Publications by authors named "John P Phelan"

This study examined the effects of maternal and/or post-weaning Bacillus altitudinis supplementation on the microbiota in sow colostrum and faeces, and offspring digesta and faeces. Sows (n = 12/group) were assigned to: (1) standard diet (CON), or (2) CON supplemented with probiotic B. altitudinis spores (PRO) from day (d)100 of gestation to weaning (d26 of lactation).

View Article and Find Full Text PDF

The objective of this study was to evaluate the effect of feeding Bacillus altitudinis spores to sows and/or offspring on growth and health indicators. On day (D) 100 of gestation, twenty-four sows were selected and grouped as: control (CON), fed with a standard diet; and probiotic (PRO), fed the standard diet supplemented with B. altitudinis WIT588 spores from D100 of gestation until weaning.

View Article and Find Full Text PDF

Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles.

View Article and Find Full Text PDF

Faced with the continued emergence of antibiotic resistance to all known classes of antibiotics, a paradigm shift in approaches toward antifungal therapeutics is required. Well characterized in a broad spectrum of bacterial and fungal pathogens, biofilms are a key factor in limiting the effectiveness of conventional antibiotics. Therefore, therapeutics such as small molecules that prevent or disrupt biofilm formation would render pathogens susceptible to clearance by existing drugs.

View Article and Find Full Text PDF

A rapid decline in the development of new antimicrobial therapeutics has coincided with the emergence of new and more aggressive multidrug-resistant pathogens. Pathogens are protected from antibiotic activity by their ability to enter an aggregative biofilm state. Therefore, disrupting this process in pathogens is a key strategy for the development of next-generation antimicrobials.

View Article and Find Full Text PDF

Low-carbohydrate diets (LCD) are increasing in popularity, but their effect on vascular health has been questioned. Endothelial microvesicles (EMV) are membrane-derived vesicles with the potential to act as a sensitive prognostic biomarker of vascular health and endothelial function. The aim of this study was to examine the influence of a LCD on EMV and other endothelial biomarkers of protein origin.

View Article and Find Full Text PDF

Introduction: Bone marrow-derived endothelial progenitor cells (EPC) are involved in vascular growth and repair. They increase in the circulation after a single bout of aerobic exercise, potentially related to muscle ischemia. Muscular endurance resistance exercise (MERE) bouts also have the potential to induce muscle ischemia if appropriately structured.

View Article and Find Full Text PDF

The last steps of multivesicular body (MVB) formation, human immunodeficiency virus (HIV)-1 budding and cytokinesis require a functional endosomal sorting complex required for transport (ESCRT) machinery to facilitate topologically equivalent membrane fission events. Increased sodium tolerance (IST) 1, a new positive modulator of the ESCRT pathway, has been described recently, but an essential function of this highly conserved protein has not been identified. Here, we describe the previously uncharacterized KIAA0174 as the human homologue of IST1 (hIST1), and we report its conserved interaction with VPS4, CHMP1A/B, and LIP5.

View Article and Find Full Text PDF

Phosphoinositide signalling through the eukaryotic plasma membrane makes essential contributions to many processes, including remodelling of the actin cytoskeleton, vesicle trafficking and signalling from the cell surface. A proteome-wide screen performed in Saccharomyces cerevisiae revealed that Ypp1 interacts physically with the plasma-membrane-associated phosphoinositide 4-kinase, Stt4. In the present study, we demonstrate that phenotypes of ypp1 and stt4 conditional mutants are identical, namely osmoremedial temperature sensitivity, hypersensitivity to cell wall destabilizers and defective organization of actin.

View Article and Find Full Text PDF

In S. cerevisiae synthesis of phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] by Fab1p is required for several cellular events, including an as yet undefined step in the ubiquitin-dependent trafficking of some integral membrane proteins from the trans-Golgi network to the vacuole lumen. AP-1 is a heterotetrameric clathrin adaptor protein complex that binds cargo proteins and clathrin coats, and regulates bi-directional protein trafficking between the trans-Golgi network and the endocytic/secretory pathway.

View Article and Find Full Text PDF

Evolutionary theory leads to the general expectation that dietary restriction will often result in increased survival probabilities, and thus increased lifespan. The reaction norm is a basic tool of evolutionary analysis that quantifies the relationship between environmental parameters and functional characters, including reproduction and longevity. In rodents, the reaction norm connecting adult longevity to caloric intake is fairly steep; small changes in intake lead to large changes in longevity.

View Article and Find Full Text PDF

Weak organic acids are used as food preservatives to inhibit the growth of spoilage yeasts, including Saccharomyces cerevisiae. Long-term adaptation to weak acids requires the increased expression of the ATP-binding cassette transporter Pdr12p, which catalyses the active efflux of the weak acids from the cytosol; however, very little is known about the signalling events immediately following application of weak acid stress. We have investigated the effects of weak acids on two stress-responsive signalling molecules, PtdIns(3,5)P2 and PtdIns(4,5)P2, which in S.

View Article and Find Full Text PDF

Caloric restriction (CR) extends maximum longevity and slows aging in mice, rats, and numerous non-mammalian taxa. The apparent generality of the longevity-increasing effects of CR has prompted speculation that similar results could be obtained in humans. Longevity, however, is not a trait that exists in a vacuum; it evolves as part of a life history and the physiological mechanisms that determine longevity are undoubtedly complex.

View Article and Find Full Text PDF

We trace the evolutionary correlation between stress resistance and longevity in populations of Drosophila melanogaster selected for stress resistance over many generations. Females selected for desiccation resistance and both females and males selected for increasing starvation resistance initially show concurrent increases in longevity, but then begin to decrease in longevity, even as stress resistance continues to increase. We demonstrate that the correlation between two fitness traits can change and that this change is due to sustained selection rather than a genotype-by-environment interaction or inbreeding depression.

View Article and Find Full Text PDF

We provide evidence from comparisons of populations of Drosophila that evolutionary correlations between longevity and stress resistance break down over the course of laboratory evolution. Using 15 distinct evolutionary regimes, we created 75 populations that were differentiated for early fecundity, longevity, starvation resistance, desiccation resistance, and developmental time. In earlier experiments, selection for postponed aging produced increases in stress resistance, whereas selection for increased stress resistance produced increases in longevity.

View Article and Find Full Text PDF

We report the 2.1 A crystal structure of the core G protein domain of the unusual Rho family member RhoE/Rnd3 in complex with endogenous GTP and magnesium. Unlike other small G proteins, RhoE, along with two other proteins Rnd1/Rho6 and Rnd2/RhoN, does not hydrolyze GTP.

View Article and Find Full Text PDF

The gamma-aminobutyric acid receptor type A (GABA(A)) receptor-associated protein (GABARAP) has been reported to mediate the interaction between the GABA(A) receptor and microtubules. We present the three-dimensional structure of GABARAP obtained by x-ray diffraction at 1.75 A resolution.

View Article and Find Full Text PDF