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Dopamine Cell Therapy : From Cell Replacement to Circuitry Repair

Cell therapy for Parkinson's disease (PD) is aimed to replace the degenerated midbrain dopamine (mDA) neurons and restore DA neurotransmission in the denervated forebrain targets. A limitation of the intrastriatal grafting approach, which is currently used in clinical trials, is that the mDA neurons are implanted into the target area, in most cases the putamen, and not in the ventral midbrain wher

Associations Between Endometriosis and Gut Microbiota

The gut microbiota has been associated with many diseases, including endometriosis. However, very few studies have been conducted on this topic in human. This study aimed to investigate the association between endometriosis and gut microbiota. Women with endometriosis (N=66) were identified at the Department of Gynaecology and each patient was matched with three controls (N=198) from the general p

Exploring Patient-Specific Cell Replacement Therapy for Parkinson's Disease

Parkinson’s disease (PD) affects over six million people worldwide and is characterised by the progressive loss of dopaminergic (DA) neurons in the substantia nigra, accumulation of pathological alpha-synuclein (αSyn), and inflammation in the brain. This leads to motor impairments including rigidity, akinesia, bradykinesia, resting tremor, and postural instability. Cell replacement therapy aims to

Single-Cell Profiling of Coding and Noncoding Genes in Human Dopamine Neuron Differentiation

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson's disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling

A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer

Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein

Cadmium exposure and coronary artery atherosclerosis : A cross-sectional population-based study of swedish middle-aged adults

BACKGROUND: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined. OBJE

Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b bindi

Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer

Splicing is a central RNA-based process commonly altered in human cancers; however, how spliceosomal components are co-opted during tumorigenesis remains poorly defined. Here we unravel the core splice factor SF3A3 at the nexus of a translation-based program that rewires splicing during malignant transformation. Upon MYC hyperactivation, SF3A3 levels are modulated translationally through an RNA st

A drug screen with approved compounds identifies amlexanox as a novel Wnt/β-catenin activator inducing lung epithelial organoid formation

Background and Purpose: Emphysema is an incurable disease characterized by loss of lung tissue leading to impaired gas exchange. Wnt/β-catenin signalling is reduced in emphysema, and exogenous activation of the pathway in experimental models in vivo and in human ex vivo lung tissue improves lung function and structure. We sought to identify a pharmaceutical able to activate Wnt/β-catenin signallin

Social belonging as the main concern for achieving life satisfaction when adapting to parkinson’s disease

Parkinson’s disease (PD) is a complex, progressive neurological condition that impacts daily life and reduces life satisfaction (LS). To achieve and maintain high LS, persons with PD (PwPD) must go through a process of change to adapt to their new life situation. However, our knowledge about this process is very limited. The aim of this study was to investigate the process of change, and the main

Low lung function, sudden cardiac death and non-fatal coronary events in the general population

BACKGROUND: Many of those who suffer from a first acute coronary event (CE) die suddenly during the day of the event, most of them die outside hospital. Poor lung function is a strong predictor of future cardiac events; however, it is unknown whether the pattern of lung function impairment differs for the prediction of sudden cardiac death (SCD) versus non-fatal CEs. We examined measures of lung f

Wolbachia-driven selective sweep in a range expanding insect species

Background: Evolutionary processes can cause strong spatial genetic signatures, such as local loss of genetic diversity, or conflicting histories from mitochondrial versus nuclear markers. Investigating these genetic patterns is important, as they may reveal obscured processes and players. The maternally inherited bacterium Wolbachia is among the most widespread symbionts in insects. Wolbachia typ

Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection

Excessive bleeding is a serious complication associated with impaired survival after surgery for acute type A aortic dissection (ATAAD). Different ABO blood groups are associated with variable levels of circulating von Willebrand factor and therefore potentially altered risks of surgical haemorrhage. The current study aimed to assess the impact of blood group on bleeding complications after ATAAD

Premature ovarian failure after childhood cancer and risk of metabolic syndrome : A cross-sectional analysis

Objective: Female childhood cancer survivors (CCS) are at risk of several late effects, such as metabolic syndrome (MetS) and premature ovarian insufficiency (POI). The objective is to study if POI is associated with risk of MetS and increased cardiovascular risk in CSS. Design: A cross-sectional study with a median time since the cancer diagnosis of 25 (12-41) years. Patients and controls were re

A retrospective study assessing the accuracy of [18F]–fluorocholine PET/CT for primary staging of lymph node metastases in intermediate and high-risk prostate cancer patients undergoing robotic-assisted laparoscopic prostatectomy with extended lymph node dissection

Background: Previous studies have investigated [18F]-fluorocholine (FCH) positron emission tomography with computed tomography (PET/CT) in primary staging of men with intermediate or high-risk prostate cancer and have generally shown high specificity and poor sensitivity. FCH PET/CT is not recommended for the primary staging of metastases in the European guidelines for prostate cancer. However, it

Understanding User Involvement in Research in Aging and Health

User involvement in research is advocated as an avenue for efficient societal developments. In this article, we identify potentials, problems, and challenges related to research on aging and health, and identify and illustrate research priorities using an evolving research program as an example. Involving user representatives in the development phase, the UserAge program engages researchers at fou

Risks of non-ovarian cancers in women with borderline ovarian tumor : a national cohort study in Sweden

Background: Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. Aim: To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. Methods: An open cohort study (1995–2018) was conducted where a diagnosis of BOTs as wel

On the interactions between RNA and titrateable lipid layers : implications for RNA delivery with lipid nanoparticles

Characterising the interaction between cationic ionisable lipids (CIL) and nucleic acids (NAs) is key to understanding the process of RNA lipid nanoparticle (LNP) formation and release of NAs from LNPs. Here, we have used different surface techniques to reveal the effect of pH and NA type on the interaction with a model system of DOPC and the CIL DLin-MC3-DMA (MC3). At only 5% MC3, differences in