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Biogenic Selenium Nanoparticles: Potential Strategy to Oxidative Strain Mediated Inflammation in Arthritis rheumatoid along with Related Problems.
Microbial communities (microbiomes) have been harnessed in biotechnology applications such as wastewater treatment and bioremediation for over a century. Traditionally, engineering approaches have focused on shaping the environment to steer microbiome function versus direct manipulation of the microbiome's metabolic network. While these selection-based approaches have proven to be invaluable for guiding bioprocess engineering, they do not enable the precise manipulation and control of microbiomes required for unlocking their full potential. Over the past 2 decades, systems biology has revolutionized our understanding of the metabolic networks driving microbiome processes, and more recently genetic engineering tools have started to emerge for nonmodel microorganisms and microbiomes. In this commentary, I discuss how systems biology approaches are being used to generate actionable understanding of microbiome functions in engineered ecosystems. I also highlight how integrating synthetic biology, automation, and machine learning can accelerate microbiome engineering to meet the sustainability challenges of the future.The antibiotic growth promoters (AGPs) flavophospholipol and virginiamycin have been widely used for decades in food animal production. AGP activity is believed to be partly modulated by gut microbial composition although exact AGP-induced changes remain unclear. In a controlled intervention study, we studied the effect of flavophospholipol and virginiamycin on the broiler chicken ileal microbiota spanning from birth to 39 days. Using 16S rRNA gene profiling and prediction of metabolic activity, we show that both AGPs result in dynamic microbial shifts that potentially increase anti-inflammatory mechanisms and bioavailability of several essential nutrients by decreasing degradation (flavophospholipol) or increasing biosynthesis (virginiamycin). Further, virginiamycin-supplemented broilers showed increased colonization with potentially pathogenic bacteria, Clostridium perfringens, Campylobacter, and Escherichia/Shigella spp. Overall, we show that both AGPs induce microbial changes potentially beneficial for growth. However, the increase in (foodborne) pathogens shown here with virginiamycin use could impact not only broiler mortality but also human health. IMPORTANCE Antibiotic growth promoters (AGPs) are commonly used within poultry farming to increase muscle growth. Microbial composition in the gut is known to be influenced by AGP use although exact AGP-induced changes remain unclear. Utilizing 16S rRNA gene profiling, this study provides a first head-to-head comparison of the effect of the two most commonly used AGPs, flavophospholipol and virginiamycin, on the broiler chicken ileum microbiota over time. We found that supplementation with both AGPs altered ileal microbial composition, thereby increasing potential bioavailability of essential nutrients and weight gain. Flavophospholipol showed a slight benefit over virginiamycin as the latter resulted in more extensive microbial perturbations including increased colonization by enteropathogens, which could impact broiler mortality.With the advent of metagenomics, a quest began to identify the dynamics of the microbial communities in different ecological niches. Altogether, this has resulted in identification of microorganisms but is limited to only a small number of phylogenetic groups that can be easily cultured. The majority of metagenomic sequencing data remains unassigned to any known microbial group and is regarded as the "microbial dark matter." Our group is now working on integrating culturomics (isolation of pure cultures) and metagenomics from extreme environments, particularly from hot water springs and chemically contaminated soils. Our target is to culture the rare extremophiles with biotechnological significance by designing culture media based on inputs from metagenomics. While culturomics integrated with metagenomics has been extensively employed for updating the microbial catalog from the human gut, there is a need to extend this approach to extreme environmental settings to explore the microbial dark matter.Technological advances in community sequencing have steadily increased the taxonomic resolution at which microbes can be delineated. In high-resolution metagenomics, bacterial strains can now be resolved, enhancing medical microbiology and the description of microbial evolution in vivo. In the Hildebrand lab, we are researching novel approaches to further increase the phylogenetic resolution of metagenomics. I propose that ultra-resolution metagenomics will be the next qualitative level of community sequencing, classified by the accurate resolution of ultra-rare genetic events, such as subclonal mutations present in all populations of evolving cells. This will be used to quantify evolutionary processes at ecologically relevant scales, monitor the progress of infections within a patient, and accurately track pathogens in food and infection chains. However, to develop this next metagenomic generation, we first need to understand the currently imposed limits of sequencing technologies, metagenomic strain delineation, and genome reconstructions.Microbes produce structurally diverse natural products to interact with their environment. Many of the biosynthetic products involved in this "metabolic small talk" have been exploited for the treatment of various diseases. As an alternative to the traditional bioactivity-guided workflow, genome mining has been introduced for targeted natural product discovery based on genome sequence information. In this commentary, we will discuss the evolution of genome mining, as well as its current limitations. The Helfrich laboratory aims to play a leading role in overcoming these limitations with the development of computational strategies to identify noncanonical biosynthetic pathways and to decipher the principles that govern the production of the associated metabolites. We will use these insights to develop algorithms for the prediction of natural product scaffolds. These studies will pave the way toward a more comprehensive understanding of the full biosynthetic repertoire encoded in microbial genomes and provide access to novel metabolites.The virosphere (i.e., global virome) represents a vast library of unknown genes on the planet. click here Synthetic biology through engineering principles could be the key to unlocking this massive global gene repository. Synthetic viruses may also be used as tools to understand "the rules of life" in diverse microbial ecosystems. Such insights may be crucial for understanding the assembly, diversity, structure, and scale of virus-mediated function. Viruses directly affect resilience, stability, and microbial community selection via death resistance cycles. Interpreting and clarifying these effects is essential for predicting the system's ecology, evolution, and ecosystem stability in an increasingly unstable global climate. A "silent looming pandemic" due to multidrug-resistant microbes will directly impact the global economy, and synthetic virology could provide a future strategy of treatment using targeted viral therapy. This commentary will discuss current techniques for manipulating viruses synthetically, contributing to improved human health and sustainable agriculture.Mammals maintain close associations with gut microbes that provide numerous nutritional benefits, including vitamin synthesis. While most mammals obtain sufficient vitamins from their diets, deficiencies in various B vitamins (biotin, cobalamin, riboflavin, thiamine, etc.) are reported in captive animals. Biomedical and agricultural research has shown that gut microbes are capable of synthesizing B vitamins and assisting with host vitamin homeostasis. However, we have a poor understanding of distribution and abundance of B-vitamin synthesis across mammalian hosts. Here, we leveraged a publicly available metagenomic data set from 39 mammalian species and used MG-RAST to compare the abundance and composition of B-vitamin-synthesizing microbes across mammalian feeding strategies. We predicted that herbivores would have the highest abundance of genes associated with vitamin synthesis, as plant material is often low in B vitamins. However, this hypothesis was not supported. Instead, we found that relative abundanc, our understanding of processes of vitamin synthesis across animals is severely limited. Here, we compared the abundance of genes associated with the synthesis of B vitamins and the taxonomic composition of the microbes containing these genes. We found that herbivores, omnivores, and carnivores harbor distinct communities of microbes that putatively conduct vitamin synthesis. Additionally, carnivores exhibited the highest abundance of genes associated with synthesis of specific B vitamins, cobalamin and thiamine. These data uncover the potential importance of microbes in the vitamin homeostasis of various mammals, especially carnivorous mammals. These findings have implications for understanding the microbial interactions that contribute to the nutritional requirements of animals held in captivity.Viral infections are associated with extensive remodeling of the cellular proteome. Viruses encode gene products that manipulate host proteins to redirect cellular processes or subvert antiviral immune responses. Adenovirus (AdV) encodes proteins from the early E4 region which are necessary for productive infection. Some cellular antiviral proteins are known to be targeted by AdV E4 gene products, resulting in their degradation or mislocalization. However, the full repertoire of host proteome changes induced by viral E4 proteins has not been defined. To identify cellular proteins and processes manipulated by viral products, we developed a global, unbiased proteomics approach to analyze changes to the host proteome during infection with adenovirus serotype 5 (Ad5) virus. We used whole-cell proteomics to measure total protein abundances in the proteome during Ad5 infection. Since host antiviral proteins can antagonize viral infection by associating with viral genomes and inhibiting essential viral processes, weto understanding how virus-host interactions influence the outcome of infection. Adenovirus encodes early gene products from the E4 genomic region that are known to alter host response pathways and promote replication, but the full extent of proteome modifications they mediate is not known. We used an integrated proteomics approach to quantitate protein abundance and protein associations with viral DNA during virus infection. Systems-level analysis identifies cellular proteins and processes impacted in an E4-dependent manner, suggesting ways that adenovirus counteracts potentially inhibitory host defenses. This study provides a global view of adenovirus-mediated proteome remodeling, which can serve as a model to investigate virus-host interactions of DNA viruses.Language constitutes an essential set of scientific construction tools, not only for communicating knowledge, but for conceptualizing the world. Metaphors in particular, as conventions that guide and reproduce analogical reasoning, merit attention that they largely do not receive. My research addresses this deficit by examining how metaphors for handling microbes shape possibilities for working with yeast and bacteria in synthetic biology, microbiome research, and other fields that reconfigure what microbes can be. Though poised to reexamine assumptions, these fields routinely rest on metaphors and other language tools that quietly embed ways of thinking that may work against wider aims-for example, imagining bacteria as imperfect machines that should therefore be rendered increasingly passive and controllable. Researchers, therefore, need to examine how language tools structure their observations and expectations so that the tools they choose are appropriate for the work they want to do.
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