First principles investigation of ferroelectricity in epitaxially strained Pb2_2TiO4_4

The structure and polarization of the as-yet hypothetical Ruddlesden-Popper compound Pb$_2$TiO$_4$ are investigated within density-functional theory. Zone enter phonons of the high-symmetry K$_2$NiF$_4$-type reference structure, space group $I4/mmm$, were calculated. At the theoretical ground-state lattice constants, there is one unstable infrared-active phonon. This phonon freezes in to give the $I2mm$ ferroelectric state. As a function of epitaxial strain, two additional ferroelectric phases are found, with space groups $I4mm$ and $F2mm$ at compressive and tensile strains, respectively.Comment: 4 pages, 4 figure

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Actin-dependent vacuolar occupancy of the cell determines auxin-induced growth repression

The cytoskeleton is an early attribute of cellular life and its main components are composed of conserved proteins (Fletcher and Mullins, 2010). The actin cytoskeleton has a direct impact on cell size control in animal cells (Fletcher and Mullins, 2010; Faix et al., 1996), but its mechanistic contribution to cellular growth in plants remains largely elusive. Here, we reveal a role of actin in cell size regulation in plants. The actin cytoskeleton shows proximity to vacuoles, and the phytohormone auxin not only controls the organisation of actin filaments, but also impacts on vacuolar morphogenesis in an actin-dependent manner. Pharmacological and genetic interference with the actin-myosin system abolishes the auxin effect on vacuoles and thus disrupts its negative influence on cellular growth. SEM-based 3D nanometre resolution imaging of the vacuoles revealed that auxin controls the constriction and luminal size of the vacuole. We show that this actin-dependent mechanism controls the relative cellular occupancy of the vacuole, thus proposing an unanticipated mechanism for cytosol homeostasis during cellular growth

Detecting Machine-obfuscated Plagiarism

Related dataset is at https://doi.org/10.7302/bewj-qx93 and also listed in the dc.relation field of the full item record.Research on academic integrity has identified online paraphrasing tools as a severe threat to the effectiveness of plagiarism detection systems. To enable the automated identification of machine-paraphrased text, we make three contributions. First, we evaluate the effectiveness of six prominent word embedding models in combination with five classifiers for distinguishing human-written from machine-paraphrased text. The best performing classification approach achieves an accuracy of 99.0% for documents and 83.4% for paragraphs. Second, we show that the best approach outperforms human experts and established plagiarism detection systems for these classification tasks. Third, we provide a Web application that uses the best performing classification approach to indicate whether a text underwent machine-paraphrasing. The data and code of our study are openly available.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152346/1/Foltynek2020_Paraphrase_Detection.pdfDescription of Foltynek2020_Paraphrase_Detection.pdf : Foltynek2020_Paraphrase_Detectio

Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells

Mechanisms leading to age-related reductions in bone formation and subsequent osteoporosis are still incompletely understood. We recently demonstrated that kynurenine (KYN), a tryptophan metabolite, accumulates in serum of aged mice and induces bone loss. Here, we report on novel mechanisms underlying KYN's detrimental effect on bone aging. We show that KYN is increased with aging in murine bone marrow mesenchymal stem cells (BMSCs). KYN reduces bone formation via modulating levels of CXCL12 and its receptors as well as histone deacetylase 3 (Hdac3). BMSCs responded to KYN by significantly decreasing mRNA expression levels of CXCL12 and its cognate receptors, CXCR4 and ACKR3, as well as downregulating osteogenic gene RUNX2 expression, resulting in a significant inhibition in BMSCs osteogenic differentiation. KYN's effects on these targets occur by increasing regulatory miRNAs that target osteogenesis, specifically miR29b-1-5p. Thus, KYN significantly upregulated the anti-osteogenic miRNA miR29b-1-5p in BMSCs, mimicking the up-regulation of miR-29b-1-5p in human and murine BMSCs with age. Direct inhibition of miR29b-1-5p by antagomirs rescued CXCL12 protein levels downregulated by KYN, while a miR29b-1-5p mimic further decreased CXCL12 levels. KYN also significantly downregulated mRNA levels of Hdac3, a target of miR-29b-1-5p, as well as its cofactor NCoR1. KYN is a ligand for the aryl hydrocarbon receptor (AhR). We hypothesized that AhR mediates KYN's effects in BMSCs. Indeed, AhR inhibitors (CH-223191 and 3',4'-dimethoxyflavone [DMF]) partially rescued secreted CXCL12 protein levels in BMSCs treated with KYN. Importantly, we found that treatment with CXCL12, or transfection with an miR29b-1-5p antagomir, downregulated the AhR mRNA level, while transfection with miR29b-1-5p mimic significantly upregulated its level. Further, CXCL12 treatment downregulated IDO, an enzyme responsible for generating KYN. Our findings reveal novel molecular pathways involved in KYN's age-associated effects in the bone microenvironment that may be useful translational targets for treating osteoporosis

Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig

<p>Abstract</p> <p>Background</p> <p><it>Dichrostachys cinerea </it>(L.) Wight et Arn. (Mimosaceae) is largely used in ethno-medically across Africa, and mainly employed for the treatment of asthma in Ivory Coast and Gabon. The paper analyses the relaxation induced by the methanolic extract of <it>D. cinerea </it>(Edici) in the guinea-pig trachea preparations (GPTPs). Purpose: This study aimed to bring out the scientific basis to the use of this plant leading to the validation of this phytomedicine.</p> <p>Method</p> <p>The aorta obtained from guinea-pigs was immediately placed in a Mac Ewen solution. Experiments were performed in preparations suspended between two L-shaped stainless steel hooks in a 10 ml organ bath containing Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. The different drugs were directly administered into the organ bath and the magnitude of GPTPs was evaluated.</p> <p>Results</p> <p>Phytochemical analysis of the methanolic extract of Dichrostachys <it>cinerea </it>(Edici) using chemical methods revealed the presence of flavenoids, tannins, sterols, triterpenes and polyphenols. Pharmacological studies performed in GPTPs show that of <it>Dichrostachys cinerea </it>(0.1 mg/ml - 2 mg/ml) evoked a broncho-constriction in GPTPs. Whereas, at concentration up to 2 mg/ml, Edici induced a significant dose-dependent relaxation in the GPTPs. KCl-, ACh- or histamine-evoked contractions of isolated trachea was significantly inhibited by increasing concentrations of Edici (3.5-10 mg/ml). Edici (10 mg/ml) as well as promethazine (0.25 mg/ml) significantly inhibited contractions induced by increasing concentrations of histamine (1×10^-7-1×10^-4mg/ml). In the presence of atropine at a concentration of 10^-6mg/ml, contractile response curve (CRC) evoked by ACh (1×10^-5-1×10^-2mg/ml) was significantly abolished in concentration-dependent manner. Edici did not significantly reduced ACh evoked contraction (10^-5-10^-2mg/ml).</p> <p>Conclusion</p> <p>These observations suggest that Edici could act through two mechanisms: firstly by activation of β-adrenergic or histaminergic receptors; and secondly muscarinic receptors may not be greatly involved, that justifying the use of the extract in traditional Medicine in Africa.</p

ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness. = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable.Our results indicate that D allele or DD homozygous can't become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS