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OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
Epstein Barr virus (EBV) infects 95% of the global population and is associated with up to 2% of cancers globally. Immunoglobulin G (IgG) antibody levels to EBV have been shown to be heritable and associated with developing malignancies. We, therefore, performed a pilot genome-wide association analysis of anti-EBV IgG traits in an African population, using a combined approach including array genotyping, whole-genome sequencing and imputation to a panel with African sequence data. In 1562 Ugandans, we identify a variant in human leukocyte antigen (HLA)-DQA1, rs9272371 (p = 2.6 × 10−17) associated with anti-EBV nuclear antigen-1 responses. Trans-ancestry meta-analysis and fine-mapping with European-ancestry individuals suggest the presence of distinct HLA class II variants driving associations in Uganda. In addition, we identify four putative, novel, very rare African-specific loci with preliminary evidence for association with anti-viral capsid antigen IgG responses which will require replication for validation. These findings reinforce the need for the expansion of such studies in African populations with relevant datasets to capture genetic diversity.
During 2000–07, five giant icebergs (B15A, B15J, B15K, C16 and C25) adrift in the southwestern Ross Sea, Antarctica, were instrumented with global positioning system (GPS) receivers and other instruments to monitor their behavior in the near-coastal environment. The measurements show that collision processes can strongly influence iceberg behavior and delay their progress in drifting to the open ocean. Collisions appear to have been a dominant control on the movement of B15A, the largest of the icebergs, during the 4-year period it gyrated within the limited confines of Ross Island, the fixed Ross Ice Shelf and grounded C16. Iceberg interactions in the near-coastal regime are largely driven by ocean tidal effects which determine the magnitude of forces generated during collision and break-up events. Estimates of forces derived from the observed drift trajectories during the iceberg-collisioninduced calving of iceberg C19 from the Ross Ice Shelf, during the iceberg-induced break-off of the tip of the Drygalski Ice Tongue and the break-up of B15A provide a crude estimate of the stress scale involved in iceberg calving. Considering the total area the vertical face of new rifts created in the calving or break-up process, and not accounting for local stress amplification near rift tips, this estimated stress scale is 104 Pa.
Observations of the water level in Beaver Lake, an epishelf lake in East Antarctica, show a regular tidal signal that is lagged and attenuated from the tides beneath the adjacent Amery Ice Shelf. The phase lag and amplitude attenuation can be created by a narrow inlet connection between Beaver Lake and the cavity beneath the Amery Ice Shelf. A forced linear damped oscillator is used to determine the inlet dimensions that are required to produce the observed phase lag and amplitude attenuation. The model shows that the observations are consistent with a tidal flow that is restricted by the drag created by flow in the narrow inlet. Analysis shows that the phase lag and amplitude attenuation of the tides in Beaver Lake has increased over the years 1991-2002, probably due to a thickening of the overlying ice shelf. The response is sensitive to subtle variations in the dimensions of the inlet.
To assess iodine status among pregnant women in rural Zinder, Niger and to compare their status with the iodine status of school-aged children from the same households.
Seventy-three villages in the catchment area of sixteen health centres were randomly selected to participate in the cross-sectional survey.
Salt iodization is mandatory in Niger, requiring 20–60 ppm iodine at the retail level.
A spot urine sample was collected from randomly selected pregnant women (n 662) and one school-aged child from the same household (n 373). Urinary iodine concentration (UIC) was assessed as an indicator of iodine status in both groups. Dried blood spots (DBS) were collected from venous blood samples of pregnant women and thyroglobulin (Tg), thyroid-stimulating hormone and total thyroxine were measured. Iodine content of household salt samples (n 108) was assessed by titration.
Median iodine content of salt samples was 5·5 ppm (range 0–41 ppm), 98 % had an iodine content <20 ppm. Median (interquartile range) UIC of pregnant women and school-aged children was 69·0 (38·1–114·3) and 100·9 (61·2–163·2) µg/l, respectively. Although nearly all pregnant women were euthyroid, their median (interquartile range) DBS-Tg was 34·6 (23·9–49·7) µg/l and 38·4 % had DBS-Tg>40 µg/l.
In this region of Niger, most salt is inadequately iodized. UIC in pregnant women indicated iodine deficiency, whereas UIC of school-aged children indicated marginally adequate iodine status. Thus, estimating population iodine status based solely on monitoring of UIC among school-aged children may underestimate the risk of iodine deficiency in pregnant women.
With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.
Pigweeds are among the most abundant and troublesome weed species across Midwest and mid-South soybean production systems because of their prolific growth characteristics and ability to rapidly evolve resistance to several herbicide sites of action. This has renewed interest in diversifying weed management strategies by implementing integrated weed management (IWM) programs to efficiently manage weeds, increase soybean light interception, and increase grain yield. Field studies were conducted across 16 site-years to determine the effectiveness of soybean row width, seeding rate, and herbicide strategy as components of IWM in glufosinate-resistant soybean. Sites were grouped according to optimum adaptation zones for soybean maturity groups (MGs). Across all MG regions, pigweed density and height at the POST herbicide timing, and end-of-season pigweed density, height, and fecundity were reduced in IWM programs using a PRE followed by (fb) POST herbicide strategy. Furthermore, a PRE fb POST herbicide strategy treatment increased soybean cumulative intercepted photosynthetically active radiation (CIPAR) and subsequently, soybean grain yield across all MG regions. Soybean row width and seeding rate manipulation effects were highly variable. Narrow row width (≤ 38 cm) and a high seeding rate (470,000 seeds ha−1) reduced end-of-season height and fecundity variably across MG regions compared with wide row width (≥ 76 cm) and moderate to low (322,000 to 173,000 seeds ha−1) seeding rates. However, narrow row widths and high seeding rates did not reduce pigweed density at the POST herbicide application timing or at soybean harvest. Across all MG regions, soybean CIPAR increased as soybean row width decreased and seeding rate increased; however, row width and seeding rate had variable effects on soybean yield. Furthermore, soybean CIPAR was not associated with end-of-season pigweed growth and fecundity. A PRE fb POST herbicide strategy was a necessary component for an IWM program as it simultaneously managed pigweeds, increased soybean CIPAR, and increased grain yield.
This paper briefly describes the principle of operation and science goals of the AMANDA high energy neutrino telescope located at the South Pole, Antarctica. Results from an earlier phase of the telescope, called AMANDA-BIO, demonstrate both reliable operation and the broad astrophysical reach of this device, which includes searches for a variety of sources of ultrahigh energy neutrinos: generic point sources, Gamma-Ray Bursts and diffuse sources. The predicted sensitivity and angular resolution of the telescope were confirmed by studies of atmospheric muon and neutrino backgrounds. We also report on the status of the analysis from AMANDA-II, a larger version with far greater capabilities. At this stage of analysis, details of the ice properties and other systematic uncertainties of the AMANDA-II telescope are under study, but we have made progress toward critical science objectives. In particular, we present the first preliminary flux limits from AMANDA-II on the search for continuous emission from astrophysical point sources, and report on the search for correlated neutrino emission from Gamma Ray Bursts detected by BATSE before decommissioning in May 2000. During the next two years, we expect to exploit the full potential of AMANDA-II with the installation of a new data acquisition system that records full waveforms from the in-ice optical sensors.
We present new, infrared and millimeter views of the Helix nebula which illustrate the critical role of remnant, neutral AGB envelopes in the formation and evolution of planetary nebulae. Large scale ∼ 1 000″ mapping of the entire nebula in the CO (J = 2 − 1) line with the CSO reveals the global structure of the envelope. The CO emission forms the familiar ring structure seen in optical images of the Helix, and indicates a massive remnant with ≳ 50% the mass of the ionized nebula. High resolution CO mapping with the IRAM 30 m telescope shows that the whole envelope is fragmented into an intricate array of small clumps, closely related to the cometary globules seen in the central, ionized cavity. 5–17 μm spectroscopy of the Helix with ISOCAM reveals a remarkable near infrared spectrum, dominated by the pure (v = 0 − 0) rotational lines of H2. The H2 lines are excited to a temperature of ∼ 900 K, and likely arise in warm, outer layers of the small clumps seen in CO. Imaging of the H2 emission with ISOCAM over the whole nebula provides a striking portrait of the fragmented neutral envelope. 3-dimensional views of the envelope are also presented, based on CO mapping and using 3-dimensional visualization techniques. Point symmetries dominate the toroidal structure, and suggest an origin for the Helix in equatorial mass-loss on the AGB, shaped by the action of bipolar outflows or jets.
During the past three years the measurement of stellar radial velocities has formed an important part of the spectroscopic programme of most observatories possessing large telescopes. As observations are carried to fainter and fainter stars and the number of observable objects increases rapidly, a natural development has been the selection of special groups and types of stars, the radial velocities of which will aid in the solution of certain specific problems. Illustrations are the studies of the O, B and A type stars made at the Dominion Astrophysical, the Lick, and the Simeis Observatories, of the members of the galactic clusters at the Lick Observatory, and of the fainter Cepheid variables and early-type stars with strong interstellar lines at the Mount Wilson Observatory.
Palmer amaranth and waterhemp have become increasingly troublesome weeds throughout the United States. Both species are highly adaptable and emerge continuously throughout the summer months, presenting the need for a residual PRE application in soybean. To improve season-long control of Amaranthus spp., 19 PRE treatments were evaluated on glyphosate-resistant Palmer amaranth in 2013 and 2014 at locations in Arkansas, Indiana, Nebraska, Illinois, and Tennessee; and on glyphosate-resistant waterhemp at locations in Illinois, Missouri, and Nebraska. The two Amaranthus species were analyzed separately; data for each species were pooled across site-years, and site-year was included as a random variable in the analyses. The dissipation of weed control throughout the course of the experiments was compared among treatments with the use of regression analysis where percent weed control was described as a function of time (the number of weeks after treatment [WAT]). At the mean (i.e., average) WAT (4.3 and 3.2 WAT for Palmer amaranth and waterhemp, respectively) isoxaflutole + S-metolachlor + metribuzin had the highest predicted control of Palmer amaranth (98%) and waterhemp (99%). Isoxaflutole + S-metolachlor + metribuzin, S-metolachlor + mesotrione, and flumioxazin + pyroxasulfone had a predicted control ≥ 97% and similar model parameter estimates, indicating control declined at similar rates for these treatments. Dicamba and 2,4-D provided some, short-lived residual control of Amaranthus spp. When dicamba was added to metribuzin or S-metolachlor, control increased compared to dicamba alone. Flumioxazin + pyroxasulfone, a currently labeled PRE, performed similarly to treatments containing isoxaflutole or mesotrione. Additional sites of action will provide soybean growers more opportunities to control these weeds and reduce the potential for herbicide resistance.
Two of the most problematic Amaranthus species in soybean production today are tall waterhemp and Palmer amaranth. This study determined the percentage of tall waterhemp and Palmer amaranth seed that was retained by the weed at soybean maturity to assess the likelihood of using at-harvest weed seed control tactics for soil seedbank management. Palmer amaranth plants were collected from fields in Arkansas, Tennessee, Illinois, Missouri, and Nebraska, and tall waterhemp plants were collected from fields in Nebraska, Missouri, Wisconsin, and Illinois. Collected plants were assessed for at-harvest weed seed retention in 2013 and 2014. Within 1 wk of soybean maturity, Amaranthus plants were harvested and the loose soil and debris beneath the plants were swept into a pan with a hand broom to collect any shattered seed. Percent seed retention ranged from 95 to 100% for all states both years, regardless of species. There was a strong correlation between weed biomass (g) and total seed production (no. plant−1) in that the larger the plant, the more seeds it produced. However, there was no correlation between percent seed retention and weed biomass, which indicates that regardless of plant size and likely time of emergence, seed retention is high at the time of crop maturity. Overall, this study demonstrated that there is great opportunity for Palmer amaranth and tall waterhemp seed capture or destruction at soybean harvest. It is likely that nearly all of the seeds produced for both Amaranthus species passes through the combine during harvest to be returned to the soil seedbank. Thus, there is continued need for research focused on developing and testing harvest weed seed control tactics that aim at reducing the soil seedbank and lowering risks for evolution of herbicide resistance.
Herbicide-resistant Amaranthus spp. continue to cause management difficulties in soybean. New soybean technologies under development, including resistance to various combinations of glyphosate, glufosinate, dicamba, 2,4-D, isoxaflutole, and mesotrione, will make possible the use of additional herbicide sites of action in soybean than is currently available. When this research was conducted, these soybean traits were still regulated and testing herbicide programs with the appropriate soybean genetics in a single experiment was not feasible. Therefore, the effectiveness of various herbicide programs (PRE herbicides followed by POST herbicides) was evaluated in bare-ground experiments on glyphosate-resistant Palmer amaranth and glyphosate-resistant waterhemp (both tall and common) at locations in Arkansas, Illinois, Indiana, Missouri, Nebraska, and Tennessee. Twenty-five herbicide programs were evaluated; 5 of which were PRE herbicides only, 10 were PRE herbicides followed by POST herbicides 3 to 4 wks after (WA) the PRE application (EPOST), and 10 were PRE herbicides followed by POST herbicides 6 to 7 WA the PRE application (LPOST). Programs with EPOST herbicides provided 94% or greater control of Palmer amaranth and waterhemp at 3 to 4 WA the EPOST. Overall, programs with LPOST herbicides resulted in a period of weed emergence in which weeds would typically compete with a crop. Weeds were not completely controlled with the LPOST herbicides because weed sizes were larger (≥ 15 cm) compared with their sizes at the EPOST application (≤ 7 cm). Most programs with LPOST herbicides provided 80 to 95% control at 3 to 4 WA applied LPOST. Based on an orthogonal contrast, using a synthetic-auxin herbicide LPOST improves control of Palmer amaranth and waterhemp over programs not containing a synthetic-auxin LPOST. These results show herbicides that can be used in soybean and that contain auxinic- or HPPD-resistant traits will provide growers with an opportunity for better control of glyphosate-resistant Palmer amaranth and waterhemp over a wide range of geographies and environments.
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.
A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the ‘slow tail’ of the distribution).
Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09–0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07–1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60–1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.
Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.
A segment of the debate surrounding the commercialization and use of glyphosate-resistant (GR) crops focuses on the theory that the implementation of these traits is an extension of the intensification of agriculture that will further erode the biodiversity of agricultural landscapes. A large field-scale study was initiated in 2006 in the United States on 156 different field sites with a minimum 3-yr history of GR-corn, -cotton or -soybean in the cropping system. The impact of cropping system, crop rotation, frequency of using the GR crop trait, and several categorical variables on seedbank weed population density and diversity was analyzed. The parameters of total weed population density of all species in the seedbank, species richness, Shannon's H′ and evenness were not affected by any management treatment. The similarity between the seedbank and aboveground weed community was more strongly related to location than management; previous year's crops and cropping systems were also important while GR trait rotation was not. The composition of the weed flora was more strongly related to location (geography) than any other parameter. The diversity of weed flora in agricultural sites with a history of GR crop production can be influenced by several factors relating to the specific method in which the GR trait is integrated (cropping system, crop rotation, GR trait rotation), the specific weed species, and the geographical location. Continuous GR crop, compared to fields with other cropping systems, only had greater species diversity (species richness) of some life forms, i.e., biennials, winter annuals, and prostrate weeds. Overall diversity was related to geography and not cropping system. These results justify further research to clarify the complexities of crops grown with herbicide-resistance traits to provide a more complete characterization of their culture and local adaptation to the weed seedbank.