The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway

Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge Aplysina aerophoba that has been previously characterized by our group as a potent antiangiogenic compound in vitro and in vivo. In this work, we provide evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells. Studies on the nuclear morphology of treated cells revealed that aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it increases the percentage of cells with sub-diploid DNA content in endothelial, but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells. Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases-2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly (ADP-ribose) polymerase and lamin-A in a caspase-dependent mechanism. Our data indicate a relevant role of the mitochondria in the apoptogenic activity of this compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad relates to the mitochondria-mediated induction of apoptosis by this compound.     

Assessment of the Bacteriocinogenic Potential of Marine Bacteria Reveals Lichenicidin Production by Seaweed-Derived Bacillus spp.

The objectives of this study were (1) to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2) to identify at least some of the bacteriocins produced, if any and (3) to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins.     

Antinociceptive and Anti-Inflammatory Activities of Crude Methanolic Extract of Red Alga Bryothamnion triquetrum

The marine environment is an extraordinary reservoir of bioactive natural products, many of which exhibit chemical and structural features not found in terrestrial natural products. In this regard, the aim of this study was to investigate the possible antinociceptive and anti-inflammatory activities of a crude methanolic extract of the red alga Bryothamnion triquetrum (BT-MeOH) in murine models. Groups of Swiss mice of both sexes (25–30 g) were used throughout the experiments. The potential antinociceptive of BT-MeOH was evaluated by means of the following tests: acetic acid-induced writhing, hot-plate test and glutamate- and formalin-induced nociception. The anti-inflammatory activity of BT-MeOH was investigated using the zymosan A-induced peritonitis test. The tests were conducted using 100 mg/kg (p.o.) BT-MeOH, 33.3 mg/kg (p.o.) dipyrone, 35.7 mg/kg (p.o.) indomethacin and 5.7 mg/kg (s.c.) morphine. The extract and all standard drugs were administered 40 min before the nociceptive/inflammatory stimulus. In the acetic acid-induced writhing test, BT-MeOH and dipyrone inhibited the nociceptive response by 55.9% (22.2 ± 2.0 writhings; p < 0.01) and 80.9% (9.6 ± 2.1 writhings; p < 0.01). In the hot-plate test, BT-MeOH did not increase the latency time of the animals in the time evaluated. In addition, BT-MeOH inhibited glutamate-induced nociception by 50.1%. While BT-MeOH did not inhibit the neurogenic phase in formalin-induced nociception, the inflammatory phase was inhibited by 53.1% (66.8 ± 14.2 s; p < 0.01). Indomethacin inhibited the inflammatory phase by 60.2% (56.8 ± 8.7 s; p < 0.01). In the zymosan-induced peritonitis test, BT-MeOH inhibited 55.6% (6.6 ± 0.2 × 10⁶ leukocytes/mL; p < 0.01) of leukocyte migration, while indomethacin inhibited 78.1% (3.2 ± 0.1 × 10⁶ leukocytes/mL; p < 0.01). Based on the results obtained in this study, we conclude that BT-MeOH has peripheral antinociceptive and anti-inflammatory activities. However, more studies need to be conducted to confirm these properties.     

Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei

Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.     

Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions

After detection of a high prevalence of scrapie in a large dairy goat herd, 72 infected animals were examined by immunohistochemistry with prion protein (PrP) antibody Bar224 to study the pathogenesis of the infection. Tissues examined included the brain and thoracic spinal cord (TSC), a wide selection of lymphoreticular system (LRS) tissues, the distal ileum and its enteric nervous system (ENS), and other organs, including the mammary gland. The whole open reading frame of the PRNP gene was sequenced and antibodies to caprine arthritis-encephalitis virus (CAEV) infection were determined. Unexpectedly, accumulation of disease-associated PrP (PrP^d) in the brain was more frequent in methionine carriers at codon 142 (24/32, 75.0%) than amongst isoleucine homozygotes (14/40, 35.0%). The latter, however, showed significantly greater amounts of brain PrP^d than the former (average scores of 9.3 and 3.0, respectively). A significant proportion of the 38 goats that were positive in brain were negative in the ENS (44.7%) or in the TSC (39.5%). These results, together with the early and consistent involvement of the circumventricular organs and the hypothalamus, point towards a significant contribution of the haematogenous route in the process of neuroinvasion. Chronic enteritis was observed in 98 of the 200 goats examined, with no association with either scrapie infection or presence of PrP^d in the gut. Lymphoproliferative interstitial mastitis was observed in 13/31 CAEV-positive and scrapie-infected goats; PrP^d in the mammary gland was detected in five of those 13 goats, suggesting a possible contribution of CAEV infection in scrapie transmission via milk.     

A core set of microsatellite markers for conservation genetics studies of Korean goral (Naemorhedus caudatus) and its cross-species amplification in Caprinae species

In order to screen microsatellites for conservation genetics studies of the species, a total of 23 microsatellite loci from Korean goral (Naemorhedus caudatus), including 15 previously developed loci and 8 new loci in this study, were tested. Eleven microsatellites were screened and subjected to cross-species amplification using a test panel of four Caprinae species, Japanese serows (Capricornis crispus), Chinese gorals (Naemorhedus goral), Northern chamois (Rupicapra rupicapra) and domestic goats (Capra hircus). In addition, all eleven microsatellites (SY3A, SY12A, SY12B, SY48, SY58, SY71, SY76, SY84, SY84B, SY112, and SY129) satisfied the criteria to be a core set of microsatellites. This core set of microsatellites and cross-species amplification of Korean goral microsatellites were found to be helpful for high-resolution studies for conservation and management of Korean goral and other endangered Caprinae species.     

The Economic Monitoring Network for Private Forests in Hungary

The private forestry sector in Hungary was reintroduced in the early 1990s, as a part of the initial economic reform package aimed at transforming the economy from central planning to a market economy. The fundamental changes required a complete restructuring of the forestry sector, which is still going on, with sound information becoming ever more important. The Economic Monitoring Network for Private Forests in Hungary (EMN-PF) is supporting a price and cost reference database, financial analysis of forestry processes, forestry holding analysis and estimation of the economic output of the private forestry sector. Each output is based on data collecting methods that are balanced between accuracy and ease of data collection. EMN-PF applies surveys and uses open databases as data sources. Forest owners’ and integrators’ estimates are an easy way of collecting data, but the accuracy of data is difficult to control. The analysis of forest holdings can be based on the annual financial reports of forest enterprises with pure forest activity. These reports are already existing documents, which therefore are easy to collect in large numbers, but do not provide highly detailed data. Based on the National Forest Inventory and the results of the financial analysis, the economic output of the private forestry sector can be estimated.     

Capacity for Timber Management in Small and Medium Forest Enterprises: A Case Study from the Peruvian Amazon

With the implementation of a new legal framework for more responsible forest management in Peru, private small-medium forest enterprises (SMFEs) have become the most important social actors engaged in commercial forestry in the Peruvian Amazon. Despite the role of SMFEs in contributing to employment and local economic growth, there is little information with respect to their economic performance and capacities. This is a hindrance to efforts aimed at better characterizing this important sector and its influence on the development and conservation of tropical forests. For this study, 29 private SMFEs were surveyed to inventory their capital assets in order to evaluate their capacities to carry out timber management. Results indicate that SMFEs vary greatly in terms of their produced and natural capital assets, and consequently in their forest management capabilities as well. While most SMFEs lack adequate capacity for sustainable forest management, those that had more valuable timber resources and physical infrastructure attained forest certification. SMFE capacities depend greatly on external mechanisms to ensure consistent technical and financial assistance.     

Diversification of Pinus halepensis forests by sowing Quercus ilex and Quercus pubescens acorns: testing the effects of different vegetation and soil treatments

The goal of this study was to develop management strategies favouring establishment and survival of holm oak (Quercus ilex L.) and downy oak (Quercus pubescens Willd.)??two species co-occurring in Southern France??in mature Allepo pine forests (Pinus halepensis Mill subsp. halepensis). An experimental design was assessed in a partially cut mature stand of Aleppo pine in which five soil and vegetation treatments??chopping, chopping followed by scarification in one or two directions, prescribed burning, control??and two slash treatments (presence/absence) were applied. A total of 1,600 sowing points, each composed of 3 Q. ilex or Q. pubescens acorns, were installed in the different treatments in November of two consecutive years at 6 and 18 months, after the end of treatments. Survival was monitored 3 and 2 years after sowing, soil surface at the sowing points was characterized at different dates, and predawn leaf water potentials were measured during the dry season. High mortality occurred after the first summer, but survival after 1 year was 2.3?C5.2 higher in Q. ilex than in Q. pubescens, confirming that Q. ilex was better adapted to the drier parts of the Mediterranean area. Survival was significantly influenced by the treatments, but there was a variable response between the two sowing years under most of the treatments. Only intense fire proved the most beneficial treatment for seedling survival in both years. The micro-local soil cover conditions induced by the treatments played a major role in explaining oak survival. In particular, grass cover (mainly Brachypodium retusum) proved to be largely unfavourable to seedling survival and growth, and this detrimental effect was also confirmed by lower predawn leaf water potential values with increasing grass cover. Acorn introduction designed to diversify mature Aleppo pine forest after soil and vegetation treatments therefore has to be considered for treatments that most efficiently impair the pre-existing competing grass cover such as prescribed high-intensity fire treatment.