The binding epitopes of neurotrophin-3 to its receptors trkC and gp75 and the design of a multifunctional human neurotrophin.

Survival and maintenance of vertebrate neurons are influenced by neurotrophic factors which mediate their signal by binding to specific cell surface receptors. We determined the binding sites of human neurotrophin-3 (NT-3) to its receptors trkC and gp75 by mutational analysis and compared them to the analogous interactions of nerve growth factor (NGF) with trkA and gp75. The trkC binding site extends around the central beta-strand bundle and in contrast to NGF does not make use of non-conserved loops and the six N-terminal residues. The gp75 epitope is dominated by loop residues and the C-terminus of NT-3. A novel rapid biological screening procedure allowed the identification of NT-3 mutants that are able to signal efficiently through the non-preferred receptors trkA and trkB, which are specific for NGF and BDNF respectively. Mutation of only seven residues in NT-3 resulted in a human neurotrophin variant which bound to all receptors of the trk family with high affinity and efficiently supported the survival of NGF-, BDNF- and NT-3-dependent neurons. Our results suggest that the specificity among neurotrophic factors is not solely encoded in sequence diversity, but rather in the way each neurotrophin interacts with its preferred receptor.     

Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways.     

Isolation and Characterization of Two Lytic Bacteriophages, φSt2 and φGrn1; Phage Therapy Application for Biological Control of Vibrio alginolyticus in Aquaculture Live Feeds

Bacterial infections are a serious problem in aquaculture since they can result in massive mortalities in farmed fish and invertebrates. Vibriosis is one of the most common diseases in marine aquaculture hatcheries and its causative agents are bacteria of the genus Vibrio mostly entering larval rearing water through live feeds, such as Artemia and rotifers. The pathogenic Vibrio alginolyticus strain V1, isolated during a vibriosis outbreak in cultured seabream, Sparus aurata, was used as host to isolate and characterize the two novel bacteriophages φSt2 and φGrn1 for phage therapy application. In vitro cell lysis experiments were performed against the bacterial host V. alginolyticus strain V1 but also against 12 presumptive Vibrio strains originating from live prey Artemia salina cultures indicating the strong lytic efficacy of the 2 phages. In vivo administration of the phage cocktail, φSt2 and φGrn1, at MOI = 100 directly on live prey A. salina cultures, led to a 93% decrease of presumptive Vibrio population after 4 h of treatment. Current study suggests that administration of φSt2 and φGrn1 to live preys could selectively reduce Vibrio load in fish hatcheries. Innovative and environmental friendly solutions against bacterial diseases are more than necessary and phage therapy is one of them.     

Effects of congested match periods on acceleration and deceleration profiles in professional soccer

The aim of the present study was to analyse the influence of congested periods of matches on the acceleration (Acc) and deceleration (Dec) profiles of elite soccer players. Twenty-three elite male professional soccer players participated in the study across 31 official matches. Assessed periods included: (i) congested periods (three to four days between games), and (ii) non-congested periods (more than four days between games). Physical activity during matches was recorded during games using a 10Hz global positioning system device, coupled with a 100 Hz accelerometer, and was analysed according to the periods. Maximal Acc- (73.2 ± 20.3 vs. 84.918.5 m), high Acc- (244.0 ± 49.5 vs. 267.0 ± 37.8 m), maximal Dec- (139.0 ± 44.8 vs. 152.039.3 m) and the total decelerating- distance (5132 ± 690 vs. 5245 ± 552 m) were lower in congested than in non-congested periods (p < 0.05, effect size 0.31–0.70). Neither a main effect of playing position nor a period*playing position interaction on Acc and Dec were observed (p > 0.05). It was concluded that Acc and Dec match activities were significantly affected during congested periods compared to non-congested highlighting a possible fatigue accumulation being responsible for the observed decrement in physical activity. Monitoring Acc and Dec metrics throughout particular periods of congested fixtures amongst professional soccer teams is advised and may be a way to assess physical and fatigue status.     

Biting indices,host-seeking activity and natural infection rates of anopheline species in Boa Vista,Roraima, Brazil from 1996 to 1998

The epidemiology of the transmission of malaria parasites varies ecologically. To observe some entomological aspects of the malaria transmission in an urban environment, a longitudinal survey of anopheline fauna was performed in Boa Vista, Roraima, Brazil. A total of 7,263 anophelines was collected in human bait at 13 de Setembro and Caran? districts: Anopheles albitarsis sensu lato (82.8%), An. darlingi (10.3%), An. braziliensis (5.5%), An. peryassui (0.9%) and An. nuneztovari (0.5%). Nightly 12 h collections showed that An. albitarsis was actively biting throughout the night with peak activities at sunset and at midnight. An. darlingi bit during all night and did not demonstrate a defined biting peak. Highest biting indices, entomological inoculation rates and malaria cases were observed seasonally during the rainy season (April-November). Hourly collections showed host seek activity for all mosquitoes peaked during the first hour after sunset. An. darlingi showed the highest plasmodial malaria infection rate followed by An. albitarsis, An. braziliensis and An. nuneztovari (8.5%, 4.6%, 3% and 2.6%, respectively). An. albitarsis was the most frequently collected anopheline, presented the highest biting index and it was the second most frequently collected infected species infected with malaria parasites. An. albitarsis and An. darlingi respectively, are the primary vectors of malaria throughout Boa Vista.     

Viewing Complex,Dynamic Scenes “Through the Eyes” of Another Person: The Gaze-Replay Paradigm

We present a novel “Gaze-Replay” paradigm that allows the experimenter to directly test how particular patterns of visual input—generated from people’s actual gaze patterns—influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze “donor.” This was intended to simulate the donor’s visual selection, such that a participant could effectively view scenes “through the eyes” of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition.