Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans

Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have 12 isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive green fluorescent protein (GFP) expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.Fil: Hughes, Kiley. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Shah, Ashka. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Bai, Xiaofei. National Institutes of Health; Estados UnidosFil: Adams, Jessica. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Bauer, Rosemary. University of Chicago; Estados UnidosFil: Jackson, Janelle. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Harris, Emily. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Ficca, Alyson. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Freebairn, Ploy. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Mohammed, Shawn. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Fernandez, Eliana Mailen. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Bainbridge, Chance. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Brocco, Marcela Adriana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Stein, Wolfgang. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Vidal Gadea, Andrés G.. University Of Illinois. Deparment Of Biological Science; Estados Unido

Treatment of hepatic encephalopathy by on-line hemodiafiltration: a case series study

<p>Abstract</p> <p>Background</p> <p>It is thought that a good survival rate of patients with acute liver failure can be achieved by establishing an artificial liver support system that reliably compensates liver function until the liver regenerates or a patient undergoes transplantation. We introduced a new artificial liver support system, on-line hemodiafiltration, in patients with acute liver failure.</p> <p>Methods</p> <p>This case series study was conducted from May 2001 to October 2008 at the medical intensive care unit of a tertiary care academic medical center. Seventeen consecutive patients who admitted to our hospital presenting with acute liver failure were treated with artificial liver support including daily on-line hemodiafiltration and plasma exchange.</p> <p>Results</p> <p>After 4.9 ± 0.7 (mean ± SD) on-line hemodiafiltration sessions, 16 of 17 (94.1%) patients completely recovered from hepatic encephalopathy and maintained consciousness for 16.4 ± 3.4 (7-55) days until discontinuation of artificial liver support (a total of 14.4 ± 2.6 [6-47] on-line hemodiafiltration sessions). Significant correlation was observed between the degree of encephalopathy and number of sessions of on-line HDF required for recovery of consciousness. Of the 16 patients who recovered consciousness, 7 fully recovered and returned to society with no cognitive sequelae, 3 died of complications of acute liver failure except brain edema, and the remaining 6 were candidates for liver transplantation; 2 of them received living-related liver transplantation but 4 died without transplantation after discontinuation of therapy.</p> <p>Conclusions</p> <p>On-line hemodiafiltration was effective in patients with acute liver failure, and consciousness was maintained for the duration of artificial liver support, even in those in whom it was considered that hepatic function was completely abolished.</p

Plants as river system engineers

I would like to acknowledge three research grants/contracts that are supporting my current research on this theme: Grant F/07 040/AP from the Leverhulme Trust; Grant NE/F014597/1 from the Natural Environment Research Council, UK, and the REFORM collaborative project funded by the European Union Seventh Framework Programme under grant agreement 282656

Modeling the interactions between river morphodynamics and riparian vegetation

The study of river-riparian vegetation interactions is an important and intriguing research field in geophysics. Vegetation is an active element of the ecological dynamics of a floodplain which interacts with the fluvial processes and affects the flow field, sediment transport, and the morphology of the river. In turn, the river provides water, sediments, nutrients, and seeds to the nearby riparian vegetation, depending on the hydrological, hydraulic, and geomorphological characteristic of the stream. In the past, the study of this complex theme was approached in two different ways. On the one hand, the subject was faced from a mainly qualitative point of view by ecologists and biogeographers. Riparian vegetation dynamics and its spatial patterns have been described and demonstrated in detail, and the key role of several fluvial processes has been shown, but no mathematical models have been proposed. On the other hand, the quantitative approach to fluvial processes, which is typical of engineers, has led to the development of several morphodynamic models. However, the biological aspect has usually been neglected, and vegetation has only been considered as a static element. In recent years, different scientific communities (ranging from ecologists to biogeographers and from geomorphologists to hydrologists and fluvial engineers) have begun to collaborate and have proposed both semiquantitative and quantitative models of river-vegetation interconnections. These models demonstrate the importance of linking fluvial morphodynamics and riparian vegetation dynamics to understand the key processes that regulate a riparian environment in order to foresee the impact of anthropogenic actions and to carefully manage and rehabilitate riparian areas. In the first part of this work, we review the main interactions between rivers and riparian vegetation, and their possible modeling. In the second part, we discuss the semiquantitative and quantitative models which have been proposed to date, considering both multi- and single-thread river

Muscular Exertion Exacerbates Degeneration In A C. Elegans Model Of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of dystrophin, responsible for connecting actin to the sarcolemma and transferring force into the extracellular matrix. In humans, DMD presents at a young age, resulting in developmental delays, muscle necrosis, increased sarcoplasmic calcium, loss of ambulation, and early death. Current animal models do not model the severity of DMD without the addition of sensitizing mutations. Thus, it remains elusive if increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle’s disrupted contractile machinery. This knowledge has important implications for patients, as physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. We observe that sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes and can be mitigated by silencing calmodulin. Recently, we showed that burrowing dystrophic (dys-1) worms recapitulate many salient phenotypes of DMD. Here, we report dys-1 worms display early pathogenesis and increased lethality. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring either high intensity or high frequency muscle exertion during locomotion. We find that several muscular parameters (such as size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion regardless of the duration of the effort. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insights into DMD’s underlying pathology and to assess potential treatment strategies.https://ir.library.illinoisstate.edu/urs2021bio/1020/thumbnail.jp

Understanding the Pathogenesis of Duchenne Muscular Dystrophy Using a Caenorhabditis Elegans Model

Duchenne muscular dystrophy (DMD) is an x-linked degenerative disease that affects one out of every 3,500 males. This disease is produced by loss of function mutations in the dystrophin gene that results in the absence of the dystrophin protein from muscles and other tissues. Loss of dystrophin leads to progressive muscle weakness, loss of ambulation, and premature death. At the cellular level, patients present with increased sarcoplasmic calcium, loss of sarcomeric integrity, and mitochondrial damage. There is no cure for DMD. Understanding the progression of the disease and developing effective treatments has been hampered by lack of animal models able to recapitulate the disease at both the genotypic and phenotypic levels. Our lab recently showed that dystrophic C. elegans nematodes (dys-1) raised in burrowing environments recapitulate key phenotypes associated with dystrophic patients. My doctoral work focuses on understanding the progression of Duchenne muscular dystrophy, and in identifying molecular pathways that may be amenable to therapeutic interventions. My dissertation evaluates the extent to which dystrophic nematodes model Duchenne muscular dystrophy; contributes to our understanding of the pathophysiology of this disorder; and investigates different potential therapeutic avenues that might help stop or slow down the progression of this disease. In chapter I, I develop a method for modeling neurodegenerative diseases in C. elegans by altering their culture conditions to closely match what worms experience in nature. By having worms burrow in three dimensions through agar, rather than crawl around on an agar plate as is typically done in the lab, muscular exertion is increased and dystrophin mutants show locomotor defects. In chapter II I further characterize our dystrophic animals. I find that burrowing dystrophic worms undergo severe muscle degeneration, are slower in speed, do not develop normally, have swollen mitochondria, and die prematurely. Like human patients, dystrophic worms have excess levels of calcium. Furthermore, I found that while calcium release from the sarcoplasmic reticulum occurs normally, calcium clearance following a contraction cycle is slower. I found that deficits are already apparent in freshly-hatched larvae. These include excess calcium and slower development. During normal muscle function, calcium is important in both force generation but also in proprioceptive feedback. In chapter IV I discuss the mechanoreceptor pezo-1. Here, we focus on both the expression and function of different isoforms of pezo-1, which is the building blocks for an ongoing project exploring the role of long pezo-1 isoforms in body wall muscle and production of normal locomotion. Understanding how healthy muscles function and adapt is necessary to uncovering how muscles fail in disease states such as DMD. Dystrophic nematodes model known Duchenne muscular dystrophy pathology with a high degree of genotypic and phenotypic faithfulness which, coupled with its great experimental amenability, makes dystrophic worms a useful vehicle to understand this disorder and develop new therapeutics able to slow degeneration and improve the lives of Duchenne muscular dystrophy patients

Molecular and Behavioral Effects of In-Utero Stress on Subsequent Generations of Caenorhabditis elegans

Previous studies have implicated that in-utero stress can result in neuronal loss, memory deficits, and depression in adult rats. Other studies have proposed that maternal stress during pregnancy can cause epigenetic changes in the offspring associated with increased risk for anxiety disorders and autism. This likely occurs because of an elevation in glutamate receptors, such as the NMDA and AMPA receptors. Therefore, it is suggested that in-utero stressors in Caenorhabditis elegans acts via glutamate receptors, resulting in behavioral abnormalities. In the current study, this was tested by exposing wild-type N2 C. elegans to constant and repetitive motion stress for the duration of in-utero development (approximately 3 hours). Worms were then bleached to harvest embryos and adult offspring were examined for number of spontaneous reversals performed over a ten minute period. Worms that experienced in-utero stress showed significantly fewer spontaneously reversals than their control counterparts. Research in rats has suggested that stress increases the release of glutamate in the female dams and crosses the placental barrier resulting in the same effect in offspring. To study this effect in C. elegans, qRT-PCR was performed on adult offspring that had experience in utero stress to quantify GLR-1 glutamate receptor (AMPA) expression.These data together support what is known about the effects of stress in utero and provide a foundation for studying affected pathways and behavioral outcomes across generations in C. elegans

University Scholars Day

This paper discusses research on the effects of tutoring with concrete manipulatives and real life concepts

University Scholars Day

Presentation for the 2012 University Scholars Day at the University of North Texas discussing research on the effects of tutoring with concrete manipulatives and real life concepts