Investigation of the N-terminus amino functional of Arg10-Teixobactin

Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In this regard, a large number of analogs with substitutions in both the cycle and the tail has been described. Here, we report the contribution of the N-terminus residue, N-Me-d-Phe, to the activity of Arg10-teixobactin. On the basis of our findings, we conclude that the N-terminus accepts minimum changes but not the presence of long alkyl chains. The presence of a positive charge is a requirement for the activity of the peptide. Furthermore, acylation of the N-terminus leads to total loss of activity

Schistosoma mansoni cercarial elastase (SmCE): differences in immunogenic properties of native and recombinant forms

The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude pre- parations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum gluta- thione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization. The IgG antibody response to rSmCE- SjGST was mainly of the IgG1 subclass. These results suggest that inactive forms of the antigen could be used to obtain the optimum immunogenic effects as a vaccine candidate against schistosomiasis. Mice immunized with the rSmCE- SjGST on alum had smaller mean worm burdens and lower tissue egg counts when compared with adjuvant alone- and recombinant SjGST-injected controls. The native SmCE was antigenically cross-reactive with homologous enzymes of Schistosoma haematobium and Schistosoma margrebowiei

Synthesis, X-ray structure, Hirshfeld surface analysis and antimicrobial assessment of tetranuclear s-triazine hydrazine Schiff base ligand

Funding: The Deputyship for Research and Innovation, “Ministry of Education”, King Saud University (IFKSUOR3-188-3), Saudi Arabia.The unexpected tetranuclear [Cu4(DPPT)2Cl6] complex was obtained by self-assembly of CuCl2.2H2O and (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine, ( HDPPT ) in ethanol. In this tetranuclear [Cu4(DPPT)2Cl6] complex, the organic ligand acts as mononegative chelate bridging two crystallographically independent Cu(II) sites. The DPPT− anion acts as a bidentate ligand with respect to Cu(1), while it is a tridentate for Cu(2). The Cu(1)N2Cl3 and Cu(2)N3Cl spheres have square pyramidal and square planar coordination geometries with some distortion, respectively. Two of the chloride ions coordinating the Cu(1) are bridging between two crystallographically related Cu(1) sites connecting two [Cu2(DPPT)Cl3] units together, leading to the tetranuclear formula [Cu4(DPPT)2Cl6]. The packing of the [Cu4(DPPT)2Cl6] complex is dominated by C-H…Cl contacts, leading to one-dimensional hydrogen-bond polymeric structure. According to Hirshfeld surface analysis of molecular packing, the non-covalent interactions H…H, Cl…H, Cl…C, C…H, and N…H are the most significant. Their percentages are 52.8, 19.0, 3.2, 7.7, and 9.7%, respectively. Antimicrobial assessment showed good antifungal activity of the Cu(II) complex against A. fumigatus and C. albicans compared to Ketoconazole as positive control. Moreover, the [Cu4(DPPT)2Cl6] complex has higher activity against Gram-positive bacteria than Gentamycin as positive control. The opposite was observed when testing the tetranuclear [Cu4(DPPT)2Cl6] complex against the Gram-negative bacteria.Publisher PDFPeer reviewe

A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

Programmed cell death or apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics

Search for nonresonant Higgs boson pair production in the four leptons plus two b jets final state in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.10657v2 [hep-ex], https://arxiv.org/abs/2206.10657 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at this http URL (CMS Public Pages). Report number: CMS-HIG-20-004, CERN-EP-2022-114.The first search for nonresonant production of Higgs boson pairs (HH) with one H decaying into four leptons and the other into a pair of b quarks is presented, using proton-proton collisions recorded at a center-of-mass energy of s = 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 138 fb−1. A 95% confidence level upper limit of 32.4 is set on the signal strength modifier μ, defined as the ratio of the observed HH production rate in the HH→ ZZ∗b b ¯ → 4 ℓb b ¯ decay channel to the standard model (SM) expectation. Possible modifications of the H trilinear coupling λ HHH with respect to the SM value are investigated. The coupling modifier κλ, defined as λ HHH divided by its SM prediction, is constrained to be within the observed (expected) range −8.8 (−9.8) < κλ < 13.4 (15.0) at 95% confidence level. [Figure not available: see fulltext.].SCOAP3

Search for long-lived particles decaying to a pair of muons in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2205.08582v2 [hep-ex], https://arxiv.org/abs/2205.08582 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures and tables, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-006 (CMS Public Pages).An inclusive search for long-lived exotic particles decaying to a pair of muons is presented. The search uses data collected by the CMS experiment at the CERN LHC in proton-proton collisions at s = 13 TeV in 2016 and 2018 and corresponding to an integrated luminosity of 97.6 fb−1. The experimental signature is a pair of oppositely charged muons originating from a common secondary vertex spatially separated from the pp interaction point by distances ranging from several hundred μm to several meters. The results are interpreted in the frameworks of the hidden Abelian Higgs model, in which the Higgs boson decays to a pair of long-lived dark photons ZD, and of a simplified model, in which long-lived particles are produced in decays of an exotic heavy neutral scalar boson. For the hidden Abelian Higgs model with m(ZD) greater than 20 GeV and less than half the mass of the Higgs boson, they provide the best limits to date on the branching fraction of the Higgs boson to dark photons for cτ(ZD) (varying with m(ZD)) between 0.03 and ≈0.5 mm, and above ≈0.5 m. Our results also yield the best constraints on long-lived particles with masses larger than 10 GeV produced in decays of an exotic scalar boson heavier than the Higgs boson and decaying to a pair of muons. [Figure not available: see fulltext.].SCOAP3

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2301.08096v2 [hep-ex], https://arxiv.org/abs/2301.08096 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-003 (CMS Public Pages).A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (t ~1), is presented. The search targets the four-body decay of the t ~1 , which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (χ~10), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(t ~1) and m(χ~10). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(t ~1) − m(χ~10) = 10 and 80 GeV, respectively. [Figure not available: see fulltext.].SCOAP3

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as ΓH=3.2−1.7+2.4MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs