Resolvin D1 attenuates acid-induced DNA damage in esophageal epithelial cells and rat models of acid reflux.

The role of resolvin D1 (RvD1) in gastroesophageal reflux disease (GERD) remains largely unknown. Here, we investigated the potential role of RvD1 in acid-induced DNA damage in esophageal epithelial cells, patients with refractory GERD and a rat model of acid reflux. Weak acid exposure induced longer comet tails, reactive oxygen species (ROS) generation, oxidative DNA damage and DNA double-strand breaks (DSBs) in cells and RvD1 (0.1 µM) blocked all these effects. Mechanistic analyses showed that apart from ROS-reducing effects, RvD1 possessed a strong capacity to promote DNA damage repair, augmenting cell cycle checkpoint activity and DSB repair by modulating phosphatase and tensin homolog (PTEN) in cells. We also detected the surface expression of formyl peptide receptor 2 (FPR2), a receptor for RvD1, in the esophageal epithelial cells, and inhibition of FPR2 abrogated the protective effects of RvD1 on cells. Furthermore, a positive correlation between RvD1 and PTEN was observed predominantly in the esophageal epithelium from patients with refractory GERD (r = 0.67, P < 0.05). Additionally, RvD1 administration upregulated PTEN, suppressed DNA DSBs and alleviated microscopic damage in the rat model of gastric reflux. FPR2 gene silencing abolished the therapeutic effects of RvD1 on the rat model. Taken together, RvD1 binding to FPR2 protects the esophageal epithelium from acid reflux-induced DNA damage via a mechanism involving the inhibition of ROS production and facilitation of DSB repair. These findings support RvD1 as a promising approach that may be valuable for the treatment of GERD.

Interactive effects of freshwater acidification and selenium pollution on biochemical changes and neurotoxicity in Oreochromis mossambicus.

Effect of selenium and acidification in freshwater environment was assessed solitary but no reports are available on the impacts of both factors act together. In the present study, effects of combined simultaneous exposure to selenium (Se) and low pH were assessed in Mozambique tilapia, Oreochromis mossambicus. Responses were measured based on antioxidant defenses (enzymatic SOD, CAT, GPx and non-enzymatic GSH), biotransformation enzyme (GST), metallothionein levels (MT), oxidative damage (LPO, CP), Na+/K+-ATPase (NKA) activity in gills and liver tissues and neurotoxicity (acetylcholinesterase, AChE) response in brain tissue. Fish were exposed to combined treatment at different pH levels (7.5, control (optimum pH for tilapia growth); 5.5, low pH) and Se concentrations (0, 10, and 100 µg L-1). Toxicity levels of Se were not significantly different under control and low pH indicating that pH did not affect Se toxicity. Levels of GSH and MT were enhanced in Se-exposed fish at both pH. Combined effects of high Se concentration and low pH decreased SOD and CAT activities and increased those of GPx and GST. However, organisms were not able to prevent cellular damage (LPO and CP), indicating a condition of oxidative stress. Furthermore, inhibition of Na+/K+-ATPase activity was showed. Additionally, neurotoxicity effect was observed by inhibition of cholinesterase activity in organisms exposed to Se at both pH conditions. As a result, the combined stress of selenium and freshwater acidification has a slight impact on antioxidant defense mechanisms while significantly inhibiting cholinesterase and Na+/K + -ATPase activity in fish. The mechanisms of freshwater acidification mediating the toxic effects of trace non-metal element on freshwater fish need to investigate further.

A pH-Dependent Gene Expression Enables Bacillus amyloliquefaciens MBNC to Adapt to Acid Stress.

Acid tolerance response (ATR), a process by which bacteria optimize their growth conditions for cellular functions, is a well-characterized bacterial stress response. A bacterial isolate identified, as Bacillus amyloliquefaciens MBNC, was isolated from acidic soil and studied for its acid tolerance response under several range of acidic stress conditions imposed through inorganic acid, organic acid, acetate buffer, and soil extract. The ability of the B. amyloliquefaciens MBNC to tolerate extreme acidic conditions (pH 4.5) increased when exposed to moderate-acidic pH (pH 5.5). Along with ATR, the bacterial cell density was also critical to its ability to tolerate low pH as the cells of late log phase were more tolerant to low pH stress compared to the early log phase cells. A comparative expression study of 28 genes of B. amyloliquefaciens MBNC was assessed in cells grown in neutral (pH 7.0) and acidic condition (pH 4.5) through qRT-PCR. Among the 28 genes analyzed, 24 genes showed increased expression whereas the expression of 4 genes was downregulated under acid stress indicating to the involvement of the genes in acid stress response.

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model.

Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1-/- mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves's tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir and/or ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.

The use of WHAM-FTOX, parameterized with laboratory data, to simulate zooplankton species richness in acid- and metal- contaminated lakes.

The WHAM-FTOX model quantifies cation toxicity towards freshwater organisms, assuming an additive toxic response to the amounts of protons and metals accumulated by an organism. We combined a parameterization of the model, using data from multi-species laboratory toxicity tests, with a fitted field species sensitivity distribution, to simulate the species richness (nsp) of crustacean zooplankton in acid- and metal-contaminated lakes near Sudbury, Ontario over several decades, and also in reference (uncontaminated) lakes. A good description of variation in toxic response among the zooplankton species was achieved with a log-normal distribution of a new parameter, ß, which characterizes an organism's intrinsic sensitivity towards toxic cations; the greater is ß, the more sensitive is the species. The use of ß assumes that while species vary in their sensitivity, the relative toxicities of different metals are the same for each species (common relative sensitivity). Unbiased agreements between simulated and observed nsp were obtained with a high correlation (r2 = 0.81, p < 0.0001, n = 217). Variations in zooplankton species richness in the Sudbury lakes are calculated to be dominated by toxic responses to H, Al, Cu and Ni, with a small contribution from Zn, and negligible effects of Cd, Hg and Pb. According to the model, some of the Sudbury lakes were affected predominantly by acidification (H and Al), while others were most influenced by toxic heavy metals (Ni, Cu, Zn); for lakes in the latter category, the relative importance of heavy metals, compared to H and Al, has increased over time. The results suggest that, if common relative sensitivity operates, nsp can be modelled on the basis of a single set of parameters characterizing the average toxic effects of different cations, together with a species sensitivity distribution.

Global transcriptome analysis of Rhizobium favelukesii LPU83 in response to acid stress.

Acidic environments naturally occur worldwide and inappropriate agricultural management may also cause acidification of soils. Low soil pH values are an important barrier in the plant-rhizobia interaction. Acidic conditions disturb the establishment of the efficient rhizobia usually used as biofertilizer. This negative effect on the rhizobia-legume symbiosis is mainly due to the low acid tolerance of the bacteria. Here, we describe the identification of relevant factors in the acid tolerance of Rhizobium favelukesii using transcriptome sequencing. A total of 1924 genes were differentially expressed under acidic conditions, with ∼60% underexpressed. Rhizobium favelukesii acid response mainly includes changes in the energy metabolism and protein turnover, as well as a combination of mechanisms that may contribute to this phenotype, including GABA and histidine metabolism, cell envelope modifications and reverse proton efflux. We confirmed the acid-sensitive phenotype of a mutant in the braD gene, which showed higher expression under acid stress. Remarkably, 60% of the coding sequences encoded in the symbiotic plasmid were underexpressed and we evidenced that a strain cured for this plasmid featured an improved performance under acidic conditions. Hence, this work provides relevant information in the characterization of genes associated with tolerance or adaptation to acidic stress of R. favelukesii.

The Acidic Stress Response of the Intracellular Pathogen Brucella melitensis: New Insights from a Comparative, Genome-Wide Transcriptome Analysis.

The intracellular pathogenic bacteria belonging to the genus Brucella must cope with acidic stress as they penetrate the host via the gastrointestinal route, and again during the initial stages of intracellular infection. A transcription-level regulation has been proposed to explain this but the specific molecular mechanisms are yet to be determined. We recently reported a comparative transcriptomic analysis of the attenuated vaccine Brucella melitensis strain Rev.1 against the virulent strain 16M in cultures grown under either neutral or acidic conditions. Here, we re-analyze the RNA-seq data of 16M from our previous study and compare it to published transcriptomic data of this strain from both an in cellulo and an in vivo model. We identify 588 genes that are exclusively differentially expressed in 16M grown under acidic versus neutral pH conditions, including 286 upregulated genes and 302 downregulated genes that are not differentially expressed in either the in cellulo or the in vivo model. Of these, we highlight 13 key genes that are known to be associated with a bacterial response to acidic stress and, in our study, were highly upregulated under acidic conditions. These genes provide new molecular insights into the mechanisms underlying the acid-resistance of Brucella within its host.

Whole-genome sequencing and genomic-based acid tolerance mechanisms of Lactobacillus delbrueckii subsp. bulgaricus LJJ.

The probiotic efficacy and fermentative ability of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus), a widely used probiotic, is majorly affected by its acid tolerance. Here, we conducted whole-genome sequencing of the high acid-tolerant L. bulgaricus LJJ stored in the laboratory. Compared with the whole genome of low acid-tolerant strain L. bulgaricus ATCC11842, the results show that 16 candidate acid-tolerant genes may be involved in the regulation of the acid tolerance of L. bulgaricus LJJ. Association analysis of candidate acid-tolerant genes and acid-tolerant traits of different L. bulgaricus strains revealed that the three genes dapA, dapH, and lysC are the main reasons for the strong acid tolerance of L. bulgaricus LJJ. The results of real-time quantitative PCR (RT-qPCR) supported this conclusion. KEGG pathway analysis showed that these three acid-tolerant genes are involved in the synthesis of lysine; the synthesis of lysine may confer L. bulgaricus LJJ strong acid tolerance. This study successfully revealed the acid tolerance mechanism of L. bulgaricus LJJ and provides a theoretical basis for the subsequent selection of strains with high acid tolerance for improved probiotic functions. KEY POINTS: • Three genes are identified as acid-tolerant genes, respectively, lysC, dapA, and dapH. • LysC and dapA are the major key genes in the synthesis of lysine. • The synthesis of lysine may confer L. bulgaricus LJJ strong acid tolerance.

The recruitment of bacterial communities by the plant root system changed by acid mine drainage pollution in soils.

This study aims to better understand the relationship between the response to acid mine drainage (AMD) stress of tolerant plants and changes in root-related bacterial communities. In this study, reed stems were planted in AMD-polluted and unpolluted soils, and high-throughput sequencing was conducted to analyze the bacterial community composition in the soil, rhizosphere, rhizoplane and endosphere. The results showed that the effect of AMD pollution on root-associated bacterial communities was greater than that of rhizo-compartments. Proteobacteria were dominant across the rhizo-compartments between treatments. The microbiomes of unpolluted treatments were enriched by Alphaproteobacteria and Betaproteobacteria and depleted in Gammaproteobacteria ranging from the rhizoplane into the endosphere. However, the opposite trend was observed in the AMD pollution treatment, namely, Gammaproteobacteria were enriched, and Alphaproteobacteria and Deltaproteobacteria were mostly depleted. In addition, endophytic microbiomes were dominated by Comamonadaceae and Rhodocyclaceae in the unpolluted treatment and by Enterobacteriaceae in the AMD-polluted soils. PICRUSt showed that functional categories associated with membrane transport, metabolism and cellular processes and signaling processes were overrepresented in the endosphere of the AMD-polluted treatment. In conclusion, our study reveals significant variation in bacterial communities colonizing rhizo-compartments in two soils, indicating that plants can recruit functional bacteria to the roots in response to AMD pollution.

An assessment of the impacts of litter treatments on the litter quality and broiler performance: A systematic review and meta-analysis.

OBJECTIVE: The choice of the most suitable litter treatment should be based on scientific evidence. This systematic review assessed the effectiveness of litter treatments on ammonia concentration, pH, moisture and pathogenic microbiota of the litter and their effects on body weight, feed intake, feed conversion and mortality of broilers. METHODS: The systematic literature search was conducted using PubMed (Medline), Google Scholar, ScienceDirect and Scielo databases to retrieve articles published from January 1998 to august 2019. Means, standard deviations and sample sizes were extracted from each study. The response variables were analyzed using the mean difference (MD) or standardized mean difference (SMD), (litter treatment minus control group). All variables were analyzed using random effects meta-analyses. RESULTS: Subgroup meta-analysis revealed that acidifiers reduce pH (P<0.001), moisture (P = 0.002) ammonia (P = 0.011) and pathogenic microbiota (P <0.001) of the litter and improves the weight gain (P = 0.019) and decreases the mortality rate of broilers (P<0.001) when compared with controls. Gypsum had a positive effect on ammonia reduction (P = 0.012) and improved feed conversion (P = 0.023). Alkalizing agents raise the pH (P = 0.035), worsen feed conversion (P<0.001), increase the mortality rate (P <0.001), decrease the moisture content (P<0.001) and reduce the pathogenic microbiota of the litter (P<0.001) once compared to controls. Superphosphate and adsorbents reduce, respectively, pH (P<0.001) and moisture (P = 0.007) of the litter compared to control groups. CONCLUSION: None of the litter treatments influenced the feed intake of broilers. Meta-analyses of the selected studies showed positive and significant effects of the litter treatments on broiler performance and litter quality when compared with controls. Alkalizing was associated with worse feed conversion and high mortality of broilers.

Application of the hard and soft, acids and bases (HSAB) theory as a method to predict cumulative neurotoxicity.

Xenobiotic electrophiles can form covalent adducts that may impair protein function, damage DNA, and may lead a range of adverse effects. Cumulative neurotoxicity is one adverse effect that has been linked to covalent protein binding as a Molecular Initiating Event (MIE). This paper describes a mechanistic in silico chemical screening approach for neurotoxicity based on Hard and Soft Acids and Bases (HSAB) theory. We evaluated the applicability of HSAB-based electrophilicity screening protocol for neurotoxicity on 19 positive and 19 negative reference chemicals. These reference chemicals were identified from the literature, using available information on mechanisms of neurotoxicity whenever possible. In silico screening was based on structural alerts for protein binding motifs and electrophilicity index in the range of known neurotoxicants. The approach demonstrated both a high positive prediction rate (82-90 %) and specificity (90 %). The overall sensitivity was relatively lower (47 %). However, when predicting the toxicity of chemicals known or suspected of acting via non-specific adduct formation mechanism, the HSAB approach identified 7/8 (sensitivity 88 %) of positive control chemicals correctly. Consequently, the HSAB-based screening is a promising approach of identifying possible neurotoxins with adduct formation molecular initiating events. While the approach must be expanded over time to capture a wider range of MIEs involved in neurotoxicity, the mechanistic nature of the screen allows users to flag chemicals for possible adduct formation MIEs. Thus, the HSAB based toxicity screening is a promising strategy for toxicity assessment and chemical prioritization in neurotoxicology and other health endpoints that involve adduct formation.

Predicting Uncoupling Toxicity of Organic Acids Based on Their Molecular Structure Using a Biophysical Model.

We present a purely mechanistic model to predict protonophoric uncoupling activity ECw of organic acids. All required input information can be derived from their chemical structure. This makes it a convenient predictive model to gain valuable information on the toxicity of organic chemicals already at an early stage of development of new commercial chemicals (e.g., in agriculture or pharmaceutical industries). A critical component of the model is the consideration of the possible formation of heterodimers from the neutral and anionic monomer, and its permeation through the membrane. The model was tested against literature data measured in chromatophores, submitochondrial particles, isolated mitochondria, and intact green algae cells with good success. It was also possible to reproduce pH-dependencies in isolated mitochondria and intact cells. Besides the prediction of the ECw, the mechanistic nature of the model allows researchers to draw direct conclusions on the impact of single input factors such as pH- and voltage-gradients across the membrane, the anionic and neutral membrane permeability, and the heterodimerization constant. These insights are of importance in drug design or chemical regulation.

Evolution of Predicted Acid Resistance Mechanisms in the Extremely Acidophilic Leptospirillum Genus.

Organisms that thrive in extremely acidic environments (≤pH 3.5) are of widespread importance in industrial applications, environmental issues, and evolutionary studies. Leptospirillum spp. constitute the only extremely acidophilic microbes in the phylogenetically deep-rooted bacterial phylum Nitrospirae. Leptospirilli are Gram-negative, obligatory chemolithoautotrophic, aerobic, ferrous iron oxidizers. This paper predicts genes that Leptospirilli use to survive at low pH and infers their evolutionary trajectory. Phylogenetic and other bioinformatic approaches suggest that these genes can be classified into (i) "first line of defense", involved in the prevention of the entry of protons into the cell, and (ii) neutralization or expulsion of protons that enter the cell. The first line of defense includes potassium transporters, predicted to form an inside positive membrane potential, spermidines, hopanoids, and Slps (starvation-inducible outer membrane proteins). The "second line of defense" includes proton pumps and enzymes that consume protons. Maximum parsimony, clustering methods, and gene alignments are used to infer the evolutionary trajectory that potentially enabled the ancestral Leptospirillum to transition from a postulated circum-neutral pH environment to an extremely acidic one. The hypothesized trajectory includes gene gains/loss events driven extensively by horizontal gene transfer, gene duplications, gene mutations, and genomic rearrangements.

Bacterial response to sharp geochemical gradients caused by acid mine drainage intrusion in a terrace: Relevance of C, N, and S cycling and metal resistance.

A unique terrace with sharp gradient of environmental conditions was selected to study the microbial response and survival strategies to the extreme environments introduced by acid mine drainage (AMD) contamination. A combination of geochemical analyses, metagenomic sequencing, ex-situ microcosm setups, and statistical analyses were used to investigate the environment-microbe interactions. The microbial communities and metabolic potentials along the terrace were studied by focusing on the genes associated with important biogeochemical processes (i.e., C, N, S cycling and metal resistance). Results show that the variations of geochemical parameters substantially shaped the indigenous microbial communities. Sharp environmental gradients also impacted the microbial metabolic potentials, especially for C, N, and S cycling. Although the relative abundances of carbon fixing genes did not significantly vary along the environmental gradients, the taxa for carbon fixation varied significantly in more contaminated fields versus less contaminated fields, indicating the effects of AMD contamination on the autotrophic microbial communities. AMD input also influenced the N cycling, especially for nitrogen fixation and dissimilatory nitrate reduction to ammonium (DNRA). In addition, ex situ experiments were undertaken to evaluate the effects of AMD contamination on nitrogen fixation rates. Random Forest (RF) analysis indicated that nitrate, pH, total N, TOC exhibited positive correlations with the rates of nitrogen fixation while total Fe, Fe(III), and sulfate showed negative effects. Two co-occurrence networks at taxonomic and genomic levels indicated that geochemical parameters such as pH, TOC, total N, total S, and total Fe substantially influenced the innate microbial communities and their metabolic potentials. The current study provides an understanding for microbial response to AMD contamination and lays the foundation for future potential AMD bioremediation.

Pyrethroid-Derived Acids and Alcohols: Bioactivity and Synergistic Effects on Mosquito Repellency and Toxicity.

Pyrethroids are one of the most commonly used classes of insecticides, and their acid and alcohol components are esterase degradation products, usually considered to be biologically inactive. In this study, it was found that several pyrethroid acids had a spatial repellent activity that was greater than DEET, often more active than the parent pyrethroids, and showed little cross resistance in a pyrethroid-resistant Puerto Rico strain of Aedes aegypti mosquitoes. Further investigation revealed that the acids can synergize not only contact repellent standards but also other pyrethroid components as well as the parent pyrethroids themselves. Synergism by the pyrethroid acids is expressed as both increased spatial repellency and vapor toxicity as well as human bite protection. Electrophysiological studies confirmed that pyrethroid acids (100 µM) had no effect on neuronal discharge in larval Drosophila melanogaster CNS and were detected by electroantennography, and there was little resistance to olfactory sensing of these acids in antennae from Puerto Rico strain mosquitoes carrying kdr mutations. Thus, the data suggest that the pyrethroid acids have a different mode of action than the parent pyrethroids, unrelated to the voltage-sensitive sodium channel. The results highlight the potential of pyrethroid acids to be useful in future repellent formulations.

PAC proton-activated chloride channel contributes to acid-induced cell death in primary rat cortical neurons.

Severe local acidosis causes tissue damage and pain, and is associated with many diseases, including cerebral and cardiac ischemia, cancer, infection, and inflammation. However, the molecular mechanisms of the cellular response to extracellular acidic environment are not fully understood. We recently identified a novel and evolutionarily conserved membrane protein, PAC (also known as PACC1 or TMEM206), encoding the proton-activated chloride (Cl-) channel, whose activity is widely observed in human cell lines. We demonstrated that genetic deletion of Pac abolished the proton-activated Cl- currents in mouse neurons and also attenuated the acid-induced neuronal cell death and brain damage after ischemic stroke. Here, we show that the proton-activated Cl- currents are also conserved in primary rat cortical neurons, with characteristics similar to those observed in human and mouse cells. Pac gene knockdown nearly abolished the proton-activated Cl- currents in rat neurons and reduced the neuronal cell death triggered by acid treatment. These data further support the notion that activation of the PAC channel and subsequent Cl- entry into neurons during acidosis play a pathogenic role in acidotoxicity and brain injury.

Opposite and synergistic physiological responses to water acidity and predator cues in spadefoot toad tadpoles.

Organisms are exposed to multiple environmental factors simultaneously to which they often respond behaviorally, morphologically and/or physiologically. Amphibian larvae are quite plastic and efficiently adjust their phenotype and physiology to the reigning local conditions. Here we tested whether the combination of predator presence and low water pH induces alterations in the morphology and physiology of spadefoot toad tadpoles. We raised Pelobates cultripes tadpoles in the laboratory in water at either pH 4 or 7, and in the presence or absence of caged dragonfly nymphs, and determined their changes in shape through geometric morphometrics to assess whether predator recognition was impaired or not at low pH. We also measured levels of plasma corticosterone, activity of four antioxidant enzymes, as well as markers of oxidative damage and redox status. We found that tadpoles altered their body shape in response to predator cues even at low pH, indicating that predator recognition was not interfered by water acidity and developmental responses were robust even under abiotic stress. Water acidity was associated with increased corticosterone levels in tadpoles, whereas predator presence consistently reduced corticosterone levels. Predator presence was linked to reduced antioxidant enzyme activity, whereas the combination of both factors resulted in negative synergistic effects on lipid peroxidation and the antioxidant capacity of tadpoles. Here we show that tadpoles detect predators even at low pH but that the development of adaptive anti-predatory morphology can magnify physiological imbalances when other stressors co-occur. These results emphasize the need to understand how multiple environmental perturbations can affect animal homeostasis.

Endoscopic findings and outcome in caustic ingestion of acidic and alkaline agents in adults: A retrospective analysis.

Caustic ingestion in adults is a rare but potentially life-threatening problem. It remains controversial whether endoscopic findings and mortality differ between acid and alkali ingestion. We compared ingestion of these agents and evaluated prediction parameters for survival and complications.Adult patients who presented with caustic ingestion were analyzed from 2005 to 2016. Mucosal injury was graded endoscopically by Zargar's score. Age, gender, intent of ingestion, caustic agents, comorbidities, management, complications, and mortality were examined.Thirty-one patients met inclusion criteria and were divided into acid (n = 10) and alkali group (n = 21). Ingestion of alkali resulted in higher grades (≥III) of esophageal (56% vs 24%, P = .01) and stomach injuries (43% vs 13%, P = .05) and was mostly done with suicidal intent (76% vs 30%, P = .003). Patients in the alkali group received more often surgical interventions, mechanical ventilation and tracheotomy. Overall complications including Zargar's-score ≥ grade III, mediastinitis, and aspiration pneumonia were higher in alkali group but all showed no statistical significance (P = .73). Mortality (acid: 1 (10%), alkali: 4 (19%), P = .52), age, gender, comorbidities, and intensive care management did not differ significantly between the groups. Chronic renal failure and mediastinitis were promising prediction parameters for mortality but did not reach statistical significance. No independent risk factors for the development of esophageal stenosis were identified.Alkaline agents caused a higher mucosal injury severity and were more often used in suicidal intent. Mediastinitis and chronic renal failure might be potential prediction parameters for survival but need to be evaluated in larger studies.

Complex Gene Regulation Underlying Mineral Nutrient Homeostasis in Soybean Root Response to Acidity Stress.

Proton toxicity is one of the major environmental stresses limiting crop production and becomes increasingly serious because of anthropogenic activities. To understand acid tolerance mechanisms, the plant growth, mineral nutrients accumulation, and global transcriptome changes in soybean (Glycine max) in response to long-term acidity stress were investigated. Results showed that acidity stress significantly inhibited soybean root growth but exhibited slight effects on the shoot growth. Moreover, concentrations of essential mineral nutrients were significantly affected by acidity stress, mainly differing among soybean organs and mineral nutrient types. Concentrations of phosphorus (P) and molybdenum (Mo) in both leaves and roots, nitrogen (N), and potassium (K) in roots and magnesium (Mg) in leaves were significantly decreased by acidity stress, respectively. Whereas, concentrations of calcium (Ca), sulfate (S), and iron (Fe) were increased in both leaves and roots. Transcriptome analyses in soybean roots resulted in identification of 419 up-regulated and 555 down-regulated genes under acid conditions. A total of 38 differentially expressed genes (DEGs) were involved in mineral nutrients transportation. Among them, all the detected five GmPTs, four GmZIPs, two GmAMTs, and GmKUPs, together with GmIRT1, GmNramp5, GmVIT2.1, GmSKOR, GmTPK5, and GmHKT1, were significantly down-regulated by acidity stress. Moreover, the transcription of genes encoding transcription factors (e.g., GmSTOP2s) and associated with pH stat metabolic pathways was significantly up-regulated by acidity stress. Taken together, it strongly suggests that maintaining pH stat and mineral nutrient homeostasis are adaptive strategies of soybean responses to acidity stress, which might be regulated by a complex signaling network.