4α-methylergosta-8,24(28)-dien-3β-ol,a minor sterol in the seed of horse chestnut

From ripe horse chestnut seed the 4α-methyl sterol fraction was isolated representing 4.5% of the unsaponifiable matter, i.e. 3 mg% of the seed. This fraction was investigated by capillary GC and combined GC-MS. It contains at least 12 components, of which 5 were identified as: obtusifoliol 4α-methylergosta-8,24(28)-dien-3β-ol, gramisterol, cycloeucalenol and citrostadienol. The distribution of these five 4α-methyl sterols in the seed was also determined and they represent about 90% of the investigated fraction. 4α-Methylergosta-8,24(28)-dien-3β-ol up to now been found in higher plants only in traces, while in this fraction it was found in the amount of about 5%.     

Howlers Are Able to Survive in Eucalyptus Plantations Where Remnant and Regenerating Vegetation Is Available

Reversing forest loss through reforestation has become a critical strategy to decrease global climate change, and such programs are more likely to be initiated if they can produce a subsequent monetary gain for the host country. As a result, the planting of monocultures of harvestable trees has become widespread and the practice is accelerating. However, little is known about the effect of such reforestation strategies on biodiversity. Here we quantify the demographic patterns of a population of black howlers (Alouatta pigra) living in a 200-ha eucalyptus plantation with connected remnant forests in southeastern Mexico. We compare our results to data from the literature from forest fragments, extensive forest tracts, and different agrosystems. The howler population inhabiting the plantation grew from 69 individuals in 2007 to 77 in 2008 (11.6% growth) and to 84 in 2009 (9.1% growth). During this time the howlers fed extensively on the native vegetation that was growing under the eucalyptus, vines that grew on the plantation trees, and adjacent areas of native secondary growth, but they almost never fed on eucalyptus. Howler density in the plantation was greater than in extensive forest tracts or forest fragments, whereas mean group size was similar to that in the forest tracts and greater than in the fragments and agrosystems. There was no apparent difference in the adult female-to-immature ratio among sites. Our results indicate that plantations that have associated native vegetation can play a positive role in the conservation of this species, but suggest that harvesting regimens must be carefully orchestrated to prevent associated food scarcity.     

Coinoculation with hepatitis B surface and core antigen promotes a Th1 immune response to a multiepitopic protein of HIV-1

It has been defined that strong and multispecific cellular immune responses correlate with a better prognosis during the course of chronic diseases. A cross-enhancing effect on the resulting immune response obtained by the coadministration of recombinant hepatitis B virus (HBV) surface and core Ag was recently observed. With the objective of studying the effect of such Ag on the immune response to coinoculated heterologous Ag and vice versa, several formulations containing the recombinant HBV Ag and a multiepitopic protein (CR3) composed by CTL and Th epitopes from HIV-1 were evaluated by s.c. and mucosal administration. Combinations of two and three Ag were evaluated for cellular and humoral immune responses. The results showed that the best Ag combination for nasal immunization was the mixture comprising the CR3 recombinant HIV protein and both HBV Ag. Similarly, it was also the best formulation for s.c. immunization in aluminium phosphate adjuvant. In conclusion, it is possible to induce a Th1 stimulation of the cellular immune response specific for a HIV-based recombinant protein by formulating this Ag with the recombinant HBV Ag.     

Recovery from a near-lethal exposure to ultraviolet-C radiation in a scleractinian coral

Hermatypic (reef building) corals live in an environment characterized by high ambient levels of photosynthetically active radiation (PAR) and ultraviolet radiation (UVR). Photoadaptive mechanisms have evolved to protect the sensitive cell structures of the host coral and their photosynthetic, endosymbiotic zooxanthellae. Environmental stressors may destabilize the coral-zooxanthellae system resulting in the expulsion of zooxanthellae and/or loss of photosynthetic pigment within zooxanthellae, causing a condition known as bleaching. It is estimated that 1% of the world’s coral population is lost yearly, partly due to bleaching. Despite intensive research efforts, a single unified mechanism cannot explain this phenomenon. Although UVA and UVB cellular damage is well documented, UVC damage is rarely reported due to its almost complete absorption in the stratosphere. A small scale coral propagation system at the University of Maine was accidentally exposed to 15.5 h of UVC radiation (253.7 nm) from a G15T8 germicidal lamp, resulting in a cumulative surface irradiance of 8.39 × 10⁴ J m⁻². An experiment was designed to monitor the progression of UVC induced damage. Branch sections from affected scleractinian corals, Acropora yongei and Acropora formosa were submitted to histopathology to provide an historical record of tissue response. The death of gastrodermal cells and necrosis resulted in the release of intracellular zooxanthellae into the gastrovascular canals. Zooxanthellae were also injured as evidenced by pale coloration, increased vacuolization and loss of membrane integrity. The recovery of damaged coral tissue likely proceeds by re-epithelialization and zooxanthellae repopulation of gastrodermal cells by adjacent healthy tissue.     

A Multicenter,Open-Label,Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

Background

Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

Objective

This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

Methods

Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

Results

The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.

Limitations

The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.

Conclusion

MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.

Trial Registration

ClinicalTrials.gov NCT00316602     

Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain

Inhibitor of apoptosis proteins (IAPs) regulate the activity of caspases in apoptosis. The human X chromosome-encoded IAP (XIAP) is one of the more potent members of the IAP family and it has been described as a central regulator of apoptosis. Thus, molecules that inhibit XIAP could offer therapeutic opportunities to treat unwanted apoptosis inhibition. In the present study we have applied the selective optimization of side activities (SOSA) approach to the discovery of XIAP inhibitors. In this sense, we have identified dequalinium hydrochloride (Dq) as an inhibitor of the XIAP/caspase-3 interaction both in vitro and in cellular assays.     

Th2-associated alternative Kupffer cell activation promotes liver fibrosis without inducing local inflammation

Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.