Biology subjects

Newman, E.

Publications and source records attributed to Newman, E..

3 recordsLinked to original sources

bioRxiv2018

Characterization of L-serine deaminases, SdaA (PA2448) and SdaB (PA5379), and their potential role in Pseudomonas aeruginosa pathogenesis

Regardless of the site of infectivity, all pathogens require high energetic influxes. This energy is required to counterattack the host immune system and in the absence the bacterial infections are easily cleared by the immune system. This study is an investigation into one highly bioenergetic pathway in Pseudomonas aeruginosa involving the amino acid L-serine and the enzyme L-serine deaminase (L-SD). P. aeruginosa is an opportunistic pathogen causing infections in patients with compromised immune systems as well as patients with cystic fibrosis. L-SD has been linked directly to the pathogenicity of several organisms including but not limited to Campylobacter jejuni, Mycobacterium bovis, Streptococcus pyogenes, and Yersinia pestis. We hypothesized that P. aeruginosa L-SD is likely to be critical for its virulence. The genome sequence analysis revealed the presence of two L-SD homologs encoded by sdaA and sdaB. We analyzed the ability of P. aeruginosa to utilize serine and the role of SdaA and SdaB in serine deamination by comparing mutant strains of sdaA (PAOsdaA) and sdaB (PAOsdaB) with their isogenic parent P. aeruginosa PAO1. We demonstrate that P. aeruginosa is unable to use serine as a sole carbon source. However, serine utilization is enhanced in the presence of glycine. Both SdaA and SdaB contribute to L-serine deamination, 34 % and 66 %, respectively. Glycine was also shown to increase the L-SD activity especially from SdaB. Glycine-dependent induction requires the inducer serine. The L-SD activity from both SdaA and SdaB is inhibited by the amino acid L-leucine. These results suggest that P. aeruginosa L-SD is quite different from the characterized E. coli L-SD that is glycine-independent but leucine-dependent for activation. Growth mutants able to use serine as sole carbon source were isolated. In addition, suicide vectors were constructed which allow for selective mutation of the sdaA and sdaB genes on any P. aeruginosa strain of interest. Future studies with a double mutant will reveal the importance of these genes for pathogenicity.

microbiology↗

bioRxiv2018

Canonical Wnt signaling regulates patterning, differentiation and nucleogenesis in mouse hypothalamus and prethalamus.

The hypothalamus is a small, but anatomically and functionally complex, region of the brain whose development is poorly understood. In this study, we have explored its development by studying the canonical Wntsignalling pathway, generating gain and loss of function mutations of betacaten in(Ctnnb1) in both hypothalamic and prethalamic neuroepithelium. Deletion of Ctnnb1 resulted in an anteriorized and hypoplastic hypothalamus. Posterior structures were lost or reduced, and anterior structures were expanded. In contrast, over expression of a constitutively active mutant form of Ctnnb1 resulted in severe hyperplasia of prethalamus and hypothalamus, and expanded expression of a subset of posterior and premamillary hypothalamic markers. Moderate defects in differentiation of Arx-positive GABAergic neural precursors were observed in both prethalamus and hypothalamus of Ctnnb1 loss of function mutants, while in gain of function mutants, their differentiation was completely suppressed, although markers of prethalamic progenitors were preserved. Multiple other region-specific markers, including several specific posterior hypothalamic structures, were also suppressed in Ctnnb1 gain of function mutations. Severe, region-specific defects in hypothalamic nucleogenesis were also observed in both gain and loss of function mutations of Ctnnb1. Finally, both gain and loss of function of Ctnnb1 also produced severe, cell nonautonomous disruptions of pituitary development. These findings demonstrate acentral and multifaceted role for canonical Wnt signalling in regulating growth, patterning, differentiation and nucleogenesis in multiple diencephalic regions.\n\nHighlightsO_LICanonical Wnt signalling regulates anteroposterior patterning in the hypothalamus.\nC_LIO_LICanonical Wnt signalling regulates differentiation of GABAergic neurons in both prethalamus and hypothalamus.\nC_LIO_LICanonical Wnt signalling regulates differentiation and nucleogenesis of multiple hypothalamic neuronal subtypes.\nC_LIO_LICanonical Wnt signalling in hypothalamic neuroepithelium regulates pituitary morphogenesis and differentiation.\nC_LI

developmental biology↗

bioRxiv2017

Analyzing ecological networks of species interactions

Networks provide one of the best representations for ecological communities, composed of many species with sometimes complex connections between them. Yet the methodological literature allowing one to analyze and extract meaning from ecological networks is dense, fragmented, and unwelcoming. We provide a general overview to the field of using networks in community ecology, outlining both the intent of the different measures, their assumptions, and the contexts in which they can be used. When methodologically justified, we suggest good practices to use in the analysis of ecological networks. We anchor this synopsis with examples from empirical studies, and conclude by highlighting what identified as needed future developments in the field.

ecology↗