Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2

<p>Abstract</p> <p>Background</p> <p>Shiga toxins (Stxs) are the major agents responsible for hemorrhagic colitis and hemolytic-uremic syndrome (HUS) during infections caused by Stx-producing <it>Escherichia coli </it>(STEC) such as serotype O157:H7. Central nervous system (CNS) involvement is an important determinant of mortality in diarrhea associated-HUS. It has been suggested that vascular endothelial injuries caused by Stxs play a crucial role in the development of the disease. The current study investigates the relationship between the cytotoxic effects of Stxs and inflammatory responses in a rabbit brain treated with Stx2.</p> <p>Methods</p> <p>In a rabbit model treated with purified Stx2 or PBS(-), we examined the expression of the Stx receptor globotriaosylceramide (Gb3)/CD77 in the CNS and microglial activation using immunohistochemistry. The relationship between inflammatory responses and neuronal cell death was analyzed by the following methods: real time quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) to determine the expression levels of pro-inflammatory cytokines, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method to detect apoptotic changes.</p> <p>Results</p> <p>Gb3/CD77 expression was detected in endothelial cells but not in neurons or glial cells. In the spinal cord gray matter, significant levels of Gb3/CD77 expression were observed. Severe endothelial injury and microvascular thrombosis resulted in extensive necrotic infarction, which led to acute neuronal damage. Conversely, in the brain, Stx receptor expression was much lower. The observed neuropathology was less severe. However, neuronal apoptosis was observed at the onset of neurological symptoms, and the number of apoptotic cells significantly increased in the brain at a later stage, several days after onset. Microglial activation was observed, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA in the CNS parenchyma was significantly up-regulated. There was significant overexpression of TNF-α transcripts in the brain.</p> <p>Conclusion</p> <p>This study indicates that Stx2 may not directly damage neural cells, but rather inflammatory responses occur in the brain parenchyma in response to primary injury by Stx2 in vascular endothelial cells expressing Gb3/CD77. These findings suggest that neuroinflammation may play a critical role in neurodegenerative processes during STEC infection and that anti-inflammatory intervention may have therapeutic potential.</p

Probing Intergalactic Magnetic Fields in the GLAST Era through Pair Echo Emission from TeV Blazars

More than a dozen blazars are known to be emitters of multi-TeV gamma rays, often with strong and rapid flaring activity. By interacting with photons of the cosmic microwave and infrared backgrounds, these gamma rays inevitably produce electron-positron pairs, which in turn radiate secondary inverse Compton gamma rays in the GeV-TeV range with a characteristic time delay that depends on the properties of the intergalactic magnetic field (IGMF). For sufficiently weak IGMF, such "pair echo" emission may be detectable by the Gamma-ray Large Area Space Telescope (GLAST), providing valuable information on the IGMF. We perform detailed calculations of the time-dependent spectra of pair echos from flaring TeV blazars such as Mrk 501 and PKS 2155-304, taking proper account of the echo geometry and other crucial effects. In some cases, the presence of a weak but non-zero IGMF may enhance the detectability of echos. We discuss the quantitative constraints that can be imposed on the IGMF from GLAST observations, including the case of non-detections.Comment: 4 pages, 3 figures, minor revisions, accepted for publication in APJ

Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRα-Regulated and CLOCK/BMAL1-Regulated Systems

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXRα was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPARα/RXRα. These results suggest that there may be crosstalk between the PPARs/RXRα-regulated system and the CLOCK/BMAL1-regulated system

トレーニング計画立案におけるトレーニングカテゴリーの有用性について

The purpose of this study was to evaluate the usefulness of training categories in yearly training programs. Programs designed with the use of training categories in 1998 and 1999 were compared from the results of blood lactate tests and percentage of individual best records broken. The primary findings of this study were as follows : 1) A comparison of the two programs revealed that the general endurance training period and the specific endurance training period during the off-season in 1998 may have been insufficient for improvement of endurance capacity; 2) the percentage of sprint training in competitive period in 1998, moreover, was low and may not have been sufficient to improve anaerobic capacity, as demonstrated by lower blood lactate accumulation and slower performance times in maximal effort swimming than in 1999; and 3) the above may account for the low number of individual best records broken. These results suggested that training categories are useful in planning yearly training programs for competitive swimmers. More investigation will be needed, however, into the relationship between training conditions and intensities

Neutrino-Driven Jets and Rapid-Process Nucleosynthesis

We have studied whether the jet in a collapse-driven supernova can be a key process for the rapid-process (r-process) nucleosynthesis. We have examined the features of a steady, subsonic, and rigidly rotating jet in which the centrifugal force is balanced by the magnetic force. As for the models in which the magnetic field is weak and angular velocity is small, we found that the r-process does not occur because the final temperature is kept to be too high and the dynamical timescale becomes too long when the neutrino luminosities are set to be high. Even if the luminosities of the neutrinos are set to be low, which results in the low final temperature, we found that the models do not give a required condition to produce the r-process matter. Furthermore, the amount of the mass outflow seems to be too little to explain the solar-system abundance ratio in such low-luminosity models. As for the models in which the magnetic field is strong and angular velocity is large, we found that the entropy per baryon becomes too small and the dynamical timescale becomes too long. This tendency is, of course, a bad one for the production of the r-process nuclei. As a conclusion, we have to say that it is difficult to cause a successful r-process nucleosynthesis in the jet models in this study.Comment: 34 pages and 6 postscript figures. submitted to Astrophysical Journa

Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells

Statins increase peroxisome proliferator-activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α. (2) PPARα mRNA expression was increased by statin treatment. (3) The PPARα levels in nuclear fractions were increased by statin treatment. (4) Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPARα/RXRα expression vectors. In summary, these data demonstrate that PPARα production and activation are upregulated through the PPARα promoter activity by statin treatment

The Influence of Latvian Labor Emigration Abroad on Latvia's Competitiveness

Today, as the world is becoming more global, countries are competing against each other on different terms. Country competitiveness depends on different factors that distinguish one nation from another. As labor force is a valuable asset for any nation, the emigration of it can affect the country in many ways, thus affecting the country's competitiveness. This thesis aimed to find out how Latvian labor force emigration to work abroad will affect Latvia and its competitiveness. Moreover, the thesis also strived to answer how competitive is Latvian economy, who are the people who emigrate from Latvia and what are their experiences, what are the possible consequences for this emigration of Latvian workforce, as well as how these consequences might affect Latvia's competitiveness? To be able to answer the above mentioned research questions quantitative and qualitative research methods were used. First, an Internet survey was made to collect data from Latvian emigrants who have gone to work abroad themselves. After that, a structured interview with researchers from Institute of Philosophy and Sociology, University of Latvia's project about emigration was conducted. The research found out that the emigration of Latvian workforce affects Latvian economy and its competitiveness both in positive and negative ways. The research found that the factors regarding emigration that influence Latvia's economy are: leaving of young and educated people, remittances sent back to Latvia, possible brain drain and brain waste, relief of Latvian economy as well as changing level of entrepreneurship and innovation in the country. The results also showed that emigration has a positive influence on the entrepreneurship in the country, thus improving Latvia's competitiveness among other countries.Tänään, koska maailma on yhä maailmanlaajuinen, maat kilpailevat toisiaan vastaan eri ehdoin. Maa kilpailukyky riippuu eri kertoimiin, jotka erottavat yhden kansakunnan toisesta. Koska työvoima on arvokas voimavara kaikille kansakunta, maastamuutto se voi vaikuttaa maan monin tavoin, mikä vaikuttaa maan kilpailukykyä. Opinnäytetyön tavoitteena oli selvittää, miten Latvian työvoiman maastamuutto työskennellä ulkomailla vaikuttaa Latvian ja sen kilpailukykyä. Lisäksi opinnäytetyön myös pyritty vastaamaan kuinka kilpailukykyinen on Latvian talous, jotka ovat ihmisiä, jotka muuttavat maasta Latvia ja mitkä ovat niiden kokemuksia, mitä mahdollisia seurauksia tälle maastamuuton Latvian työvoiman sekä miten nämä seuraukset voivat vaikuttaa Latvian kilpailukykyyn? Voidakseen vastata edellä mainitun tutkimuksen kysymyksiä määrällisiä ja laadullisia tutkimusmenetelmiä käytettiin. Ensinnäkin, Internet-kysely tehtiin kerätä tietoa Latvian siirtolaisten jotka ovat menneet ulkomaille töihin itse. Sen jälkeen, jäsennelty haastattelu tutkijoiden instituutin filosofian ja sosiologian University of Latvian projekti noin maastamuutto tehtiin. Tutkimuksessa kävi ilmi, että maastamuutto Latvian työvoimasta vaikuttaa Latvian talous ja sen kilpailukyky sekä myönteisiä että kielteisiä keinoja. Tutkimus havaitsi, että tekijät, maastamuutto, jotka vaikuttavat Latvian talous ovat: jätetään nuorten ja koulutettujen ihmisten, rahalähetykset takaisin Latviaan, mahdollinen aivovuoto ja aivotuhlauksen, helpotus Latvian talouden sekä muuttaa tason yrittäjyyden ja innovaatioiden maassa. Tulokset osoittivat myös, että maastamuutto on positiivinen vaikutus yrittäjyyteenyrittäjyyttä maassa, mikä parantaa Latvian kilpailukykyä muun maissa