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Aquaculture of the Pacific white shrimp Litopenaeus vannamei in low-salinity water is a viable industry and production strategy in the southeastern United States. A major challenge facing this industry is a phenomenon called late-term mortality which is thought to be driven by thermal stress at the end of the growing season when water temperatures can reach or exceed 36 °C in shrimp production ponds. To investigate the physiological mechanisms behind upper lethal limits in shrimp, we evaluated linkages between empirically measured thermal limits and absolute aerobic scope (AAS), or ability to provide energy above that needed for basic maintenance. In this study, we tested whether thermal tolerance decreases with increasing shrimp age/size and whether AAS is a useful concept for understanding the physiological basis of thermal tolerance in shrimp. We exposed two size classes (small: 2.07 ± 0.86 and large: 24.64 ± 2.55 g) of shrimp to increasing temperature at a rate of 1 °C/h from 28 to 42 °C. At each temperature, we used intermittent respirometry to estimate resting metabolic rate and we directly measured lethal thermal tolerance by evaluating critical thermal maximum (CT max). Additionally, we used the electron transport system assay to estimate maximum metabolic rate (RMR) at temperatures from 9 to 45 °C. Small shrimp had a higher CT max than large shrimp, with upper lethal limits of 40.6 and 39.0 °C, respectively. For both size-classes, AAS reached its minimum (AAS min) at temperatures near the peak RMR (RMR peak) and within 2 °C of CT max. Large shrimp exhibited a lower temperature at AAS min than that of the smaller shrimp. Reductions in AAS appear to be one of the underlying physiological drivers of thermal tolerance in L. vannamei and an indicator of increasing thermal stress. Changes in the temperature at which AAS reaches its minimum may be a useful predictor of shifts in thermal tolerance among shrimp size-classes. • Pacific white shrimp were exposed to increasing temperature to measure physiological response to acute thermal stress • Upper thermal limits (CT max) decreased with increased shrimp size • Absolute aerobic scope declined to minimum values at temperatures near the RMRpeak and within 2 °C of CT max • Reductions in absolute aerobic scope appear to be one of the underlying physiological drivers of shrimp thermal tolerance [ABSTRACT FROM AUTHOR]

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50–80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO. [ABSTRACT FROM AUTHOR]

With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored on a regular basis, and their stability in the environment is not well understood. Laboratory studies have linked delta 9-tetrahydrocannabinol (Δ9-THC) exposure with behavioral abnormalities in some fish species; however, their effects on endocrine organs are less understood. To understand the effects of THC on the brain and gonads, we exposed adult medaka (Oryzias latipes, Hd-rR strain, both male and female) to 50 ug/L THC for 21 days spanning their complete spermatogenic and oogenic cycles. We examined transcriptional responses of the brain and gonads (testis and ovary) to Δ9-THC, particularly molecular pathways associated with behavioral and reproductive functions. The Δ9-THC effects were more profound in males than females. The Δ9-THC-induced differential expression pattern of genes in the brain of the male fish suggested pathways to neurodegenerative diseases and pathways to reproductive impairment in the testis. The present results provide insights into endocrine disruption in aquatic organisms due to environmental cannabinoid compounds. [ABSTRACT FROM AUTHOR]

Investigates decomposition in constructed wetlands in Ohio. Activities of soil enzymes; Decrease of phosphate and nitrate concentrations in outflow water; Exhibition of water quality amelioration function.

Freshwater biodiversity of the United States has long been recognized for its high level of species richness. The US crayfish fauna is richer than that found in any other country or continent in the world. Crayfishes are critically important members of freshwater ecosystems and have long been utilized for human consumption. Combined, these factors argue for effective conservation. When compared to other diverse aquatic groups such as fishes or unionid mussels, conservation efforts for US crayfishes are lacking. We review here, knowledge gaps that prevent effective conservation and past and ongoing crayfish conservation and management activities. We conclude by proposing a strategy of actions to improve the conservation standing of this important group of organisms. These action items include improved outreach efforts, funding and research to fill numerous knowledge gaps, and the inclusion of crayfishes in broader scale aquatic conservation activities. [ABSTRACT FROM AUTHOR]

We analyzed ecoenzyme activities related to organic matter processing in 1879 streams and rivers across the continental U.S. as part of the USEPA's National Rivers and Streams Assessment. Ecoenzymatic stoichiometry was used to construct models for carbon use efficiency (CUE) and decomposition (− k). Microbial respiration ( Rm) was estimated from sediment organic carbon stocks, CUE, and − k. The streams and rivers were classified by size (headwaters: 1st-order; streams: 2nd-3rd order; small rivers: 4th-5th order; big rivers 6th-7th order; and great rivers ≥ 8th order) and condition class (least, intermediate, and most disturbed), and grouped into nine ecoregions. There were ecoregion, stream size, and condition class effects for CUE, − k, and Rm, with Rm increasing from eastern ecoregions through the plains to the western ecoregions. CUE, − k, and Rm decreased with increasing streams size and increased with increasing disturbance. Rm, CUE, and − k were correlated with water and sediment chemistry; CUE and − k were also correlated with stream bed fine sediments; and CUE was further correlated with catchment land cover. Rm was extrapolated to ecoregional and national scales, and the results suggest that microbial assemblages account for 12% of the total CO2 outgassing, and nearly 50% of the aquatic metabolism C losses, from U.S. streams and rivers. Cumulative respiratory C losses increased from headwaters to small streams, then decreased with increasing stream size. This U-shaped respiration curve was not evident when streams were viewed by disturbance classes, suggesting that anthropogenic disturbances mask the expected organic matter processing signature of the river continuum. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is still the leading cause of disability in young adults worldwide. The major mechanisms - diffuse axonal injury, cerebral contusion, ischemic neurological damage, and intracranial hematomas have all been shown to be associated with mitochondrial dysfunction in some form. Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal/astrocytic metabolism to improve outcomes have been met with limited translational success. Previously, several preclinical and clinical studies on TBI induced mitochondrial dysfunction have focused on opening of the mitochondrial permeability transition pore (PTP), consequent neurodegeneration and attempts to mitigate this degeneration with cyclosporine A (CsA) or analogous drugs, and have been unsuccessful. Recent insights into normal mitochondrial dynamics and into diseases such as inherited mitochondrial neuropathies, sepsis and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. This review summarizes those aspects of mitochondrial dysfunction underlying TBI pathology with special attention to models of penetrating traumatic brain injury, an epidemic in modern American society. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis of NALFD; however the key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated. Accumulating and emerging evidence indicate that hepatic mitochondria play a critical role in the development and pathogenesis of steatosis and NAFLD. Here, we review studies that document a link between the pathogenesis of NAFLD and hepatic mitochondrial dysfunction with particular focus on new insights into the role of impaired fatty acid oxidation, the transcription factor peroxisome proliferator-activated receptor-? coactivator-1a (PGC-1α), and sirtuins in development and progression of NAFLD. [ABSTRACT FROM AUTHOR]

US military physicians and researchers helped identify the optimum treatment dose of the naturally occurring compound quinine and collaborated with the pharmaceutical industry in the development and eventual US Food and Drug Administration approval of the synthetic antimalarial drugs chloroquine, primaquine, chloroquine-primaquine, sulfadoxine-pyrimethamine, mefloquine, doxycycline, halofantrine, and atovaquone-proguanil. Because malaria parasites develop drug resistance, the US military must continue to support the creation and testing of new drugs to prevent and treat malaria until an effective malaria vaccine is developed. New antimalarial drugs also benefit civilians residing in and traveling to malarious areas. [ABSTRACT FROM AUTHOR]

The Hydrogen Sulfide Health Research and Risk Assessment Symposium came about for several reasons: (1) increased interest by the U.S. Environmental Protection Agency (EPA) and several state agencies in regulating hydrogen sulfide (H 2 S); (2) uncertainty about ambient exposure to H 2 S; (3) confusion and disagreement in the literature about possible health effects at low-level exposures; and (4) presentation of results of a series of recent animal bioassays. The American Petroleum Institute (API) proposed this symposium and the EPA became an early co-sponsor, with the Chemical Industry Institute of Toxicology (CIIT) and the American Forest & Paper Association (AF&PA) contributing expertise and funding assistance. The topics covered in this symposium included Animal Research, Human Research, Mode-of-Action and Dosimetry Issues, Environmental Exposure and Monitoring, Assessment and Regulatory Issues, and closed with a panel discussion. The overall goals of the symposium were to: gather together experts in H 2 S health effects research and individuals from governmental agencies charged with protecting the public health, provide a venue for reporting of recent research findings, identify gaps in the current information, and outline new research directions and promote research collaboration. During the course of the symposium, presenters provided comprehensive reviews of the state of knowledge for each topic. Several new research proposals discussed at the symposium have subsequently been initiated. This report provides a summary of the talks, poster presentations, and panel discussions that occurred at the Hydrogen Sulfide Health and Risk Assessment Symposium. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that gene expression profiling can reveal indicators of subtle injury to the liver induced by a low dose of a substance that does not cause overt toxicity as defined by conventional criteria of toxicology (e.g., abnormal clinical chemistry and histopathology). For the purpose of this study we defined this low dose as subtoxic, i.e., a dose that elicits effects which are below the detection of conventional toxicological parameters. Acetaminophen (APAP) was selected as a model hepatotoxicant because (1) considerable information exists concerning the mechanism of APAP hepatotoxicity that can occur following high doses, (2) intoxication with APAP is the leading cause of emergency room visits involving acute liver failure within the United States, and (3) conventional clinical markers have poor predictive value. Rats treated with a single dose of 0, 50, 150, or 1500 mg/kg APAP were examined at 6, 24, or 48 h after exposure for conventional toxicological parameters and for gene expression alterations. Patterns of gene expression were found which indicated cellular energy loss as a consequence of APAP toxicity. Elements of these patterns were apparent even after exposure to subtoxic doses. With increasing dose, the magnitude of changes increased and additional members of the same biological pathways were differentially expressed. The energy loss suggested by gene expression changes was confirmed at the 1500 mg/kg dose exposure by measuring ATP levels. Only by ultrastructural examination could any indication of toxicity be identified after exposure to a subtoxic dose of APAP and that was occasional mitochondrial damage. In conclusion, this study provides evidence that supports the hypothesis that gene expression profiling may be a sensitive means of identifying indicators of potential adverse effects in the absence of the occurrence of overt toxicity. [ABSTRACT FROM AUTHOR]

The concentrations of dissolved oxygen and chlorophyll have declined in the Seneca River, New York since 1991 as a result of zebra mussel respiration and filtering. Recently measured data were used to approximate flux rates of zebra mussel respiration, filtering, and phosphorus and ammonia mobilization. A model is developed that for the first time links dissolved oxygen, phytoplankton growth, and zebra mussel respiration and filtering. Good agreement is attained between the model calculations and longitudinal profiles of both dissolved oxygen and chlorophyll measured at low flow during 1997-1999. Flux rates derived from these analyses are consistent with results from other studies when normalized on the basis of zebra mussel number and tissue dry weight. Kinetic formulations for the zebra mussels are developed that describe respiration and filtering rates as a function of density, size distribution, and dissolved oxygen concentration. Several plausible test scenarios are examined using the model that indicate that both zebra mussel numbers and size distributions have a profound effect on the water quality of the Seneca River and therefore have important management and planning ramifications. [ABSTRACT FROM AUTHOR]

1. Benthic microbial respiration was measured in 214 streams in the Appalachian Mountain, Piedmont, and Coastal Plains regions of the eastern United States in summer 1997 and 1998. 2. Respiration was measured as both O2 consumption in sealed microcosms and as dehydrogenase activity (DHA) of the sediments contained within the microcosms. 3. Benthic microbial respiration in streams of the eastern U.S., as O2 consumption, was 0.37 ± 0.03 mg O2 m–2 day–1. Respiration as DHA averaged 1.21 ± 0.08 mg O2 m–2 day–1 4. No significant differences in O2 consumption or DHA were found among geographical provinces or stream size classes, nor among catchment basins for O2 consumption, but DHA was significantly higher in the other Atlantic (non-Chesapeake Bay) catchment basins. 5. Canonical correlation analyses generated two environmental axes. The stronger canonical axis (W1) represented a chemical disturbance gradient that was negatively correlated with signatures of anthropogenic impacts (ANC, Cl–, pH, SO42), and positively correlated with riparian canopy cover and stream water dissolved organic carbon concentration (DOC). A weaker canonical axis (W2) was postively correlated with pH, riparian zone agriculture, and stream depth, and negatively correlated with DOC and elevation of the stream. Oxygen consumption was significantly correlated with W2 whereas DHA was significantly correlated with W1. 6. The strengths of the correlations of DHA with environmental variables, particularly those that are proven indicators of catchment disturbances and with the canonical axis, suggest that DHA is a more responsive measure of benthic microbial activity than is O2 consumption. [ABSTRACT FROM AUTHOR]

Antioxidant metabolism has been examined in red spruce growing at two sites with similar levels of ozone pollution but different winter temperatures. The northern site was Whiteface Mountain, New York with a latitude of 44° 31' (NY). The southern site was Whitetop Mountain, Virginia with a latitude of 30° 54' (VA). The northern site has lower winter temperatures. At the NY site two populations of trees were defined with respect to cold tolerance. An effort was made to establish a temporal relationship between the antioxidant capacity of conifer needles on one hand and the different stages of winter hardening/dehardening, and the induction of dormancy, on the other. The hypothesis tested was that winter injury of red spruce was due to an increased demand for glutathione at levels exceeding the inherent capacity of the needles and/or the altered activities of glutathione reductase. In the autumn, as temperatures began to decrease, photosynthetic potential decreased as spruce entered dormancy. At the same time, cold tolerance (measured as needle electrolyte leakage) gradually increased. Glutathione metabolism appeared to be coupled to these processes. At both sites, seasonal changes in glutathione levels were observed. These changes were found to coincide temporally with the onset and cessation of dormancy (as measured by decline in photosynthetic activity). The same pattern was observed at the northern and the southern site with the winter increases being greater at the former. Glutathione began to increase as soon as needles entered dormancy and began hardening. Glutathione reductase activities closely followed the dehardening process during spring, while glutathione concentration continued to stay relativeIy high with prehardening levels reached only by summer. At the northern site during the winter, cold-tolerant trees had significantly higher glutathione reductase activities compared with cold-sensitive ones. Based on these data, it is proposed that individuals that cannot respond to the increased demand for glutathione reductase activity during the hardening, winter and dehardening periods, become susceptible to winter injury. [ABSTRACT FROM AUTHOR]

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and "morning sickness" anti-nausea medication targeting pregnant women in the 1950's. The "thalidomide babies" became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients). Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of "social responsibility" allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines. The primary reason? It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction. It is known that mitochondrial uncouplers specifically target the entire organelle's physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca2+) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca2+ overload. There is evidence that elevation of isoprostanes precedes disease onset, in Alzheimer's Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS). Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair? If ROS production were managed, could disease onset due to aging be delayed or prevented? Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction? Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight neutral doses. DNP will be addressed as a treatment for "metabesity", an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP's induction of neurotrophic growth factors involved in neuronal heath, learning and cognition. For the first time in 80's years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans. Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI). [ABSTRACT FROM AUTHOR]

Presents an abstract on what acetogens do in the laboratory versus elsewhere taken from the Art of Anaerobes Conference last August 15-16, 1996 at Athens, Georgia. How acetogenic bacteria can produce copious amounts of acetate concommitant to growth.

Investigates the role of bacteria in removing arsenic from an aqueous environment in the U.S. Occurrence of arsenic in rocks; Level of arsenic concentrations in groundwater in the country; Assessment of the effectiveness of biological processes for arsenite oxidation.

Provides a graph showing the percentage of cancer deaths in the U.S. attributable to smoking in 1995-1999.

Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.