Homologous p35 proteins of baculoviruses show distinctive anti-apoptotic activities which correlate with the apoptosis-inducing activity of each virus1The last author, Professor Maeda, has passed away after the acceptance of the paper. The rest of the authors would like this paper to be a memorial to him.1

AbstractThe anti-apoptotic activity of p35s from two baculoviruses, Autographa californica nucleopolyhedrovirus (AcNPV) and Bombyx mori NPV (BmNPV), was compared in mammalian cells. AcNPV p35 efficiently blocked apoptosis induced by caspase overexpression, but BmNPV p35 did so very poorly. Analysis of chimeric p35s and in vitro cleavage of wild type p35s suggest that the cleavage efficiency of p35 correlates with the blocking activity. Single amino acid substitutions of BmNPV p35 with those observed in AcNPV p35, however, resulted in significant loss of its anti-apoptotic activity. We speculate that sequences flanking the cleavage site have uniquely evolved during baculovirus evolution

Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia.

Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia,yielding 50-58 phage plaques in each cell type. Analyses of the sequences of this collection identified one candidate homing peptide targeting astrocytes (AS1[C-LNSSQPS-C]) and two candidate homing peptides targeting microglia (MG1[C-HHSSSAR-C] and MG2[C-NTGSPYE-C]). To determine peptide specificity for the target cell in vitro, each peptide was synthesized and introduced into the primary cultures of astrocytes or microglia. Those peptides could bind to the target cells and be selectively taken up by the corresponding cell, namely, astrocytes, M1 microglia, or M2 microglia. To confirm cell-specific gene delivery to M1 microglia, the complexes between peptide MG1 and siRNA-interferon regulatory factor 5 were prepared and intrathecally injected into a mouse model of neuropathic pain. The complexes successfully suppressed hyperalgesia with high efficiency in this neuropathic pain model. Here, we describe a novel gene therapy for the treatment neuropathic pain, which has a high potential to be of clinical relevance. This strategy will ensure the targeted delivery of therapeutic genes while minimizing side effects to non-target tissues or cells

Preemptive Striking in Individual and Group Conflict

<div><p>In this study, we conducted a laboratory experiment to assess preemptive striking by and towards individuals or groups. In the framework of a preemptive strike game, we set the following four conditions: one person faced another person, one person faced a three-person group, a three-person group faced an individual, and a three-person group faced another three-person group. Previous studies have revealed that greed is activated when participants belong to a group, while fear is activated when participants interact with a group, and further, that attacking behaviors in the preemptive strike game are driven by fear. These observations led to a hypothesis that high attack rates would be realized when participants interact with a group, regardless of whether the participants make decisions as individuals or a group. The results of our experiment, however, rejected this hypothesis. Among the four conditions, the attack rate was highest when a three-person group faced an individual. As possible reasons for our observation, we discuss the potential threat stemming from the imbalance in the effectiveness of attack between individuals and groups, and the (incorrect) belief by groups that single individuals would be more likely to attack out of fear.</p></div

Attack rate in the four conditions.

<p>Attack rate in the four conditions.</p

Inhibitory Effects of Quassinoid Derivatives on Epstein-Barr Virus Early Antigen Activation.

Short-term in vitro assays for tumor promoters and antitumor promoters (Epstein-Barr virus activation test) were carried out for semisynthetic quassinoids (3-7), which were obtained by esterification of the C-15 OH group of deacetylated isobrucein-B (2). All the ester derivatives showed higher antitumor promoting activity than that of the potent compound 2. A compound containing a fluorinated aliphatic ester showed the highest potency