Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98139/1/bjh12342.pd

High-Tc Cuprate Superconductivity in a Nutshell

Since the discovery of high-Tc cuprate superconductivity in 1986 many new experimental techniques and theoretical concepts have been developed. In particular it was shown that the BCS theory of d-wave superconductivity describes semi-quantitatively the high-Tc superconductivity. Furthermore, it was demonstrated that Volovik's approach is extremely useful for finding the quasiparticle properties in the vortex state. Here we survey these developments and forecast future directions.Comment: 11 pages, 3 figure

ATF4 Is an Oxidative Stress–Inducible, Prodeath Transcription Factor in Neurons in Vitro and in Vivo

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative death by ATF4 deletion was associated with decreased consumption of the antioxidant glutathione. Forced expression of ATF4 was sufficient to promote cell death and loss of glutathione. In ATF4(-/-) neurons, restoration of ATF4 protein expression reinstated sensitivity to oxidative death. In addition, ATF4(-/-) mice experienced significantly smaller infarcts and improved behavioral recovery as compared with wild-type mice subjected to the same reductions in blood flow in a rodent model of ischemic stroke. Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo

Genomics and proteomics of immune modulatory effects of a butanol fraction of echinacea purpurea in human dendritic cells

<p>Abstract</p> <p>Background</p> <p><it>Echinacea </it>spp. extracts and the derived phytocompounds have been shown to induce specific immune cell activities and are popularly used as food supplements or nutraceuticals for immuno-modulatory functions. Dendritic cells (DCs), the most potent antigen presenting cells, play an important role in both innate and adaptive immunities. In this study, we investigated the specific and differential gene expression in human immature DCs (iDCs) in response to treatment with a butanol fraction containing defined bioactive phytocompounds extracted from stems and leaves of <it>Echinacea purpurea</it>, that we denoted [BF/S+L/Ep].</p> <p>Results</p> <p>Affymetrix DNA microarray results showed significant up regulation of specific genes for cytokines (IL-8, IL-1β, and IL-18) and chemokines (CXCL 2, CCL 5, and CCL 2) within 4 h after [BF/S+L/Ep] treatment of iDCs. Bioinformatics analysis of genes expressed in [BF/S+L/Ep]-treated DCs revealed a key-signaling network involving a number of immune-modulatory molecules leading to the activation of a downstream molecule, adenylate cyclase 8. Proteomic analysis showed increased expression of antioxidant and cytoskeletal proteins after treatment with [BF/S+L/Ep] and cichoric acid.</p> <p>Conclusion</p> <p>This study provides information on candidate target molecules and molecular signaling mechanisms for future systematic research into the immune-modulatory activities of an important traditional medicinal herb and its derived phytocompounds.</p

Mobile Cloud-Based Blood Pressure Healthcare for Education

Mercury, pneumatic, and electronic sphygmomanometers were widely used for traditional blood pressure (BP) measurement. Cloud BP database, and mobile information and communication technology (MICT) do not integrate to these BP measurement methods. Pen and papers were employed to record BP values for nurses and physicians, and recording errors are possible to occur. In the chapter, the cloud-based BP platform solution and advanced wireless hospital BP measurement technologies were studied. These cloud-based BT measurement technologies were used as teaching aids to train students of electrical and nursing fields for mobile BP healthcare and health promotion education, and hence interdisciplinary teaching and learning were conducted. The teachers include professors of electrical and nursing fields, physicians, hospital nurses, and the engineer and health management experts of Microlife. The interdisciplinary teaching and learning of mobile BP healthcare and health promotion for smart aging were conducted in the Department of Nursing Division, Chang Cung Memorial Hospital, Keelung Branch, Department of Nursing Ching Kuo Institute of Management and Health, School of Nursing Chung Shan Medical University, and Department of Electrical Engineering, National Taiwan Ocean University. The students of electrical and nursing fields participated for joint interdisciplinary learning. The concepts of interdisciplinary mobile BP healthcare learning and teaching involve nursing and technology, healthy aging, BP health care for smart aging, telenursing, BP care for smart aging, community/home telecare, and MICT. The objective of teaching and learning is training the design and making electrical engineers to understand BP healthcare and health promotion, and nurses to understand mobile BP healthcare and health promotion system for smart aging

Effect of controlled disorder on quasiparticle thermal transport in Bi2_2Sr2_2CaCu2_2O8_8

Low temperature thermal conductivity, $\kappa$, of optimally-doped Bi2212 was studied before and after the introduction of point defects by electron irradiation. The amplitude of the linear component of $\kappa$ remains unchanged, confirming the universal nature of heat transport by zero-energy quasiparticles. The induced decrease in the absolute value of $\kappa$ at finite temperatures allows us to resolve a nonuniversal term in $\kappa$ due to conduction by finite-energy quasiparticles. The magnitude of this term provides an estimate of the quasiparticle lifetime at subkelvin temperatures.Comment: 5 pages including 2 .eps figuer

Phylogeographical Analysis on Squalidus argentatus Recapitulates Historical Landscapes and Drainage Evolution on the Island of Taiwan and Mainland China

Phylogeographical analyses on Squalidus argentatus samples from thirteen localities within mainland China and Taiwan were conducted for biogeographic studies, as their dispersal strictly depends on geological evolution of the landmasses. A total of 95 haplotypes were genotyped for mtDNA cyt b gene in 160 specimens from nine river systems. Relatively high levels of haplotype diversity (h = 0.984) and low levels of nucleotide diversity (π = 0.020) were detected in S. argentatus. Two major phylogenetic haplotype groups, A and B, were revealed via phylogenetic analysis. The degree of intergroup divergence (3.96%) indicates that these groups diverged about 4.55 myr (million years) ago. Haplotype network and population analyses indicated significant genetic structure (FST = 0.775), largely concordant with the geographical location of the populations. According to SAMOVA analysis, we divided these populations into four units: Yangtze-Pearl, Qiantang-Minjiang, Jiulong-Beijiang and Taiwan groups. Mismatch distribution analysis, neutrality tests and Bayesian skyline plots indicated a significant population expansion for lineage A and B, approximately dated 0.35 and 0.04 myr ago, respectively. We found strong geographical organization of the haplotype clades across different geographic scales that can be explained by episodes of dispersal and population expansion followed by population fragmentation and restricted gene flow

Nardilysin-Regulated Scission Mechanism Activates Polo-Like Kinase 3 To Suppress the Development of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism

Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection

Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples