Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.

Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of \u3b1 catalytic and \u3b2 regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2\u3b1 immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-\u3baB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL

Assessment of culture and environment in the Adolescent Brain and Cognitive Development Study: Rationale, description of measures, and early data.

Neurodevelopmental maturation takes place in a social environment in addition to a neurobiological one. Characterization of social environmental factors that influence this process is therefore an essential component in developing an accurate model of adolescent brain and neurocognitive development, as well as susceptibility to change with the use of marijuana and other drugs. The creation of the Culture and Environment (CE) measurement component of the ABCD protocol was guided by this understanding. Three areas were identified by the CE Work Group as central to this process: influences relating to CE Group membership, influences created by the proximal social environment, influences stemming from social interactions. Eleven measures assess these influences, and by time of publication, will have been administered to well over 7,000 9-10 year-old children and one of their parents. Our report presents baseline data on psychometric characteristics (mean, standard deviation, range, skewness, coefficient alpha) of all measures within the battery. Effectiveness of the battery in differentiating 9-10 year olds who were classified as at higher and lower risk for marijuana use in adolescence was also evaluated. Psychometric characteristics on all measures were good to excellent; higher vs. lower risk contrasts were significant in areas where risk differentiation would be anticipated

Residential setting and parent-adolescent relationships during the college years

The relationship of residential setting (living with parents vs. living away from home while attending college) and gender with late adolescents' perceptions of their relationships with parents was examined. Four hundred four undergraduates students (mean age=20 years, 4 months) from two midwestern universities completed surveys. Two hundred four subjects lived with their parents and commuted to school, and 200 lived away at college. Controlling for student's age, parents' education, and financial and family considerations as factors in the choice of a college, living away was associated with greater independence, support, and mutual respect between parents and adolescents. In contrast, students who lived at home felt parents underestimated their maturity, and reported more conflict and avoidance in their relationships with parents. Regardless of residential setting, women reported more mutuality and support in their relationships with parents than men. The results suggest the importance of considering contextual issues during the transition to adulthood .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45280/1/10964_2005_Article_BF01536651.pd

Growing in generosity?:The effects of giving magnitude, target, and audience on the neural signature of giving in adolescence

Giving is essential for forming and maintaining social relationships, which is an important developmental task for adolescents. This pre-registered fMRI study investigated behavioral and neural correlates of adolescents’ (N = 128, ages 9 – 19 years) small versus large size giving in different social contexts related to target (i.e., giving to a friend or unfamiliar peer) and peer presence (i.e., anonymous versus audience giving). Participants gave more in the small size than large size condition, more to friends than to unfamiliar peers, and more in the audience compared to anonymous condition. Giving very small or large amounts was associated with increased activity in the medial prefrontal cortex (mPFC) and anterior insula (AI), and older adolescents showed increased lateral and anterior PFC activation for small size giving. We observed activity in the intraparietal cortex (IPL), dorsolateral prefrontal cortex, and AI for giving to friends, but no age-related differences in this activity. Behaviorally, in contrast, we observed that older adolescents differentiated more in giving between friends and unfamiliar peers. Finally, we observed interactions between peer presence and target in the AI, and between giving magnitude and target in the precuneus. Together, findings reveal higher context-dependency of giving and more lateral PFC activity for small versus large giving in older adolescents

Neural Mechanisms Underlying Trust to Friends, Community Members, and Unknown Peers in Adolescence

Trust plays an important role during adolescence for developing social relations. Although prior developmental studies give us insight into adolescents' development of differentiation between close (e.g., friends) and unknown (e.g., unknown peers) targets in trust choices, less is known about the development of trust to societal targets (e.g., members of a community organization) and its underlying neural mechanisms. Using a modified version of the Trust Game, our preregistered fMRI study examined the underlying neural mechanisms of trust to close (friend), societal (community member), and unknown others (unknown peer) during adolescence in 106 participants (aged 12-23 years). Adolescents showed most trust to friends, less trust to community members, and the least trust to unknown peers. Neural results show that target differentiation in adolescents' trust behavior is associated with activity in social brain regions implicated during mentalizing, reward processing, and cognitive control. Recruitment of the medial prefrontal cortex (mPFC) and OFC was higher for closer targets (i.e., friend and community member). For the mPFC, this effect was most pronounced during no trust choices. Trust to friends was additionally associated with increased activity in the precuneus and bilateral temporal parietal junction. In contrast, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex were most active for trust to unknown peers. The mPFC showed increased activity with age and consistent relations with individual differences in feeling needed/useful.</p

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P&lt;0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Enly: improving draft genomes through reads recycling

The reconstruction of the complete genome sequence of an organism is an important point for comparative, functional and evolutionary genomics. Nevertheless, overcoming the problems encountered while completing the sequence of an entire genome can still be demanding in terms of time and resources. We have developed Enly, a simple tool based on the iterative mapping of sequence reads at contig edges, capable to extend the genomic contigs deriving from high-throughput sequencing, especially those deriving by Newbler-like assemblies. Testing it on a set of de novo draft genomes led to the closure of up to 20% of the gaps originally present. Enly is cross-platform and most of the steps of its pipeline are parallelizable, making easy and fast to improve a draft genome resulting from a de novo assembly