the activation energy and Q 10 of AOM dropped significantly from 5–20 to 20–35°C, indicating that AOM is a highly temperature‐dependent microbial process. Nonetheless, the Q 10 of AOM and of methanogenesis were similar at 5–35°C, implying a comparable temperature dependence of AOM and methanogenesis in paddy soil. The continuous increase of AOM Q 10 over the 28‐day experiment reflects the successive utilization of electron acceptors according to their thermodynamic efficiency. The basic constant for Q 10 of AOM was calculated to be 0.1 units for each 3.2 kJ mol −1 increase of activation energy. We estimate the AOM in paddy soils to consume 2.2~5.5 Tg CH 4 per year on a global scale. Considering these results in conjunction with literature data, the terrestrial AOM in total consumes ~30% of overall CH 4 production. Our data corroborate a similar Q 10 of AOM and methanogenesis. As the rate of AOM in paddy soils is lower than methanogenesis, however, it will not fully compensate for an increased methane production under climate warming.
The Protective Effect of Heme Oxygenase-1 on Liver Injury Caused by DON-Induced Oxidative Stress and Cytotoxicity
2021-10-17

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. Oxidative stress and DNA damage play a critical role in the toxicity of DON. However, previous studies focused more on acute toxicity in vivo/vitro models and lacked subchronic toxicity study in vivo. The potentially harmful effect of DON given at doses comparable to the daily human consumption in target organs, especially the liver, which is the main detoxification organ of DON, is also still not fully understood. Otherwise, Heme Oxygenase-1 (HO-1) has also reduced cell damage under the DON condition according to our previous study. Therefore, we used a rodent model that mimicked daily human exposure to DON and further explored its mechanism of toxic effects on liver tissue and Hepa 1–6 cell line. We also used adeno-associated virus (AAV)-modified HO-1 expressing by tail vein injection and constructed lentivirus-Hepa 1–6 cell line for mimicking HO-1 protective ability under the DON condition. The main results showed that both 30 d and 90 d exposures of DON could cause low-grade inflammatory infiltration around hepatic centrilobular veins. The reactive oxygen species (ROS) and 8-hydroxy-2 deoxyguanosine (8-OHdG) increased during DON exposure, indicating oxidation stress and DNA damage. Significantly, AAV-mediated liver-specific overexpression of HO-1 reduced DON-induced liver damage and indirectly protected the abilities of antioxidant enzyme/DNA damage repair system, while AAV-mediated silence of HO-1 produced the opposite effect. In addition, we found that overexpression of HO-1 could enhance autophagy and combined it with an antioxidant enzyme/DNA damage repair system to inhibit DON-induced hepatocyte damage. Altogether, these data suggest that HO-1 reduces the oxidative stress and DNA damage caused by DON sub-chronic exposure through maintaining DNA repair, antioxidant activity, as well as autophagy.
Distance Covariance: A Nonlinear Extension of Riemannian Geometry for EEG-based Brain-Computer Interfacing
2021-10-17

Riemannian frameworks are the basis for some of the best-performing decoding methods in EEG-based Brain-Computer Interfacing. In this work, we consider whether a nonlinear extension of the Riemannian framework, obtained by replacing the channel-wise covariance of the EEG signal with the nonlinear distance covariance, improves decoding performance. We study the theoretical properties of the distance covariance metric in this framework, in particular invariance to affine transformations, and compare the proposed method with established Riemannian methods on three different EEG data sets. We do not find evidence that the distance covariance extension improves decoding performance in comparison to the linear Riemannian framework.
Genetic and epigenetic characterization of posterior pituitary tumors
2021-10-18

Abstract Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group ( n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group ( n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group ( p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.
The Role of Alkyl Chain Length and Halide Counter Ion in Layered Dion−Jacobson Perovskites with Aromatic Spacers
2021-10-18

Layered hybrid perovskites based on Dion-Jacobson phases are of interest to various optoelectronic applications. However, the understanding of their structure-property relationships remains limited. Here, we present a systematic study of Dion-Jacobson perovskites based on (S)PbX<sub>4</sub> (<i>n</i> = 1) compositions incorporating phenylene-derived aromatic spacers (S) with different anchoring alkylammonium groups and halides (X = I, Br). We focus our study on 1,4-phenylenediammonium (PDA), 1,4-phenylenedimethylammonium (PDMA), and 1,4-phenylenediethylammonium (PDEA) spacers. Systems based on PDA did not form a well-defined layered structure, showing the formation of a 1D structure instead, whereas the extension of the alkyl chains to PDMA and PDEA rendered them compatible with the formation of a layered structure, as shown by X-ray diffraction and solid-state NMR spectroscopy. In addition, the control of the spacer length affects optical properties and environmental stability, which is enhanced for longer alkyl chains and bromide compositions. This provides insights into their design for optoelectronic applications.