Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies

Background  

All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences.     

Dissecting TRPV1: lessons to be learned?

The transient receptor potential channel TRPV1 is a polymodal nociceptor. It is primarily expressed in dorsal root ganglia and peripheral sensory nerve endings, and to a much lesser extent, in the central nervous system. It has also been implicated in the functional properties of e.g. urinary and bronchial epithelia. TRPV1 has long been under intensive investigation by the pharmaceutical industry as a candidate drug target especially for pain conditions. This review summarizes the current knowledge of the molecular determinants of TRPV1 channel activation by heat, protons and capsaicin. Newly discovered heat and proton activation sites within the pore domain are discussed as well as potential consequences for drug discovery. Polymodal TRPV1 antagonists were found to cause hyperthermia in a species-dependent manner in-vivo, hence the discovery of euthermic compounds with an appropriate modality selectivity profile will be crucial for TRPV1's future as a drug target.     

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer

AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.     

The taxonomy of the family Paramphistomidae Fischoeder, 1901 with special reference to the morphology of species occurring in ruminants IV. Revision of the genusGigantocotyle Näsmark, 1937 and elevation of the subgenusExplanatum Fukui, 1929 to full generic status

Summary The genusGigantocotyle Näsmark, 1937 is redefined and restricted to contain four valid species, namely,G. gigantocotyle (Brandes in Otto, 1896) Näsmark, 1937 (type species);G. formosanum (Fukui, 1929) Näsmark, 1937;G. symmeri Näsmark, 1937 andG. duplicitestorum Näsmark, 1937.G. lerouxi Yeh, 1957 is regarded as a synonym ofG. symmeri Näsmark, 1937.The subgenusExplanatum Fukui, 1929 is redefined and raised to full generic rank to contain three valid species, namely,E. explanatum (Creplin, 1847) Fukui, 1929;E. bathycotyle (Fischoeder, 1901) Yamaguti, 1958 andE. anisocotylea (Faust, 1920) Yamaguti, 1958.Paramphistomum siamense Stiles & Goldberger, 1910 andP. fraternum Stiles & Goldberger, 1910 are considered synonyms ofExplanatum explanatum (Creplin, 1847) Fukui, 1929.The valid species are redescribed and illustrated and scanning electron microphotographs of the tegumental surfaces of some species are provided. A key to the species of each genus is given.Part of a thesis approved by the University of London for the award of the Ph.D. degree.Part of a thesis approved by the University of London for the award of the Ph.D. degree.     

Alarm scent-marking during predatory attempts in the Cabrera vole (Microtus cabrerae Thomas, 1906)

The alarm pheromones often released by animals under stressful situations seem to elicit behavioral changes in conspecifics, which in the appropriate context can be viewed as anti-predatory responses. However, the releasing of alarm pheromones associated with predatory events has not been demonstrated in mammals. In the current study with wild-caught Cabrera voles, we carried out experiments in the laboratory and in the field to assess the release of alarm pheromones in scent-marks during simulated predatory events and disclose their effects on conspecifics. We first conducted an assay wherein voles where let to scent-mark a clean substrate in the absence of disturbance (control) and under the simulation of predatory events. Contrarily to the control, no fecal boli were released and the area marked with urine was significantly larger during the predatory simulation. In a subsequent assay, we assessed the voles’ preference between urine-marks released under predatory simulation and in control conditions. Voles showed a significant preference by control substrates. Finally, a third assay was carried out in the vole’s habitat wherein the individual activity was monitored by radio-tracking before and after placement of urine-marks obtained during the conditions described above. The vole’s activity was only reduced near the urine-marks released during the simulated predatory events. The results suggest that: (1) during predatory attempts, Cabrera voles release an alarm pheromone in their urine-marks; (2) the putative alarm pheromone reduces the voles’ activity in the surroundings of the marked area; (3) the putative alarm pheromone persists in the field affecting conspecifics’ activity for several days.     

Disturbances, elevation, topography and spatial proximity drive vegetation patterns along an altitudinal gradient of a top biodiversity hotspot

The correlation between vegetation patterns (species distribution and richness) and altitudinal variation has been widely reported for tropical forests, thereby providing theoretical basis for biodiversity conservation. However, this relationship may have been oversimplified, as many other factors may influence vegetation patterns, such as disturbances, topography and geographic distance. Considering these other factors, our primary question was: is there a vegetation pattern associated with substantial altitudinal variation (10–1,093 m a.s.l.) in the Atlantic Rainforest—a top hotspot for biodiversity conservation—and, if so, what are the main factors driving this pattern? We addressed this question by sampling 11 1-ha plots, applying multivariate methods, correlations and variance partitioning. The Restinga (forest on sandbanks along the coastal plains of Brazil) and a lowland area that was selectively logged 40 years ago were floristically isolated from the other plots. The maximum species richness (>200 spp. per hectare) occurred at approximately 350 m a.s.l. (submontane forest). Gaps, multiple stemmed trees, average elevation and the standard deviation of the slope significantly affected the vegetation pattern. Spatial proximity also influenced the vegetation pattern as a structuring environmental variable or via dispersal constraints. Our results clarify, for the first time, the key variables that drive species distribution and richness across a large altitudinal range within the Atlantic Rainforest.     

Biodegradation kinetic constants and sorption coefficients of micropollutants in membrane bioreactors

In order to elucidate the capability of biomass developed in membrane bioreactors (MBR) to degrade and sorb emerging micropollutants, biodegradation (k_biol) and sorption (k_sor) kinetic constants as well as solid–liquid partition coefficients (K_d) of 13 selected pharmaceutical and personal care products (PPCPs) were determined with MBR heterotrophic biomass adding a pulse (100 ppb of each compound) and following the liquid and solid phase concentrations over time. The results obtained were compared to literature data referring to conventional activated sludge (CAS) systems. Two experiments were performed: one in the MBR itself and the second one in a batch reactor with the same type and concentration of biomass as in the MBR. Overall, both biodegradation and sorption coefficients were in the same range as previously reported by other studies in CAS systems, indicating that MBR biomass does not show better capabilities for the biological degradation and/or sorption of PPCPs compared to the biomass developed in CAS reactors. Therefore, the higher PPCPs removal efficiencies found in MBRs are explained by the high biomass concentrations obtained at the long sludge retention times at which this type of reactors are usually operated.