3D morphometric analysis of calcified cartilage properties using micro-computed tomography

Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mu CT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n = 15) used in this study were harvested from human lateral tibial plateau (n = 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r(s) = -0.600, P = 0.018), entropy of patterns (EP) (r(s) = -0.648, P = 0.018), homogeneity index (HI) (r(s) = 0.555, P = 0.032)) and tidemark roughness (TMR) (r(s) = -0.579, P = 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r(p) = 0.876, P <0.0001; r(p) = 0.665, P = 0.007, respectively) and channel density (CD) (r(p) = 0.680, P = 0.011; r(p) = 0.582, P = 0.023, respectively). TMR was associated with CAF (r(p) = 0.926, P <0.0001) and average channel size (r(p) = 0.574, P = 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a mu-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA. (c) 2018 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Establishment of Protein Delivery Systems Targeting Podocytes

Podocytes are uniquely structured cells that are critical to the kidney filtration barrier. Their anatomic location on the outer side of the glomerular capillaries expose podocytes to large quantities of both plasma and urinary components and thus are reachable for drug delivery. Recent years have made clear that interference with podocyte-specific disease pathways can modulate glomerular function and influence severity and progression of glomerular disease.Here, we describe studies that show efficient transport of proteins into the mammalian cells mouse 3T3 fibroblasts and podocytes, utilizing an approach termed profection. We are using synthetic lipid structures that allow the safe packing of proteins or antibodies resulting in the subsequent delivery of protein into the cell. The uptake of lipid coated protein is facilitated by the intrinsic characteristic of cells such as podocytes to engulf particles that are physiologically retained in the extracellular matrix. Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an increase in DNA degradation. Moreover, purified proteins such as beta-galactosidase and the large GTPase dynamin could be profected into podocytes using two different profection reagents with the success rate of 95-100%. The delivered beta-galactosidase enzyme was properly folded and able to cleave its substrate X-gal in podocytes. Diseased podocytes are also potential recipients of protein cargo as we also delivered fluorophore labeled IgG into puromycin treated podocytes. We are currently optimizing our protocol for in vivo profection.Protein transfer is developing as an exciting tool to study and target highly differentiated cells such as podocytes

How are podocytes affected in nail–patella syndrome?

Nail–patella syndrome is an autosomal-dominant hereditary disease named for dysplastic fingernails and toenails and hypoplastic or absent kneecaps evident in patients with the syndrome. Prognosis is determined by the nephropathy that develops in many such patients. Besides podocyte foot-process effacement, pathognomonic changes in the kidney comprise electron-lucent areas and fibrillar inclusions in the glomerular basement membrane. These characteristic symptoms are caused by mutations in the gene encoding the transcription factor LMX1B, a member of the LIM-homeodomain gene family. Comparable with the human syndrome, homozygous Lmx1b knockout mice lack patellae and suffer from severe podocyte damage. In contrast, however, podocin and the α3 and α4 chains of collagen IV are absent in the glomeruli of Lmx1b knockout mice. Further studies with podocyte-specific Lmx1b knockout mice have confirmed the importance of LMX1B in podocytes, as these mice apparently develop foot processes initially but lose them later on. We therefore conclude that LMX1B is essential for the development of metanephric precursor cells into podocytes and possibly also for maintaining the differentiation status of podocytes. LMX1B can serve as a model system to elucidate a genetic program in podocytes

Congenital nephrotic syndrome

Congenital nephrotic syndrome (CNS) is a rare kidney disorder characterized by heavy proteinuria, hypoproteinemia, and edema starting soon after birth. The majority of cases are caused by genetic defects in the components of the glomerular filtration barrier, especially nephrin and podocin. CNS may also be a part of a more generalized syndrome or caused by a perinatal infection. Immunosuppressive medication is not helpful in the genetic forms of CNS, and kidney transplantation is the only curative therapy. Before the operation, management of these infants largely depends on the magnitude of proteinuria. In severe cases, daily albumin infusions are required to prevent life-threatening edema. The therapy also includes hypercaloric diet, thyroxin and mineral substitution, prevention of thrombotic episodes, and prompt management of infectious complications. The outcome of CNS patients without major extrarenal manifestations is comparable with other patient groups after kidney transplantation

New national and regional biological records for Finland 11. Contributions to Bryophyta and Marchantiophyta 10

Ten species of mosses (Bryophyta: Entosthodon obtusus, Entosthodon ulvinenii, Eurhynchiastrum diversifolium, Hedwigia emodica, Hedwigia mollis, Hygrohypnum styriacum, Plagiothecium rossicum, Polytrichum perigoniale, Tortella alpicola and Ulota intermedia) are presented as new for Finland. Cephalozia lacinulata, previously considered to be regionally extinct from Finland, is reported to being found again. New records in biogeographical provinces for 67 species of mosses and 34 species of liverworts are listed. Finally, 6 occurrences in provinces are removed due to misidentifications or missing specimens

A human glomerular SAGE transcriptome database

Background: To facilitate in the identification of gene products important in regulating renal glomerular structure and function, we have produced an annotated transcriptome database for normal human glomeruli using the SAGE approach. Description: The database contains 22,907 unique SAGE tag sequences, with a total tag count of 48,905. For each SAGE tag, the ratio of its frequency in glomeruli relative to that in 115 non-glomerular tissues or cells, a measure of transcript enrichment in glomeruli, was calculated. A total of 133 SAGE tags representing well-characterized transcripts were enriched 10-fold or more in glomeruli compared to other tissues. Comparison of data from this study with a previous human glomerular Sau3A-anchored SAGE library reveals that 47 of the highly enriched transcripts are common to both libraries. Among these are the SAGE tags representing many podocyte-predominant transcripts like WT-1, podocin and synaptopodin. Enrichment of podocyte transcript tags SAGE library indicates that other SAGE tags observed at much higher frequencies in this glomerular compared to non-glomerular SAGE libraries are likely to be glomerulus-predominant. A higher level of mRNA expression for 19 transcripts represented by glomerulus-enriched SAGE tags was verified by RT-PCR comparing glomeruli to lung, liver and spleen. Conclusions: The database can be retrieved from, or interrogated online at http://cgap.nci.nih.gov/SAGE. The annotated database is also provided as an additional file with gene identification for 9,022, and matches to the human genome or transcript homologs in other species for 1,433 tags. It should be a useful tool for in silico mining of glomerular gene expression

Aalto-1, multi-payload CubeSat: design, integration and launch

The design, integration, testing, and launch of the first Finnish satellite Aalto-1 is briefly presented in this paper. Aalto-1, a three-unit CubeSat, launched into Sun-synchronous polar orbit at an altitude of approximately 500 km, is operational since June 2017. It carries three experimental payloads: Aalto Spectral Imager (AaSI), Radiation Monitor (RADMON), and Electrostatic Plasma Brake (EPB). AaSI is a hyperspectral imager in visible and near-infrared (NIR) wavelength bands, RADMON is an energetic particle detector and EPB is a de-orbiting technology demonstration payload. The platform was designed to accommodate multiple payloads while ensuring sufficient data, power, radio, mechanical and electrical interfaces. The design strategy of platform and payload subsystems consists of in-house development and commercial subsystems. The CubeSat Assembly, Integration & Test (AIT) followed Flatsat -- Engineering-Qualification Model (EQM) -- Flight Model (FM) model philosophy for qualification and acceptance.The paper briefly describes the design approach of platform and payload subsystems, their integration and test campaigns, and spacecraft launch. The paper also describes the ground segment & services that were developed by the Aalto-1 team.</p

Users and non-users of web-based health advice service among Finnish university students – chronic conditions and self-reported health status (a cross-sectional study)

<p>Abstract</p> <p>Background</p> <p>The Internet is increasingly used by citizens as source of health information. Young, highly educated adults use the Internet frequently to search for health-related information. Our study explores whether reported chronic conditions or self-reported health status differed among Finnish university students using the Finnish Student Health Services web-based health advice service compared with those not using the service.</p> <p>Methods</p> <p>Cross-sectional study performed by a national postal survey in 2004. Material: A random sample (n = 5 030) of a population of 101 805 undergraduate Finnish university students aged 19–35. The response rate: 63% (n = 3 153). Main outcome measures: Proportion of university students reporting use a of web-based health advice service, diagnosed chronic conditions, and self-reported health status of users and non-users of a web-based health advice service. Statistical methods: Data were presented with frequency distributions and cross-tabulations and the χ²test was used.</p> <p>Results</p> <p>12% (n = 370) of Finnish undergraduate students had used the web-based health advice service and were identified as 'users'. The proportion of male students reporting allergic rhinitis or conjunctivitis was greater among users than non-users (24%, n = 22 vs. 15%, n = 154, χ², P = .03). The proportion of female students reporting chronic mental health problems was greater among users than non-users (12%, n = 34 vs. 8%, n = 140, χ², P = .03). There was no statistical significance between the group differences of male or female users and non-users in self-reported health status (good or fairly good, average, rather poor or poor).</p> <p>Conclusion</p> <p>Among young, highly educated adults the use of a web-based health advice service is not associated with self-reported health status. However, a web-based health advice service could offer support for managing several specific chronic conditions. More research data is needed to evaluate the role of web-based health advice services that supplement traditional forms of health services.</p