SEARCH · Engineering Papers

Results for “PATHOLOGY”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18

All sources NASA NTRS DOE OSTI

DOE OSTI2023

Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats

Long-duration space exploratory missions to the Earth’s moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Five key aspects of metaproteomics as a tool to understand functional interactions in host-associated microbiomes

Host-associated microbial communities (microbiomes) play critical roles in human, animal, and plant health and development. However, interactions between the host, members of the microbiome, and invading pathogens are in most cases still poorly understood. Such interactions are multidimensional and can alter the taxonomic composition and/or the functional metabolic activities of the microbiome in response to disease or treatment conditions. For example, after 2 days of antibiotic treatment, the mouse gut microbiome is altered and more susceptible to invasion by the pathogen Clostridioides difficile. Studies of these multidimensional interactions have been fueled by the ability to use high-throughput sequencing of phylogenetic marker genes to profile microbial community composition and shotgun metagenomics to profile functional potential. However, many protein-coding genes predicted from metagenomes are not necessarily expressed under a given condition, and thus, it is difficult to assess the activities and functional interactions in microbial communities based on DNA sequencing data alone. The physiological and pathological processes expressed in these communities under specific conditions are better reflected by the abundances of transcripts or proteins. In this Pearl, we provide a brief introduction to metaproteomics, which is a tool for the large-scale analysis of proteins in microbiomes that allows researchers to address a diversity of questions related to functions and interactions in microbiomes. The term “metaproteomics” was first used in 2004 for “the large-scale characterization of the entire protein complement of environmental microbiota at a given point in time”, and since then, a large array of metaproteomics approaches have been developed. Our objective in this Pearl is to highlight what we feel are 5 essential elements to be considered for a metaproteomics research campaign and to introduce nonexpert readers to the topic without going into too much technical detail.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Is Mini Beam Ready for Human Trials? Results of Randomized Study of Treating De-Novo Brain Tumors in Canines Using Linear Accelerator Generated Mini Beams

The main challenge in treating malignant brain neoplasms lies in eradicating the tumor while minimizing treatmentrelated damage. Conventional radiation treatments are associated with considerable side effects. Synchrotron generated micro-beam radiation (SMBRT) has shown to preserve brain architecture while killing tumor cells, however physical characteristics and limited facility access restrict its use. We have created a new clinical device which produces mini beams on a linear accelerator, to provide a new type of treatment called mini-beam radiation therapy (MBRT). The objective of this study is to compare the treatment outcomes of linear accelerator based MBRT versus standard radiation treatment (SRT), to evaluate the tumor response and the treatment-related changes in the normal brain with respect to each treatment type. Pet dogs with de-novo brain tumors were accrued for treatment. Dogs were randomized between standard fractionated stereotactic (9 Gy in 3 fractions) radiation treatment vs. a single fraction of MBRT (26 Gy mean dose). Dogs were monitored after treatment for clinical assessment and imaging. When the dogs were euthanized, a veterinary pathologist assessed the radiation changes and tumor response. We accrued 16 dogs, 8 dogs in each treatment arm. In the MBRT arm, 71% dogs achieved complete pathological remission. The radiation-related changes were all confined to the target region. Structural damage was not observed in the beam path outside of the target region. In contrast, none of the dogs in control group achieved remission and the treatment related damage was more extensive. Therapeutic superiority was observed with MBRT, including both tumor control and the normal structural preservation. The MBRT findings are suggestive of an immune related mechanism which is absent in standard treatment. These findings together with the widespread availability of clinical linear accelerators make MBRT a promising research topic to explore further treatment and clinical trial opportunities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2020

Development of the finite slab geometry in the NORA code

In this work we develop the complete linearization formalism for the radiation transfer equation in slab geometry. This development was motivated by an observed convergence instability arising from the NORA code’s inner boundary while modeling a suite of simple test problems in slab geometry presented at the Line Transfer Workshop held in LLNL in May of 2019. The convergence issue was seen to emerge early on in Newton-Raphson iterations. These test problems required parameters in the former NORA inner boundary to achieve the asymptotic limit of zero incoming intensity. In this work we derive the limiting case directly to gain insight into the former algorithm’s pathology.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2020

Blunt Impact Brain Injury using Cellular Injury Criterion

The Advanced Combat Helmet (\ACH") military specification (\mil-spec") requires a helmeted magnesium (\Mg") Department of Transportation (\DOT") headform be dropped vertically, with an impact speed of 3.1 m/s (10 ft/s), onto a steel hemispherical target. The pass/fail criteria are based on translational acceleration (150 G) alone, absent of any rotational component. Without a rotational component, the specification's injury risk application is limited to skull fracture and peripheral hematomas (subdural, subarachnoid), since this translational acceleration injury risk assessment is based on the Wayne State Tolerance Curve (\WSTC"). To provide a more comprehensive view of injury for the entire brain, an alternative approach is needed. To meet this need, we worked with a larger group called PANTHER, a collaboration between national laboratories, industry, and academia. Collaborations specific to research and results presented here come from efforts led by Mr. Ron Szalkowski and Mr. Sushant Malave, Ms. Alice Fawzi, and Dr. Christian Franck. We have developed a prototypical injury risk criterion based on the neuronal response to abrupt changes in general motion (translation, rotation, or both). The cellular-based mild traumatic brain injury (\cbmTBI") criterion utilizes both the strain and strain rate of brain tissue to account for the stretch and rate of stretch that occurs throughout the brain as a result of blunt impact to the head. We conducted physical experiments of an ACH-fitted magnesium headform, which produced repeatable headform peak accelerations. Then, we developed a simulation of the experiment, and validated the simulation output with the experimental data. We then substituted the magnesium headform with a human headform, consisting of skin, muscle, bone, gray matter, white matter, cerebral-spinal fluid, membranes, vasculature, intravertebral discs, airway and sinus. We quantified brain injury risk using the cbmTBI criterion, using the current mil-spec test and a modified test. The modified mil-spec test used an inclined anvil target that was located posterior to the crown of the helmet in the axial plane. While the current mil-spec test produced brain deformation from head translation alone, the modified test produced brain deformation from head translation and rotation, which is closer to most real world and combat theater impacts (e.g., such as occur in tertiary blast exposure). Compared to the current mil-spec test, the modified test produced elevated strains in the human digital twin. These data, mapped to the cbmTBI criterion, suggest increased injury risk for blunt impacts that cause rotation and translation, rather than just translation alone. Moreover, these data may lead to a rotational performance metric, which is rooted in the biology and pathology of the brain's response to impact and blast, and which should be used to improve next-generation helmet designs.

42 ENGINEERING↗

DOE OSTI2021

LLNLs Neurotechnology Portfolio Presentation to Society for Brain Mapping and Therapeutics (SBMT) [Slides]

Lawrence Livermore National Laboratory has a long history in Bioengineering. They developed the first-ever bionic eye, as one example given. LLNL works in the Electroceuticals area. ELECTROnic pharmaCEUTICAL: Bioelectronic devices designed to stimulate electrically active tissues to affect biological systems in such a fashion as to alleviate or mitigate symptomatology and/or pathology. The market outlook in the Brain Computer Interface (BCI) area is discussed, as is Polymeric Opto-Electro-Mechanical Systems (POEMS). The presentation ends with iCHIP and Tissue Research topics.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Cineradiography System and Initial 3D-printed Brain Phantoms

Traumatic brain injury (TBI) is a significant cause of death in tactical, sport and civilian populations. According to the Center for Disease Control (CDC) report in 2016, TBI accounted for 227,000 hospitalizations and 60,000 related deaths. In the military, the prevalence of traumatic brain injuries is related to the type of conflict U.S. forces are involved in and are typically classified as mild traumatic brain injuries (mTBIs). Troops returning from Operation Enduring Freedom and Operation Iraqi Freedom had a TBI rate estimated at 15.2% to 22.8%; nearly 320,000 troops. These mTBIs were primarily blast-induced and often lacked any accompanying symptoms. Left untreated, these mild injuries have been linked to chronic disorders and cognitive alterations. One such disorder that has been frequently recorded in literature is chronic traumatic encephalopathy (CTE). CTE is a progressive neurodegenerative tauopathy resulting from repetitive mTBIs. The repetitive head injuries involved in sport, classified as mTBIs, has resulted in CTE development in athletes involved in contact sports. While the association between mTBIs and CTE has been pathologically verified, the mechanisms have yet to be identified. In order to better understand these mechanisms, the use of flash x-ray radiography is being considered.

42 ENGINEERING↗

DOE OSTI2022

High throughput single cell multiomics platform [Abstract]

In this collaborative project, PNNL and Scienion will co-develop an integrated microfluidic technology to co-measure the transcriptome and proteome in single cells. The technology will enable us to efficiently separate proteins from mRNA transcripts between two microchips, barcode the molecules, and measure them separately with next-generation sequencing and mass spectrometry, respectively. Multicellular organisms contain diverse cell types and tremendous cell-to-cell heterogeneity that dictates a multitude of biological functions in both physiological and pathological environments. Even in the case of microbes, these genetically identical organisms can randomly differentiate into many subpopulations that assume different roles for the survival of the community. Bulk-scale measurements are insufficient to resolve such complexities. The development and applications of high throughput single-cell omics technologies have transformed our understanding of cellular heterogeneities and their differential responses to internal signaling events or external stimulations. Despite these advances, most current single-cell omic technologies provide information on only one type of biomolecule. Perse, such measurements provide incomplete information because the cell phenotype is determined by multiple layers of biomolecules and the interplay between genome, epigenome, transcriptome, and proteome. For example, mRNA abundance in one cell can not be precisely referred to the corresponding DNA and protein in other cells because of the potential subtle difference in genotype (e.g., somatic mutation or copy number variation) or phenotype (external microenvironment and cell-cell interactions). As such, parallel measurement of multiple biomolecules in the same single cells can offer unique advantages compared with measuring them separately in different single cells. Scienion is a world-leading biotech company focusing on precision liquid handling and its application in single-cell whole-genome sequencing and RNA sequencing. PNNL is the leading institution in ultrasensitive mass spectrometry, microfluidics, and untargeted single-cell proteomics (scProteomics). This collaboration will facilitate a unique fusion between scTranscriptomics capability at Scienion and scProteomics capabilities at PNNL to, for the first time, perform both untargeted transcriptomics and proteomics from the same single cells.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Optical Microsystems for Molecular Sensing (CRADA Final Report)

As part of the Cyclotron Road program, NuSight Photonics sought to implement and investigate an optical Raman spectroscopy instrument for material and molecular analysis. Raman spectroscopy is widely used for quick and non-invasive material measurement when accurate results are needed – e.g., for monitoring manufacturing process in pharmaceutical plants, or identifying illicit substances and explosives by Law Enforcement. This technique is also growing rapidly in popularity as it is applied successfully to a broad range of applications, from pathology and non-invasive early cancer detection, to food and drug safety. The biggest challenge for Raman spectroscopy to achieve its full potential is the hardware cost, ranging from $\$ $25k to $\$ $250k, with the lower cost solutions significantly limited in sensitivity—or detection limit. NuSight Photonics aimed to tackle this obstacle through a novel hardware approach: Swept-Source Raman Spectroscopy.

36 MATERIALS SCIENCE↗

DOE OSTI2025

CRCNS US-France Research Proposal: Collaborative Research: Encoding reward expectation in Drosophilia

The fruit fly Drosophila melanogaster has been a valuable model for investigating the genetic and neural bases that underlie learning and memory. Early and most current studies use basic behavior conditioning protocols to study learning in controlled laboratory settings. More recently, the ability to transgenically manipulate many of the brain neurons in the fruit fly with exquisite specificity, and the recent knowledge of the synaptic ‘connectome’ of the fruit fly brain, makes these animals almost unique as a comprehensive model for studies of learning, memory and motivated behavior. In fact, the connectome has revealed many types of new connections that had until now been overlooked. Within this context, the thesis of this proposal is that studies of learning and memory will be greatly enhanced by using more sophisticated means for evaluating memory representations, such as have been developed in vertebrates, and combining those studies with information from the connectome guided by computational modelling. We propose to push beyond the boundaries of existing conditioning protocols for fruit flies to investigate more complex memory representations. In particular, we will investigate the function of reinforcement pathways in relation to the absence of expected reinforcement. More specifically, we propose a series of experiments designed to investigate the memory representations in fruit flies when an expected consequence of a Conditioned Stimulus (CS) fails to occur. Although studies have evaluated how this failure can establish extinction memory for the CS, our studies will go beyond studying extinction. Specifically, we predict that in Drosophila when a CS is associated with a failed expectation of an appetitive food reinforcement it will acquire aversive value, and vice versa for a failed expectation of an aversive reinforcer. We combine these studies with manipulations of reinforcement pathways in the CNS inspired from the connectome, iteratively knitted in with established computational models. Intellectual Merit: The concept of reinforcement expectation and incentive contrast have been influential in the development of studies of associative learning in mammals. These questions are particularly challenging to answer in vertebrates because they require exquisite cellular, temporal, and genetic specificity of experimental manipulations. The recent development of work with identified neurons and their connectomes makes the larval and adult fly brains ripe as models for pushing our understanding of neural bases for these higher- order conditioning phenomena. Broader Impacts: Public health: These analyses and the conceptual framework of prediction error processing underlying them have a profound impact on our understanding of reinforcement-related behavior in humans, including monetary rewards and the mnemonic consequences of traumatic experiences, and for pathologies of the dopamine reinforcement system. Educational: This project will provide interdisciplinary training for postdoctoral researchers, Ph.D. and undergraduate students. The PIs will act as co-supervisors or mentors of students working in the different labs via face-to-face and internet-based technologies. We will also work with ASU’s award-winning Ask- A-Biologist program. This is an online science program designed to enrich the learning experiences of students of all ages and to provide classroom material for use by K-12 teachers. We will develop an extension of a game developed under a prior NSF award, and the new game will include modules to teach K-12 students about how insects learn. We will also integrate into the AAB site a program developed by a collaborator (B Gerber) at the Leibniz Institut für Neurobiologie, Magdeburg, and now in use in schools in Germany, to teach K-12 students how to train animals using the fruit fly larval learning paradigm. Underrepresented groups: All PIs will work with their university offices of Academic Diversity and Equal Opportunity for reaching underrepresented students.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Risks Associated with Sharing the MOSSAIC APIs

The MOSSAIC APIs contain two files which, in theory, could be used to discover information about the pathology report data from the SEER registries on which the AI models were trained. In this document, we explain the contents of these files and assess the associated risk. APPENDIX A contains a set of slides to aid in the dissemination of this information.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2025

LDRD 2024 Annual Report: Laboratory Directed Research and Development Program Activities

One fundamental question underlying all living organisms is the need to understand their hierarchical organizations and physical changes with the necessary spatial and temporal resolutions under physiological or pathological conditions. This is a multi-scale challenge requiring imaging from sub-nanometers to micrometers in a cellular context. While individual imaging techniques are available, there is a critical need to integrate them into a workflow capability. Our objective is to develop an integrated multi-disciplinary and multi-scale bioimaging capability at Brookhaven National Laboratory (BNL). The capability expands BNL’s existing facility operation program in bioimaging and positions BNL in a leadership position in bioimaging research. The capability also addresses the grand challenges of the Department of Energy (DOE) science programs for national bioenergy sustainability and security.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2023

Monitoring the readout temperature in the ICARUS TPC (2023 Italian Students Program Final Report)

Being a Liquid Argon Time Projection Chamber (LAr-TPC) detector, ICARUS exploits a series of three parallel wire planes to measure and collect the ionization charge coming from an event inside the active volume. The wires are read out by A2795 custom boards, arranged in crates located on top of the two liquid Argon vessels. Each board is provided with two temperature sensors that allow temperature monitoring while the experiment is running: this is key in order to ensure data reliability and maintain hardware in safe conditions. Moreover, temperature-related problems may force unplanned shutdowns that result in losing valuable time for the experiment to run. In this work we are discussing the characterization of the ICARUS TPC board temperatures and the system we implemented in order to monitor them effectively. Among the tools used, Grafana results in a valid application for both displaying temperature data and sending alerts to the shifters whenever a pathological situation occurs.

42 ENGINEERING↗

DOE OSTI2021

Altered ß-cell Prohormone Processing and Secretion in Type 1 Diabetes

Analysis of data from clinical cohorts and more recently from human pancreatic tissue, indicate that defects in prohormone processing are an early and persistent component of type 1 diabetes pathogenesis. In this Perspectives article, we review the current state of knowledge of alterations in islet prohormone expression and processing in type 1 diabetes, and consider the clinical impact of these findings. Lingering questions, including pathologic etiologies and consequences of altered prohormone expression and secretion in type 1 diabetes, and the natural history of circulating prohormone production in health and disease are considered. Finally, key steps required to move forward in this area are outlined, including longitudinal testing of relevant clinical populations, studies that probe the genetics of altered prohormone processing, the need for combined functional and histologic testing of human pancreatic tissues, continued interrogation of the intersection between prohormone processing and autoimmunity, and optimal assays or approaches for analysis. Successful resolution of these questions may offer the potential to use altered prohormone processing as a pathogenic anchor that can be used to cluster different endotypes enveloping a large set of variables, and inform therapeutic strategies aimed at personalized intervention in the natural history of type 1 diabetes.

Islets, Insulin, Proinsulin, Islet Amyloid Polypep↗

DOE OSTI2026

Human RNome Project draft human RNome sequence of GM12878, B-cell line, obtained by mass-spectrometry sequencing, long-read sequencing and short-read sequencing.

Here we report the first draft of the human RNome sequence, a reference map of RNA chemical modifications in a human B-cell line. RNA carries a diverse repertoire of chemical modifications that regulate gene expression, cellular function, and responses to physiological and pathological cues. Yet, unlike the genome, no reference map of RNA modifications is available for any human cell. To generate this resource, the Human RNome Project Consortium analyzed a shared RNA preparation from the well-characterized GM12878 B-cell line using short-read sequencing, long-read direct RNA sequencing, and mass spectrometry, generating more than 7.1 billion sequencing reads spanning approximately 1.2 trillion nucleotides. The resulting maps of the human RNome reveal that RNA modifications are organized according to function, transcript architecture, and cellular identity. Modifications concentrate at functional centers of ribosomal and transfer RNAs, follow the canonical topology of N6-methyladenosine in coding transcripts, and form coordinated hotspots in immune regulatory genes. This first reference human RNome provides a foundation for understanding how RNA chemistry shapes cellular identity, human disease, and the development of RNA-based therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Deep learning applications in visual data for benign and malignant hematologic conditions: a systematic review and visual glossary

Deep learning (DL) is a subdomain of artificial intelligence algorithms capable of automatically evaluating subtle graphical features to make highly accurate predictions, which was recently popularized in multiple imaging-related tasks. Because of its capabilities to analyze medical imaging such as radiology scans and digitized pathology specimens, DL has significant clinical potential as a diagnostic or prognostic tool. Coupled with rapidly increasing quantities of digital medical data, numerous novel research questions and clinical applications of DL within medicine have already been explored. Similarly, DL research and applications within hematology are rapidly emerging, although these are still largely in their infancy. Given the exponential rise of DL research for hematologic conditions, it is essential for the practising hematologist to be familiar with the broad concepts and pitfalls related to these new computational techniques. This narrative review provides a visual glossary for key deep learning principles, as well as a systematic review of published investigations within malignant and non-malignant hematologic conditions, organized by the different phases of clinical care. In order to assist the unfamiliar reader, this review highlights key portions of current literature and summarizes important considerations for the critical understanding of deep learning development and implementations in clinical practice.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Microscopic Visualization of Cell-Cell Adhesion Complexes at Micro and Nanoscale

Considerable progress has been made in our knowledge of the morphological and functional varieties of anchoring junctions. Cell-cell adhesion contacts consist of discrete junctional structures responsible for the mechanical coupling of cytoskeletons and allow the transmission of mechanical signals across the cell collective. The three main adhesion complexes are adherens junctions, tight junctions, and desmosomes. Microscopy has played a fundamental role in understanding these adhesion complexes on different levels in both physiological and pathological conditions. In this review, we discuss the main light and electron microscopy techniques used to unravel the structure and composition of the three cell-cell contacts in epithelial and endothelial cells. It functions as a guide to pick the appropriate imaging technique(s) for the adhesion complexes of interest. We also point out the latest techniques that have emerged. At the end, we discuss the problems investigators encounter during their cell-cell adhesion research using microscopic techniques.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Novel interaction interfaces mediate the interaction between the NEIL1 DNA glycosylase and mitochondrial transcription factor A

The maintenance of human mitochondrial DNA (mtDNA) is critical for proper cellular function as damage to mtDNA, if left unrepaired, can lead to a diverse array of pathologies. Of the pathways identified to participate in DNA repair within the mitochondria, base excision repair (BER) is the most extensively studied. Protein-protein interactions drive the step-by-step coordination required for the successful completion of this pathway and are important for crosstalk with other mitochondrial factors involved in genome maintenance. Human NEIL1 is one of seven DNA glycosylases that initiates BER in both the nuclear and mitochondrial compartments. In the current work, we scrutinized the interaction between NEIL1 and mitochondrial transcription factor A (TFAM), a protein that is essential for various aspects of mtDNA metabolism. We note, for the first time, that both the N- and C- terminal domains of NEIL1 interact with TFAM revealing a unique NEIL1 protein-binding interface. The interaction between the two proteins, as observed biochemically, appears to be transient and is most apparent at concentrations of low salt. The presence of DNA (or RNA) also positively influences the interaction between the two proteins, and molar mass estimates indicate that duplex DNA is required for complex formation at higher salt concentrations. Hydrogen deuterium exchange mass spectrometry data reveal that both proteins exchange less deuterium upon DNA binding, indicative of an interaction, and the addition of NEIL1 to the TFAM-DNA complex alters the interaction landscape. The transcriptional activity of TFAM appears to be independent of NEIL1 expression under normal cellular conditions, however, in the presence of DNA damage, we observe a significant reduction in the mRNA expression of TFAM-transcribed mitochondrial genes in the absence of NEIL1. Overall, our data indicate that the interaction between NEIL1 and TFAM can be modulated by local environment such as salt concentrations, protein availability, the presence of nucleic acids, as well as the presence of DNA damage.

59 BASIC BIOLOGICAL SCIENCES↗