Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Helical organization of microtubules occurs in a minority of tunneling membrane nanotubes in normal and cancer urothelial cells

Abstract Tunneling membrane nanotubes (TnTs) are membrane protrusions connecting nearby or distant cells in vitro and in vivo. Functions of TnTs in cellular processes are various and rely on TnT structure, which also depends on cytoskeletal composition. In the present study, we focused on the organization of microtubules (MTs) and intermediate filaments (IFs) in TnTs of urothelial cells. We analysed TnTs of normal porcine urothelial cells, which morphologically and physiologically closely resemble normal human urothelial cells, and of cancer cells derived from invasive human urothelial neoplasm. Wide-field fluorescence, confocal and super-resolution microscopy techniques, together with image analyses and 3D reconstructions enlightened specific MT-IF organization in TnTs, and for the first time revealed that MTs and IFs co-occur in the majority of normal and cancer urothelial cell TnTs. Our findings show that in the initiation segment of TnTs, MTs are cross-linked with each other into filamentous network, however in the middle and the attaching segment of TnT, MTs can helically enwrap IFs, the phenomenon that has not been shown before within the TnTs. In this study, we assess MT-IF co-occurrence in TnTs and present evidence that such helical organization of MTs enwrapping IFs is only occurring in a minority of the TnTs. We also discuss the possible cell-biological and physiological reasons for helical organization of MTs in TnTs

Rör på er! : Användning av rörelsesensorer i smartphones för att skapa fysisk aktivitet i en föreläsningspublik

It takes only about 10-30 minutes into a sedentary lecture before audience attention is decreasing. There are different ways to avoid this. One is to use a web-based audience response systems (ARS), where the audience interact with the lecturer through their smartphones, and another is to take short breaks, including physical movements, to re-energize both the body and the brain. In this study, these two methods have been combined and explored. By utilizing the motion sensors that are integrated in almost every smartphone, a physical activity for a lecture audience was created and implemented in the ARS platform Mentimeter. The proof of concept was evaluated in two lectures, based on O’Brien and Toms' model of engagement. The aim was to explore the prerequisites, both in terms of design and implementation, for creating an engaging physical activity within a lecture audience, using smartphone motion sensors to capture movements and a web-based ARS to present the data. The results showed that the proof of concept was perceived as fun and engaging, where important factors for creating engagement were found to be competition and a balanced level of task difficulty. The study showed that feedback is complicated when it comes to motion gesture interactions, and that there are limitations as to what can be done with smartphone motion sensors using web technologies. There is great potential for further research in how to design an energizing lecture activity using smartphones, as well as in exploring the area of feedback in motion gesture interaction.Efter bara 10-30 minuter på en stillasittande föreläsning börjar publiken tappa i koncentration. Det går undvika på olika sätt. Ett sätt kan vara genom att låta publiken bli mer aktiva i föreläsningen med hjälp av ett webb-baserat röstningsverktyg, där de använder sina smartphones för att interagera med föreläsaren, och ett annat sätt kan vara att ta korta pauser där publiken får röra på sig för att syresätta hjärna och kropp. I den här studien kombinerades dessa två metoder genom att utnyttja rörelsesensorerna som finns inbyggda i de flesta smartphones. En fysisk aktivitet för en föreläsningspublik togs fram och implementerades i ARS-plattformen Mentimeter och konceptet utvärderades sedan under två föreläsningar baserat på O’Brien and Toms' modell för engagemang. Målet var att utforska förutsättningarna, både inom teknik och design, för att skapa en engagerande fysisk aktivitet för en föreläsningspublik, där smartphonens rörelsesensorer används för att fånga rörelse och ett webb-baserat röstningssystem för att presentera data. Resultatet visade att konceptet upplevdes som kul och engagerande, där viktiga faktorer för att skapa engagemang fanns i att ha ett tävlingsmoment och en lagom svårighetsgrad. Studien visade även att feedback är komplicerat när det kommer till rörelseinteraktion, och att det finns begräsningarna i vad som kan göras med rörelsesensorerna i en smartphone med hjälp av webbteknologi. Det finns stor potential för ytterligare undersökningar både inom hur man kan skapa interaktiva aktiviteter på föreläsningar som ger publiken mer energi, men också inom området kring feedback för rörelseinteraktion