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At least 109 records · Page 6

2-Methylhopanoids: Biomarkers for Cyanobacteria and for Oxygenic Photosynthesis

This paper reports new biomarker and carbon isotopic data for cultured cyanobacteria, cyano-bacterially- dominated ecosystems and ancient sedi-ments and petroleum. We found that cyanobacteria are the predominant source of a distinctive membrane lipid biomarker, namely 2- methylbacteriohopanepolyol (2-Me-BHP). We then sought evidence for a geochemical record of the fossil hydrocarbon analogues of these compounds (2- methylhopanes) and found a trend toward their in-creased relative abundance in marine sediments going back through geological time to 2500 Ma. We conclude that cyanobacteria were the dominant form of phytoplankton and source of molecular oxygen in the Proterozoic ocean. Extending the geological record of cyanobacteria further to Archean times is now a matter of finding a suitably preserved rock record. Additional information is contained in the original extended abstract.

Summons, R. E.↗

Biomarkers in ALH84001???

D. McKay and colleagues suggested that four sets of features in ALH84001 were biomarkers, signs of an ancient martian biota that once inhabited the meteorite. Subsequent work has not validated their hypothesis; each suggested biomarker has been found to be ambiguous or immaterial. Nor has their hypothesis been disproved. Rather, it is now one of many hypotheses about the alteration of ALH84001. Additional information is contained in the original extended abstract.

Treiman, Allen H.↗

A Structural and Molecular Approach for the Study Biomarkers

Investigation of the nucleation and growth of crystals in both abiotic and biotic systems is critical to seemingly diverse disciplines of geology, biology, environmental science, and astrobiology. While there are abundant studies devoted to the determination of the structure and composition of inorganic crystals, as well as to the development of thermodynamic and kinetic models, it is only recently that research efforts have been directed towards understanding mineralization in biological systems (i.e., biomineralization). Biomineralization refers to the processes by which living organisms form inorganic solids. Studies of the processes of biomineralization under low temperature aqueous conditions have focused primarily on magnetite forming bacteria and shell forming marine organisms. Many of the biological building materials consist of inorganic minerals (calcium carbonate, calcium phosphate, silica or iron oxide) intricately combined with organic polymers (like proteins). More recently, efforts have been undertaken to explore the nature of biological activities in ancient rocks. In the absence of well-preserved microorganisms or genetic material required for the polmerase chain reaction (PCR) method in molecular phylogenetic studies, using biominerals as biomarkers offers an alternative approach for the recognition of biogenic activity in both terrestrial and extraterrestrial environments. The primary driving force in biomineralization is the interaction between organic and inorganic phases. Thus, the investigation of the ultrastructure and the nature of reactions at the molecular level occurring at the interface between inorganic and organic phases is essential to understanding the processes leading to the nucleation and growth of crystals. It is recognized that crystal surfaces can serve as the substrate for the organization of organic molecules that lead to the formation of polymers and other complex organic molecules, and in discussions of the origins of life, is referred to as organic synthesis on mineral surfaces. Furthermore, it is suggested that the interaction between mineral surfaces and simple organic molecules resulted in the formation of amino acids, RNA, and perhaps other more complex molecules such as proteins. On the other hand, in natural systems, it is recognized that functional groups on cell walls or membranes of microorganisms serve as sites of nucleation and crystallization. The precise replication of biominerals with controlled structure, morphology, size and texture is not confined to higher organisms as it also occurs in primitive prokaryotic cells such as magnetotactic bacteria and cyanobacteria. This suggests that the principal strategies of biomineralization were established early on in the evolutionary history of organisms. It is critical, therefore, to search for common mechanisms within diverse biological systems. One such common factor is the capability for organization and self-assembly. Organic macromolecules such as proteins and lipids can aggregate and polymerize forming membranes or extracellular matrix. At the organic-inorganic interface, several factors such as lattice geometry, polarity, stereochemistry and topography may act in concert to control nucleation and growth of crystals. Although several models have been proposed that discuss the significance of these factors for biomineralization, no comprehensive experimental data are available. In contrast to crystallization in exclusively inorganic systems, the kinetics of reaction and structural relationships between organic and inorganic phases in biominerals or biomimetic material is poorly understood. For example, it is not clear if the concept of epitactic growth (geometrical matching of unit cells at the interface of a secondary crystal growing on a primary crystal) applies to organic-inorganic systems. In contrast to inorganic templates that often have a smooth and rigid surface that promotes epitactic growth, biological substrates are usually rough and result in a large degree of mismatch. It is apparent that factors controlling the reaction at the crystal-matrix interface are strongly dependent upon the nature of the substrate. Therefore, characterization of the assembled organic surface and surface structure of the inorganic phase is crucial to understanding the processes of biomineralization. The focus of our research is the investigation of the processes leading to the nucleation and growth of crystals on both natural and synthetic systems through an interdisciplinary approach that integrates molecular biology, morphology and mineralogy using advanced preparation and analytical techniques. We have studied run-products, particularly magnetite, siderite and other carbonates, that resulted from extracellular biomineralization by extremophiles isolated from a variety of extreme environments ranging from permafrost to hydrothermal vent systems. The results of this study are critical to recognizing biomarkers in terrestrial and extraterrestrial environments.

Thomas-Keprta, Kathie↗

Visualization of Microbial Biomarkers by Scanning Electron Microscopy

We are developing tools to link the biochemical structure of selected biomarkers with putative biogenic structures observed in mineralized samples. The detection of evidence of life on Mars and other planets will rely on methods that can discriminate compounds formed exclusively by living organisms. While biogenic compounds, such as amino acids and nucleotides have been discovered in extraterrestrial sources, such as meteorites and comets, their formation can be explained by abiotic means. The formation of cellular structures, or more elaborate organic molecules, such as complex lipids, proteins or nucleic acids, however, is strongly correlated to the presence of even the most primitive life processes. Recent evidence lends support to the hypothesis that life may have once existed on Mars. Carbonate globules and ppm concentrations of polycyclic aromatic hydrocarbons (PAHs) have been described in ALH84001, a meteorite originating from Mars ejecta captured by Earth over 13,000 years ago. The localized high concentration of PAHs that follow an increasing gradient from the intact fusion crust towards the interior corresponds to microgram quantities of hydrocarbon. Even though ALH84001 and other similar meteorites have withstood the forces capable of ejecting rock through Mars' escape velocity, upon entering Earth's atmosphere, their core temperatures are likely not to have been raised significantly, as evidenced by the survival of remanent magnetic signatures. Ideal biomarkers of ancient or modern biological life would include molecules that are (or were) pervasive and highly resistant to degradation. Also, requisite methods of detection should be simple, extremely sensitive and broadly inclusive (NASA SP-530). Lipopolysaccharide (LPS), peptidoglycan or pseudopeptidoglycan and beta-glucan are microbial cell wall components which together cover the entire microbial spectrum of eubacteria, archea and fungi. They are all remarkably resistant to thermal degradation. Fortunately, many antimicrobial defense systems of higher organisms require sensitive detection to combat microbial pathogens. We employ here the primitive immune system of the evolutionarily ancient horseshoe crab, Limulus polyphemus. This species relies on multi-enzyme signal amplification detection of cell wall molecules and they can be applied to the development of useful detectors of life. An extension of this work includes the visualization of microbial signatures by labeling LAL components with chromogenic or electron dense markers. The protein Limulus Anti-LPS Factor (LALF) has an extremely high affinity for LPS. By coupling LALF binding with colloidal gold labels we demonstrate a correlation of the structures visible by electron microscopy with biochemical evidence of microbial cell wall materials. Pure silica particles were mixed with cultures of E. coli (10(exp 6) cfu/mL). Samples were washed sequentially with buffered saline, LALF, antibody to LALF and finally colloidal gold-labeled Protein A. Negative controls were not exposed to E. coli but received identical treatment otherwise. Samples were coated with carbon and imaged on a JEOL JSM-840 scanning electron microscope with LaB6 source in the back scatter mode with the JEOL annular back scatter detector. 20 nm-scale black spots in this contrast-reversed image originate from electrons back-scattered by gold atoms. Negative controls did not give any signal. Future work will expand application of this technique to soil simulants and mineralized rock samples.

Wainwright, Norman R.↗

Maghemite Formation via Organics and the Prospect for Maghemite as a Biomarker Mineral on Mars

One of the major questions on Mars is the origin of the magnetic component in the surface material. Our work on maghemite formation suggests that alteration of femhydrite in the presence of organics would provide a plausible formation scenario for this magnetic soil component and further suggests that maghemite might be an important biomarker mineral on Mars. Identification of biomarker minerals is an important aspect of Astrobiology . The iron oxide mineral maghemite is thought to be one of the magnetic components in the Martian surface material; however, it is a rare mineral on the Earth and requires a reducing agent for synthesis. Organic material serves as a reductant in maghemite formation during forest fires on Earth and may play an important role in maghemite formation on Mars through low-temperature heating (e.g., volcanism, impacts). This study involves analysis of magnetite, maghemite and hematite formation under Martian environmental conditions from femhydrite in the presence and absence of organics. A dehydrated version of the mineral femhydrite is thought to be present in Martian soil/dust grains and could have formed at an earlier time on Mars when water was present. Our work indicates that low-temperature alteration of femhydrite in the presence of organic material could be an important mechanism on Mars.

Bishop, Janice↗

Analysis of complex-type chromosome exchanges in astronauts' lymphocytes after space flight as a biomarker of high-LET exposure

High-LET radiation is more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. To investigate if complex chromosome exchanges are induced by the high-LET component of space radiation exposure, damage was assessed in astronauts' blood lymphocytes before and after long duration missions of 3-4 months. The frequency of simple translocations increased significantly for most of the crewmembers studied. However, there were few complex exchanges detected and only one crewmember had a significant increase after flight. It has been suggested that the yield of complex chromosome damage could be underestimated when analyzing metaphase cells collected at one time point after irradiation, and analysis of chemically-induced PCC may be more accurate since problems with complicated cell-cycle delays are avoided. However, in this case the yields of chromosome damage were similar for metaphase and PCC analysis of astronauts' lymphocytes. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.

manned↗

Microscopic physical biomarkers in carbonate hot springs: implications in the search for life on Mars

Physical evidence of life (physical biomarkers) from the deposits of carbonate hot springs were documented at the scale of microorganisms--submillimeter to submicrometer. The four moderate-temperature (57 to 72 degrees C), neutral pH springs reported on in this study, support diverse communities of bacteria adapted to specific physical and chemical conditions. Some of the microbes coexist with travertine deposits in endolithic communities. In other cases, the microbes are rapidly coated and destroyed by precipitates but leave distinctive mineral fabrics. Some microbes adapted to carbonate hot springs produce an extracellular polymeric substance which forms a three-dimensional matrix with living cells and cell remains, known as a biofilm. Silicon and iron oxides often coat the biofilm, leading to long-term preservation. Submicrometer mineralized spheres composed of calcium fluoride or silica are common in carbonate hot spring deposits. Sphere formation is biologically mediated, but the spheres themselves are apparently not fossils or microbes. Additionally, some microbes selectively weather mineral surfaces in distinctive patterns. Hot spring deposits have been cited as prime locations for exobiological exploration of Mars. The presence of preserved microscopic physical biomarkers at all four sites supports a strategy of searching for evidence of life in hot spring deposits on Mars.

NASA Center JSC↗

The Role of Radiation in Making Meteoritic Organics and False Biomarkers

The tons of organic material that come to the Earth every day on meteorites and dust particles probably helped to make the Earth habitable, and possibly played a role in the origin of life. These compounds."include amino acids, nucleo bases, vesicle forming fatty acids, and many others. Lab experiments suggest that low temperature radiation chemistry could account for many of these chemicals. If we find evidence of Life elsewhere in the Solar System it will probably be in form of chemical biomarkers, quintessentially biological molecules that indicate the presence of micro-organisms. While most people think of the molecules above as good biomarkers, they are not.

Bernstein, Max↗

Biomarker for Space Radiation Risk: Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Over the years, we have studied chromosomal damage in human fibroblast, epithelia and lymphocyte cells exposed in vitro to energetic charged particles generated at several accelerator facilities in the world. We have also studied chromosome aberrations in astronaut s peripheral blood lymphocytes before and after space flight. Various fluorescence in situ hybridization painting techniques have been used to identify from only the telomere region of the chromosome to every chromosome in a human cell. We will summarize the results of the investigations, and discuss the unique radiation signatures and biomarkers for space radiation exposure.

Hada, Megumi↗

Hydrocyclone/Filter for Concentrating Biomarkers from Soil

The hydrocyclone-filtration extractor (HFE), now undergoing development, is a simple, robust apparatus for processing large amounts of soil to extract trace amounts of microorganisms, soluble organic compounds, and other biomarkers from soil and to concentrate the extracts in amounts sufficient to enable such traditional assays as cell culturing, deoxyribonucleic acid (DNA) analysis, and isotope analysis. Originally intended for incorporation into a suite of instruments for detecting signs of life on Mars, the HFE could also be used on Earth for similar purposes, including detecting trace amounts of biomarkers or chemical wastes in soils.

Ponce, Adrian↗

Organic Biomarker-Based Assays to Evaluate Total Bioburden and Organic Compounds on Space Flight Hardware

Meeting planetary protection (PP) requirements for space flight hardware may involve bioburden reduction by dry heat microbial reduction (DHMR). The NASA standard assay to demonstrate the reduction of organisms involves the swabbing of surfaces, heat shock of the extracted samples, plating of the samples on Trypticase Soy Agar (TSA), and counting colony forming units after an incubation period. The standard assay uses enumeration of heat tolerant spore-formers as a proxy for total bioburden and is generally expected to provide a lower limit. We suggest that a better estimate of the total bioburden could be obtained through sampling and analysis of organic biomarkers. As biological organisms are fundamentally organic in chemistry (i.e. carbon containing materials) it is important to characterize the biomarker compounds that are released from organisms that 1) exist on flight hardware before microbial reduction and 2) left behind from the killed organisms following microbial reduction.

Locke, Darren R.↗

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms. The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-one ISS crewmembers have been tested to date, including 6 from this past year after testing resumed post-COVID. This cohort includes 9 first-time fliers, 4F, and mission durations lasting 182 ± 32 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 21 participants to date. Based on a partial sample using an ordinal scale survey, 80% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures; however, additional data is needed to draw conclusions. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

S J Wood↗

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed(1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms(adaptive Functional Mobility Test, aFMT). The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure(using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-seven ISS crewmembers have been tested to date, including 6 from this past year. This cohort includes 10first-time fliers, 6F, and mission durations lasting 178.6 ± 30.5 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 27participants to date. Based on a partial sample using an ordinal scale survey, 70% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures, e.g., the cumulative time to complete the aFMT is significantly correlated to pre-to-post-flight changes in tandem walk (rho= 0.64, p = 0.001). Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures

S J Wood↗

Oculometric Biomarkers of Visuomotor Deficits in Clinically Asymptomatic Patients With Systemic Lupus Erythematosus Undergoing Long-Term Hydroxychloroquine Treatment

Introduction: This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

eye movements↗

NNA-DNA adducts as biomarkers for detecting exposure to thirdhand smoke

NNA-derived specific adducts represent an integrated biomarker of exposure to thirdhand smoke (THS) as NNA is unique to THS. The NNA-dG covalent binding adduct could serve as such a biomarker, and play a role in identifying individuals exposed to THS, thus providing critical information for early detection and prevention.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions

A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts’ opinion on the development and application of multi-omic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular and functional aberrations within the lesion and within individual cells. Additionally, single-cell proteomic data will be essential for the establishment of new tools that with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included: • The best way/s to analyze single-cells from fresh and preserved tissue • Detection and analysis of secreted molecules and from single cells, especially from a tissue slice • Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment • Multi-omic integration of data to support and inform proteomic measurements • Subcellular organelles – identifying abnormal structure, function, distribution and location within individual premalignant and malignant cells • How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post translational modifications (PTM) • The depth of coverage measured concurrently using single-cell techniques • Quantitation - absolute or semiquantitative? • Single methodology or multiplexed combinations? • Application of analytical methods for identification of biologically significant subsets • Data visualization of N-dimensional datasets • How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME) • Associations between intrinsic cellular processes and extrinsic stimuli • How to predict cellular responses to stress inducing stimuli • Identification of new markers for prediction of progression from precursor, benign and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells • Identification of new targets for immunoprevention or immunotherapy – identification of neoantigens and surfactome of individual cells within a lesion

59 BASIC BIOLOGICAL SCIENCES↗

Longitudinal Changes in Immune Activation Serum Biomarkers Prior to Diagnosis and Risk of B-cell NHL Subtypes

To examine the contribution of B-cell activation molecules to B-cell follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), a prospective study was conducted using pre-diagnosis serial serum samples from the US Department of Defense Serum Repository. Each case (n = 142 FL, n = 211 DLBCL) was matched to two controls on age, gender, race, military branch, and blood collection dates. Immune activation molecules (IL1β, IL2, IL4, IL5, IL6, IL10, IL12, CXCL13, IL8, TNFα, IFNγ, GM-CSF, VEGF, sCD30, IgE) were quantified using ELISA or multiplex immunometric (Luminex) assay. Longitudinal data were analyzed using linear mixed modeling. As serial specimens were collected over several years before diagnosis, we evaluated the temporal dynamics of these markers. Increased serum levels of sCD30, CXCL13, and to a lesser extent IL10, were associated with both FL and DLBCL in cases compared with controls, with a median follow-up of 5.5 years from the earliest specimen collection to diagnosis date. Significant increasing sCD30 and CXCL13 trajectories for FL and DLBCL subtypes were noted starting at the earliest time points and with IL10 levels increasing significantly at time points closer to diagnosis. In conclusion, these results suggest that sCD30, CXCL13, and IL10 may contribute to the etiology of FL and DLBCL and are potential biomarkers for these non–Hodgkin lymphoma subtypes. The increasing trajectories of the B-cell activation molecules, sCD30, CXCL13, and to a lesser extent IL10, may indicate early disease-induced effects or reflect the chronic stimulation of B-cells that promotes the development of FL and DLBCL subtypes.

60 APPLIED LIFE SCIENCES↗

MicroRNAs as diagnostic and prognostic biomarkers of age-related macular degeneration: advances and limitations

A main cause of vision loss in the elderly is age-related macular degeneration (AMD). Among the cellular, biochemical, and molecular changes linked to this disease, inflammation and angiogenesis appear as being crucial in AMD pathogenesis and progression. There are two forms of the disease: dry AMD, accounting for 80–90% of cases, and wet AMD. The disease usually begins as dry AMD associated with retinal pigment epithelium and photoreceptor degeneration, whereas wet AMD is associated with choroidal neovascularization resulting in severe vision impairment. The new vessels are largely malformed, leading to blood and fluid leakage within the disrupted tissue, which provokes inflammation and scar formation and results in retinal damage and detachment. MicroRNAs are dysregulated in AMD and may facilitate the early detection of the disease and monitoring disease progression. Two recent reviews of microRNAs in AMD had indicated weaknesses or limitations in four earlier investigations. Studies in the last three years have shown considerable progress in overcoming some of these concerns and identifying specific microRNAs as biomarkers for AMD. Further large-scale studies are warranted using appropriate statistical methods to take into account gender and age disparity in the study populations and confounding factors such as smoking status.

60 APPLIED LIFE SCIENCES↗