Evaluation of a Single Nucleotide Polymorphism Baseline for Genetic Stock Identification of Chinook Salmon (Oncorhynchus tshawytscha) in the California Current Large Marine Ecosystem

Chinook Salmon (Oncorhynchus tshawytscha) is an economically and ecologically important species, and populations from the west coast of North America are a major component of fisheries in the North Pacific Ocean. The anadromous life history strategy of this species generates populations (or stocks) that typically are differentiated from neighboring populations. In many cases, it is desirable to discern the stock of origin of an individual fish or the stock composition of a mixed sample to monitor the stock-specific effects of anthropogenic impacts and alter management strategies accordingly. Genetic stock identification (GSI) provides such discrimination, and we describe here a novel GSI baseline composed of genotypes from more than 8000 individual fish from 69 distinct populations at 96 single nucleotide polymorphism (SNP) loci. The populations included in this baseline represent the likely sources for more than 99% of the salmon encountered in ocean fisheries of California and Oregon. This new genetic baseline permits GSI with the use of rapid and cost-effective SNP genotyping, and power analyses indicate that it provides very accurate identification of important stocks of Chinook Salmon. In an ocean fishery sample, GSI assignments of more than 1000 fish, with our baseline, were highly concordant (98.95%) at the reporting unit level with information from the physical tags recovered from the same fish. This SNP baseline represents an important advance in the technologies available to managers and researchers of this species

MTHFD1 controls DNA methylation in Arabidopsis.

DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases

Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

Objective The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. Methods We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10–14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario “Dr. Jose Eleuterio Gonzalez”. Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing. Results We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time. Conclusion The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors’ sample.Peer reviewedFinal Published versio

American Neurogastroenterology and Motility Society (ANMS) Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic

The ANMS organized a Task Force for developing guidance strategies regarding re-opening of motility laboratories. This document describes how to stratify urgency of motility physiologic procedures, screen prior to the procedures, optimize personal protective equipment (PPE) utilization, clean and prepare the motility laboratory space during the COVID-19 pandemic

Early Ocean Distribution of Juvenile Chinook Salmon in an Upwelling Ecosystem

Extreme variability in abundance of California salmon populations is often ascribed to ocean conditions, yet relatively little is known about their marine life-history. To investigate which ocean conditions influence their distribution and abundance, we surveyed juvenile Chinook salmon (Oncorhynchus tshawytscha) within the California Current (central California (37o 30’ N) to Newport, Oregon (44o 00’ N)) for a two-week period over three summers (2010-2012). At each station, we measured chlorophyll a as an indicator of primary productivity, acoustic-based metrics of zooplankton density as an indicator of potential prey availability, and physical characteristics such as bottom depth, temperature, and salinity. We also measured fork lengths and collected genetic samples from each salmon that was caught. Genetic stock identification revealed that the majority of juvenile salmon were from the Central Valley and the Klamath Basin (91-98%). We constructed generalized logistic-linear negative binomial hurdle models and chose the best model(s) using AIC to determine which covariates influenced salmon presence and, at locations where salmon were present, determined the variables that influenced their abundance. The probability of salmon presence was highest in shallower waters with high chlorophyll a concentration and close to an individual’s natal river. Catch abundance was primarily influenced by year, mean fork length, and proximity to natal rivers. At the scale of sampling stations, presence and abundance was not related to acoustic indices of zooplankton density. In the weeks to months following ocean entry, California’s juvenile Chinook salmon population appears to be primarily constrained to coastal waters near natal river outlets

Use of Genetic Stock Identification Data for Comparison of the Ocean Spatial Distribution, Size at Age, and Fishery Exposure of an Untagged Stock and Its Indicator: California Coastal versus Klamath River Chinook Salmon

Managing weak stocks in mixed-stock fisheries often relies on proxies derived from data-rich indicator stocks. For example, full cohort reconstruction of tagged Klamath River fall run Chinook salmon (Oncorhynchus tshawytscha) of northern California, USA, enables the use of detailed models to inform management. Information gained from this stock is also used in the management of the untagged, threatened California Coastal Chinook (CCC) salmon stock, by capping Klamath harvest rates. To evaluate use of this proxy, we used genetic stock identification (GSI) data to compare the two stocks\u27 size-at-age and ocean distribution, two key factors influencing fishery exposure. We developed methods to account for both sampling and genetic assignment uncertainty in catch estimates. We found that, in 2010, the stocks were similar in size-at-age early in the year (age-3 and age-4), but CCC fish were larger later in the year. The stocks appeared similarly distributed early in the year (2010), but more concentrated near their respective source rivers later in the year (2010 and 2011). If these results are representative, relative fishery impacts on the two stocks might scale similarly early in the year but management changes later in the year might have differing impacts on the two stocks

Neurobiological Mechanisms That Contribute to Stress-related Cocaine Use

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the bed nucleus of the stria terminalis to the VTA that is regulated by norepinephrine via actions at beta adrenergic receptors. In addition to the neurobiological mechanisms that underlie stress-induced cocaine seeking, we review findings suggesting that the ability of stressful stimuli to trigger cocaine use emerges and intensifies in an intake-dependent manner with repeated cocaine self-administration. Further, we discuss evidence that the drug-induced neuroadaptations that are necessary for heightened susceptibility to stress-induced drug use are reliant on elevated levels of glucocorticoid hormones at the time of cocaine use. Finally, the potential ability of stress to function as a “stage setter” for drug use – increasing sensitivity to cocaine and drug-associated cues – under conditions where it does not directly trigger cocaine seeking is discussed. As our understanding of the mechanisms through which stress promotes drug use advances, the hope is that so too will the available tools for effectively managing addiction, particularly in cocaine addicts whose drug use is stress-driven

Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

<p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq^®and Truview^®laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq^®and Truview^®laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan^®manikin.</p> <p>Results</p> <p>The Airtraq^®reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview^®increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq^®devices.</p> <p>Conclusion</p> <p>The Airtraq^®laryngoscope performed more favourably than the Macintosh and Truview^®devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p