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

Phase-Insensitive Scattering of Terahertz Radiation

The nonlinear interaction between Near-Infrared (NIR) and Terahertz pulses is principally investigated as a means for the detection of radiation in the hardly accessible THz spectral region. Most studies have targeted second-order nonlinear processes, given their higher efficiencies, and only a limited number have addressed third-order nonlinear interactions, mainly investigating four-wave mixing in air for broadband THz detection. We have studied the nonlinear interaction between THz and NIR pulses in solid-state media (specifically diamond), and we show how the former can be frequency-shifted up to UV frequencies by the scattering from the nonlinear polarisation induced by the latter. Such UV emission differs from the well-known electric-field-induced second harmonic (EFISH) one, as it is generated via a phase-insensitive scattering, rather than a sum- or difference-frequency four-wave-mixing process

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

Laser-assisted guiding of electric discharges around objects

Electric breakdown in air occurs for electric fields exceeding 34 kV/cm and results in a large current surge that propagates along unpredictable trajectories. Guiding such currents across specific paths in a controllable manner could allow protection against lightning strikes and high-voltage capacitor discharges. Such capabilities can be used for delivering charge to specific targets, for electronic jamming, or for applications associated with electric welding and machining. We show that judiciously shaped laser radiation can be effectively used to manipulate the discharge along a complex path and to produce electric discharges that unfold along a predefined trajectory. Remarkably, such laser-induced arcing can even circumvent an object that completely occludes the line of sight

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

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

Tendon tissue engineering : An overview of biologics to promote tendon healing and repair

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge operating grant support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 955685, www.helsinki.fi/p4fit .Peer reviewedPublisher PD

Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

Tetrahydro-4H-(pyrrolo[3,4-d]isoxazol-3-yl)methanamine : a bicyclic diamino scaffold stabilizing parallel turn conformations

Tetrahydro-4H-(pyrrolo[3,4-d]isoxazol-3-yl)methanamine scaffold was designed as diamino derivative to stabilize parallel turn conformations. Its synthesis took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile oxide derived from the inexpensive enantiopure L-phenylalanine, and N-benzyl-3-pyrroline. Two diastereoisomers were formed whose distribution depends on the selected base. 3aR,6aS-Isomer is favoured in organic bases which formation is driven by pi-interactions. On the other hand, the above interactions were significantly prevented using an inorganic base due to the chaotropic effect of the cation, decreasing the amount of the above isomer. Finally, we demonstrated that this isomer is able of stabilizing parallel turn conformations when inserted in short peptide sequences