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PubMed2025

Comprehensive proteomic and pathological profiling identifies PRAS40 as a novel biomarker and mediator of primary immune checkpoint blockade resistance in non-small cell lung cancer.

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), yet primary resistance remains a significant clinical challenge. Recent evidence implicates PRAS40 (AKT1S1) in regulating cellular survival and immune responses, but its role in immunotherapy resistance is not fully understood. METHODS: Transcriptomic data from TCGA and GTEx cohorts were analyzed to assess PRAS40 expression. Prognostic value was evaluated using Cox regression. Immune microenvironment features were characterized with CIBERSORT and TIMER. Predictive efficacy for ICB response was examined using TIDE and IPS. Plasma PRAS40 levels in 66 NSCLC patients receiving ICB were quantified by proximity extension assay (PEA), and multiplex immunohistochemistry assessed associations among PRAS40, PD-L1, and CD8+ T cells in tumor tissues. RESULTS: High PRAS40 expression was associated with poor prognosis, reduced CD8+ T cell infiltration, and downregulation of immune checkpoint genes. Elevated circulating PRAS40 predicted primary ICB resistance and shorter progression-free survival, independent of PD-L1 or CD8+ T cell status. CONCLUSION: PRAS40 is strongly associated with primary ICB resistance in NSCLC and may serve as a novel predictive biomarker. These findings support its potential to guide personalized immunotherapy in lung cancer.

Humans↗
PubMed2003

Influence of water allocation and freshwater inflow on oyster production: a hydrodynamic-oyster population model for Galveston Bay, Texas, USA.

A hydrodynamic-oyster population model was developed to assess the effect of changes in freshwater inflow on oyster populations in Galveston Bay, Texas, USA. The population model includes the effects of environmental conditions, predators, and the oyster parasite, Perkinsus marinus, on oyster populations. The hydrodynamic model includes the effects of wind stress, river runoff, tides, and oceanic exchange on the circulation of the bay. Simulations were run for low, mean, and high freshwater inflow conditions under the present (1993) hydrology and predicted hydrologies for 2024 and 2049 that include both changes in total freshwater inflow and diversions of freshwater from one primary drainage basin to another. Freshwater diversion to supply the Houston metropolitan area is predicted to negatively impact oyster production in Galveston Bay. Fecundity and larval survivorship both decline. Mortality from Perkinsus marinus increases, but to a lesser extent. A larger negative impact in 2049 relative to 2024 originates from the larger drop in fecundity under that hydrology. Changes in recruitment and mortality, resulting in lowered oyster abundance, occur because the bay volume available for mixing freshwater input from the San Jacinto and Buffalo Bayou drainage basins that drain metropolitan Houston is small in comparison to the volume of Trinity Bay that presently receives the bulk of the bay's freshwater inflow. A smaller volume for mixing results in salinities that decline more rapidly and to a greater extent under conditions of high freshwater discharge.Thus, the decline in oyster abundance results from a disequilibrium between geography and salinity brought about by freshwater diversion. Although the bay hydrology shifts, available hard substrate does not. The simulations stress the fact that it is not just the well-appreciated reduction in freshwater inflow that can result in decreased oyster production. Changing the location of freshwater inflow can also significantly impact the bay environment, even if the total amount of freshwater inflow does not change.

Animals↗
PubMed2006

Distorting gene pools by conservation: Assessing the case of doomed turtle eggs.

Sea turtles have a high reproductive output and high mortality at early stages of the life cycle. In particular, many nests are laid below or close to high tide lines, and subsequently large numbers of eggs may be inundated and destroyed. A common conservation procedure is to relocate such doomed eggs to higher ground. This article examines this practice in the light of recent data revealing that some individual turtles tend to nest relatively near the water and others relatively higher up the beach. Discussion is focused on the question of why apparently poor placement of nests has not been selected against. Comparison between the ecology of leatherback and hawksbill turtle nesting beaches suggests that predictability of environmental conditions on the nesting beaches has an important influence on patterns of nest-site selection. Options are outlined for the management of nesting beaches where a high proportion of turtle eggs is subject to destruction by flooding.

Animals↗
PubMed2006

Temperature acclimation alters cardiac performance in the lobster Homarus americanus.

The American lobster is a poikilotherm that inhabits a marine environment where temperature varies over a 25 degrees C range and depends on the winds, the tides and the seasons. To determine how cardiac performance depends on the water temperature to which the lobsters are acclimated we measured lobster heart rates in vivo. The upper limit for cardiac function in lobsters acclimated to 20 degrees C is approximately 29 degrees C, 5 degrees C warmer than that measured in lobsters acclimated to 4 degrees C. Warm acclimation also slows the lobster heart rate within the temperature range from 4 to 12 degrees C. Both effects are apparent after relatively short periods of warm acclimation (3-14 days). However, warm acclimation impairs cardiac function at cold temperatures: following several hours exposure to frigid (<5 degrees C) temperatures heart rates become slow and arrhythmic in warm acclimated, but not cold acclimated, lobsters. Thus, acclimation temperature determines the thermal limits for cardiac function at both extremes of the 25 degrees C temperature range lobsters inhabit in the wild. These observations suggest that regulation of cardiac thermal tolerance by the prevailing environmental temperature protects against the possibility of cardiac failure due to thermal stress.

Acclimatization↗
PubMed2001

The sleeper Bostrichthys sinensis (family Eleotridae) stores glutamine and reduces ammonia production during aerial exposure.

Bostrichthys sinensis inhabits brackish water, living in the crevices of the river mouths of Shang Xi and Guangdong, China. In its natural habitat, it may encounter aerial exposure frequently during low tides, and it usually remains quiescent in the absence of water. Upon aerial exposure in the laboratory, the ammonia excretion rate decreased to one-fourth that of the submerged control. Although all the enzymes of the ornithine-urea cycle were detected in the liver of this fish, the activity of hepatic carbamoyl phosphate synthetase was too low for the cycle to be functioning. Indeed, ammonia accumulated in the tissues and was not converted to urea. Results indicate that ammonia produced through amino acid catabolism was detoxified to glutamine during the first 24 h of aerial exposure. The excess amount of glutamine stored in the muscle during this period couldaccount approximately for the reduction in ammonia equivalent excreted. There was indeed a significant increase in the activity of glutamine synthetase from the liver of specimens exposed to terrestrial conditions. In contrast to the production of alanine, formation of glutamine is energetically expensive. Since B. sinensis remained relatively inactive on land, the reduction in energy demand for muscular activity might provide it with the opportunity to exploit glutamine formation as a means to detoxify ammonia. After 72 h of aerial exposure, B. sinensis reduced internal ammonia production, possibly through reductions in proteolysis and amino acid catabolism, to avoid excessive accumulation of ammonia.

Adaptation, Physiological↗
PubMed1997

[Systematic reviews in cardiology: approaches to evidence-based medicine and the Cochrane Collaboration].

The ever growing tide of results from great numbers of clinical studies clearly outweighs the abilities of the individual clinician to keep abreast of the actual state of scientific evidence and to apply it in his clinical decision-making in a timely and valid manner. Evidence-based medicine, with its central demand to link best individual clinical knowledge with best available external, scientific evidence to achieve optimal patient care, has clearly identified the urgent need for scientific techniques which allow the synthesis of scientific evidence, as collected in numerous singular studies, in an explicit, reproducible, and critically appraisable report format, and to update these reports regularly. The methods of Systematic Reviews, encompassing the techniques of meta-analysis, were developed for this purpose. They are explained and presented here in detail as they relate to the field of cardiology. Various problematic aspects have recently dominated cardiologists' discussion of meta-analyses. We point out that the techniques of Systematic Reviews hold promising solutions for many of them and that work on technical improvements is ongoing. The International Cochrane Collaboration is introduced as a global network of scientists and experts from varying fields of medicine with the aim of producing highest quality Systematic Reviews on a wide scope of topics. However, to date only few cardiologists have joined the rapidly rising numbers of Cochrane collaborators.

Cardiology↗
PubMed2005

Molecular characterization of spontaneous and growth-factor-augmented chondrogenesis in periosteum-bone tissue transferred into a joint.

Multilineage potential of progenitor cells from periosteum is well established, but conditions for differentiation within their native niche are unclear. We evaluated at cellular and molecular levels whether chondrogenesis of periosteal progenitor cells is promoted spontaneously or by growth-factor mixture (GFM) application when transferring periosteum-bone cylinders into cartilage defects. Osteochondral defects in the patellar groove of minipigs were filled with periosteum-bone cylinders and randomly supplemented with GFM. Neochondrogenesis was characterized by histology, immunohistology, and quantitative gene expression analysis. According to morphology and glycosaminoglycan accumulation, spontaneous neocartilage formation occurred in the cambium layer already at 6 weeks, increased after 12 weeks, but declined until 52 weeks, independent of GFM. Multiple cartilage differentiation markers were induced after transfer. Expression of aggrecan, COMP, decorin, and Col10a1 increased significantly within 52 weeks. Sox 9 and Col2a1 mRNA levels were elevated at 6 versus 52 weeks in the GFM group and resulted in higher collagen type II protein accumulation. Neochondrogenesis was promoted in lower periosteum layers by transfer of periosteum-bone plugs into a joint, and collagen type II protein deposition was enhanced by GFM. The final tissue subsumed typical features of periosteum and fibrocartilage but lacked an intact tide mark and features of hyaline cartilage desired for cartilage repair.

Animals↗
PubMed2003

Factors limiting the intertidal distribution of the mangrove species Xylocarpus granatum.

The tree species Xylocarpus granatum is commonly described as occurring in the upper intertidal zone of mangrove forests, but mature trees are occasionally found at lower elevations. In the Utwe River basin, on the Pacific island of Kosrae, we investigated the relative importance of several biotic and abiotic factors that may control the intertidal distribution of X. granatum. Factors we evaluated included differential seed predation across the lower, mid, and upper intertidal zones and seedling responses to salinity, tidal flooding, and shade. Seed predation was 22.4% over the first 34 days and varied little among zones or in gaps versus under the forest canopy. By day 161, there were still no differences in seed mortality, but a significant difference was found in seedling establishment, with much greater establishment in the upper intertidal plots. X. granatum seedlings in a greenhouse experiment exhibited greater growth in freshwater than seedlings in 23 ppt salinity, which is typical of salinity levels found in the mid intertidal zone in our field study sites in Micronesia, where mature X. granatum trees are generally absent. Seedlings grown in 23 ppt salinity, however, exhibited few visible signs of stress associated with patterns in growth. Seedlings grown in a simulated tidal flooding treatment (with 23 ppt salinity) also showed few signs of stress. Growth declined dramatically under 80% shade cloths, but there were few interactions of shading with either 23 ppt salinity or simulated tidal flooding. Differential seed predation is not likely to be the primary factor responsible for the intertidal distribution of X. granatum on Kosrae. However, seedling tolerance of flooding or salinity may be more important, especially relative to a potential contribution to secondary stress mortality. Other factors may ultimately prove to be more critical, such as physiological effects of salinity on seed germination, effects of tides on seed dispersal and rooting, or differential herbivory on seedlings.

Adaptation, Physiological↗
PubMed2003

Blue- and green-light signals for gamete release in the brown alga, Silvetia compressa.

The intertidal brown alga Silvetia compressa releases gametes from receptacles (the reproductive tissue) rapidly upon a dark transfer (following a photosynthesis-dependent period in the light, termed potentiation). In this study, the wavelength-dependence of this process was investigated. During the potentiation period in white light (WL), gametes are not released. However, gametes were released during potentiation in blue light (BL), or in low red light/blue light (RL/BL) ratios, but not in RL alone, high RL/BL ratios, or in broadband blue-green light (B-GL) (presence of BL, but absence of RL). RL was as effective as WL for potentiation, i.e., both lead to gamete release following transfer to darkness. Rates of linear photosynthetic electron transport were similar in RL and BL. Gamete release in BL was inhibited by equal amounts of additional narrow-waveband light between the green and red regions of the spectrum, with light-induced gamete release restricted between <491 nm and 509 nm. Very little light-induced gamete release occurred between 530 nm and 650 nm. It is proposed that a BL-responsive photoreceptor is responsible for light-induced gamete release. Transfer of WL-potentiated receptacles to GL near 530 nm resulted in significant de-potentiation and reduced gamete release during a subsequent dark transfer. This effect was not seen at 509 nm or 560 nm and revealed the presence of a second photoreceptor system repressing or counteracting potentiation in the light. We propose that the restriction of gamete release to periods when irradiance is blue-shifted may constitute a depth-sensing mechanism for this intertidal alga, allowing controlled release of gametes at high tide and/or less turbid periods, thus minimizing gamete dilution, and promoting fertilization success.

Fertilization↗
PubMed2004

Environmentally-controlled, density-dependent secondary dispersal in a local estuarine crab population.

The mechanisms driving the pelagic secondary dispersal of aquatic organisms following initial settlement to benthic habitats are poorly characterized. We examined the physical environmental (wind, diel cycle, tidal phase) and biological (ontogenetic, density-dependent) factors that contribute to the secondary dispersal of a benthic marine invertebrate, the blue crab (Callinectes sapidus) in Pamlico Sound, NC, USA. Field studies conducted in relatively large (0.05 km2) seagrass beds determined that secondary dispersal is primarily undertaken by the earliest juvenile blue crab instar stages (J1 crabs). These crabs emigrated pelagically from seagrass settlement habitats using nighttime flood tides during average wind conditions (speed approximately 5 m s-1). Moreover, the secondary dispersal of J1 crabs was density-dependent and regulated by intra-cohort (J1) crab density in seagrass. Our results suggest that dispersal occurs rapidly following settlement, and promotes blue crab metapopulation persistence by redistributing juveniles from high-density settlement habitats to areas characterized by low postlarval supply. Collectively, these data indicate that blue crab secondary dispersal is an active process under behavioral control and can alter initial distribution patterns established during settlement. This study highlights the necessity of considering secondary dispersal in ecological studies to improve our understanding of population dynamics of benthic organisms.

Analysis of Variance↗
PubMed2006

Dopamine functions as an antiherbivore defense in the temperate green alga Ulvaria obscura.

On northeastern Pacific coasts, Ulvaria obscura is a dominant component of subtidal "green tide" blooms, which can be harmful to marine communities, fisheries, and aquaculture facilities. U. obscura is avoided by herbivores relative to many other locally common macrophytes, which may contribute to its ability to form persistent blooms. We used a bioassay-guided fractionation method to experimentally determine the cause of reduced feeding on Ulvaria by echinoderms, molluscs, and arthropods. Our results indicated that dopamine, which constituted an average of 4.4% of the alga's dry mass, was responsible for decreased feeding by sea urchins (Strongylocentrotus droebachiensis). Subsequent experiments demonstrated that dopamine also reduced the feeding rates of snails (Littorina sitkana) and isopods (Idotea wosnesenskii). Dopamine is a catecholamine that is a common neurotransmitter in animals. The catecholamines dopamine, epinephrine (adrenaline), and norepinephrine also occur in at least 44 families of higher plants. The functions of catecholamines in plants are less well known than in animals but are likely to be diverse and include both physiological and ecological roles. Our results are the first experimental demonstration of a plant or algal catecholamine functioning as a feeding deterrent. This novel use of dopamine by Ulvaria may contribute to the formation and persistence of harmful Ulvaria blooms in northeastern Pacific coastal waters.

Animals↗
PubMed2006

Spatial heterogeneity in parasite infections at different spatial scales in an intertidal bivalve.

Spatial heterogeneities in the abundance of free-living organisms as well as in infection levels of their parasites are a common phenomenon, but knowledge on parasitism in invertebrate intermediate hosts in this respect is scarce. We investigated the spatial pattern of four dominant trematode species which utilize a common intertidal bivalve, the cockle Cerastoderma edule, as second intermediate host in their life cycles. Sampling of cockles from the same cohort at 15 sites in the northern Wadden Sea (North Sea) over a distance of 50 km revealed a conspicuous spatial heterogeneity in infection levels in all four species over the total sample as well as among and within sampling sites. Whereas multiple regression analyses indicated the density of first intermediate upstream hosts to be the strongest determinant of infection levels in cockles, the situation within sites was more complex with no single strong predictor variable. However, host size was positively and host density negatively correlated with infection levels and there was an indication of differential susceptibility of cockle hosts. Small-scale differences in physical properties of the habitat in the form of residual water at low tide resulted in increased infection levels of cockles which we experimentally transferred into pools. A complex interplay of these factors may be responsible for within-site heterogeneities. At larger spatial scales, these factors may be overridden by the strong effect of upstream hosts. In contrast to first intermediate trematode hosts, there was no indication for inter-specific interactions. In other terms, the recruitment of trematodes in second intermediate hosts seems to be largely controlled by pre-settlement processes both among and within host populations.

Animals↗
PubMed2004

Pseudoaneurysm of the superior pancreaticoduodenal artery, a rare cause of hemosuccus pancreaticus: report of a case.

Chronic pancreatitis with a pseudoaneurysm is an established cause of hemosuccus pancreaticus. We herein describe a patient with chronic alcoholic pancreatitis associated with hemosuccus pancreaticus due to a pseudoaneurysm of the anterior superior pancreaticoduodenal artery rupturing in a pseudocyst of pancreas in the head region. Angiographic embolization was unsuccessful and therefore a laparotomy, ligation, and excision of the pseudoaneurysm with external drainage of pseudocyst were performed. Hemosuccus pancreaticus is a rare cause of upper gastrointestinal bleeding. Contrast-enhanced computed tomography and angiography is diagnostic in the majority of the cases. Surgery is the treatment of choice. Selective angiographic embolization may be helpful in tiding over the emergency until surgery can be performed.

Adult↗
PubMed2003

Inhibition of cell proliferation by mechanical agitation involves transient cell cycle arrest at G1 phase in dinoflagellates.

Cell proliferation of dinoflagellates is negatively affected by mechanical agitation and red tides caused by members of the group have been correlated with periods of calm sea conditions. The mechanism involved in the mechanically transduced inhibition of cell proliferation is thought to involve the disruption of the cell division apparatus. In this study, we used highly synchronized cells and flow cytometry to study the effects of mechanical agitation on cell cycle progression. We observed that mechanical agitation induced transient cell cycle arrest at G(1) phase, in both the heterotrophic dinoflagellate Crypthecodinium cohniiand the photosynthetic dinoflagellate Heteroscapsa triquetra.

Animals↗
PubMed2005

Salt-regulated mannitol metabolism in algae.

Mannitol, one of the most widely occurring sugar alcohol compounds, is found in bacteria, fungi, algae, and plants. In these organisms the compound acts as a compatible solute and has multiple functions, including osmoregulation, storage, and regeneration of reducing power, and scavenging of active oxygen species. Because of the diverse functions of mannitol, introducing the ability to accumulate it has been a hallmark of attempts to generate highly salt-tolerant transgenic plants. However, transgenic plants have not yet improved significantly in their salt tolerance. Recently, we purified and characterized 2 enzymes that biosynthesize mannitol, mannitol-1-phosphate dehydrogenase (M1PDH) and mannitol-1-phosphate-specific phosphatase, from the marine red alga Caloglossa continua, which grows in estuarine areas where tide levels fluctuate frequently. The activation of Caloglossa M1PDH is unique in that it is regulated by salt concentration at enzyme level. In this review we focus on the metabolism of mannitol, mainly in marine photosynthetic organisms, and suggest how this might be applied to producing salt-tolerant transgenic plants.

Bacteria↗
PubMed2006

Quantification of water, salt and nutrient exchange processes at the mouth of a Mediterranean coastal lagoon.

Vassova lagoon is a typical Mediterranean (small, shallow, micro-tidal, well-mixed) coastal lagoon, receiving limited seasonal freshwater inflows from direct precipitation and underground seepage. An intensive study was carried out in order to quantify the mechanisms responsible for the intra-tidal and residual transport of water, salt, nutrients and chlorophyll at the mouth of this lagoon and to assess the lagoon's flushing behavior. Results indicated that although the system is micro-tidal, tidal effects appeared to be the dominant factor for the longitudinal distribution of physical and chemical parameters, while the associated residual flow is also important and serves as a baseline measure of overall circulation. However, analysis of the net longitudinal currents and fluxes of water, salt and nutrients revealed the importance of non-tidal effects (wind effect and precipitation incidents) in the mean tidal transport. It is shown that the Eulerian residual currents transported water and its properties inwards under southern winds, while a seaward transport was induced during precipitation incidents and northern winds. The Stokes drift effect was found an order of magnitude lower than the Eulerian current, directed towards the lagoon, proving the partially-progressive nature of the tide. Nutrients and chlorophyll-alpha loads are exported from the lagoon to the open sea during the ebb phase of the autumn and winter tidal cycles, associated with the inflow of nutrient-rich freshwater, seeped through the surrounding drainage canal. The reverse transport occurs in spring and early summer, when nutrients enter the lagoon during the flood tidal phase, from the nutrient-rich upper layer of the stratified adjacent sea. Application of a tidal prism model shows that Vassova lagoon has a mean flushing time of 7.5 days, ranging between 4 to 18 days, affected inversely by the tidal oscillation.

Environmental Monitoring↗
PubMed2006

Mapping invasive aquatic vegetation in the Sacramento-San Joaquin Delta using hyperspectral imagery.

The ecological and economic impacts associated with invasive species are of critical concern to land managers. The ability to map the extent and severity of invasions would be a valuable contribution to management decisions relating to control and monitoring efforts. We investigated the use of hyperspectral imagery for mapping invasive aquatic plant species in the Sacramento-San Joaquin Delta in the Central Valley of California, at two spatial scales. Sixty-four flightlines of HyMap hyperspectral imagery were acquired over the study region covering an area of 2,139 km(2) and field work was conducted to acquire GPS locations of target invasive species. We used spectral mixture analysis to classify two target invasive species; Brazilian waterweed (Egeria densa), a submerged invasive, and water hyacinth (Eichhornia crassipes), a floating emergent invasive. At the relatively fine spatial scale for five sites within the Delta (average size 51 ha) average classification accuracies were 93% for Brazilian waterweed and 73% for water hyacinth. However, at the coarser, Delta-wide scale (177,000 ha) these accuracy results were 29% for Brazilian waterweed and 65% for water hyacinth. The difference in accuracy is likely accounted for by the broad range in water turbidity and tide heights encountered across the Delta. These findings illustrate that hyperspectral imagery is a promising tool for discriminating target invasive species within the Sacramento-San Joaquin Delta waterways although more work is needed to develop classification tools that function under changing environmental conditions.

California↗
PubMed2006

Calibration and validation of far field dilution models for outfall at Worli, Mumbai.

The city of Mumbai, India with a population of 15 million discharges about 2225 MLD of domestic wastewater after partial treatment to adjoining marine water body. Under the Mumbai Sewage Disposal Project Scheme, sewage is being disposed to the west coast at Worli and Bandra through 3.4 kms long submarine outfalls. A field study was conducted at recently commissioned outfall diffuser location at Worli, at the onset of neap flood tide to study the dispersion patterns and measure the far field dilutions using radio and dye tracers. Estimated dilutions using different tracers were compared with outputs from an empirical model (Brooks) and a 2D numerical model (DIVAST). Validation using parameters such as BOD and FC, indicated a good match for BOD in near field compared to FC. The radiotracer (82)Br and Rhodamine WT generally gave good correlation with Brooks' and DIVAST models for nearfield, however at further distances predictions were not accurate.

Calibration↗