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Structure-Based Discovery of Small-Molecule Inhibitors of the Autocatalytic Proliferation of α-Synuclein Aggregates

The presence of amyloid fibrils of α-synuclein is closely associated with Parkinson's disease and related synucleinopathies. It is still very challenging, however, to systematically discover small molecules that prevent the formation of these aberrant aggregates. Here, we describe a structure-based approach to identify small molecules that specifically inhibit the surface-catalyzed secondary nucle

Amyloids and protein aggregation

A general discovery in protein science in the past few decades has been the finding that a number of unrelated proteins and peptides all have a marked propensity to form amyloid fibrils in vivo and in vitro. These structures have become known as the pathological hallmark of some of the most prevalent neurodegenerative diseases. More recently, the process of amyloid formation has been demystified t

Gas-Phase Anion Exchange for Multisegment Heterostructured CsPb(Br1xClx)3 Perovskite Nanowires

Metal-halide perovskites (MHPs) are promising as active optoelectronic materials for a diverse range of devices. Anion exchange is a post-growth modification of MHP materials that allows tuning of the band gap and crystal structure by exposure to alternative halides, normally using solution methods. Here, low temperature gas-phase anion exchange for the conversion of CsPbBr3 nanowires (NW) into Cs

Investigating the prognostic value of mammographic breast density and mammographic tumor appearance in women with invasive breast cancer : The Malmö Diet and cancer study

Background: High breast density is a risk factor for breast cancer. However, whether density is a prognostic factor is debatable. Also, tumor appearances are related to tumor characteristics. Here we investigate the relationship between breast cancer-specific survival and mammographic breast density and mammographic tumor appearances. Methods: Women in the Malmö Diet and Cancer study with invasive

Coronary artery restenosis and target lesion revascularisation in women by pregnancy history

Background Women's pregnancy history is associated with incident risk of coronary artery disease with some evidence also suggesting a relevance for prognosis following treatment. Objectives To study the associations between maternal history of preterm delivery, a history of small for gestational age infant, parity and age at first delivery with clinical restenosis after percutaneous coronary inter

Pain and labor outcomes : A longitudinal study of adults with cerebral palsy in Sweden

BACKGROUND: Pain is a global health concern with substantial societal costs and limits the activity participation of individuals. The prevalence of pain is estimated to be high among individuals with cerebral palsy (CP).OBJECTIVES: To estimate the association between pain and labor outcomes for adults with CP in Sweden.METHODS: A longitudinal cohort study based on data from Swedish population-base

The role of pain and walking difficulties in shaping willingness to undergo joint surgery for osteoarthritis : Data from the Swedish BOA register

OBJECTIVES: To investigate whether the association between pain intensity and willingness to undergo surgery is explained by walking difficulties, in patients with knee or hip osteoarthritis (OA).METHODS: This is an observational study using data from the Better management of patients with Osteoarthritis (BOA) register, which collects data from a publicly financed self-management programme for peo

Amyloid formation as a protein phase transition

The formation of amyloid fibrils is a general class of protein self-assembly behaviour, which is associated with both functional biology and the development of a number of disorders, such as Alzheimer and Parkinson diseases. In this Review, we discuss how general physical concepts from the study of phase transitions can be used to illuminate the fundamental mechanisms of amyloid self-assembly. We

Using Endogenous MicroRNA Expression Patterns to Visualize Neural Differentiation of Human Pluripotent Stem Cells

Many existing protocols for neuronal differentiation of human pluripotent cells result in heterogeneous cell populations and unsynchronized differentiation, necessitating the development of methods for labeling specific cell populations. Here we describe how microRNA-regulated lentiviral vectors can be used to visualize specific cell populations by exploiting endogenous microRNA expression pattern

Age-Dependent Metastatic Spread and Survival : Cancer of Unknown Primary as a Model

In order to describe a novel approach for the clinical study of metastases, we provide here age-specific incidence and survival data for cancer of unknown primary (CUP). Metastases in various organs are found at CUP diagnosis, which have implications for prognosis, and we hypothesize similar prognostic implications for metastases found at diagnosis of primary cancers. We identified 33,224 CUP pati

Proinflammatory Role of Sphingolipids and Glycosphingolipids in the Human Atherosclerotic Plaque

OBJECTIVE: Lipids are central to the development of atherosclerotic plaques. Specifically, which lipids are culprits remains controversial, and promising targets have failed in clinical studies. Sphingolipids are bioactive lipids present in atherosclerotic plaques, and they have been suggested to have both proatherogenic and antiatherogenic. However, the biological effects of these lipids remain u

Cyclic AMP Signaling through Epac Axis Modulates Human Hemogenic Endothelium and Enhances Hematopoietic Cell Generation

Hematopoietic cells emerge from hemogenic endothelium in the developing embryo. Mechanisms behind human hematopoietic stem and progenitor cell development remain unclear. Using a human pluripotent stem cell differentiation model, we report that cyclic AMP (cAMP) induction dramatically increases HSC-like cell frequencies. We show that hematopoietic cell generation requires cAMP signaling through th

Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study

Background ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. Objective To evaluate the predictive value of the BSI in metastatic castration-r

Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele

Background: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based

Radioimmunotherapy for Prostate Cancer-Current Status and Future Possibilities.

Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximate

Copy number variants in the kallikrein gene cluster.

The kallikrein gene family (KLK1-KLK15) is the largest contiguous group of protease genes within the human genome and is associated with both risk and outcome of cancer and other diseases. We searched for copy number variants in all KLK genes using quantitative PCR analysis and analysis of inheritance patterns of single nucleotide polymorphisms. Two deletions were identified: one 2235-bp deletion

Tracking the small with the smallest--using nanotechnology in tracking zooplankton.

A major problem when studying behavior and migration of small organisms is that many of the questions addressed for larger animals are not possible to formulate due to constraints on tracking smaller animals. In aquatic ecosystems, this problem is particularly problematic for zoo- and phytoplankton, since tracking devices are too heavy to allow the organism to act naturally. However, recent advanc

Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.

Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melan

Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study.

The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovas