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Robertson, G. P.

Publications and source records attributed to Robertson, G. P..

6 recordsLinked to original sources

Assessing the Potential of Switchgrass (Panicum virgatum L.) for Storing Carbon Belowground: Insights from a Multi-Site US Study

Agricultural intensification depletes belowground carbon (C) stocks, partly due to the exclusion of deep-rooted perennial species from landscapes where they were once dominant. Reintroducing deep-rooted perennials to cultivated land may help to mitigate SOC loss and restore ecosystem function. We quantified the effect of replacing shallow-rooted annual crops with a deep-rooted perennial grass, switchgrass (Panicum virgatum L.), by comparing 10 to 30 year-old switchgrass stands with paired annual row crop fields across the central and eastern USA. We hypothesized that switchgrass would store more root C and SOC than neighboring shallow-rooted annual crops, and that these effects would extend deeper than 30 cm. We also evaluated whether switchgrass stimulates decomposition of SOC at depth using radiocarbon (14C) to quantify replacement of slow cycling isotopically depleted SOC. Finally, we explored whether the effect of switchgrass on SOC is moderated by soil chemical and physical properties. While the effect of switchgrass on SOC in the surface 100 cm was positive at most sites, the average effect was highly uncertain and statistically indistinguishable from zero (mean difference in SOC = 0.6 kg C m-2 [95% CI -0.8 to +1.9 kg C m-2]). By contrast, we found that root biomass C was consistently more deeply distributed and more abundant under switchgrass, yielding an estimated additional 0.6 kg C m-2 in the surface 100 cm of soil under switchgrass [95% CI +0.5 to +0.7 kg C m-2]. 14C measurements suggested that root C inputs were adding to existing SOC without stimulating decomposition. The effect of switchgrass on belowground C was not strongly related to any of the environmental factors that we evaluated. Our observations show that root biomass C can contribute substantially to belowground C stocks when deep-rooted perennial grasses replace shallow-rooted annual crops.

ecology↗

Novel Pan-ALDH Inhibitor KS100 Effectively Targets ALDH+/CD138- Stem-like Cells to Overcome Relapse in Multiple Myeloma

Multiple myeloma (MM), a clonal plasma cell disorder is the second most frequent hematological malignancy in the United States. This malignancy is characterized by a series of symptoms such as bone lesions, hypercalcemia, renal failure, and anemia. The current clinical drugs in the market are successful in treating multiple myeloma patients into remission but does not address relapse where a more aggressive phenotype of the cancer remains untreatable. We hypothesize that a small subset of multiple myeloma stem-like cells (MMSLCs) that overexpress aldehyde dehydrogenases (ALDH+) is the cause of the relapse. Overexpression of ALDH bolsters drug resistance via detoxification and stemness via the retinoic acid signaling pathway. The phenotype of MMSLCs is not yet known for certainty but there are a few well established markers such CD138 negative (CD138neg) cells that are known to overexpress ALDH. In this study, we target regular MM cells and bortezomib resistant ALDH+/CD138neg MMSLCs with a novel, potent, pan-ALDH inhibitor, KS100. Here we report KS100 effectively lowered ALDH expression in regular and bortezomib resistant ALDH+/CD138neg cells, MM cell viability as well as proteins associated with MMSLCs. Most importantly we showed that KS100 lowered ALDH+ populations in regular, bortezomib resistant and CD138neg cells via ALDEFLUOR assay.

molecular biology↗

A Multi-Model Ensemble Reveals Soil Carbon Gains from Regenerative Practices in the U.S. Midwest Cropland

Process-based cropping systems models (CSMs) are key components of measurement, monitoring, reporting, and verification (MMRV) frameworks of carbon markets, but their application suffers from model-specific differences that keep any one model from working well across all combinations of soils, climates, crops, and agronomic practices at varying scales. Multi-model ensemble (MME), successfully used to quantify soil, management and climate impact on crop productivity, provide an opportunity to better estimate changes in soil organic carbon (SOC) outcomes for agronomic practices that have the potential to mitigate SOC loss at scale. We used an MME across 46 million hectares of US Midwest cropland at a resolution of 4- km2 to assess the aggregate ability of different regenerative practices to sequester SOC at this scale compared to their dynamic baselines. MME was validated with long-term experimental data and compared to its constituent CSMs, showing greater accuracy and lower uncertainty. The results show that adopting no-till combined with cover crops increased SOC stocks by 0.36 {+/-} 0.12 Mg ha-1 yr-1 aggregated across the entire U.S. Midwest cropland. At the regional scale, this corresponds to a net SOC gain of 16.4 Tg C yr-1 compared to business-as-usual baselines. These benefits are approximately halved when each management change is practiced individually, and the modest gains are only fully realized when continued over the long-term in soils with low initial carbon stock. Results demonstrate the power of MMEs run at high resolution for providing robust estimates of environmental outcomes following agricultural practice change, and for pinpointing locations for most effective intervention. This approach can alleviate many producer carbon market participation barriers and help address market issues while ultimately supporting large-scale regenerative agriculture initiatives.

ecology↗

Development of a Novel Bruton's Tyrosine Kinase Inhibitor that exerts Anti-Cancer Activities Potentiates Response of Chemotherapeutic Agents In Multiple Myeloma Stem Cell-Like Cells

Despite recent improvements in multiple myeloma (MM) treatment, MM remains an incurable disease and most patients experience a relapse. The major reason for myeloma recurrence is the persistent stem cell-like population. It has been demonstrated that overexpression of Brutons tyrosine kinase (BTK) in MM stem cell-like cells is correlated with drug resistance and poor prognosis. We have developed a novel small BTK inhibitor, KS151, which is unique compared to other BTK inhibitors. Unlike ibrutinib, and the other BTK inhibitors such as acalabrutinib, orelabrutinib, and zanubrutinib that covalently bind to the C481 residue in the BTK kinase domain, KS151 can inhibit BTK activities without binding to C481. This feature of KS151 is important because C481 becomes mutated in many patients and causes drug resistance. We demonstrated that KS151 inhibits in vitro BTK kinase activities and is more potent than ibrutinib. Furthermore, by performing a semi-quantitative, sandwich-based array for 71-tyrosine kinase phosphorylation, we found that KS151 specifically inhibits BTK. Our western blotting data showed that KS151 inhibits BTK signaling pathways and is effective against bortezomib-resistant cells as well as MM stem cell-like cells. Moreover, KS151 potentiates the apoptotic response of bortezomib, lenalidomide, and panobinostat in both MM and stem cell-like cells. Interestingly, KS151 inhibits stemness markers and is efficient in inhibiting Nanog and Gli1 stemness markers even when MM cells were co-cultured with bone marrow stromal cells (BMSCs). Overall, our results show that we have developed a novel BTK inhibitor effective against the stem cell-like population, and potentiates the response of chemotherapeutic agents.

molecular biology↗

Long-term research needed to avoid spurious and misleading trends in sustainability attributes of no-till

Agricultural management recommendations based on short-term studies can produce findings inconsistent with long-term reality. Here, we test the long-term relative profitability and environmental sustainability of continuous no-till agriculture practices on crop yield, soil moisture, and N2O fluxes. Using a moving window approach, we investigate the development and stability of several attributes of continuous no-till as compared to conventional till agriculture over a 29-year period at a site in the upper Midwest, U.S. We find that over a decade is needed to detect the consistent benefits of no-till on important attributes at this site. Both crop yield and soil moisture required periods 15 years or longer to generate patterns consistent with 29-year trends. Only marginally significant trends for N2O fluxes appeared in this period. Importantly, significant but misleading short-term trends appeared in more than 20% of the periods examined. Relative profitability analysis suggests that 10 years after initial implementation, 86% of periods recuperated the initial expense of no-till implementation, with the probability of higher relative profit increasing with longevity. Results underscore the essential importance of decade and longer studies for revealing the long-term dynamics and emergent outcomes of agricultural practices for different sustainability attributes and are consistent with recommendations to support the long-term adoption of no-till management.\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC=\"FIGDIR/small/788240v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (42K):\norg.highwire.dtl.DTLVardef@1e7529eorg.highwire.dtl.DTLVardef@1e11268org.highwire.dtl.DTLVardef@17f8995org.highwire.dtl.DTLVardef@2196fe_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIWe test long-term effects of no-till on yield, soil moisture, and N2O fluxes\nC_LIO_LIWe examine 29 years of data with a moving window and relative profitability method\nC_LIO_LIIt takes at least a decade to detect consistent benefits of no-till\nC_LIO_LIShorter studies can produce significant but misleading findings\nC_LIO_LILong studies are essential to reveal the dynamics of agricultural management\nC_LI

ecology↗

Suppression of p16 increases nucleotide synthesis via mTORC1

Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in reprogramming metabolism by increasing nucleotide synthesis. This occurred via activation of mTORC1 signaling, which directly mediated increased translation of the mRNA encoding ribose-5-phosphate isomerase A (RPIA), a pentose phosphate pathway enzyme. p16 loss correlated with activation of the mTORC1-RPIA axis in multiple cancer types. Suppression of RPIA inhibited proliferation only in p16-low cells by inducing senescence both in vitro and in vivo. These data reveal the molecular basis whereby p16 loss modulates pro-tumorigenic metabolism through mTORC1-mediated upregulation of nucleotide synthesis and reveals a metabolic vulnerability of p16-null cancer cells.\n\nHighlightsO_LImTORC1 is activated by p16 knockdown to increase nucleotide synthesis and bypass senescence\nC_LIO_LImTORC1 directly increases translation RPIA to increase ribose-5-phosphate\nC_LIO_LIActivation of mTORC1 pathway downstream of p16 suppression is independent of RB\nC_LIO_LIRPIA suppression induces senescence only in cells and tumors with low p16\nC_LI

cancer biology↗