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BACKGROUND: Type 2 diabetes (T2D) is a complex polygenic disease with unclear mechanism. In an attempt to identify novel genes involved in β-cell function, we harness a bioinformatics method called Loss-of-function tool (LoFtool) gene score. METHODS: RNA-sequencing data from human islets were used to cross-reference genes within the 1st quartile of most intolerant LoFtool score with the 100th most
The host defense peptide LL-37 is active against both gram-positive and gram-negative bacteria, but it has also been shown to reduce human host cell viability. However, the mechanisms behind LL-37-induced human host cell cytotoxicity are not yet fully understood. Here, we assess if LL-37-evoked attenuation of human osteoblast-like MG63 cell viability is associated with apoptosis, and if the underl
Aims: To clarify whether parasympathetic neuropathy in Type 2 diabetic patients is associated with features of the insulin resistance syndrome. Methods: Blood pressures, glycaemic control (HbA(IC)), plasma lipids, residual β-cell function (fasting plasma C-peptide), autonomic nerve function, urinary albumin excretion and glomerular filtration rate (Cr-EDTA clearance) were evaluated in 82 Type 2 di
Urbanization represents a fierce driver of phenotypic change, yet the molecular mechanisms underlying observed phenotypic patterns are poorly understood. Epigenetic changes are expected to facilitate more rapid adaption to changing or novel environments, such as our towns and cities, compared with slow changes in gene sequence. A comparison of liver and blood tissue from great tits Parus major ori
The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 and Periphilin — contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture rese
Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (M
In Information Gap Decision Theory (IGDT) a system is said to be robust to uncertainty if specified goals are achieved with satisfaction despite large info-gaps. Under this theory an info-gap expresses the disparity between what is known and unknown in structures for which uncertainty is judged as severe. We discuss how robustness in IGDT can be merged with a perspective on risk which allows for d
CD44 is a cell surface adhesion molecule and its principal ligand is hyaluronic acid (HA), a key component of the brain’s extracellular matrix. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in genome wide association study as a possible risk gene in suicidal behavior. In order to define the pathobiological mechanisms by w
Background: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. Objective: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. Methods: A populat
Inventory control systems used in practice are quite often modeling the lead-time demand by a normal distribution. This may result in considerable errors when the real demand is low and discrete. For such demand, it is usually better to use a discrete demand distribution. However, this will increase the computational effort. A natural question is under what circumstances a normal approximation is
PURPOSE: Circular smooth muscle of the urethra generates spontaneous myogenic tone of relevance for the maintenance of continence. We tested if Rho guanosine triphosphatases (GTPases) and Rho-associated kinase (ROK) are involved in the generation of urethral tone. MATERIALS AND METHODS: Small circular strips of female pig urethra were dissected out and mounted for recording isometric force. The ef
Using bird atlas data from south-central Sweden and information on survey effort for the corresponding 5 x 5 km grid squares, we assessed how much time is required to get reliable presence/absence data for forest birds. We restricted the analyses to a suite of 28 species considered common enough and sufficiently generalised in their requirements to be present in all survey squares largely dominate
Objective A Valsalva maneuver is used clinically and on imaging in order to determine female pelvic organ prolapse. We have examined the Potential confounding effect of levator co-activation at the time of a Valsalva maneuver and the impact of repetition with biofeedback instruction. Methods Fifty nulliparous women at 36-38 weeks' gestation received 3D/4D translabial ultrasound investigation in th
