Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function

Post-translational acylation of lysine side chains is a common mechanism of protein regulation. Modification by long-chain fatty acyl groups is an understudied form of lysine acylation that has gained increasing attention recently due to the characterization of enzymes that catalyze the addition and removal this modification. In this review we summarize what has been learned about lysine fatty acylation in the approximately 30 years since its initial discovery. We report on what is known about the enzymes that regulate lysine fatty acylation and their physiological functions, including tumorigenesis and bacterial pathogenesis. We also cover the effect of lysine fatty acylation on reported substrates. Generally, lysine fatty acylation increases the affinity of proteins for specific cellular membranes, but the physiological outcome depends greatly on the molecular context. Finally, we will go over the experimental tools that have been used to study lysine fatty acylation. While much has been learned about lysine fatty acylation since its initial discovery, the full scope of its biological function has yet to be realized.

Co-infections as Modulators of Disease Outcome: Minor Players or Major Players?

Human host and pathogen interaction is dynamic in nature and often modulated by co-pathogens with a functional role in delineating the physiological outcome of infection. Co-infection may present either as a pre-existing pathogen which is accentuated by the introduction of a new pathogen or may appear in the form of new infection acquired secondarily due to a compromised immune system. Using diverse examples of co-infecting pathogens such as Human Immunodeficiency Virus, Mycobacterium tuberculosis and Hepatitis C Virus, we have highlighted the role of co-infections in modulating disease severity and clinical outcome. This interaction happens at multiple hierarchies, which are inclusive of stress and immunological responses and together modulate the disease severity. Already published literature provides much evidence in favor of the occurrence of co-infections during SARS-CoV-2 infection, which eventually impacts the Coronavirus disease-19 outcome. The availability of biological models like 3D organoids, mice, cell lines and mathematical models provide us with an opportunity to understand the role and mechanism of specific co-infections. Exploration of multi-omics-based interactions across co-infecting pathogens may provide deeper insights into their role in disease modulation.

Smart Shirts for Monitoring Physiological Parameters: Scoping Review

Background The recent trends of technological innovation and widescale digitization as potential solutions to challenges in health care, sports, and emergency service operations have led to the conception of smart textile technology. In health care, these smart textile systems present the potential to aid preventative medicine and early diagnosis through continuous, noninvasive tracking of physical and mental health while promoting proactive involvement of patients in their medical management. In areas such as sports and emergency response, the potential to provide comprehensive and simultaneous physiological insights across multiple body systems is promising. However, it is currently unclear what type of evidence exists surrounding the use of smart textiles for the monitoring of physiological outcome measures across different settings. Objective This scoping review aimed to systematically survey the existing body of scientific literature surrounding smart textiles in their most prevalent form, the smart shirt, for monitoring physiological outcome measures. Methods A total of 5 electronic bibliographic databases were systematically searched (Ovid Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Scopus, Cumulative Index to Nursing and Allied Health Literature, and SPORTDiscus). Publications from the inception of the database to June 24, 2019 were reviewed. Nonindexed literature relevant to this review was also systematically searched. The results were then collated, summarized, and reported. Results Following the removal of duplicates, 7871 citations were identified. On the basis of title and abstract screening, 7632 citations were excluded, whereas 239 were retrieved and assessed for eligibility. Of these, 101 citations were included in the final analysis. Included studies were categorized into four themes: (1) prototype design, (2) validation, (3) observational, and (4) reviews. Among the 101 analyzed studies, prototype design was the most prevalent theme (50/101, 49.5%), followed by validation (29/101, 28.7%), observational studies (21/101, 20.8%), and reviews (1/101, 0.1%). Presented prototype designs ranged from those capable of monitoring one physiological metric to those capable of monitoring several simultaneously. In 29 validation studies, 16 distinct smart shirts were validated against reference technology under various conditions and work rates, including rest, submaximal exercise, and maximal exercise. The identified observational studies used smart shirts in clinical, healthy, and occupational populations for aims such as early diagnosis and stress detection. One scoping review was identified, investigating the use of smart shirts for electrocardiograph signal monitoring in cardiac patients. Conclusions Although smart shirts have been found to be valid and reliable in the monitoring of specific physiological metrics, results were variable for others, demonstrating the need for further systematic validation. Analysis of the results has also demonstrated gaps in knowledge, such as a considerable lag of validation and observational studies in comparison with prototype design and limited investigation using smart shirts in pediatric, elite sports, and emergency service populations.

Smart Shirts for Monitoring Physiological Parameters: Scoping Review (Preprint)

BACKGROUND The recent trends of technological innovation and widescale digitization as potential solutions to challenges in health care, sports, and emergency service operations have led to the conception of smart textile technology. In health care, these smart textile systems present the potential to aid preventative medicine and early diagnosis through continuous, noninvasive tracking of physical and mental health while promoting proactive involvement of patients in their medical management. In areas such as sports and emergency response, the potential to provide comprehensive and simultaneous physiological insights across multiple body systems is promising. However, it is currently unclear what type of evidence exists surrounding the use of smart textiles for the monitoring of physiological outcome measures across different settings. OBJECTIVE This scoping review aimed to systematically survey the existing body of scientific literature surrounding smart textiles in their most prevalent form, the smart shirt, for monitoring physiological outcome measures. METHODS A total of 5 electronic bibliographic databases were systematically searched (Ovid Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Scopus, Cumulative Index to Nursing and Allied Health Literature, and SPORTDiscus). Publications from the inception of the database to June 24, 2019 were reviewed. Nonindexed literature relevant to this review was also systematically searched. The results were then collated, summarized, and reported. RESULTS Following the removal of duplicates, 7871 citations were identified. On the basis of title and abstract screening, 7632 citations were excluded, whereas 239 were retrieved and assessed for eligibility. Of these, 101 citations were included in the final analysis. Included studies were categorized into four themes: (1) prototype design, (2) validation, (3) observational, and (4) reviews. Among the 101 analyzed studies, prototype design was the most prevalent theme (50/101, 49.5%), followed by validation (29/101, 28.7%), observational studies (21/101, 20.8%), and reviews (1/101, 0.1%). Presented prototype designs ranged from those capable of monitoring one physiological metric to those capable of monitoring several simultaneously. In 29 validation studies, 16 distinct smart shirts were validated against reference technology under various conditions and work rates, including rest, submaximal exercise, and maximal exercise. The identified observational studies used smart shirts in clinical, healthy, and occupational populations for aims such as early diagnosis and stress detection. One scoping review was identified, investigating the use of smart shirts for electrocardiograph signal monitoring in cardiac patients. CONCLUSIONS Although smart shirts have been found to be valid and reliable in the monitoring of specific physiological metrics, results were variable for others, demonstrating the need for further systematic validation. Analysis of the results has also demonstrated gaps in knowledge, such as a considerable lag of validation and observational studies in comparison with prototype design and limited investigation using smart shirts in pediatric, elite sports, and emergency service populations. CLINICALTRIAL

Unique coupling of mono- and dioxygenase chemistries in a single active site promotes heme degradation

Bacterial pathogens must acquire host iron for survival and colonization. Because free iron is restricted in the host, numerous pathogens have evolved to overcome this limitation by using a family of monooxygenases that mediate the oxidative cleavage of heme into biliverdin, carbon monoxide, and iron. However, the etiological agent of tuberculosis, Mycobacterium tuberculosis, accomplishes this task without generating carbon monoxide, which potentially induces its latent state. Here we show that this unusual heme degradation reaction proceeds through sequential mono- and dioxygenation events within the single active center of MhuD, a mechanism unparalleled in enzyme catalysis. A key intermediate of the MhuD reaction is found to be meso-hydroxyheme, which reacts with O2 at an unusual position to completely suppress its monooxygenation but to allow ring cleavage through dioxygenation. This mechanistic change, possibly due to heavy steric deformation of hydroxyheme, rationally explains the unique heme catabolites of MhuD. Coexistence of mechanistically distinct functions is a previously unidentified strategy to expand the physiological outcome of enzymes, and may be applied to engineer unique biocatalysts.