Role of detrusor PDGFRα+ cells in mouse model of cyclophosphamide-induced detrusor overactivity

Cyclophosphamide (CYP)-induced cystitis is a rodent model that shares many features common to the cystitis occurring in patients, including detrusor overactivity (DO). Platelet-derived growth factor receptor alpha positive (PDGFRα(+)) cells have been proposed to regulate muscle excitability in murine bladders during filling. PDGFRα(+) cells express small conductance Ca(2+)-activated K(+) channels (predominantly SK3) that provide stabilization of membrane potential during filling. We hypothesized that down-regulation of the regulatory functions of PDGFRα(+) cells and/or loss of PDGFRα(+) cells generates the DO in CYP-treated mice. After CYP treatment, transcripts of Pdgfrα and Kcnn3 and PDGFRα and SK3 protein were reduced in detrusor muscle extracts. The distribution of PDGFRα(+) cells was also reduced. Inflammatory markers were increased in CYP-treated detrusor muscles. An SK channel agonist, CyPPA, increased outward current and hyperpolarization in PDGFRα(+) cells. This response was significantly depressed in PDGFRα(+) cells from CYP-treated bladders. Contractile experiments and ex vivo cystometry showed increased spontaneous contractions and transient contractions, respectively in CYP-treated bladders with a reduction of apamin sensitivity, that could be attributable to the reduction in the SK conductance expressed by PDGFRα(+) cells. In summary, PDGFRα(+) cells were reduced and the SK3 conductance was downregulated in CYP-treated bladders. These changes are consistent with the development of DO after CYP treatment

Herbivory and nutrients shape grassland soil seed banks

Anthropogenic nutrient enrichment and shifts in herbivory can lead to dramatic changes in the composition and diversity of aboveground plant communities. In turn, this can alter seed banks in the soil, which are cryptic reservoirs of plant diversity. Here, we use data from seven Nutrient Network grassland sites on four continents, encompassing a range of climatic and environmental conditions, to test the joint effects of fertilization and aboveground mammalian herbivory on seed banks and on the similarity between aboveground plant communities and seed banks. We find that fertilization decreases plant species richness and diversity in seed banks, and homogenizes composition between aboveground and seed bank communities. Fertilization increases seed bank abundance especially in the presence of herbivores, while this effect is smaller in the absence of herbivores. Our findings highlight that nutrient enrichment can weaken a diversity maintaining mechanism in grasslands, and that herbivory needs to be considered when assessing nutrient enrichment effects on seed bank abundance.EEA Santa CruzFil: Eskelinen, Anu. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eskelinen, Anu. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Eskelinen, Anu. University of Oulu. Ecology & Genetics; FinlandiaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Jessen, Maria Theresa. German Centre for Integrative Biodiversity Research; AlemaniaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Bahamonde, Hector Alejandro. Universidad Nacional de La Plata. Ciencias Agrarias y Forestales; Argentina.Fil: Bakker, Jonathan D. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Caldeira, Maria C. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Harpole, William Stanley. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Harpole, William Stanley. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Harpole, William Stanley. Martin Luther University. Institute of Biology; AlemaniaFil: Jia, Meiyu. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Jia, Meiyu. East China University of Technology. School of Water Resources & Environmental Engineering; China.Fil: Jia, Meiyu. Beijing Normal University. College of Life Sciences; China.Fil: Lannes, Luciola S. São Paulo State University-UNESP. Department of Biology and Animal Sciences; Brasil.Fil: Nogueira, Carla. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Venterink, Harry Olde. Vrije Universiteit Brussel (VUB). Department of Biology; BélgicaFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Porath-Krause, Anita J. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Seabloom, Eric William. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Georgia. Odum School of Ecology; Estados UnidosFil: Tognetti, Pedro M. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Tognetti, Pedro M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA); Argentina.Fil: Tognetti, Pedro M. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Yasui, Simone-Louise E. Queensland University of Technology. School of Biological and Environmental Sciences; Australia.Fil: Virtanen, Risto. University of Oulu. Ecology & Genetics; FinlandiaFil: Sullivan, Lauren L. University of Missouri. Division of Biological Sciences; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Department of Plant Biology; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. W. K. Kellogg Biological Station; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Ecology, Evolution and Behavior Program; Estados Unido

Variation in Reproductive Success Across Captive Populations: Methodological Differences, Potential Biases and Opportunities

Our understanding of fundamental organismal biology has been disproportionately influenced by studies of a relatively small number of model\u27 species extensively studied in captivity. Laboratory populations of model species are commonly subject to a number of forms of past and current selection that may affect experimental outcomes. Here, we examine these processes and their outcomes in one of the most widely used vertebrate species in the laboratory - the zebra finch (Taeniopygia guttata). This important model species is used for research across a broad range of fields, partly due to the ease with which it can be bred in captivity. However despite this perceived amenability, we demonstrate extensive variation in the success with which different laboratories and studies bred their subjects, and overall only 64% of all females that were given the opportunity, bred successfully in the laboratory. We identify and review several environmental, husbandry, life-history and behavioural factors that potentially contribute to this variation. The variation in reproductive success across individuals could lead to biases in experimental outcomes and drive some of the heterogeneity in research outcomes across studies. The zebra finch remains an excellent captive animal system and our aim is to sharpen the insight that future studies of this species can provide, both to our understanding of this species and also with respect to the reproduction of captive animals more widely. We hope to improve systematic reporting methods and that further investigation of the issues we raise will lead both to advances in our fundamental understanding of avian reproduction as well as to improvements in future welfare and experimental efficiency

Nothing lasts forever: Dominant species decline under rapid environmental change in global grasslands

Dominance often indicates one or a few species being best suited for resource capture and retention in a given environment. Press perturbations that change availability of limiting resources can restructure competitive hierarchies, allowing new species to capture or retain resources and leaving once dominant species fated to decline. However, dominant species may maintain high abundances even when their new environments no longer favour them due to stochastic processes associated with their high abundance, impeding deterministic processes that would otherwise diminish them. Here, we quantify the persistence of dominance by tracking the rate of decline in dominant species at 90 globally distributed grassland sites under experimentally elevated soil nutrient supply and reduced vertebrate consumer pressure. We found that chronic experimental nutrient addition and vertebrate exclusion caused certain subsets of species to lose dominance more quickly than in control plots. In control plots, perennial species and species with high initial cover maintained dominance for longer than annual species and those with low initial cover respectively. In fertilized plots, species with high initial cover maintained dominance at similar rates to control plots, while those with lower initial cover lost dominance even faster than similar species in controls. High initial cover increased the estimated time to dominance loss more strongly in plots with vertebrate exclosures than in controls. Vertebrate exclosures caused a slight decrease in the persistence of dominance for perennials, while fertilization brought perennials' rate of dominance loss in line with those of annuals. Annual species lost dominance at similar rates regardless of treatments. Synthesis. Collectively, these results point to a strong role of a species' historical abundance in maintaining dominance following environmental perturbations. Because dominant species play an outsized role in driving ecosystem processes, their ability to remain dominant—regardless of environmental conditions—is critical to anticipating expected rates of change in the structure and function of grasslands. Species that maintain dominance while no longer competitively favoured following press perturbations due to their historical abundances may result in community compositions that do not maximize resource capture, a key process of system responses to global change.Fil: Wilfahrt, Peter A.. University of Minnesota; Estados UnidosFil: Seabloom, Eric. University of Minnesota; Estados UnidosFil: Bakker, Jonathan. University of Washington; Estados UnidosFil: Biederman, Lori. Iowa State University; Estados UnidosFil: Bugalho, Miguel N.. Universidade Nova de Lisboa; PortugalFil: Cadotte, Marc W.. University of Toronto–Scarborough; Estados UnidosFil: Caldeira, Maria C.. Universidade Nova de Lisboa; PortugalFil: Catford, Jane A.. University of Melbourne; AustraliaFil: Chen, Qingqing. Peking University; China. German Centre for Integrative Biodiversity Research; AlemaniaFil: Donohue, Ian. Trinity College Dublin; IrlandaFil: Ebeling, Anne. University of Jena; AlemaniaFil: Eisenhauer, Nico. German Centre for Integrative Biodiversity Research; Alemania. Leipzig University; AlemaniaFil: Haider, Sylvia. Martin Luther University Halle-Wittenberg; Alemania. Leuphana University of Lüneburg; AlemaniaFil: Heckman, Robert W.. University of Texas; Estados Unidos. United States Forest Service; Estados UnidosFil: Jentsch, Anke. University of Bayreuth; AlemaniaFil: Koerner, Sally E.. University of North Carolina Greensboro; Estados UnidosFil: Komatsu, Kimberly J.. University of North Carolina Greensboro; Estados UnidosFil: Laungani, Ramesh. Poly Prep Country Day School; Estados UnidosFil: MacDougall, Andrew. University of Guelph; CanadáFil: Smith, Nicholas G.. Texas Tech University; Estados UnidosFil: Stevens, Carly J.. Lancaster University; Reino UnidoFil: Sullivan, Lauren L.. Michigan State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tedder, Michelle. University of KwaZulu-Natal; SudáfricaFil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Tecnológica Nacional. Facultad Regional Santa Cruz. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Nacional de la Patagonia Austral. Centro de Investigaciones y Transferencia de Santa Cruz; ArgentinaFil: Tognetti, Pedro Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Veen, Ciska. Netherlands Institute of Ecology; Países BajosFil: Wheeler, George. University of Nebraska-Lincoln; Estados UnidosFil: Young, Alyssa L.. University of North Carolina Greensboro; Estados UnidosFil: Young, Hillary. University of California; Estados UnidosFil: Borer, Elizabeth. University of Minnesota; Estados Unido

Author Correction: Drivers of seedling establishment success in dryland restoration efforts

1 Pág. Correción errata.In the version of this Article originally published, the surname of author Tina Parkhurst was incorrectly written as Schroeder. This has now been corrected.Peer reviewe

The Pannexin 1 Channel and the P2X7 Receptor Are in Complex Interplay to Regulate the Release of Soluble Ectonucleotidases in the Murine Bladder Lamina Propria

The bladder urothelium releases ATP into the lamina propria (LP) during filling, which can activate P2X receptors on afferent neurons and trigger the micturition reflex. Effective ATP concentrations are largely dependent on metabolism by membrane-bound and soluble ectonucleotidases (s-ENTDs), and the latter are released in the LP in a mechanosensitive manner. Pannexin 1 (PANX1) channel and P2X7 receptor (P2X7R) participate in urothelial ATP release and are physically and functionally coupled, hence we investigated whether they modulate s-ENTDs release. Using ultrasensitive HPLC-FLD, we evaluated the degradation of 1,N6-etheno-ATP (eATP, substrate) to eADP, eAMP, and e-adenosine (e-ADO) in extraluminal solutions that were in contact with the LP of mouse detrusor-free bladders during filling prior to substrate addition, as an indirect measure of s-ENDTS release. Deletion of Panx1 increased the distention-induced, but not the spontaneous, release of s-ENTDs, whereas activation of P2X7R by BzATP or high concentration of ATP in WT bladders increased both. In Panx1−/− bladders or WT bladders treated with the PANX1 inhibitory peptide 10Panx, however, BzATP had no effect on s-ENTDS release, suggesting that P2X7R activity depends on PANX1 channel opening. We concluded, therefore, that P2X7R and PANX1 are in complex interaction to regulate s-ENTDs release and maintain suitable ATP concentrations in the LP. Thus, while stretch-activated PANX1 hinders s-ENTDS release possibly to preserve effective ATP concentration at the end of bladder filling, P2X7R activation, presumably in cystitis, would facilitate s-ENTDs-mediated ATP degradation to counteract excessive bladder excitability

Regulation of gastric electrical and mechanical activity by cholinesterases in mice

BACKGROUND/AIMS: Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. METHODS: Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. RESULTS: Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 μM) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (> 1 μM) caused aberrant contractile frequency and propagation and ectopic pacemaking. CONCLUSIONS: Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns

Excitatory Neuronal Responses of Ca 2+

Interstitial cells of Cajal (ICC) regulate smooth muscle excitability and motility in the gastrointestinal (GI) tract. ICC in the deep muscular plexus (ICC-DMP) of the small intestine are aligned closely with varicosities of enteric motor neurons and thought to transduce neural responses. ICC-DMP generate Ca2+ transients that activate Ca2+ activated Cl-channels and generate electrophysiological responses. We tested the hypothesis that excitatory neurotransmitters regulate Ca2+ transients in ICC-DMP as a means of regulating intestinal muscles. High-resolution confocal microscopy was used to image Ca2+ transients in ICC-DMP within murine small intestinal muscles with cell-specific expression of GCaMP3. Intrinsic nerves were stimulated by electrical field stimulation (EFS). ICC-DMP exhibited ongoing Ca2+ transients before stimuli were applied. EFS caused initial suppression of Ca2+ transients, followed by escape during sustained stimulation, and large increases in Ca2+ transients after cessation of stimulation. Basal Ca2+ activity and the excitatory phases of Ca2+ responses to EFS were inhibited by atropine and neurokinin 1 receptor (NK1) antagonists, but not by NK2 receptor antagonists. Exogenous ACh and substance P (SP) increased Ca2+ transients, atropine and NK1 antagonists decreased Ca2+ transients. Neurokinins appear to be released spontaneously (tonic excitation) in small intestinal muscles and are the dominant excitatory neurotransmitters. Subcellular regulation of Ca2+ release events in ICC-DMP may be a means by which excitatory neurotransmission organizes intestinal motility patterns

Is Metacognition Enough? Comparing Two Workshop Interventions in College Biology

Background. College introductory biology places high expectations on the quality and quantity of learning (Yazedjian et al., 2008). There has been a growing focus on developing metacognitive abilities to support success in college science courses (Dye & Stanton, 2017; Sebesta & Speth, 2017; Stanton et al., 2015). Workshop-style metacognition interventions can make a positive impact on academic outcomes (Hoffmann & McGuire, 2010; McGuire, 2015), yet an emphasis on metacognition alone may be incomplete. Although metacognition is an important component of self-regulated learning, it is just one of the areas that effective learners regulate; other areas include motivation, behavior, and context (Kim et al., 2020; Panadero, 2017). Engaging in effective time management invokes a fuller range of self-regulatory processes, as it involves devoting time and effort toward academic work, managing distractions in the environment, and generating the motivation not to procrastinate (Claessens et al., 2007; Wolters & Brady, 2020). Prior research on academic workshops suggests their academic benefits, but the studies also have shortcomings such as no pre-test strategy/belief measures or lack of a comparison group (Cook et al., 2013; Zhao et al., 2014). Aims & Methods. In this study, a team of researchers and educators from a student learning center and life sciences education center collaborated to design and compare two workshop-style interventions delivered in an undergraduate biology class. Because embedding learning strategy training within a specific context may lead to deeper understanding of the target strategy (Hattie & Donoghue, 2016), both workshops took place in students’ regularly scheduled laboratory class soon after students had received their first exam results. The seventeen laboratory sections were randomly assigned to one of two workshop interventions. The baseline workshop (“Metacognition,” n = 133) taught students about metacognitive learning strategies, while the extended workshop added content on time management and procrastination (“Metacognition+TM,” n = 116). All participating students also completed a pre-survey (prior to intervention) and post-survey (end of semester) that included self-reported measures of academic beliefs and strategies (e.g., Davidson et al., 2009). Students’ demographics (see Table 1), academic backgrounds, and grades were gathered from university records. Findings. Using an SEM residualized change approach that included academic, demographic, and pre-test covariates, we found statistically significant differences in students’ exam scores and pre-post levels of self-reported commitment toward earning a college degree, with greater increases for students who participated in the Metacognition+TM workshop (see Table 2). In addition, race/ethnicity moderated the effect of the intervention, with the Metacognition+TM intervention being especially effective in increasing the self-reported use of time management tools by students from minoritized groups (see Table 3 and Figure 1). Significance. The study provides evidence of the academic value of teaching college students how to regulate their learning, particularly the aspects associated with time management. Our discussion of implications will address the need for further research that includes additional assessments of students’ strategies, as well as instructional practices that approach study strategies from the perspective of creating equity and fostering inclusion (Asai, 2020; Matthews & López, 2020)