“
“Impaired programmed cell death is an important

factor in the pathogenesis of chronic lymphocytic leukemia (CLL) and in the development of resistance to chemoimmunotherapy. Hence, the reactivation of apoptotic processes is likely to be a pertinent strategy for circumventing this resistance. Proteins from the Bcl-2 family are critical elements in defective apoptosis. Some compounds induce the apoptosis of CLL cells ex vivo by downregulation of prosurvival members of this family (for example, Bcl-2 and Mcl-1), whereas others act by upregulation of proapoptotic Bcl-2 homology (BH) 3-only members (for example, Noxa and Bim). The concept of BH3 mimetics was prompted by the fact that BH3-only proteins are specific antagonistic ligands of prosurvival Bcl-2 family members. This led to the design of small molecules capable of inhibiting the activity of prosurvival Bcl-2 proteins and inducing apoptosis learn more PND-1186 in leukemia cells in vitro and antileukemic effects in animal models. Several putative or actual BH3 mimetics are currently being trialed in the clinic. Two

novel BH3 mimetics that can specifically bind to and antagonize Mcl-1 (a crucial antiapoptotic factor in CLL) have recently been discovered. The evaluation of this type of compound’s clinical impact in CLL can now be considered.”
“Echolocation in bats requires a precise temporal processing of complex signals. This processing of time includes the encoding of echo-delay, which gives an estimation of target distance, and sound duration, which is considered to be important for own sound or echo recognition. In this study, we report that delay-tuned neurons in the inferior colliculus of the mustached bat (Pteronotus parnellii) are also tuned to sound duration. Collicular delay-tuned neurons showed three types of duration tuning: short-pass (12 of 64),

band-pass (16 of 64), and long-pass (17 of 64). The remaining 19 delay-tuned neurons are not selective for sound duration. All short-pass and 10 band-pass neurons’ characteristic delays were similar to characteristic duration. In six band-pass neurons, characteristic delay was different AZD7762 from characteristic duration. Neurons processing unmatched delay and durations could be participating in complex kinds of processing where the same neuron has different functions depending on the activated neural network. NeuroReport 24:404-409 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“The present study examined the interaction of anticipatory anxiety and selective emotion processing. Toward this end, a rapid stream of pleasant, neutral, and unpleasant pictures was presented in alternating blocks of threat-of-shock or safety, which were signaled by colored picture frames.