Emerging methods in therapeutics using multifunctional nanoparticles

Clinical translation of nanoparticle‐based drug delivery systems is hindered by an array of challenges including poor circulation time and limited targeting. Novel approaches including designing multifunctional particles, cell‐mediated delivery systems, and fabrications of protein‐based nanoparticles have gained attention to provide new perspectives to current drug delivery obstacles in the interdisciplinary field of nanomedicine. Collectively, these nanoparticle devices are currently being investigated for applications spanning from drug delivery and cancer therapy to medical imaging and immunotherapy. Here, we review the current state of the field, highlight opportunities, identify challenges, and present the future directions of the next generation of multifunctional nanoparticle drug delivery platforms.This article is categorized under:Biology‐Inspired Nanomaterials > Protein and Virus‐Based StructuresNanotechnology Approaches to Biology > Nanoscale Systems in BiologyNovel approaches in designing nanoparticles to overcome challenges faced by traditional nanoparticle‐based drug delivery systems.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155963/1/wnan1625.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155963/2/wnan1625_am.pd

Impacts of elevated dissolved CO2 on a shallow groundwater system: reactive transport modeling of a controlled-release field test

One of the risks that CO2 geological sequestration imposes on the environment is the impact of potential CO2/brine leakage on shallow groundwater. The reliability of reactive transport models predicting the response of groundwater to CO2 leakage depends on a thorough understanding of the relevant chemical processes and key parameters affecting dissolved CO2 transport and reaction. Such understanding can be provided by targeted field tests integrated with reactive transport modeling. A controlled-release field experiment was conducted in Mississippi to study the CO2-induced geochemical changes in a shallow sandy aquifer at about 50 m depth. The field test involved a dipole system in which the groundwater was pumped from one well, saturated with CO2 at the pressure corresponding to the hydraulic pressure of the aquifer, and then re-injected into the same aquifer using a second well. Groundwater samples were collected for chemical analyses from four monitoring wells before, during and after the dissolved CO2 was injected. In this paper, we present reactive transport models used to interpret the observed changes in metal concentrations in these groundwater samples. A reasonable agreement between simulated and measured concentrations indicates that the chemical response in the aquifer can be interpreted using a conceptual model that encompasses two main features: (a) a fast-reacting but limited pool of reactive minerals that responds quickly to changes in pH and causes a pulse-like concentration change, and (b) a slow-reacting but essentially unlimited mineral pool that yields rising metal concentrations upon decreased groundwater velocities after pumping and injection stopped. During the injection, calcite dissolution and Ca-driven cation exchange reactions contribute to a sharp pulse in concentrations of Ca, Ba, Mg, Mn, K, Li, Na and Sr, whereas desorption reactions control a similar increase in Fe concentrations. After the injection and pumping stops and the groundwater flow rate decreases, the dissolution of relatively slow reacting minerals such as plagioclase drives the rising concentrations of alkali and alkaline earth metals observed at later stages of the test, whereas the dissolution of amorphous iron sulfide causes slowly increasing Fe concentrations

A High-Quality Assembly of the Nine-Spined Stickleback (Pungitius pungitius) Genome

The Gasterosteidae fish family hosts several species that are important models for eco-evolutionary, genetic, and genomic research. In particular, a wealth of genetic and genomic data has been generated for the three-spined stickleback (Gasterosteus aculeatus), the "ecology's supermodel," whereas the genomic resources for the nine-spined stickleback (Pungitius pungitius) have remained relatively scarce. Here, we report a high-quality chromosome-level genome assembly of P. pungitius consisting of 5,303 contigs (N50 = 1.2Mbp) with a total size of 521 Mbp. These contigs were mapped to 21 linkage groups using a high-density linkage map, yielding a final assembly with 98.5% BUSCO completeness. A total of 25,062 protein-coding genes were annotated, and about 23% of the assembly was found to consist of repetitive elements. A comprehensive analysis of repetitive elements uncovered centromere-specific tandem repeats and provided insights into the evolution of retrotransposons. A multigene phylogenetic analysis inferred a divergence time of about 26 million years ago (Ma) between nine- and three-spined sticklebacks, which is far older than the commonly assumed estimate of 13 Ma. Compared with the three-spined stickleback, we identified an additional duplication of several genes in the hemoglobin cluster. Sequencing data from populations adapted to different environments indicated potential copy number variations in hemoglobin genes. Furthermore, genome-wide synteny comparisons between three- and nine-spined sticklebacks identified chromosomal rearrangements underlying the karyotypic differences between the two species. The high-quality chromosome-scale assembly of the nine-spined stickleback genome obtained with long-read sequencing technology provides a crucial resource for comparative and population genomic investigations of stickleback fishes and teleosts.Peer reviewe

Population transcriptomics reveals weak parallel genetic basis in repeated marine and freshwater divergence in nine-spined sticklebacks

Abstract The degree to which adaptation to similar selection pressures is underlain by parallel vs. non-parallel genetic changes is a topic of broad interest in contemporary evolutionary biology. Sticklebacks provide opportunities to characterize and compare the genetic underpinnings of repeated marine-freshwater divergences at both intra- and interspecific levels. While the degree of genetic parallelism in repeated marine-freshwater divergences has been frequently studied in the three-spined stickleback (Gasterosteus aculeatus), much less is known about this in other stickleback species. Using a population transcriptomic approach, we identified both genetic and gene expression variations associated with marine-freshwater divergence in the nine-spined stickleback (Pungitius pungitius). Specifically, we used a genome-wide association study approach, and found that ~1% of the total 173,491 identified SNPs showed marine-freshwater ecotypic differentiation. A total of 861 genes were identified to have SNPs associated with marine-freshwater divergence in nine-spined stickleback, but only 12 of these genes have also been reported as candidates associated with marine-freshwater divergence in the three-spined stickleback. Hence, our results indicate a low degree of interspecific genetic parallelism in marine-freshwater divergence. Moreover, 1,578 genes in the brain and 1,050 genes in the liver were differentially expressed between marine and freshwater nine-spined sticklebacks, ~5% of which have also been identified as candidates associated with marine-freshwater divergence in the three-spined stickleback. However, only few of these (e.g., CLDND1) appear to have been involved in repeated marine-freshwater divergence in nine-spined sticklebacks. Taken together, the results indicate a low degree of genetic parallelism in repeated marine-freshwater divergence both at intra- and interspecific levels.Peer reviewe

Gut Microbial Trimethylamine Is Elevated in Alcohol-Associated Hepatitis and Contributes to Ethanol-Induced Liver Injury in Mice

There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury

Sustainable food security in India—Domestic production and macronutrient availability

<div><p>India has been perceived as a development enigma: Recent rates of economic growth have not been matched by similar rates in health and nutritional improvements. To meet the second Sustainable Development Goal (SDG2) of achieving zero hunger by 2030, India faces a substantial challenge in meeting basic nutritional needs in addition to addressing population, environmental and dietary pressures. Here we have mapped—for the first time—the Indian food system from crop production to household-level availability across three key macronutrients categories of ‘calories’, ‘digestible protein’ and ‘fat’. To better understand the potential of reduced food chain losses and improved crop yields to close future food deficits, scenario analysis was conducted to 2030 and 2050. Under India’s current self-sufficiency model, our analysis indicates severe shortfalls in availability of all macronutrients across a large proportion (>60%) of the Indian population. The extent of projected shortfalls continues to grow such that, even in ambitious waste reduction and yield scenarios, enhanced domestic production alone will be inadequate in closing the nutrition supply gap. We suggest that to meet SDG2 India will need to take a combined approach of optimising domestic production and increasing its participation in global trade.</p></div

Summary Report on CO{sub 2} Geologic Sequestration &amp; Water Resources Workshop

The United States Environmental Protection Agency (EPA) and Lawrence Berkeley National Laboratory (LBNL) jointly hosted a workshop on “CO{sub 2} Geologic Sequestration and Water Resources” in Berkeley, June 1–2, 2011. The focus of the workshop was to evaluate R&D needs related to geological storage of CO{sub 2} and potential impacts on water resources. The objectives were to assess the current status of R&amp;D, to identify key knowledge gaps, and to define specific research areas with relevance to EPA’s mission. About 70 experts from EPA, the DOE National Laboratories, industry, and academia came to Berkeley for two days of intensive discussions. Participants were split into four breakout session groups organized around the following themes: Water Quality and Impact Assessment/Risk Prediction; Modeling and Mapping of Area of Potential Impact; Monitoring and Mitigation; Wells as Leakage Pathways. In each breakout group, participants identified and addressed several key science issues. All groups developed lists of specific research needs; some groups prioritized them, others developed short-term vs. long-term recommendations for research directions. Several crosscutting issues came up. Most participants agreed that the risk of CO{sub 2} leakage from sequestration sites that are properly selected and monitored is expected to be low. However, it also became clear that more work needs to be done to be able to predict and detect potential environmental impacts of CO{sub 2} storage in cases where the storage formation may not provide for perfect containment and leakage of CO{sub 2}–brine might occur