Inhibition of protein misfolding and aggregation by natural phenolic compounds

Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases.     

Historical review and redescription of three poorly known species of the catfish genus Trichomycterus from south-eastern Brazil (Siluriformes: Trichomycteridae)

ABSTRACT

This study is primarily directed to the most poorly known species of the genus Trichomycterus, comprising five nominal species (T. florensis, T. immaculatus, T. nigricans, T. paquequerensis and T. santaeritae) endemic to south-eastern Brazil. One of them, T. nigricans, is the type species of the genus, involved in taxonomic problems for over 150 years. A detailed historical review, accompanied by examination of type specimens and recent collections, revealed that the correct type locality of T. nigricans is in the vicinity of Rio de Janeiro, not Santa Catarina as commonly appears in the literature; specimens previously misidentified as T. nigricans from Santa Catarina belong to a possibly undescribed species of the genus Cambeva; T. paquequerensis is a synonym of T. immaculatus, and T. florensis is a synonym of T. santaeritae; and the hypothesis that T. santaeritae is closely related to the Amazon Sarcoglanidinae is refuted. The three valid species are redescribed. These species are members of a clade also including T. caipora that is highly supported by molecular data, diagnosed by a pronounced posterior maxillary process and caudal fin emarginate at least in larger specimens. A subclade comprising T. caipora, T. nigricans and T. santaeritae is diagnosed by a long maxilla and a bifid anterior extremity of hypobranchial 3.     

Morphology of tube-like threads related to Limnochares aquatica (L., 1758) (Acariformes: Hydrachnidia: Limnocharidae) in the laboratory

Water mites Limnochares aquatica (L., 1758) during maintenance in the laboratory for a long period of time in constant conditions periodically produced certain whitish flocculent material consisting of long rigid unbranched tube-like threads 1.3 ± 0.3 µm in diameter crossing freely. These threads were studied using light-optical as well as transmission electron microscopical and scanning electron microscopical methods. Microbiological staining was also applied to the threads to exclude their bacterial or fungal origin. The thread wall is built of fine fibrils arranged at different angles to the long axis of threads that is reflected in a certain stratification of the wall. Threads are mostly hollow or may contain electron-dense homogeneous material. No cell components are present in the thread composition. Numerous dermal glands with their small slit-like orifice scattered throughout the mite body surface are thought to produce these threads. Most probably the thread formation is a reaction of mites to stress under laboratory conditions, and this is expected to be a type of defensive reaction.     

The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Exploring the Potency of Rich Pictures in a Systemic Lean Intervention Process

Systemic Practice and Action Research - This paper explores the usefulness of rich pictures as a method in Systemic Lean Intervention (SLI) process. It combines Lean and Systems Thinking analytical...     

Diversity and dispersal history of the talitrids (Crustacea: Amphipoda: Talitridae) of Bermuda

Five taxa of talitrid amphipods were found in the archipelago of Bermuda, of which three were recorded there for the first time. Four of these are supralittoral wrack generalists: Platorchestia monodi BOLD:AAB3402, (a unique Molecular Operational Taxonomic Unit according to the Barcode Index Number system), a related species recognized by molecular methods, Platorchestia platensis BOLD:AAA2949, Mexorchestia carpenteri carpenteri BOLD:AAC1491 and Tethorchestia antillensis; and one a terrestrial leaf-litter generalist: Talitroides alluaudi. A key is provided to discriminate between the formally described talitrids of Bermuda. Dispersal mechanisms from the American continent to Bermuda were considered for all taxa based on species distributions along the North American Atlantic coast and also investigated by molecular methods, using genetic population differentiation and haplotype network analysis based on the barcode region of cytochrome c oxidase subunit I gene. For P. monodi BOLD:AAB3402 the genetic results suggest that some dispersal events occurred before human colonization of Bermuda but are equivocal about the source population and therefore the direction of dispersal. Some very recent synanthropic dispersal is possible with this species. For the other two species studied genetically, P. platensis BOLD:AAA2949 and M. c. carpenteri BOLD:AAC1491, the small population samples analysed support dispersal to Bermuda from the American mainland, before human occupation of Bermuda, although the available sample size was limited for these species. The available limited direct, non-genetic evidence supports synanthropic transport for Talitroides alluaudi. Platorchestia monodi BOLD:AAB3402 is found in the same wrack habitat as P. platensis BOLD:AAA2949 on Bermuda, apparently without interbreeding. No evidence was found that driftwood specialist talitrids had become established in Bermuda.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.