466 research outputs found
Piperazine-Based Metallopolymers for Bioengineering Applications
Engineering realistic and functional tissue models presents promising possibilities in drug discovery and other biomedical research. A novel polymer with potential applications in biomedical studies was developed. I report the first synthesis and characterization (with NMR, IR, GPC, UVâvis spectroscopy, and thermal analysis) of two thermoplastic poly(alkyl piperazine succinate) diols with either propyl or hexyl alkane chains bridging the piperazines. These polyester diols were chain extended with hexamethylene diisocyanate to create highly amorphous polyester urethane thermoplastic polymers. Ru(III) and Fe(III) was then successfully coordinated with these polymers, producing a total of four different metallopolymers. The crosslinking of these complexes introduces degradative properties to the polymer, which could be valuable in biomedical studies
Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay
Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic
infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied.
Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and
limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations.
We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the
intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture
and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and
untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α).
The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (âyesâno responseâ).
TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine,
and infiximab) with an R2
of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate
establishing an âEfcacy Outcome Pathways (EOPs)â framework for drug efcacy assays. The in vitro assay ofers an easy
and scalable method for IBD drug screening with a focus on human data, which requires further validation
Enhancement and suppression effects resulting from information structuring in sentences
Information structuring through the use of cleft sentences increases the processing efficiency of references to elements within the scope of focus. Furthermore, there is evidence that putting certain types of emphasis on individual words not only enhances their subsequent processing, but also protects these words from becoming suppressed in the wake of subsequent information, suggesting mechanisms of enhancement and suppression. In Experiment 1, we showed that clefted constructions facilitate the integration of subsequent sentences that make reference to elements within the scope of focus, and that they decrease the efficiency with reference to elements outside of the scope of focus. In Experiment 2, using an auditory text-change-detection paradigm, we showed that focus has similar effects on the strength of memory representations. These results add to the evidence for enhancement and suppression as mechanisms of sentence processing and clarify that the effects occur within sentences having a marked focus structure
Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report
Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment
Complete genome sequence and lifestyle of black-pigmented Corynebacterium aurimucosum ATCC 700975 (formerly C. nigricans CN-1) isolated from a vaginal swab of a woman with spontaneous abortion
Trost E, Götker S, Schneider J, et al. Complete genome sequence and lifestyle of black-pigmented Corynebacterium aurimucosum ATCC 700975 (formerly C. nigricans CN-1) isolated from a vaginal swab of a woman with spontaneous abortion. BMC Genomics. 2010;11(1): 91.Background
Corynebacterium aurimucosum is a slightly yellowish, non-lipophilic, facultative anaerobic member of the genus Corynebacterium and predominantly isolated from human clinical specimens. Unusual black-pigmented variants of C. aurimucosum (originally named as C. nigricans) continue to be recovered from the female urogenital tract and they are associated with complications during pregnancy. C. aurimucosum ATCC 700975 (C. nigricans CN-1) was originally isolated from a vaginal swab of a 34-year-old woman who experienced a spontaneous abortion during month six of pregnancy. For a better understanding of the physiology and lifestyle of this potential urogenital pathogen, the complete genome sequence of C. aurimucosum ATCC 700975 was determined.
Results
Sequencing and assembly of the C. aurimucosum ATCC 700975 genome yielded a circular chromosome of 2,790,189 bp in size and the 29,037-bp plasmid pET44827. Specific gene sets associated with the central metabolism of C. aurimucosum apparently provide enhanced metabolic flexibility and adaptability in aerobic, anaerobic and low-pH environments, including gene clusters for the uptake and degradation of aromatic amines, L-histidine and L-tartrate as well as a gene region for the formation of selenocysteine and its incorporation into formate dehydrogenase. Plasmid pET44827 codes for a non-ribosomal peptide synthetase that plays the pivotal role in the synthesis of the characteristic black pigment of C. aurimucosum ATCC 700975.
Conclusions
The data obtained by the genome project suggest that C. aurimucosum could be both a resident of the human gut and possibly a pathogen in the female genital tract causing complications during pregnancy. Since hitherto all black-pigmented C. aurimucosum strains have been recovered from female genital source, biosynthesis of the pigment is apparently required for colonization by protecting the bacterial cells against the high hydrogen peroxide concentration in the vaginal environment. The location of the corresponding genes on plasmid pET44827 explains why black-pigmented (formerly C. nigricans) and non-pigmented C. aurimucosum strains were isolated from clinical specimens
Faecal metabolome and its determinants in inflammatory bowel disease
OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.</p
The Contribution of HI-Rich Galaxies to the Damped Absorber Population at z=0
We present a study of HI-rich galaxies in the local universe selected from
blind emission-line surveys. These galaxies represent the emission-line
counterparts of local damped Lyman-alpha systems. We find that the HI
cross-section of galaxies is drawn from a large range of galaxy masses below
M_star, 66% of the area comes from galaxies in the range 8.5 < Log M_star <
9.7. Both because of the low mass galaxy contribution, and because of the range
of galaxy types and luminosities at any given HI mass, the galaxies
contributing to the HI cross-section are not exclusively L_star spirals, as is
often expected. The optical and near infrared counterparts of these galaxies
cover a range of types (from spirals to irregulars), luminosities (from L_star
to <0.01 L_star), and surface brightnesses. The range of optical and near
infrared properties as well as the kinematics for this population are
consistent with the properties for the low-z damped Lyman-alpha absorbers. We
also show that the number of HI-rich galaxies in the local universe does not
preclude evolution of the low-z damped absorber population, but it is
consistent with no evolution.Comment: 10 pages, 7 figures. To appear in "Extragalactic Gas at Low Redshift"
(ASP Conf. Series, Weymann Conf.
The Democratic Biopolitics of PrEP
PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts âsexual-somatic ethicsâ and âdemocratic biopoliticsâ, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. âBiopolitical democratizationâ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma
Associations between employee and manager gender: impacts on gender-specific risk of acute occupational injury in metal manufacturing
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