Project description:Herein, a case describing how point-of-care lung ultrasound was used to identify the source of progressive multiorgan failure when a chest x-ray and other routine tests failed to provide a conclusive answer is presented. The discussion after the case focuses on the following: (1) the relative strengths and weaknesses of chest x-ray versus lung ultrasound in screening for lung disease and (2) suggestions of how lung ultrasound practice can be standardized within the field of anesthesiology.
Project description:Central nervous system (CNS) immune privilege is an experimentally defined phenomenon. Tissues that are rapidly rejected by the immune system when grafted in sites, such as the skin, show prolonged survival when grafted into the CNS. Initially, CNS immune privilege was construed as CNS isolation from the immune system by the blood-brain barrier (BBB), the lack of draining lymphatics, and the apparent immunoincompetence of microglia, the resident CNS macrophage. CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounter with CNS antigens. Recent data have dramatically altered this viewpoint by revealing that the CNS is neither isolated nor passive in its interactions with the immune system. Peripheral immune cells can cross the intact BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses, and microglia are immunocompetent but differ from other macrophage/dendritic cells in their ability to direct neuroprotective lymphocyte responses. This newer view of CNS immune privilege is opening the door for therapies designed to harness autoreactive lymphocyte responses and also implies (i) that CNS autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal and/or glial dysfunction as from immune system dysfunctions and (ii) that the severe neuronal and glial dysfunction associated with neurodegenerative disorders (i.e. Alzheimer's disease) likely alters CNS-specific regulation of lymphocyte responses affecting the utility of immune-based therapies (i.e. vaccines).
Project description:There are approximately 38 million people globally living with Human immunodeficiency virus 1 (HIV-1) and given the tremendous success of combination antiretroviral therapy (cART) this has dramatically reduced mortality and morbidity with prevention benefits. However, HIV-1 persists during cART within the human body and re-appears upon cART interruption. This HIV-1 reservoir remains a barrier to cure with cellular sites of viral persistence not fully understood. In this study we provide evidence corroborating a recently published article in STM demonstrating the role of platelets as a novel cellular disseminator of HIV-1 particles in the setting of viral suppression. Using classical transmission electron microscopy with and without immunogold labeling, we visualize HIV-1 in both platelets and monocytes in cART suppressed HIV donors. Our study suggests that due to the close proximity of platelets and monocytes an alternative life cycle of HIV-1 cycling within monocytes and platelets without the need of active replication under cART occurs. Our findings are supported by the lack of detectable HIV-1 particles in platelets derived from HIV uninfected donors or the 'Berlin' patient suggesting that platelets may serve as an underappreciated hidden bearer for HIV-1 and should be considered in HIV remission studies and trials.
Project description:Bacterial candidate phylum PAUC34f was originally discovered in marine sponges and is widely considered to be composed of sponge symbionts. Here, we report 21 single amplified genomes (SAGs) of PAUC34f from a variety of environments, including the dark ocean, lake sediments, and a terrestrial aquifer. The diverse origins of the SAGs and the results of metagenome fragment recruitment suggest that some PAUC34f lineages represent relatively abundant, free-living cells in environments other than sponge microbiomes, including the deep ocean. Both phylogenetic and biogeographic patterns, as well as genome content analyses suggest that PAUC34f associations with hosts evolved independently multiple times, while free-living lineages of PAUC34f are distinct and relatively abundant in a wide range of environments.
Project description:Cultivation in the laboratory is essential for understanding the phenotypic characteristics and environmental preferences of bacteria. However, basic phenotypic information is not readily accessible. Here, we compiled phenotypic and environmental tolerance information for >5,000 bacterial strains described in the International Journal of Systematic and Evolutionary Microbiology (IJSEM) with all information made publicly available in an updatable database. Although the data span 23 different bacterial phyla, most entries described aerobic, mesophilic, neutrophilic strains from Proteobacteria (mainly Alpha- and Gammaproteobacteria), Actinobacteria, Firmicutes, and Bacteroidetes isolated from soils, marine habitats, and plants. Most of the routinely measured traits tended to show a significant phylogenetic signal, although this signal was weak for environmental preferences. We demonstrated how this database could be used to link genomic attributes to differences in pH and salinity optima. We found that adaptations to high salinity or high-pH conditions are related to cell surface transporter genes, along with previously uncharacterized genes that might play a role in regulating environmental tolerances. Together, this work highlights the utility of this database for associating bacterial taxonomy, phylogeny, or specific genes to measured phenotypic traits and emphasizes the need for more comprehensive and consistent measurements of traits across a broader diversity of bacteria. IMPORTANCE Cultivation in the laboratory is key for understanding the phenotypic characteristics, growth requirements, metabolism, and environmental preferences of bacteria. However, oftentimes, phenotypic information is not easily accessible. Here, we compiled phenotypic and environmental tolerance information for >5,000 bacterial strains described in the International Journal of Systematic and Evolutionary Microbiology (IJSEM). We demonstrate how this database can be used to link bacterial taxonomy, phylogeny, or specific genes to measured phenotypic traits and environmental preferences. The phenotypic database can be freely accessed (https://doi.org/10.6084/m9.figshare.4272392), and we have included instructions for researchers interested in adding new entries or curating existing ones.
Project description:An 87 year old male with obstructive uropathy was initially diagnosed with acute kidney injury (AKI), a new renal mass and hydronephrosis. When transferred to a facility with a hospital medicine POCUS program, the renal mass was correctly identified as a perinephric abscess, which was percutaneously drained leading to resolution of AKI and the underlying infection. Renal POCUS is readily taught via brief educational interventions and empowers providers to identify common (hydronephrosis) and uncommon (perinephric abscess) renal pathology at the bedside.
Project description:Cydippid ctenophores of genus Euplokamis have been rarely reported from the north-east Atlantic in the scientific literature. The conspicuous lack of previous records is likely attributable to methodological constraints detrimental to sampling ctenophores, including the use of plankton nets and preservation of samples as well as poor identification literature and a lack of taxonomic expertise on gelatinous zooplankton. Here, we have compiled published and novel records as well as documented diver observations, of Euplokamis spp. in Norwegian waters. Despite scant earlier reports, our data suggest that the genus Euplokamis is widely distributed and relatively common along the entire Norwegian coast, including Svalbard. Euplokamis was recorded from samples taken from several hundred meters depth to surface, from fjords as well as offshore. Most of the observations reported in this study are from the period between April and July, whereas specimens have been found nearly throughout the year. Specimens from Norwegian waters were morphologically most similar to Euplokamis dunlapae, and conservative 18S rDNA sequences of some specimens had a 100% match with an E. dunlapae specimen from Friday Harbor, USA, the type locality for the species. However, the morphological and molecular variation of Euplokamis demonstrates the need for systematic global sampling of multiple individuals of many ctenophore species.
Project description:Hearing loss (HL) is the most common congenital sensory impairment. Usher syndrome (USH) is the leading genetic etiology of congenital deafness combined with progressive vision loss, and individuals presenting with these symptoms are often assumed to have USH. This can be an erroneous assumption, as there are additional genetic causes of deaf-blindness. Our objective is to describe and accurately diagnose non-USH genetic causes of deaf-blindness. We present three children with hearing and vision loss with clinical and genetic findings suggestive of USH. However, ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals. Updated genetic testing showed pathogenic variants in ALMS1 in the first individual and TUBB4B in the second and third. Although HL in all three was consistent with USH type 2, vision impairment with retinal changes was noted by age 2 yr, which is unusual for USH. In all three the updated genotype more accurately fit the clinical phenotype. Because USH is the most common form of genetic deaf-blindness, individuals with HL, early vision impairment, and retinal dysfunction are often assumed to have USH. However, additional genes associated with HL and retinal impairment include ALMS1, TUBB4B, CEP78, ABHD12, and PRPS1 Accurate genetic diagnosis is critical to these individuals' understanding of their genetic conditions, prognosis, vision and hearing loss management, and future access to molecular therapies. If clinically or genetically USH seems uncertain, updated genetic testing for non-USH genes is essential.
Project description:5-Oxoproline (OP) is well-known as an enzymatic intermediate in the eukaryotic γ-glutamyl cycle, but it is also an unavoidable damage product formed spontaneously from glutamine and other sources. Eukaryotes metabolize OP via an ATP-dependent 5-oxoprolinase; most prokaryotes lack homologs of this enzyme (and the γ-glutamyl cycle) but are predicted to have some way to dispose of OP if its spontaneous formation in vivo is significant. Comparative analysis of prokaryotic genomes showed that the gene encoding pyroglutamyl peptidase, which removes N-terminal OP residues, clusters in diverse genomes with genes specifying homologs of a fungal lactamase (renamed prokaryotic 5-oxoprolinase A, pxpA) and homologs of allophanate hydrolase subunits (renamed pxpB and pxpC). Inactivation of Bacillus subtilis pxpA, pxpB, or pxpC genes slowed growth, caused OP accumulation in cells and medium, and prevented use of OP as a nitrogen source. Assays of cell lysates showed that ATP-dependent 5-oxoprolinase activity disappeared when pxpA, pxpB, or pxpC was inactivated. 5-Oxoprolinase activity could be reconstituted in vitro by mixing recombinant B. subtilis PxpA, PxpB, and PxpC proteins. In addition, overexpressing Escherichia coli pxpABC genes in E. coli increased 5-oxoprolinase activity in lysates ≥1700-fold. This work shows that OP is a major universal metabolite damage product and that OP disposal systems are common in all domains of life. Furthermore, it illustrates how easily metabolite damage and damage-control systems can be overlooked, even for central metabolites in model organisms.
Project description:The transfer of phosphate groups is an essential function of many intracellular biological enzymes. The transfer is in many cases facilitated by a protein scaffold involving two closely spaced magnesium "ions". It has long been a mystery how these "ions" can retain their closely spaced positions throughout enzymatic phosphate transfer: Coulomb's law would dictate large repulsive forces between these ions at the observed distances. Here we show, however, that the electron density can be borrowed from nearby electron-rich oxygens to populate a bonding molecular orbital that is largely localized between the magnesium "ions". The result is that the Mg-Mg core of these phosphate transfer enzymes is surprisingly similar to a metastable [Mg2]2+ ion in the gas phase, an ion that has been identified experimentally and studied with high-level quantum-mechanical calculations. This similarity is confirmed by comparative computations of the electron densities of [Mg2]2+ in the gas phase and the Mg-Mg core in the structures derived from QM/MM studies of high-resolution X-ray crystal structures. That there is a level of covalent bonding between the two Mg "ions" at the core of these enzymes is a novel concept that enables an improved vision of how these enzymes function at the molecular level. The concept is broader than magnesium-other biologically relevant metals (e.g., Mn and Zn) can also form similar stabilizing covalent Me-Me bonds in both organometallic and inorganic crystals.