Targeting NF-κB-Inducing Kinase (NIK) in Immunity,Inflammation, and Cancer

NF-κB-inducing kinase (NIK), the essential upstream kinase, which regulates activation of the noncanonical NF-κB pathway, has important roles in regulating immunity and inflammation. In addition, NIK is vital for maintaining cellular health through its control of fundamental cellular processes, including differentiation, growth, and cell survival. As such aberrant expression or regulation of NIK is associated with several disease states. For example, loss of NIK leads to severe immune defects, while the overexpression of NIK is observed in inflammatory diseases, metabolic disorders, and the development and progression of cancer. This review discusses recent studies investigating the therapeutic potential of NIK inhibitors in various diseases.     

Methyltransferase Contingencies in the Pathway of Everninomicin D Antibiotics and Analogues

Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A₁, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A₁- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A₁-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates.     

A New Method to Determine the Number Concentrations of Refractory Black Carbon Ice Nucleating Particles

Ice nucleating particles (INP) initiate heterogeneous ice nucleation in mixed-phase clouds, influencing cloud phase and onset temperatures for ice formation. Determination of particle types contributing to atmospheric INP populations requires isolation of the relatively rare INP from a total particle sample, typically followed by time-consuming single-particle characterization. We propose a method to estimate the contributions of light-absorbing, primarily refractory black carbon (rBC), particles to INP populations by selectively removing them prior to determination of INP concentrations. Absorbing particles are heated to their vaporization temperature using laser induced incandescence in a single particle soot photometer (SP2) and the change in INP number concentrations, compared to unheated samples, is assessed downstream in the CSU Continuous Flow Diffusion Chamber (CFDC). We tested this approach in the laboratory using strongly-absorbing and nonabsorbing aerosol types to confirm effective removal of rBC INP and to explore the impact of the processing on non-light-absorbing INP. An INP-active rBC particle type was efficiently removed, while nonabsorbing kaolinite and a soil-based INP were not affected by laser exposure. Results for the products of wiregrass combustion indicated that absorbing particles, primarily rBC, accounted for about 40% of all INP, consistent with electron microscopy of INP emitted during prescribed burns of this fuel type. However, kaolinite internally mixed with rBC exhibited reduced activity after passing through the SP2, suggesting that the validity of the method for realistic internal mixtures needs additional research. The sensitivity of the CFDC presently limits applicability of the method to relatively high INP number concentration samples.

Copyright 2014 American Association for Aerosol Research     

A developmental-genetic analysis of aggressive behavior in mice: I. Behavioral outcomes.

In Exp I, stable lines of mice that differed in the frequency and latency of attacks were rapidly established in 2 series (by S? in the 1st series and S? or S? in the 2nd). For evaluation of the developmental-genetic proposal, an analysis was made of the ontogeny of aggressive expression in male mice of the 2 series, with a report provided of the S? and S? generations of the 2nd breeding series (Exps II and III). Comparisons between results of a longitudinal design and results of a new type of cross-sectional design (involving only siblings, or co-sibial) indicated (a) a reliable developmental course of attack expression, with a sharp rise in early maturity and a slow decline thereafter; (b) a convergence in later maturity of the behavior of lines selectively bred for high or low aggressive behavior, if Ss had been assigned to the longitudinal design; (c) a strong effect of repeated testing on attack latency and frequency, even though the dyadic tests were brief in duration and separated by long intervals. In addition, cross-generational comparisons suggested that the selective breeding differences came about primarily by changes in the behavior of the low aggressive lines, in that these Ss failed to show in early maturity the sharp increases in attack occurrence that were observed in earlier generations. Implications for developmental and evolutionary concepts (e.g., neoteny, acceleration, and heterochrony) are discussed. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Crisis intervention training at a predoctoral internship in professional psychology.

Describes the model for crisis intervention at the internship level at a university counseling center. The program is organized around 3 components: orientation and didactic training in crisis intervention; crisis team membership in a local community mental health agency; and supervision of crisis intervention experiences. Data on the evaluation of the program are presented. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

More aggressive cartoons are funnier.

Independent rankings of humor and aggressiveness were obtained for sets of cartoons drawn randomly from 2 magazines. The correlation of median humor and median aggressiveness rankings ranged from .49 to .90 in 6 studies involving 6 sets of cartoons and 6 different groups of Ss, including children and adults, high and low SES individuals, and native- and foreign-born Ss. It was found that this correlation was consistent with Freudian, arousal, and superiority theories of humor. Another prediction of Freudian theory, that high-SES Ss should be more appreciative of aggressive humor than low-SES Ss, was not supported. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Online Social Network Adoption: A Cross-Cultural Study

This research explores the extent to which users across cultures adopt the technology of online social networks (OSNs) in order to promote or support a social cause. By surveying graduate-level university students at institutions in the United States, China and India, this research builds on prior work in technology acceptance to model and explain how three elements of the task domain – the cultural aspects of the user, the social nature of the technology, and the social nature of the task – combine to influence the constructs and relationships within a modified Technology Acceptance Model (TAM) framework as well as the behavior that flows from it. This study contributes to our understanding of technology adoption by showing how OSNs are adopted by users across cultures in promoting and supporting social causes.     

The ethics of asking about abuse and the harm of "don't ask, don't tell."

Replies to comments by J. Read (see record 2007-07130-012), D. Gleaves et al (see record 2007-07130-013), V. Edwards et al (see record 2007-07130-014), M. Black and R. Black (see record 2007-07130-015), and S. Ullman (see record 2007-07130-016), which raised important points about the authors' original article (see record 2006-03947-003). Those comments extend our thinking about how to ask participants about abuse in an ethical way. Together, the comments point to the importance of researchers examining our own reasons for asking--or not asking--about abuse and of paying attention to how we respond when we ask. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity.

γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA) provide innervation to cortical and subcortical regions of the brain. To solidify the importance of these VTA GABA neurons in behavioral function, we employed the neurotoxin dermorphin-saporin (DS) to selectively lesion VTA GABA neurons prior to assessing spontaneous motor activity. Rats were bilaterally microinfused with DS (1.0 or 2.0 pmol/200 nl/side) or blank-saporin control (BS, 200 nl/side) into the VTA. Seven days later, DS-treated rats exhibited significantly elevated motility in comparison with BS-treated rats; this elevated motility normalized by Day 14 following pretreatment with 1.0 pmol of DS but was sustained on Day 14 after pretreatment with 2.0 pmol of DS. A selective loss of VTA GABA neurons on Day 14 was demonstrated through reduced expression of mRNA for glutamic acid decarboxylase-67 and μ-opioid receptor, but not tyrosine hydroxylase (a dopamine neuron marker), in the VTA. Thus, a dose- and time-related selective loss of VTA GABA neurons was accomplished using this novel neurotoxin. This loss of GABA VTA neurons was associated with hypermotility, further supporting their important regulatory role in the generation of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The perceived urgency of speech warnings: semantics versus acoustics

The relationship between the semantics of words and the acoustics of the way they are spoken is explored. Actors spoke warning signal words in an urgent, nonurgent and monotone style, and participants rated the urgency of the words. Results showed effects for signal word and style of presentation. Acoustic analysis showed that the urgent words were spoken at higher frequency with a broader pitch range and were louder than the nonurgent or monotone words. These acoustic differences were used to synthesize artificial versions of signal words in urgent and nonurgent formats. The urgent words were rated as more urgent than the nonurgent words, a finding attributable to their differing acoustics. Within each speaking style the words were acoustically the same, yet effects for signal word were found, suggesting that semantics is also important in urgency perception. This research has implications for the design and implementation of speech warning systems, particularly those in which urgency mapping is required.