Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia.

Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder. Patients have episodes that last 1 to 4 hours and are precipitated by alcohol, coffee, and stress. Previous research has shown that mutations in an uncharacterized gene on chromosome 2q33-q35 (which is termed PNKD) are responsible for PNKD. Here, we report the generation of antibodies specific for the PNKD protein and show that it is widely expressed in the mouse brain, exclusively in neurons. One PNKD isoform is a membrane-associated protein. Transgenic mice carrying mutations in the mouse Pnkd locus equivalent to those found in patients with PNKD recapitulated the human PNKD phenotype. Staining for c-fos demonstrated that administration of alcohol or caffeine induced neuronal activity in the basal ganglia in these mice. They also showed nigrostriatal neurotransmission deficits that were manifested by reduced extracellular dopamine levels in the striatum and a proportional increase of dopamine release in response to caffeine and ethanol treatment. These findings support the hypothesis that the PNKD protein functions to modulate striatal neuro-transmitter release in response to stress and other precipitating factors

Mixed Analog-Digital (MAD) Converters for High Power Density DC-DC Conversions

Conventional switched-mode power supplies (SMPSs) have intrinsic instantaneous power pulsation at the switching frequency thus require bulky filters. To improve the power density, this paper proposes a concept named the Mixed Analog-Digital (MAD) which can be applied as DC-DC converters. By inserting an analog voltage component between the load and source, the output voltage naturally has much smaller fluctuation thereby much smaller passive filter is required. Simulations and experiments validate that the proposed MAD concept can be applied as DC-DC converters to significantly increase the power density

A Case Study of Applying Blended Learning in an Accelerated Post-Baccalaureate Teacher Education Program

Blended learning has potential to improve teacher education in terms of accessibility and quality. This paper reports findings from a case study with mixed methods data collection analysis to examine the application of blended learning in accelerated post-baccalaureate teacher education at the program level. One hundred and sixty-seven recent graduates from a chosen teacher education program participated in the study by completing an online survey. Eight of the survey participants and six faculty members were interviewed. Findings from this study support the viability and benefits of applying blended learning in teacher education at the program level. On the other hand, teacher candidates and faculty members reported challenges in such blended learning teacher education programs. Suggestions for applying blended learning in teacher education at the program level are discussed in this paper

Cachexia and protein-energy wasting in children with chronic kidney disease

Children with chronic kidney disease (CKD) are at risk for “cachexia” or “protein-energy wasting” (PEW). These terms describe a pathophysiologic process resulting in the loss of muscle, with or without loss of fat, and involving maladaptive responses, including anorexia and elevated metabolic rate. PEW has been defined specifically in relation to CKD. We review the diagnostic criteria for cachexia and PEW in CKD and consider the limitations and applicability of these criteria to children with CKD. In addition, we present an overview of the manifestations and mechanisms of cachexia and PEW. A host of pathogenetic factors are considered, including systemic inflammation, endocrine perturbations, and abnormal neuropeptide signaling, as well as poor nutritional intake. Mortality risk, which is 100- to 200-fold higher in patients with end-stage renal disease than in the general population, is strongly correlated with the components of cachexia/PEW. Further research into the causes and consequences of wasting and growth retardation is needed in order to improve the survival and quality of life for children with CKD

A 0.76-pJ/Pulse 0.1-1 Gpps Microwatt IR-UWB CMOS Pulse Generator with Adaptive PSD Control Using A Limited Monocycle Precharge Technique

Document Version Author final version (often known as postprint) Link to publication from Aalborg University Citation for published version (APA)

Increasing trend of scientists to switch between topics

We analyze the publication records of individual scientists, aiming to quantify the topic switching dynamics of scientists and its influence. For each scientist, the relations among her publications are characterized via shared references. We find that the co-citing network of the papers of a scientist exhibits a clear community structure where each major community represents a research topic. Our analysis suggests that scientists tend to have a narrow distribution of the number of topics. However, researchers nowadays switch more frequently between topics than those in the early days. We also find that high switching probability in early career (<12y) is associated with low overall productivity, while it is correlated with high overall productivity in latter career. Interestingly, the average citation per paper, however, is in all career stages negatively correlated with the switching probability. We propose a model with exploitation and exploration mechanisms that can explain the main observed features.Comment: 37 pages, 21 figure

Cross-Talk Between JNK/SAPK and ERK/MAPK Pathways: Sustained Activation of JNK Blocks ERK Activation by Mitogenic Factors

Mixed lineage kinases (MLKs) are a family of serine/threonine kinases that function in the SAPK signaling cascade. MLKs activate JNK/SAPK in vivo by directly phosphorylating and activating the JNK kinase SEK-1 (MKK4 and -7). Importantly, the MLK member MLK3/SPRK has been shown recently to be a direct target of ceramide and tumor necrosis factor-α (TNF-α) and to mediate the TNF-α and ceramide-induced JNK activation in Jurkat cells. Here we report that MLK3 can phosphorylate and activate MEK-1 directly in vitro and also can induce MEK phosphorylation on its activation sites in vivo in COS-7 cells. Surprisingly, this induction of MEK phosphorylation does not result in ERK activation in vivo. Rather, in cells expressing active MLK3, ERK becomes resistant to activation by growth factors and mitogens. This restriction in ERK activation requires MLK3 kinase activity, is independent of Raf activation, and is reversed by JNK pathway inhibition either at the level of SEK-1, JNK, or Jun. These results demonstrate that sustained JNK activation uncouples ERK activation from MEK in a manner requiring Jun-mediated gene transcription. This in turn points to the existence of a negative cross-talk relationship between the stress-activated JNK pathway and the mitogen-activated ERK pathway. Thus, our findings imply that some of the biological functions of JNK activators, such as TNF-α and ceramide, may be attributed to their ability to block cell responses to growth and survival factors acting through the ERK/MAPK pathway

Mast Cells Modulate Acute Toxoplasmosis in Murine Models

The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P \u3c 0.01), spleen (P \u3c 0.05), and mesentery (P \u3c 0.05) tissues, higher parasite burden in the peritoneal lavage fluids (P \u3c 0.01), and increased levels of mRNA transcripts of T. gondii tachyzoite surface antigen 1 (SAG1) gene in the spleen and liver tissues (P \u3c 0.01), accompanied with significantly increased Th1 cytokine (IFN-γ, IL-12p40, and TNF-α) (P \u3c 0.01) and decreased IL-10 (P \u3c 0.01) mRNA expressions in the liver, and increased IFN-γ (P \u3c 0.01) and IL-12p40 (P \u3c 0.01) but decreased TNF-α (P \u3c 0.01) and IL-4 (P \u3c 0.01) in the spleens of infected mice treated with C48/80 at day 9-10 p.i. Whereas mice treated with DSCG had significantly decreased tissue lesions (P \u3c 0.01), lower parasite burden in the peritoneal lavage fluids (P \u3c 0.01) and decreased SAG1 expressions in the spleen and liver tissues (P \u3c 0.01), accompanied with significantly increased IFN-γ (P \u3c 0.01) and IL-12p40 (P \u3c 0.05) in the liver, and decreased IFN-γ (P \u3c 0.05) and TNF-α (P \u3c 0.01) in the spleens; IL-4 and IL-10 expressions in both the spleen and liver were significantly increased (P \u3c 0.01) in the infected mice treated with DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection