Study of cosolvent-induced α-chymotrypsin fibrillogenesis: Does protein surface hydrophobicity trigger early stages of aggregation reaction?

The misfolding of specific proteins is often associated with their assembly into fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterize amyloid formation in vitro, there is no deep knowledge about the environment (in which aggregation occurs) as well as mechanism of this type of protein aggregation. Alpha-chymotrypsin was recently driven toward amyloid aggregation by the addition of intermediate concentrations of trifluoroethanol. In the present study, approaches such as turbidimetric, thermodynamic, intrinsic fluorescence and quenching studies as well as chemical modification have been successfully used to elucidate the underlying role of hydrophobic interactions (involved in early stages of amyloid formation) in α-chymotrypsin-based experimental system. © 2009 Springer Science+Business Media, LLC

Utilising daily diaries to examine oral health experiences associated with dentine hypersensitivity

Background: The current investigation examined the determinants of oral health experiences associated with dentine hypersensitivity using prospective diary methodology. Methods: Staff and students from a large UK university who had self-diagnosed dentine hypersensitivity completed an online daily diary and text survey for two weeks recording their mood, oral health-related coping behaviours, coping and pain appraisals, pain experiences and functional limitations. Cross sectional and lagged path analyses were employed to examine relationships. Results: 101 participants took part in the diary study. Participants had a mean age of 26.3 years (range=18-63) and most were female (N=69). Individuals who used more oral health-related coping behaviours predicted and experienced greater levels of pain on subsequent days. Negative mood also predicted worse pain outcomes. The daily diary method provided a useful avenue for investigating variations in oral health experiences and relationships between variables that can fluctuate daily. Conclusions: Psychological variables such as coping and mood play an important role in the pain experiences of people with dentine hypersensitivity. The study highlights the benefits of using prospective methods to elucidate the experiences of people with oral condition

The heteronomy of choice architecture

Choice architecture is heralded as a policy approach that does not coercively reduce freedom of choice. Still we might worry that this approach fails to respect individual choice because it subversively manipulates individuals, thus contravening their personal autonomy. In this article I address two arguments to this effect. First, I deny that choice architecture is necessarily heteronomous. I explain the reasons we have for avoiding heteronomous policy-making and offer a set of four conditions for non-heteronomy. I then provide examples of nudges that meet these conditions. I argue that these policies are capable of respecting and promoting personal autonomy, and show this claim to be true across contrasting conceptions of autonomy. Second, I deny that choice architecture is disrespectful because it is epistemically paternalistic. This critique appears to loom large even against non-heteronomous nudges. However, I argue that while some of these policies may exhibit epistemically paternalistic tendencies, these tendencies do not necessarily undermine personal autonomy. Thus, if we are to find such policies objectionable, we cannot do so on the grounds of respect for autonomy

An in vitro approach to study effects of prebiotics and probiotics on the faecal microbiota and selected immune parameters relevant to the elderly

The aging process leads to alterations of gut microbiota and modifications to the immune response, such changes may be associated with increased disease risk. Prebiotics and probiotics can modulate microbiome changes induced by aging; however, their effects have not been directly compared. The aim of this study was to use anaerobic batch culture fermenters to assess the impact of various fermentable carbohydrates and microorganisms on the gut microbiota and selected immune markers. Elderly volunteers were used as donors for these experiments to enable relevance to an aging population. The impact of fermentation supernatants on immune markers relevant to the elderly were assessed in vitro. Levels of IL-1β, IL-6, IL-8, IL-10 and TNF-α in peripheral blood mononuclear cell culture supernatants were measured using flow cytometry. Trans-galactooligosaccharides (B-GOS) and inulin both stimulated bifidobacteria compared to other treatments (p<0.05). Fermentation supernatants taken from faecal batch cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus and Ba. coagulans inhibited LPS induced TNF-α (p<0.05). IL-10 production, induced by LPS, was enhanced by fermentation supernatants from faecal batch cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus, Ba. coagulans and Bac. thetaiotaomicron (p<0.05). To conclude, prebiotics and probiotics could lead to potentially beneficial effects to host health by targeting specific bacterial groups, increasing saccharolytic fermentation and decreasing inflammation associated with aging. Compared to probiotics, prebiotics led to greater microbiota modulation at the genus level within the fermenters

Academic careers in Computer Science: Continuance and transience of lifetime co-authorships

International audienceScholarly publications reify fruitful collaborations between co-authors. A branch of research in the Science Studies focuses on analyzing the co-authorship networks of established scientists. Such studies tell us about how their collaborations developed through their careers. This paper updates previous work by reporting a transversal and a longitudinal studies spanning the lifelong careers of a cohort of researchers from the DBLP bibliographic database. We mined 3,860 researchers' publication records to study the evolution patterns of their co-authorships. Two features of co-authors were considered: 1) their expertise, and 2) the history of their partnerships with the sampled researchers. Our findings reveal the ephemeral nature of most collaborations: 70% of the new co-authors were only one-shot partners since they did not appear to collaborate on any further publications. Overall, researchers consistently extended their co-authorships 1) by steadily enrolling beginning researchers (i.e., people who had never published before), and 2) by increasingly working with confirmed researchers with whom they already collaborated

Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer Institution

Background: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.info:eu-repo/semantics/publishedVersio

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Repeated Methamphetamine Administration Differentially Alters Fos Expression in Caudate-Putamen Patch and Matrix Compartments and Nucleus Accumbens

Background: The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase (‘‘sensitization’’) in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatum—the so-called patch/striosome and matrix. Methodology/Principal Findings: In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens). Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but no

Desferrioxamine decreases NAD redox potential of intact red blood cells: evidence for desferrioxamine as an inducer of oxidant stress in red blood cells

BACKGROUND: Desferrioxamine (DFO) is an important iron chelating agent. It has also been thought of as an agent with anti-oxidant potential as it chelates ferric iron in various parts of the body. However, there is evidence suggesting that it may paradoxically affect red blood cells (RBC) by inducing intracellular oxidant stress. To further understand the mechanism of DFO's interaction with RBC, we conducted a study to determine the effect of DFO upon RBC's redox status. METHODS: We examined NAD redox potential in intact RBC (N = 5) incubated with DFO. RBC were incubated with 6 mM DFO for 2 hours. RESULTS: Significant decreases in NAD redox potential were observed after incubation of RBC with 6 mM DFO. The mean decrease was 10.01 ± 1.98% (p < 0.0004). CONCLUSIONS: The data confirm the oxidant effect of DFO on RBC

The Bile Acid Synthesis Pathway Is Present and Functional in the Human Ovary

Background: Bile acids, end products of the pathway for cholesterol elimination, are required for dietary lipid and fat-soluble vitamin absorption and maintain the balance between cholesterol synthesis in the liver and cholesterol excretion. They are composed of a steroid structure and are primarily made in the liver by the oxidation of cholesterol. Cholesterol is also highly abundant in the human ovarian follicle, where it is used in the formation of the sex steroids. Methodology/Principal Findings: Here we describe for the first time evidence that all aspects of the bile acid synthesis pathway are present in the human ovarian follicle, including the enzymes in both the classical and alternative pathways, the nuclear receptors known to regulate the pathway, and the end product bile acids. Furthermore, we provide functional evidence that bile acids are produced by the human follicular granulosa cells in response to cholesterol presence in the culture media. Conclusions/Significance: These findings establish a novel pathway present in the human ovarian follicle that has the capacity to compete directly with sex steroid synthesis