Dissociating Two Stages of Preparation in the Stop Signal Task Using fMRI

Often we must balance being prepared to act quickly with being prepared to suddenly stop. The stop signal task (SST) is widely used to study inhibitory control, and provides a measure of the speed of the stop process that is robust to changes in subjects’ response strategy. Previous studies have shown that preparation affects inhibition. We used fMRI to separate activity that occurs after a brief (500 ms) warning stimulus (warning-phase) from activity that occurs during responses that follow (response-phase). Both of these phases could contribute to the preparedness to stop because they both precede stop signals. Warning stimuli activated posterior networks that signal the need for top-down control, whereas response phases engaged prefrontal and subcortical networks that implement top-down control. Regression analyses revealed that both of these phases affect inhibitory control in different ways. Warning-phase activity in the cerebellum and posterior cingulate predicted stop latency and accuracy, respectively. By contrast, response-phase activity in fronto-temporal areas and left striatum predicted go speed and stop accuracy, in pre-supplementary motor area affected stop accuracy, and in right striatum predicted stop latency and accuracy. The ability to separate hidden contributions to inhibitory control during warning-phases from those during response-phases can aid in the study of models of preparation and inhibitory control, and of disorders marked by poor top-down control.     

Between cheap and costly signals: the evolution of partially honest communication

Costly signalling theory has become a common explanation for honest communication when interests conflict. In this paper, we provide an alternative explanation for partially honest communication that does not require significant signal costs. We show that this alternative is at least as plausible as traditional costly signalling, and we suggest a number of experiments that might be used to distinguish the two theories.     

Which sharks attract research? Analyses of the distribution of research effort in sharks reveal significant non-random knowledge biases

Reviews in Fish Biology and Fisheries - Research effort is unevenly distributed across species, which can cause important biases in our understanding of evolutionary and ecological processes and...     

p21WAF1 modulates drug-induced apoptosis and cell cycle arrest in B-cell precursor acute lymphoblastic leukemia

p21^WAF1 is a well-characterized mediator of cell cycle arrest and may also modulate chemotherapy-induced cell death. The role of p21^WAF1 in drug-induced cell cycle arrest and apoptosis of acute lymphoblastic leukemia (ALL) cells was investigated using p53-functional patient-derived xenografts (PDXs), in which p21^WAF1 was epigenetically silenced in T-cell ALL (T-ALL), but not in B-cell precursor (BCP)-ALL PDXs. Upon exposure to diverse cytotoxic drugs, T-ALL PDX cells exhibited markedly increased caspase-3/7 activity and phosphatidylserine (PS) externalization on the plasma membrane compared with BCP-ALL cells. Despite dramatic differences in apoptotic characteristics between T-ALL and BCP-ALL PDXs, both ALL subtypes exhibited similar cell death kinetics and were equally sensitive to p53-inducing drugs in vitro, although T-ALL PDXs were significantly more sensitive to the histone deacetylase inhibitor vorinostat. Transient siRNA suppression of p21^WAF1 in the BCP-ALL 697 cell line resulted in a moderate depletion of the cell fraction in G1 phase and marked increase in PS externalization following exposure to etoposide. Furthermore, stable lentiviral p21^WAF1 silencing in the BCP-ALL Nalm-6 cell line accelerated PS externalization and cell death following exposure to etoposide and vorinostat, supporting previous findings. Finally, the Sp1 inhibitor, terameprocol, inhibited p21^WAF1 expression in Nalm-6 cells exposed to vorinostat and also partially augmented vorinostat-induced cell death. Taken together, these findings demonstrate that p21^WAF1 regulates the early stages of drug-induced apoptosis in ALL cells and significantly modulates their sensitivity to vorinostat.     

Polymorphism due to variable number of repeats in the human involucrin gene.

The coding region of the involucrin gene in higher primates contains a segment consisting of numerous tandem repeats of a 10-codon sequence. The process of repeat addition began in a common ancestor of all higher primates and subsequent repeats were added vectorially. As a result, the principal site of repeat addition has moved in the 3' to 5' direction and the most recently generated repeats (the late region) are close to the 5' end of the segment of repeats. In the human, most of the late region is made up of two different blocks, each consisting of nearly identical repeats. We describe here five polymorphic forms resulting from the addition of differing numbers of repeats to each block. As the variety and nature of the polymorphic alleles are different in different human populations, we postulate that the process of repeat addition is genetically determined.     

A Survey Investigating the Infection of Fusarium langsethiae and Production of HT‐2 and T‐2 Mycotoxins in UK Oat Fields

Fusarium langsethiae is a toxigenic fungal species that has been reported in European small‐grain cereal crops such as oats, wheat and barley. Although its relative contribution to fusarium head blight (FHB) symptoms is not well understood, it is reported to contaminate these cereals with high levels of HT‐2 and T‐2 trichothecenes mycotoxins that are currently under consideration for legislation by the European Commission. Ten commercial oat fields in Shropshire and Staffordshire (two adjacent counties in the Midlands) in the UK were surveyed in the 2006/2007 growing season. Samples were taken from predetermined field locations at Zadoks growth stages 32/33, 69, 77‐85 and 90‐92 for F. langsethiae biomass and HT‐2 and T‐2 toxins quantification. The results from this study showed that oats can be heavily infected with F. langsethiae and have high concentrations of HT‐2 and T‐2 toxins with no apparent FHB symptoms. The regression of HT‐2 + T‐2 toxins on F. langsethiae DNA concentration was highly significant (P < 0.001, r² = 0.55). The results indicated that although F. langsethiae had no direct effect on crop yield, it may result in indirect economic losses where the grain can be rejected or downgraded as a result of intolerable levels of HT‐2 and T‐2 toxins, which are of human food and animal feed safety concern. The influence of cultural field practices on the infection and HT‐2 and T‐2 toxins accumulation in oats was not clear and warrants further studies to identify the sources of F. langsethiae inoculum and conditions favourable for infection and mycotoxin production.