STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection.

UnlabelledSTING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ligand remains unknown. In this report, we provide evidence that Chlamydia synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite not previously identified in Gram-negative bacteria, and that this metabolite is a prominent ligand for STING-mediated activation of IFN responses during infection. We used primary mouse lung fibroblasts and HEK293T cells to compare IFN-β responses to Chlamydia infection, c-di-AMP, and other type I IFN-inducing stimuli. Chlamydia infection and c-di-AMP treatment induced type I IFN responses in cells expressing STING but not in cells expressing STING variants that cannot sense cyclic dinucleotides but still respond to cytoplasmic DNA. The failure to induce a type I IFN response to Chlamydia and c-di-AMP correlated with the inability of STING to relocalize from the endoplasmic reticulum to cytoplasmic punctate signaling complexes required for IFN activation. We conclude that Chlamydia induces STING-mediated IFN responses through the detection of c-di-AMP in the host cell cytosol and propose that c-di-AMP is the ligand predominantly responsible for inducing such a response in Chlamydia-infected cells.ImportanceThis study shows that the Gram-negative obligate pathogen Chlamydia trachomatis, a major cause of pelvic inflammatory disease and infertility, synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite that thus far has been described only in Gram-positive bacteria. We further provide evidence that the host cell employs an endoplasmic reticulum (ER)-localized cytoplasmic sensor, STING (stimulator of interferon [IFN] genes), to detect c-di-AMP synthesized by Chlamydia and induce a protective IFN response. This detection occurs even though Chlamydia is confined to a membrane-bound vacuole. This raises the possibility that the ER, an organelle that innervates the entire cytoplasm, is equipped with pattern recognition receptors that can directly survey membrane-bound pathogen-containing vacuoles for leaking microbe-specific metabolites to mount type I IFN responses required to control microbial infections

Changes in Cognitive State Alter Human Functional Brain Networks

The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole-brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation). Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level

The production, characteristics and utilization of forage-fed beef

Cover title.Includes bibliographical references (pages 75-78)

Coping with brief periods of food restriction: mindfulness matters

The obesity epidemic had spawned considerable interest in understanding peoples' responses to palatable food cues that are plentiful in obesogenic environments. In this paper we examine how trait mindfulness of older, obese adults may moderate brain networks that arise from exposure to such cues. Nineteen older, obese adults came to our laboratory on two different occasions. Both times they ate a controlled breakfast meal and then were restricted from eating for 2.5 h. After this brief period of food restriction, they had an fMRI scan in which they were exposed to food cues and then underwent a 5 min recovery period to evaluate brain networks at rest. On one day they consumed a BOOST® liquid meal prior to scanning, whereas on the other day they only consumed water (NO BOOST® condition). We found that adults high in trait mindfulness were able to return to their default mode network (DMN), as indicated by greater global efficiency in the precuneus, during the post-exposure rest period. This effect was stronger for the BOOST® than NO BOOST® treatment condition. Older adults low in trait mindfulness did not exhibit this pattern in the DMN. In fact, the brain networks of those low on the MAAS suggests that they continued to be pre-occupied with the elaboration of food cues even after cue exposure had ended. Further work is needed to examine whether mindfulness-based therapies alter brain networks to food cues and whether these changes are related to eating behavior

Auditory enhancement of visual temporal order judgment

Abstract: Although numerous studies have shown that response times can be speeded by the presentation of multisensory stimuli, here we show that such speeding can be seen even when the second sensory channel fails to provide any task-relevant (i.e. redundant) information, and where cueing appears an unlikely explanation. Study participants performed a visual temporal order judgment task in the presence of task uninformative auditory cues, with the latter sound delayed relative to the latter visual cue. Responses were maximally speeded when the auditory stimulus was delayed by a short time (i.e. 100 ms) relative to the second visual target. These results illustrate a unique form of temporal benefit underlying a multisensory interaction, and form the basis for a novel explanation of these perceptual enhancements

The Effect of Work Rate on Oxygen Uptake Kinetics During Exhaustive Severe Intensity Cycling Exercise

The effect of work rate on oxygen uptake kinetics during exhaustive severe intensity cycling exercise Jennifer L. Sylvester, Samantha D. Burdette, Steven W. Cross, Nosa O. Idemudia, John, H. Curtis, Jakob L. Vingren, David W. Hill. Applied Physiology Laboratory, University of North Texas, Denton, TX During exhaustive severe intensity exercise, the oxygen uptake (VO2) increases exponentially, with a time constant of ~30 s. After ~1 to 2 min, a slow component emerges and drives the VO2 to its maximum. There are clear differences in the VO2 response profile across exercise intensity domains. These disparities might not be attributable to metabolic demand but, rather, to characteristics of the various intensity domains, such as the consequences of lactic acid production. PURPOSE: To investigate the role of exercise intensity on the VO2 response profile at intensities wholly within the severe domain. METHODS: Four women (mean ± SD: age 22 ± 2 years, height 167 ± 7 cm, mass 66 ± 5 kg) and eight men (age 23 ± 2 yr, height 179 ± 9 cm, mass 78 ± 10 kg) performed exhaustive constant-power cycle ergometer tests at two different severe intensity work rates (263 ± 78 W and 214 ± 64 W). Smoothed breath-by-breath VO2 data were fitted to a two-component (primary response and slow component) model using iterative regression. RESULTS: Times to exhaustion were 217 ± 27 s and 590 ± 82 s, respectively. The VO2max values were the same at the two different work rates (2973 ± 691 ml·min-1 and 3011 ± 728 ml·min-1). The amplitude of the primary response was greater (p \u3c 0.05) at the higher work rate (2095 ± 716 ml·min-1) than at the lower work rate (1857 ± 618 ml·min-1) and the amplitude of the slow component was smaller (367 ± 177 ml·min-1 vs 645 ± 347 ml·min-1). In addition, the time delay before the emergence of the slow component was shorter at the higher work rate (92 ± 22 s vs 116 ± 42 s). CONCLUSION: The results show that exercise intensity per se affects the VO2 response profile within the severe intensity domain and suggest that metabolic demand drives the primary response of VO2 kinetics within this domain. Category to be judged: Master\u27

Precision mass measurements of magnesium isotopes and implications on the validity of the Isobaric Mass Multiplet Equation

If the mass excess of neutron-deficient nuclei and their neutron-rich mirror partners are both known, it can be shown that deviations of the Isobaric Mass Multiplet Equation (IMME) in the form of a cubic term can be probed. Such a cubic term was probed by using the atomic mass of neutron-rich magnesium isotopes measured using the TITAN Penning trap and the recently measured proton-separation energies of $^{29}$Cl and $^{30}$Ar. The atomic mass of $^{27}$Mg was found to be within 1.6$\sigma$ of the value stated in the Atomic Mass Evaluation. The atomic masses of $^{28,29}$Mg were measured to be both within 1$\sigma$, while being 8 and 34 times more precise, respectively. Using the $^{29}$Mg mass excess and previous measurements of $^{29}$Cl we uncovered a cubic coefficient of $d$ = 28(7) keV, which is the largest known cubic coefficient of the IMME. This departure, however, could also be caused by experimental data with unknown systematic errors. Hence there is a need to confirm the mass excess of $^{28}$S and the one-neutron separation energy of $^{29}$Cl, which have both come from a single measurement. Finally, our results were compared to ab initio calculations from the valence-space in-medium similarity renormalization group, resulting in a good agreement.Comment: 7 pages, 3 figure

Serving God and Country? Religious Involvement and Military Service Among Young Adult Men

Despite important connections between religion and military action throughout world history, scholars have seldom explored the association between religiosity and military enlistment. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we used a person-oriented analysis to categorize young men according to patterns of adolescent religious involvement. Youth indentified as “highly religious evangelical” are more likely to enlist in the military compared to their “highly religious non-evangelical” and “non-religious” counterparts; however, these findings hold only for those young men without college experience. These findings are discussed along with study limitations and promising directions for future research

Universal fractal scaling of self-organized networks

There is an abundance of literature on complex networks describing a variety of relationships among units in social, biological, and technological systems. Such networks, consisting of interconnected nodes, are often self-organized, naturally emerging without any overarching designs on topological structure yet enabling efficient interactions among nodes. Here we show that the number of nodes and the density of connections in such self-organized networks exhibit a power law relationship. We examined the size and connection density of 46 self-organizing networks of various biological, social, and technological origins, and found that the size-density relationship follows a fractal relationship spanning over 6 orders of magnitude. This finding indicates that there is an optimal connection density in self-organized networks following fractal scaling regardless of their sizes

Using Network Science to Evaluate Exercise-Associated Brain Changes in Older Adults

Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise