Latika Singh

Bio: Latika Singh is an academic researcher from University of California, Davis. The author has contributed to research in topics: Medicine & Asparagopsis taxiformis. The author has an hindex of 5, co-authored 11 publications receiving 98 citations.

Effect of the macroalgae Asparagopsis taxiformis on methane production and rumen microbiome assemblage

Abstract: Recent studies using batch-fermentation suggest that the red macroalgae Asparagopsis taxiformis has the potential to reduce methane (CH4) production from beef cattle by up to ~ 99% when added to Rhodes grass hay; a common feed in the Australian beef industry. These experiments have shown significant reductions in CH4 without compromising other fermentation parameters (i.e. volatile fatty acid production) with A. taxiformis organic matter (OM) inclusion rates of up to 5%. In the study presented here, A. taxiformis was evaluated for its ability to reduce methane production from dairy cattle fed a mixed ration widely utilized in California, the largest milk producing state in the US. Fermentation in a semi-continuous in-vitro rumen system suggests that A. taxiformis can reduce methane production from enteric fermentation in dairy cattle by 95% when added at a 5% OM inclusion rate without any obvious negative impacts on volatile fatty acid production. High-throughput 16S ribosomal RNA (rRNA) gene amplicon sequencing showed that seaweed amendment effects rumen microbiome consistent with the Anna Karenina hypothesis, with increased β-diversity, over time scales of approximately 3 days. The relative abundance of methanogens in the fermentation vessels amended with A. taxiformis decreased significantly compared to control vessels, but this reduction in methanogen abundance was only significant when averaged over the course of the experiment. Alternatively, significant reductions of CH4 in the A. taxiformis amended vessels was measured in the early stages of the experiment. This suggests that A. taxiformis has an immediate effect on the metabolic functionality of rumen methanogens whereas its impact on microbiome assemblage, specifically methanogen abundance, is delayed. The methane reducing effect of A. taxiformis during rumen fermentation makes this macroalgae a promising candidate as a biotic methane mitigation strategy for dairy cattle. But its effect in-vivo (i.e. in dairy cattle) remains to be investigated in animal trials. Furthermore, to obtain a holistic understanding of the biochemistry responsible for the significant reduction of methane, gene expression profiles of the rumen microbiome and the host animal are warranted.

Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer's disease.

Abstract: Author(s): Jin, Lee-Way; Lucente, Jacopo Di; Nguyen, Hai M; Singh, Vikrant; Singh, Latika; Chavez, Monique; Bushong, Trevor; Wulff, Heike; Maezawa, Izumi | Abstract: ObjectiveMicroglia play a pivotal role in the initiation and progression of Alzheimer's disease (AD). We here tested the therapeutic hypothesis that the Ca2+-activated potassium channel KCa3.1 constitutes a potential target for treating AD by reducing neuroinflammation.MethodsTo determine if KCa3.1 is relevant to AD, we tested if treating cultured microglia or hippocampal slices with Aβ oligomer (AβO) activated KCa3.1 in microglia, and if microglial KCa3.1 was upregulated in 5xFAD mice and in human AD brains. The expression/activity of KCa3.1 was examined by qPCR, Western blotting, immunohistochemistry, and whole-cell patch-clamp. To investigate the role of KCa3.1 in AD pathology, we resynthesized senicapoc, a clinically tested KCa3.1 blocker, and determined its pharmacokinetic properties and its effect on microglial activation, Aβ deposition and hippocampal long-term potentiation (hLTP) in 5xFAD mice.ResultsWe found markedly enhanced microglial KCa3.1 expression/activity in brains of both 5xFAD mice and AD patients. In hippocampal slices, microglial KCa3.1 expression/activity was increased by AβO treatment, and its inhibition diminished the proinflammatory and hLTP-impairing activities of AβO. Senicapoc exhibited excellent brain penetrance and oral availability, and in 5xFAD mice, reduced neuroinflammation, decreased cerebral amyloid load, and enhanced hippocampal neuronal plasticity.InterpretationOur results prompt us to propose repurposing senicapoc for AD clinical trials, as senicapoc has excellent pharmacological properties and was safe and well-tolerated in a prior phase-3 clinical trial for sickle cell anemia. Such repurposing has the potential to expedite the urgently needed new drug discovery for AD.

Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity.

Abstract: We have synthesized and established the structure of a long-suspected, but hitherto unknown, benzofuran side product (EBI) formed during the synthesis of NH-3. Understanding the mechanism of its formation has enabled isotope (D) labeling. We further developed a highly efficient method for separating EBI from NH-3. Interestingly, EBI was found to be a very potent thyroid hormone receptor (THR) agonist, while NH-3 is an antagonist. In this process, we have also achieved a significantly improved synthesis of NH-3.

The Trials and Tribulations of Structure Assisted Design of KCa Channel Activators.

Abstract: Calcium-activated K+ channels constitute attractive targets for the treatment of neurological and cardiovascular diseases. To explain why certain 2-aminobenzothiazole/oxazole-type KCa activators (SKAs) are KCa3.1 selective we previously generated homology models of the C-terminal calmodulin-binding domain (CaM-BD) of KCa3.1 and KCa2.3 in complex with CaM using Rosetta modeling software. We here attempted to employ this atomistic level understanding of KCa activator binding to switch selectivity around and design KCa2.2 selective activators as potential anticonvulsants. In this structure-based drug design approach we used RosettaLigand docking and carefully compared the binding poses of various SKA compounds in the KCa2.2 and KCa3.1 CaM-BD/CaM interface pocket. Based on differences between residues in the KCa2.2 and KCa.3.1 models we virtually designed 168 new SKA compounds. The compounds that were predicted to be both potent and KCa2.2 selective were synthesized, and their activity and selectivity tested by manual or automated electrophysiology. However, we failed to identify any KCa2.2 selective compounds. Based on the full-length KCa3.1 structure it was recently demonstrated that the C-terminal crystal dimer was an artefact and suggested that the "real" binding pocket for the KCa activators is located at the S4-S5 linker. We here confirmed this structural hypothesis through mutagenesis and now offer a new, corrected binding site model for the SKA-type KCa channel activators. SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine) is binding in the interface between the CaM N-lobe and the S4-S5 linker where it makes van der Waals contacts with S181 and L185 in the S45A helix of KCa3.1.

The future of food from the sea.

Abstract: Global food demand is rising, and serious questions remain about whether supply can increase sustainably1 Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services2–6 As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050 Here we examine the main food-producing sectors in the ocean—wild fisheries, finfish mariculture and bivalve mariculture—to estimate ‘sustainable supply curves’ that account for ecological, economic, regulatory and technological constraints We overlay these supply curves with demand scenarios to estimate future seafood production We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21–44 million tonnes by 2050, a 36–74% increase compared to current yields This represents 12–25% of the estimated increase in all meat needed to feed 98 billion people by 2050 Increases in all three sectors are likely, but are most pronounced for mariculture Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand Modelled supply curves show that, with policy reform and technological innovation, the production of food from the sea may increase sustainably, perhaps supplying 25% of the increase in demand for meat products by 2050

Global and regional drivers of land-use emissions in 1961–2017

Abstract: Historically, human uses of land have transformed and fragmented ecosystems1,2, degraded biodiversity3,4, disrupted carbon and nitrogen cycles5,6 and added prodigious quantities of greenhouse gases (GHGs) to the atmosphere7,8. However, in contrast to fossil-fuel carbon dioxide (CO2) emissions, trends and drivers of GHG emissions from land management and land-use change (together referred to as ‘land-use emissions’) have not been as comprehensively and systematically assessed. Here we present country-, process-, GHG- and product-specific inventories of global land-use emissions from 1961 to 2017, we decompose key demographic, economic and technical drivers of emissions and we assess the uncertainties and the sensitivity of results to different accounting assumptions. Despite steady increases in population (+144 per cent) and agricultural production per capita (+58 per cent), as well as smaller increases in emissions per land area used (+8 per cent), decreases in land required per unit of agricultural production (–70 per cent) kept global annual land-use emissions relatively constant at about 11 gigatonnes CO2-equivalent until 2001. After 2001, driven by rising emissions per land area, emissions increased by 2.4 gigatonnes CO2-equivalent per decade to 14.6 gigatonnes CO2-equivalent in 2017 (about 25 per cent of total anthropogenic GHG emissions). Although emissions intensity decreased in all regions, large differences across regions persist over time. The three highest-emitting regions (Latin America, Southeast Asia and sub-Saharan Africa) dominate global emissions growth from 1961 to 2017, driven by rapid and extensive growth of agricultural production and related land-use change. In addition, disproportionate emissions are related to certain products: beef and a few other red meats supply only 1 per cent of calories worldwide, but account for 25 per cent of all land-use emissions. Even where land-use change emissions are negligible or negative, total per capita CO2-equivalent land-use emissions remain near 0.5 tonnes per capita, suggesting the current frontier of mitigation efforts. Our results are consistent with existing knowledge—for example, on the role of population and economic growth and dietary choice—but provide additional insight into regional and sectoral trends. Trends in the rate of region- and sector-specific land-use greenhouse gas emissions in 1961–2017 show an acceleration of about 20% per decade after 2001.

Red seaweed (Asparagopsis taxiformis) supplementation reduces enteric methane by over 80 percent in beef steers

Abstract: The red macroalgae (seaweed) Asparagopsis spp. has shown to reduce ruminant enteric methane (CH4) production up to 99% in vitro. The objective of this study was to determine the effect of Asparagopsis taxiformis on CH4 production (g/day per animal), yield (g CH4/kg dry matter intake (DMI)), and intensity (g CH4/kg ADG); average daily gain (ADG; kg gain/day), feed conversion efficiency (FCE; kg ADG/kg DMI), and carcass and meat quality in growing beef steers. Twenty-one Angus-Hereford beef steers were randomly allocated to one of three treatment groups: 0% (Control), 0.25% (Low), and 0.5% (High) A. taxiformis inclusion based on organic matter intake. Steers were fed 3 diets: high, medium, and low forage total mixed ration (TMR) representing life-stage diets of growing beef steers. The Low and High treatments over 147 days reduced enteric CH4 yield 45 and 68%, respectively. However, there was an interaction between TMR type and the magnitude of CH4 yield reduction. Supplementing low forage TMR reduced CH4 yield 69.8% (P <0.01) for Low and 80% (P <0.01) for High treatments. Hydrogen (H2) yield (g H2/DMI) increased (P <0.01) 336 and 590% compared to Control for the Low and High treatments, respectively. Carbon dioxide (CO2) yield (g CO2/DMI) increased 13.7% between Control and High treatments (P = 0.03). No differences were found in ADG, carcass quality, strip loin proximate analysis and shear force, or consumer taste preferences. DMI tended to decrease 8% (P = 0.08) in the Low treatment and DMI decreased 14% (P <0.01) in the High treatment. Conversely, FCE tended to increase 7% in Low (P = 0.06) and increased 14% in High (P <0.01) treatment compared to Control. The persistent reduction of CH4 by A. taxiformis supplementation suggests that this is a viable feed additive to significantly decrease the carbon footprint of ruminant livestock and potentially increase production efficiency.