Variable Expression of Cre Recombinase Transgenes Precludes Reliable Prediction of Tissue-Specific Gene Disruption by Tail-Biopsy Genotyping

The Cre/loxP-system has become the system of choice for the generation of conditional so-called knockout mouse strains, i.e. the tissue-specific disruption of expression of a certain target gene. We here report the loss of expression of Cre recombinase in a transgenic mouse strain with increasing number of generations. This eventually led to the complete abrogation of gene expression of the inserted Cre cDNA while still being detectable at the genomic level. Conversely, loss of Cre expression caused an incomplete or even complete lack of disruption for the protein under investigation. As Cre expression in the tissue of interest in most cases cannot be addressed in vivo during the course of a study, our findings implicate the possibility that individual tail-biopsy genotypes may not necessarily indicate the presence or absence of gene disruption. This indicates that sustained post hoc analyses in regards to efficacy of disruption for every single study group member may be required

Exploring the relationships between International Classification of Functioning, Disability and Health (ICF) constructs of Impairment, Activity Limitation and Participation Restriction in people with osteoarthritis prior to joint replacement

<p>Abstract</p> <p>Background</p> <p>The International Classification of Functioning, Disability and Health (ICF) proposes three main constructs, impairment (I), activity limitation (A) and participation restriction (P). The ICF model allows for all paths between the constructs to be explored, with significant paths likely to vary for different conditions. The relationships between I, A and P have been explored in some conditions but not previously in people with osteoarthritis prior to joint replacement. The aim of this paper is to examine these relationships using separate measures of each construct and structural equation modelling.</p> <p>Methods</p> <p>A geographical cohort of 413 patients with osteoarthritis about to undergo hip and knee joint replacement completed the Aberdeen measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP). Confirmatory factor analysis was used to test the three factor (I, A, P) measurement model. Structural equation modelling was used to explore the I, A and P pathways in the ICF model.</p> <p>Results</p> <p>There was support from confirmatory factor analysis for the three factor I, A, P measurement model. The structural equation model had good fit [S-B Chi-square = 439.45, df = 149, CFI robust = 0.91, RMSEA robust = 0.07] and indicated significant pathways between I and A (standardised coefficient = 0.76 p < 0.0001) and between A and P (standardised coefficient = 0.75 p < 0.0001). However, the path between I and P was not significant (standardised coefficient = 0.01).</p> <p>Conclusion</p> <p>The significant pathways suggest that treatments and interventions aimed at reducing impairment, such as joint replacement, may only affect P indirectly, through A, however, longitudinal data would be needed to establish this.</p

Short Telomeres Compromise β-Cell Signaling and Survival

The genetic factors that underlie the increasing incidence of diabetes with age are poorly understood. We examined whether telomere length, which is inherited and known to shorten with age, plays a role in the age-dependent increased incidence of diabetes. We show that in mice with short telomeres, insulin secretion is impaired and leads to glucose intolerance despite the presence of an intact β-cell mass. In ex vivo studies, short telomeres induced cell-autonomous defects in β-cells including reduced mitochondrial membrane hyperpolarization and Ca2+ influx which limited insulin release. To examine the mechanism, we looked for evidence of apoptosis but found no baseline increase in β-cells with short telomeres. However, there was evidence of all the hallmarks of senescence including slower proliferation of β-cells and accumulation of p16INK4a. Specifically, we identified gene expression changes in pathways which are essential for Ca2+-mediated exocytosis. We also show that telomere length is additive to the damaging effect of endoplasmic reticulum stress which occurs in the late stages of type 2 diabetes. This additive effect manifests as more severe hyperglycemia in Akita mice with short telomeres which had a profound loss of β-cell mass and increased β-cell apoptosis. Our data indicate that short telomeres can affect β-cell metabolism even in the presence of intact β-cell number, thus identifying a novel mechanism of telomere-mediated disease. They implicate telomere length as a determinant of β-cell function and diabetes pathogenesis

Arrayed waveguide gratings

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Two dimensional array of AR-coated diffractive microlenses fabricated by thin film deposition

Two dimensional arrays of Fresnel zone microlenses were fabricated and coated with antireflection layers by ion-beam-sputter deposition technique. The thickness of the layers was controlled by a reflection-wideband-monitoring system with high accuracy. The lenses have a circular aperture of 2 mm and focal lengths of 70 mm and 20 mm for the wavelength of 0.63 mu m and focal lengths of 29 mm, 8 mm and 5.7 mm for the wavelength of 1.52 mu m. The blazed profile in each zone was approximated by an eight level profile. Such stepped profiles were recorded with several masks, written with e-beam and with photolithographic technology. The measurements reveal that the spot-sizes of the fabricated microlenses are close to the diffraction limited values, and the diffraction efficiency for the eight level structure is 83 %

High activity enables life on a high-sugar diet:blood glucose regulation in nectar-feeding bats

High blood glucose levels caused by excessive sugar consumption are detrimental to mammalian health and life expectancy. Despite consuming vast quantities of sugar-rich floral nectar, nectar-feeding bats are long-lived, provoking the question of how they regulate blood glucose. We investigated blood glucose levels in nectar-feeding bats (Glossophaga soricina) in experiments in which we varied the amount of dietary sugar or flight time. Blood glucose levels increased with the quantity of glucose ingested and exceeded 25 mmol l(-1) blood in resting bats, which is among the highest values ever recorded in mammals fed sugar quantities similar to their natural diet. During normal feeding, blood glucose values decreased with increasing flight time, but only fell to expected values when bats spent 75 per cent of their time airborne. Either nectar-feeding bats have evolved mechanisms to avoid negative health effects of hyperglycaemia, or high activity is key to balancing blood glucose levels during foraging. We suggest that the coevolutionary specialization of bats towards a nectar diet was supported by the high activity and elevated metabolic rates of these bats. High activity may have conferred benefits to the bats in terms of behavioural interactions and foraging success, and is simultaneously likely to have increased their efficiency as plant pollinators

Photonic beam forming of mm-wave smart antennas

In this contribution we present experimental results of optically controlled mm-wave array antennas which may be used in broadband mobile communication systems. Two operation principles have been investigated: downlink beam forming for transmission and uplink beam steering for optimization of the reception. In both cases the field distributions of the antennas were formed by a Silica based photonic beam forming network

Experiments on DOA-estimation and beamforming for 60 GHz smart antennas

In this paper we present experimental results on direction of arrival (DOA) estimation and optical beamforming. In the first part of the paper we describe the experimental setup for the antenna calibration and DOA estimation at 60 GHz. A pilot signal generator and an array receiver are implemented. The feasibility of the DOA estimation is evaluated for real conditions. The experimental results show that the array calibration works reliable and there is a good agreement between simulation and experiment in the DOA estimation. In the second part, we present the experimental results on beamforming, which is performed using optical millimeter-wave generation technique. The millimeter-wave signals are generated by heterodyning the signals of two lasers. Beamforming is accomplished by a newly developed SiO /Si beamforming network, which enables individual control of amplitudes and hases of millimeter-wave signals feeding a planar 1x4 array antenna by means of the maximum directivity beamformer algorithm. Farfield measurements show good agreement between theory and experiment

Factors explaining limitations in activities and restrictions in participation in rheumatoid arthritis

AIM: The objectives of this study were to examine which factors, according to the International Classification of Functioning, Disability and Health (ICF) framework contribute to the explanation of activity limitations measured by the Health Assessment Questionnaire (HAQ - model I) and which factors contribute to the explanation of participation restrictions measured by the Social Function Scale of SF-36 (model II) in patients with rheumatoid arthritis (RA). METHODS: Cross-sectional data collection of variables concerning the health status of 239 consecutively included patients with RA at the outpatient Departments of Physical Medicine and Rehabilitation of the University Hospital of Zurich and of the University Hospital of Munich was conducted. Measures included: disease activity score (DAS-28), Rheumatoid Arthritis Disease Activity Index (RADAI), HAQ, Short-form-36 (SF-36), Sociodemo-graphy Questionnaire, Comorbidity Questionnaire (SCQ), Muscle Strength Index (MSI), range of motion (EPM-ROM), grip strength, Sequentional Occupational and Dexterity Assessment (SODA), radiologic score (Ratingen Score). Multivariate regression analyses were conducted building models of explanation. RESULTS: Model I included vitality, RADAI, DAS, SODA PAIN Score, MSI and EPM-ROM as explaining variables with a globally explained variance of 53%. Model II included vitality, mental health, the HAQ and living alone as explaining variables with a globally explained variance of 42.4%. CONCLUSION: Activity limitations in RA were mainly explained by vitality and disease activity factors. Restrictions in participation in RA were mainly explained by vitality and mental health