An intrinsic limit to quantum coherence due to spontaneous symmetry breaking

We investigate the influence of spontaneous symmetry breaking on the decoherence of a many-particle quantum system. This decoherence process is analyzed in an exactly solvable model system that is known to be representative of symmetry broken macroscopic systems in equilibrium. It is shown that spontaneous symmetry breaking imposes a fundamental limit to the time that a system can stay quantum coherent. This universal timescale is $t_{spon} \simeq 2\pi N \hbar / (k_B T)$, given in terms of the number of microscopic degrees of freedom $N$, temperature $T$, and the constants of Planck ($\hbar$) and Boltzmann ($k_B$).Comment: 4 pages, 3 figure

Chemical ecology of antibiotic production by actinomycetes

Actinomycetes are a diverse family of filamentous bacteria that produce a plethora of natural products relevant for agriculture, biotechnology and medicine, including the majority of the antibiotics we use in the clinic. Rather than as free-living bacteria, many actinomycetes have evolved to live in symbiosis with among others plants, fungi, insects and sponges. As a common theme, these organisms profit from the natural products and enzymes produced by the actinomycetes, for example, for protection against pathogenic microbes, for growth promotion or for the degradation of complex natural polymers such as lignocellulose. At the same time, the actinomycetes benefit from the resources of the hosts they interact with. Evidence is accumulating that these interactions control the expression of biosynthetic gene clusters and have played a major role in the evolution of the high chemical diversity of actinomycete-produced secondary metabolites. Many of the biosynthetic gene clusters for antibiotics are poorly expressed under laboratory conditions, but they are likely expressed in response to host-specific demands. Here, we review the environmental triggers and cues that control natural product formation by actinomycetes and provide pointers as to how these insights may be harnessed for drug discovery

Occurrence, Fate, and Related Health Risks of PFAS in Raw and Produced Drinking Water

This study investigates human exposure to per- and polyfluoroalkyl substances (PFAS) via drinking water and evaluates human health risks. An analytical method for 56 target PFAS, including ultrashort-chain (C2–C3) and branched isomers, was developed. The limit of detection (LOD) ranged from 0.009 to 0.1 ng/L, except for trifluoroacetic-acid and perfluoropropanoic-acid with higher LODs of 35 and 0.24 ng/L, respectively. The method was applied to raw and produced drinking water from 18 Dutch locations, including groundwater or surface water as source, and applied various treatment processes. Ultrashort-chain (300 to 1100 ng/L) followed by the group of perfluoroalkyl-carboxylic-acids (PFCA, ≥C4) (0.4 to 95.1 ng/L) were dominant. PFCA and perfluoroalkyl-sulfonic-acid (≥C4), including precursors, showed significantly higher levels in drinking water produced from surface water. However, no significant difference was found for ultrashort PFAS, indicating the need for groundwater protection. Negative removal of PFAS occasionally observed for advanced treatment indicates desorption and/or degradation of precursors. The proportion of branched isomers was higher in raw and produced drinking water as compared to industrial production. Drinking water produced from surface water, except for a few locations, exceed non-binding provisional guideline values proposed; however, all produced drinking waters met the recent soon-to-be binding drinking-water-directive requirements

TURBULENCE IN MOLECULAR CLOUDS

We generate random Gaussian turbulent velocity fields with a Kolmogorov spectrum and use these to obtain synthetic line-of-sight velocity profiles. The profiles are found to be similar to line profiles observed in molecular clouds. We suggest methods for analysing measured line profiles to test whether they might arise from Gaussian Kolmogorov turbulence.Comment: accepted in ApJ, compressed postscript, figures not included. Complete preprint available at http://ucowww.ucsc.edu/~dubinski/home.html or by request to [email protected]

Low frequency of POLD1 and POLE exonuclease domain variants in patients with multiple colorectal polyps

Background Germline mutations affecting the exonuclease domains of POLE and POLD1 predispose to colorectal adenomas and carcinoma. Here, we aimed to screen the exonuclease domains to find the genetic causes of multiple colorectal polyps in unexplained cases. Methods Using a custom next-generation sequencing panel, we sequenced the exonuclease domains of POLE and POLD1 in 332 index patients diagnosed with multiple colorectal polyps without germline alteration in colorectal polyposis predisposing genes. Results We identified two variants of unknown significance. One germline POLD1 c.961G>A, p.(Gly321Ser) variant was found in two cases. The first patient was diagnosed with multiple polyps at age 35 and colorectal cancer (CRC) at age 37, with no known family history of CRC. The second patient was diagnosed with CRC at age 44 and cumulatively developed multiple polyps; this patient had two sisters with endometrial cancer who did not carry the variant. Furthermore, we identified a novel POLD1 c.955 T>G, p.(Cys319Gly) variant in a patient diagnosed with multiple colorectal adenomas at age 40. Co-segregation analysis showed that one sister who cumulatively developed multiple adenomas from age 34, and another sister who developed CRC at age 38 did not carry the variant. We did not identify pathogenic variants in POLE and POLD1. Conclusion This study confirms the low frequency of causal variants in these genes in the predisposition for multiple colorectal polyps, and also establishes that these genes are a rare cause of the disease.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Continuous Tcr signaling in the atherosclerotic environment induces immunomodulatory Cd8+ T-cells expressing Cd39

CD8+ T-cells can be atheroprotective in clinically relevant advanced stages of atherosclerosis, as their depletion results in less stable lesions with a more inflammatory phenotype. However, the phenotype and function of these cells in the lesional microenvironment remains to be determined. Here, we address how the atherosclerotic environment affects the functionality of CD8+ T-cells.We compared the cytokine production of CD8+ T-cells derived from spleens and aortas of apoE-/- mice with advanced atherosclerosis by flow cytometry.CD8+ T-cells isolated from atherosclerotic lesions produced lower amounts of IFN-γ and TNF-α than their splenic counterparts. The observed dysfunctional phenotype of the lesion-derived CD8+ T-cells was associated with an increased expression of the ectonucleotidase CD39, which converts inflammatory extracellular ATP into immunomodulatory adenosine. Indeed, pharmacological inhibition of CD39 in apoE-/- mice partly restored cytokine production by CD8+ T-cells. Using a bone-marrow transplantation approach, we showed that induction of CD39 was a consequence of antigen-specific CD8+ T-cell activation via T-cell receptor (TCR) signaling within the lesions. Importantly, analysis of human endarterectomy samples showed a clear microenvironment specific upregulation of CD39 on CD8+ T-cells in the plaques of human patients compared to matched CD8+ T-cells from the blood .Our results indicate that the continuous TCR signaling in the atherosclerotic plaque induces an immune regulatory CD8+ T-cell phenotype that is associated with decreased cytokine production through increased CD39 expression in both a murine atherosclerotic model and in atherosclerosis patients. This provides a new understanding of atheroprotective immune regulation by CD8+ T-cells.Biopharmaceutic

CD39 identifies a microenvironment-specific anti-inflammatory CD8+ T-cell population in atherosclerotic lesions

CD8+T-cells have been attributed both atherogenic and atheroprotective properties, butanalysis of CD8+T-cells has mostly been restricted to the circulation and secondary lymphoid organs. Theatherosclerotic lesion, however, is a complex microenvironment containing a plethora of inflammatory signals,which may affect CD8+T-cell activation. Here, we address how this environment affects the functionality ofCD8+T-cells. We compared the cytokine production of CD8+T-cells derived from spleens and en-zymatically digested aortas ofapoE−/−mice with advanced atherosclerosis byflow cytometry. Aortic CD8+T-cells produced decreased amounts of IFN-γand TNF-αcompared to their systemic counterparts. The observeddysfunctional phenotype of the lesion-derived CD8+T-cells was not associated with classical exhaustion mar-kers, but with increased expression of the ectonucleotidase CD39. Indeed, pharmacological inhibition of CD39 inapoE−/−mice partly restored cytokine production by CD8+T-cells. Using a bone-marrow transplantation ap-proach, we show that TCR signaling is required to induce CD39 expression on CD8+T-cells in atheroscleroticlesions. Importantly, analysis of human endarterectomy samples showed a strong microenvironment specificupregulation of CD39 on CD8+T-cells in the plaques of human patients compared to matched blood samples. Our results suggest that the continuous TCR signaling in the atherosclerotic environment in thevessel wall induces an immune regulatory CD8+T-cell phenotype that is associated with decreased cytokineproduction through increased CD39 expression in both a murine atherosclerotic model and in atherosclerosispatients. This provides a new understanding of immune regulation by CD8+T-cells in atherosclerosis.BiopharmaceuticsDrug Delivery Technolog