The administration of amnion-derived multipotent cell secretome ST266 protects against necrotizing enterocolitis in mice and piglets.

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and is steadily rising in frequency. Patients who develop NEC have a very high mortality, illustrating the importance of developing novel prevention or treatment approaches. We and others have shown that NEC arises in part from exaggerated signaling via the bacterial receptor, Toll-like receptor 4 (TLR4) on the intestinal epithelium, leading to widespread intestinal inflammation and intestinal ischemia.

Exploratory Phase II Multicenter, Open-Label, Clinical Trial of ST266, a Novel Secretome for Treatment of Persistent Corneal Epithelial Defects.

Objective: An exploratory phase II, multicenter, open-label, clinical trial (NCT03687632) was conducted to evaluate the safety and effectiveness in treating persistent corneal epithelial defects (PEDs) with ST266, a proprietary novel multi-cytokine platform biologic solution secreted by cultured Amnion-derived Multipotent Progenitor (AMP) cells.

Methods: Subjects with a PED were treated with ST266 eye drops 4 times daily for 28 days, then followed for 1 week. Safety was assessed by monitoring of adverse events (AEs) and serious adverse events (SAEs).

Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells.

ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice.

Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis.

The human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion-derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration and reduce inflammation.

Coupled Downscaled Climate Models and Ecophysiological Metrics Forecast Habitat Compression for an Endangered Estuarine Fish.

Climate change is driving rapid changes in environmental conditions and affecting population and species' persistence across spatial and temporal scales. Integrating climate change assessments into biological resource management, such as conserving endangered species, is a substantial challenge, partly due to a mismatch between global climate forecasts and local or regional conservation planning. Here, we demonstrate how outputs of global climate change models can be downscaled to the watershed scale, and then coupled with ecophysiological metrics to assess climate change effects on organisms of conservation concern.

Estuarine fish communities respond to climate variability over both river and ocean basins.

Estuaries are dynamic environments at the land-sea interface that are strongly affected by interannual climate variability. Ocean-atmosphere processes propagate into estuaries from the sea, and atmospheric processes over land propagate into estuaries from watersheds. We examined the effects of these two separate climate-driven processes on pelagic and demersal fish community structure along the salinity gradient in the San Francisco Estuary, California, USA.

Correspondence of biological condition models of California streams at statewide and regional scales.

We used boosted regression trees (BRT) to model stream biological condition as measured by benthic macroinvertebrate taxonomic completeness, the ratio of observed to expected (O/E) taxa. Models were developed with and without exclusion of rare taxa at a site. BRT models are robust, requiring few assumptions compared with traditional modeling techniques such as multiple linear regression.

Stream macroinvertebrate response models for bioassessment metrics: addressing the issue of spatial scale.

We developed independent predictive disturbance models for a full regional data set and four individual ecoregions (Full Region vs. Individual Ecoregion models) to evaluate effects of spatial scale on the assessment of human landscape modification, on predicted response of stream biota, and the effect of other possible confounding factors, such as watershed size and elevation, on model performance. We selected macroinvertebrate sampling sites for model development (n = 591) and validation (n = 467) that met strict screening criteria from four proximal ecoregions in the northeastern U.

Projected evolution of California's San Francisco Bay-Delta-river system in a century of climate change.

Background: Accumulating evidence shows that the planet is warming as a response to human emissions of greenhouse gases. Strategies of adaptation to climate change will require quantitative projections of how altered regional patterns of temperature, precipitation and sea level could cascade to provoke local impacts such as modified water supplies, increasing risks of coastal flooding, and growing challenges to sustainability of native species.

Methodology/principal Findings: We linked a series of models to investigate responses of California's San Francisco Estuary-Watershed (SFEW) system to two contrasting scenarios of climate change.

Bayesian change point analysis of abundance trends for pelagic fishes in the upper San Francisco Estuary.

We examined trends in abundance of four pelagic fish species (delta smelt, longfin smelt, striped bass, and threadfin shad) in the upper San Francisco Estuary, California, USA, over 40 years using Bayesian change point models. Change point models identify times of abrupt or unusual changes in absolute abundance (step changes) or in rates of change in abundance (trend changes). We coupled Bayesian model selection with linear regression splines to identify biotic or abiotic covariates with the strongest associations with abundances of each species.

Managing water to protect fish: a review of California's Environmental Water Account, 2001-2005.

The Sacramento-San Joaquin Delta, the landward reach of the San Francisco Estuary, provides habitat for threatened delta smelt, endangered winter-run Chinook salmon, and other species of concern. It is also the location of huge freshwater diversion facilities that entrain large numbers of fish. Reducing the entrainment of listed fishes into these facilities has required curtailment of pumping, reducing the reliability of water deliveries.

Promise of multiphoton detection in discovery and diagnostic proteomics.

Proteomics has lacked adequate methods for handling the complexity (hundreds of thousands of different proteins) and range of protein concentrations (> or =10(6)) of eukaryotic proteomes. New multiphoton-detection methods for ultrasensitive detection of proteins produce 10,000-fold gains in sensitivity and allow highly quantitative, linear detection of 50 zmol (30,000 molecules) to 500 fmol of proteins in complex samples. The potential of multiphoton detection in top-down proteomics analyses is illustrated with applications in monitoring proteomes in very small numbers of cells, in identifying and monitoring complex functional isoforms of cancer-related proteins, and in super-sensitive immunoassays of serum proteins for high-performance detection of cancer.

Looking for Thom's biomarkers with proteomics.

In recent years, large numbers of putative disease biomarkers have been identified. Combinations of protein biomarkers have been proposed to overcome the lack of single, magic-bullet identifiers of disease conditions. The number of biomarkers in a panel must be kept small to avoid the combinatorial explosion that requires very large, uneconomical sample cohorts for validation.

High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics.

We have developed several new methods for blood-based cancer detection by diagnostic proteomics. Ultrasensitive methods of immunoassay using multiphoton-detection (IA/MPD) increase sensitivity by 200- to 1,000-fold (1 femtogram/mL). This has allowed the measurement of cancer biomarkers with very low concentrations in blood that could not be measured for full patient cohorts with conventional immunoassays.

Ultra-sensitive immunoassays using multi-photon-detection in diagnostic proteomics of blood.

Multiphoton-detection methods that detect as little as 1000 atoms of (125)I-streptavidin increase the sensitivity of immunoassays by 200- to 1000-fold (1 femtogram/mL). Improved background suppression allows 20- to 100-fold improvements in sensitivity for conventional immunoassays (10-50 femtogram/mL). Quantitation of low abundance biomarkers in blood (PSA, TNFalpha, VEGF, IL-1beta, IL-6, and IL-8), for the first time for complete patient cohorts, indicates that very high analytical sensitivity and new statistical methods are crucial for serum-based diagnostic proteomics.

Commercial challenges of protein drug delivery.

The discovery of insulin in 1922 marked the beginning of research and development to improve the means of delivering protein therapeutics to patients. From that period forward, investigators have contemplated every possible route of delivery. Their research efforts have followed two basic pathways: one path has focused on non-invasive means of delivering proteins to the body; and the second path has been primarily aimed at increasing the biological half-life of the therapeutic molecules.

Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus.

Proteomics methods were used to characterize proteins that change their form or abundance in the nucleus of NRK49F rat kidney fibroblasts during prolonged hypoxia (1% O(2), 12 h). Of the 791 proteins that were monitored, about 20% showed detectable changes. The 51 most abundant proteins were identified by mass spectrometry.

Perspectives in spicing up proteomics with splicing.

In the post-genomics era there has been an acceleration of understanding of cellular and organismal biology and this acceleration has moved the goalposts for proteomics. Higher eukaryotes use alternative promoters, alternative splicing, RNA editing and post-translational modification to produce multiple isoforms of proteins from single genes. Switching amongst these isoforms is a major mechanism for control of cellular function.

Proteomics approaches to elucidation of signal transduction pathways.

Recent applications have shown that proteomics can provide crucial new information regarding cellular signaling processes. Bottom-up and small-scale top-down proteomics approaches related to routine biochemical methods have become widely applied to identify new aspects of established signaling pathways. Top-down, global proteomics methods are developing rapidly and are beginning to deliver information on global integration of signaling processes that has been difficult to obtain with conventional approaches.