Monitoring changes in the position and boundaries of climate clusters at different time intervals

This article describes the development of a web application for the study of the correlation-regression analysis of meteorological data and search, the shift of the geographic center of clusters of different time intervals

Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands

Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further drug improvement is urgently needed. Herein, we report on triple-action platinum­(IV) prodrugs, which, in addition to tumor targeting via maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT). Unexpectedly, structure–activity relationship analysis showed that the mode of 1-MDT conjugation distinctly impacts the reducibility and thus activation of the prodrugs. This in turn affected ligand release, pharmacokinetic properties, efficiency of immunomodulation, and the anticancer activity in vitro and in a mouse model in vivo. Moreover, we could demonstrate that the design of albumin-targeted multi-modal prodrugs using platinum­(IV) is a promising strategy to enhance the cellular uptake of bioactive ligands with low cell permeability (1-MDT) and to improve their selective delivery into the malignant tissue. This will allow tumor-specific anticancer therapy supported by a favorably tuned immune microenvironment

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms’ role in ecology and human health

Hypoxia and myocardial remodeling in human cardiac allografts: a time-course study.

BACKGROUND: Cardiac allografts are known to develop myocardial fibrosis, which may be a cause of progressive cardiac dysfunction. Apart from the renin-angiotensin and transforming growth factor-beta system, hypoxia has been proposed as an important player in the pathogenesis of fibrosis, but its significance remains unclear. This study examines the degree of myocardial fibrosis, cellular remodeling and hypoxic signaling over a time-course of 10 years after human cardiac allograft transplantation. METHODS: Serial right ventricular biopsies of 57 patients were collected in 6-month intervals after cardiac transplant surgery for a total of 10 years to allow a retrospective longitudinal analysis. Over this period, tissue remodeling, including interstitial fibrosis and cellular changes, were determined morphometrically. Immunohistochemistry (IHC) was used to analyze expression of the following hypoxia-related proteins: hypoxia-induced factor 1-alpha (HIF1alpha); the oxygen sensor prolyl hydroxylase 3 (PHD3); and vascular endothelial growth factor (VEGF). RESULTS: Fibrosis increased significantly from 12.6 +/- 6.5% at the point of transplantation throughout follow-up to 28.8 +/- 7.7% at 10 years. The DNA content and number of nuclei changed over the period of follow-up, displaying signs of cellular hypertrophy and a loss of myocytes. Whereas HIF1alpha expression revealed a U-shaped pattern with both early and late elevation during fibrogenesis, PHD3 and VEGF expression patterns showed a gradual increase with PHD3 decreasing again in later fibrogenesis. CONCLUSIONS: In cardiac allografts, extensive and progressive tissue remodeling is present. Hypoxia may play a role in this process by up-regulating HIF1alpha and leading to differential regulation of pro-angiogenic signals