Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction

Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM) 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen. © 2014 Lim et al

Transitional disks and their origins: an infrared spectroscopic survey of Orion A

Transitional disks are protoplanetary disks around young stars, with inner holes or gaps which are surrounded by optically thick outer, and often inner, disks. Here we present observations of 62 new transitional disks in the Orion A star-forming region. These were identified using the \textit{Spitzer Space Telescope}'s Infrared Spectrograph and followed up with determinations of stellar and accretion parameters using the Infrared Telescope Facility's SpeX. We combine these new observations with our previous results on transitional disks in Taurus, Chamaeleon I, Ophiuchus and Perseus, and with archival X-ray observations. This produces a sample of 105 transitional disks of "cluster" age 3 Myr or less, by far the largest hitherto assembled. We use this sample to search for trends between the radial structure in the disks and many other system properties, in order to place constraints on the possible origins of transitional disks. We see a clear progression of host star accretion rate and the different disk morphologies. We confirm that transitional disks with complete central clearings have median accretion rates an order of magnitude smaller than radially continuous disks of the same population. Pre-transitional disks --- those objects with gaps that separate inner and outer disks --- have median accretion rates intermediate between the two. Our results from the search for statistically significant trends, especially related to $\dot{M}$, strongly support that in both cases the gaps are far more likely to be due to the gravitational influence of Jovian planets or brown dwarfs orbiting within the gaps, than to any of the photoevaporative, turbulent or grain-growth processes that can lead to disk dissipation. We also find that the fraction of Class II YSOs which are transitional disks is large, 0.1-0.2, especially in the youngest associations.Comment: 96 pages, 25 figures, resubmitted to Ap

The Future of Women\u27s Studies (Continued)

from the CALIFORNIA STATE UNIVERSITY, CHICO Women\u27s Studies at Chico developed from courses offered by women in their different departments, gathered to form a minor degree program in spring, 1973. Two specifically women\u27s studies courses were designed at that time: a team-taught Introduction to Women\u27s Studies (draws around 80 students a semester, changes women students\u27 expectations and horizons by projecting models of achieving women) and a Senior Research Seminar designed to integrate the students\u27 major and minor. Both are taught by the Women\u27s Studies Coordinator. Student demand has led to the development of new courses whose content received a great deal of student input: Women\u27s Health, Women in the Working World, Women in Art, Minority Women and the Re-Entry Program for Mature Women. There are now 20 courses offered through the Women\u27s Studies Program. Students are designing special degrees on the B.A. and M.A. level in areas such as Women and Counseling, Psychology and Art. ...from the CITY COLLEGE OF THE CITY UNIVERSITY OF NEW YORK... ...from FLORIDA INTERNATIONAL UNIVERSITY... ...from the JERSEY CITY STATE COLLEGE... ...from the UNIVERSITY OF MARYLAND... ...from UNIVERSITY OF MASSACHUSETTS/AMHERST... ...from the UNIVERSITY OF MINNESOTA... ...from the UNIVERSITY OF SOUTH FLORIDA..

Towards country-specific nitrous oxide emission factors for manures applied to arable and grassland soils in the UK

Nitrous oxide (N2O) emission factors (EFs) were calculated from measurements of emissions from livestock manures applied to UK arable crops and grassland as part of a wider research programme to reduce uncertainty in the UK national agricultural N2O inventory and to enhance regional inventory reporting through increased understanding of processes and factors controlling emissions. Field studies were undertaken between 2011 and 2013 at 3 arable and 3 grassland sites in the UK. Nitrous oxide emissions were measured following the autumn and spring application of different manures (pig slurry, cattle slurry, cattle farmyard manure (FYM), pig FYM, poultry layer manure, and broiler litter) at typical rates, using representative manure application and soil incorporation methods. In addition, ammonia emissions and nitrate leaching losses (1 site on a light sandy soil) were measured to calculate indirect N2O losses. IPCC comparable, direct N2O EFs ranged from −0.05 to 2.30% of total nitrogen applied, with the variability driven by a range of factors including differences in manure composition, application method, incorporation and climatic conditions. When data from the autumn applications were pooled, the mean N2O EF from poultry manure (1.52%) was found to be greater (P < 0.001) than from FYM (0.37%) and slurry (0.72%), with no difference found (P = 0.784) in the EF for bandspread compared with surface broadcast slurry application, and no effect (P = 0.328) of the nitrification inhibitor, Dicyandiamide (DCD). For the spring applications, the mean N2O EF for bandspread slurry (0.56%) was greater (P = 0.028) than from surface broadcast slurry (0.31%), but there were no differences (P = 0.212) in the mean N2O EFs from poultry manure (0.52%), slurry (0.44%), and FYM (0.22%). The study did confirm, however, that DCD reduced N2O emissions from slurries applied in the spring by 45%. EF data from this project have been used in the derivation of robust Tier 2 country specific EFs for inclusion in the UK national agriculture greenhouse gas inventory

Effect of increasing the time between slurry application and first rainfall event on phosphorus concentrations in runoff

Publication history: Accepted - 26 May 2021; Published online - 12 August 2021.Minimizing slurry phosphorus (P) losses in runoff requires careful management in the context of both soil P surpluses and changing patterns in rainfall. Increasing the time interval between slurry application and the first rainstorm event is known to reduce P loss in runoff although the risk period for elevated P concentrations in runoff can extend for weeks. This study investigated the impact of increasing the time interval between slurry application and first rainstorm event on P concentrations in runoff. Simulated rainfall (40 mm h−1) was applied at 2, 4, 10, 18, 30 and 49 days after dairy slurry was surface-applied to a grassland sward in Ireland. Increasing time to runoff resulted in a decrease in dissolved reactive P concentrations from 5.0 to 1.0 mg P L−1 and a P signal in runoff for 18 days. Beyond 18 days, elevated P concentrations were observed in runoff collected from natural rainfall that preceded the day 49 rainstorm event. A published surface phosphorus and runoff model (SurPhos) was used to understand the slurry P dynamics controlling P interactions with runoff. Dissolved reactive P in runoff was predicted with accuracy by SurPhos, R2 = .89. The SurPhos model implied thatslurry P mineralization occurred during the experimental period that resulted in a small spike in P concentrations beyond the defined risk period. This study shows that the experimental data have the potential to be extrapolated to different weather scenarios using SurPhos and could test when and where slurry P could be most safely spread.Open access funding provided by IReL. WOA Institution: University College Dublin Blended DEAL: IReL

Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human Platelets

Background Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. Methodology/Principal Findings In this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. Conclusions These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI

Bioinformatics Training Network (BTN): a community resource for bioinformatics trainers

Funding bodies are increasingly recognizing the need to provide graduates and researchers with access to short intensive courses in a variety of disciplines, in order both to improve the general skills base and to provide solid foundations on which researchers may build their careers. In response to the development of ‘high-throughput biology’, the need for training in the field of bioinformatics, in particular, is seeing a resurgence: it has been defined as a key priority by many Institutions and research programmes and is now an important component of many grant proposals. Nevertheless, when it comes to planning and preparing to meet such training needs, tension arises between the reward structures that predominate in the scientific community which compel individuals to publish or perish, and the time that must be devoted to the design, delivery and maintenance of high-quality training materials. Conversely, there is much relevant teaching material and training expertise available worldwide that, were it properly organized, could be exploited by anyone who needs to provide training or needs to set up a new course. To do this, however, the materials would have to be centralized in a database and clearly tagged in relation to target audiences, learning objectives, etc. Ideally, they would also be peer reviewed, and easily and efficiently accessible for downloading. Here, we present the Bioinformatics Training Network (BTN), a new enterprise that has been initiated to address these needs and review it, respectively, to similar initiatives and collections

A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development.

We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in a syndrome of pancreatic agenesis and abnormal forebrain development in three individuals and a similar phenotype in mice. CNOT1 is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state. These findings suggest that CNOT1 plays a critical role in pancreatic and neurological development and describe a novel genetic syndrome of pancreatic agenesis and holoprosencephaly.IB is funded by Wellcome (WT206194). ATH and SE are the recipients of a Wellcome Trust Senior Investigator award and ATH is employed as a core member of staff within the NIHR funded Exeter Clinical Research Facility and is an NIHR senior investigator. EDF was a Naomi Berrie Fellow in Diabetes Research during the study. SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number: 105636/Z/14/Z). CCW holds a Wellcome Trust Intermediate Clinical Fellowship (Grant Number: 105914/Z/14/Z). HH is funded by the Research Foundation-Flanders (FWO), the VUB Research Council and Stichting Diabetes Onderzoek Nederland