Development of a novel anti-biofilm peptide derived from profilin of Spodoptera frugiperda

Abstract

Candida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide—PEP-IA18—was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5?µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10?×?MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species.     

Influence of sea turtle nesting on hunting behavior and movements of jaguars in the dry forest of northwest Costa Rica

Jaguars (Panthera onca) are opportunistic predators that prey on large profitable prey items, such as sea turtles at nesting beaches. Here, we use jaguar and sea turtle track-count surveys, combined with satellite telemetry of one jaguar, to evaluate whether jaguar hunting behavior and movements are influenced by seasonal sea turtle nesting in the Sector Santa Rosa of Área de Conservación Guanacaste in northwest Costa Rica. We used generalized linear models to evaluate the effect of moon phase and sea surface temperature on olive ridley (Lepidochelis olivacea) and green turtle (Chelonia mydas) nesting abundance, as well as the combination of these predictors on the frequency of jaguar predation activity (proximity to nesting beaches) and movements. For home-range size and location analyses, we calculated kernel density estimates for each season at three different temporal scales. Sea turtle nesting season influenced jaguar activity patterns, as well as sea turtle abundance was related to jaguar locations and predation events, but jaguar home-range size (88.8 km² overall) did not differ between nesting seasons or among temporal scales. Environmental conditions influenced sea turtle nesting and, as a consequence, also influenced jaguar movements and foraging activity. Our study defined the home range of a female jaguar in the tropical dry forest and its relationship to seasonally abundant turtles. Additional information related to the effect of tourism on jaguar–sea turtle interactions would improve conservation of these species at unique nesting beaches in the area.     

Current genetic engineering strategies for the production of antihypertensive ACEI peptides

Hypertension is a major and highly prevalent risk factor for various diseases. Among the most frequently prescribed antihypertensive first-line drugs are synthetic angiotensin I-converting enzyme inhibitors (ACEI). However, since  their use in hypertension therapy has been linked to various side effects, interest in the application of food-derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods such as chemical synthesis or enzymatic hydrolysis of food proteins has been proven troublesome. We here provide an overview of current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome the limitations of ACEIp large-scale production. Latest advances in ACEIp research and current genetic engineering-based strategies for heterologous production of ACEIp (and precursors) are also presented. Cloning approaches include tandem repeats of single ACEIp, ACEIp fusion to proteins/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp-containing modified plant storage proteins. Although bacteria have been privileged ACEIp heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae-based platforms are now emerging. Besides being generally safer, cost-effective and scalable, these “pharming” platforms can perform therelevant posttranslational modifications and produce (and eventually deliver) biologically active protein/peptide-based antihypertensive medicines.     

Highways are a threat for giant armadillos that underpasses can mitigate

We report 24 records of giant armadillo roadkill on Brazilian highways in the Cerrado, Pantanal and Amazon biomes illustrating that highways are a threat to this species. However, we also documented the species using underpasses, demonstrating that these structures could help to reduce the risk of roadkill for giant armadillos.     

Relationship between epipelon,epiphyton and phytoplankton in two limnological phases in a shallow tropical reservoir with high Nymphaea coverage

Macrophytes and phytoplankton are recognized as having roles in determining alternative stable states in shallow lakes and reservoirs, while the role of periphyton has been poorly investigated. Temporal and spatial variation of phytoplankton, epipelon and epiphyton was examined in a shallow reservoir with high abundance of aquatic macrophytes. The relationships between algae communities and abiotic factors, macrophyte coverage and zooplankton density were also analyzed. Monthly sampling was performed in three zones of the depth gradient of the reservoir. Two phases of algal dominance were found: a phytoplankton phase and epipelon phase. The phase of phytoplankton dominance was characterized by high macrophyte coverage. Rotifera was the dominant zooplankton group in all the zones. Flagellate algae were dominant in phytoplankton, epipelon and epiphyton. Macrophyte coverage was found to be a predictor for algal biomass. Changes in biomass and species composition were associated with macrophyte cover variation, mainly the Nymphaea. In addition to the abiotic factors, the macrophyte coverage was a determining factor for changes to the algal community, contributing to the alternation between dominance phases of phytoplankton and epipelon. The macrophyte–phytoplankton–periphyton relationship needs to be further known in shallow reservoirs, especially the role of epipelon as an alternate stable state.

     

Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme

Background

Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.

Methods

Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4⁺ and CD8⁺ T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.

Results

Median overall survival among 27 patients was 9.6 months (95 % CI 3.2–16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS⁺ T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.

Conclusions

Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS⁺ T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required.     

Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV-1-infected children

Background

Variability in MDR1 and PXR has been associated with differences in drug plasma levels and response to antiretroviral therapy. We investigated whether polymorphisms in MDR1 (T-129C, C1236T and C3435T) and PXR (C63396T) affect lopinavir plasma concentration and the virological or immunological response to HAART in HIV-1-infected children.

Methods

Genotypes were identified in 100 blood donors and 38 HIV-1-infected children. All children received HAART with lopinavir boosted with ritonavir (LPV/r) at the time of LPV plasma level quantification, before (C_trough) and between 1 and 2 h after (C_post-dose) the administration of the next dose of drug. CD4⁺ T-cell counts and plasma viral load were analyzed before and after the initiation of LPV/r.

Results

MDR1 1236T, MDR1 3435T and PXR 63396T alleles showed a frequency of ~ 50% while the MDR1 -129C allele only reached 5%. Children heterozygotes 1236CT showed a significantly lower LPV C_post-dose than homozygotes 1236TT (median C_post-dose = 3.04 μg/ml and 6.50 μg/ml, respectively; p = 0.016). Children heterozygotes 1236CT also had a lower decrease of viral load after 36 weeks of LPV/r exposure compared with homozygotes 1236CC (median viral load changes = − 0.50 log₁₀ copies/ml and − 2.08 log₁₀ copies/ml, respectively; p = 0.047). No effect on the immunological response was observed for polymorphisms of MDR1 or PXR.

Conclusions

Our results suggest that the MDR1 C1236T SNP significantly reduces LPV plasma concentration affecting the virological response to HAART. Heterozygotes 1236CT might have an altered level of P-gp expression/activity in enterocytes and CD4⁺ T lymphocytes that limits the absorption of LPV leading to an impaired virological suppression.     

Regulation of stem cell therapies under attack in Europe: for whom the bell tolls

At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non‐medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context—social, financial, medical, legal—in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of ‘translational medicine’. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients.     

ADAM9 silencing inhibits breast tumor cell invasion in vitro

ADAM9 (A Disintegrin And Metalloproteinase 9) is a member of the ADAM protein family which contains a disintegrin domain. This protein family plays key roles in many physiological processes, including fertilization, migration, and cell survival. The ADAM proteins have also been implicated in various diseases, including cancer. Specifically, ADAM9 has been suggested to be involved in metastasis. To address this question, we generated ADAM9 knockdown clones of MDA-MB-231 breast tumor cells using silencing RNAs that were tested for cell adhesion, proliferation, migration and invasion assays. In RNAi-mediated ADAM9 silenced MDA-MB-231 cells, the expression of ADAM9 was lower from the third to the sixth day after silencing and inhibited tumor cell invasion in matrigel by approximately 72% when compared to control cells, without affecting cell adhesion, proliferation or migration. In conclusion, the generation of MDA-MB-231 knockdown clones lacking ADAM9 expression inhibited tumor cell invasion in vitro, suggesting that ADAM9 is an important molecule in the processes of invasion and metastasis.