Synthesis, Conformation and Antiproliferative Activity of Isothiazoloisoxazole 1,1-dioxides

Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included

Reply to Comment on: Hawking radiation from ultrashort laser pulse filaments

A comment by R. Schutzhold et al. raises possible concerns and questions regarding recent measurements of analogue Hawking radiation. We briefly reply to the opinions expressed in the comment and sustain that the origin of the radiation may be understood in terms of Hawking emission

Herpes simplex virus type 1 and Alzheimer’s disease : link and potential impact on treatment

Introduction: Alzheimer\u2019s disease (AD), the most common form of dementia worldwide, is a multifactorial disease with a still unknown etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to be one of the factors involved in the pathogenesis of the disease. Areas covered: We review the literature focusing on viral characteristics of HSV-1, the mechanisms this virus uses to infect neural cells, its interaction with the host immune system and genetic background and summarizes results and research that support the hypothesis of an association between AD and HSV-1. The possible usefulness of virus-directed pharmaceutical approaches as potential treatments for AD will be discussed as well. Expert opinion: We highlight crucial aspects that must be addressed to clarify the possible role of HSV-1 in the pathogenesis of the disease, and to allow the design of new therapeutical approaches for AD

Identification of the first enantiopure Rac1–Tiam1 protein–protein interaction inhibitor and its optimized synthesis via phosphine free remote group directed hydroarylation

A phospine free hydroarylation reaction applied to norbornene derivatives is described for the first time and was exploited for the regioselective gram scale synthesis of AR-148, a known Rac1\u2013Tiam1 PPI inhibitor. Umpolung conversion of the nitro group into free amine allowed the regiocontrol of the key arylation step via a long range effect. The effect of AR-148 in comparison with its enantiomers on Rac1 activation of has been evaluated and ( 12)AR-148 has been identified as the first enantiomerically pure inhibitor of Rac1\u2013Tiam1 PPI

Circulatory miR-223-3p Discriminates Between Parkinson’s and Alzheimer’s Patients

MiR-223-3p is involved in the regulation of a broad range of cellular processes and in many types of pathological processes as cancer, autoimmune and inflammatory diseases. MiR-223-3p has been indicated as negative regulator of NLRP3 protein, a key protein of inflammasome. The chronic inflammasome activation, an underlying feature of neurodegenerative disorders, is induced by misfolded protein aggregates, including amyloid-beta and alpha-synuclein, resulting in pro-inflammatory cytokines secretion and propagating of neuroinflammation. The aim of the study was to analyze whether circulatory miR-223-3p could be used as biomarker in neurodegeneration and to clarify its possible relationship with inflammasome activation. miR-223-3p concentration was evaluated in serum of Alzheimer\u2019s (AD) and Parkinson\u2019s disease (PD) or mild cognitive impairment (MCI) patients and healthy controls (HC). Compared to HC, miR-223-3p serum concentration was reduced in MCI and AD, but up-regulated in PD (p < 0.0001), and it decreased progressively from MCI to moderate (p < 0.0001) to severe AD (p = 0.0016). Receiver operating characteristic analysis showed that miR-223-3p concentration discriminates between AD, PD and MCI vs. HC, as well as between AD and PD. miR-223-3p serum concentration discriminates between AD/MCI and PD, suggesting that this molecule could be a potential non-invasive biomarker for differential diagnosis and prognosis of these neurodegenerative conditions

The Origin of Massive Compact Galaxies: Lessons from IllustrisTNG

We investigate the formation and evolution of z=0 massive compact galaxies (MCGs) in the IllustrisTNG cosmological simulation. We found that, as in observations, MCGs are mainly old (median age $\sim 10.8$ Gyr), have super-solar metallicities (median $\log Z/Z_{\odot}\sim0.35$) and are $\alpha$-enhanced (median $[\alpha/Fe]\sim0.25$). The age distribution extends to younger ages, however, and a few MCGs are as young as $\sim7$ Gyr. In general, MCGs assemble their mass early and accrete low angular momentum gas, significantly increasing their mass while growing their size much slower. A small fraction of MCGs follow another evolutionary path, going through a compaction event, with their sizes shrinking by 40% or more. The accretion of low angular momentum gas leads to enhanced SMBH growth, and MCGs reach the threshold SMBH mass of $\log M_\mathrm{BH}\sim10^{8.5} M_\odot$ - when kinetic AGN feedback kicks in and quenches the galaxy - earlier than non-compact galaxies. Comparing MCGs to a sample of median-sized quiescent galaxies matched in effective velocity dispersion, we find that their accretion histories are very different. 71% of MCGs do not merge after quenching compared to 37% of median-sized quiescent galaxies. Moreover, tracing these populations back in time, we find that at least a third of median-sized quiescent galaxies do not have a compact progenitor, underscoring that both dry mergers and progenitor bias effects are responsible for the differences in the kinematics and stellar population properties of MCGs and median-sized quiescent galaxies.Comment: 15 pages, 15 figures (not including appendices). Accepted for publication in the Monthly Notices of the Royal Astronomical Societ

Palladium-catalyzed domino carbopalladation/5-exo-allylic amination of \u3b1-amino allenamides: an efficient entry to enantiopure imidazolidinones

Allenamides of alpha-amino acids were converted into enantiopure 2-vinylimidazolidin-4-ones by a carbopalladation/exo-cyclization process. The products were obtained in 2.5:1-5.5:1 dr, with 94-99% ee. The palladium-catalyzed carbonylative cyclization of the same substrates afforded enone structures. Starting from properly substituted allenamides, an intramolecular carbopalladation followed by intramolecular amination gave rise to tricyclic fused-ring imidazolidinones

Seroprevalence and incidence of Toxoplasma gondii infection in the Legnano area of Italy

ABSTRACTThe decreasing prevalence of anti-Toxoplasma antibodies in Europe has re-opened the question of the appropriateness of serological screening during pregnancy. A study of 3426 pregnant women, resident in the Legnano area of Italy, revealed that the IgG seroprevalence according to ELISA was 21.5%, and that of IgM according to ELISA and enzyme-linked fluorescent assay was 1.2% and 0.9%, respectively. The incidence of infection, estimated on the basis of IgG avidity, was 0.9%. These results confirm a decrease in the prevalence of IgG, but indicate a high incidence of infection, thus suggesting that screening for anti-Toxoplasma antibodies during pregnancy should be maintained