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MEN1 tumorigenesis in the pituitary and pancreatic islet requires CDK4 but not Cdk2

Recent studies suggest that physiological and tumorigenic proliferation of mammalian cells is controlled by multiple cyclin-dependent kinases (CDKs) largely in tissue-specific manners. We and others previously demonstrated that adult mice deficient for the Cyclin D partner CDK4 (Cdk4-/- mice) exhibit hypoplasia in the pituitary and pancreatic islet due to primary postnatal defects in proliferation

Undifferentiated pleomorphic sarcomas with PRDM10 fusions have a distinct gene expression profile

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive soft tissue tumor. A subset of UPS is characterized by a CITED2–PRDM10 or a MED12–PRDM10 gene fusion. Preliminary data suggest that these so-called PRDM10-rearranged tumors (PRT) are clinically more indolent than classical high-grade UPS, and hence important to recognize. Here, we assessed the spectrum of accompanying mutations and

Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes

CONTEXT: Both bone mineral density (BMD) and fracture risk have a strong genetic component. Estrogen receptor alpha (ESR1) is a candidate gene for osteoporosis, but previous studies of ESR1 polymorphisms in this field were hampered by small sample size, lack of standardization, and inconclusive results.OBJECTIVE: To generate large-scale evidence on whether 3 common ESR1 polymorphisms (intron 1 pol

Genetic and environmental determinants of peak bone mass in young men and women

Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms o

The effects of high glucose exposure on global gene expression and DNA methylation in human pancreatic islets

Background: Type 2 diabetes (T2D) is a complex disease characterised by chronic hyperglycaemia. The effects of elevated glucose on global gene expression in combination with DNA methylation patterns have not yet been studied in human pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19 mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin secretion, ge

Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium

Previous studies have shown the beneficial effects of the hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size but not on the regional strain in relationship to global left ventricular function. A noninvasive magnetic resonance (MR) study was performed to determine the effect of a new HGF gene, VM202, expressing two isoforms of HGF, on regional and global left ventricula

The Preboreal oscillation around the Nordic Seas : Terrestrial and lacustrine responses

The occurrence of an early Preboreal climatic cooling/oscillation (PBO) in lacustrine and glacial records from northwest Europe, Iceland and Greenland is reviewed and documented. The often subtle response of the proxy records to this oscillation, in combination with its short duration, make it difficult to detect. Owing to its chronostratigraphic position between the 10000-9900 and 9600-9500 14C p

In vivo quantification of glial activation in minipigs overexpressing human α-synuclein

Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergi

Migration distance affects stopover use but not travel speed : contrasting patterns between long- and short-distance migrating ospreys

The development of migratory behaviour is a continuous process which is not only determined by genes, but also moulded by individual differences based on life-history variations occurring at each ontogenetic stage. Assessing consistency and plasticity in migratory traits between long distance (LDM) and short distance migratory (SDM) populations within the same species that may express dissimilarit

Coupling an aerosol box model with one-dimensional flow : A tool for understanding observations of new particle formation events

Field observations of new particle formation and the subsequent particle growth are typically only possible at a fixed measurement location, and hence do not follow the temporal evolution of an air parcel in a Lagrangian sense. Standard analysis for determining formation and growth rates requires that the time-dependent formation rate and growth rate of the particles are spatially invariant; air p

Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation

Motivation: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity a

Family history of cancer and subsequent risk of cancer : A large-scale population-based prospective study in Japan

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the associatio

Si cycling in transition zones : a study of Si isotopes and biogenic silica accumulation in the Chesapeake Bay through the Holocene

Si fluxes from the continents to the ocean are a key element of the global Si cycle. Due to the ability of coastal ecosystems to process and retain Si, the ‘coastal filter’ has the potential to alter Si fluxes at a global scale. Coastal zones are diverse systems, sensitive to local environmental changes, where Si cycling is currently poorly understood. Here, we present the first palaeoenvironmenta

Comparison of the Regenerative Potential for Lung Tissue of Mesenchymal Stromal Cells from Different Sources/Locations Within the Body

Chronic obstructive pulmonary disease (COPD) is a progressive life-threatening disease that is significantly increasing in prevalence and is predicted to become the third leading cause of death worldwide by 2030. At present, there are no true curative treatments that can stop the progression of the disease, and new therapeutic strategies are desperately needed. Advances in cell-based therapies proTo date, bone marrow-derived mesenchymal stromal cells (MSCs) have been considered the golden standard among MSC cell-based therapies. However, the harvesting of bone marrow is a highly invasive procedure and the number of MSCs isolated is low, and it declines with increasing age. MSCs with immune-regulatory and regenerative properties can be isolated from many different tissues; however, bone mar

The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible pat