Neural dynamics of shooting decisions and the switch from freeze to fight

Real-life shooting decisions typically occur under acute threat and require fast switching between vigilant situational assessment and immediate fight-or-flight actions. Recent studies suggested that freezing facilitates action preparation and decision-making but the neurocognitive mechanisms remain unclear. We applied functional magnetic resonance imaging, posturographic and autonomic measurements while participants performed a shooting task under threat of shock. two independent studies, in unselected civilians (N = 22) and police recruits (N = 54), revealed that preparation for shooting decisions under threat is associated with postural freezing, bradycardia, midbrain activity (including the periaqueductal gray-PAG) and PAG-amygdala connectivity. Crucially, stronger activity in the midbrain/pAG during this preparatory stage of freezing predicted faster subsequent accurate shooting. Finally, the switch from preparation to active shooting was associated with tachycardia, perigenual anterior cingulate cortex (pgACC) activity and pgACC-amygdala connectivity. These findings suggest that threat-anticipatory midbrain activity centred around the PAG supports decision-making by facilitating action preparation and highlight the role of the pgACC when switching from preparation to action. These results translate animal models of the neural switch from freeze-to-action. In addition, they reveal a core neural circuit for shooting performance under threat and provide empirical evidence for the role of defensive reactions such as freezing in subsequent action decision-making

Modulation of Aβ(42 )low-n oligomerization using a novel yeast reporter system

BACKGROUND: While traditional models of Alzheimer's disease focused on large fibrillar deposits of the Aβ(42 )amyloid peptide in the brain, recent work suggests that the major pathogenic effects may be attributed to SDS-stable oligomers of Aβ(42). These Aβ(42 )oligomers represent a rational target for therapeutic intervention, yet factors governing their assembly are poorly understood. RESULTS: We describe a new yeast model system focused on the initial stages of Aβ(42 )oligomerization. We show that the activity of a fusion of Aβ(42 )to a reporter protein is compromised in yeast by the formation of SDS-stable low-n oligomers. These oligomers are reminiscent of the low-n oligomers formed by the Aβ(42 )peptide in vitro, in mammalian cell culture, and in the human brain. Point mutations previously shown to inhibit Aβ(42 )aggregation in vitro, were made in the Aβ(42 )portion of the fusion protein. These mutations both inhibited oligomerization and restored activity to the fusion protein. Using this model system, we found that oligomerization of the fusion protein is stimulated by millimolar concentrations of the yeast prion curing agent guanidine. Surprisingly, deletion of the chaperone Hsp104 (a known target for guanidine) inhibited oligomerization of the fusion protein. Furthermore, we demonstrate that Hsp104 interacts with the Aβ(42)-fusion protein and appears to protect it from disaggregation and degradation. CONCLUSION: Previous models of Alzheimer's disease focused on unravelling compounds that inhibit fibrillization of Aβ(42), i.e. the last step of Aβ(42 )assembly. However, inhibition of fibrillization may lead to the accumulation of toxic oligomers of Aβ(42). The model described here can be used to search for and test proteinacious or chemical compounds for their ability to interfere with the initial steps of Aβ(42 )oligomerization. Our findings suggest that yeast contain guanidine-sensitive factor(s) that reduce the amount of low-n oligomers of Aβ(42). As many yeast proteins have human homologs, identification of these factors may help to uncover homologous proteins that affect Aβ(42 )oligomerization in mammals

The Schizosaccharomyces pombe Hsp104 Disaggregase Is Unable to Propagate the [PSI+] Prion

The molecular chaperone Hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. Under stress conditions, the disaggregase activity of Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also involved in the propagation of fungal prions. For instance, the well-characterized [PSI+] prion of Saccharomyces cerevisiae does not propagate in Δhsp104 cells or in cells overexpressing Hsp104. In this study, we characterized the functional homolog of Hsp104 from Schizosaccharomyces pombe (Sp_Hsp104). As its S. cerevisiae counterpart, Sp_hsp104+ is heat-inducible and required for thermotolerance in S. pombe. Sp_Hsp104 displays low disaggregase activity and cannot propagate the [PSI+] prion in S. cerevisiae. When overexpressed in S. cerevisiae, Sp_Hsp104 confers thermotolerance to Δhsp104 cells and reactivates heat-aggregated proteins. However, overexpression of Sp_Hsp104 does not propagate nor eliminate [PSI+]. Strikingly, [PSI+] was cured by overexpression of a chimeric chaperone bearing the C-terminal domain (CTD) of the S. cerevisiae Hsp104 protein. Our study demonstrates that the ability to untangle aggregated proteins is conserved between the S. pombe and S. cerevisiae Hsp104 homologs, and points to a role of the CTD in the propagation of the S. cerevisiae [PSI+] prion

Apple Fruit Quality Identification using Clustering

An apples a day keeps doctor away" this proverb gives us important of apple in our healthy life. Apples fruit is consist of plenty of nutrition's therefore, doctors are always prefer to advice to eat the apple in most of the diseases. Hence, there is a huge demand of apples in market. To fulfill this demands suppliers need to provide the good quality fruit. There is a need of quality fruits in market. In this work studied various types of apples quality by using clustering approach. Comparative analysis is performed and given results are much better as compare to earlier work