Miracle-dz/UniFAR-FTUs huggingface dataset:
Charge Redistribution Effects on the UV–Vis Spectra of Small Ligated Gold Clusters: a Computational Study

We analyze and compare the UV–visible absorption profiles, computed at the TD-DFT level, of several thiolate, chloride, and phosphine ligand protected gold clusters with Au13, Au25, and Au28 metallic cores. We show by investigating several model clusters and experimentally reported ones that the charge redistribution between the gold core and the ligand shell can be controlled by the electron acceptor or electron donor character of the ligands and their spatial distribution around the metallic core. A correlation between the increase of electronic charge in the gold core and a shift of the optical absorption band toward lower transition energies is highlighted. The identified correlation between the partial charge on the metallic gold core and the position of the lowest electronic transition is robust and remains valid even for small clusters with little structural or electronic similarity.
Therapeutic IL-6 trans-signalling inhibition by olamkicept (sgp130Fc) in patients with active inflammatory bowel disease.

BACKGROUND A large unmet therapeutic need exists in inflammatory bowel diseases (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL-6/IL-6R blockade is limited by profound immunosuppression. Evidence has emerged, that chronic pro-inflammatory activity of IL-6 is mainly mediated by trans-signalling via a complex of IL-6 bound to soluble IL-6R engaging the gp130 receptor without the need of membrane bound IL6R. We have developed a decoy protein, sgp130Fc, which exclusively blocks IL-6 pro-inflammatory trans-signalling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression. METHODS We present a 12-week, open label, prospective phase IIa trial (FUTURE) in 16 patients with active IBD treated with the trans-signalling inhibitor olamkicept (sgp130Fc) to assess molecular mechanisms, safety and effectiveness of IL-6 trans-signalling blockade in vivo. We performed in-depth molecular profiling at various time points before and after therapy induction to identify the mechanism of action of olamkicept. RESULTS Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-TNF (infliximab) or anti-integrin (vedolizumab) therapies was identified. CONCLUSION Our data suggest that blockade of IL-6 trans-signaling holds large promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy of IBD.
The dynamic behaviours of protein BMP-2 on hydroxyapatite nanoparticles

The interaction between proteins and nanoscale inorganic particles is one of the most important topics in many fields. In this study, the dynamic behaviours of protein bone morphogenetic protein-2 (BMP-2) (with six different orientations) on hydroxyapatite (HAP) (001) surface were studied using the molecular dynamics and steered molecular dynamics simulation. The results show that the orientation of protein BMP-2 has obvious influence on its adsorption–desorption behaviours. Among the six systems studied in this article, system I exhibits the strongest interaction with the HAP (001) surface, and the number of the adsorbed residues is more than any one of the other five systems correspondingly. These findings suggest that there will be a preferential orientation when a protein is adsorbed onto a nanoscale interface. For protein BMP-2 interacting with the HAP (001) surface, the preferential orientation is the orientation in system I.
Osteopontin Blockade Immunotherapy Increases Cytotoxic T Lymphocyte Lytic Activity and Suppresses Colon Tumor Progression

Simple Summary Despite the breakthrough in human cancer immunotherapy, colorectal cancer, except for the small subset of microsatellite instable colorectal cancer (MSI, ~4% total cases), is one of the few human cancers that does not respond to current immune checkpoint inhibitor (ICI) immunotherapy. CTLs are present in both MSI and microsatellite stable (MSS) human colon carcinoma, suggesting that PD-L1-independent mechanisms may exist and suppress CTL activation in the colon tumor microenvironment. We determined that osteopontin (OPN) inhibits tumor-specific cytotoxic T lymphocyte (CTL) lytic activity to promote colon tumor growth in vivo. Accordingly, OPN blockade immunotherapy using OPN neutralization monoclonal antibodies 100D3 and 103D6 suppressed colon tumor growth in vivo. Our findings indicate that 100D3 and 103D6 has the potential to be further developed for colorectal cancer immunotherapy. Abstract Human colorectal cancers are mostly microsatellite-stable with no response to anti-PD-1 blockade immunotherapy, necessitating the development of a new immunotherapy. Osteopontin (OPN) is elevated in human colorectal cancer and may function as an immune checkpoint. We aimed at elucidating the mechanism of action of OPN and determining the efficacy of OPN blockade immunotherapy in suppression of colon cancer. We report here that OPN is primarily expressed in tumor cells, myeloid cells, and innate lymphoid cells in human colorectal carcinoma. Spp1 knock out mice exhibit a high incidence and fast growth rate of carcinogen-induced tumors. Knocking out Spp1 in colon tumor cells increased tumor-specific CTL cytotoxicity in vitro and resulted in decreased tumor growth in vivo. The OPN protein level is elevated in the peripheral blood of tumor-bearing mice. We developed four OPN neutralization monoclonal antibodies based on their efficacy in blocking OPN inhibition of T cell activation. OPN clones 100D3 and 103D6 increased the efficacy of tumor-specific CTLs in killing colon tumor cells in vitro and suppressed colon tumor growth in tumor-bearing mice in vivo. Our data indicate that OPN blockade immunotherapy with 100D3 and 103D6 has great potential to be further developed for colorectal cancer immunotherapy and for rendering a colorectal cancer response to anti-PD-1 immunotherapy.
Chemical characterization of basil (Ocimum spp.) based on volatile oils

Essential oils extracted from basil (Ocimum spp.) by steam distillation are used to flavor foods, oral products, in fragrances and in traditional medicines. The genus Ocimum contains around 30 species native to the tropics and subtropics, with some species naturalized and/or cultivated in temperate areas. Inter- and intraspecific hybridization have created significant confusion in the botanical systematics of the Ocimum genus. The taxonomy of O. basilicum is further complicated by the existence of numerous varieties, cultivars and chemotypes within the species that do not differ significantly in morphology. The composition of volatile oil constituents was used to characterize the diversity among the most economically important Ocimum species. Using principal component analysis on the aromatic volatile oils, the Ocimum accessions could be separated into five groups, which do not correspond to the different species: (1) citral–spathulenol accessions; (2) linalool-rich accessions; (3) methylchavicol-rich accessions; (4) linalool–methylchavicol accessions; and (5) methyl(E)-cinnamate-rich accessions. The fact that the groups of Ocimum species are based on morphological characteristics does not correspond to the groups based on volatile oil constituents. Copyright © 2006 John Wiley & Sons, Ltd.
ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer’s Disease

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.
Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.
3D-Printed Gelatin Methacryloyl-Based Scaffolds with Potential Application in Tissue Engineering

The development of materials for 3D printing adapted for tissue engineering represents one of the main concerns nowadays. Our aim was to obtain suitable 3D-printed scaffolds based on methacrylated gelatin (GelMA). In this respect, three degrees of GelMA methacrylation, three different concentrations of GelMA (10%, 20%, and 30%), and also two concentrations of photoinitiator (I-2959) (0.5% and 1%) were explored to develop proper GelMA hydrogel ink formulations to be used in the 3D printing process. Afterward, all these GelMA hydrogel-based inks/3D-printed scaffolds were characterized structurally, mechanically, and morphologically. The presence of methacryloyl groups bounded to the surface of GelMA was confirmed by FTIR and 1H-NMR analyses. The methacrylation degree influenced the value of the isoelectric point that decreased with the GelMA methacrylation degree. A greater concentration of photoinitiator influenced the hydrophilicity of the polymer as proved using contact angle and swelling studies because of the new bonds resulting after the photocrosslinking stage. According to the mechanical tests, better mechanical properties were obtained in the presence of the 1% initiator. Circular dichroism analyses demonstrated that the secondary structure of gelatin remained unaffected during the methacrylation process, thus being suitable for biological applications.
A Workflow for Selection of Single Nucleotide Polymorphic Markers for Studying of Genetics of Ischemic Stroke Outcomes

In this paper we propose a workflow for studying the genetic architecture of ischemic stroke outcomes. It develops further the candidate gene approach. The workflow is based on the animal model of brain ischemia, comparative genomics, human genomic variations, and algorithms of selection of tagging single nucleotide polymorphisms (tagSNPs) in genes which expression was changed after ischemic stroke. The workflow starts from a set of rat genes that changed their expression in response to brain ischemia and results in a set of tagSNPs, which represent other SNPs in the human genes analyzed and influenced on their expression as well.
A New Approach to the Application of Molecular Surface Electrostatic Potential in the Study of Detonation

In a sample of 22 nitramines, the simplest features of surface electrostatic potentials (SEPs), their positive (VS,max) and negative (VS,min) extremes, are related to their detonation velocities, D, at maximal theoretical densities. The relationships between the VS,min and D values logically show the nitramino group as responsible for detonation initiation for these compounds. On the other hand, the VS,max values gave complicated relationships. As a criterion of the imbalance between the VS,max and VS,min extremes their sum was derived and used as a new simple characteristic of SEPs, VS,Σ. The VS,Σ values have close relationships with the D values and the corresponding relationships uniquely determine the nitramino grouping as a reactivity center for detonation of nitramines. This new criterion is shown to be the best SEP characteristic for the study of detonation initiation. In all the relationships mentioned in this study of nitramines, the increase in potentials and/or their sum correspond with an increase in the D values (energy content of molecules).
The Process of Injection Drug Use Among Homeless Women: A Qualitative Study

Background The literature on women who use injection drugs (WUID) is antiquated and diluted by data from men. Due to the higher rates of morbidity and mortality among WUID, we undertook a qualitative study to better understand their drug use practices. Methods We adopted a Deleuze–Guattarian lens and engaged in semi-structured interviews with 35 women in Ottawa, Canada. Data from 31 of these women were analyzed using applied thematic analysis. Results We divided these themes into (a) how WUID obtain resources to acquire drugs, and (b) the steps involved in preparing, using, and discarding drugs. From our Deleuze–Guattarian perspective, these findings highlighted that participants stratified their worlds according to rules of cleanliness to create hierarchies of appropriateness and acceptability. Conclusions These findings, overall, highlight the importance of understanding the constructed world of WUID, particularly regarding the ways in which nurses interact with these women to provide care.
Orbit/CLASP determines centriole length by antagonising Klp10A in Drosophila spermatocytes

ABSTRACT After centrosome duplication, centrioles elongate before M phase. To identify genes required for this process and to understand the regulatory mechanism, we investigated the centrioles in Drosophila premeiotic spermatocytes expressing fluorescently tagged centriolar proteins. We demonstrated that an essential microtubule polymerisation factor, Orbit (the Drosophila CLASP orthologue, encoded by chb), accumulated at the distal end of centrioles and was required for the elongation. Conversely, a microtubule-severing factor, Klp10A, shortened the centrioles. Genetic analyses revealed that these two proteins functioned antagonistically to determine centriole length. Furthermore, Cp110 in the distal tip complex was closely associated with the factors involved in centriolar dynamics at the distal end. We observed loss of centriole integrity, including fragmentation of centrioles and earlier separation of the centriole pairs, in Cp110-null mutant cells either overexpressing Orbit or depleted of Klp10A. Excess centriole elongation in the absence of the distal tip complex resulted in the loss of centriole integrity, leading to the formation of multipolar spindle microtubules emanating from centriole fragments, even when they were unpaired. Our findings contribute to understanding the mechanism of centriole integrity, disruption of which leads to chromosome instability in cancer cells. Summary: A microtubule polymerising factor, Orbit, localises on centrioles and determines centriole length by antagonising Klp10A in Drosophila spermatocytes.
A Comparative Perspective on Three Primate Species’ Responses to a Pictorial Emotional Stroop Task

Simple Summary As animals cannot tell us how they feel, we must develop tests to make inferences about how they are feeling to assess their welfare. Here, we adapted a task that has been previously used with humans and chimpanzees to assess how chimpanzees, gorillas, and Japanese macaques respond to pictures of different emotional valences. Specifically, if the primates perceive emotionally arousing photographs differently as compared to neutral photographs, we would expect them to “trip up” more when responding to emotional stimuli. We presented the primates with a touchscreen task in which they had to select one of two differently colored squares. However, the squares always contained either positive photographs (a preferred food), negative photographs (a snake), or neutral photographs (human-made objects). The primates made more errors in selecting the correct square when the squares contained positive or negative photographs as compared to neutral photographs, indicating that they perceived these differentially, and that this caused them to make mistakes. Thus, the primates’ cognitive ability was disrupted by emotional stimuli. This offers important insights into how primates perceive the world around them, and how they process elements that may have negative or positive associations. Abstract The Stroop effect describes interference in cognitive processing due to competing cognitive demands. Presenting emotionally laden stimuli creates similar Stroop-like effects that result from participants’ attention being drawn to distractor stimuli. Here, we adapted the methods of a pictorial Stroop study for use with chimpanzees (N = 6), gorillas (N = 7), and Japanese macaques (N = 6). We tested all subjects via touchscreens following the same protocol. Ten of the 19 subjects passed pre-test training. Subjects who reached criterion were then tested on a standard color-interference Stroop test, which revealed differential accuracy in the primates’ responses across conditions. Next, to test for an emotional Stroop effect, we presented subjects with photographs that were either positively valenced (a preferred food) or negatively valenced (snakes). In the emotional Stroop task, as predicted, the primates were less accurate in trials which presented emotionally laden stimuli as compared to control trials, but there were differences in the apes’ and monkeys’ response patterns. Furthermore, for both Stroop tests, while we found that subjects’ accuracy rates were reduced by test stimuli, in contrast to previous research, we found no difference across trial types in the subjects’ response latencies across conditions.
Preparation of thermal‐responsive poly(propylene) membranes grafted with n‐isopropylacrylamide by plasma‐induced polymerization and their water permeation

Poly(propylene) (PP) membrane grafted with poly(N-isopropylacrylamide) (PNIPAAm), which is known to have a lower critical solution temperature (LCST) at around 32°C, was prepared by the plasma-induced graft polymerization technique. Graft polymerization of PNIPAAm onto a PP membrane was confirmed by microscopic attenuated total reflection/Fourier transform IR spectroscopy. The grafting yield of PNIPAAm increased with the concentration of N-isopropylacrylamide monomer and the reaction time of graft polymerization. The average pore size of the PP membrane also affected the grafting yield. From the field emission scanning electron microscopy (FE-SEM) measurement, we observed a morphological change in the PP-g-PNIPAAm membrane under wet conditions at 25°C below LCST. The permeability of water through the PP-g-PNIPAAm membrane was controlled by temperature. The PP-g-PNIPAAm membrane (PN05 and PN10) exhibited higher water permeability (Lp) than the original PP substrate membrane below LCST. As the temperature increased to above LCST, Lp gradually decreased. In addition, the graft yield of PNIPAAm and the average pore size of the PP substrate influenced water permeability. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1168–1177, 2002; DOI 10.1002/app.10410
Contribution of Particle-Induced Lysosomal Membrane Hyperpolarization to Lysosomal Membrane Permeabilization

Lysosomal membrane permeabilization (LMP) has been proposed to precede nanoparticle-induced macrophage injury and NLRP3 inflammasome activation; however, the underlying mechanism(s) of LMP is unknown. We propose that nanoparticle-induced lysosomal hyperpolarization triggers LMP. In this study, a rapid non-invasive method was used to measure changes in lysosomal membrane potential of murine alveolar macrophages (AM) in response to a series of nanoparticles (ZnO, TiO2, and CeO2). Crystalline SiO2 (micron-sized) was used as a positive control. Changes in cytosolic potassium were measured using Asante potassium green 2. The results demonstrated that ZnO or SiO2 hyperpolarized the lysosomal membrane and decreased cytosolic potassium, suggesting increased lysosome permeability to potassium. Time-course experiments revealed that lysosomal hyperpolarization was an early event leading to LMP, NLRP3 activation, and cell death. In contrast, TiO2- or valinomycin-treated AM did not cause LMP unless high doses led to lysosomal hyperpolarization. Neither lysosomal hyperpolarization nor LMP was observed in CeO2-treated AM. These results suggested that a threshold of lysosomal membrane potential must be exceeded to cause LMP. Furthermore, inhibition of lysosomal hyperpolarization with Bafilomycin A1 blocked LMP and NLRP3 activation, suggesting a causal relation between lysosomal hyperpolarization and LMP.