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The genetic basis of adaptation to copper pollution in Drosophila melanogaster
Get PDFIntroduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations.
Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance.
Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance
What constitutes a community? A co-occurrence exploration of the Costa Rican avifauna
Get PDFThe concept of a “community” as a form of organization for natural biological systems is both widespread and widely accepted within the ecological and biological sciences. Communities have been defined as groups of organisms that interact in ways that denote interdependence between individuals and taxa (e.g. as defined by “food webs”) but they have also been defined as groups of co-occurring organisms that are assumed to interact by virtue of their shared spatiotemporal existence. The latter definition has been debated and challenged in the literature, with mounting evidence for co-occurrence being more indicative of coincident ecological niches in space and time rather than being evidence of ecological interaction or dependency. Using a dataset of 460 Costa Rican bird species divided into breeding and non-breeding season datasets, we empirically demonstrate the ways in which co-occurrence can create illusory communities based on similar occupied ecological niches and similar patterns of co-occurrence at different times of year. We discuss the importance of discerning coincidental co-occurrence from true ecological interactions that would manifest a true community, and further address the importance of differentiating communities of co-occurrence from communities of demonstrable ecological interaction. While co-occurrence is a necessary aspect of interspecific interactions, we discuss and demonstrate here that such co-occurrence does not make a community, nor should explicit patterns of co-occurrence be seen as evidence for evolutionarily important ecological interactions
Dynamic Fracture and Crack Arrest Toughness Evaluation of High-Performance Steel Used in Highway Bridges
Get PDFImpact energy tests are an efficient method of verifying adequate toughness of steel prior to it being put into service. Based on a multitude of historical correlations between impact energy and fracture toughness, minimum impact energy requirements that correspond to desired levels of fracture toughness are prescribed by steel bridge design specifications. Research characterizing the fracture behavior of grade 485 and 690 (70 and 100) high-performance steel utilized impact, fracture toughness, and crack arrest testing to verify adequate performance for bridge applications. Fracture toughness results from both quasi-static and dynamic stress intensity rate tests were analyzed using the most recently adopted master curve methodology. Both impact and fracture toughness tests indicated performance significantly greater than the minimum required by material specifications. Even at the AASHTO Zone III service temperature, which is significantly colder than prescribed test temperatures, minimum average impact energy requirements were greatly exceeded. All master curve reference temperatures, both for quasi-static and dynamic loading rates, were found to be colder than the Zone III minimum service temperature. Three correlations between impact energy and fracture toughness were evaluated and found to estimate reference temperatures that are conservative by 12 to 50 °C (22 to 90 °F) on average for the grades and specimen types tested. The evaluation of two reference temperature shifts intended to account for the loading rate was also performed and the results are discussed
A Simple Micromilled Microfluidic Impedance Cytometer with Vertical Parallel Electrodes for Cell Viability Analysis
Get PDFMicrofluidic impedance cytometry has been demonstrated as an effective platform for single cell analysis, taking advantage of microfabricated features and dielectric cell sensing methods. In this study, we present a simple microfluidic device to improve the sensitivity, accuracy, and throughput of single suspension cell viability analysis using vertical sidewall electrodes fabricated by a widely accessible negative manufacturing method. A microchannel milled through a 75 µm platinum wire, which was embedded into poly-methyl-methacrylate (PMMA), created a pair of parallel vertical sidewall platinum electrodes. Jurkat cells were interrogated in a custom low-conductivity buffer (1.2 ± 0.04 mS/cm) to reduce current leakage and increase device sensitivity. Confirmed by live/dead staining and electron microscopy, a single optimum excitation frequency of 2 MHz was identified at which live and dead cells were discriminated based on the disruption in the cell membrane associated with cell death. At this frequency, live cells were found to exhibit changes in the impedance phase with no appreciable change in magnitude, while dead cells displayed the opposite behavior. Correlated with video microscopy, a computational algorithm was created that could identify cell detection events and determine cell viability status by application of a mathematical correlation method
Ampicillin-induced seizures in a 4-month-old with bacterial meningitis: a case report
Get PDFA grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Seizure is a rare but documented adverse event associated with ampicillin, which is one of the most commonly used antibiotics used in pediatrics. We report a case of a 4-month-old male infant with Haemophilus influenzae type A meningitis that experienced recurrent tonic-clonic seizures, possibly secondary to ampicillin treatment. After ampicillin administration was withdrawn and antiepileptic agents were administered, the seizures resolved, improving the patient’s clinical status rapidly. This case report adds to the growing body of literature on ampicillin-induced seizures
Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model
Get PDFMolecular characterization of antibody immunity and human antibody discovery is mainly carried out using peripheral memory B cells, and occasionally plasmablasts, that express B cell receptors (BCRs) on their cell surface. Despite the importance of plasma cells (PCs) as the dominant source of circulating antibodies in serum, PCs are rarely utilized because they do not express surface BCRs and cannot be analyzed using antigen-based fluorescence-activated cell sorting. Here, we studied the antibodies encoded by the entire mature B cell populations, including PCs, and compared the antibody repertoires of bone marrow and spleen compartments elicited by immunization in a human immunoglobulin transgenic mouse strain. To circumvent prior technical limitations for analysis of plasma cells, we applied single-cell antibody heavy and light chain gene capture from the entire mature B cell repertoires followed by yeast display functional analysis using a cytokine as a model immunogen. We performed affinity-based sorting of antibody yeast display libraries and large-scale next-generation sequencing analyses to follow antibody lineage performance, with experimental validation of 76 monoclonal antibodies against the cytokine antigen that identified three antibodies with exquisite double-digit picomolar binding affinity. We observed that spleen B cell populations generated higher affinity antibodies compared to bone marrow PCs and that antigen-specific splenic B cells had higher average levels of somatic hypermutation. A degree of clonal overlap was also observed between bone marrow and spleen antibody repertoires, indicating common origins of certain clones across lymphoid compartments. These data demonstrate a new capacity to functionally analyze antigen-specific B cell populations of different lymphoid organs, including PCs, for high-affinity antibody discovery and detailed fundamental studies of antibody immunity
Post-ischemic reorganization of sensory responses in cerebral cortex
Get PDFIntroduction: Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response.
Methods: We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats’ forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation.
Results: Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex.
Discussion: The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption
Critical Non-Covalent Binding Intermediate for an Allosteric Covalent Inhibitor of SUMO E1
No full textThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry Letters, copyright © Copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jpclett.3c00253.Post-translational modifications by small ubiquitin-like modifiers (SUMOs) are dysregulated in many types of cancers. The SUMO E1 enzyme has recently been suggested as a new immuno-oncology target. COH000 was recently identified as a highly specific allosteric covalent inhibitor of SUMO E1. However, a marked discrepancy was found between the X-ray structure of the covalent COH000-bound SUMO E1 complex and the available structure–activity relationship (SAR) data of inhibitor analogues due to unresolved noncovalent protein–ligand interactions. Here, we have investigated noncovalent interactions between COH000 and SUMO E1 during inhibitor dissociation through novel Ligand Gaussian accelerated molecular dynamics (LiGaMD) simulations. Our simulations have identified a critical low-energy non-covalent binding intermediate conformation of COH000 that agreed excellently with published and new SAR data of the COH000 analogues, which were otherwise inconsistent with the X-ray structure. Altogether, our biochemical experiments and LiGaMD simulations have uncovered a critical non-covalent binding intermediate during allosteric inhibition of the SUMO E1 complex
First Report of Small Skeletal Fossils from the Upper Guojiaba Formation (Series 2, Cambrian), Southern Shaanxi, South China
Get PDFA small skeletal fossil assemblage is described for the first time from the bioclastic limestone interbeds of the siltstone-dominated Guojiaba Formation, southern Shaanxi, China. The carbonate-hosted fossils include brachiopods (Eohadrotreta zhujiahensis, Eohadrotreta zhenbaensis, Spinobolus sp., Kuangshanotreta malungensis, Kyrshabaktella sp., Lingulellotreta yuanshanensis, Eoobolus incipiens, and Eoobolus sp.), sphenothallids (Sphenothallus sp.), archaeocyaths (Robustocyathus sp. and Yukonocyathus sp.), bradoriids (Kunmingella douvillei), chancelloriids sclerites (Onychia sp., Allonnia sp., Diminia sp., Archiasterella pentactina, and Chancelloria cf. eros), echinoderm plates, fragments of trilobites (Eoredlichia sp.), and hyolithelminths. The discovery of archaeocyaths in the Guojiaba Formation significantly extends their stratigraphic range in South China from the early Tsanglangpuian at least to the late Chiungchussuan. Thus, the Guojiaba Formation now represents the lowest known stratigraphic horizon where archaeocyath fossils have been found in the southern Shaanxi area. The overall assemblage is most comparable, in terms of composition, to Small skeletal fossil (SSF) assemblages from the early Cambrian Chengjiang fauna recovered from the Yu’anshan Formation in eastern Yunnan Province. The existing position that the Guojiaba Formation is correlated with Stage 3 in Cambrian Series 2 is strongly upheld based on the fossil assemblage recovered in this study
Distinguishing academic science writing from humans or ChatGPT with over 99% accuracy using off-the-shelf machine learning tools
Get PDFChatGPT has enabled access to artificial intelligence (AI)-generated writing for the masses, initiating a culture shift in the way people work, learn, and write. The need to discriminate human writing from AI is now both critical and urgent. Addressing this need, we report a method for discriminating text generated by ChatGPT from (human) academic scientists, relying on prevalent and accessible supervised classification methods. The approach uses new features for discriminating (these) humans from AI; as examples, scientists write long paragraphs and have a penchant for equivocal language, frequently using words like “but,” “however,” and “although.” With a set of 20 features, we built a model that assigns the author, as human or AI, at over 99% accuracy. This strategy could be further adapted and developed by others with basic skills in supervised classification, enabling access to many highly accurate and targeted models for detecting AI usage in academic writing and beyond