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At least 19 records

Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380

NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. - Highlights: • NSC-743380 induced biliary hyperplasia in rats. • Toxicity of NSC-743380 appears to be related to its anticancer activity. • The model provides an opportunity to explore biomarkers of biliary hyperplasia.

60 APPLIED LIFE SCIENCES↗

Effects of cerebrolysin on motor-neuron-like NSC-34 cells

Although the peripheral nervous system is capable of regeneration, this capability is limited. As a potential means of augmenting nerve regeneration, the effects of cerebrolysin (CL) – a proteolytic peptide fraction – were tested in vitro on the motor-neuron-like NSC-34 cell line and organotypic spinal cord cultures. Therefore, NSC-34 cells were subjected to mechanical stress by changing media and metabolic stress by oxygen glucose deprivation. Afterwards, cell survival/proliferation using MTT and BrdU-labeling (FACS) and neurite sprouting using ImageJ analysis were evaluated. Calpain-1, Src and α-spectrin protein expression were analyzed by Western blot. In organotypic cultures, the effect of CL on motor neuron survival and neurite sprouting was tested by immunohistochemistry. CL had a temporary anti-proliferative but initially neuroprotective effect on OGD-stressed NSC-34 cells. High-dosed or repeatedly applied CL was deleterious for cell survival. CL amplified neurite reconstruction to limited extent, affected calpain-1 protein expression and influenced calpain-mediated spectrin cleavage as a function of Src expression. In organotypic spinal cord slice cultures, CL was not able to support motor neuron survival/neurite sprouting. Moreover, it hampered astroglia and microglia activities. The data suggest that CL may have only isolated positive effects on injured spinal motor neurons. High-dosed or accumulated CL seemed to have adverse effects in treatment of spinal cord injury. Further experiments are required to optimize the conditions for a safe clinical administration of CL in spinal cord injuries. - Highlights: • Cerebrolysin (CL) is anti-proliferative but initially neuroprotective in OGD-stressed NSC-34 cells. • CL amplified neurite reconstruction of NSC-34 cells. • CL affected calpain-1 expression and calpain-mediated spectrin cleavage as function of Src expression. • In organotypic spinal cord cultures, CL hampered motor neuron survival and glia activity. • Findings pose a contraindication for unchallenged use of CL in spinal cord injuries.

60 APPLIED LIFE SCIENCES↗

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

Rice plants ( Oryza sativa ) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, established an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. Lastly, we find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.

59 BASIC BIOLOGICAL SCIENCES↗

2016 Panama ENSO Non-Structural Carbohydrates (NSC), Feb2016-May2016, PA-SLZ, PA-PNM, PA-BCI

Results from Non-Structural Carbohydrate analysis of leaf and branch samples are provided in 2016ENSO_Panama_NSC.xlsx. The metadata files (Metadata_description_2016_ENSO_Panama.docx, File_Submission_Metadata_v1_2016ENSO_Panama_NSC.xlsx), field log (E-Field_Log_2016ENSO_Panama.xlsx), and protocols (ENSO NSC field protocol.pdf, Tropics NSC Assay protocol.pdf) contain additional information. Contact lee@lanl.gov for additional information. VERSION 2 update. The identification of a species from the PNM site has been corrected as follows: the identification of the tree initially identified as Pseudosamanea guachapele (ALBIED) has been revised to Albizia adinocephala (ALBIAD). The updated data package includes revised data, metadata and protocol documents updated to reflect this change.

54 ENVIRONMENTAL SCIENCES↗

Tree mortality after a spring fire: the role of reduced live leaf area in depletion of early growing season bole NSC

Prescribed fire is used as a tool to achieve various ecological objectives in fire-adapted ecosystems (Ryan et al. 2013). These objectives often include targeted mortality of encroaching species to minimize the risk of catastrophic wildfire (Ryan et al. 2013). Achieving mortality of some species while protecting others requires a foundational understanding of how different species respond to different types of fire at different times of year.

59 BASIC BIOLOGICAL SCIENCES↗

MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression

Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3′-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders. - Highlights: • miR-378 targeted and regulated TLX. • miR-378 was increased during NSC differentiation. • miR-378 regulated NSC proliferation and differentiation. • miR-378 regulated NSC self-renew through TLX.

60 APPLIED LIFE SCIENCES↗

Homeostatic levels of nonstructural carbohydrates after 13 yr of drought and irrigation in Pinus sylvestris

Nonstructural carbohydrates (NSCs) are important for the growth and survival of trees. Drought may lead to a decrease in tree growth and to NSC depletion, whereas increased soil moisture in otherwise dry ecosystems may increase growth and NSC concentrations. A long-term (13 yr) irrigation experiment was conducted in a Pinus sylvestris-dominated forest located at the dry margin of the species in southern Switzerland. We measured the relative leaf area, growth, NSCs, needle d13C, [N] and [P] in trees on control and irrigated plots. Irrigation resulted in higher growth rates and carbon isotope discrimination, but did not alter NSC levels. Growth and NSC decreased with decreasing leaf area in both treatments, but NSC did not correlate with leaf-level gas exchange indices, such as foliar d13C, [N] or [P]. A legacy effect was shown, as trees with initially low leaf area had limited ability to respond to prolonged irrigation. The NSC constancy across treatments provides evidence that carbohydrate storage may stay constant when climate changes are sufficiently slow to allow acclimation. Moreover, we speculate that total leaf area, rather than leaf gas exchange per unit leaf area, drives the variation in whole-tree carbohydrate dynamics in this system.

Schonbeck, Leonie↗

MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1

Highlights: • miR-374b expression was upregulated during NSC differentiation. • miR-374b promoted NSC proliferation and differentiation to neurons. • Hes1 was identified as a target gene of miR-374b. • miR-374b regulated NSC proliferation and differentiation by Hes1 Accumulating evidence has documented that microRNAs (miRNAs) are critical regulators of neural stem cell (NSC) proliferation and differentiation. MiRNA-374b (miR-374b) has been reported to play an important role in regulating various cellular processes, such as proliferation and differentiation. However, whether miR-374b is involved in NSC proliferation and differentiation remains unclear. In this study, we investigated the potential role of miR-374b in regulating NSC proliferation and differentiation to elucidate the underlying molecular mechanism. Our results showed that miR-374b expression was significantly upregulated during NSC differentiation. Functional experiments showed that overexpression of miR-374b promoted NSC proliferation and differentiation to neurons. By contrast, miR-374b inhibition showed the opposite effect. Hairy and enhancer of split 1 (Hes1), a master regulator of neurogenesis, was predicted as a potential target gene of miR-374b by bioinformatics analysis. Dual-luciferase reporter assays showed that miR-374b could directly target the 3′-untranslated region of Hes1. Further experiments showed that miR-374b negatively regulated the mRNA and protein expression of Hes1 in NSCs. Moreover, overexpression of Hes1 significantly reversed the miR-374b overexpression-mediated effect on NSC proliferation and differentiation. In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis.

60 APPLIED LIFE SCIENCES↗

The Near-infrared Spectrum of the Nuclear Star Cluster: Looking below the Tip of the Iceberg, and Comparisons with Extragalactic Nuclei

Long-slit near-infrared (NIR) spectra of the Galactic nuclear star cluster (NSC) are discussed. The spectra sample the major axis of the NSC out to its half-light radius. The absorption spectrum of the central regions of the NSC is averaged over angular scales of tens of arc seconds in order to sample globular cluster-like total luminosities, and the results are compared with model spectra. The equivalent widths of Na i2.21 μm and Ca 2.26 μm outside of the center of the NSC, where light from nuclear bulge stars contributes a large fraction to the total flux, are consistent with solar chemical mixtures. In contrast, the equivalent widths of Na i2.21 μm and Ca i2.26 μm near the center of the NSC are larger than expected from models with solar chemical mixtures, even after light from the brightest evolved stars is removed. The depths of spectroscopic features changing along the major axis of the NSC are consistent with imaging studies that have found evidence of population gradients in the NSC. That Na i2.21 μm and Ca i2.26 μm are deeper than predicted for solar chemical mixtures over a range of evolutionary states is consistent with previous studies that find that the majority of stars near the center of the NSC formed from material that had nonsolar chemical mixtures. The depths of the Na i2.21 μm and Ca i2.26 μm features in the central regions of the NSC are comparable to those in the nuclear spectrum of the early-type Virgo disk galaxy NGC 4491, and are deeper than in the central spectra of NGC 253 and 7793. A spectrum of nebular emission and the youngest stars near the galactic center is also extracted. The equivalent widths of emission features in the extracted NIR spectrum are similar to those in the nuclear spectrum of NGC 253, and it is argued that this agreement is best achieved if the current episode of star formation near the center of the NSC has been in progress for at least a few megayears.

79 ASTRONOMY AND ASTROPHYSICS↗

Differential effects of drought on nonstructural carbohydrate storage in seedlings and mature trees of four species in a subtropical forest

Nonstructural carbohydrates (NSC) play important roles in forest vulnerability to climate change, especially under increasing drought intensity and frequency. Understanding NSC dynamics is essential for accurately predicting the resistance and resilience of forests in response to drought. However, our knowledge of NSC re-sponses to drought is still limited due to the lack of research in trees of di?erent life stages. In this study, we conducted a throughfall exclusion experiment (TFE) with four subtropical evergreen tree species to examine drought e?ects on NSC in mature trees and understory seedlings. Our results showed the differential effects of drought on NSC dynamics of understory seedlings and mature trees. In the TFE experiment, mature trees of all four species were relatively homoeostatic with the insigni?cantly changed NSC pools, photosynthesis, and growth under the drought treatment compared to the control. In contrast, understory seedlings displayed sig-ni?cant decreases in total NSC and soluble sugars (-14.70 ± 3.66% and -16.93 ± 3.85%, respectively) with the exception of Lithocarpus glaber (L. glaber). The seedlings of L. glaber with the highest hydraulic resistance maintained or slightly increased NSC and its components in response to drought. Our study highlights the im-portance of life stage in assessing drought e?ects of trees on NSC storage and then forest C cycling, which could be incorporated into the dynamic global vegetation models (DGVMs) to better understand drought effects on forest C balance in the future.

Zhang, Peipei↗

Non-structural carbohydrates mediate seasonal water stress across Amazon forests

Non-structural carbohydrates (NSC) are major substrates for plant metabolism and have been implicated in mediating drought-induced tree mortality. Despite their significance, NSC dynamics in tropical forests remain little studied. We present leaf and branch NSC data for 82 Amazon canopy tree species in six sites spanning a broad precipitation gradient. During the wet season, total NSC (NSC T ) concentrations in both organs were remarkably similar across communities. However, NSC T and its soluble sugar (SS) and starch components varied much more across sites during the dry season. Notably, the proportion of leaf NSC T in the form of SS (SS:NSC T ) increased greatly in the dry season in almost all species in the driest sites, implying an important role of SS in mediating water stress in these sites. This adjustment of leaf NSC balance was not observed in tree species less-adapted to water deficit, even under exceptionally dry conditions. Thus, leaf carbon metabolism may help to explain floristic sorting across water availability gradients in Amazonia and enable better prediction of forest responses to future climate change.

54 ENVIRONMENTAL SCIENCES↗

Whole‐tree nonstructural carbohydrate storage and seasonal dynamics in five temperate species

Summary Despite the importance of nonstructural carbohydrates ( NSC ) for growth and survival in woody plants, we know little about whole‐tree NSC storage. The conventional theory suggests that NSC reserves will increase over the growing season and decrease over the dormant season. Here, we compare storage in five temperate tree species to determine the size and seasonal fluctuation of whole‐tree total NSC pools as well as the contribution of individual organs. NSC concentrations in the branches, stemwood, and roots of 24 trees were measured across 12 months. We then scaled up concentrations to the whole‐tree and ecosystem levels using allometric equations and forest stand inventory data. While whole‐tree total NSC pools followed the conventional theory, sugar pools peaked in the dormant season and starch pools in the growing season. Seasonal depletion of total NSC s was minimal at the whole‐tree level, but substantial at the organ level, particularly in branches. Surprisingly, roots were not the major storage organ as branches stored comparable amounts of starch throughout the year, and root reserves were not used to support springtime growth. Scaling up NSC concentrations to the ecosystem level, we find that commonly used, process‐based ecosystem and land surface models all overpredict NSC storage.

Furze, Morgan E.↗

Performance Test and Validation Evaluation for the Neutron Slab Counter

This Performance Testing and Validation Evaluation (PTVE) reviews and analyzes the data collected with the Neutron Slab Counter (NSC) according to the Performance Test and Validation Plan (PTVP, UCOR-4443) and reported in the NSC Performance Test and Validation Report (PTVR, NDA-13-0622). The NSC was designed for quantitative Nondestructive Assay (NDA) measurements of compressor volutes from the K25/K27 Buildings. The NSC PTVP (UCOR-4443) prescribed a methodology and set of field measurements to determine the NSC system efficiency, calibrate the system, perform verification measurements, define the components of the system's total measurement uncertainty, and perform a calibration confirmation measurement. All of the required measurements of the NSC PTVP (UCOR-4443) were completed according to the Calibration of NDA Equipment Procedure (PROC-DE-0714) and the Quantitative Measurements Using the Neutron Slab Counter Procedure (PROC-DE-0723). Following the completion of this PTVE, if the data quality objectives (DQO) of the NSC PTVP (UCOR-4443) are met, a commissioning report will be prepared which specifies the limits of use of the NSC.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Beyond carbon flux partitioning: Carbon allocation and nonstructural carbon dynamics inferred from continuous fluxes

Carbon (C) allocation and nonstructural carbon (NSC) dynamics play essential roles in plant growth and survival under stress and disturbance. However, quantitative understanding of these processes remains limited. Here, in this work, we propose a framework where we connect commonly measured carbon cycle components (eddy covariance fluxes of canopy CO 2 exchange, soil CO 2 efflux, and allometry-based biomass and net primary production) by a simple mass balance model to derive ecosystem-level NSC dynamics (NSC i ), C translocation (dC i ), and the biomass production efficiency (BPE i ) in above- and belowground plant (i = agp and bgp) compartments. We applied this framework to two long-term monitored loblolly pine (Pinus taeda) plantations of different ages in North Carolina and characterized the variations of NSC and allocation in years under normal and drought conditions. The results indicated that the young stand did not have net NSC flux at the annual scale, whereas the mature stand stored a near-constant proportion of new assimilates as NSC every year under normal conditions, which was comparable in magnitude to new structural growth. Roots consumed NSC in drought and stored a significant amount of NSC post drought. The above- and belowground dC i and BPE i varied more from year to year in the young stand and approached a relatively stable pattern in the mature stand. The belowground BPE bgp differed the most between the young and mature stands and was most responsive to drought. With the internal C dynamics quantified, this framework may also improve biomass production estimation, which reveals the variations resulting from droughts. Overall, these quantified ecosystem-scale dynamics were consistent with existing evidence from tree-based manipulative experiments and measurements and demonstrated that combining the continuous fluxes as proposed here can provide additional information about plant internal C dynamics. Given that it is based on broadly available flux data, the proposed framework is promising to improve the allocation algorithms in ecosystem C cycle models and offers new insights into observed variability in soil–plant–climate interactions.

54 ENVIRONMENTAL SCIENCES↗

Modeling starch dynamics from seasonal variations of photosynthesis, growth and respiration

Abstract Nonstructural carbohydrates (NSCs) buffer differences in plant carbon supply (photosynthesis) and demand (respiration, growth, etc.), but the regulation of their dynamics remains unresolved. Seasonal variations in NSCs are well-documented, but differences in the time-average, amplitude, phase and other characteristics across ecosystems and functional types lack explanation; furthermore, observed dynamics do not always match expectations. The failure to match observed and expected dynamics has stimulated debate on whether carbon supply or demand drives NSC dynamics. To gain insight into how carbon supply and demand drive seasonal NSC dynamics, we derive a simple model of NSC dynamics based on carbon mass balance and linearizing the NSC demand to determine how supply-driven and demand-driven seasonal NSC dynamics differ. We find that supply-driven and demand-driven dynamics yield distinct timings of seasonal extrema, and supply overrides demand when carbon supply is low in winter (e.g., at high latitudes). Our results also suggest that NSC dynamics often lag changes carbon mass balance. We also predict differences in NSC dynamics across mass, suggesting that saplings are more dynamic and respond more quickly to the environment than mature trees. Our findings suggest that substrate-dependent regulation with environmental variation is sufficient to generate complex NSC dynamics.

Forestry↗

Contrasting coordination of non‐structural carbohydrates with leaf and root economic strategies of alpine coniferous forests

Non-structural carbohydrates (NSCs), as the labile fraction and dominant carbon currency, are essential mediators of plant adaptation to environments. However, whether and how NSC coordinates with plant economic strategy frameworks, particularly the well-recognized leaf economics spectrums (LES) and root economics space (RES), remains unclear. We examined the relationships between NSC and key plant economics traits in leaves and fine roots across 90 alpine coniferous populations on the Tibetan Plateau, China. We observed contrasting coordination of NSC with economics traits in leaves and roots. Leaf total NSC and soluble sugar aligned with the leaf economic spectrum, conveying a trade-off between growth and storage in leaves. However, NSC in roots was independent of the root economic spectrum, but highly coordinated with root foraging, with more starch and less sugar in forage-efficient, thinner roots. Further, NSC-trait coordination in leaves and roots was, respectively, driven by local temperature and precipitation. These findings highlight distinct roles of NSC in shaping the above- and belowground multidimensional economics trait space, and NSC-based carbon economics provides a mechanistic understanding of how plants adapt to heterogeneous habitats and respond to environmental changes.

54 ENVIRONMENTAL SCIENCES↗