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Multiscale granular mechanics: A neutron diffraction based experimental approach
Granular media (i.e., assemblies of grains, containing voids), such as sand, are highly complex materials, possessing inherently heterogeneous structure and properties that are manifested by the mobility and interaction of their constituent particles. Despite having been widely studied for centuries (i.e., the study of granular media in modern science essentially begins with the work of Charles-Au
Non-invasive ultrasound measurements of vascular impedance : Rekindling an old in-house concept on in vivo measurements
Trots dess introduktion under början av 1950-talet används vaskulär impedans ännu inte i klinisk omfattning för att förutsäga tidiga stadier av hjärt-kärlsjukdomar. Definierad som förhållandet mellan blodtryck och blodflöde beskriver vaskulär impedans motståndet mot blodflödet i det vaskulära systemet.Under detta avhandlingsprojekt uppskattades den lokala pulsvåghastigheten (PWV) och vaskulära impDespite its introduction in the early 1950´s, vascular impedance has yet to be applied in clinical use to predict early stages of cardiovascular disease (CVD). It is defined as the ratio between blood pressure and flow and describes the opposition to blood flow within the cardiovascular system.During this thesis project, local pulse wave velocity (PWV) and vascular impedance was estimated from in
Curative therapy in cancer- a perspective
2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension : The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT
The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), per
Functions of Pericytes in Ischemic Stroke
Ischemic stroke remains one of the leading causes of death and disability worldwide, and its burden is predicted to further increase due to the aging population. The only available treatments, thrombolysis or thrombectomy, can only be applied within a limited time window after stroke onset, and thus are applicable only to a small proportion of stroke patients. Therefore, there is an increasing nee
CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays
In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners wi
Emi2 Is Essential for Mouse Spermatogenesis
The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2—in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, in
Cyclin-dependent kinasedependent phosphorylation of Sox2 at serine 39 regulates neurogenesis
Sox2 is known to be important for neuron formation, but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal of stem cells remain elusive. In this study, we identified a highly conserved cyclin-dependent kinase (Cdk) phosphorylation site on serine 39 (S39) in Sox2. In neural stem cells (NSCs), phosphorylation
Quo Vadis cell growth and division?
Cell size control – a mechanism for maintaining fitness and function
The maintenance of cell size homeostasis has been studied for years in different cellular systems. With the focus on ‘what regulates cell size’, the question ‘why cell size needs to be maintained’ has been largely overlooked. Recent evidence indicates that animal cells exhibit nonlinear cell size dependent growth rates and mitochondrial metabolism, which are maximal in intermediate sized cells wit
MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice
In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mec
Loss of cyclin-dependent kinase 2 in the pancreas links primary β-cell dysfunction to progressive depletion of β-cell mass and diabetes
The failure of pancreatic isletβ-cells is a major contributor to the etiology of type 2 diabetes.β-Cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear whether they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (CDK2), couples primary β-cell dysfunction to the progressive deterioration
Identification of transcriptional and metabolic programs related to mammalian cell size
SummaryBackground Regulation of cell size requires coordination of growth and proliferation. Conditional loss of cyclin-dependent kinase 1 in mice permits hepatocyte growth without cell division, allowing us to study cell size in vivo using transcriptomics and metabolomics. Results Larger cells displayed increased expression of cytoskeletal genes but unexpectedly repressed expression of many genes