Anticancer and anti-inflammatory effects of tomentosin: Cellular and molecular mechanisms

Tomentosin is a natural compound known for its presence in some medicinal plants of the Asteraceae family such as Inula viscosa. Recent studies have highlighted its anticancer and anti-inflammatory properties. Its anticancer mechanisms are unique and act at different levels ranging from cellular organization to molecular transcriptional factors and epigenetic modifications. Tomentosin’s possession of the modulatory effect on telomerase expression on tumor cell lines has captured the interest of researchers and spurred a more robust study on its anticancer effect. Since inflammation has a close link with cancer disease, this natural compound appears to be a potential cancer-fighting drug. Indeed, its recently demonstrated anti-inflammatory action can be considered as a starting point for its evaluation as an anticancer chemo-preventive agent

Static Critical Behavior of the Spin-Freezing Transition in the Geometrically Frustrated Pyrochlore Antiferromagnet Y2Mo2O7

Some frustrated pyrochlore antiferromagnets, such as Y2Mo2O7, show a spin-freezing transition and magnetic irreversibilities below a temperature Tf similar to what is observed nonlinear magnetization measurements on Y2Mo2O7 that provide strong evidence that there is an underlying thermodynamic phase transition at Tf, which is characterized by critical exponents \gamma \approx 2.8 and \beta \approx 0.8. These values are typical of those found in random spin glasses, despite the fact that the level of random disorder in Y2Mo2O7 is immeasurably small.Comment: Latex file, calls for 4 encapsulated postscript figures (included). Submitted to Phys. Rev. Letters

Bolus residue scale: an easy-to-use and reliable videofluoroscopic analysis tool to score bolus residue in patients with dysphagia

Background. We aimed to validate an easy-to-use videofluoroscopic analysis tool, the bolus residue scale (BRS), for detection and classification of pharyngeal retention in the valleculae, piriform sinuses, and/or the posterior pharyngeal wall. Methods. 50 randomly selected videofluoroscopic images of 10 mL swallows (recorded in 18 dysphagia patients and 8 controls) were analyzed by 4 experts and 6 nonexpert observers. A score from 1 to 6 was assigned according to the number of structures affected by residue. Inter- and intrarater reliabilities were assessed by calculation of intraclass correlation coefficients (ICCs) for expert and nonexpert observers. Sensitivity, specificity, and interrater agreement were analyzed for different BRS levels. Results. Intrarater reproducibility was almost perfect for experts (mean ICC 0.972) and ranged from substantial to almost perfect for nonexperts (mean ICC 0.835). Interjudge agreement of the experts ranged from substantial to almost perfect (mean ICC 0.780), but interrater reliability of nonexperts ranged from substantial to good (mean 0.719). BRS shows for experts a high specificity and sensitivity and for nonexperts a low sensitivity and high specificity. Conclusions. The BRS is a simple, easy-to-carry-out, and accessible rating scale to locate pharyngeal retention on videofluoroscopic images with a good specificity and reproducibility for observers of different expertise levels.Nathalie Rommel, Charlotte Borgers, Dirk Van Beckevoort, Ann Goeleven, Eddy Dejaeger, and Taher I. Omar

Pressure flow analysis in the assessment of preswallow pharyngeal bolus presence in dysphagia

Objectives: Preswallow pharyngeal bolus presence is evident in patients with oropharyngeal dysphagia. Pressure flow analysis (PFA) using high resolution manometry with impedance (HRMI) with AIMplot software is a method for objective interpretation of pharyngeal and upper esophageal sphincter (UES) pressures and bolus flow patterns during swallowing. This study aimed to observe alterations in PFA metrics in the event of preswallow pharyngeal bolus presence as seen on videofluoroscopy (VFSS). Methods: Swallows from 40 broad dysphagia patients and 8 controls were recorded with a HRMI catheter during simultaneous VFSS. Evidence of bolus presence and level reached prior to pharyngeal swallow onset was recorded. AIMPlot software derived automated PFA functional metrics. Results: Patients with bolus movement to the pyriform sinuses had a higher SRI, indicating greater swallow dysfunction. Amongst individual metrics, TNadImp to PeakP was shorter and flow interval longer in patient groups compared to controls. A higher pharyngeal mean impedance and UES mean impedance differentiated the two patient groups. Conclusions: This pilot study identifies specific altered PFA metrics in patients demonstrating preswallow pharyngeal bolus presence to the pyriform sinuses. PFA metrics may be used to guide diagnosis and treatment of patients with oropharyngeal dysphagia and track changes in swallow function over time.Lara Ferris, Taher Omari, Margot Selleslagh, Eddy Dejaeger, Jan Tack, Dirk Vanbeckevoort and Nathalie Romme

Deterministic control of magnetic vortex wall chirality by electric field

Concepts for information storage and logical processing based on magnetic domain walls have great potential for implementation in future information and communications technologies. To date, the need to apply power hungry magnetic fields or heat dissipating spin polarized currents to manipulate magnetic domain walls has limited the development of such technologies. The possibility of controlling magnetic domain walls using voltages offers an energy efficient route to overcome these limitations. Here we show that a voltage-induced uniaxial strain induces reversible deterministic switching of the chirality of a magnetic vortex wall. We discuss how this functionality will be applicable to schemes for information storage and logical processing, making a significant step towards the practical implementation of magnetic domain walls in energy efficient computing

Gendered vulnerabilities to climate change: insights from the semi-arid regions of Africa and Asia

Emerging and on-going research indicates that vulnerabilities to impacts of climate change are gendered. Still, policy approaches aimed at strengthening local communities’ adaptive capacity largely fail to recognize the gendered nature of everyday realities and experiences. This paper interrogates some of the emerging evidence in selected semi-arid countries of Africa and Asia from a gender perspective, using water scarcity as an illustrative example. It emphasizes the importance of moving beyond the counting of numbers of men and women to unpacking relations of power, of inclusion and exclusion in decision-making, and challenging cultural beliefs that have denied equal opportunities and rights to differently positioned people, especially those at the bottom of economic and social hierarchies. Such an approach would make policy and practice more relevant to people’s differentiated needs and responses

Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks

Natural products are often uniquely suited to modulate protein-protein interactions (PPIs) due to their architectural and functional group complexity relative to synthetic molecules. Here we demonstrate that the natural product garcinolic acid allosterically blocks the CBP/p300 KIX PPI network and displays excellent selectivity over related GACKIX motifs. It does so via a strong interaction (KD 1 μM) with a non-canonical binding site containing a structurally dynamic loop in CBP/p300 KIX. Garcinolic acid engages full-length CBP in the context of the proteome and in doing so effectively inhibits KIX-dependent transcription in a leukemia model. As the most potent small-molecule KIX inhibitor yet reported, garcinolic acid represents an important step forward in the therapeutic targeting of CBP/p300

Automatische Impedantie Manometrie (AIM): objectieve diagnostiek van oro-faryngale dysfagie

Dit overzichtsartikel wil het klinisch potentieel aantonen van Automatische Impedantie Manometrie (AIM) als nieuwe, nietradiologische techniek voor screening en diagnostiek van faryngale dysfagie, zijnde slikstoornissen in de mond, keelholte en bovenste slokdarm. Deze AIM-techniek maakt gebruik van een katheter met druksensoren en impedantie-elektroden om slikken kwantitatief te beschrijven. Een geïntegreerde – eerder dan afzonderlijke – analyse van de gemeten druk- en impedantiepatronen die ontstaan bij het doorslikken van een voedselbolus, kan een zinvolle aanvulling zijn op de dynamische beeldvormingsonderzoeken die vandaag de dag als gouden standaard worden gezien. Belangrijke voordelen zijn het objectieve karakter van de techniek en de geautomatiseerde berekening van diverse slikparameters. Een globale maat voor de slikfunctie kan worden bekomen (Slik Risico Index, SRI) en houdt verband met (de ernst van) het aspiratierisico van de patiënt en de aanwezigheid van bolusresidu. Zo kan een accurate detectie van aspiratie met een sensitiviteit van 0,88 en specificiteit van 0,96 niet via radiologisch onderzoek bereikt worden. Verschillende slikparameters zijn ook voldoende gevoelig om veranderingen in voedselconsistentie te detecteren en om de effecten van slikmanoeuvres objectief te beschrijven. Recent werd ook aangetoond dat deze AIM-analyse snel en betrouwbaar kan worden uitgevoerd door clinici met variërende ervaring en opleiding. Bovendien worden in verschillende patiëntengroepen andere patronen van afwijkende slikparameters aangetroffen. Of deze observatie aanleiding kan geven tot specifieke slikdiagnoses en dus meer gerichte behandelingen is momenteel onderwerp van onderzoek

Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of household recent TB transmission in Ghana

OBJECTIVE: We investigated the cause of recurring tuberculosis (rcTB) among pulmonary TB participants recruited from a prospective population-based study conducted between July 2012 and December 2015. METHODS: Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools in addition to whole genome sequencing, followed by phylogenetic analysis to assess strain relatedness. RESULTS: A greater proportion (58.3%, 21/36) of individuals with rcTB episodes had TB recurrence within 12 months post treatment. Only 19.4% (7/36) of participants with rcTB harbored a strain with isoniazid (INH) resistance at baseline of which 29% (2/7) were additionally resistant to rifampicin. However, 27.8% (10/36) harbored an INH resistant strain upon recurring of which 40% (4/10) were MDR-TB strains. Recurrent TB was attributed to relapse (same strain) in 75.0% (27/36) of participants with 25.0% (9/36) attributed to re-infection. CONCLUSION: Our findings indicate that unresolved previous infection due to inadequate treatment may be the major cause of rcTB

CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination

BACKGROUND: The functional role of ELR-positive CXC chemokines during viral-induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR+ chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV-induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS