Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase

ERK5 is a mitogen-activated protein (MAP) kinase regulated in human cells by diverse mitogens and stresses but also suspected of mediating the effects of a number of oncogenes. Its expression in the slt2Delta Saccharomyces cerevisiae mutant rescued several of the phenotypes caused by the lack of Slt2p (Mpk1p) cell integrity MAP kinase. ERK5 is able to provide this cell integrity MAP kinase function in yeast, as it is activated by the cell integrity signaling cascade that normally activates Slt2p and, in its active form, able to stimulate at least one key Slt2p target (Rlm1p, the major transcriptional regulator of cell wall genes). In vitro ERK5 kinase activity was abolished by Hsp90 inhibition. ERK5 activity in vivo was also lost in a strain that expresses a mutant Hsp90 chaperone. Therefore, human ERK5 expressed in yeast is an Hsp90 client, despite the widely held belief that the protein kinases of the MAP kinase class are non-Hsp90-dependent activities. Two-hybrid and protein binding studies revealed that strong association of Hsp90 with ERK5 requires the dual phosphorylation of the TEY motif in the MAP kinase activation loop. These phosphorylations, at positions adjacent to the Hsp90-binding surface recently identified for a number of protein kinases, may cause a localized rearrangement of this MAP kinase region that leads to creation of the Hsp90-binding surface. Complementation of the slt2Delta yeast defect by ERK5 expression establishes a new tool with which to screen for novel agonists and antagonists of ERK5 signaling as well as for isolating mutant forms of ERK5

Biomechanical Response to Changes in Natural Turf during Running and Turning

publication-status: Publishedtypes: Article© Human Kinetics Inc, 2011Integrated biomechanical and engineering assessments were used to determine how humans responded to variations in turf during running and turning. Ground reaction force (AMTI, 960 Hz) and kinematic data (Vicon Peak Motus, 120 Hz) were collected from eight participants during running (3.83 m/s) and turning (10 trials per condition) on three natural turf surfaces in the laboratory. Surface hardness (Clegg hammer) and shear strength (cruciform shear vane) were measured before and after participant testing. Peak loading rate during running was significantly higher (p < .05) on the least hard surface (sandy; 101.48 BW/s ± 23.3) compared with clay (84.67 BW/s ± 22.9). There were no significant differences in running kinematics. Compared with the “medium” condition, fifth MTP impact velocities during turning were significantly (RM-ANOVA, p < .05) lower on clay (resultant: 2.30 m/s [± 0.68] compared with 2.64 m/s [± 0.70]), which was significantly (p < .05) harder “after” and had the greatest shear strength both “before” and “after” participant testing. This unique finding suggests that further study of foot impact velocities are important to increase understanding of overuse injury mechanisms

A Comparison of Intermittent and Continuous Exercise Bouts at Different Intensities on Appetite and Postprandial Metabolic Responses in Healthy Men

Exercise intensity affects many potential postprandial responses, but there is limited information on the influence of exercise modality. Therefore, the aim of this study was to investigate if the nature of exercise at two different intensities would affect gastric emptying rate (GER), appetite and metabolic responses following ingestion of a semi-solid meal. Twelve healthy men completed, in a random order, four 60-min cycles at 60% VO2peak (MOD), 40% VO2peak (LOW) and in a continuous (CON) or intermittent (INT) manner. INT consisted of 20 × 1-min exercise bouts with 2-min rest breaks. INT and CON were matched for total work output at each intensity. GER of the post-exercise meal was measured for 2 h using the 13C-breath method. Blood glucose, substrate utilisation and appetite ratings were measured at regular intervals throughout all trials and 24-h energy intake (EI) post-trials was assessed. GER-Delta over Baseline (DOB) was lower (p 0.05). 24-h post-trial EI was similar between LOW-CON vs. LOW-INT (p > 0.05), although MOD-INT vs. MOD-CON 3500 ± 1419 vs. 2556 ± 989 kCal: p < 0.001 was elevated. In summary, MOD-INT exercise delays GER without stimulating perceived appetite in the 2 h period after meal ingestion, although EI was greater in the 24-h post-trial

A putative serine protease, SpSsp1, from Saprolegnia parasitica is recognised by sera of rainbow trout, Oncorhynchus mykiss

Acknowledgements Our work was supported by the BBSRC (BB/C518457/1, BB/G012075/1, BB/J018333/1) (K.L.M., C.J.S., J.S.C., K.S.D., and P.v.W.), the University of Aberdeen (V.L.A., C.J.S., and P.v.W.), MSD Animal Health (J.S.C., K.S.D., and A.H.v.d.B), and The Royal Society (P.v.W.). This work was also supported by a Marie Curie Initial Training Networks with the SAPRO (sustainable approaches to reduce Oomycete (Saprolegnia) infections in aquacultures) grant PITN-GA-2009-238550 (A.H.v.d.B., L.L., C.J.S., P.v.W.). We would like to acknowledge Aberdeen Proteomics for carrying out LC–MS/MS and Laura Grenville-Briggs for valuable discussion and technical help. We are grateful to the Broad Institute (Carsten Russ, Rays Jiang, Brian Haas, and Chad Nusbaum), Brett Tyler (VBI), and P.v.W. for early release of draft supercontigs of the genome sequence of isolate CBS233.65, which helped us identify SpSsp1.Peer reviewedPublisher PD

The characteristics and dynamics of wave-driven flow across a platform coral reef in the Red Sea

Author Posting. © American Geophysical Union, 2016. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 121 (2016): 1360–1376, doi:10.1002/2015JC011141.Current dynamics across a platform reef in the Red Sea near Jeddah, Saudi Arabia, are examined using 18 months of current profile, pressure, surface wave, and wind observations. The platform reef is 700 m long, 200 m across with spatial and temporal variations in water depth over the reef ranging from 0.6 to 1.6 m. Surface waves breaking at the seaward edge of the reef cause a 2–10 cm setup of sea level that drives cross-reef currents of 5–20 cm s−1. Bottom stress is a significant component of the wave setup balance in the surf zone. Over the reef flat, where waves are not breaking, the cross-reef pressure gradient associated with wave setup is balanced by bottom stress. The quadratic drag coefficient for the depth-average flow decreases with increasing water depth from Cda = 0.17 in 0.4 m of water to Cda = 0.03 in 1.2 m of water. The observed dependence of the drag coefficient on water depth is consistent with open-channel flow theory and a hydrodynamic roughness of zo = 0.06 m. A simple one-dimensional model driven by incident surface waves and wind stress accurately reproduces the observed depth-averaged cross-reef currents and a portion of the weaker along-reef currents over the focus reef and two other Red Sea platform reefs. The model indicates the cross-reef current is wave forced and the along-reef current is partially wind forced.This research is based on work supported by awards USA 00002 and KSA 00011 KAUST. K. Davis was supported by a WHOI Postdoctoral Fellowship. T. Farrar was partly supported by NSF grant OCE-1435665. S. Lentz was partly supported by NSF grants OCE-1332646 and OCE-1357290.2016-08-1

Daily bathing with chlorhexidine-based soap and the prevention of Staphylococcus aureus transmission and infection

OBJECTIVE: Determine if daily bathing with chlorhexidine-based soap decreased methicillin-resistant Staphylococcus aureus (MRSA) transmission and ICU-acquired S. aureus infection among ICU patients. DESIGN: Prospective pre-post-intervention study with control unit SETTING: 1,250 bed tertiary-care teaching hospital PATIENTS: Medical and surgical intensive care unit (ICU) patients METHODS: Active surveillance for MRSA colonization was performed in both ICUs. In June 2005, a chlorhexidine bathing protocol was implemented in the surgical ICU. Changes in S. aureus transmission and infection rate before and after implementation were analyzed using time-series methodology. RESULTS: The intervention unit had a 20.68% decrease in MRSA acquisition after institution of the bathing protocol [pre-intervention 12.64 vs. post-intervention 10.03 cases/1000 patient-days-at-risk (95% CI: −5.19 – −0.04, p = 0.046)]. There was no significant change in MRSA acquisition in the control ICU during the study period [10.97 pre-June 2005 vs. 11.33/1000 patient-days at risk post-June 2005 (95% CI −37.40 – 15.19, p = 0.40)]. There was a 20.77% decrease in all S. aureus (including MRSA) acquisition in the intervention ICU from 2002-2007 [19.73 pre-intervention to 15.63 cases per 1000 patient-days at risk post-intervention (95% CI −7.25 – −0.95, p=0.012)]. The incidence of ICU-acquired MRSA infections decreased by 41.37% in the intervention ICU (1.96 pre-intervention vs. 1.15 infections per 1000 patient-days at risk post-intervention; p=0.001). CONCLUSIONS: Institution of daily chlorhexidine bathing in an ICU resulted in a decrease in the transmission of S. aureus, including MRSA. These data support the use of routine daily chlorhexidine baths to decrease rates of S. aureus transmission and infections

Stemming the Tide of Disinformation in Public Health

Context: Disinformation, or incorrect information that is intended to mislead, was pronounced during the COVID pandemic. Disinformation that steers away from life-saving practices or toward life-threatening practices can be fatal. The European Union has in place policies and offices to combat disinformation. However, they lack the full mandate and clarity of systems to meet the needs for quick and effective responses.Policy Options:Means to enhance the effectiveness of existing policies include [1] clarifying a rapid response framework, [2] enhancing media literacy in the public, [3] inoculating the public against anticipated disinformation, and [4] engendering public trust through coordinated and consistent communication. Recommendations:Among these four, options 2 and 3 were deemed the best opportunities for quick action, early successes, and the fewest institutional or political hurdles. We recommend [a] that the EU Commission establishes an EU Media Agency with a solid governance structure to support innovative media literacy undertakings and successful implementation; [b] that the existing Media Literacy Expert Group create a media literacy program implementation framework; and [c] that existing EU initiatives on disinformation debunking, media literacy, and inoculation strategies be merged into a single Misinformation Community within the European Institute of Innovation and Technology [EIT]

Immune response to rabies vaccination in pediatric transplant patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75049/1/j.1399-3046.2008.00936.x.pd