Immunomodulatory effects of 17-O-acetylacuminolide in RAW264.7 cells and HUVECs : involvement of MAPK and NF-κB pathways

The terpenoid 17-O-acetylacuminolide (AA) was shown to inhibit the production of several inflammatory mediators. However, the mechanisms by which this compound elicited its anti-inflammatory activity remain to be elucidated. In this study, we analyzed the effects of AA on inflammatory gene expression in two different cell types with primordial importance in the inflammatory processes-endothelial cells and macrophages. In human umbilical vein endothelial cells, AA inhibited the expression of inflammatory proteins including the adhesion molecules intercellular adhesion molecule 1; vascular cell adhesion molecule 1; and E-selectin, as well as the release of the chemokine interleukin-8. Additionally, AA hindered the formation of capillary-like tubes in an in vitro model of angiogenesis. AA's effects in endothelial cells can be attributed at least in part to AA's inhibition of tumor necrosis factor alpha-induced nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappa B)'s translocation. Also, in lipopolysaccharide-stimulated macrophage-like RAW264.7 cells, AA was able to downregulate the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase, interleukin-6, and chemokine (C-C motif) ligand 2. Moreover, AA inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (I kappa B alpha), I kappa B kinase (IKK), and the mitogen-activated protein kinases JNK, ERK, and p38. In conclusion, the present results further support the anti-inflammatory potential of AA in different models of inflammation

Inclusive leadership : realizing positive outcomes through belongingness and being valued for uniqueness

We introduce a theoretically-grounded conceptualization of inclusive leadership and present a framework for understanding factors that contribute to and follow from inclusive leadership within work groups. We conceptualize inclusive leadership as a set of positive leader behaviors that facilitate group members perceiving belongingness in the work group while maintaining their uniqueness within the group as they fully contribute to group processes and outcomes. We propose that leader pro-diversity beliefs, humility, and cognitive complexity increase the propensity of inclusive leader behaviors. We identify five categories of inclusive leadership behaviors that facilitate group members' perceptions of inclusion, which in turn lead to member work group identification, psychological empowerment, and behavioral outcomes (creativity, job performance, and reduced turnover) in the pursuit of group goals. This framework provides theoretical grounding for the construct of inclusive leadership while advancing our understanding of how leaders can increase diverse work group effectiveness

Work group inclusion : test of a scale and model

We develop a theoretically based 10-item measure of work group inclusion comprised of two components (belongingness and uniqueness) and use this measure to empirically test the nomological network of work group inclusion developed by Shore et al. In Phase 1, we use two samples of full-time employees to develop and refine items as well as establish content validity. In Phase 2, we demonstrate convergent, discriminant, and incremental validity with both conceptually related and unrelated constructs. In Phase 3, we use data from an additional sample of employees and supervisors to test criterion-related validity and mediation by examining the multilevel relationships between inclusion and important antecedents and outcomes. Across the three phases of our study, the results demonstrate support not only for the factor structure, reliability, and validity of our work group inclusion measure but also for a theoretical model in which the construct of inclusion has important implications for individuals and organizations

Computational aberration compensation by coded-aperture-based correction of aberration obtained from optical Fourier coding and blur estimation

We report a novel generalized optical measurement system and computational approach to determine and correct aberrations in optical systems. The system consists of a computational imaging method capable of reconstructing an optical system’s pupil function by adapting overlapped Fourier coding to an incoherent imaging modality. It recovers the high-resolution image latent in an aberrated image via deconvolution. The deconvolution is made robust to noise by using coded apertures to capture images. We term this method coded-aperture-based correction of aberration obtained from overlapped Fourier coding and blur estimation (CACAO-FB). It is well-suited for various imaging scenarios where aberration is present and where providing a spatially coherent illumination is very challenging or impossible. We report the demonstration of CACAO-FB with a variety of samples including an in vivo imaging experiment on the eye of a rhesus macaque to correct for its inherent aberration in the rendered retinal images. CACAO-FB ultimately allows for an aberrated imaging system to achieve diffraction-limited performance over a wide field of view by casting optical design complexity to computational algorithms in post-processing

Outer membrane β-barrel protein folding is physically controlled by periplasmic lipid head groups and BamA.

Outer membrane β-barrel proteins (OMPs) are crucial for numerous cellular processes in prokaryotes and eukaryotes. Despite extensive studies on OMP biogenesis, it is unclear why OMPs require assembly machineries to fold into their native outer membranes, as they are capable of folding quickly and efficiently through an intrinsic folding pathway in vitro. By investigating the folding of several bacterial OMPs using membranes with naturally occurring Escherichia coli lipids, we show that phosphoethanolamine and phosphoglycerol head groups impose a kinetic barrier to OMP folding. The kinetic retardation of OMP folding places a strong negative pressure against spontaneous incorporation of OMPs into inner bacterial membranes, which would dissipate the proton motive force and undoubtedly kill bacteria. We further show that prefolded β-barrel assembly machinery subunit A (BamA), the evolutionarily conserved, central subunit of the BAM complex, accelerates OMP folding by lowering the kinetic barrier imposed by phosphoethanolamine head groups. Our results suggest that OMP assembly machineries are required in vivo to enable physical control over the spontaneously occurring OMP folding reaction in the periplasm. Mechanistic studies further allowed us to derive a model for BamA function, which explains how OMP assembly can be conserved between prokaryotes and eukaryotes.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.132247311

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Hierarchical Hough all-sky search for periodic gravitational waves in LIGO S5 data

We describe a new pipeline used to analyze the data from the fifth science run (S5) of the LIGO detectors to search for continuous gravitational waves from isolated spinning neutron stars. The method employed is based on the Hough transform, which is a semi-coherent, computationally efficient, and robust pattern recognition technique. The Hough transform is used to find signals in the time-frequency plane of the data whose frequency evolution fits the pattern produced by the Doppler shift imposed on the signal by the Earth's motion and the pulsar's spin-down during the observation period. The main differences with respect to previous Hough all-sky searches are described. These differences include the use of a two-step hierarchical Hough search, analysis of coincidences among the candidates produced in the first and second year of S5, and veto strategies based on a $\chi^2$ test.Comment: 7 pages, 2 figures, Amaldi08 proceedings, submitted to JPC

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development