Paradoxical activation of oncogenic signaling as a cancer treatment strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

Group Climate in Residential Youth Care: Development and Validation of the Group Climate Instrument-Revised.

Group climate in residential youth care is considered to be essential for treatment of youth and young adults. Various instruments exist to measure quality of living group climate, but some are lengthy, use complicated wording, which make them difficult to fill out by youth and individuals with a mild intellectual disability. The present study describes the development and rationale for the Group Climate Instrument-Revised (GCI-R). Construct validity and reliability of the GCI-R were examined by means of Confirmatory Factor Analysis (CFA) in a two-step validation process using a construction sample (n = 190 youth, representing 41 groups) and a validation sample (n = 207 youth, representing 42 groups). Results indicated a good fit of a five-factor model (Support, Growth, Physical Environment, Peer interactions, and Repression). Reliability of the scales was good. These findings indicate that the GCI-R can be used as a parsimonious, valid, and reliable instrument to assess perceptions of group climate in youth. Recommendations for future research and practice are suggested.

Young people's Perception of Group Climate in Juvenile Justice Centers in an Australian State, a Pilot Study.

There is ample evidence to demonstrate that a positive group climate in juvenile justice centers contributes to improvements in motivation for positive behavior and reducing incidents and even recidivism. Being provided opportunities for growth and development and being actively supported by well-trained staff creates a positive atmosphere and minimal repression. Such a pedagogical group climate is strongly related to fulfilling the basic psychological needs of the young people and is promoted by relational security. Following a series of challenging situations inside youth justice centers in Australia, we explored the opportunities for investing in staff training on awareness of basic psychological needs of these young people and introducing the concept of an open, positive group climate. This study reports the results of an explorative measurement of perceived group climate in four units of two juvenile justice centers in Victoria (Australia). The young people (N = 57) were provided with the Prison Group Climate Instrument. The results of the group climate research and a cross-cultural comparison show that there are inherent strengths but also important opportunities for improvement in the group climate experienced by young people. Recommendations to improve the group climate are discussed in this paper.

Ciliate protozoa of the forestomach of llamas (Lama glama) from locations at different altitude in Argentina.

This study describes the diversity and concentration of the protozoal population from the forestomach of llamas in Argentina at three altitudinal locations. Protozoal diversity was studied in samples from eight llamas from Hurlingham (Buenos Aires, 43 m altitude), four from Tilcara (Jujuy, 2465 m altitude) and six llamas from Cieneguillas (Jujuy, 3800 m altitude). The total concentrations of protozoa in the forestomach contents were 7.9, 9.1 and 4.1 cells x 104 ml-1 in Hurlingham, Tilcara and Cieneguillas, respectively (P>0.05). Entodinium spp. represented 97.9, 92.3 and 71.4% of the protozoal community in Hurlingham, Tilcara and Cieneguillas, respectively, and the remaining protozoa belonged to the Eudiplodinium genus. Entodinium spp. were identified as E. caudatum (mostly morphotype dubardi), E. longinucleatum, E. parvum, E. bovis, E. exiguum, E. dubardi, and a minor presence of E. bimastus (in three animals) and E. ovibos (in one animal). In regards to the rest of protozoal species, Eudiplodinium maggii is the first reported host record for the genus in llamas. This species was present in the forestomach of 14 out of 18 llamas tested, and in one case it was the unique protozoal species. The vestibuliferids, Dasytricha and Isotricha were absent from the forestomach of llamas. Similarly, other species such as those from the Caloscolex genus, Diplodinium cameli and Entodinium ovumrajae, commonly found in Old World Camelids, were also absent from llamas.