25 research outputs found

    The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP

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    The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ankank/ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ankank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality

    Critical Epitopes in the Nucleocapsid Protein of SFTS Virus Recognized by a Panel of SFTS Patients Derived Human Monoclonal Antibodies

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    BACKGROUND: SFTS virus (SFTSV) is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS) in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs) recognized the nucleocapsid (N) protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection

    OCT (Optical Coherense Tomography) : Teknik och tillÀmpning

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    Before year 1895, the doctors could only make a probable diagnosis based on what the patient could tell and it was hurt and there was no discernable change to the outside of the body. With X-ray, it was possible to see inside the patient without first cutting it, you can say that the X-ray was the starting point for diagnostic imaging.The further development of X-ray gave CT (Computed Tomography), where X-ray tubes and detectors rotate around the patient while the patient table moves. Besides CT also developed MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) and Ultrasound. Common to these methods is that the produced 3D images.In 1990 a completely new approach for diagnostic imaging, OCT (optical coherence tomography), by measuring the phase shift and the intensity of reflected light, it provides real-time and non-destructive measurements (in vivo) a resolution of 1 to 15 microns, much higher than all other standard imaging techniques. You could say that OCT machine can be compared to ultrasound, which uses the reflection of sound waves to interpretation.The first OCT machines were of type TD (Time Domain), these had low resolution and low scanning speed. In 2005 came the SD-OCT, they had higher resolution and scanning speed, SD stands for spectral domain, SD-OCT is sometimes called FD-OCT as Fourier transformed signals and operating in the frequency domain.The development of OCT machines are only in their infancy, resolution, scanning speed and accuracy will increase all the time, this allows new uses and ways to diagnose developed. OCT can be used in such Oncology, MSD (Musculoskeletal disorders), cardiovascular medicine, teeth, nerves, but the largest field is the eye and then the back of the eye called the retina (retina).This thesis is limited to the eye, the purpose is to provide input to those who are likely to purchase an OCT-machine, but also show the measurement data OCT-machines are performing and how to use the OCT-machine more than to see age-related macular degeneration. Another aim is to increase understanding of the physics behind an OCT-machine for ease of understanding the output given.The manufacture/model that have selected for evaluation are Zeiss Cirrus 4000, Topcon 3D OCT-2000 and Heidelberg Spectralis, the reason is that there are only these three on the Swedish market and all are SD-OCT. The way to evaluate OCT-machines is to scan performance and what the various analysis programs can handle. Furthermore, each OCT-machine scans the macula and optic disk on a experimental person/ reference eye, in order to get the output of the precision, or if you want to call it repeatability, which is very important if one wants to follow a solitary disease course.The conclusion of this thesis is to OCT machines are quite similar. When it comes to ease of use when doing scans is the Cirrus is lightened by the use of the extra screen where you always look eye (iris camera), which makes it easy to adjust the sharpness and position of the mouse buttons. Topcon and Heidelberg is not difficult to use but requires more experience of the person making the OCT scans. Most measurement functions in the analysis program is Topcon and Heidelberg and best accuracy/repeatability is Heidelberg, both the macula and RFNL.OCT machine is a good tool to use on the anterior segment, but in the case the precision allows the precision used to monitor RNFL thickness changes in those with glaucoma.Validerat; 20131029 (global_studentproject_submitter)</p

    Om testamentes tolkning : Den yttersta viljans grÀnser, presumtioner och principer

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    The interpretation of a will is indeed a delicate matter. The government committee that developed the Wills Act (SFS 1930:104) described it as an area that ”offers particular difficulties”. When there is a will to be executed, however, the difficulties must be overcome. Frequently, a great deal of time has elapsed since the will was written, which may have led to several changes in different regards. For example, the testator may no longer be in possession of the property named in the will, or changes in the circle of legatees might have occured. When a will is to be interpreted, one must identify the actual underlying intent of the provision. If that is not possible, the executor must ask what the testator’s hypothetical intent would be in the particular situation. Hence, the interpretation process is strictly subjective. If, and only if, the determination of the actual or hypothetical intent of the testator is unsuccessful can one use supplementary presumptions. The Wills Act, which was incorporated almost unmodified into the Inheritance Code (SFS 1958:637), offers a few presumption rules that ”the normal testator” is presumed to approve. This phase of the interpretation is therefore objective. The presumption rules are subsidiary to the actual or hypothetical intent of the testator and ought only be used as an exception. The Supreme Court has, in accordance with this principle of subsidiarity, seldom applied a presumption rule. The court seems to prefer an interpretation of the testator’s intent, even if the intent is rather vague. The court’s case law shows that it does not take much to rebut one of the subsidiary presumptions. Due to the continuing development of society and its constellation of families, the need for development in the law of wills is likewise perpetual. Cohabitants, for example, do not inherit one another according to Swedish law, and thus it is crucial to make a will in favour of a cohabitant to provide for their protection. This paper does not propose a right of inheritance for cohabitants, but rather a presumption rule under specific circumstances: An explicit provision for free disposal of the property left for the surviving cohabitant is presumed to contain a provision for secondary inheritance due to the 3rd chapter of the Inheritance Code. Such a presumption would harmonise with established law and hopefully prevent future interpretation disputes

    Pronounced difference in Covid-19 antibody prevalence indicates cluster transmission in Stockholm, Sweden

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    The prevalence of COVID-19 antibodies on June 17–18, 2020 was investigated in two residential areas of Stockholm, Sweden. Among the residents in Norra DjurgĂ„rdsstaden, a newly built upper- and middle-class area of Stockholm, 4.1% of study participants had SARS-CoV-2-specific antibodies, while in Tensta, a highly segregated low-income area, 30% of the participants tested antibody positive

    Vid texternas vÀgskÀl. Textkritiska uppsatser. Red. Lars Burman, Barbro StÄhle Sjönell : (Nordiskt NÀtverk för Editionsfilologer. Skrifter. 1). Svenska Vitterhetssamfundet. Stockholm 1999

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    Sport participation for youth with immigrant background is often argued to play an important role for migrant youth integration into their new host society. Although few well sampled longitudinal studies has been conducted. The aim of this study was to study the impact that sport participation has on two integration-related outcomes (problem behaviours and native friends) by using the Swedish version of the longitudinal CILS4EU study. The multi-group latent growth curve models showed that although youth active or starting in sport independent of immigrant background did less problem behaviours and had more native friends than their peers with the same immigrant background that was not engaged in sport. However, the trajectories were very similar and often very close to zero, which makes it difficult to claim that sport participation has any significant impact on integration in the Swedish society

    Has the second ‘running boom’ democratized running? : A study on the sociodemographic characteristics of finishers at the world’s largest half marathon

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    Previous studies have shown that runners differ in terms of sociodemographic characteristics. However, given the increase in participants at running races, the question arises whether these sociodemographic differences have been erased and if the second running boom has democratized running. An online questionnaire was sent to a randomized sample (n = 2378) of finishers at the 2017 Gothenburg half marathon (Göteborgsvarvet). The self-reported sociodemographic variables were then compared to Swedish national averages. The results show that Göteborgsvarvet finishers are considerably more likely to be men, well-educated and employed, compared to the general population of Sweden. This study indicates, therefore, that half marathon finishers are still distinctly different in terms of sociodemographic variables compared to the general population. These differences need to be taken into consideration when conclusions are drawn concerning running and its health effects on runners
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