Tracing the Paleobiology of Paedotherium and Tremacyllus (Pachyrukhinae,Notoungulata), the Latest Sciuromorph South American Native Ungulates – Part II: Orbital,Auditory, and Occipito-Cervical Regions

Journal of Mammalian Evolution - The caudal cranium and occipito-cervical region, although usually overlooked, are informative about the paleobiology of fossil mammals, allowing inquiry into vision...     

Evaluation of APOE polymorphisms and the risk for age-related macular degeneration in a Southeastern Brazilian population

This study aimed to evaluate the role of APOE polymorphisms (rs429358 and rs7412) in the risk of age-related macular degeneration in a sample of the Southeastern Brazilian population. Seven hundred and five unrelated individuals were analyzed, 334 with age-related macular degeneration (case group), and 371 without the disease (control group). In the case group, patients were further stratified according to disease phenotypes, divided into dry and wet age-related macular degeneration, and non-advanced and advanced age-related macular degeneration. APOE polymorphisms (rs429358 and rs7412) were evaluated through polymerase chain reaction and direct sequencing. In the comparison of cases vs. controls, none of the associations reached statistical significance, considering the Bonferroni-adjusted P-value, although there was a suggestive protection for the E3/E4 genotype (OR = 0.626; P-value = 0.037) and E4 carriers (OR = 0.6515; P-value = 0.047). Statistically significant protection for both the E3/E4 genotype and E4 carriers was observed in the comparisons: advanced age-related macular degeneration vs. controls (OR = 0.3665, P-value = 0.491 × 10⁻³ and OR = 0.4031, P-value = 0.814 × 10⁻³, respectively), advanced age-related macular degeneration vs. non-advanced age-related macular degeneration (OR = 0.2529, P-value = 0.659 × 10⁻⁴ and OR = 0.2692, P-value = 0.631 × 10⁻⁴, respectively). In the comparison of wet age-related macular degeneration vs. control, protection was statistically significant only for E3/E4 (OR = 0.4052, P-value = 0.001). None of the comparisons demonstrated any significant association for E2 genotypes or E2 carriers in age-related macular degeneration risk in this study. Findings suggest a protective role of the E4 haplotype in the APOE gene in the risk for advanced and wet forms of age-related macular degeneration, in a sample of the Brazilian population. To our knowledge, this is the first Brazilian study to show the association between APOE polymorphisms and age-related macular degeneration.     

Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi

Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four had significant anti-malarial activity; and three inhibited the growth of T. cruzi. Anticancer activity was demonstrated in four isolates. Of the active isolates, Edenia sp. strain F0755, Xylaria sp. strain F1220, Aspergillus sp. strain F1544, Mycoleptodiscus sp. strain F0194, Phomopsis sp. strain F1566, Pycnoporus sp. strain F0305, and Diaporthe sp. strain F1647 showed the most promise based on their selective bioactivity and lack of toxicity in the assays.     

Caloric restriction and redox state: does this diet increase or decrease oxidant production?

Calorie restriction (CR) is well established to enhance the lifespan of a wide variety of organisms, although the mechanisms are still being uncovered. Recently, some authors have suggested that CR acts through hormesis, enhancing the production of reactive oxygen species (ROS), activating stress response pathways, and increasing lifespan. Here, we review the literature on the effects of CR and redox state. We find that there is no evidence in rodent models of CR that an increase in ROS production occurs. Furthermore, results in Caenorhabditis elegans and Saccharomyces cerevisiae suggesting that CR increases intracellular ROS are questionable, and probably cannot be resolved until adequate, artifact free, tools for real-time, quantitative, and selective measurements of intracellular ROS are developed. Overall, the largest body of work indicates that CR improves redox state, although it seems improbable that a global improvement in redox state is the mechanism through which CR enhances lifespan.     

Conversation between apoptosis and autophagy: “Is it your turn or mine?”

Drug resistance of cancer cells is often correlated with apoptosis evasion; however, an active involvement of autophagy in this scenario has been recently proposed, based on the evidence that autophagy could exert a protective role toward the activation of apoptosis in cancer cells. In this review, we briefly review the basic features of apoptosis, and we describe in details the molecular patterns of autophagy, with a special emphasis on its still controversial physiological function(s). The crucial factors governing the cross talk between autophagy and apoptosis will be illustrated.     

Effect of endplate calcification and mechanical deformation on the distribution of glucose in intervertebral disc: a 3D finite element study

The intervertebral disc (IVD) is avascular, receiving nutrition from surrounding vasculature. Theoretical modelling can supplement experimental results to understand nutrition to IVD more clearly. A new, 3D finite element model of the IVD was developed to investigate effects of endplate calcification and mechanical deformation on glucose distributions in IVD. The model included anatomical disc geometry, non-linear coupling of cellular metabolism with pH and oxygen concentration and strain-dependent properties of the extracellular matrix. Calcification was simulated by reducing endplate permeability (～79%). Mechanical loading was applied based on in vivo disc deformation during the transition from supine to standing positions. Three static strain conditions were considered: supine, standing and weight-bearing standing. Minimum glucose concentrations decreased 45% with endplate calcification, whereas disc deformation led to a 4.8-63% decrease, depending on the endplate condition (i.e. normal vs. calcified). Furthermore, calcification more strongly affected glucose concentrations in the nucleus compared to the annulus fibrous region. This study provides important insight into nutrient distributions in IVD under mechanical deformation.     

Feasibility of the use of ELISA in an immunogenicity-based potency test of anthrax vaccines

Complexities of lethal challenge animal models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. An ELISA was used to measure the antibody response to protective antigen (PA) in mice immunized once with a commercially available (AVA) or a recombinant PA vaccine (rPAV) formulated in-house with aluminum hydroxide. Results from the anti-PA ELISA were used to select a single dose appropriate for the development of a potency test. Immunization with 0.2 mL of AVA induced a measurable response in the majority of animals. This dose was located in the linear range of the vaccine dose–antibody response curve. In the case of rPAV, practical limitations prevented the finding of the best single dose for the potency testing of purified vaccines. In additional immunogenicity experiments neither the magnitude of the response to a single dose of vaccine, nor the estimation of the dose necessary to induce a measurable response were able to consistently detect brief exposure of vaccines to potentially damaging temperatures. However, differences detected for rPAV in the proportion of mice responding to the same dose of treated and untreated vaccine suggested that further assay development to increase the sensitivity of the latter design may be warranted.     

Isozymes from the herbivorous gecarcinid land crab, Gecarcoidea natalis that possess both lichenase and endo-β-1,4-glucanase activity

Three isozymes with both lichenase and endo-β-1,4-glucanase activity were purified and characterised from the midgut gland of the herbivorous gecarcinid land crab, Gecarcoidea natalis. The three isozymes, termed 1a, 1b and 2, had respective molecular masses of 53 ± 0 (3), 43 ± 0 (3) and 47.4 ± 0(3) kDa. All isozymes possessed similar V(max) values and thus hydrolysed both carboxy methyl cellulose and lichenan equally. Furthermore the chromatography profiles for lichenase activities mirrored that for endo-β-1,4-glucanase activities suggesting that the same enzyme possessed both activities. Given this, the endo-β-1,4-glucanase enzymes described for other animals, may, like the isozymes described in this study, may be able to hydrolyse lichenan. However this ability needs to be confirmed. The main digestive function of these isozymes may be to hydrolyse hemicelluloses such as lichenan and mixed beta-D-glucan. All three isozymes randomly hydrolysed internal glycosidic bonds within carboxy methyl cellulose and lichenan to release short oligomers of 4-5 glucose units in length. They also hydrolysed cellotetraose to either two units of cellobiose or cellotriose and glucose. Cellotriose was hydrolysed to cellobiose and glucose. All three enzymes lacked β-1,4-glucosidase activity as they could not hydrolyse cellobiose.     

Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina

Background

There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA) which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin) against reference strains of Staphylococcus aureus.

Methods and Results

The activity of the standard antibiotics and compounds on reference methicillin-sensitive and resistant strains of S. aureus were determined using the macrodilution broth method. The minimum inhibitory concentration (MIC) of the compounds was compared with that of the standard antibiotics. The interaction between any two antimicrobial agents was estimated by calculating the fractional inhibitory concentration (FIC index) of the combination. The various combinations of antibiotics and compounds reduced the MIC to a range of 0.05 to 50%.

Conclusion

Pentacyclic triterpenoids have shown anti-staphylococcal activities and although individually weaker than common antibiotics produced from bacteria and fungi, synergistically these compounds may use different mechanism of action or pathways to exert their antimicrobial effects, as implicated in the lowered MICs. Therefore, the use of current antibiotics could be maintained in their combination with plant-derived antibacterial agents as a therapeutic option in the treatment of S. aureus infections.