Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.

BACKGROUND: There is limited available data on the strain diversity of M tuberculosis in Peru, though there may be interesting lessons to learn from a setting where multidrug resistant TB has emerged as a major problem despite an apparently well-functioning DOTS control programme. METHODS: Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community-based patients and 241 hospital-based HIV co-infected patients with pulmonary tuberculosis in Lima, Peru. Phylogenetic and epidemiologic analyses permitted identification of clusters and exploration of spoligotype associations with drug resistance. RESULTS: Mean patient age was 31.9 years, 63% were male and 30.4% were known to be HIV+. Rifampicin mono-resistance, isoniazid mono-resistance and multidrug resistance (MDR) were identified in 4.7%, 8.7% and 17.3% of strains respectively. Of 794 strains from 794 patients there were 149 different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498 strains (62.7%) were clustered in the nine most common spoligotypes: 16.4% SIT 50 (clade H3), 12.3% SIT 53 (clade T1), 8.3% SIT 33 (LAM3), 7.4% SIT 42 (LAM9), 5.5% SIT 1 (Beijing), 3.9% SIT 47 (H1), 3.0% SIT 222 (clade unknown), 3.0% SIT1355 (LAM), and 2.8% SIT 92 (X3). Amongst HIV-negative community-based TB patients no associations were seen between drug resistance and specific spoligotypes; in contrast HIV-associated MDRTB, but not isoniazid or rifampicin mono-resistance, was associated with SIT42 and SIT53 strains. CONCLUSION: Two spoligotypes were associated with MDR particularly amongst patients with HIV. The MDR-HIV association was significantly reduced after controlling for SIT42 and SIT53 status; residual confounding may explain the remaining apparent association. These data are suggestive of a prolonged, clonal, hospital-based outbreak of MDR disease amongst HIV patients but do not support a hypothesis of strain-specific propensity for the acquisition of resistance-conferring mutations

Impurities throughout the EGRIP ice core – a microstructural perspective

Impurities in polar ice cores are analyzed for various reasons, ranging from the reconstruction of the climate of the past to the absolute positioning of age markers. In particular, microstructural impurity research provides insights into the internal deformation of ice and post-depositional stratigraphy changes. However, most stud- ies offer limited snapshots of impurity characteristics at a few specific depth regimes, highlighting the need to determine the localization and chemistry of impurities throughout one ice core with complementary methods. We report a detailed investigation of solid and dissolved impurities throughout the 2120 m long East Green- land Ice Core Project (EGRIP) ice core. Using microstructure mapping and confocal Cryo-Raman spectroscopy, we analyzed solid micro-inclusions inside 25 solid ice samples covering the last 50 ka. Micro-inclusions are heterogeneously distributed inside the ice matrix and in Holocene ice, as an upper limit assumption, between 22.3 and 42.4% are located in the vicinity of grain boundaries. We identified the mineralogy of more than 1600 solid inclusions. Most are terrestrial dust minerals, such as quartz, feldspar, mica, carbonaceous particles, and sulfate minerals, such as gypsum. Less common minerals are e.g., dolomite, hematite, nitrates, rutile, and anatase. However, the upper 900 m are characterized by various sulfate minerals, while gypsum is the domi- nant sulfate species below. In the deepest 400 m of the core, we expose the mineralogy inside and surrounding distinct cloudy bands. Aiming at a holistic picture of soluble and insoluble impurities, we combined two meth- ods for the first time: We further analyzed most samples with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Due to recent adaptions, LA-ICP-MS now enables us to image the 2D distribution of elements, such as Na, Mg, Al, and Fe, with a resolution of up to 10 microns showing element-depended dif- ferences in localization. For example, Na is primarily located at grain boundaries, and Al indicates dispersed particle clusters. Mg, and to some extent also Fe, are found in both regimes. Our results illustrate the merit of combining cryo-Raman spectroscopy and LA-ICP-MS to obtain new insights into small-scale deformation, chemical stratigraphy, and processes in deep ice and the future potential to enhance our understanding of impurities by exploiting such a multi-method approach

A Novel Porous Ti-Squarate as Efficient Photocatalyst in the Overall Water Splitting Reaction under Simulated Sunlight Irradiation

[EN] A new porous titanium(IV) squarate metal¿organic framework (MOF), denoted as IEF-11, having a never reported titanium secondary building unit, is successfully synthesized and fully characterized. IEF-11 not only exhibits a permanent porosity but also an outstanding chemical stability. Further, as a consequence of combining the photoactive Ti(IV) and the electroactive squarate, IEF-11 presents relevant optoelectronic properties, applied here to the photocatalytic overall water splitting reaction. Remarkably, IEF-11 as a photocatalyst is able to produce record H2 amounts for MOF-based materials under simulated sunlight (up to 672 µmol gcatalyst in 22 h) without any activity loss during at least 10 d.P.S.-A. and A.A.B. contributed equally to this work. The authors acknowledge the Ramón Areces Foundation project H+MOFs, the M-ERA-NET C-MOF-cell (grant PCI2020-111998 funded by MCIN/AEI/10.13039/501100011033 and European Union NextGenerationEU/ PRTR) project, and Retos Investigación MOFSEIDON (grant PID2019-104228RB-I00 funded by MCIN/AEI/10.13039/501100011033) project. S.N. thanks financial support by Ministerio de Ciencia, Innovatión y Universidades RTI2018-099482-A-I00 project and Agència Valenciana de la Innovació (AVI, INNEST/2020/111) project. H.G. thanks financial support to the Spanish Ministry of Science and Innovation (Severo Ochoa and RTI2018-098237-CO21) and Generalitat Valenciana (Prometeo2017/083). T.W. acknowledges financial support from the Swedish Research Council (VR, 2019-05465). Parts of this research were carried out at ¿CRISTAL¿ at SOLEIL. P.S. and A.A.B. sincerely thank to the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020 for the support of the synchrotron experiment.Salcedo-Abraira, P.; Babaryk, AA.; Montero-Lanzuela, E.; Contreras Almengor, OR.; Cabrero-Antonino, M.; Svensson, E.; Willhammar, T.... (2021). A Novel Porous Ti-Squarate as Efficient Photocatalyst in the Overall Water Splitting Reaction under Simulated Sunlight Irradiation. Advanced Materials. 33(52):1-9. https://doi.org/10.1002/adma.20210662719335

Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells

BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells

No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p

<p>Abstract</p> <p>Background</p> <p>The scaffold attachment factor B1 and B2 genes, <it>SAFB1/SAFB2 </it>(both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in <it>SAFB1/SAFB2 </it>have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of <it>SAFB1/SAFB2 </it>on familiar breast cancer by inherited mutations in either of the two genes.</p> <p>Results</p> <p>Mutation analysis in families showing linkage to the <it>SAFB1/2 </it>locus was performed by DNA sequencing. The complete coding sequence of the two genes <it>SAFB1 </it>and <it>SAFB2 </it>was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in <it>SAFB1 </it>and eight polymorphisms were detected in <it>SAFB2</it>. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.</p> <p>Conclusion</p> <p><it>SAFB1 </it>and <it>SAFB2 </it>are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.</p

Compositions of professionalism in counselling work: an embodied intersectionality framework

This paper explores the embodied constitution of professionalism in the context of the counselling psychology profession in Russia. We develop an embodied intersectionality framework for theorizing embodied compositions of professionalism, which allows us to explain how multiple embodied categories of difference intersect and are relationally co-constitutive in producing credible professionals, and how these intersections are contingent on intercorporeal encounters that take place in localized professional settings. Our exploration of how professionalism and professional credibility are established in Russian counselling shows that, rather than assuming that a hegemonic ‘ideal body’ is given preference in a professional context, different embodied compositions may be deemed credible in various work settings within the same profession. An embodied intersectionality framework allows us to challenge the notion of a single professional ideal and offer a dynamic and contextually situated analysis of the lived experiences of professional privilege and disadvantage

Psychophysiological effects of a web-based stress management system: A prospective, randomized controlled intervention study of IT and media workers [ISRCTN54254861]

BACKGROUND: The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool. METHODS: A randomized, prospectively controlled study was conducted with before and after measurements, involving 303 employees (187 men and 116 women, age 23–64) from four information technology and two media companies. Half of the participants were offered web-based health promotion and stress management training (intervention) lasting for six months. All other participants constituted the reference group. Different biological markers were measured to detect possible physiological changes. RESULTS: After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress, sleep quality, mental energy, concentration ability and social support. The anabolic hormone dehydroepiandosterone sulphate (DHEA-S) decreased significantly in the reference group as compared to unchanged levels in the intervention group. Neuropeptide Y (NPY) increased significantly in the intervention group compared to the reference group. Chromogranin A (CgA) decreased significantly in the intervention group as compared to the reference group. Tumour necrosis factor α (TNFα) decreased significantly in the reference group compared to the intervention group. Logistic regression analysis revealed that group (intervention vs. reference) remained a significant factor in five out of nine predictive models. CONCLUSION: The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinically relevant and common stress and health issues of today