22 research outputs found
6âČâČâThioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/1/ange_201200761_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/2/5750_ftp.pd
Predictors of positive health in disability pensioners: a population-based questionnaire study using Positive Odds Ratio
BACKGROUND: Determinants of ill-health have been studied far more than determinants of good and improving health. Health promotion measures are important even among individuals with chronic diseases. The aim of this study was to find predictors of positive subjective health among disability pensioners (DPs) with musculoskeletal disorders. METHODS: Two questionnaire surveys were performed among 352 DPs with musculoskeletal disorders. Two groups were defined: DPs with positive health and negative health, respectively. In consequence with the health perspective in this study the conception Positive Odds Ratio was defined and used in the logistic regression analyses instead of the commonly used odds ratio. RESULTS: Positive health was associated with age â„ 55 years, not being an immigrant, not having fibromyalgia as the main diagnosis for granting an early retirement, no regular use of analgesics, a high ADL capacity, a positive subjective health preceding the study period, and good quality of life. CONCLUSION: Positive odds ratio is a concept well adapted to theories of health promotion. It can be used in relation to positive outcomes instead of risks. Suggested health promotion and secondary prevention efforts among individuals with musculoskeletal disorders are 1) to avoid a disability pension for individuals <55 years of age; if necessary, to make sure rehabilitation actions continue, 2) to increase efforts to support immigrants to adjust to circumstances connected to ill-health and retirement, 3) to pay special attention to individuals with fibromyalgia and other general pain disorders, and 4) to strengthen ADL activities to support an independent active life among disability pensioners
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients
The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements
The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennuâs surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennuâs surface has been most recently migrating towards its equator (given Bennuâs increasing spin rate), we infer that Bennuâs surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennuâs top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennuâs top-shape morphology and its link to the formation of binary asteroids
Evidence for widespread hydrated minerals on asteroid (101955) Bennu
Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7â”m and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4â”m) Bennuâs spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth
Effects of 5â<i>O</i>âRibosylation of Aminoglycosides on Antimicrobial Activity and Selective Perturbation of Bacterial Translation
We studied six pairs of aminoglycosides
and their corresponding
ribosylated derivatives synthesized by attaching a ÎČ-<i>O</i>-linked ribofuranose to the 5-OH of the deoxystreptamine
ring of the parent pseudo-oligosaccharide antibiotic. Ribosylation
of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside kanamycin
B led to improved selectivity for inhibition of prokaryotic relative
to cytosolic eukaryotic in vitro translation. For the pseudodisaccharide
aminoglycoside scaffolds neamine and nebramine, ribosylated derivatives
were both more potent antimicrobials and more selective to inhibition
of prokaryotic translation. On the basis of the results of this study,
we suggest that modification of the 5-OH position of the streptamine
ring of other natural or semisynthetic pseudodisaccharide aminoglycoside
scaffolds containing an equatorial amine at the 2âČ sugar position
with a ÎČ-<i>O</i>-linked ribofuranose is a promising
avenue for the development of novel aminoglycoside antibiotics with
improved efficacy and reduced toxicity
Site-Selective Displacement of Tobramycin Hydroxyls for Preparation of Antimicrobial Cationic Amphiphiles
A short site-selective strategy for the activation and derivatization of alcohols of the clinically important aminoglycoside tobramycin is reported. The choice of amine protecting group affected the site-selective conversion of secondary alcohols of tobramycin into leaving groups. Temperature-dependent, chemoselective sequential nucleophilic displacements resulted in hetero- and homodithioether tobramycin-based cationic amphiphiles that demonstrated marked antimicrobial activity and impressive membrane selectivity
Cationic Pillararenes Potently Inhibit Biofilm Formation without Affecting Bacterial Growth and Viability
It
is estimated that up to 80% of bacterial infections are accompanied
by biofilm formation. Since bacteria in biofilms are less susceptible
to antibiotics than are bacteria in the planktonic state, biofilm-associated
infections pose a major health threat, and there is a pressing need
for antibiofilm agents. Here we report that water-soluble cationic
pillararenes differing in the quaternary ammonium groups efficiently
inhibited the formation of biofilms by clinically important Gram-positive
pathogens. Biofilm inhibition did not result from antimicrobial activity;
thus, the compounds should not inhibit growth of natural bacterial
flora. Moreover, none of the cationic pillararenes caused detectable
membrane damage to red blood cells or toxicity to human cells in culture.
The results indicate that cationic pillararenes have potential for
use in medical applications in which biofilm formation is a problem
Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall
Here,
we describe the preparation and evaluation of α,ÎČ-unsaturated
carbonyl derivatives of the bacterial translation inhibiting antibiotic
chloramphenicol (CAM). Compared to the parent antibiotic, two compounds
containing α,ÎČ-unsaturated ketones (<b>1</b> and <b>4</b>) displayed a broader spectrum of activity against a panel
of Gram-positive pathogens with a minimum inhibitory concentration
range of 2â32 ÎŒg/mL. Interestingly, unlike the parent
CAM, these compounds do not inhibit bacterial translation. Microscopic
evidence and metabolic labeling of a cell wall peptidoglycan suggested
that compounds <b>1</b> and <b>4</b> caused extensive
damage to the envelope of <i>Staphylococcus aureus</i> cells by inhibition of the early stage of cell wall peptidoglycan
biosynthesis. Unlike the effect of membrane-disrupting antimicrobial
cationic amphiphiles, these compounds did not rapidly permeabilize
the bacterial membrane. Like the parent antibiotic CAM, compounds <b>1</b> and <b>4</b> had a bacteriostatic effect on <i>S. aureus</i>. Both compounds <b>1</b> and <b>4</b> were cytotoxic to immortalized nucleated mammalian cells;
however, neither caused measurable membrane damage to mammalian red
blood cells. These data suggest that the reported CAM-derived antimicrobial
agents offer a new molecular scaffold for development of novel bacterial
cell wall biosynthesis inhibiting antibiotics
Innentitelbild: 6âČâČâThioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes (Angew. Chem. 23/2012)
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91346/1/5602_ftp.pd