Winter storms in California's Sierra Nevada increase seasonal snowpack and provide critical water resources and hydropower for the state. Thus, the mechanisms influencing precipitation in this region ...have been the subject of research for decades. Previous studies suggest Asian dust enhances cloud ice and precipitation, whereas few studies consider biological aerosols as an important global source of ice nuclei (IN). Here, we show that dust and biological aerosols transported from as far as the Sahara were present in glaciated high-altitude clouds coincident with elevated IN concentrations and ice-induced precipitation. This study presents the first direct cloud and precipitation measurements showing that Saharan and Asian dust and biological aerosols probably serve as IN and play an important role in orographie precipitation processes over the western United States.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the ...treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40-MK-8666 binary complex reveals an induced-fit conformational coupling between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.
Full text
Available for:
IJS, NUK, SBMB, UL, UM, UPUK
Pacific salmon are a keystone resource in Alaska, generating annual revenues of well over ~US$500 million/year. Due to their anadromous life history, adult spawners distribute amongst thousands of ...streams, posing a huge management challenge. Currently, spawners are enumerated at just a few streams because of reliance on human counters and, rarely, sonar. The ability to detect organisms by shed tissue (environmental DNA, eDNA) promises a more efficient counting method. However, although eDNA correlates generally with local fish abundances, we do not know if eDNA can accurately enumerate salmon. Here we show that daily, and near‐daily, flow‐corrected eDNA rate closely tracks daily numbers of returning sockeye and coho spawners and outmigrating sockeye smolts. eDNA thus promises accurate and efficient enumeration, but to deliver the most robust numbers will need higher‐resolution stream‐flow data, at‐least‐daily sampling, and a focus on species with simple life histories, since shedding rate varies amongst jacks, juveniles, and adults.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Sea otters (
) and wolves (
) are two apex predators with strong and cascading effects on ecosystem structure and function. After decades of recovery from near extirpation, their ranges now overlap, ...allowing sea otters and wolves to interact for the first time in the scientific record. We intensively studied wolves during 2015 to 2021 in an island system colonized by sea otters in the 2000s and by wolves in 2013. After wolf colonization, we quantified shifts in foraging behavior with DNA metabarcoding of 689 wolf scats and stable isotope analyses, both revealing a dietary switch from Sitka black-tailed deer (
), the terrestrial in situ primary prey, to sea otters. Here we show an unexpected result of the reintroduction and restoration of sea otters, which became an abundant marine subsidy for wolves following population recovery. The availability of sea otters allowed wolves to persist and continue to reproduce, subsequently nearly eliminating deer. Genotypes from 390 wolf scats and telemetry data from 13 wolves confirmed island fidelity constituting one of the highest known wolf population densities and upending standardly accepted wolf density predictions based on ungulate abundance. Whereas marine subsidies in other systems are generally derived from lower trophic levels, here an apex nearshore predator became a key prey species and linked nearshore and terrestrial food webs in a recently deglaciated and rapidly changing ecosystem. These results underscore that species restoration may serve as an unanticipated nutrient pathway for recipient ecosystems even resulting in cross-boundary subsidy cascades.
Previous studies have shown that selection for starvation resistance in Drosophila melanogaster results in delayed eclosion and increased adult fat stores. It is assumed that these traits are caused ...by the starvation selection pressure, but its mechanism is unknown. We found that our starvation-selected (SS) population stores more fat during larval development and has extended larval development and pupal development time. Developmental checkpoints in the third instar associated with ecdysteroid hormone pulses are increasingly delayed. The delay in the late larval period seen in the SS population is indicative of reduced and delayed ecdysone signaling. An enzyme immunoassay for ecdysteroids (with greatest affinity to the metabolically active 20-hydroxyecdysone and the α-ecdysone precursor) confirmed that the SS population had reduced and delayed hormone production compared with that of fed control (FC) flies. Feeding third instar larvae on food supplemented with α-ecdysone partially rescued the developmental delay and reduced subsequent adult starvation resistance. This work suggests that starvation selection causes reduced and delayed production of ecdysteroids in the larval stage and affects the developmental delay phenotype that contributes to subsequent adult fat storage and starvation resistance.
Some vertebrate species have evolved means of extending their visual sensitivity beyond the range of human vision. One mechanism of enhancing sensitivity to long-wavelength light is to replace the ...11-cis retinal chromophore in photopigments with 11-cis 3,4-didehydroretinal. Despite over a century of research on this topic, the enzymatic basis of this perceptual switch remains unknown. Here, we show that a cytochrome P450 family member, Cyp27c1, mediates this switch by converting vitamin A1 (the precursor of 11-cis retinal) into vitamin A2 (the precursor of 11-cis 3,4-didehydroretinal). Knockout of cyp27c1 in zebrafish abrogates production of vitamin A2, eliminating the animal’s ability to red-shift its photoreceptor spectral sensitivity and reducing its ability to see and respond to near-infrared light. Thus, the expression of a single enzyme mediates dynamic spectral tuning of the entire visual system by controlling the balance of vitamin A1 and A2 in the eye.
Display omitted
•Vitamin A2 and cyp27c1 expression are correlated in bullfrog and zebrafish•Cyp27c1 is sufficient to convert vitamin A1 into vitamin A2 in vitro•Cyp27c1 is necessary for A2 production and red-shifted photosensitivity in zebrafish•Cyp27c1 is necessary in zebrafish for enhanced phototaxis toward far red light
The visual system of freshwater vertebrates contains vitamin A2, which shifts photoreceptor sensitivity to longer wavelengths. Enright et al. demonstrate that Cyp27c1 is responsible for producing vitamin A2 and show that the resulting red-shift in photoreceptor sensitivity is translated into an enhanced behavioral response to long-wavelength light.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Understanding how a pathogen can grow on different substrates and how this growth impacts its dispersal are critical to understanding the risks and control of emerging infectious diseases. ...Pseudogymnoascus destructans (Pd) causes white-nose syndrome (WNS) in many bat species and can persist in, and transmit from, the environment. We experimentally evaluated Pd growth on common substrates to better understand mechanisms of pathogen persistence, transmission and viability. We inoculated autoclaved guano, fresh guano, soil, and wood with live Pd fungus and evaluated (1) whether Pd grows or persists on each (2) if spores of the fungus remain viable 4 months after inoculation on each substrate, and (3) whether detection and quantitation of Pd on swabs is sensitive to the choice to two commonly used DNA extraction kits. After inoculating each substrate with 460,000 Pd spores, we collected ~ 0.20 g of guano and soil, and swabs from wood every 16 days for 64 days to quantify pathogen load through time using real-time qPCR. We detected Pd on all substrates over the course of the experiment. We observed a tenfold increase in pathogen loads on autoclaved guano and persistence but not growth in fresh guano. Pathogen loads increased marginally on wood but declined ~ 60-fold in soil. After four months, apparently viable spores were harvested from all substrates but germination did not occur from fresh guano. We additionally found that detection and quantitation of Pd from swabs of wood surfaces is sensitive to the DNA extraction method. The commonly used PrepMan Ultra Reagent protocol yielded substantially less DNA than did the QIAGEN DNeasy Blood and Tissue Kit. Notably the PrepMan Ultra Reagent failed to detect Pd in many wood swabs that were detected by QIAGEN and were subsequently found to contain substantial live conidia. Our results indicate that Pd can persist or even grow on common environmental substrates with results dependent on whether microbial competitors have been eliminated. Although we observed clear rapid declines in Pd on soil, viable spores were harvested four months after inoculation. These results suggest that environmental substrates and guano can in general serve as infectious environmental reservoirs due to long-term persistence, and even growth, of live Pd. This should inform management interventions to sanitize or modify structures to reduce transmission risk as well early detection rapid response (EDRR) planning.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Display omitted
Despite its widespread clinical use in load-bearing orthopedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface-porous ...PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer was 399.6±63.3μm thick and possessed a mean pore size of 279.9±31.6μm, strut spacing of 186.8±55.5μm, porosity of 67.3±3.1% and interconnectivity of 99.9±0.1%. Monotonic tensile tests showed that PEEK-SP preserved 73.9% of the strength (71.06±2.17MPa) and 73.4% of the elastic modulus (2.45±0.31GPa) of as-received, injection-molded PEEK. PEEK-SP further demonstrated a fatigue strength of 60.0MPa at one million cycles, preserving 73.4% of the fatigue resistance of injection-molded PEEK. Interfacial shear testing showed the pore layer shear strength to be 23.96±2.26MPa. An osseointegration model in the rat revealed substantial bone formation within the pore layer at 6 and 12weeks via microcomputed tomography and histological evaluation. Ingrown bone was more closely apposed to the pore wall and fibrous tissue growth was reduced in PEEK-SP when compared to non-porous PEEK controls. These results indicate that PEEK-SP could provide improved osseointegration while maintaining the structural integrity necessary for load-bearing orthopedic applications.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: In addition to lifestyle modifications, pharmacotherapy is often required to achieve glycemic goals. In clinical practice, optimal treatment is not consistently implemented, often due to ...inadequate adherence to recommended guidelines.
Objective: To demonstrate the impact of a pharmacist-led diabetes clinical intervention program.
Methods: A retrospective analysis using collected diabetes program clinical interventions from July 1, 2019 through December 31, 2019 was performed. Members at least 18 years of age enrolled in a prescription plan administered by the pharmacy benefit manager with the pharmacist-led diabetes program who attempted to obtain diabetes medications were included in the analysis. A diabetes specialist reviewed members that did not meet previously established clinical algorithm programmed into the adjudication platform. Total number of clinical interventions and type of clinical intervention were described using descriptive statistics.
Results: The diabetes specialist pharmacist reviewed a total of 85 interventions. Out of these interventions, approximately 34% did not require additional clinical information from the provider and the medication adjudicated. Of the remaining interventions, providers accepted 75% of the recommendations: 30% “Medication changed to cost-effective therapeutic equivalent”, 27% “Medication discontinued”, 9% “New medication initiated”, and the remaining categories included “Medication dose decreased”, “Medication dose increased”, and “Medication dosing interval increased.”
Conclusion: The diabetes specialist pharmacist intervened to promote adherence to ADA guidelines and educate providers on patient specific factors such as medication adherence, polypharmacy, gaps-in-care, and financial considerations. Providers accepted recommendations 75% of the time, demonstrating willingness to collaborate with other clinicians to ensure optimal patient care.
Disclosure
J.M. Banks: None. P. Taddei-Allen: Advisory Panel; Self; Novo Nordisk A/S.
Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the ...monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
