Role of Macrophage Apoptosis in Atherosclerosis.

The presence of apoptotic cells in atherosclerotic lesions has been broadly reported in the past ten years. The majority of these apoptotic cells are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains to be elucidated. Elevated expression of Bax, one of the pivotal pro-apoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol treated mouse macrophages. In this study, we evaluated the influence of Bax deficiency on apoptosis in macrophage-like P388D1 cells by using small interfering RNA (siRNA) to suppress Bax expression, as well as in peritoneal macrophages isolated from Bax null mice (Bax-/-). Apoptotic activities in both cell types deficient for Bax were significantly reduced compared to that in control cells. To examine the effect of macrophage Bax deficiency on the development of atherosclerosis, fourteen 8-week-old male LDL-receptor null (LDLR-/-) mice were lethally irradiated and reconstituted with either wild type (WT) C57BL6 or Bax-/- bone marrow. Three weeks later, the mice were challenged with a Western diet for 10 weeks. No differences were found in the plasma cholesterol level between the WT and Bax-/- group. However, quantitation of cross sections from proximal aortas revealed a 49.2% increase (P=0.0259) in the mean lesion area of the Bax-/- group compared to the WT group. A 53% decrease in apoptotic macrophages in the Bax-/- group was found by TUNEL staining (P\u3c0.05). In conclusion, Bax deficiency produces a reduction of apoptotic activity in macrophages and is associated with the accelerated atherosclerosis in LDLR null mice fed a Western diet. These results strongly support our hypothesis that macrophage apoptosis suppresses the development of atherosclerosis

A sensitive and specific blocking ELISA for the detection of rabbit calicivirus RCV-A1 antibodies

BACKGROUND: Antibodies to non-pathogenic rabbit caliciviruses (RCVs) cross-react in serological tests for rabbit hemorrhagic disease virus (RHDV) and vice versa, making epidemiological studies very difficult where both viruses occur. It is important to understand the distribution and interaction of the two viruses because the highly pathogenic RHDV has been used as a biocontrol agent for wild rabbits in Australia and New Zealand for the past 17 years. The presence of the benign RCV Australia 1 (RCV-A1) is considered a key factor for the failure of RHDV mediated rabbit control in cooler, wetter areas of Australia. RESULTS: A highly sensitive and specific blocking ELISA was developed for the detection of RCV-A1 antibodies. When sera from rabbits with a known infection history for either RCV-A1 or RHDV were tested, this assay showed 100% sensitivity and no cross-reactivity with RHDV sera (100% specificity). CONCLUSIONS: This new ELISA not only allows the detection of RCV-A1 at a population level, but also permits the serological status of individual rabbits to be determined more reliably than previously described methods. This robust and simple to perform assay is therefore the tool of choice for studying RCV-A1 epidemiology in Australian wild rabbit populations

Pitfalls for Prospective International Student-Athletes Planning to Play for NCAA-DIII: Case Study

More than 20,000 international student-athletes are currently competing at the NCAA level and the numbers are expected to rise (NCAA, 2019), which illustrates the successful combination of higher education and sports in North America since the 1990s (Danylchuk & Grbac, 2016). Some studies have addressed international student-athletes’ experiences at NCAA Division I and II levels (Popp, 2007, Bentzinger, 2016, Hong, 2018), but few have investigated the Division III (DIII) level on the struggles faced by international student-athletes. Thus, the purpose of this study is to explore the experiences of former international student-athletes (ISAs) in order to gain understanding of the potential pitfalls for prospective international student-athletes (PISA) who plan to pursue college sports at NCAA DIII schools. The significance of this study is to provide suggestions for better international college athletic experiences and prevent dropout. Two former international student-athletes were recruited via purposeful sampling strategy in the Midwest, U.S. Human Subject Institute Review Board approval was granted. Data were collected through approximately 60-minute, semi-structured interviews and transcribed using Otter software. Three-dimensional inquiry model (Clandinin & Connelly, 2000) and Leisure Constraint Theory (LCT, Crane & Temple, 2015) guided this study. A non-linear process was utilized to describe, analyze and interpret the data. Two first level approaches were supplied: an inductive approach based on the LCT and a deductive open coding in-vivo. To reduce researchers bias, epoche and bracketing were employed. Applying LCT, pitfalls related to intrapersonal constraints would be negative perspectives on teams or coaches, lack of enjoyment, the mindset change of playing for school rather than for themselves and their failed expectations. For interpersonal constraints, pitfalls would be negative recruiting experiences, difficulties in adapting to cultural differences, academic challenges, and interest shift away from sports to more sustainable career development. For structural constraints, pitfalls would be less time commitment, less practice and game play, dissatisfaction with their academic programs, and lack of outside interest in their sports. To avoid pitfalls and pursue better athletic and academic international experiences, prospective international student-athletes may need to be more open-minded to adapt to the coaching and team culture and adjust to circumstances different than their expectations. They also need to study more about the recruiting process and devote greater efforts in the relationship with coaches, teammates and classmates. Lastly, they should not be in a rush to make a decision before a thorough study of institutions’ athletic and academic programs, and careers

Acceptance Of Wireless Internet Via Mobile Technology In China

This study explores factors associated with the acceptance of Wireless Internet via Mobile Technology (WIMT) in China. The results indicate that the acceptance of WIMT is related to the factors of perceived usefulness, perceived ease of use, social influences, wireless trust environment, and facilitating conditions. It provides diagnostic insight into how different factors influence user intention to accept WIMT in China, and thus help business develop strategy to prompt WIMT communications and mobile commerce there

Manipulating 1-dimensinal skyrmion motion by external magnetic field gradient

We have investigated an analytic formula of the 1-dimensional magnetic skyrmion dynamics under external magnetic field gradient. We find excellent agreement between the analytical model and micromagnetic simulation results for various magnetic parameters such as the magnetic field gradient, Gilbert damping constant. We also observe much faster velocity of the chiral domain wall (DW) motion. The chiral DW is exist with smaller interfacial Dzyaloshinskii-Moriya interaction energy density cases. These results provide to develop efficient control of skyrmion for spintronic devices.Comment: 15 pages, 5 figures, 1 tabl

Long range magnetic ordering in Na2_2IrO3_3

We report a combined experimental and theoretical investigation of the magnetic structure of the honeycomb lattice magnet Na$_2$IrO$_3$, a strong candidate for a realization of a gapless spin-liquid. Using resonant x-ray magnetic scattering at the Ir L$_3$-edge, we find 3D long range antiferromagnetic order below T$_N$=13.3 K. From the azimuthal dependence of the magnetic Bragg peak, the ordered moment is determined to be predominantly along the {\it a}-axis. Combining the experimental data with first principles calculations, we propose that the most likely spin structure is a novel "zig-zag" structure

Probing the A1 to L10 Transformation in FeCuPt Using the First Order Reversal Curve Method

The A1- L10 phase transformation has been investigated in (001) FeCuPt thin films prepared by atomic-scale multilayer sputtering and rapid thermal annealing (RTA). Traditional x-ray diffraction is not always applicable in generating a true order parameter, due to non-ideal crystallinity of the A1 phase. Using the first-order reversal curve (FORC) method, the A1 and L10 phases are deconvoluted into two distinct features in the FORC distribution, whose relative intensities change with the RTA temperature. The L10 ordering takes place via a nucleation-and-growth mode. A magnetization-based phase fraction is extracted, providing a quantitative measure of the L10 phase homogeneity.Comment: 17 pages, 5 figures, 4 page supplementary material (4 figures

A Cryptic Modifier Causing Transient Self-Incompatibility in Arabidopsis thaliana

SummaryBreakdown of the pollination barrier of self-incompatibility (SI) in older flowers, a phenomenon known as pseudo-self-compatibility or transient SI, has been described as an advantageous reproductive assurance strategy that allows selfing after opportunities for out-crossing have been exhausted [1–9]. Pseudo-self-compatibility is quite prevalent as a mixed mating strategy in nature, but the underlying molecular mechanisms are not known. We had previously shown that Arabidopsis thaliana exhibits cryptic natural variation for pseudo-self-compatibility, which is uncovered by transformation of different accessions with SI specificity-determining SRK and SCR genes from its self-incompatible sister species A. lyrata [10, 11]. Here, by using this transgenic A. thaliana model, we show that pseudo-self-compatibility is caused by a hypomorphic allele of PUB8, an S-locus-linked gene encoding a previously uncharacterized ARM repeat- and U box-containing protein that regulates SRK transcript levels. This is the first gene underlying pseudo-self-compatibility to be identified and the first report in which cryptic natural variation unveiled by a transgene enabled the cloning of a gene for a complex trait

The non-pathogenic Australian rabbit calicivirus RCV-A1 provides temporal and partial cross protection to lethal Rabbit Haemorrhagic Disease Virus infection which is not dependent on antibody titres

The endemic non-pathogenic Australian rabbit calicivirus RCV-A1 is known to provide some cross protection to lethal infection with the closely related Rabbit Haemorrhagic Disease Virus (RHDV). Despite its obvious negative impacts on viral biocontrol of introduced European rabbits in Australia, little is known about the extent and mechanisms of this cross protection. In this study 46 rabbits from a colony naturally infected with RCV-A1 were exposed to RHDV. Survival rates and survival times did not correlate with titres of serum antibodies specific to RCV-A1 or cross reacting to RHDV, but were instead influenced by the time between infection with the two viruses, demonstrating for the first time that the cross protection to lethal RHDV infection is transient. These findings are an important step towards a better understanding of the complex interactions of co-occurring pathogenic and non-pathogenic lagoviruses

Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors

NMDA receptors (NMDARs) are a major class of ionotropic glutamate receptors that can undergo activity-dependent changes in surface expression. Clathrin-mediated endocytosis is a mechanism by which the surface expression of NR2B-containing NMDA receptors is regulated. The C terminus of the NMDA receptor subunit NR2B contains the internalization motif YEKL, which is the binding site for the clathrin adaptor AP-2. The tyrosine (Y1472) within the YEKL motif is phosphorylated by the Src family of kinases and this phosphorylation inhibits the binding of AP-2 and promotes surface expression of NMDA receptors. Cdk5 is a serine/threonine kinase that has been implicated in synaptic plasticity, learning, and memory. Here we demonstrate that inhibition of Cdk5 results in increased phosphorylation of Y1472 NR2B at synapses and decreased binding of NR2B to beta2-adaptin, a subunit of AP-2, thus blocking the activity-dependent endocytosis of NMDA receptors. Furthermore, we show that inhibition of Cdk5 increases the binding of Src to postsynaptic density-95 (PSD-95), and that expression of PSD-95 facilitates the phosphorylation of Y1472 NR2B by Src. Together, these results suggest a model in which inhibition of Cdk5 increases the binding of Src to PSD-95 and the phosphorylation of Y1472 NR2B by Src, which results in decreased binding of NR2B to AP-2, and NR2B/NMDAR endocytosis. This study provides a novel molecular mechanism for the regulation of the surface expression of NR2B-containing NMDA receptors and gives insight into the Cdk5-dependent regulation of synaptic plasticity