Etiology, pathogenesis and future prospects for developing improved vaccines against bluetongue virus: A Review

Bluetongue is a viral disease that primarily affects sheep, occasionally goats and deer and, very rarely, cattle. The disease is caused by an icosahedral, non-enveloped, double-stranded RNA (dsRNA) virus within the Orbivirus genus of the family Reoviridae. It is non-contagious and is only transmitted by insect vectors. BTV serotypes are known to occur in Africa, Asia, South America, North America, Middle East, India, and Australia generally between latitudes 35°S and 50°N. It occurs around the Mediterranean in summer, subsiding when temperatures drop in winter. The replication phase of the bluetongue virus (BTV) infection cycle is initiated when the virus core is delivered into the cytoplasm of a susceptible host cell. The 10 segments of the viral genome remain packaged within the core throughout the replication cycle, helping to prevent the activation of host defense mechanisms that would be caused by direct contact between the dsRNA and the host cell cytoplasm. This review presents comprehensive information on etiology, pathogenesis, prevention and control of the disease.Key words: Bluetongue, orbivirus, pathogenesis, prevention

Kavezno izlaganje lubina (Dicentrarchus labrax) u procjeni genotoksičnog utjecaja onečišćenja

Genotoxic effects are often the earliest signs of pollution-related environmental disturbance. In this study, we used the comet assay and micronucleus test to assess DNA damage in the erythrocytes of the European sea bass (Dicentrarchus labrax) exposed to environmental pollution in situ. Fish were collected from a fi sh farm in the Trogir Bay and their cages placed at an unpolluted reference site Šolta (Nečujam Bay) and a polluted site Vranjic (Kaštela Bay) for four weeks. A group of fi sh which remained at the fi sh farm Trogir Bay were used as the second control group. Fish exposed at the Vranjic site showed a signifi cantly higher erythrocyte DNA damage, measured by the comet assay, than either control group. Micronucleus induction showed a similar gradient of DNA damage, but did not reach statistical signifi cance. Our results show that cage exposure of a marine fi sh D. labrax can be useful in environmental biomonitoring and confi rm the comet assay as a suitable tool for detecting pollution-related genotoxicity.Genotoksični učinak često je jedan od najranijih pokazatelja štetnog djelovanja onečišćenja okoliša. U ovom radu procijenjeno je oštećenje DNA u eritrocitima lubina (Dicentrarchus labrax) izloženima okolišnom onečišćenju s pomoću komet-testa i mikronukleus-testa. Lubini su prikupljeni na ribogojilištu i kavezno izloženi u periodu od četiri tjedna na dvije postaje različitog stupnja onečišćenja na jadranskoj obali: na kontrolnoj postaji Šolta (zaljev Nečujam) i na onečišćenoj postaji Vranjic (Kaštelanski zaljev). Zasebna skupina lubina skupljena na ribogojilištu poslužila je kao druga kontrola. Rezultati komet-testa pokazali su statistički značajan porast oštećenja DNA na postaji Vranjic u usporedbi s obje kontrolne postaje. Rezultati mikronukleus-testa pokazali su sličan gradijent onečišćenja, iako nisu dosegli statističku značajnost. Ovi rezultati upućuju na primjenjivost kaveznog izlaganja lubina D. labrax u biomonitoringu vodenog okoliša te potvrđuju korisnost komet-testa kao prikladne metode za detekciju genotoksičnog utjecaja onečišćenja

The deleterious role of the prostaglandin E2 EP3 receptor in angiotensin II hypertension

Angiotensin II (ANG II) plays a key role in regulating blood pressure and inflammation. Prostaglandin E2 (PGE2) signals through four different G protein-coupled receptors, eliciting a variety of effects. We reported that activation of the EP3 receptor reduces cardiac contractility. More recently, we have shown that overexpression of the EP4 receptor is protective in a mouse myocardial infarction model. We hypothesize in this study that the relative abundance of EP3 and EP4 receptors is a major determinant of end-organ damage in the diseased heart. Thus EP3 is detrimental to cardiac function and promotes inflammation, whereas antagonism of the EP3 receptor is protective in an ANG II hypertension (HTN) model. To test our hypothesis, male 10- to 12-wk-old C57BL/6 mice were anesthetized with isoflurane and osmotic minipumps containing ANG II were implanted subcutaneously for 2 wk. We found that antagonism of the EP3 receptor using L798,106 significantly attenuated the increase in blood pressure with ANG II infusion. Moreover, antagonism of the EP3 receptor prevented a decline in cardiac function after ANG II treatment. We also found that 10- to 12-wk-old EP3-transgenic mice, which overexpress EP3 in the cardiomyocytes, have worsened cardiac function. In conclusion, activation or overexpression of EP3 exacerbates end-organ damage in ANG II HTN. In contrast, antagonism of the EP3 receptor is beneficial and reduces cardiac dysfunction, inflammation, and HTN.NEW & NOTEWORTHY This study is the first to show that systemic treatment with an EP3 receptor antagonist (L798,106) attenuates the angiotensin II-induced increase in blood pressure in mice. The results from this project could complement existing hypertension therapies by combining blockade of the EP3 receptor with antihypertensive drugs

Modulation of the Pulmonary Type 2 T-Cell Response to Cryptococcus neoformans by Intratracheal Delivery of a Tumor Necrosis Factor Alpha-Expressing Adenoviral Vector▿ †

C57BL/6 mice develop an allergic bronchopulmonary mycosis following intratracheal inoculation of Cryptococcus neoformans 24067. We determined that only low levels of tumor necrosis factor alpha (TNF-α) are produced in the lungs following infection. Thus, the objective of the present studies was to determine whether treatment with a TNF-α-expressing adenoviral vector (adenoviral vector with the murine TNF-α transgene under the control of the human cytomegalovirus promoter [AdTNFα]) could switch the type 2 (T2) T-cell response/T1 T-cell response balance toward the T1 T-cell response. AdTNFα induced an increase in TNF-α expression at days 3 and 7. At days 7 to 14, the number of cryptococcal lung CFU continued to increase in both untreated and control adenoviral vector (empty adenovirus type 5 backbone)-treated mice, but the number was ultimately 100-fold lower following AdTNFα treatment. AdTNFα markedly increased neutrophil and macrophage numbers, and pulmonary eosinophilia did not develop. CXCL1, CXCL2, and gamma interferon were also up-regulated, while eotaxin, interleukin-4 (IL-4), and IL-5 were down-regulated. AdTNFα treatment also increased the number of CD80+ and CD40+ cells and decreased the number of CD86+ cells (CD11b+ and CD11c+) in the lungs. Major histocompatibility complex class II levels on CD11b+ cells were increased. Whole-lung expression of inducible nitric oxide synthase was increased, while YM2 expression and acidic mammalian chitinase expression were decreased. None of these effects were observed with the control (empty) adenoviral vector. Overall, these results support the hypothesis that early TNF-α expression promotes a shift in T-cell and macrophage polarization from T2/alternatively activated macrophages toward T1/classically activated macrophages, resulting in control of the fungal infection and prevention of the allergic response

Syntheses and Determination of Absolute Configurations and Biological Activities of the Enantiomers of the Longtailed Mealybug Pheromone

Preparation and assignment of absolute configurations to both enantiomers of the sex pheromone of the longtailed mealybug, an irregular monoterpenoid with extraordinary biological activity, has been completed. Comparison of the biological activities of both enantiomers and the racemate in field trials showed that the (<i>S</i>)-(+)-enantiomer was highly attractive to male mealybugs, strongly suggesting that female longtailed mealybugs produce this enantiomer. The (<i>R</i>)-(−)-enantiomer was benign, being neither attractive nor inhibitory