The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

We thank Cowen lab members for helpful discussions. We also thank David Rogers (University of Tennessee) for sharing microarray analysis of the CAS5 homozygous mutant, and Li Ang (University of Macau) for assistance in optimizing the ChIP-Seq experiments. J.L.X. is supported by a Canadian Institutes of Health Research Doctoral award and M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072). B.T.G. holds an Ontario Graduate Scholarship. C.B. and B.J.A. are supported by the Canadian Institutes of Health Research Foundation Grants (FDN-143264 and -143265). D.J.K. is supported by a National Institute of Allergy and Infectious Diseases grant (1R01AI098450) and J.D.L.C.D. is supported by the University of Rochester School of Dentistry and Medicine PREP program (R25 GM064133). A.S. is supported by the Creighton University and the Nebraska Department of Health and Human Services (LB506-2017-55). K.H.W. is supported by the Science and Technology Development Fund of Macau S.A.R. (FDCT; 085/2014/A2). L.E.C. is supported by the Canadian Institutes of Health Research Operating Grants (MOP-86452 and MOP-119520), the Natural Sciences and Engineering Council (NSERC) of Canada Discovery Grants (06261 and 462167), and an NSERC E.W.R. Steacie Memorial Fellowship (477598).Peer reviewedPublisher PD

Effects of Terrestrial Buffer Zones on Amphibians on Golf Courses

A major cause of amphibian declines worldwide is habitat destruction or alteration. Public green spaces, such as golf courses and parks, could serve as safe havens to curb the effects of habitat loss if managed in ways to bolster local amphibian communities. We reared larval Blanchard's cricket frogs (Acris blanchardi) and green frogs (Rana clamitans) in golf course ponds with and without 1 m terrestrial buffer zones, and released marked cricket frog metamorphs at the golf course ponds they were reared in. Larval survival of both species was affected by the presence of a buffer zone, with increased survival for cricket frogs and decreased survival for green frogs when reared in ponds with buffer zones. No marked cricket frog juveniles were recovered at any golf course pond in the following year, suggesting that most animals died or migrated. In a separate study, we released cricket frogs in a terrestrial pen and allowed them to choose between mown and unmown grass. Cricket frogs had a greater probability of using unmown versus mown grass. Our results suggest that incorporating buffer zones around ponds can offer suitable habitat for some amphibian species and can improve the quality of the aquatic environment for some sensitive local amphibians

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Interactions of an insecticide, herbicide, and natural stressors in amphibian community mesocosms

Abstract. Amphibians developing in wetlands embedded within or near agricultural lands may frequently encounter chemical mixtures. The objectives of our study were to determine the effects that post-application concentrations of an insecticide (carbaryl) and an herbicide (atrazine) have on body mass, development, and survival of two anuran species (southern leopard frog, Rana sphenocephala; American toad, Bufo americanus) and two caudate species (spotted salamander, Ambystoma maculatum; small-mouthed salamander, A. texanum) reared in outdoor cattle tank mesocosms. In one experiment, we manipulated tadpole density (low or high), carbaryl exposure (0, 3.5, 7.0 mg/L), and atrazine exposure (0 or 200 g/L) to test for effects on development, mass, and survival of larvae. In a second experiment, we manipulated pond hydroperiod (constant or drying), carbaryl exposure (0 or 5 mg/L), and atrazine exposure (0 or 200 g/L) to test for effects on mass, time, and survival to metamorphosis. Salamanders were virtually eliminated in carbaryl treatments, indicating that at realistic levels, this insecticide could cause population declines for salamanders in contaminated habitats. Carbaryl also had negative effects on toad survival. Exposure to atrazine had negative effects on body size, development, and time to metamorphosis in anuran species, which were associated with reduced chlorophyll levels. Both chemicals interacted significantly with density or hydroperiod, indicating that the environmental conditions could influence the impact of a contaminant. A significant atrazine-bycarbaryl interaction resulted in smaller and less developed spotted salamander larvae than in control ponds. Atrazine exposure, however, appeared to moderate negative effects of carbaryl for spotted salamanders. Our research suggests that important changes in the community's food web result from chemical exposure, which influence the susceptibility of amphibian species to contaminants

Changes in the abundance of phytoplankton in buffered and unbuffered golf course ponds over time.

<p>Shown is phytoplankton abundance (µg/L) measured in buffered and unbuffered golf course ponds from July-Sept-2008. HW =  Hueston Woods, TR =  Twin Run, OCC =  Oxford Country Club, NB =  No Buffer Zone, and B =  Buffer Zone. Error bars represent ± 1 SE.</p

Mass of green frogs and cricket frogs in buffered and unbuffered golf course ponds.

<p>Shown is mass of (A) green frog tadpoles at end of study (B) cricket frog mass at metamorphosis reared in buffered and unbuffered ponds on golf courses (OCC =  Oxford Country Club). Error bars represent one standard error of the mean.</p

Survival of green frogs and cricket frogs in buffered and unbuffered golf course ponds.

<p>Shown is survival of (A) green frog tadpoles to end of study and (B) cricket frog tadpoles to metamorphosis reared in buffered and unbuffered ponds on golf courses (OCC =  Oxford Country Club). Error bars represent one standard error of the mean.</p

Summary of nested ANOVAs for phytoplankton abundance, pH, dissolved oxygen (DO), and temperature.

<p>Summary of nested ANOVAs for phytoplankton abundance, pH, dissolved oxygen (DO), and temperature.</p