Atypical Presentation of a Right Atrial Myxoma.

Primary cardiac tumors are exceptionally rare and predominantly located in the left atrium with occasional involvement on the right side of the heart. We present the case of a 52-year-old man who presented with chest pain, leading to suspicion of acute coronary syndrome. However, further investigation revealed a right atrial tumor measuring 6.3 cm. After surgical removal, the pathology analysis of the mass confirmed the histology of myxoma. Differential diagnoses for atrial myxomas include thrombus and other tumors, such as rhabdomyomas. More than half of these tumors arise in the left atrium and may be complicated by neurologic symptoms secondary to embolization. Right atrial myxomas are rare and described in the literature with a myriad of symptoms (signs of right heart failure [i.e., fatigue, peripheral edema, hepatomegaly, ascites], a diastolic murmur, and symptoms of pulmonary emboli). In other cases, they may be asymptomatic. Due to the low incidence and variety in their clinical picture, careful documentation of these cases is suggested for early recognition and directed management.

Monoamine oxidase binding not expected to significantly affect [18F]flortaucipir PET interpretation.

PURPOSE: [18F]-labeled positron emission tomography (PET) radioligands permit in vivo assessment of Alzheimer's disease biomarkers, including aggregated neurofibrillary tau (NFT) with [18F]flortaucipir. Due to structural similarities of flortaucipir with some monoamine oxidase A (MAO-A) inhibitors, this study aimed to evaluate flortaucipir binding to MAO-A and MAO-B and any potential impact on PET interpretation. METHODS: [18F]Flortaucipir autoradiography was performed on frozen human brain tissue slices, and PET imaging was conducted in rats. Dissociation constants were determined by saturation binding, association and dissociation rates were measured by kinetic binding experiments, and IC50 values were determined by competition binding. RESULTS: Under stringent wash conditions, specific [18F]flortaucipir binding was observed on tau NFT-rich Alzheimer's disease tissue and not control tissue. In vivo PET experiments in rats revealed no evidence of [18F]flortaucipir binding to MAO-A; pre-treatment with MAO inhibitor pargyline did not impact uptake or wash-out of [18F]flortaucipir. [18F]Flortaucipir bound with low nanomolar affinity to human MAO-A in a microsomal preparation in vitro but with a fast dissociation rate relative to MAO-A ligand fluoroethyl-harmol, consistent with no observed in vivo binding in rats of [18F]flortaucipir to MAO-A. Direct binding of flortaucipir to human MAO-B was not detected in a microsomal preparation. A high concentration of flortaucipir (IC50 of 1.3 µM) was found to block binding of the MAO-B ligand safinamide to MAO-B on microsomes suggesting that, at micromolar concentrations, flortaucipir weakly binds to MAO-B in vitro. CONCLUSION: These data suggest neither MAO-A nor MAO-B binding will contribute significantly to the PET signal in cortical target areas relevant to the interpretation of [18F]flortaucipir.

To Detect and Reject, Parallel Roles for Taste and Immunity.

PURPOSE OF REVIEW: From single cells to entire organisms, biological entities are in constant communication with their surroundings, deciding what to 'allow' in, and what to reject. In very different ways, the immune and taste systems both fulfill this function, with growing evidence suggesting a relationship between the two, through shared signaling pathways, receptors, and feedback loops. The purpose of this review was to explore recent reports on taste and immunity in model animals and in humans to explore our understanding of the interplay between these systems. RECENT FINDINGS: Acute infections in the upper airway, as with SARS-CoV-2, are associated with a proinflammatory state, and blunted taste perception. Further, recent findings highlight taste receptors working as immune sentinels throughout the body. Work in humans and mice also points to inflammation from obesity impacting taste, altering taste bud abundance and composition. There is accumulating evidence that taste cells, and particularly their receptors, play a role in airway and gut immunity, responsive to invading organisms. Inflammation itself may further act on taste buds and other taste receptor expressing cells throughout the body as a form of homeostatic control.

Decrease in sweet taste response and T1R3 sweet taste receptor expression in pregnant mice highlights a potential mechanism for increased caloric consumption in pregnancy.

While much is known on how the maternal diet affects offspring fitness, less is known on the role of taste in guiding and promoting food intake during this crucial period. Women have intense food cravings and exhibit altered taste preferences during pregnancy, however the mechanistic details underlying these changes are presently unclear. We performed longitudinal brief-access taste testing in female mice before, during, and after pregnancy, along with quantitative PCR on taste buds and morphological analysis of taste tissues from pregnant and non-pregnant mice. Sucrose licking response decreased progressively during pregnancy compared to that prior to mating, with partial recovery in the post-partum period. No change in taste morphology was evident between pregnant and non-pregnant mice, however a notable decrease in T1R3 sweet taste receptor mRNA expression was recorded in pregnant dams. We conclude that altered taste preferences during pregnancy likely result from changes in the expression profile of taste buds in the mother, which may promote a less healthy diet while expecting.

Experimental and Simulation Efforts in the Astrobiological Exploration of Exooceans.

The icy satellites of Jupiter and Saturn are perhaps the most promising places in the Solar System regarding habitability. However, the potential habitable environments are hidden underneath km-thick ice shells. The discovery of Enceladus' plume by the Cassini mission has provided vital clues in our understanding of the processes occurring within the interior of exooceans. To interpret these data and to help configure instruments for future missions, controlled laboratory experiments and simulations are needed. This review aims to bring together studies and experimental designs from various scientific fields currently investigating the icy moons, including planetary sciences, chemistry, (micro-)biology, geology, glaciology, etc. This chapter provides an overview of successful in situ, in silico, and in vitro experiments, which explore different regions of interest on icy moons, i.e. a potential plume, surface, icy shell, water and brines, hydrothermal vents, and the rocky core.

Snowball Earth climate dynamics and Cryogenian geology-geobiology.

Geological evidence indicates that grounded ice sheets reached sea level at all latitudes during two long-lived Cryogenian (58 and ≥5 My) glaciations. Combined uranium-lead and rhenium-osmium dating suggests that the older (Sturtian) glacial onset and both terminations were globally synchronous. Geochemical data imply that CO2 was 102 PAL (present atmospheric level) at the younger termination, consistent with a global ice cover. Sturtian glaciation followed breakup of a tropical supercontinent, and its onset coincided with the equatorial emplacement of a large igneous province. Modeling shows that the small thermal inertia of a globally frozen surface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere. Oceanic ice thickens, forming a sea glacier that flows gravitationally toward the equator, sustained by the hydrologic cycle and by basal freezing and melting. Tropical ice sheets flow faster as CO2 rises but lose mass and become sensitive to orbital changes. Equatorial dust accumulation engenders supraglacial oligotrophic meltwater ecosystems, favorable for cyanobacteria and certain eukaryotes. Meltwater flushing through cracks enables organic burial and submarine deposition of airborne volcanic ash. The subglacial ocean is turbulent and well mixed, in response to geothermal heating and heat loss through the ice cover, increasing with latitude. Terminal carbonate deposits, unique to Cryogenian glaciations, are products of intense weathering and ocean stratification. Whole-ocean warming and collapsing peripheral bulges allow marine coastal flooding to continue long after ice-sheet disappearance. The evolutionary legacy of Snowball Earth is perceptible in fossils and living organisms.

Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices.

The atomic-level mechanisms by which G protein-coupled receptors (GPCRs) transmit extracellular ligand binding events through their transmembrane helices to activate intracellular G proteins remain unclear. Using a comprehensive library of mutations covering all 352 residues of the GPCR CXC chemokine receptor 4 (CXCR4), we identified 41 amino acids that are required for signaling induced by the chemokine ligand CXCL12 (stromal cell-derived factor 1). CXCR4 variants with each of these mutations do not signal properly but remain folded, based on receptor surface trafficking, reactivity to conformationally sensitive monoclonal antibodies, and ligand binding. When visualized on the structure of CXCR4, the majority of these residues form a continuous intramolecular signaling chain through the transmembrane helices; this chain connects chemokine binding residues on the extracellular side of CXCR4 to G protein-coupling residues on its intracellular side. Integrated into a cohesive model of signal transmission, these CXCR4 residues cluster into five functional groups that mediate (i) chemokine engagement, (ii) signal initiation, (iii) signal propagation, (iv) microswitch activation, and (v) G protein coupling. Propagation of the signal passes through a "hydrophobic bridge" on helix VI that coordinates with nearly every known GPCR signaling motif. Our results agree with known conserved mechanisms of GPCR activation and significantly expand on understanding the structural principles of CXCR4 signaling.

Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein.

Numerous broadly neutralizing antibodies (Abs) target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes). Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs), we previously used HIV virus-like particles (VLPs) to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection.

A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs.

BACKGROUND: Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the response to other flavor characteristics. Studies of domestic cat taste perception are limited, in part, due to the lack of receptor sequence information. Several studies have described the phylogenetic relationship of specific cat taste receptor sequences as compared with other carnivores. For example, domestic cats are obligate carnivores and their receptor Tas1r2, associated with the human perception of sweet, is present only as a pseudogene. Similarly, the cat perception of bitter may differ from that of other mammals due to variations in their repertoire of bitter receptor (Tas2r) genes. This report includes the first functional characterization of domestic cat taste receptors. RESULTS: We functionally expressed two uncharacterized domestic sequences Tas2r38 and Tas2r43 and deorphanized the receptors using a cellular functional assay. Statistical significance was determined using an unpaired, two-tailed t-test. The cat sequence for Tas2r38 contains 3 major amino acid residues known to confer the taster phenotype (PAI), which is associated with sensitivity to the bitter compounds PROP and PTC. However, in contrast to human TAS2R38, cat Tas2r38 is activated by PTC but not by PROP. Furthermore, like its human counterpart, cat Tas2r43 is activated by aloin and denatonium, but differs from the human TAS2R43 by insensitivity to saccharin. The responses of both cat receptors to the bitter ligands were concentration-dependent and were inhibited by the human bitter blocker probenecid. CONCLUSIONS: These data demonstrate that the response profiles of the cat bitter receptors Tas2r38 and Tas2r43 are distinct from those of their orthologous human receptors. Results with cat Tas2r38 also demonstrate that additional residues beyond those classically associated with PROP sensitivity in humans influence the sensitivity to PROP and PTC. Functional studies of the human bitter receptor family are being applied to the development of food and medicinal products with more appealing flavor profiles. Our work lays the foundation for similar work applied to felines.

Development of a Childhood Attachment and Relational Trauma Screen (CARTS): a relational-socioecological framework for surveying attachment security and childhood trauma history.

BACKGROUND: Current psychometric measures of childhood trauma history generally fail to assess the relational-socioecological context within which childhood maltreatment occurs, including the relationship of abusers to abused persons, the emotional availability of caregivers, and the respondent's own thoughts, feelings, and actions in response to maltreatment. OBJECTIVE: To evaluate a computerized approach to measuring the relational-socioecological context within which childhood maltreatment occurs. METHOD: The psychometric properties of a Childhood Attachment and Relational Trauma Screen (CARTS) were evaluated as a retrospective survey of childhood maltreatment history designed to be appropriate for completion by adults. Participants were undergraduates (n=222), an internet sample (n=123), and psychiatric outpatients (n=30). RESULTS: The internal reliability, convergent, and concurrent validity of the CARTS were supported across samples. Paired differences in means and correlations between rated item-descriptiveness to self, mothers, and fathers also accorded with findings of prior attachment and maltreatment research, illustrating the utility of assessing the occurrence and effects of maltreatment within a relational-socioecological framework. CONCLUSIONS: Results preliminarily support a new survey methodology for assessing childhood maltreatment within a relational-socioecological framework. Further psychometric evaluation of the CARTS is warranted.