Reinforcement context and resistance to change

Eight pigeons responded in a multiple variable-interval (VI) schedule in which a constant component always delivered 40rft/h, and an alternated component was either rich (200rft/h) or lean (6.67rft/h) in different conditions. Four tests of resistance to change were conducted in each condition: prefeeding, full extinction, constant-component-only extinction, and response-independent food. Resistance to both prefeeding and full extinction in the constant component varied inversely with the reinforcement rate in the alternated component, but resistance to response-independent food did not. The extinction and response-independent food results were consistent with [J. Exp. Psychol.: Anim. Behav. Proc. 25 (1999) 256] behavioral momentum model. Maintaining reinforcement in the alternated component increased resistance to extinction in the constant component, as predicted by the behavioral momentum model but not accounts of multiple-schedule performance based on [J. Exp. Anal. Behav. 13 (1970) 243] equation. Overall, the momentum model gave a good account of the results with the exception of the prefeeding data. Possible ways to reconcile the prefeeding results with behavioral momentum theory are considered.     

DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative‐associated proteins

It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans‐synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease‐associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP‐43, α‐synuclein, and the microtubule‐associated protein tau, can be driven out of the cell by an Hsc70 co‐chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins.     

Lipid induced conformation of the tachykinin peptide Kassinin

Both the aqueous and lipid-induced structure of Kassinin, a dodecapeptide of amphibian origin, has been studied by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry calculations. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained from the NMR data have been utilized in a distance geometry algorithm to generate a family of structures, which have been refined using restrained energy minimization and dynamics. These data show that, while in water Kassinin prefers to be in an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system, helical conformation is induced in the central core and C-terminal region (K4-M12) of the peptide. N-terminus though less defined also displays some degree of order and a possible turn structure. The conformation adopted by Kassinin in the presence of DPC micelles is consistent with the structural motif typical of neurokinin-1 selective agonists and with that reported for Eledoisin in hydrophobic environment.     

A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2

The regulation of apoptosis is critical for controlling tissue homeostasis and preventing tumor formation and growth. Reactive oxygen species (ROS) generation plays a key role in such regulation. Here, we describe a HIF-1 target, Vasn/ATIA (anti-TNFα-induced apoptosis), which protects cells against TNFα- and hypoxia-induced apoptosis. Through the generation of ATIA knockout mice, we show that ATIA protects cells from apoptosis through regulating the function of the mitochondrial antioxidant, thioredoxin-2, and ROS generation. ATIA is highly expressed in human glioblastoma, and ATIA knockdown in glioblastoma cells renders them sensitive to hypoxia-induced apoptosis. Therefore, ATIA is not only a HIF-1 target that regulates mitochondrial redox pathways but also a potentially diagnostic marker and therapeutic target in human glioblastoma.     

Evidence of hybridization between Taenia saginata and Taenia asiatica

There has long been a debate as to the specific status of the cestode Taenia asiatica, with some people regarding it as a distinct species and some preferring to recognize it as a strain of Taenia saginata. The balance of current opinion seems to be that T. asiatica is a distinct species. In this study we performed an allelic analysis to explore the possibility of gene exchange between these closely related taxa. In total, 38 taeniid tapeworms were collected from humans living in many localities including Kanchanaburi Province, Thailand where the two species are sympatric. A mitochondrial DNA (mtDNA)-based multiplex PCR tentatively identified those parasites as T. asiatica (n = 20) and T. saginata (n = 18). Phylogenetic analyses of a mitochondrial cytochrome c oxidase subunit 1 (cox1) gene and two nuclear loci, for elongation factor-1 alpha (ef1) and ezrin-radixin-moesin (ERM)-like protein (elp), assigned all except two individual parasites to the species indicated by multiplex PCR. The two exceptional individuals, from Kanchanaburi Province, showed a discrepancy between the mtDNA and nuclear DNA phylogenies. In spite of their possession of sequences typical of the T. saginata cox1 gene, both were homozygous at the elp locus for one of the alleles found in T. asiatica. At the ef1 locus, one individual was homozygous for the allele found at high frequency in T. asiatica while the other was homozygous for the major allele in T. saginata. These findings are evidence of occasional hybridization between the two species, although the possibility of retention of ancestral polymorphism cannot be excluded.     

The ratio and allometric scaling of speed, power, and strength in elite male rugby union players

This study compared the effectiveness of ratio and allometric scaling for normalizing speed, power, and strength in elite male rugby union players. Thirty rugby players (body mass [BM] 107.1 ± 10.1 kg, body height [BH] 187.8 ± 7.1 cm) were assessed for sprinting speed, peak power during countermovement jumps and squat jumps, and horizontal jumping distance. One-repetition maximum strength was assessed during a bench press, chin-up, and back squat. Performance was normalized using ratio and allometric scaling (Y/X), where Y is the performance, X, the body size variable (i.e., BM or BH), and b is the power exponent. An exponent of 1.0 was used during ratio scaling. Allometric scaling was applied using proposed exponents and derived exponents for each data set. The BM and BH variables were significantly related, or close to, performance during the speed, power and/or strength tests (p < 0.001-0.066). Ratio scaling and allometric scaling using proposed exponents were effective in normalizing performance (i.e., no significant correlations) for some of these tests. Allometric scaling with derived exponents normalized performance across all the tests undertaken, thereby removing the confounding effects of BM and BH. In terms of practical applications, allometric scaling with derived exponents may be used to normalize performance between larger rugby forwards and smaller rugby backs, and could provide additional information on rugby players of similar body size. Ratio scaling may provide the best predictive measure of performance (i.e., strongest correlations).     

Phenotypic characterization of HIV-specific CD8+ T cells during early and chronic infant HIV-1 infection

Although CD8⁺ T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1 infection is not as well understood. Impaired HIV-specific CD8⁺ T cell responses may underlie the persistently high viral loads observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8⁺ T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT. The frequency (0.088–3.9% of CD3⁺CD8⁺ cells) and phenotype (CD27⁺CD28⁻, CD45RA^+/−, CD57^+/−, HLA-DR⁺, CD95⁺) of infant HIV-specific CD8⁺ T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23–24 months post-infection a high frequency of HIV-specific CD8⁺ T cells expressed HLA-DR (mean 80%, range 68–85%) and CD95 (mean 88%, range 79–96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIV-specific CD8⁺ T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.     

Effect of habitable space on substrate selection by Paragnetina media (Walker) (Plecoptera: Perlidae)

A biological measure of space available within substrates was used as an index to examine substrate selection by the stonefly nymph Paragnetina media (Walker). Physical measures, such as total surface area of substrate, have not worked well in the past in explaining distribution of aquatic invertebrates. Although analysis of habitable space within substrate did not explain selection completely, the technique provided a precise measure and might be a more rigorous means by which substrate selection could be examined.     

Geographic and host‐mediated population genetic structure in a cestode parasite of the three‐spined stickleback

Comparative studies of genetic diversity and population structure can shed light on the ecological and evolutionary factors that influence host–parasite interactions. Here we examined whether geography, time and genetic variation in Alaskan three‐spined stickleback (Gasterosteus aculeatus Linneaus) hosts shape the population genetic structure of the diphyllobothridean cestode parasite Schistocephalus solidus (Müller, 1776). Host lineages and haplotypes were identified by sequencing the mitochondrial cytochrome b gene, and host population structure was assessed by Bayesian clustering analysis of allelic variation at 11 microsatellite loci. Parasite population structure was characterized according to allelic variation at eight microsatellite loci. Mantel tests and canonical redundancy analysis were conducted to evaluate the proportion of parasite genetic variation attributable to time and geography vs. host lineage, haplotype, and genotypic cluster. Host and parasite population structure were largely discordant across the study area, probably reflecting differences in gene flow, environmental influences external to the host, and genomic admixture among host lineages. We found that geography explained the greatest proportion of parasite genetic variation, but that variation also reflects time, host lineage, and host haplotype. Associations with host haplotypes suggest that one parasite genotypic cluster exhibits a narrower host range, predominantly infecting the most common host haplotypes, whereas the other parasite cluster infects all haplotypes equally, including rare haplotypes. Although experimental infection trials might prove otherwise, distributional differences in hosts preferentially infected by S. solidus could underlie the observed pattern of population structure.