Detection of interferon alpha protein reveals differential levels and cellular sources in disease.

Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging.

Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience.

A fast track "Hot Start" process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution.

Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations.

Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts.

Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure.

Impact of small vessel disease in the brain on gait and balance.

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71-74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions.

Exact Product Formation Rates for Stochastic Enzyme Kinetics.

The rate of product formation is an important measure of the speed of enzyme reactions. Classical studies of enzyme reactions have been conducted in dilute solutions and under conditions that justified the substrate abundance assumption. However, such assumption is well-known to break down in the context of cellular biochemistry.

The other side of the coin: Harm due to the non-use of health-related data.

Introduction: It is widely acknowledged that breaches and misuses of health-related data can have serious implications and consequently they often carry penalties. However, harm due to the omission of health data usage, or data non-use, is a subject that lacks attention. A better understanding of this 'other side of the coin' is required before it can be addressed effectively.

Genetic variants linked to education predict longevity.

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length.

Relative Abundance of apoE and Aβ1-42 Associated with Abnormal Prion Protein Differs between Creutzfeldt-Jakob Disease Subtypes.

Aggregated and protease-resistant mammalian prion protein (PrP) is the primary protein component of infectious prions. Enriched PrP preparations are often used to study the mechanisms that underly prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrP components including various proteins that could confound functional and structural studies.

Conditional Deletion of the Prolactin Receptor Reveals Functional Subpopulations of Dopamine Neurons in the Arcuate Nucleus of the Hypothalamus.

Unlabelled: Tuberoinfundibular dopamine (TIDA) neurons, known as neuroendocrine regulators of prolactin secretion from the pituitary gland, also release GABA within the hypothalamic arcuate nucleus. As these neurons express prolactin receptors (Prlr), prolactin may regulate GABA secretion from TIDA neurons, potentially mediating actions of prolactin on hypothalamic function. To investigate whether GABA is involved in feedback regulation of TIDA neurons, we examined the physiological consequences of conditional deletion of Prlr in GABAergic neurons.

Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.

Genome-wide association studies (GWAS) have identified hundreds of cardiometabolic disease (CMD) risk loci. However, they contribute little to genetic variance, and most downstream gene-regulatory mechanisms are unknown. We genotyped and RNA-sequenced vascular and metabolic tissues from 600 coronary artery disease patients in the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task study (STARNET).

Algorithmic methods to infer the evolutionary trajectories in cancer progression.

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the "selective advantage" relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level.

A review of clinical trial designs used to detect a disease-modifying effect of drug therapy in Alzheimer's disease and Parkinson's disease.

Background: Disease-modification clinical trials in neurodegenerative disorders have struggled to separate symptomatic effects of putative agents from disease-modification. In response, a variety of clinical trial designs have been developed. A systematic review was undertaken to examine which trial designs have been used in Alzheimer's disease (AD) and Parkinson's disease (PD) to detect disease-modifying, as opposed to symptomatic, drug effects.

Exploring Synthetic and Systems Biology at the University of Edinburgh.

The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact.

Anti-Müllerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations.

Study Question: Do women with ITALIC! BRCA1 or ITALIC! BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-Müllerian hormone (AMH) concentration?

Summary Answer: Women with a germline mutation in ITALIC! BRCA1 have reduced ovarian reserve as measured by AMH.

What Is Known Already: The DNA repair enzymes encoded by ITALIC! BRCA1 and ITALIC! BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan.

Culture shapes the evolution of cognition.

A central debate in cognitive science concerns the nativist hypothesis, the proposal that universal features of behavior reflect a biologically determined cognitive substrate: For example, linguistic nativism proposes a domain-specific faculty of language that strongly constrains which languages can be learned. An evolutionary stance appears to provide support for linguistic nativism, because coordinated constraints on variation may facilitate communication and therefore be adaptive. However, language, like many other human behaviors, is underpinned by social learning and cultural transmission alongside biological evolution.

Airway foreign bodies: A critical review for a common pediatric emergency.

Background: Airway foreign bodies (AFBs) is an interdisciplinary area between emergency medicine, pediatrics and otolaryngology. It is a life-threatening condition that is not infrequently seen; however, it is poorly covered in medical literature. Accidental aspiration of an element into airways is a widespread clinical scenario among children under 3 years, predominantly males.

Feeling the future: A meta-analysis of 90 experiments on the anomalous anticipation of random future events.

In 2011, one of the authors (DJB) published a report of nine experiments in the Journal of Personality and Social Psychology purporting to demonstrate that an individual's cognitive and affective responses can be influenced by randomly selected stimulus events that do not occur until after his or her responses have already been made and recorded, a generalized variant of the phenomenon traditionally denoted by the term precognition. To encourage replications, all materials needed to conduct them were made available on request. We here report a meta-analysis of 90 experiments from 33 laboratories in 14 countries which yielded an overall effect greater than 6 sigma, z = 6.