Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development

In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR–to–NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR–expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus. Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.IOS-1354935 - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); 1262934 - National Science Foundation (NSF); 2014-BSP - Arnold and Mabel Beckman Foundatio

Bosonic Colored Group Field Theory

Bosonic colored group field theory is considered. Focusing first on dimension four, namely the colored Ooguri group field model, the main properties of Feynman graphs are studied. This leads to a theorem on optimal perturbative bounds of Feynman amplitudes in the "ultraspin" (large spin) limit. The results are generalized in any dimension. Finally integrating out two colors we write a new representation which could be useful for the constructive analysis of this type of models

OH-Stretch Vibrational Spectroscopy of Hydroxymethyl Hydroperoxide

We report measurement and analysis of the photodissociation spectrum of hydroxymethyl hydroperoxide (HOCH_2OOH) and its partially deuterated analogue, HOCD_2OOH, in the OH-stretching region. Spectra are obtained by Fourier transform infrared spectroscopy in the 1ν_(OH) and 2ν_(OH) regions, and by laser induced fluorescence detection of the OH fragment produced from dissociation of HOCH_2OOH initiated by excitation of the 4ν_(OH) and 5ν_(OH) overtone regions (action spectroscopy). A one-dimensional local-mode model of each OH chromophore is used with ab initio calculated OH-stretching potential energy and dipole moment curves at the coupled-cluster level of theory. Major features in the observed absorption and photodissociation spectra are explained by our local-mode model. In the 4ν_(OH) region, explanation of the photodissocation spectrum requires a nonuniform quantum yield, which is estimated by assuming statistical energy distribution in the excited state. Based on the estimated dissociation threshold, overtone photodissociation is not expected to significantly influence the atmospheric lifetime of hydroxymethyl hydroperoxide

The Impact of Instrument-Specific Musical Training on Rhythm Perception and Production

Studies comparing musicians and non-musicians have shown that musical training can improve rhythmic perception and production. These findings tell us that training can result in rhythm processing advantages, but they do not tell us whether practicing a particular instrument could lead to specific effects on rhythm perception or production. The current study used a battery of four rhythm perception and production tasks that were designed to test both higher- and lower-level aspects of rhythm processing. Four groups of musicians (drummers, singers, pianists, string players) and a control group of non-musicians were tested. Within-task differences in performance showed that factors such as meter, metrical complexity, tempo, and beat phase significantly affected the ability to perceive and synchronize taps to a rhythm or beat. Musicians showed better performance on all rhythm tasks compared to non-musicians. Interestingly, our results revealed no significant differences between musician groups for the vast majority of task measures. This was despite the fact that all musicians were selected to have the majority of their training on the target instrument, had on average more than 10 years of experience on their instrument, and were currently practicing. These results suggest that general musical experience is more important than specialized musical experience with regards to perception and production of rhythms

Characterizing metabolic drivers of Clostridioides difficile infection with activity-based hydrazine probes

Many enzymes require post-translational modifications or cofactor machinery for primary function. As these catalytically essential moieties are highly regulated, they act as dual sensors and chemical handles for context-dependent metabolic activity. Clostridioides difficile is a major nosocomial pathogen that infects the colon. Energy generating metabolism, particularly through amino acid Stickland fermentation, is central to colonization and persistence of this pathogen during infection. Here using activity-based protein profiling (ABPP), we revealed Stickland enzyme activity is a biomarker for C. difficile infection (CDI) and annotated two such cofactor-dependent Stickland reductases. We structurally characterized the cysteine-derived pyruvoyl cofactors of D-proline and glycine reductase in C. difficile cultures and showed through cofactor monitoring that their activity is regulated by their respective amino acid substrates. Proline reductase was consistently active in toxigenic C. difficile, confirming the enzyme to be a major metabolic driver of CDI. Further, activity-based hydrazine probes were shown to be active site-directed inhibitors of proline reductase. As such, this enzyme activity, via its druggable cofactor modality, is a promising therapeutic target that could allow for the repopulation of bacteria that compete with C. difficile for proline and therefore restore colonization resistance against C. difficile in the gut

Birth Weight for Gestational Age Norms for a Large Cohort of Infants Born to HIV-Negative Women in Botswana Compared with Norms for U.S.-Born Black Infants

Background: Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes. Methods: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States. Results: During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02). Conclusions: We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero

Open-resorcinarenes, a new family of multivalent scaffolds

A new family of multivalent ligand platforms, the open-resorcinarenes, has been prepared in a straightforward two-step reaction. Modification of the core gives a range of topologically diverse scaffolds; functionalisation confirms the versatility of this approach, as shown through the formation of an octacalixarene array