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

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

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

Endotenon-Derived Type II Tendon Stem Cells Have Enhanced Proliferative and Tenogenic Potential

Funding This project received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement, No. 955685. This research also received funding support from the Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Regenerative Medicine (EP/L015072/1).Peer reviewedPublisher PD

Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson’s disease

Background: Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that is mainly characterized by movement dysfunction. Neurovascular unit (NVU) disruption has been proposed to be involved in the disease, but its role in PD neurodegenerative mechanisms is still unclear. The aim of this study was to investigate cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within the regions belonging to the motor network, in patients with mild to moderate stages of PD. Methods: Twenty-eight PD patients (66.6 \ub1 8.6 years, 22 males, median [interquartile range, IQR] Hoehn & Yahr = 1.5 [1\u20131.9]) and 32 age- and sex-matched healthy controls (HCs) were scanned with arterial spin labeling (ASL) magnetic resonance imaging (MRI) for CBF assessment. ASL MRI was also acquired in hypercapnic conditions to induce vasodilation and subsequently allow for CVR measurement in a subgroup of 13 PD patients and 13 HCs. Median CBF and CVR were extracted from cortical and subcortical regions belonging to the motor network and compared between PD patients and HCs. In addition, the correlation between these parameters and the severity of PD motor symptoms [quantified with Unified Parkinson\u2019s Disease Rating Scale part III (UPDRS III)] was assessed. The false discovery rate (FDR) method was used to correct for multiple comparisons. Results: No significant differences in terms of CBF and CVR were found between PD patients and HCs. Positive significant correlations were observed between CBF and UPDRS III within the precentral gyrus, postcentral gyrus, supplementary motor area, striatum, pallidum, thalamus, red nucleus, and substantia nigra (pFDR < 0.05). Conversely, significant negative correlation between CVR and UPDRS III was found in the corpus striatum (pFDR < 0.05). Conclusion: CBF and CVR assessment provides information about NVU integrity in an indirect and noninvasive way. Our findings support the hypothesis of NVU involvement at the mild to moderate stages of PD, suggesting that CBF and CVR within the motor network might be used as either diagnostic or prognostic markers for PD