Molecular Epidemiology of Norovirus in Outbreaks of Gastroenteritis in Southwest Germany from 2001 to 2004

The identification and molecular epidemiology of norovirus in outbreaks of gastroenteritis were studied during a 3-year period in Germany. Specimens (n = 316) from 159 nonbacterial gastroenteritis outbreaks from March 2001 to June 2004 were analyzed for the presence of noroviruses by reverse transcriptase PCR. Outbreaks were most frequent in elderly people's homes and care centers (43%), followed by hospitals (24%). Molecular analyses of strains from 148 outbreaks showed that there were up to 12 genotypes involved in the outbreaks. Genogroup II noroviruses were responsible for 95% of the outbreaks. Cocirculation of more than one strain in the same outbreak and cocirculation of genogroup I and II strains in the same place were observed. Genogroup II4 (Grimsby-like) was the most prevalent strain, accounting for 48% and 67% of the outbreaks in 2002 and 2003, respectively. The genogroup IIb (Castell/Suria) genotype was observed in all the years of the study. Epidemiological and molecular data indicated that there was a major shift of the predominant strain that coincided with the appearance of a new variant of genogroup II4 in 2002. By the application of reverse transcriptase PCR, this study has demonstrated the importance and dynamism of noroviruses in Germany

Osmotic pressure modulates single cell cycle dynamics inducing reversible growth arrest and reactivation of human metastatic cells

Biophysical cues such as osmotic pressure modulate proliferation and growth arrest of bacteria, yeast cells and seeds. In tissues, osmotic regulation takes place through blood and lymphatic capillaries and, at a single cell level, water and osmoregulation play a critical role. However, the effect of osmotic pressure on single cell cycle dynamics remains poorly understood. Here, we investigate the effect of osmotic pressure on single cell cycle dynamics, nuclear growth, proliferation, migration and protein expression, by quantitative time-lapse imaging of single cells genetically modified with fluorescent ubiquitination-based cell cycle indicator 2 (FUCCI2). Single cell data reveals that under hyperosmotic stress, distinct cell subpopulations emerge with impaired nuclear growth, delayed or growth arrested cell cycle and reduced migration. This state is reversible for mild hyperosmotic stress, where cells return to regular cell cycle dynamics, proliferation and migration. Thus, osmotic pressure can modulate the reversible growth arrest and reactivation of human metastatic cells

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Public opinion about solar radiation management: A cross-cultural study in 20 countries around the world

Some argue that complementing climate change mitigation measures with solar radiation management (SRM) might prove a last resort to limit global warming to 1.5 °C. To make a socially responsible decision on whether to use SRM, it is important to consider also public opinion, across the globe and particularly in the Global South, which would face the greatest risks from both global warming and SRM. However, most research on public opinion about SRM stems from the Global North. We report findings from the first large-scale, cross-cultural study on the public opinion about SRM among the general public (N = 2,248) and students (N = 4,583) in 20 countries covering all inhabited continents, including five countries from the Global South and five ‘non-WEIRD’ (i.e. not Western, Educated, Industrialised, Rich, and Democratic) countries from the Global North. As public awareness of SRM is usually low, we provided participants with information on SRM, including key arguments in favour of and against SRM that appear in the scientific debate. On average, acceptability of SRM was significantly higher in the Global South than in the ‘non-WEIRD’ Global North, while acceptability in the ‘WEIRD’ Global North was in between. However, we found substantial variation within these clusters, especially in the ‘non-WEIRD’ Global North, suggesting that countries do not form homogenous clusters and should thus be considered individually. Moreover, the average participants’ views, while generally neither strong nor polarised, differed from some expert views in important ways, including that participants perceived SRM as only slightly effective in limiting global warming. Still, our data suggests overall a conditional, reluctant acceptance. That is, while on average, people think SRM would have mostly negative consequences, they may still be willing to tolerate it as a potential last resort to fight global warming, particularly if they think SRM has only minor negative (or even positive) impacts on humans and nature.info:eu-repo/semantics/publishedVersio

Highly specific miniaturized fluorescent monoacylglycerol lipase probes enable translational research

Monoacylglycerol lipase (MAGL) is the pivotal catabolic enzyme responsible for signal termination in the endocannabinoid system. Inhibition of MAGL offers unique advantages over the direct activation of cannabinoid receptors in treating cancer, metabolic disorders, and inflammatory diseases. Although specific fluorescent molecular imaging probes are commonly used for the real-time analysis of the localization and distribution of drug targets in cells, they are almost invariably composed of a linker connecting the pharmacophore with a large fluorophore. In this study, we have developed miniaturized fluorescent probes targeting MAGL by incorporating a highly fluorescent boron-dipyrromethene (BODIPY) moiety into the inhibitor structure that interacts with the MAGL active site. These miniaturized fluorescent probes exhibit favorable drug-like properties such as high solubility and permeability, picomolar potency for MAGL across various species, and high cell selectivity and specificity. A range of translational investigations were conducted, including cell-free fluorescence polarization assays, fluorescence-activated cell sorting analysis, and confocal fluorescence microscopy of live cancer cells, live primary neurons, and human-induced pluripotent stem cell-derived brain organoids. Furthermore, the application of red-shifted analogs or 18F positron emission labeling illustrated the significant versatility and adaptability of the fluorescent ligands in various experimental contexts.Molecular Physiolog

Colony Collapse Disorder: A Descriptive Study

BACKGROUND: Over the last two winters, there have been large-scale, unexplained losses of managed honey bee (Apis mellifera L.) colonies in the United States. In the absence of a known cause, this syndrome was named Colony Collapse Disorder (CCD) because the main trait was a rapid loss of adult worker bees. We initiated a descriptive epizootiological study in order to better characterize CCD and compare risk factor exposure between populations afflicted by and not afflicted by CCD. METHODS AND PRINCIPAL FINDINGS: Of 61 quantified variables (including adult bee physiology, pathogen loads, and pesticide levels), no single measure emerged as a most-likely cause of CCD. Bees in CCD colonies had higher pathogen loads and were co-infected with a greater number of pathogens than control populations, suggesting either an increased exposure to pathogens or a reduced resistance of bees toward pathogens. Levels of the synthetic acaricide coumaphos (used by beekeepers to control the parasitic mite Varroa destructor) were higher in control colonies than CCD-affected colonies. CONCLUSIONS/SIGNIFICANCE: This is the first comprehensive survey of CCD-affected bee populations that suggests CCD involves an interaction between pathogens and other stress factors. We present evidence that this condition is contagious or the result of exposure to a common risk factor. Potentially important areas for future hypothesis-driven research, including the possible legacy effect of mite parasitism and the role of honey bee resistance to pesticides, are highlighted