Synergic Effect of Photodynamic Therapy with Methylene Blue and Surfactants in the Inhibition of Candida albicans

Photodynamic therapy (PDT) has been originally developed for the treatment of cancer, but it has been successfully employed in the treatment of infectious diseases, including fungal infections. Surfactants are amphiphilic compounds that also have antifungal properties. The present work demonstrates the synergic effect of PDT with methylene blue (MB) and LED combined with four different surfactants in the killing of Candida albicans. Subinhibitory concentrations of CTAC, HPS, SDS and Triton X-100 were tested with MB PDT. The combined therapies proved to be more efficient than PDT or surfactants separately. The best results were obtained with CTAC and HPS and PDT with MB at the concentration of 32 μg/mL. In conclusion, the combination of surfactants and PDT is an alternative antifungal treatment that can achieve more effective performance with minimal discomfort to the patient.     

To converge or not to converge in environmental space: testing for similar environments between analogous succulent plants of North America and Africa

Background and Aims

Convergent evolution is invoked to explain similarity between unrelated organisms in similar environments, but most evaluations of convergence analyse similarity of organismal attributes rather than of the environment. This study focuses on the globular succulent plants of the Americas, the cacti, and their counterparts in Africa in the ice-plant, spurge and milkweed families. Though often held up as paragons of convergent morphological evolution, the environmental similarity of these plants has remained largely unexamined from a quantitative perspective.

Methods

Five hotspots (centres of high species diversity of globular succulents) were selected, two in Mexico and three in South Africa. Their environments were compared using niche modelling tools, randomization tests of niche similarity and multivariate analyses to test for environmental similarity.

Key Results

Although the sites selected have ‘similar’ but unrelated life forms, almost all our results highlighted more climate differences than similarities between the hotspots. Interprediction of niches within and between continents, a niche equivalence test, and MANOVA results showed significant differences. In contrast, a niche similarity test showed that the comparisons of Cuatrociénegas–Richtersveld, Huizache–Knersvlakte and Huizache–Richtersveld were similar.

Conclusions

Differences in rainfall and temperature regimes and the potential effect of edaphic factors may be involved in the differences between the hotspots. In addition, differences in structure, morphology and physiology of the globular succulents may coincide with some of the climatic dissimilarities; i.e. given convergence as the evolution of similar morphologies under similar conditions, then it may be that differing environments diagnose inconspicuous morphological differences. Moreover, although fine-scale differences between sites were found, a coarser perspective shows that these sites are clearly similar as drylands with relatively moderate drought and mild temperatures, illustrating how all studies of convergence must address the issue of how similar two entities must be before they are considered convergent.     

Thiophenacetamide as a potential modulator to NF-κB: structure and dynamics study using in silico and molecular biology assays

Abstract

Nuclear factor kappa B (NF-κB) plays critical roles in the regulation of many pathophysiological processes, including inflammation and immune responses, cell growth and apoptosis. This DNA-binding protein receptor is considered an important molecular target to treat many diseases through host-directed therapy. In this line, several drugs containing thiophene cores have been extensively evaluated due to their ability to interfere on NF-κB translocation to the nucleus. In this work, assays using drug affinity responsive target stability (DARTS) revealed that the parent compound N-(Aryl)-2-thiophen-2-ylacetamide referred to as thiophenacetamide (TAA) specifically binds to the p65 subunit of the NF-κB. Since no experimental binding mode of TAA with p65 is available, we explored TAA within putative sites in silico to gain insights into its possible binding mode and behavior. The binding mode of TAA found in Site 1 formed hydrogen bonds with Lys37 and Asp125 on p65, important residues near DNA-binding region. Molecular dynamics simulations showed the stability of this mode of binding in contrast to the other also tested modes. Our results suggest that TAA binding could occur in regions close to residues responsible for DNA binding, increasing NF-κB protein rigidity and affecting the association between DNA and NF-κB.

Communicated by Ramaswamy H. Sarma     

Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension

Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced by MCT in mice reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients. This is a pre-requisite for widespread use of mice to examine mechanisms of cachexia and diaphragm abnormalities in PH. Thus, we measured body and soleus muscle weight, food intake, and diaphragm contractile properties in mice after 6–8 weeks of saline (control) or MCT (600 mg/kg) injections. Body weight progressively decreased in PH mice, while food intake was similar in both groups. PH decreased (P<0.05) diaphragm maximal isometric specific force, maximal shortening velocity, and peak power. Protein carbonyls in whole-diaphragm lysates and the abundance of select myofibrillar proteins were unchanged by PH. Our findings show diaphragm isometric and isotonic contractile abnormalities in a murine model of PH induced by MCT. Overall, the murine model of PH elicited by MCT mimics loss of body weight and diaphragm muscle weakness reported in PH patients.     

A Novel Role for Tm7sf2 Gene in Regulating TNFα Expression

We have explored the role of Tm7sf2 gene, which codifies for 3β-hydroxysterol Δ14-reductase, an endoplasmic reticulum resident protein, in the sensitivity to endoplasmic reticulum stress and in the resulting inflammatory response. We used mouse embryonic fibroblasts, derived from Tm7sf2^+/+ and Tm7sf2^−/− mice, to determine the in vitro effects of thapsigargin on NF-κB activation. Our results show that the Tm7sf2 gene controls the launch of the unfolded protein response and presides an anti-inflammatory loop thus its absence correlates with NF-κB activation and TNFα up-regulation. Our data also show that Tm7sf2 gene regulates liver X receptor activation and its absence inhibits LXR signalling. By expressing the hTm7sf2 gene in KO MEFs and observing a reduced NF-κB activation, we have confirmed that Tm7sf2 gene is linked to NF-κB activation. Finally we used genetically modified mice in an in vivo model of ER stress and of inflammation. Our results show a significant increase in renal TNFα expression after tunicamycin exposure and in the oedematogenic response in Tm7sf2^−/− mice. In conclusion, we have shown that the Tm7sf2 gene, to date involved only in cholesterol biosynthesis, also controls an anti-inflammatory loop thereby confirming the existence of cross talk between metabolic pathways and inflammatory response.     

Bipolar Disorder Affects Behavior and Social Skills on the Internet

Background

Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD.

Methods

This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN).

Results

SNN (p<0.001) and FBN (p = 0.036) of patients with BD were significantly lower than those of controls. Also, variables related with Internet use were significantly lower in patients, e.g., close contacts on Facebook (p = 0.021), Internet experience (p = 0.020), and knowledge of terms associated with social networking sites (p = 0.042). Also, patients showed lower rates of the expected pattern of Internet use (based on their age generation), including a poorer knowledge of SNS (p = 0.018) and a lower frequency of Internet use (p = 0.010).

Discussion

This study suggests that patients with BD show smaller social networks both in real-world settings and on the Internet. Also, patients tend to use the Internet and social networking sites less frequently and show a poorer knowledge of Internet and social media than healthy controls, below the expected for their generation. These significant differences between patients and controls suggest that the effects of BD on social relationships and functioning extend to electronic media.     

What smells? Developing in‐field methods to characterize the chemical composition of wild mammalian scent cues

Olfactory cues play an important role in mammalian biology, but have been challenging to assess in the field. Current methods pose problematic issues with sample storage and transportation, limiting our ability to connect chemical variation in scents with relevant ecological and behavioral contexts. Real‐time, in‐field analysis via portable gas chromatography–mass spectrometry (GC‐MS) has the potential to overcome these issues, but with trade‐offs of reduced sensitivity and compound mass range. We field‐tested the ability of portable GC‐MS to support two representative applications of chemical ecology research with a wild arboreal primate, common marmoset monkeys (Callithrix jacchus). We developed methods to (a) evaluate the chemical composition of marmoset scent marks deposited at feeding sites and (b) characterize the scent profiles of exudates eaten by marmosets. We successfully collected marmoset scent marks across several canopy heights, with the portable GC‐MS detecting known components of marmoset glandular secretions and differentiating these from in‐field controls. Likewise, variation in the chemical profile of scent marks demonstrated a significant correlation with marmoset feeding behavior, indicating these scents’ biological relevance. The portable GC‐MS also delineated species‐specific olfactory signatures of exudates fed on by marmosets. Despite the trade‐offs, portable GC‐MS represents a viable option for characterizing olfactory compounds used by wild mammals, yielding biologically relevant data. While the decision to adopt portable GC‐MS will likely depend on site‐ and project‐specific needs, our ability to conduct two example applications under relatively challenging field conditions bodes well for the versatility of in‐field GC‐MS.     

“Blockade of Nitric Oxide Overproduction and Oxidative Stress by Nigella Sativa Oil Attenuates Morphine-Induced Tolerance” by Abdel-Zaher et al.

Neurochemical Research -