PHYSICAL ASPECTS OF REVERSIBLE INACTIVATION OF ENDOTOXIN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74729/1/j.1749-6632.1966.tb52394.x.pd

Scaling properties of diffusion-limited reactions on fractal and euclidean geometries

We review our scaling results for the diffusion-limited reactions A + A → 0 and A+B→0 on Euclidean and fractal geometries. These scaling results embody the anomalies that are observed in these reactions in low dimensions; we collect these observations under a single phenomenological umbrella. Although we are not able to fix all the exponents in our scaling expressions from first principles, we establish bounds that bracket the observed numerical results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45166/1/10955_2005_Article_BF01049612.pd

Rate processes on fractals: Theory, simulations, and experiments

Heterogeneous kinetics are shown to differ drastically from homogeneous kinetics. For the elementary reaction A + A → products we show that the diffusion-limited reaction rate is proportional to t − h[A] 2 or to [A] x , where h=1- d s /2, X=1+ 2/d s =(h-2)(h-1 ), and d s is the effective spectral dimension. We note that for d = d s =1, h =1/2 and X = 3 , for percolating clusters d s = 4/3, h = 1/3 and X = 5/2 , while for “dust” d s h > 1/2 and ∞ > X > 3. Scaling arguments, supercomputer simulations and experiments give a consistent picture. The interplay of energetic and geometric heterogeneity results in fractal-like kinetics and is relevant to excitation fusion experiments in porous membranes, films, and polymeric glasses. However, in isotopic mixed crystals, the geometric fractal nature (percolation clusters) dominates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45150/1/10955_2005_Article_BF01010846.pd

Single random walker on disordered lattices

Random walks on square lattice percolating clusters were followed for up to 2×105 steps. The mean number of distinct sites visited 〈 (S N ⊃> gives a spectral dimension of d s = 1.30±0.03 consistent with superuniversality ( d s =4J3) but closer to the alternative d s = 182/139, based on the low dimensionality correction. Simulations are also given for walkers on an energetically disordered lattice, with a jump probability that depends on the local energy mismatch and the temperature. An apparent fractal behavior is observed for a low enough reduced temperature. Above this temperature, the walker exhibits a “crossover” from fractal-to-Euclidean behavior. Walks on two- and three-dimensional lattices are similar, except that those in three dimensions are more efficient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45148/1/10955_2005_Article_BF01012923.pd

Pattern formation in diffusion-limited reactions

The conditions for macroscopic segregation of A and B in a steady-state A+B → 0 reaction are studied in infinite systems. Segregation occurs in one and two dimensions and is marginal for d =3. We note the dependence of these results on the precise experimental conditions assumed in the theory. We also note the difference between these results and our earlier ones for finite systems where the critical dimension is d =2.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45155/1/10955_2005_Article_BF01044727.pd

Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor

Antidepressants increase adult hippocampal neurogenesis in animal models, but the underlying molecular mechanisms are unknown. In this study, we used human hippocampal progenitor cells to investigate the molecular pathways involved in the antidepressant-induced modulation of neurogenesis. Because our previous studies have shown that antidepressants regulate glucocorticoid receptor (GR) function, we specifically tested whether the GR may be involved in the effects of these drugs on neurogenesis. We found that treatment (for 3–10 days) with the antidepressant, sertraline, increased neuronal differentiation via a GR-dependent mechanism. Specifically, sertraline increased both immature, doublecortin (Dcx)-positive neuroblasts (+16%) and mature, microtubulin-associated protein-2 (MAP2)-positive neurons (+26%). This effect was abolished by the GR-antagonist, RU486. Interestingly, progenitor cell proliferation, as investigated by 5′-bromodeoxyuridine (BrdU) incorporation, was only increased when cells were co-treated with sertraline and the GR-agonist, dexamethasone, (+14%) an effect which was also abolished by RU486. Furthermore, the phosphodiesterase type 4 (PDE4)-inhibitor, rolipram, enhanced the effects of sertraline, whereas the protein kinase A (PKA)-inhibitor, H89, suppressed the effects of sertraline. Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27Kip1 and p57Kip2. In conclusion, our data suggest that the antidepressant, sertraline, increases human hippocampal neurogenesis via a GR-dependent mechanism that requires PKA signaling, GR phosphorylation and activation of a specific set of genes. Our data point toward an important role for the GR in the antidepressant-induced modulation of neurogenesis in humans

Expression of an Epitope-Tagged Virulence Protein in Rickettsia parkeri Using Transposon Insertion

Despite recent advances in our ability to genetically manipulate Rickettsia, little has been done to employ genetic tools to study the expression and localization of Rickettsia virulence proteins. Using a mariner-based Himar1 transposition system, we expressed an epitope-tagged variant of the actin polymerizing protein RickA under the control of its native promoter in Rickettsia parkeri, allowing the detection of RickA using commercially-available antibodies. Native RickA and epitope-tagged RickA exhibited similar levels of expression and were specifically localized to bacteria. To further facilitate protein expression in Rickettsia, we also developed a plasmid for Rickettsia insertion and expression (pRIE), containing a variant Himar1 transposon with enhanced flexibility for gene insertion, and used it to generate R. parkeri strains expressing diverse fluorescent proteins. Expression of epitope-tagged proteins in Rickettsia will expand our ability to assess the regulation and function of important virulence factors

FoxO1, A2M, and TGF-beta 1 : three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses

To date, gene-environment (GxE) interaction studies in depression have been limited to hypothesis-based candidate genes, since genome-wide (GWAS)-based GxE interaction studies would require enormous datasets with genetics, environmental, and clinical variables. We used a novel, cross-species and cross-tissues "omics" approach to identify genes predicting depression in response to stress in GxE interactions. We integrated the transcriptome and miRNome profiles from the hippocampus of adult rats exposed to prenatal stress (PNS) with transcriptome data obtained from blood mRNA of adult humans exposed to early life trauma, using a stringent statistical analyses pathway. Network analysis of the integrated gene lists identified the Forkhead box protein O1 (FoxO1), Alpha-2-Macroglobulin (A2M), and Transforming Growth Factor Beta 1 (TGF-beta 1) as candidates to be tested for GxE interactions, in two GWAS samples of adults either with a range of childhood traumatic experiences (Grady Study Project, Atlanta, USA) or with separation from parents in childhood only (Helsinki Birth Cohort Study, Finland). After correction for multiple testing, a meta-analysis across both samples confirmed six FoxO1 SNPs showing significant GxE interactions with early life emotional stress in predicting depressive symptoms. Moreover, in vitro experiments in a human hippocampal progenitor cell line confirmed a functional role of FoxO1 in stress responsivity. In secondary analyses, A2M and TGF-beta 1 showed significant GxE interactions with emotional, physical, and sexual abuse in the Grady Study. We therefore provide a successful 'hypothesis-free' approach for the identification and prioritization of candidate genes for GxE interaction studies that can be investigated in GWAS datasets.Peer reviewe

Diversity and Functional Traits of Lichens in Ultramafic Areas: A Literature Based Worldwide Analysis Integrated by Field Data at the Regional Scale

While higher plant communities found on ultramafics are known to display peculiar characteristics, the distinguishability of any peculiarity in lichen communities is still a matter of contention. Other biotic or abiotic factors, rather than substrate chemistry, may contribute to differences in species composition reported for lichens on adjacent ultramafic and non-ultramafic areas. This work examines the lichen biota of ultramafics, at global and regional scales, with reference to species-specific functional traits. An updated world list of lichens on ultramafic substrates was analyzed to verify potential relationships between diversity and functional traits of lichens in different Köppen–Geiger climate zones. Moreover, a survey of diversity and functional traits in saxicolous communities on ultramafic and non-ultramafic substrates was conducted in Valle d’Aosta (North-West Italy) to verify whether a relationship can be detected between substrate and functional traits that cannot be explained by other environmental factors related to altitude. Analyses (unweighted pair group mean average clustering, canonical correspondence analysis, similarity-difference-replacement simplex approach) of global lichen diversity on ultramafic substrates (2314 reports of 881 taxa from 43 areas) displayed a zonal species distribution in different climate zones rather than an azonal distribution driven by the shared substrate. Accordingly, variations in the frequency of functional attributes reflected reported adaptations to the climate conditions of the different geographic areas. At the regional scale, higher similarity and lower species replacement were detected at each altitude, independent from the substrate, suggesting that altitude-related climate factors prevail over putative substrate–factors in driving community assemblages. In conclusion, data do not reveal peculiarities in lichen diversity or the frequency of functional traits in ultramafic areas

Fractal chemical kinetics: Reacting random walkers

Computer simulations on binary reactions of random walkers ( A + A → A ) on fractal spaces bear out a recent conjecture: ( ρ −1 − ρ 0 −1 ) ∞ t f , where ρ is the instantaneous walker density and ρ 0 the initial one, and f = d s /2, where d s is the spectral dimension. For the Sierpinski gaskets: d =2, 2 f =1.38 ( d s =1.365); d =3, 2 f =1.56 ( d s =1.547); biased initial random distributions are compared to unbiased ones. For site percolation: d = 2, p =0.60, 2 f = 1.35 ( d s =1.35); d=3, p =0.32, 2 f =1.37 ( d s =1.4); fractal-to-Euclidean crossovers are also observed. For energetically disordered lattices, the effective 2 f (from reacting walkers) and d s (from single walkers) are in good agreement, in both two and three dimensions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45149/1/10955_2005_Article_BF01012924.pd