A Preliminary Comparison of the Katrak Hand Movement Scale With the Upper Extremity Fugl Meyer Assessment Shows a Strong Correlation After Stroke.

Objective: To investigate the concurrent validity of the KHMS with the FMA-UE.

Design: The FMA-UE and the KHMS were administered to 50 adults with stroke to evaluate their concurrent validity.

Setting: Three tertiary rehabilitation hospitals.

Concussion incidence and mechanisms differ between elite females and males in Australian Football.

Objectives: To investigate the incidence and the game circumstances of concussion in the professional female (AFLW) and male (AFL) competitions of Australian Football, to identify potential targets for risk reduction.

Design: Retrospective cohort.

Methods: Concussion data were obtained from the AFL injury database, which included all concussions sustained by AFL (Male) players from 2015 to 18 and AFLW (Female) players from 2017 to 19.

Synthetic cannabinoid use in an adult male prison in the UK.

Introduction: Synthetic cannabinoids (i.e. Spice) are a major public health problem in UK prisons, however, research in this area is limited.

Unbiased proteomic analysis of extracellular vesicles secreted by senescent human vascular smooth muscle cells reveals their ability to modulate immune cell functions.

Atherosclerosis, a common age-related disease, is characterized by intense immunological activity. Atherosclerotic plaque is composed of endothelial cells, vascular smooth muscle cells (VSMCs), lipids and immune cells infiltrating from the blood. During progression of the disease, VSMCs undergo senescence within the plaque and secrete SASP (senescence-associated secretory phenotype) factors that can actively modulate plaque microenvironment.

Therapy-induced polyploidization and senescence: Coincidence or interconnection?

Polyploid somatic cells have 'programmed' roles in normal development and stress responses. Transient polyploidy states have been observed in several tumor types at early stages of tumorigenesis. They can give rise to the aneuploidy state which is a common feature of human cancer cells.

Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells.

The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid cells produced progeny (escapers) that possessed the same amount of DNA as parental cells.

ATM-deficient neural precursors develop senescence phenotype with disturbances in autophagy.

ATM is a kinase involved in DNA damage response (DDR), regulation of response to oxidative stress, autophagy and mitophagy. Mutations in the ATM gene in humans result in ataxi A-Telangiectasia disease (A-T) characterized by a variety of symptoms with neurodegeneration and premature ageing among them. Since brain is one of the most affected organs in A-T, we have focused on senescence of neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts.

Modeling flame extinction and reignition in large eddy simulations with fast chemistry.

This work seeks to support the validation of large eddy simulation models used to simulate fire suppression. The emphasis in the present study is on the prediction of flame extinction and the prevention of spurious reignition using a fast chemistry, mixing-controlled combustion model applicable to realistic fire scenarios of engineering interest. The configuration provides a buoyant, turbulent methane diffusion flame within a controlled co-flowing oxidizer.

Is senescence-associated β-galactosidase a marker of neuronal senescence?

One of the features of cellular senescence is the activity of senescence-associated- β-galactosidase (SA-β-gal). The main purpose of this study was to evaluate this marker of senescence in aging neurons. We found that cortical neurons exhibited noticeable SA-β-gal activity quite early in culture.

NOX4 downregulation leads to senescence of human vascular smooth muscle cells.

Senescence is a stress response characterized by an irreversible growth arrest and alterations in certain cell functions. It is believed that both double-strand DNA breaks (DSB) and increased ROS level are the main culprit of senescence. Excessive ROS production is also particularly important in the development of a number of cardiovascular disorders.

Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.

Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo.

Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence.

Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise to some doubts concerning the effectiveness of the senescence-induced anticancer therapy. Similarly, it is postulated that polyploidization of cancer cells is connected with disease relapse.

Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors in vitro.

Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD(+) as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure of the weak inhibitor 5-aminoiso quinolin-1-one, 3-aryl-5-substituted-isoquinolin-1-ones were designed as inhibitors to explore the structure-activity relationships (SARs) for binding and to define the shape of a hydrophobic cavity in the active site.

[Neuronal ageing].

Ageing leads to irreversible alterations in the nervous system, which to various extent impair its functions such as capacity to learn and memory. In old neurons and brain, similarly to what may take place in other cells, there is increased oxidative stress, disturbed energetic homeostasis and metabolism, accumulation of damage in proteins and nucleic acids. Characteristic of old neurons are alterations in plasticity, synaptic transmission, sensitivity to neurotrophic factors and cytoskeletal changes.

Digital camera measurements of soot temperature and soot volume fraction in axisymmetric flames.

New diagnostics are presented that use a digital camera to measure full-field soot temperatures and soot volume fractions in axisymmetric flames. The camera is a Nikon D700 with 12 megapixels and 14 bit depth in each color plane, which was modified by removing the infrared and anti-aliasing filters. The diagnostics were calibrated with a blackbody furnace.

Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in the presence of PCSK9 in vitro.

Disrupting the binding interaction between proprotein convertase (PCSK9) and the epidermal growth factor-like domain A (EGF-A domain) in the low-density lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling and thereby lower circulating cholesterol levels. In this study, truncated 26 amino acid EGF-A analogs were designed and synthesized, and their structures were analyzed in solution and in complex with PCSK9. The most potent peptide had an increased binding affinity for PCSK9 (KD = 0.

One-pot tandem Hurtley-retro-Claisen-cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs.

Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of β-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins.

5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).

PARP-2 is a member of the poly(ADP-ribose) polymerase family, with some activities similar to those of PARP-1 but with other distinct roles. Two series of isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors of PARP-2, using the structures of the catalytic sites of the isoforms. A new efficient synthesis of 5-aminoisoquinolin-1-one was developed, and acylation with acyl chlorides gave 5-acylaminoisoquinolin-1-ones.

Synthesis of 4-alkyl-, 4-aryl- and 4-arylamino-5-aminoisoquinolin-1-ones and identification of a new PARP-2 selective inhibitor.

The considerable interest in substituted isoquinolin-1-ones related to 5-aminoisoquinolin-1-one (5-AIQ) as drugs points to a need for an efficient and straightforward synthesis of the 4,5-disubstituted bicycles. Bromination of 5-nitroisoquinolin-1-one gave 4-bromo-5-nitroisoquinolin-1-one but neither this nor 5-amino-4-bromoisoquinolin-1-one would participate in Pd-catalysed couplings. Protection of the lactam as 1-methoxy- and 1-benzyloxy-4-bromo-5-nitroisoquinolines, however, permitted Stille, Suzuki and Buchwald-Hartwig couplings to take place in high yields, insensitive to electronic demands and severe steric bulk in the arylboronic acids.

A cation-regulated and proton gradient-dependent cation transporter from Chlamydomonas reinhardtii has a role in calcium and sodium homeostasis.

The CrCAX1 gene encoding a Ca2+/H+ and Na+/H+ exchanger was cloned and characterized from the unicellular green alga Chlamydomonas reinhardtii to begin to understand the mechanisms of cation homeostasis in this model organism. CrCAX1 was more closely related to fungal cation exchanger (CAX) genes than those from higher plants but has structural characteristics similar to plant Ca2+/H+ exchangers including a long N-terminal tail. When CrCAX1-GFP was expressed in Saccharomyces cerevisiae, it localized at the vacuole.

Formation of 3-aryl-5-nitroisocoumarins from 5-nitroisocoumarins and aromatic acyl chlorides under Friedel-Crafts conditions.

Treatment of 5-nitroisocoumarin with aromatic acyl chlorides under Friedel-Crafts conditions gives 3-aryl-5-nitroisocoumarins, rather than the expected 4-acyl-5-nitroisocoumarins. This procedure was optimized for reaction temperature (150 degrees C), solvent (nitrobenzene), and Lewis acid (SnCl4). Reaction of 5-nitroisocoumarin with [13C]-carbonyl benzoyl chloride under the optimum conditions gave 5-nitro-3-phenylisocoumarin in which the 13C is located at the 3-C of the heterocycle, indicating that the benzoyl carbon framework is incorporated intact.

Thin-filament pyrometry with a digital still camera.

A novel thin-filament pyrometer is presented. It involves a consumer-grade color digital still camera with 6 megapixels and 12 bits per color plane. SiC fibers were used and scanning-electron microscopy found them to be uniform with diameters of 13.