Our ability to generate bacterial strains with unique and increasingly complex functions has rapidly expanded in recent times. The capacity for DNA synthesis is increasing and costing less; new tools ...are being developed for fast, large-scale genetic manipulation; and more tested genetic parts are available for use, as is the knowledge of how to use them effectively. These advances promise to unlock an exciting array of 'smart' bacteria for clinical use but will also challenge scientists to better optimize preclinical testing regimes for early identification and validation of promising strains and strategies. Here, we review recent advances in the development and testing of engineered bacterial diagnostics and therapeutics. We highlight new technologies that will assist the development of more complex, robust and reliable engineered bacteria for future clinical applications, and we discuss approaches to more efficiently evaluate engineered strains throughout their preclinical development.
The SERS effect was initially discovered in the 1970s. Early research focused on understanding the phenomenon and increasing enhancement to achieve single molecule detection. From the mid-1980s to ...early 1990s, research started to move away from obtaining a fundamental understanding of the phenomenon to the exploration of analytical applications. At the same time, significant developments occurred in the field of photonics that led to the advent of inexpensive, robust, compact, field-deployable Raman systems. The 1990s also saw rapid development in nanoscience. This convergence of technologies (photonics and nanoscience) has led to accelerated development of SERS substrates to detect a wide range of chemical and biological analytes. It would be a monumental task to discuss all the different kinds of SERS substrates that have been explored. Likewise, it would be impossible to discuss the use of SERS for both chemical and biological detection. Instead, a review of the most common metallic (Ag, Cu, and Au) SERS substrates for chemical detection only is discussed, as well as SERS substrates that are commercially available. Other issues with SERS for chemical detection have been selectivity, reversibility, and reusability of the substrates. How these issues have been addressed is also discussed in this review.
Ecosystem ecology sees living organisms, including people and the elements of their environment, as part of a single integrated system. The comprehensive coverage in this textbook examines the ...central processes at work, including their freshwater components.
Synthetic biology aims to develop engineering-driven approaches to the programming of cellular functions that could yield transformative technologies. Synthetic gene circuits that combine DNA, ...protein, and RNA components have demonstrated a range of functions such as bistability, oscillation, feedback, and logic capabilities. However, it remains challenging to scale up these circuits owing to the limited number of designable, orthogonal, high-performance parts, the empirical and often tedious composition rules, and the requirements for substantial resources for encoding and operation. Here, we report a strategy for constructing RNA-only nanodevices to evaluate complex logic in living cells. Our 'ribocomputing' systems are composed of de-novo-designed parts and operate through predictable and designable base-pairing rules, allowing the effective in silico design of computing devices with prescribed configurations and functions in complex cellular environments. These devices operate at the post-transcriptional level and use an extended RNA transcript to co-localize all circuit sensing, computation, signal transduction, and output elements in the same self-assembled molecular complex, which reduces diffusion-mediated signal losses, lowers metabolic cost, and improves circuit reliability. We demonstrate that ribocomputing devices in Escherichia coli can evaluate two-input logic with a dynamic range up to 900-fold and scale them to four-input AND, six-input OR, and a complex 12-input expression (A1 AND A2 AND NOT A1*) OR (B1 AND B2 AND NOT B2*) OR (C1 AND C2) OR (D1 AND D2) OR (E1 AND E2). Successful operation of ribocomputing devices based on programmable RNA interactions suggests that systems employing the same design principles could be implemented in other host organisms or in extracellular settings.
is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the
phylum, which are highly relevant in dysbiosis ...and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species:
, and
and
, and the subspecies
subspecies vulgaris (vs.
subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been isolated from patients suffering from appendicitis, and abdominal and rectal abscess. It is possible that as
spp. emerge, their identification in clinical samples may be underrepresented as novel MS-TOF methods may not be fully capable to discriminate distinct species as separate since it will require the upgrading of MS-TOF identification databases. In terms of pathogenicity, there is contrasting evidence indicating that
may have protective effects against some diseases, including liver fibrosis, colitis, cancer immunotherapy, and cardiovascular disease. In contrast, other studies indicate
is pathogenic in colorectal cancer and is associated with mental signs of depression. Gut dysbiosis seems to play a role in determining the compositional abundance of
in the feces (
., in non-alcoholic steatohepatitis, hepatic encephalopathy, and liver fibrosis). Since
is a relatively recent sub-branch genus of the
phylum, and since
are commonly associated with chronic intestinal inflammation, this narrative review illustrates emerging immunological and mechanistic implications by which
spp. correlate with human health.
Microglia are universal sensors of alterations in CNS physiology. These cells integrate complex molecular signals and undergo comprehensive phenotypical remodeling to adapt inflammatory responses. In ...the last years, single-cell analyses have revealed that microglia exhibit diverse phenotypes during development, growth and disease. Emerging evidence suggests that such phenotype transitions are mediated by reprogramming of cell metabolism. Indeed, metabolic pathways are distinctively altered in activated microglia and are central nodes controlling microglial responses. Microglial lipid metabolism has been specifically involved in the control of microglial activation and effector functions, such as migration, phagocytosis and inflammatory signaling, and minor disturbances in microglial lipid handling associates with altered brain function in disorders featuring neuroinflammation. In this review, we explore new and relevant aspects of microglial metabolism in health and disease. We give special focus on how different branches of lipid metabolism, such as lipid sensing, synthesis and oxidation, integrate and control essential aspects of microglial biology, and how disturbances in these processes associate with aging and the pathogenesis of, for instance, multiple sclerosis and Alzheimer’s disease. Finally, challenges and advances in microglial lipid research are discussed.
Local and global changes associated with anthropogenic activities are impacting marine and terrestrial ecosystems. Macroalgae, especially habitat-forming species like kelp, play critical roles in ...temperate coastal ecosystems. However, their abundance and distribution patterns have been negatively affected by warming in many regions around the globe. Along with global change, coastal ecosystems are also impacted by local drivers such as eutrophication. The interaction between global and local drivers might modulate kelp responses to environmental change. This study examines the regulatory effect of NO
on the thermal plasticity of the giant kelp Macrocystis pyrifera. To do this, thermal performance curves (TPCs) of key temperature-dependant traits-growth, photosynthesis, NO
assimilation and chlorophyll a fluorescence-were examined under nitrate replete and deplete conditions in a short-term incubation. We found that thermal plasticity was modulated by NO
but different thermal responses were observed among traits. Our study reveals that nitrogen, a local driver, modulates kelp responses to high seawater temperatures, ameliorating the negative impacts on physiological performance (i.e. growth and photosynthesis). However, this effect might be species-specific and vary among biogeographic regions - thus, further work is needed to determine the generality of our findings to other key temperate macroalgae that are experiencing temperatures close to their thermal tolerance due to climate change.
Background
For decades, parental self‐efficacy (PSE), or parents' belief in their ability to influence their child in a healthy and success‐promoting manner, has been understood as a key factor in ...promoting healthy functioning for parents and their children. In that time, an extensive collection of research examining the specific impact of PSE on parents and their children has developed. However, to the authors' knowledge, no comprehensive and systematic review of the outcomes linked to this factor exists, and the two most closely related non‐systematic reviews were published over 10 years ago.
Methods
Therefore, by utilizing an iteratively optimized set of search terms applied across four databases, the current review sought to systematically collect, synthesize, and present the extant literature concerning the role of PSE in parent and child well‐being.
Results
This search strategy yielded a total of 115 studies, the results of which were organized into three broad thematic categories relating to: the parent and child relationship, parental mental health, or child development.
Conclusions
These results recapitulate the clinical relevance of PSE, and provide an updated and comprehensive understanding of both the role PSE plays in the welfare of parents and children, as well as the gaps in the literature as it currently stands.
Excessive increased adipose tissue mass in obesity is associated with numerous co-morbid disorders including increased risk of type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, ...cardiovascular diseases, dementia, airway disease and some cancers. The causal mechanisms explaining these associations are not fully understood. Adipose tissue is an active endocrine organ that secretes many adipokines, cytokines and releases metabolites. These biomolecules referred to as adipocytokines play a significant role in the regulation of whole-body energy homeostasis and metabolism by influencing and altering target tissues function. Understanding the mechanisms of adipocytokine actions represents a hot topic in obesity research. Among several secreted bioactive signalling molecules from adipose tissue and liver, retinol-binding protein 4 (RBP4) has been associated with systemic insulin resistance, dyslipidemia, type 2 diabetes and other metabolic diseases. Here, we aim to review and discuss the current knowledge on RBP4 with a focus on its role in the pathogenesis of obesity comorbid diseases.
•Adipose tissue dysfunction is reflected by dysregulations of adipocytokine patterns.•Circulating and adipose tissue RBP4 levels rise with obesity and type 2 diabetes.•The sources and metabolic actions of RBP4 vary with different metabolic conditions.•RBP4 acts on target tissues via STAT5/JAK2, JNK and TLR4/NFkB signaling pathways.•RBP4 is a potential drug target for managing cardiometabolic and other diseases.
Ocean warming (OW), ocean acidification (OA) and their interaction with local drivers, e.g., copper pollution, may negatively affect macroalgae and their microscopic life stages. We evaluated ...meiospore development of the kelps Macrocystis pyrifera and Undaria pinnatifida exposed to a factorial combination of current and 2100-predicted temperature (12 and 16 °C, respectively), pH (8.16 and 7.65, respectively), and two copper levels (no-added-copper and species-specific germination Cu-EC
). Meiospore germination for both species declined by 5-18% under OA and ambient temperature/OA conditions, irrespective of copper exposure. Germling growth rate declined by >40%·day
, and gametophyte development was inhibited under Cu-EC
exposure, compared to the no-added-copper treatment, irrespective of pH and temperature. Following the removal of copper and 9-day recovery under respective pH and temperature treatments, germling growth rates increased by 8-18%·day
. The exception was U. pinnatifida under OW/OA, where growth rate remained at 10%·day
before and after copper exposure. Copper-binding ligand concentrations were higher in copper-exposed cultures of both species, suggesting that ligands may act as a defence mechanism of kelp early life stages against copper toxicity. Our study demonstrated that copper pollution is more important than global climate drivers in controlling meiospore development in kelps as it disrupts the completion of their life cycle.
PDF
