Solving post-prandial reduction in performance by adaptive regurgitation in a freshwater fish

Foraging animals must balance benefits of food acquisition with costs induced by a post-prandial reduction in performance. Eating to satiation can lead to a reduction in locomotor and escape performance, which increases risk should a threat subsequently arises, but limiting feeding behaviour may be maladaptive if food intake is unnecessarily reduced in the prediction of threats that do not arise. The efficacy of the trade-off between continued and interrupted feeding therefore relies on information about the future risk, which is imperfect. Here, we find that black carp (Mylopharyngodon piceus) can balance this trade-off using an a posteriori strategy; by eating to satiation but regurgitating already ingested food when a threat arises. While degrees of satiation (DS) equal to or greater than 60% reduce elements of escape performance (turning angle, angular velocity, distance moved, linear velocity), at 40% DS or lower, performance in these tasks approaches levels comparable to that at 0% satiation. After experiencing a chasing event, we find that fish are able to regurgitate already ingested food, thereby changing the amount of food in their gastrointestinal tract to consistent levels that maintain high escape performance. Remarkably, regurgitation results in degrees of satiation between 40 and 60% DS, regardless of whether they had previously fed to 40, 60 or 100% DS. Using this response, fish are able to maximize food intake, but regurgitate extra food to maintain escape performance when they encounter a threat. This novel strategy may be effective for continual grazers and species with imperfect information about the level of threat in their environment.     

Secondary (iso)BAs cooperate with endogenous ligands to activate FXR under physiological and pathological conditions

IsoBAs, stereoisomers of primary and secondary BAs, are found in feces and plasma of human individuals. BA signaling via the nuclear receptor FXR is crucial for regulation of hepatic and intestinal physiology/pathophysiology. Aim: Investigate the ability of BA-stereoisomers to bind and modulate FXR under physiological/pathological conditions. Methods: Expression-profiling, luciferase-assays, fluorescence-based coactivator-association assays, administration of (iso)-BAs to WT and cholestatic mice. Results: Compared to CDCA/isoCDCA, administration of DCA/isoDCA, UDCA/isoUDCA only slightly increased mRNA expression of FXR target genes; the induction was more evident looking at pre-mRNAs. Notably, almost 50% of isoBAs were metabolized to 3-oxo-BAs within 4 h in cell-based assays, making it difficult to study their actions. FRET-based real-time monitoring of FXR activity revealed that isoCDCA>CDCA stimulated FXR, and isoDCA and isoUDCA allowed fully activated FXR to be re-stimulated by a second dose of GW4064. In vivo co-administration of a single dose of isoBAs followed by GW4064 cooperatively activated FXR, as did feeding of UDCA in a background of endogenous FXR ligands. However, in animals with biliary obstruction and concomitant loss of intestinal BAs, UDCA was unable to increase intestinal Fgf15. In contrast, mice with an impaired enterohepatic circulation of BAs (Asbt?/?, Ostα?/?), administration of UDCA was still able to induce ileal Fgf15 and repress hepatic BA-synthesis, arguing that UDCA is only effective in the presence of endogenous FXR ligands. Conclusion: Secondary (iso)BAs cooperatively activate FXR in the presence of endogenous BAs, which is important to consider in diseases linked to disturbances in BA enterohepatic cycling.     

SARS-CoV-2 tropism,entry, replication,and propagation: Considerations for drug discovery and development

Since the initial report of the novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally. While the effects of SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum of disease ranging from mild symptoms to severe respiratory distress, hospitalization, and mortality. There are no Food and Drug Administration (FDA)-approved treatments for COVID-19 aside from remdesivir; early efforts to identify efficacious therapeutics for COVID-19 have mainly focused on drug repurposing screens to identify compounds with antiviral activity against SARS-CoV-2 in cellular infection systems. These screens have yielded intriguing hits, but the use of nonhuman immortalized cell lines derived from non-pulmonary or gastrointestinal origins poses any number of questions in predicting the physiological and pathological relevance of these potential interventions. While our knowledge of this novel virus continues to evolve, our current understanding of the key molecular and cellular interactions involved in SARS-CoV-2 infection is discussed in order to provide a framework for developing the most appropriate in vitro toolbox to support current and future drug discovery efforts.     

Interrupted incubation: How dabbling ducks respond when flushed from the nest

Nesting birds must provide a thermal environment sufficient for egg development while also meeting self‐maintenance needs. Many birds, particularly those with uniparental incubation, achieve this balance through periodic incubation recesses, during which foraging and other self‐maintenance activities can occur. However, incubating birds may experience disturbances such as predator or human activity which interrupt natural incubation patterns by compelling them to leave the nest. We characterized incubating mallard Anas platyrhynchos and gadwall Mareca strepera hens’ responses when flushed by predators and investigators in Suisun Marsh, California, USA. Diurnal incubation recesses initiated by investigators approaching nests were 63% longer than natural diurnal incubation recesses initiated by the hen (geometric mean: 226.77 min versus 142.04 min). Nocturnal incubation recesses, many of which were likely the result of predators flushing hens, were of similar duration regardless of whether the nest was partially depredated during the event (115.33 [101.01;131.68] minutes) or not (119.62 [111.96;127.82] minutes), yet were 16% shorter than natural diurnal incubation recesses. Hens moved further from the nest during natural diurnal recesses or investigator‐initiated recesses than during nocturnal recesses, and the proportion of hen locations recorded in wetland versus upland habitat during recesses varied with recess type (model‐predicted means: natural diurnal recess 0.77; investigator‐initiated recess 0.82; nocturnal recess 0.31). Hens were more likely to take a natural recess following an investigator‐initiated recess earlier that same day than following a natural recess earlier that same day, and natural recesses that followed an investigator‐initiated recess were longer than natural recesses that followed an earlier natural recess, suggesting that hens may not fulfill all of their physiological needs during investigator‐initiated recesses. We found no evidence that the duration of investigator‐initiated recesses was influenced by repeated visits to the nest, whether by predators or by investigators, and trapping and handling the hen did not affect investigator‐initiated recess duration unless the hen was also fitted with a backpack‐harness style GPS–GSM transmitter at the time of capture. Hens that were captured and fitted with GPS–GSM transmitters took recesses that were 26% longer than recesses during which a hen was captured but a GPS–GSM transmitter was not attached. Incubation interruptions had measurable but limited and specific effects on hen behavior.     

Natural Infection of Burkholderia pseudomallei in an Imported Pigtail Macaque (Macaca nemestrina) and Management of the Exposed Colony

Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff.Abbreviations: CDC, Centers for Disease Control and Prevention; IHA, indirect hemagglutination assay; PEP, postexposure prophylacticBurkholderia pseudomallei, formerly known as Pseudomonas pseudomallei, is a gram-negative, aerobic, bipolar, motile, rod-shaped bacterium. B. pseudomallei infections (melioidosis) can be severe and even fatal in both humans and animals. This environmental saprophyte is endemic to Southeast Asia and northern Australia, but it has also been found in other tropical and subtropical areas of the world.^7,22,32,42 The bacterium is usually found in soil and water in endemic areas and is transmitted to humans and animals primarily through percutaneous inoculation, ingestion, or inhalation of a contaminated source.^{8, 22,28,32,42} Human-to-human, animal-to-animal, and animal-to-human spread are rare.^8,32 In December 2012, the National Select Agent Registry designated B. pseudomallei as a Tier 1 overlap select agent.³⁹ Organisms classified as Tier 1 agents present the highest risk of deliberate misuse, with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. Select agents with this status have the potential to pose a severe threat to human and animal health or safety or the ability to be used as a biologic weapon.³⁹Melioidosis in humans can be challenging to diagnose and treat because the organism can remain latent for years and is resistant to many antibiotics.^12,37,41 B. pseudomallei can survive in phagocytic cells, a phenomenon that may be associated with latent infections.^19,38 The incubation period in naturally infected animals ranges from 1 d to many years, but symptoms typically appear 2 to 4 wk after exposure.^13,17,35,38 Disease generally presents in 1 of 2 forms: localized infection or septicemia.²² Multiple methods are used to diagnose melioidosis, including immunofluorescence, serology, and PCR analysis, but isolation of the bacteria from blood, urine, sputum, throat swabs, abscesses, skin, or tissue lesions remains the ‘gold standard.’^9,22,40,42 The prognosis varies based on presentation, time to diagnosis, initiation of appropriate antimicrobial treatment, and underlying comorbidities.^7,28,42 Currently, there is no licensed vaccine to prevent melioidosis.There are several published reports of naturally occurring melioidosis in a variety of nonhuman primates (NHP; 2,10,13,17,25,30,31,35 The first reported case of melioidosis in monkeys was recorded in 1932, and the first published case in a macaque species was in 1966.³⁰ In the United States, there have only been 7 documented cases of NHP with B. pseudomallei infection.^2,13,17 All of these cases occurred prior to the classification of B. pseudomallei as a select agent. Clinical signs in NHP range from subclinical or subacute illness to acute septicemia, localized infection, and chronic infection. NHP with melioidosis can be asymptomatic or exhibit clinical signs such as anorexia, wasting, purulent drainage, subcutaneous abscesses, and other soft tissue lesions. Lymphadenitis, lameness, osteomyelitis, paralysis and other CNS signs have also been reported.^{2,7,10,22,28,32} In comparison, human''s clinical signs range from abscesses, skin ulceration, fever, headache, joint pain, and muscle tenderness to abdominal pain, anorexia, respiratory distress, seizures, and septicemia.^7,9,21,22

Table 1.

Summary of reported cases of naturally occurring Burkholderia pseudomalleiinfections in nonhuman primates

Simulated warming does not impair seedling survival and growth of Nothofagus pumilio in the southern Andes

It has been predicted that subalpine forests will be negatively affected by global warming; however, direct responses to experimental warming have been scarcely examined in these systems. In this study we evaluated the effects of higher temperatures with and without water addition on the survival and growth of recently emerged (small) and large seedlings of the widely distributed species Nothofagus pumilio in subalpine forests of the southern Chilean Andes. We also examined the variations in seedling traits related to carbon balance in order to infer the causal mechanisms of survival and growth responses. Treatments of open top chambers (OTCs) were combined with watering in two locations with differing climates: Antillanca (40°S, humid) and Cerro Castillo (46°S, drier). OTCs increased mean and maximum air temperatures by 0.6 °C and 2–3 °C, respectively, and decreased soil humidity by 56% in Antillanca and 30% in Cerro Castillo, fulfilling methodological expectations and climate model predictions. After two complete growing seasons, the survival, relative growth rate (RGR), biomass, and a suite of seedling traits were measured and analyzed using mixed-effects models. Warming and warming in combination with watering significantly increased large seedling survival in Cerro Castillo. In Antillanca, warmer conditions increased the height, biomass, and leaf area of small seedlings, and the RGR of large seedlings. In this location, warming also caused lower leaf carbon isotopic composition in both age classes and higher specific leaf area in small seedlings, suggesting whole-plant carbon gain improvements; warming did not produce any drought effects. Our results indicate that warming produces positive effects on the seedling establishment of N. pumilio in the southern Andes, highlighting the importance of site-specific effects in response to climate change in widespread species. Site-specific effects can most likely explain the discrepancies between the results of this study and the predictions outlined by previous studies for these forests.     

Of mast and mean: differential‐temperature cue makes mast seeding insensitive to climate change

Mast‐seeding plants often produce high seed crops the year after a warm spring or summer, but the warm‐temperature model has inconsistent predictive ability. Here, we show for 26 long‐term data sets from five plant families that the temperature difference between the two previous summers (ΔT) better predicts seed crops. This discovery explains how masting species tailor their flowering patterns to sites across altitudinal temperature gradients; predicts that masting will be unaffected by increasing mean temperatures under climate change; improves prediction of impacts on seed consumers; demonstrates that strongly masting species are hypersensitive to climate; explains the rarity of consecutive high‐seed years without invoking resource constraints; and generates hypotheses about physiological mechanisms in plants and insect seed predators. For plants, ΔT has many attributes of an ideal cue. This temperature‐difference model clarifies our understanding of mast seeding under environmental change, and could also be applied to other cues, such as rainfall.