Food cleaning in gorillas: Social learning is a possibility but not a necessity

Food cleaning is widespread in the animal kingdom, and a recent report confirmed that (amongst other behaviours) wild western lowland gorillas also show food cleaning. The authors of this report conclude that this behaviour, based on its distribution patterns, constitutes a potential candidate for culture. While different conceptualisations of culture exist, some more and some less reliant on behavioural form copying, all of them assign a special role to social learning processes in explaining potentially cultural behaviours. Here we report the results of an experiment that tested to what extent food cleaning behaviour in a group of captive Western lowland gorillas (Gorilla gorilla gorilla) relies on social learning processes. Subjects were provided with clean and dirty apples. When they were provided with dirty apples, all subjects showed evidence of food cleaning in at least 75% of trials. Preferred cleaning techniques differed between individuals, four out of five of subjects expressed a behaviour analogous to that reported in wild conspecifics. Given this occurrence of food cleaning in a culturally unconnected population of gorillas, we conclude that social learning is unlikely to play a central role in the emergence of the food cleaning behavioural form in Western lowland gorillas; instead, placing a greater emphasis on individual learning of food cleaning’s behavioural form

Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, piperlongumine (PPLGM), a bioactive agent found in long peppers, to induce pancreatic cancer cell death in cell culture and animal models. We found that PPLGM inhibited the growth of pancreatic cancer cell cultures by elevating ROS levels and causing DNA damage. PPLGM-induced DNA damage and pancreatic cancer cell death was reversed by treating the cells with an exogenous antioxidant. Similar to the in vitro studies, PPLGM caused a reduction in tumor growth in a xenograft mouse model of human pancreatic cancer. Tumors from the PPLGM-treated animals showed decreased Ki-67 and increased 8-OHdG expression, suggesting PPLGM inhibited tumor cell proliferation and enhanced oxidative stress. Taken together, our results show that PPLGM is an effective inhibitor for in vitro and in vivo growth of pancreatic cancer cells, and that it works through a ROS-mediated DNA damage pathway. These findings suggest that PPLGM has the potential to be used for treatment of pancreatic cancer

Glutathione S-Transferase pi-1 Knockdown Reduces Pancreatic Ductal Adenocarcinoma Growth by Activating Oxidative Stress Response Pathways

Glutathione S-transferase pi-1 (GSTP1) plays an important role in regulating oxidative stress by conjugating glutathione to electrophiles. GSTP1 is overexpressed in breast, colon, lung, and prostate tumors, where it contributes to tumor progression and drug resistance; however, the role of GSTP1 in pancreatic ductal adenocarcinoma (PDAC) is not well understood. Using shRNA, we knocked down GSTP1 expression in three different PDAC cell lines and determined the effect on cell proliferation, cell cycle progression, and reactive oxygen species (ROS) levels. Our results show GSTP1 knockdown reduces PDAC cell growth, prolongs the G0/G1 phase, and elevates ROS in PDAC cells. Furthermore, GSTP1 knockdown results in the increased phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the decreased phosphorylation of extracellular signal-regulated kinase (ERK), p65, the reduced expression of specificity protein 1 (Sp1), and the increased expression of apoptosis-promoting genes. The addition of the antioxidant glutathione restored cell viability and returned protein expression levels to those found in control cells. Collectively, these data support the working hypothesis that the loss of GSTP1 elevates oxidative stress, which alters mitogen-activated protein (MAP) kinases and NF-κB signaling, and induces apoptosis. In support of these in vitro data, nude mice bearing orthotopically implanted GSTP1-knockdown PDAC cells showed an impressive reduction in the size and weight of tumors compared to the controls. Additionally, we observed reduced levels of Ki-67 and increased expression of cleaved caspase-3 in GSTP1-knockdown tumors, suggesting GSTP1 knockdown impedes proliferation and upregulates apoptosis in PDAC cells. Together, these results indicate that GSTP1 plays a significant role in PDAC cell growth and provides support for the pursuit of GSTP1 inhibitors as therapeutic agents for PDAC

A Novel Interplay between Rap1 and PKA Regulates Induction of Angiogenesis in Prostate Cancer

Angiogenesis inhibition is an important therapeutic strategy for advanced stage prostate cancer. Previous work from our laboratory showed that sustained stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP (8CPT) via activation of Epac, a Rap1 GEF, or by expression of a constitutively active Rap1 mutant (cRap1) suppresses endothelial cell chemotaxis and subsequent angiogenesis. When we tested this model in the context of a prostate tumor xenograft, we found that 8CPT had no significant effect on prostate tumor growth alone. However, in cells harboring cRap1, 8CPT dramatically inhibited not only prostate tumor growth but also VEGF expression and angiogenesis within the tumor microenvironment. Subsequent analysis of the mechanism revealed that, in prostate tumor epithelial cells, 8CPT acted via stimulation of PKA rather than Epac/Rap1. PKA antagonizes Rap1 and hypoxic induction of 1α protein expression, VEGF production and, ultimately, angiogenesis. Together these findings provide evidence for a novel interplay between Rap1, Epac, and PKA that regulates tumor-stromal induction of angiogenesis.</p

Investigation of a Stand-Alone Online Learning Module for Cellular Respiration Instruction

With the recent rise of alternative instructional methodologies such as flipped classrooms and active learning, many core concepts are being introduced outside of the classroom prior to scheduled class meeting times. One popular means for external concept introduction in many undergraduate biology courses is the use of stand-alone online learning modules. Using a group of four large introductory biology course sections, we investigate the use of a stand-alone online learning module developed using animations from Virtual Cell Animation Collection as a resource for the introduction of cellular respiration concepts outside of the classroom. Results from four sections of introductory biology ( = 629) randomized to treatments show that students who interacted with the stand-alone online learning module had significantly higher normalized gain scores on a cellular respiration assessment than students who only attended a traditional lecture as a means of concept introduction ( < 0.001, = 0.59). These findings suggest a superior ability to convey certain introductory cellular respiration topics in a stand-alone manner outside of the classroom than in a more traditional lecture-based classroom setting

A Novel Interplay between Rap1 and PKA Regulates Induction of Angiogenesis in Prostate Cancer

<div><p>Angiogenesis inhibition is an important therapeutic strategy for advanced stage prostate cancer. Previous work from our laboratory showed that sustained stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP (8CPT) via activation of Epac, a Rap1 GEF, or by expression of a constitutively active Rap1 mutant (cRap1) suppresses endothelial cell chemotaxis and subsequent angiogenesis. When we tested this model in the context of a prostate tumor xenograft, we found that 8CPT had no significant effect on prostate tumor growth alone. However, in cells harboring cRap1, 8CPT dramatically inhibited not only prostate tumor growth but also VEGF expression and angiogenesis within the tumor microenvironment. Subsequent analysis of the mechanism revealed that, in prostate tumor epithelial cells, 8CPT acted via stimulation of PKA rather than Epac/Rap1. PKA antagonizes Rap1 and hypoxic induction of 1α protein expression, VEGF production and, ultimately, angiogenesis. Together these findings provide evidence for a novel interplay between Rap1, Epac, and PKA that regulates tumor-stromal induction of angiogenesis.</p> </div