Bridging the gap: pathway programs for inclusion and persistence in microbiology
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Engineering topics
Mukundan, Harshini
Publications and source records attributed to Mukundan, Harshini.
Community Input on the Need, Scope, and Development Roadmap of a Proposed National Virtual Biosecurity for Bioenergy Crops Center (NVBBCC)
Brookhaven National Laboratory (BNL) was awarded a pilot project in FY22 under the U.S. Department of Energy (DOE) Office of Science Biopreparedness Research Virtual Environment (BRaVE) initiative, to define research priorities, needs, and requirements for a national virtual center devoted to the biosecurity of bioenergy crops. The mission of the proposed center, referred to as the National Virtual Biosecurity for Bioenergy Crop Center (NVBBCC), would be to provide the scientific basis and tools to detect, characterize, model, and mitigate biothreats to bioenergy crops. This function will be essential to ensure the projected increased US reliance over the next few decades on key plant-based energy products, such as biojet fuel. The NVBBCC is envisioned as a distributed, virtual center with multiple national laboratories at its core to maximize the use of existing unique facilities and expertise across the DOE complex. A major goal of the pilot project was to develop a roadmap for establishing NVBBCC through a series of meetings to gather community input. A total of about 150 individuals, drawn from DOE laboratories, the USDA, academia, NIH, DHS and the private sector participated in six planning meetings held in FY23. Four of the meetings were focused on specific research topics (disease detection, dispersion and disease propagation, biomolecular characterization of plant-pathogen interaction, and mitigation strategies). These four meetings were followed by a meeting that focused on computational needs to support collaborative, data-intensive research within a distributed center as well as workforce development. A final meeting focused on establishing and maintaining preparedness within NVBBCC to respond to an emerging disease within bioenergy crops and how it would collaborate and coordinate with USDA and DHS.
09 BIOMASS FUELS↗
Correlating transcription and protein expression profiles of immune biomarkers following lipopolysaccharide exposure in lung epithelial cells
Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy. Immune signaling is regulated by the interplay between pathogen-derived molecules with host cells resulting in cellular expression changes. However, these cellular processes are often studied by the independent assessment of either the transcriptome or the proteome. Correlation between transcription and protein analysis is lacking in a variety of studies. In order to methodically evaluate the correlation between transcription and protein expression profiles associated with innate immune signaling, we measured cytokine and chemokine levels following exposure of human cells to the PAMP lipopolysaccharide (LPS) from the Gram-negative pathogen Pseudomonas aeruginosa . Expression of 84 messenger RNA (mRNA) transcripts and 69 proteins, including 35 overlapping targets, were measured in human lung epithelial cells. We evaluated 50 biological replicates to determine reproducibility of outcomes. Following pairwise normalization, 16 mRNA transcripts and 6 proteins were significantly upregulated following LPS exposure, while only five (CCL2, CSF3, CXCL5, CXCL8/IL8, and IL6) were upregulated in both transcriptomic and proteomic analysis. This lack of correlation between transcription and protein expression data may contribute to the discrepancy in the immune profiles reported in various studies. The use of multiomic assessments to achieve a systems-level understanding of immune signaling processes can result in the identification of host biomarker profiles for a variety of infectious diseases and facilitate countermeasure design and development.
59 BASIC BIOLOGICAL SCIENCES↗
Lipoprotein capture ELISA method for the sensitive detection of amphiphilic biomarkers
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Methods to capture proteomic and metabolomic signatures from cerebrospinal fluid and serum of healthy individuals
Discovery of reliable signatures for the empirical diagnosis of neurological diseases—both infectious and non-infectious—remains unrealized. One of the primary challenges encountered in such studies is the lack of a comprehensive database representative of a signature background that exists in healthy individuals, and against which an aberrant event can be assessed. For neurological insults and injuries, it is important to understand the normal profile in the neuronal (cerebrospinal fluid) and systemic fluids (e.g., blood). Here, we present the first comparative multi-omic human database of signatures derived from a population of 30 individuals (15 males, 15 females, 23–74 years) of serum and cerebrospinal fluid. In addition to empirical signatures, we also assigned common pathways between serum and CSF. Together, our findings provide a cohort against which aberrant signature profiles in individuals with neurological injuries/disease can be assessed—providing a pathway for comprehensive diagnostics and therapeutics discovery.
59 BASIC BIOLOGICAL SCIENCES↗
Comparing variability in diagnosis of upper respiratory tract infections in patients using syndromic, next generation sequencing, and PCR-based methods
Early and accurate diagnosis of respiratory pathogens and associated outbreaks can allow for the control of spread, epidemiological modeling, targeted treatment, and decision making–as is evident with the current COVID-19 pandemic. Many respiratory infections share common symptoms, making them difficult to diagnose using only syndromic presentation. Yet, with delays in getting reference laboratory tests and limited availability and poor sensitivity of point-of-care tests, syndromic diagnosis is the most-relied upon method in clinical practice today. Here, we examine the variability in diagnostic identification of respiratory infections during the annual infection cycle in northern New Mexico, by comparing syndromic diagnostics with polymerase chain reaction (PCR) and sequencing-based methods, with the goal of assessing gaps in our current ability to identify respiratory pathogens. Of 97 individuals that presented with symptoms of respiratory infection, only 23 were positive for at least one RNA virus, as confirmed by sequencing. Whereas influenza virus (n = 7) was expected during this infection cycle, we also observed coronavirus (n = 7), respiratory syncytial virus (n = 8), parainfluenza virus (n = 4), and human metapneumovirus (n = 1) in individuals with respiratory infection symptoms. Four patients were coinfected with two viruses. In 21 individuals that tested positive using PCR, RNA sequencing completely matched in only 12 (57%) of these individuals. Few individuals (37.1%) were diagnosed to have an upper respiratory tract infection or viral syndrome by syndromic diagnostics, and the type of virus could only be distinguished in one patient. Thus, current syndromic diagnostic approaches fail to accurately identify respiratory pathogens associated with infection and are not suited to capture emerging threats in an accurate fashion. We conclude there is a critical and urgent need for layered agnostic diagnostics to track known and unknown pathogens at the point of care to control future outbreaks.
60 APPLIED LIFE SCIENCES↗
Distinguishing viruses responsible for influenza-like illness
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review
Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others present with persistent symptoms that can cause disability, neuropsychological trauma, and even death. Understanding, diagnosing, and treating TBI is extremely complex for many reasons, including the variable biomechanics of head impact, differences in severity and location of injury, and individual patient characteristics. Because of these confounding factors, the development of reliable diagnostics and targeted treatments for brain injury remains elusive. We argue that the development of effective diagnostic and therapeutic strategies for TBI requires a deep understanding of human neurophysiology at the molecular level and that the framework of multiomics may provide some effective solutions for the diagnosis and treatment of this challenging condition. To this end, we present here a comprehensive review of TBI biomarker candidates from across the multiomic disciplines and compare them with known signatures associated with other neuropsychological conditions, including Alzheimer’s disease and Parkinson’s disease. We believe that this integrated view will facilitate a deeper understanding of the pathophysiology of TBI and its potential links to other neurological diseases.
60 APPLIED LIFE SCIENCES↗
Total Internal Reflection of Two Lasers in a Single Planar Optical Waveguide
Multiplex biomarker quantitation is ideal for tracking the progression of a disease, but sensitive, specific, and quantitative multiplex biosensing remains challenging. We achieved total internal reflection with two lasers in a single planar optical waveguide by coupling 532 nm laser light into the diffraction grating of a waveguide and 635 nm laser light directly into the thin film of the same waveguide. We confirmed that the evanescent fields generated in the waveguide can excite two fluorescent dyes (Alexa Fluor 532 and Alexa Fluor 647) held to the surface of the waveguide through biotin-streptavidin chemistry. This sensing concept holds significant potential as a platform for multiplex biomarker detection.
47 OTHER INSTRUMENTATION↗
Portable Waveguide-Based Optical Biosensor
Rapid, on-site diagnostics allow for timely intervention and response for warfighter support, environmental monitoring, and global health needs. Portable optical biosensors are being widely pursued as a means of achieving fieldable biosensing due to the potential speed and accuracy of optical detection. We recently developed the portable engineered analytic sensor with automated sampling (PEGASUS) with the goal of developing a fieldable, generalizable biosensing platform. Here, we detail the development of PEGASUS’s sensing hardware and use a test-bed system of identical sensing hardware and software to demonstrate detection of a fluorescent conjugate at 1 nM through biotin-streptavidin chemistry.
47 OTHER INSTRUMENTATION↗
What is Influenza-Like Illness?
Explore the source record for details and available documents.
Spencer, Julie Allison↗
Th IV –Desferrioxamine: characterization of a fluorescent bacterial probe
Diversifying our ability to guard against emerging pathogenic threats is essential for keeping pace with global health challenges, including those presented by drug-resistant bacteria. Some modern diagnostic and therapeutic innovations to address this challenge focus on targeting methods that exploit bacterial nutrient sequestration pathways, such as the desferrioxamine (DFO) siderophore used by Staphylococcus aureus (S. aureus) to sequester Fe III . Building on recent studies that have shown DFO to be a versatile vehicle for chemical delivery, we show proof-of-principle that the Fe III sequestration pathway can be used to deliver a potential radiotherapeutic. Our approach replaces the FeIII nutrient sequestered by H 4 DFO + with Th IV and made use of a common fluorophore, FITC, which we covalently bonded to DFO to provide a combinatorial probe for simultaneous chelation paired with imaging and spectroscopy, H 3 DFO_FITC. Combining insight provided from FITC-based imaging with characterization by NMR spectroscopy, we demonstrated that the fluorescent DFO_FITC conjugate retained the Th IV chelation properties of native H4DFO+. Fluorescence microscopy with both [Th(DFO_FITC)] and [Fe(DFO_FITC)] complexes showed similar uptake by S. aureus and increased intercellular accumulation as compared to the FITC and unchelated H 3 DFO_FITC controls. Collectively, these results demonstrate the potential for the newly developed H 3 DFO_FITC conjugate to be used as a targeting vector and bacterial imaging probe for S. aureus. The results presented within provide a framework to expand H 4 DFO + and H 3 DFO_FITC to relevant radiotherapeutics (like 227Th).
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗