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Article ; Online: Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage.

Bass, Alexandrea / Liu, Yiran / Dakshanamurthy, Sivanesan

2021 Volume 13, Issue 12

Abstract: The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell ...

Abstract	The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients' organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.
MeSH term(s)	COVID-19/genetics ; COVID-19/immunology ; Cytokine Release Syndrome ; Cytokines/genetics ; Cytokines/immunology ; Fibrosis/immunology ; Gene Expression ; Humans ; Immunity, Innate ; Inflammation/immunology ; Lung/immunology ; SARS-CoV-2 ; Sequence Analysis, RNA ; Severity of Illness Index ; Single-Cell Analysis
Chemical Substances	Cytokines
Language	English
Publishing date	2021-12-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13122418
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage

Bass, Alexandrea / Liu, Yiran / Dakshanamurthy, Sivanesan

Viruses. 2021 Dec. 02, v. 13, no. 12

2021

Abstract: The SARS-CoV-2 virus’s ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell ...

Abstract	The SARS-CoV-2 virus’s ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients’ organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; fibrosis ; hypertrophy ; inflammation ; innate immunity ; interleukin-17 ; interleukin-2 ; interleukin-6 ; interleukin-8 ; therapeutics ; viruses
Language	English
Dates of publication	2021-1202
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13122418
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Transposon accumulation at xenobiotic gene family loci in aphids.

Baril, Tobias / Pym, Adam / Bass, Chris / Hayward, Alex

Genome research

2023 Volume 33, Issue 10, Page(s) 1718–1733

Abstract: The evolution of resistance is a major challenge for the sustainable control of pests and pathogens. Thus, a deeper understanding of the evolutionary and genomic mechanisms underpinning resistance evolution is required to safeguard health and food ... ...

Abstract	The evolution of resistance is a major challenge for the sustainable control of pests and pathogens. Thus, a deeper understanding of the evolutionary and genomic mechanisms underpinning resistance evolution is required to safeguard health and food production. Several studies have implicated transposable elements (TEs) in xenobiotic-resistance evolution in insects. However, analyses are generally restricted to one insect species and/or one or a few xenobiotic gene families (XGFs). We examine evidence for TE accumulation at XGFs by performing a comparative genomic analysis across 20 aphid genomes, considering major subsets of XGFs involved in metabolic resistance to insecticides: cytochrome P450s, glutathione
MeSH term(s)	Animals ; Aphids/genetics ; Xenobiotics ; Insecticides ; DNA Transposable Elements/genetics ; Genomics
Chemical Substances	Xenobiotics ; Insecticides ; DNA Transposable Elements
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.277820.123
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Article ; Online: Aridification of Colorado River Basin's Snowpack Regions Has Driven Water Losses Despite Ameliorating Effects of Vegetation

Bass, Benjamin / Goldenson, Naomi / Rahimi, Stefan / Hall, Alex

Water Resources Research. 2023 July, v. 59, no. 7 p.e2022WR033454-

2023

Abstract: The Colorado River Basin is an important natural resource for the semi‐arid southwestern United States (US), where it provides water to more than 40 million people. While nearly 1.5°C of anthropogenic warming has occurred across this region from the ... ...

Abstract	The Colorado River Basin is an important natural resource for the semi‐arid southwestern United States (US), where it provides water to more than 40 million people. While nearly 1.5°C of anthropogenic warming has occurred across this region from the 1880s to 2021, climate models show little agreement in the precipitation change during the same historical period, with no trend in the mean of the latest (sixth) generation of Global Climate Models. As such, here we focus on how the CO₂ increase and associated anthropogenic warming over the historical period has impacted runoff across the Colorado Basin. We find that the Colorado Basin's runoff over the historical period has decreased by 8.1% per degree Celsius of warming (°C⁻¹). However, the magnitude of this sensitivity is reduced to 6.8% °C⁻¹ when considering vegetation response to historical CO₂. For present‐day conditions, this translates to runoff reductions of 10.3% due to anthropogenic increases in both temperature and CO₂ since 1880. We demonstrate that Colorado Basin's natural flow has been decreased by roughly the storage of Lake Mead during the 2000–2021 megadrought due to this long term anthropogenic influence, suggesting the basin's first shortage in 2021 would likely not have occurred without anthropogenic warming. We further show warming has led to disproportionate aridification in snowpack regions, causing runoff to decline at double the rate relative to non‐snowpack regions. Thus, despite only making up ∼30% of the basin's drainage area, 86% of runoff decreases in the Colorado Basin is driven by water loss in snowpack regions.
Keywords	anthropogenic activities ; basins ; carbon dioxide ; climate ; drainage ; research ; runoff ; snowpack ; temperature ; vegetation ; watersheds ; Colorado ; Colorado River ; Lake Mead
Language	English
Dates of publication	2023-07
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	5564-5
ISSN	1944-7973 ; 0043-1397
ISSN (online)	1944-7973
ISSN	0043-1397
DOI	10.1029/2022WR033454
Database	NAL-Catalogue (AGRICOLA)

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Article: Subdural hematoma expansion in relation to measured mean and peak systolic blood pressure: A retrospective analysis.

Plowman, Keegan / Lindner, David / Valle-Giler, Edison / Ashkin, Alex / Bass, Jessica / Ruthman, Carl

Frontiers in neurology

2022 Volume 13, Page(s) 1026471

Abstract: Objective: Subdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion ... ...

Abstract	Objective: Subdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging. Methods: A single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated. Results: We found that patients with mean SBP <140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140. Patients with peak SBP > 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220. Other risk factors did not contribute to hematoma expansion. Conclusions: These results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation.
Language	English
Publishing date	2022-10-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.1026471
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Article ; Online: Improving the Accuracy of Physics-Based Hydration-Free Energy Predictions by Machine Learning the Remaining Error Relative to the Experiment.

Bass, Lewis / Elder, Luke H / Folescu, Dan E / Forouzesh, Negin / Tolokh, Igor S / Karpatne, Anuj / Onufriev, Alexey V

Journal of chemical theory and computation

2023 Volume 20, Issue 1, Page(s) 396–410

Abstract: The accuracy of computational models of water is key to atomistic simulations of biomolecules. We propose a computationally efficient way to improve the accuracy of the prediction of hydration-free energies (HFEs) of small molecules: the remaining errors ...

Abstract	The accuracy of computational models of water is key to atomistic simulations of biomolecules. We propose a computationally efficient way to improve the accuracy of the prediction of hydration-free energies (HFEs) of small molecules: the remaining errors of the physics-based models relative to the experiment are predicted and mitigated by machine learning (ML) as a postprocessing step. Specifically, the trained graph convolutional neural network attempts to identify the "blind spots" in the physics-based model predictions, where the complex physics of aqueous solvation is poorly accounted for, and partially corrects for them. The strategy is explored for five classical solvent models representing various accuracy/speed trade-offs, from the fast analytical generalized Born (GB) to the popular TIP3P explicit solvent model; experimental HFEs of small neutral molecules from the FreeSolv set are used for the training and testing. For all of the models, the ML correction reduces the resulting root-mean-square error relative to the experiment for HFEs of small molecules, without significant overfitting and with negligible computational overhead. For example, on the test set, the relative accuracy improvement is 47% for the fast analytical GB, making it, after the ML correction, almost as accurate as uncorrected TIP3P. For the TIP3P model, the accuracy improvement is about 39%, bringing the ML-corrected model's accuracy below the 1 kcal/mol threshold. In general, the relative benefit of the ML corrections is smaller for more accurate physics-based models, reaching the lower limit of about 20% relative accuracy gain compared with that of the physics-based treatment alone. The proposed strategy of using ML to learn the remaining error of physics-based models offers a distinct advantage over training ML alone directly on reference HFEs: it preserves the correct overall trend, even well outside of the training set.
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ISSN	1549-9626
ISSN (online)	1549-9626
DOI	10.1021/acs.jctc.3c00981
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Article: The Limits between Schizophrenia and Bipolar Disorder: What Do Magnetic Resonance Findings Tell Us?

Dobri, Mirona Letitia / Diaz, Alexandre Paim / Selvaraj, Sudhakar / Quevedo, Joao / Walss-Bass, Consuelo / Soares, Jair C / Sanches, Marsal

Behavioral sciences (Basel, Switzerland)

2022 Volume 12, Issue 3

Abstract: Schizophrenia and bipolar disorder, two of the most severe psychiatric illnesses, have historically been regarded as dichotomous entities but share many features of the premorbid course, clinical profile, genetic factors and treatment approaches. Studies ...

Abstract	Schizophrenia and bipolar disorder, two of the most severe psychiatric illnesses, have historically been regarded as dichotomous entities but share many features of the premorbid course, clinical profile, genetic factors and treatment approaches. Studies focusing on neuroimaging findings have received considerable attention, as they plead for an improved understanding of the brain regions involved in the pathophysiology of schizophrenia and bipolar disorder. In this review, we summarize the main magnetic resonance imaging findings in both disorders, aiming at exploring the neuroanatomical and functional similarities and differences between the two. The findings show that gray and white matter structural changes and functional dysconnectivity predominate in the frontal and limbic areas and the frontotemporal circuitry of the brain areas involved in the integration of executive, cognitive and affective functions, commonly affected in both disorders. Available evidence points to a considerable overlap in the affected regions between the two conditions, therefore possibly placing them at opposite ends of a psychosis continuum.
Language	English
Publishing date	2022-03-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651997-5
ISSN	2076-328X
ISSN	2076-328X
DOI	10.3390/bs12030078
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Article: Neuronal alterations in AKT isotype expression in schizophrenia.

Devine, Emily A / Imami, Ali S / Eby, Hunter / Hamoud, Abdul-Rizaq / Golchin, Hasti / Ryan, William / Sahay, Smita / Shedroff, Elizabeth A / Arvay, Taylen / Joyce, Alex W / Asah, Sophie M / Walss-Bass, Consuelo / O'Donovan, Sinead / McCullumsmith, Robert E

Research square

2024

Abstract: Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA ...

Abstract	Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of conical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3940448/v1
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Article: Racial Differences in Patient Satisfaction With the Hospital Experience Undergoing Primary Unilateral Hip and Knee Arthroplasty: A Retrospective Study.

Burke, Orett C / Gibbons, J Alex B / Do, Huong T / Y Lai, Emily / Bradford, Letitia / Bass, Anne R / Amen, Troy B / Russell, Linda A / Mehta, Bella / Parks, Michael / Figgie, Mark / Goodman, Susan

Arthroplasty today

2023 Volume 23, Page(s) 101212

Abstract: Background: Press Ganey (PG) inpatient survey is widely used to track patient satisfaction with the hospital experience. Our aim was to use the PG survey to determine if there are racial differences in overall hospital experience and perception of ... ...

Abstract	Background: Press Ganey (PG) inpatient survey is widely used to track patient satisfaction with the hospital experience. Our aim was to use the PG survey to determine if there are racial differences in overall hospital experience and perception of nurses and surgeons following hip and knee arthroplasty. Methods: We retrospectively analyzed Black and White patients from hip and knee arthroplasty registries from a single institution between July 2010 and February 2012. The overall assessment score for the hospital experience and perception of the nurse and surgeon questions from the PG inpatient survey were dichotomized as "not completely satisfied" or "completely satisfied". Multivariable logistic regression models were developed to determine the impact of race on the likelihood of being 'completely satisfied' in the hip and knee cohorts. Results: There were 2517 hip and 2114 knee patients who underwent surgery and completed the PG survey, of whom 3.9% were Black and 96.0% were White. Black patients were less likely to be completely satisfied with their hospital experience compared to White patients in the hip (odds ratio 0.62, confidence interval 0.39-1.00, Conclusions: We found that the PG Survey shows Black patients were less likely to be completely satisfied than White patients with the hospital experience, including their interactions with nurses and surgeons. More work is needed to understand this difference.
Language	English
Publishing date	2023-09-16
Publishing country	United States
Document type	Journal Article
ISSN	2352-3441
ISSN	2352-3441
DOI	10.1016/j.artd.2023.101212
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Article ; Online: Ten simple rules for partnering with K-12 teachers to support broader impact goals.

Warwick, Alexa R / Kolonich, Angela / Bass, Kristin M / Mead, Louise S / Reichsman, Frieda

PLoS computational biology

2020 Volume 16, Issue 10, Page(s) e1008225

Abstract: Contributing to broader impacts is an important aspect of scientific research. Engaging practicing K-12 teachers as part of a research project can be an effective approach for addressing broader impacts requirements of grants, while also advancing ... ...

Abstract	Contributing to broader impacts is an important aspect of scientific research. Engaging practicing K-12 teachers as part of a research project can be an effective approach for addressing broader impacts requirements of grants, while also advancing researcher and teacher professional growth. Our focus is on leveraging teachers' professional expertise to develop science education materials grounded in emerging scientific research. In this paper, we describe ten simple rules for planning, implementing, and evaluating teacher engagement to support the broader impact goals of your research project. These collaborations can lead to the development of instructional materials or activities for students in the classroom or provide science research opportunities for teachers. We share our successes and lessons learned while collaborating with high school biology teachers to create technology-based, instructional materials developed from basic biological research. The rules we describe are applicable across teacher partnerships at any grade level in that they emphasize eliciting and respecting teachers' professionalism and expertise.
MeSH term(s)	Biomedical Research/methods ; Biomedical Research/organization & administration ; Biomedical Research/standards ; Cooperative Behavior ; Humans ; Research Personnel ; School Teachers ; Science/education
Language	English
Publishing date	2020-10-01
Publishing country	United States
Document type	Editorial ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1008225
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