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.     

Studies on induction hardening of powder-metallurgy-processed Fe-Cr/Mo alloys

Induction hardening of dense Fe-Cr/Mo alloys processed via the powder-metallurgy route was studied. The Fe-3Cr-0.5Mo, Fe-1.5Cr-0.2Mo, and Fe-0.85Mo pre-alloyed powders were mixed with 0.4wt%, 0.6wt%, and 0.8wt% C and compacted at 500, 600, and 700 MPa, respectively. The compacts were sintered at 1473 K for 1 h and then cooled at 6 K/min. Ferrite with pearlite was mostly observed in the sintered alloys with 0.4wt% C, whereas a carbide network was also present in the alloys with 0.8wt% C. Graphite at prior particle boundaries led to deterioration of the mechanical properties of alloys with 0.8wt% C, whereas no significant induction hardening was achieved in alloys with 0.4wt% C. Among the investigated samples, alloys with 0.6wt% C exhibited the highest strength and ductility and were found to be suitable for induction hardening. The hardening was carried out at a frequency of 2.0 kHz for 2-3 s. A case depth of 2.5 mm was achieved while maintaining the bulk (interior) hardness of approximately HV 230. A martensitic structure was observed on the outer periphery of the samples. The hardness varied from HV 600 to HV 375 from the sample surface to the interior of the case hardened region. The best combination of properties and hardening depth was achieved in case of the Fe-1.5Cr-0.2Mo alloy with 0.6wt% C.     

Melatonin transport into mitochondria

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.     

Social Media as a Mean for Improved Technical Communication

Technical communication (TC) is an important activity in order to provide the users of technical artifacts with necessary information concerning the operation and maintenance of the products they are using. In the current working procedures of TC, however, the users become too passive. They are just receivers of information. Further, there is no effective feedback from the users to the producers of the information. In order to overcome those problems we here propose an application of social media (SM) in future TC. By using SM as a complementary channel for TC it becomes possible for technology firms to boost their competitive advantage and to improve the quality and completeness of their TC. This technique, however, is still more of a potential and less of a reality. Several problems, mostly concerning security and confidentiality remain to be solved. The empirical base for this work comes from TIC, an EU-funded development project involving several Swedish technology companies. Published research results are somewhat scattered but several sources coherently indicate both the need and potential for SM as a vehicle in TC. By scanning the net it is further possible to identify a number of seemingly successful applications of SM in such applications.     

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.     

Babylonian solar theory on the Antikythera mechanism

This article analyzes the angular spacing of the degree marks on the zodiac scale of the Antikythera mechanism and demonstrates that over the entire preserved 88° of the zodiac, the marks are systematically placed too close together to be consistent with a uniform distribution over 360°. Thus, in some other part of the zodiac scale (not preserved), the degree marks have been spaced farther apart. By contrast, the day marks on the Egyptian calendar scale are spaced uniformly, apart from minor errors. A solar equation of center is apparent which rises by nearly 2.7° over the preserved portion of the zodiac. The placement of the degree marks indicates that, in the preserved portion of the zodiac, the Sun was considered to run at a uniform pace of about 30° per synodic month, which is consistent with the Sun’s speed in the fast zone of the Babylonian solar theory of System A.

     

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.