3,720 research outputs found
State Dependence of Stimulus-Induced Variability Tuning in Macaque MT
Behavioral states marked by varying levels of arousal and attention modulate
some properties of cortical responses (e.g. average firing rates or pairwise
correlations), yet it is not fully understood what drives these response
changes and how they might affect downstream stimulus decoding. Here we show
that changes in state modulate the tuning of response variance-to-mean ratios
(Fano factors) in a fashion that is neither predicted by a Poisson spiking
model nor changes in the mean firing rate, with a substantial effect on
stimulus discriminability. We recorded motion-sensitive neurons in middle
temporal cortex (MT) in two states: alert fixation and light, opioid
anesthesia. Anesthesia tended to lower average spike counts, without decreasing
trial-to-trial variability compared to the alert state. Under anesthesia,
within-trial fluctuations in excitability were correlated over longer time
scales compared to the alert state, creating supra-Poisson Fano factors. In
contrast, alert-state MT neurons have higher mean firing rates and largely
sub-Poisson variability that is stimulus-dependent and cannot be explained by
firing rate differences alone. The absence of such stimulus-induced variability
tuning in the anesthetized state suggests different sources of variability
between states. A simple model explains state-dependent shifts in the
distribution of observed Fano factors via a suppression in the variance of gain
fluctuations in the alert state. A population model with stimulus-induced
variability tuning and behaviorally constrained information-limiting
correlations explores the potential enhancement in stimulus discriminability by
the cortical population in the alert state.Comment: 36 pages, 18 figure
Surficial Geology of the Davenport East 7.5\u27 Quadrangle, Scott County, Iowa
https://ir.uiowa.edu/igs_ofm/1068/thumbnail.jp
Surficial geologic materials of the Dixon 7.5\u27\u27 Quadrangle, Scott County, Iowa
https://ir.uiowa.edu/igs_ofm/1040/thumbnail.jp
Surficial Geology of the Fertile NE 7.5\u27 Quadrangle,
https://ir.uiowa.edu/igs_ofm/1082/thumbnail.jp
Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-N-(2′-Phenylethyl)-Butyramide
Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-N-(2′-phenylethyl)-butyramide, produced by a marine bacterium identified as Halobacillus salinus, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that N-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium Vibrio neptunius, similarly demonstrates QS inhibitory properties. To more fully explore structure–activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably N-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen Vibrio harveyi (IC50 = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors
Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer
Respiratory Symptoms in Relation to Residential Coal Burning and Environmental Tobacco Smoke Among Early Adolescents in Wuhan, China: A Cross-Sectional Study
Background
Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children\u27s respiratory health are not well characterized. Methods
Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment. Results
Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07–2.29] and without colds (OR = 1.44, 95% CI: 1.05–1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17–2.60) and phlegm production (OR = 2.25, 95% CI: 1.36–3.72) without colds among children who lived with two or more smokers. Conclusions
Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population
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Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase.
Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes
Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission
We previously showed that gastrin-releasing peptide receptor (GRPR) in the spinal cord is important for mediating nonhistaminergic itch. Neuromedin B receptor (NMBR), the second member of the mammalian bombesin receptor family, is expressed in a largely nonoverlapping pattern with GRPR in the superficial spinal cord, and its role in itch transmission remains unclear. Here, we report that Nmbr knock-out (KO) mice exhibited normal scratching behavior in response to intradermal injection of pruritogens. However, mice lacking both Nmbr and Grpr (DKO mice) showed significant deficits in histaminergic itch. In contrast, the chloroquine (CQ)-evoked scratching behavior of DKO mice is not further reduced compared with Grpr KO mice. These results suggest that NMBR and GRPR could compensate for the loss of each other to maintain normal histamine-evoked itch, whereas GRPR is exclusively required for CQ-evoked scratching behavior. Interestingly, GRPR activity is enhanced in Nmbr KO mice despite the lack of upregulation of Grpr expression; so is NMBR in Grpr KO mice. We found that NMB acts exclusively through NMBR for itch transmission, whereas GRP can signal through both receptors, albeit to NMBR to a much lesser extent. Although NMBR and NMBR(+) neurons are dispensable for histaminergic itch, GRPR(+) neurons are likely to act downstream of NMBR(+) neurons to integrate NMB-NMBR-encoded histaminergic itch information in normal physiological conditions. Together, we define the respective function of NMBR and GRPR in itch transmission, and reveal an unexpected relationship not only between the two receptors but also between the two populations of interneurons in itch signaling
C1q deficiency leads to the defective suppression of IFN-α in response to nucleoprotein containing immune complexes
Almost all humans with homozygous deficiency of C1q develop systemic lupus erythematosus (SLE). The precise cellular mechanism (s) by which C1q prevents the development of SLE remains unclear. In this study, we tested the role of C1q in the regulation of IFN-α induced by immune complexes (ICs) in vitro, as well as the consequences of lack of C1q in vivo. Our experiments revealed that C1q preferentially promotes the binding of SLE ICs to monocytes rather than plasmacytoid dendritic cells, but this inhibition was not due to the induction of inhibitory soluble factors. The presence of C1q also altered the trafficking of ICs within monocytes such that ICs persisted in early endosomes. In patients with C1q deficiency, serum and cerebrospinal fluid levels of IFN-α and IFN-γ–inducible protein-10 levels were elevated and strongly correlated with Ro autoantibodies, demonstrating the clinical significance of these observations. These studies therefore associate C1q deficiency with defective regulation of IFN-α and provide a better understanding of the cellular mechanisms by which C1q prevents the development of IC-stimulated autoimmunity
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