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101 result(s) for "Higgins, Benjamin M."
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Novel Use of a Shark Model to Elicit Innate Behavioral Responses in Sea Turtles: Application to Bycatch Reduction in Commercial Fisheries
Sea turtle bycatch in commercial fisheries is a serious global problem. An estimated 250,000 loggerhead (Caretta caretta) and leatherback (Dermochelys coriacea) sea turtles are taken each year as incidental catch by the pelagic longline fishing industry. Studies have examined various deterrents for their potential to repel sea turtles from the vicinity of fishing operations; visual deterrents such as shark models/silhouettes and gillnet illumination have shown the most promise. However, given the difficulty of directly observing sea turtle behavior in the wild, laboratory trials are crucial for characterizing the sea turtle response to shark models. The present study examined the response of 42 captive-reared juvenile loggerhead sea turtles to a shark model in a controlled laboratory setting. Loggerheads exhibited defensive behavior toward the shark model, taking significantly more time to bite squid bait beneath the shark model than that for squid beneath a control object (sphere) and bare squid. Also, the turtles approached the shark model less often and exhibited more defensive carapace turns toward the shark model. Although the shark model in this study elicited avoidance behavior in loggerhead sea turtles, further research is needed to identify plausible applications, which would reduce sea turtle bycatch while maintaining target fish catch rates. It may be possible to develop a “Children's Day Koinobori kite” (a three-dimensional kite) in the shape of a shark that would unfurl and “fly” underwater and could possibly clip to main or float lines in commercial fisheries.
HEMATOLOGY AND PLASMA BIOCHEMISTRY ANALYTES IN FIVE AGE GROUPS OF IMMATURE, CAPTIVE-REARED LOGGERHEAD SEA TURTLES (CARETTA CARETTA)
Blood samples of 85 immature, apparently healthy, captive-reared loggerhead sea turtles (Caretta caretta) were analyzed for 13 hematologic variables and total solids of 5 age groups (8, 20, 32, 44, and 56 mo old) and for 20 plasma biochemical analytes of 4 age groups (20 to 56 mo old). Each individual turtle was sampled under similar conditions during a blood collection period of 3 days. Hematologic analytes included packed cell volume, white blood cell (WBC) counts, WBC estimates, and leukocyte differentials. Biochemical analysis included albumin, alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, blood urea nitrogen, calcium, chloride, cholesterol, creatine kinase, creatinine, gamma glutamyltransferase, globulins, glucose, phosphorous, potassium, sodium, total bilirubin, total protein, total solids, and uric acid. In due consideration of small sample size in all five age groups, the results of hematologic and biochemical analysis were used to determine ranges for these analytes and to compare values among consecutive age groups. Several significant differences in some hematologic and biochemical variables were identified and need to be considered in the interpretation of blood work of immature, growing sea turtles in human care.
Hematology and Plasma Biochemistry Analytes in Five Age Groups of Immature, Captive-Reared Loggergead Sea Turtles (Caretta caretta)
Blood samples of 85 immature, apparently healthy, captive-reared loggerhead sea turtles (Caretta caretta) were analyzed for 13 hematologic variables and total solids of 5 age groups (8, 20, 32, 44, and 56 mo old) and for 20 plasma biochemical analytes of 4 age groups (20 to 56 mo old). Each individual turtle was sampled under similar conditions during a blood collection period of 3 days. Hematologic analytes included packed cell volume, white blood cell (WBC) counts, WBC estimates, and leukocyte differentials. Biochemical analysis included albumin, alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, blood urea nitrogen, calcium, chloride, cholesterol, creatine kinase, creatinine, gamma glutamyltransferase, globulins, glucose, phosphorous, potassium, sodium, total bilirubin, total protein, total solids, and uric acid. In due consideration of small sample size in all five age groups, the results of hematologic and biochemical analysis were used to determine ranges for these analytes and to compare values among consecutive age groups. Several significant differences in some hematologic and biochemical variables were identified and need to be considered in the interpretation of blood work of immature, growing sea turtles in human care.
Guest Editorial: Research Needed to Develop an Improved Life-long Living Tag Applicable to Carapace Scutes of Emergent Hatchling Kemp's Ridley Sea Turtles
Caillouet and Higgins stress the need of research on the development of lifelong tags for Kemp's ridley sea turtles. Among things, they discuss the contributions made by John R. and Lupe P. Hendrickson on the development and testing of living tag autografts as lifelong marks for sea turtles. Moreover, the development of improved methods of creating living tags on emergent hatchling Kemp's ridley carapaces is long-term. The most practical use of improved living tags applied to emergent hatchlings would be to identify year-classes and nesting beach origins of adults, particularly adult females on nesting beaches and adult males near nesting beaches.
Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration
Mendelian randomisation (MR) studies allow a better understanding of the causal effects of modifiable exposures on health outcomes, but the published evidence is often hampered by inadequate reporting. Reporting guidelines help authors effectively communicate all critical information about what was done and what was found. STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomisation) assists authors in reporting their MR research clearly and transparently. Adopting STROBE-MR should help readers, reviewers, and journal editors evaluate the quality of published MR studies. This article explains the 20 items of the STROBE-MR checklist, along with their meaning and rationale, using terms defined in a glossary. Examples of transparent reporting are used for each item to illustrate best practices.
Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation
Directed differentiation of human pluripotent stem cells to kidney organoids brings the prospect of drug screening, disease modelling and the generation of tissue for renal replacement. Currently, these applications are hampered by organoid variability, nephron immaturity, low throughput and limited scale. Here, we apply extrusion-based three-dimensional cellular bioprinting to deliver rapid and high-throughput generation of kidney organoids with highly reproducible cell number and viability. We demonstrate that manual organoid generation can be replaced by 6- or 96-well organoid bioprinting and evaluate the relative toxicity of aminoglycosides as a proof of concept for drug testing. In addition, three-dimensional bioprinting enables precise manipulation of biophysical properties, including organoid size, cell number and conformation, with modification of organoid conformation substantially increasing nephron yield per starting cell number. This facilitates the manufacture of uniformly patterned kidney tissue sheets with functional proximal tubular segments. Hence, automated extrusion-based bioprinting for kidney organoid production delivers improvements in throughput, quality control, scale and structure, facilitating in vitro and in vivo applications of stem cell-derived human kidney tissue. Extrusion-based bioprinting has been shown to rapidly and reproducibly generate kidney organoids from a cell-only paste, with the number and maturation of functional units within the kidney tissue capable of being further improved by bioprinting tissue sheets.
Superabsorption of light via quantum engineering
Almost 60 years ago Dicke introduced the term superradiance to describe a signature quantum effect: N atoms can collectively emit light at a rate proportional to N 2 . Structures that superradiate must also have enhanced absorption, but the former always dominates in natural systems. Here we show that this restriction can be overcome by combining several well-established quantum control techniques. Our analytical and numerical calculations show that superabsorption can then be achieved and sustained in certain simple nanostructures, by trapping the system in a highly excited state through transition rate engineering. This opens the prospect of a new class of quantum nanotechnology with potential applications including photon detection and light-based power transmission. An array of quantum dots or a molecular ring structure could provide a suitable platform for an experimental demonstration. A quantum system that super-radiates must also exhibit enhanced absorption, but the former always dominates in natural systems. However, by invoking environmental quantum control techniques, Higgins et al. demonstrate that a system can exhibit quantum-enhanced light absorption.
Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism
Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification. Diet intervention is emerging as an option to improve cancer therapy. Here, the authors show that a diet with restrictive cysteine and methionine synergizes with a ferroptosis inducer to increase cell death and survival in glioma preclinical models.
Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein
Membrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multidrug efflux pump system from Escherichia coli , AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Here, we rationalize a mechanism of inhibition against the periplasmic adaptor protein, AcrA, using a combination of hydrogen/deuterium exchange mass spectrometry, cellular efflux assays, and molecular dynamics simulations. We define the structural dynamics of AcrA and find that an inhibitor can inflict long-range stabilisation across all four of its domains, whereas an interacting efflux substrate has minimal effect. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and αβ barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multidrug adaptor protein function which could be valuable for developing antimicrobial therapeutics. Multidrug efflux protein pumps are key players in bacterial antimicrobial resistance. Here, the authors show how dynamics of a periplasmic pump component can be targeted for efflux inhibition.
A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes
Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes. Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression.