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An evolutionary basis for protein design and structure prediction

Some 4 billion years ago, nature began the experiment that led to you, that bird on the branch, that branch, and everything else which is alive that you see around you. The generating process of all this splendid life is, of course, evolution. Evolution works not only on the macroscopic scale (think eyes, muscles, wings) but also on the molecular scale (think molecular antennas, nanoscale muscles,The sequence diversity of protein families is a result of the biophysical selection pressures that shaped their evolutionary history. Among the dominant pressures is selection for protein thermostability, which in itself is an attractive target in protein engineering because of its importance for various biopharmaceutical properties, the performance of industrial enzymes, and the ability to design

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis

Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional ma

90-Day readmission after radical prostatectomy—a prospective comparison between robot-assisted and open surgery

Purpose: All types of surgery are associated with complications. The debate is ongoing whether robot-assisted radical prostatectomy can lower this risk compared to open surgery. The objective of the present study was to evaluate post-operative adverse events leading to readmissions, using clinical records to classify these adverse events systematically. Materials and methods: A prospective control

Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling

Translation of novel discoveries to human disease is limited by the availability of human tissue-based models of disease. Precision-cut lung slices (PCLS) used as 3D lung tissue cultures (3D-LTCs) represent an elegant and biologically highly relevant 3D cell culture model, which highly resemble in situ tissue due to their complexity, biomechanics and molecular composition. Tissue slicing is widely

The Preparation of Decellularized Mouse Lung Matrix Scaffolds for Analysis of Lung Regenerative Cell Potential

Lung transplantation is the only option for patients with end-stage lung disease, but there is a shortage of available lung donors. Furthermore, efficiency of lung transplantation has been limited due to primary graft dysfunction. Recent mouse models mimicking lung disease in humans have allowed for deepening our understanding of disease pathomechanisms. Moreover, new techniques such as decellular

Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases

Background: A significant subset of prostate cancer (PC) patients with a castration-resistant form of the disease (CRPC) show primary resistance to androgen receptor (AR)-targeting drugs developed against CRPC. As one explanation could be the expression of constitutively active androgen receptor splice variants (AR-Vs), our current objectives were to study AR-Vs and other AR aberrations to better

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancest

Physical Activity in a Randomized Culturally Adapted Lifestyle Intervention

Introduction: Middle Eastern immigrants exhibit high levels of physical inactivity and are at an increased risk for Type 2 diabetes. The primary aim of this study was to examine the changes in objectively assessed physical activity levels following a culturally adapted lifestyle intervention program. The secondary aim was to examine the association between objectively assessed physical activity an

Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development

Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson's disease. Understanding the diversity of mDA neurons - previously well characterized anatomically - requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA se

Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N ¼ 1,595) were used to build genetic models to predic

The population impact of familial cancer, a major cause of cancer

The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were

STED Nanoscopy of Interfaces and Interactions between Nanostructure Arrays and Living Cells

STED Nanoscopy of Interfaces and Interactions between Nanostructure Arrays and Living Cells The specific arrangement of membrane lipids and proteins in a living cell at the interface to high-aspect ratio nanostructures (nanowires and nanostraws) is still unknown – as are the dynamic structural adaptations and molecular rearrangements of living cells in the vicinity of such nanostructures. Whether

STED nanoscopy of Interfaces and Interactions between Nanostructure Arrays and Living Cells

STED Nanoscopy of Interfaces and Interactions between Nanostructure Arrays and Living Cells The specific arrangement of membrane lipids and proteins in a living cell at the interface to high-aspect ratio nanostructures (nanowires and nanostraws) is still unknown – as are the dynamic structural adaptations and molecular rearrangements of living cells in the vicinity of such nanostructures. Whether

Effects of III-V semiconductor nanowires on human lung cells

Due to unique electronic and optical properties, semiconductor nanowires (NW) are widely used in various opto-electronic devices. Concerns have been raised about using NW since they share morphological similarities with nanofibers, such as carbon nanotubes and asbestos. However, the effects of NW exposure on humans remain unknown and there is a pressing need to assess any possible NW toxicity. Dur

The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson's disease

In recent years there has been a renewed interest in the basal forebrain cholinergic system as a target for the treatment of cognitive impairments in patients with Parkinson's disease, due in part to the need to explore novel approaches to treat the cognitive symptoms of the disease and in part to the development of more refined imaging tools that have made it possible to monitor the progressive c