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Biology subjects

Lopez, J. R.

Publications and source records attributed to Lopez, J. R..

3 recordsLinked to original sources

High-throughput phenotyping of soybean transpiration response curves to rising atmospheric drying in a mapping population

In soybean, limiting whole-plant transpiration rate (TR) response to increasing vapor pressure deficit (VPD) has been associated with the slow-wilting phenotype and with water- conservation enabling higher yields under terminal drought. Despite the promise of this trait, it is still unknown whether it has a genetic basis in soybean, a challenge limiting the prospects of breeding climate-resilient varieties. Here we present the results of a first attempt at a high- throughput phenotyping of TR and stomatal conductance response curves to increasing VPD conducted on a soybean mapping population consisting of 140 recombinant inbred lines (RIL). This effort was conducted over two consecutive years, using a controlled-environment, gravimetric phenotyping platform which enabled characterizing 900 plants for these responses, yielding regression parameters (R2 from 0.92 to 0.99) that were used for genetic mapping. Several quantitative trait loci (QTL) were identified for these parameters on chromosomes (Ch) 4, 6 and 10, including a VPD-conditional QTL on Ch 4 and a constitutive QTL controlling all parameters on Ch 6. This study demonstrated for the first time that canopy water use in response to rising VPD has a genetic basis in soybean, opening novel avenues for identifying alleles enabling water conservation under current and future climate scenarios.

plant biology↗

A novel saline-soluble, rapidly-metabolized RyR1 inhibitor rescues volatile anesthesia-induced death and environmental heat stroke in a mouse model relevant to malignant hyperthermia

Mutations in the type 1 ryanodine receptor (RyR1), a Ca2+ release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for MH, has the disadvantages of having very poor water solubility and long plasma half-life. We show here that a novel RyR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (Compound 1, Cpd1), effectively prevents and treats MH and heat stroke in several mouse models relevant to MH. Cpd1 reduced resting intracellular Ca2+, inhibited halothane- and isoflurane-induced Ca2+ release, suppressed caffeine-induced contracture in skeletal muscle, reduced sarcolemmal cation influx, and prevented or reversed the fulminant MH crisis induced by isoflurane anesthesia and rescued animals from heat stroke caused by environmental heat stress. Notably, Cpd1 has great advantages of better water solubility and rapid clearance in vivo over dantrolene. Cpd1 has the potential to be a promising new candidate for effective treatment of patients carrying RyR1 mutations.

pharmacology and toxicology↗

Whole Body Periodic Acceleration Improves Survival and Microvascular Leak in a Murine Endotoxin Model

Sepsis is a life threatening condition which produces multi-organ dysfunction with profound circulatory and cellular derangements. Administration of E.Coli endotoxin (LPS) produces systemic inflammatory effects of sepsis including disruption of endothelial barrier, and if severe enough death. Whole body periodic acceleration (pGz) is the headward-footward motion of the body. pGz has been shown to induce pulsatile shear stress to the endothelium, thereby releasing vascular and cardio protective mediators. The purpose of this study was to determine whether or not pGz performed as a pre-treatment or post-treatment strategy improves survival in a lethal murine endotoxin model.\n\nThis study was designed as a prospective randomized controlled study in mice. pGz was performed in mice as pre-treatment (pGz-LPS, 3 days prior to LPS), post-treatment (LPS-pGz, 30 min after LPS) strategies or Control (LPS-CONT), in a lethal murine model of endotoxemia. Endotoxemia was induced with intraperitoneal injection of E.Coli (40mg/kg). In a separate group of mice, a nonspecific nitric oxide synthase inhibitor (L-NAME) was provided in their drinking water and pGz-LPS and LPS-pGz performed to determine the effect of nitric oxide (NO) inhibition on survival. In another subset of mice, micro vascular leakage was determined. Behavioral scoring around the clock was performed in all mice at 30 min intervals after LPS administration, until 48 hrs. survival or death. LPS induced 100% mortality in LPS-CONT animals by 30 hrs. In contrast, survival to 48 hrs. occurred in 60% of pGz-LPS and 80% of LPS-pGz. L-NAME abolished the survival effects of pGz. Microvascular leakage was markedly reduced in both pre and post pGz treated animals and was associated with increased TIE2 and p-TIE2. In a murine model of lethal endotoxemia, pGz performed as a pre or post treatment strategy significantly improved survival, and markedly reduced microvascular leakage. The effect was modulated, in part, by NO since a non-selective inhibitor of NO abolished the pGz survival effect.

physiology↗