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Reciprocal transplants reveal asymmetric local adaptation of Himalayan Rhododendron approaching elevational range limit
Abstract As plant species expand their upper limits of distribution under current warming, some retain both traditional climate space and biotic environment while others encounter novel conditions. The latter is the case for Rhododendron campanulatum , a woody shrub that grows both above and below treeline at our study site in the Eastern Himalayas where a very conspicuous, stable treeline was defined by a nearly contiguous canopy of tall Abies spectabilis trees, many of which are over a century old. Prior work showed that treeline had remained static in this region while R. campanulatum expanded its elevational range limit. We tested local adaptation of R. campanulatum by performing reciprocal transplants between the species' current elevational range limit (4023 m above sea level [asl]) and just above treeline (3876 m asl). Contrary to expectation, the coldest temperatures of late winter and early mid‐spring were experienced by plants at the lower elevation: R. campanulatum at species' limit (upper site) were covered by snow for a longer period (40 more days) and escaped the coldest temperatures suffered by conspecifics at treeline (lower site). The harsher spring conditions at treeline likely explain why leaves were smaller at treeline (15.3 cm 2 ) than at species limit (21.3 cm 2 ). Contrary to results from equivalent studies in other regions, survival was reduced more by downslope than by upslope movement, again potentially due to extreme cold temperatures observed at treeline in spring. Upslope transplantation had no effect on mortality, but mortality of species limit saplings transplanted downslope was three times higher than that of residents at both sites. A general expectation is that locals should survive better than foreign transplants, but survival of locals and immigrants at our species limit site was identical. However, those species limit saplings that survived the transplant to treeline grew faster than both locals at treeline and the transplants at species limit. Overall, we found asymmetric adaptation: Compared with treeline saplings, those at species limit (147 m above treeline) were more tolerant of extremes in the growing season but less tolerant of extremes in winter and early mid‐spring, displaying local adaptation in a more complex manner than simply home advantage, and complicating predictions about impacts of future regional climate change.
Application of Rotating Wall Vessel (RWV) Cell Culture for Pancreas Islet Cell Transplantation
Type I insulin-dependent diabetes mellitus (IDDM) remains a major cause of morbidity and mortality in both pediatric and adult populations, despite significant advances in medical management. While insulin therapy treats symptoms of acute diabetes, it fails to prevent chronic complications such as microvascular disease, blindness, neuropathy, and chronic renal failure. Strict control of blood glucose concentrations delays but does not prevent the onset and progression of secondary complications. Although, whole pancreas transplantation restores physiological blood glucose levels, a continuous process of allograft rejection causes vascular and exocrine-related complications. Recent advances in methods for isolation and purification of pancreatic islets make transplantation of islet allografts an attractive alternative to whole pancreas transplantation. However, immunosuppressive drugs are necessary to prevent rejection of islet allografts and many of these drugs are known to be toxic to the islets. Since auto-transplants of isolated islets following total pancreatectomy survive and function in vivo, it is apparent that a major obstacle to successful clinical islet transplantation is the immunogenicity of the islet allografts.
The Impact of New Accelerometer Transplant Data (ACH) on GRACE Follow-On Along-Orbit Inter-Satellite Laser Ranging Observations and Monthly Time-Variable Gravity and Mascon Solutions
GRACE-D accelerometer data show significant bias jumps since one month after the launch of the GRACE Follow-On (GRACE-FO) satellites in May 2018, making them inapplicable for correcting GRACE-FO products for non-gravitational accelerations. The GRACE-FO Science Data System (SDS) compensated this issue by transplanting the GRACE-C accelerometer data toward that of GRACE-D. Recently, GRACE-FO SDS implemented an updated transplant method, used in the latest release of GRACE-FO data. Here, we examine the impact of updated accelerometer transplant data (ACH) on GRACE-FO measurements at all levels: (a) Level-1B inter-satellite laser ranging residuals measured along satellite orbit, (b) Level-2 time-variable gravity solutions from all SDS centers (JPL, CSR, and GFZ), and (c) Level-3 mascon solutions. We show that inter-satellite laser ranging residuals are modified at low frequencies below 1 mHz, affecting the along-orbit analysis of large-scale time-variable gravity signals. When mapped into monthly Level-2 spherical harmonic coefficients of geopotential, the low-frequency change in inter-satellite ranging residuals leads to substantial improvement of coefficients associated with resonant orders (i.e., 15, 30, 45, etc.) and C 30 . We also present an improved SLR-derived C 30 which significantly improves the agreement with updated GRACE-FO C 30 at seasonal and interannual timescales. Moreover, we demonstrate the noise reduction in mass change estimates from new GRACE-FO Level-2 data over oceans, Greenland, and Antarctica for all SDS solutions. GRACE-FO mascon solutions show a moderate change in the updated release. Our comprehensive analyses demonstrate high-quality estimates of non-gravitational accelerations by the updated transplant method, resulting in more accurate GRACE-FO time-variable gravity and mass change observations.
Co-transplantation of plasmid-transfected myoblasts and myotubes into rat brains enables high levels of gene expression long-term
We have previously proposed the use of primary muscle cells as a "platform," or "vehicle" for intracerebral transgene expression. Brain grafts of minced muscle, or cultured muscle cells persisted in rat brains for at least 6 mo without any decrease in graft size, or tumor formation. Stable, but moderate levels of intracerebral transgene expression were obtained by transplanting plasmid-transfected myotubes in culture. In the present study, high and stable levels of intracerebral transgene expression were achieved by the co-transplantation of plasmid-transfected myoblasts and myotubes in culture. Approximately 5 X 10(5) myoblasts and myotubes were transfected with 10 micrograms pRSVL plasmid DNA, and 30 micrograms Lipofectin (BRL), respectively. They were mixed together (total cell number was 1 million), and stereotactically injected into the caudate nucleus of an adult rat brain. The activity of luciferase, the product of transgene expression, was stable for at least 4 mo, and much higher than the levels in myotube grafts, or co-grafts of myoblasts and minced muscle. Presumably, the myotubes served as a framework on which the myoblasts can form myotubes. The sections of brains transplanted with co-graft of myoblasts, and myotubes transfected with pRSVLac-Z were stained immunofluorescently for beta-galactosidase activity. The muscle grafts contained beta-galactosidase positive myofibers 4 mo after transplantation. Such high and stable levels of in vivo expression after postnatal gene transfer have rarely been achieved. Primary muscle cells are useful vehicle for transgene expression in brains, and potentially valuable for gene therapy of degenerative neurological disorders.
Disturbance legacies regulate coastal forest soil stability to changing salinity and inundation: A soil transplant experiment
Coastal forests worldwide are vulnerable to a dramatic transition from upland to wetland as sea-level rise accelerates and regimes of precipitation and storms change. However, the biogeochemical impacts of shifting salinity and inundation disturbance that foreshadow forest to wetland state transitions are largely unknown. This experiment used a natural salinity gradient in a tidal creek in eastern Maryland, U.S.A., to examine how soil respiration and chemistry may change under novel salinity and inundation disturbance regimes. Soil monoliths were transplanted in a reciprocal design among plots varying in seawater exposure and elevation above the creek. We monitored the monoliths’ carbon dioxide (CO 2 ) flux for two years and performed soil chemical analyses at the end of the experiment. Soil CO 2 flux was affected by changing disturbance regimes and responses were dependent upon the salinity and inundation legacies associated with each study location. Lowland soil CO 2 flux was resistant to changing salinity and inundation disturbance, with transplanted soil monolith chemistry composition in between that of its origin and destination. Conversely, upland soil CO 2 flux was sensitive to changing salinity and inundation disturbance and remained suppressed throughout the 2-year study when exposed to wetter, saline conditions. Additionally, transplanted upland soil chemistry composition was like that of its destination, rather than origin, with upland soils displaying higher pH, base saturation, and nutrient availability relative to lowland soils. Here, we hypothesize that reductions in soil respiration rates were driven by loss of soil nutrients and osmotic and redox stress on microbial communities following exposure to seawater. Together, our results suggest that disturbance legacies shape coastal forest soil responses to changing salinity and inundation disturbance regimes. However, fully understanding the dependence of system responses on disturbance legacies requires future study across a variety of systems and spatial and temporal scales.
Challenges in cell transplantation for muscular dystrophy
For decades now, cell transplantation has been considered a possible therapeutic strategy for muscular dystrophy, but failures have largely outnumbered success or at least encouraging outcomes. }In this review we will briefly recall the history of cell transplantation, discuss the peculiar features of skeletal muscle, and dystrophic skeletal muscle in particular, that make the procedure complicated and inefficient. As there are many recent and exhaustive reviews on the various myogenic cell types that have been or will be transplanted, we will only briefly describe them and refer the reader to these reviews. }Finally, we will discuss possible strategies to overcome the hurdles that prevent biological efficacy and hence clinical success.
Methane flux from transplanted soil monoliths depends on moisture, but not origin
Soils both produce and consume methane (CH 4 ), a potent greenhouse gas that contributes to climate change. In coastal forests, upland soils are shifting from being CH 4 sinks to sources as sea levels rise, increasingly flooding soils with little prior inundation history. Ecosystem CH 4 budgets are highly uncertain due in part to the difficulty in separating fluxes measured at the soil surface into individual production and consumption processes which are likely to have different responses to future environmental conditions. Here, we measured growing season CH 4 fluxes from soil monoliths transplanted four years prior along an inundation and salinity gradient to determine how changes in abiotic conditions control CH 4 flux rates. To parse net fluxes measured at the soil surface into their component gross rates, we paired field measurements with a stable isotope pool dilution incubation of surface soils. Throughout the growing season, net soil surface CH 4 flux was positively correlated with soil moisture (p < 0.01), with lowland-located soils tending towards CH 4 sources (mean 0.349 ± 1.11 mg CH 4 -C m -2 hr -1 , error is standard deviation) and upland-located soils tending towards CH 4 sinks (-0.003 ± 0.003 mg CH 4 -C m -2 hr -1 ). Transplanted soils’ fluxes were statistically identical to their native neighbors once microtopography-driven differences in soil moisture were controlled for. The pool dilution experiment revealed that production and consumption rates were similar in upland and lowland surface soils (2.82 ± 3.29 µmol CH 4 g -1 dry soil d -1 production, 3.47 ± 2.03 µmol CH 4 g -1 dry soil d -1 consumption), indicating the majority of production likely occurs at depth in lowland soils. Both gross and net fluxes from transplanted soils showed no effect of soil origin after four years, suggesting low resistance of CH 4 cycling to global change drivers. Our results indicate the strength of the coastal forest CH 4 sink is likely to decrease in proportion to sea-level rise.
Transplanting Retinal Cells using Bucky Paper for Support
A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.
Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain
After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.
The effects of interferon-alpha/beta in a model of rat heart transplantation
Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.
Motor and cognitive testing of bone marrow transplant patients after chemoradiotherapy
Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.
Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.
Diet outperforms microbial transplant to drive microbiome recovery in mice
A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth, which in turn increases risk for a wide array of metabolic, immune and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment, although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here, in this study, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.
Evolutionary Analyses of Gene Expression Divergence in Panicum hallii : Exploring Constitutive and Plastic Responses Using Reciprocal Transplants
Abstract The evolution of gene expression is thought to be an important mechanism of local adaptation and ecological speciation. Gene expression divergence occurs through the evolution of cis- polymorphisms and through more widespread effects driven by trans-regulatory factors. Here, we explore expression and sequence divergence in a large sample of Panicum hallii accessions encompassing the species range using a reciprocal transplantation experiment. We observed widespread genotype and transplant site drivers of expression divergence, with a limited number of genes exhibiting genotype-by-site interactions. We used a modified FST–QST outlier approach (QPC analysis) to detect local adaptation. We identified 514 genes with constitutive expression divergence above and beyond the levels expected under neutral processes. However, no plastic expression responses met our multiple testing correction as QPC outliers. Constitutive QPC outlier genes were involved in a number of developmental processes and responses to abiotic environments. Leveraging earlier expression quantitative trait loci results, we found a strong enrichment of expression divergence, including for QPC outliers, in genes previously identified with cis and cis–environment interactions but found no patterns related to trans-factors. Population genetic analyses detected elevated sequence divergence of promoters and coding sequence of constitutive expression outliers but little evidence for positive selection on these proteins. Our results are consistent with a hypothesis of cis-regulatory divergence as a primary driver of expression divergence in P. hallii.
A Comparison of Cs-137 γ Rays and 320-kV X-Rays in a Mouse Bone Marrow Transplantation Model
US homeland security concerns regarding the potential misuse of some radiation sources used in radiobiological research, for example, cesium-137 ( 137 Cs), have resulted in recommendations by the National Research Council to conduct studies into replacing these sources with suitable X-ray instruments. The objective of this research is to compare the effectiveness of an X-RAD 320 irradiator (PXINC 2010) with a 137 Cs irradiator (Gammacell-1000 Unit) using an established bone marrow chimeric model. Using measured radiation doses for each instrument, we characterized the dose–response relationships for bone marrow and splenocyte ablation, using a cytotoxicity-hazard model. Our results show that the X-RAD 320 photon energy spectrum was suitable for ablating bone marrow at the 3 exposure levels used, similar to that of 137 Cs photons. However, the 320-kV X-rays were not as effective as the much higher energy γ rays at depleting mouse splenocytes. Furthermore, the 3 X-ray levels used were less effective than the higher energy γ rays in allowing the successful engraftment of donor bone marrow, potentially as a result of the incomplete depletion of the spleen cells. More defined studies are warranted for determining whether bone marrow transplantation in mice can be successfully achieved using 320-kV X-rays. A higher X-ray dose then used is likely needed for transplantation success.
Novel Approaches to Cellular Transplantation from the US Space Program
Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.
Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery
Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.