Phonotactics and syntax: Investigating functional specialisation during structured sequence processing

Frontal lobe organisation displays a functional gradient, with overarching processing goals located in parts anterior to more subordinate goals, processed more posteriorly. Functional specialisation for syntax and phonology within language relevant areas has been supported by meta-analyses and reviews, but never directly tested experimentally. We tested for organised functional specialisation by manipulating syntactic case and phonotactics, creating violations at the end of otherwise matched and predictable sentences. Both violations led to increased activation in expected language regions. We observe the clearest signs of a functional gradient for language processing in the medial frontal cortex, where syntactic violations activated a more anterior portion compared to the phonotactic violations. A large overlap of syntactic and phonotactic processing in the left inferior frontal gyrus (LIFG) supports the view that general structured sequence processes are located in this area. These findings are relevant for understanding how sentence processing is implemented in hierarchically organised processing steps in the frontal lobe

The Effect Of Public And Private Unions On State Economic Activity: Evaluating The Benefits To Organized Workers, Policymakers, And Companies

Freeman and Medoff’s analysis, “What Do Unions Do?” concluded unions were beneficial to organized workers, somewhat beneficial to the economy, yet not beneficial to the corporate bottom line. While there is some evidence to support these statements for 1983-1996, we determine that neither public nor private unions’ presence are correlated with wage or growth benefits at the state level from 1992-2005. A reduction in private sector unionization increases state productivity, with no adverse impact on growth, wages or unemployment rates. Public unions are statistically less detrimental than private unions, particularly in regard to unemployment rates

Generalized Centrifugal Force Model for Pedestrian Dynamics

A spatially continuous force-based model for simulating pedestrian dynamics is introduced which includes an elliptical volume exclusion of pedestrians. We discuss the phenomena of oscillations and overlapping which occur for certain choices of the forces. The main intention of this work is the quantitative description of pedestrian movement in several geometries. Measurements of the fundamental diagram in narrow and wide corridors are performed. The results of the proposed model show good agreement with empirical data obtained in controlled experiments.Comment: 10 pages, 14 figures, accepted for publication as a Regular Article in Physical Review E. This version contains minor change

Scaling of gauge balls and static potential in the confinement phase of the pure U(1) lattice gauge theory

We investigate the scaling behaviour of gauge-ball masses and static potential in the pure U(1) lattice gauge theory on toroidal lattices. An extended gauge field action $-\sum_P(\beta \cos\Theta_P + \gamma \cos2\Theta_P)$ is used with $\gamma= -0.2$ and -0.5. Gauge-ball correlation functions with all possible lattice quantum numbers are calculated. Most gauge-ball masses scale with the non-Gaussian exponent $\nu_{ng}\approx 0.36$. The $A_1^{++}$ gauge-ball mass scales with the Gaussian value $\nu_{g} \approx 0.5$ in the investigated range of correlation lengths. The static potential is examined with Sommer's method. The long range part scales consistently with $\nu_{ng}$ but the short range part tends to yield smaller values of $\nu$. The $\beta$-function, having a UV stable zero, is obtained from the running coupling. These results hold for both $\gamma$ values, supporting universality. Consequences for the continuum limit of the theory are discussed.Comment: Contribution to the Lattice 97 proceedings, LaTeX, 3 pages, 3 figure

Universality of the gauge-ball spectrum of the four-dimensional pure U(1) gauge theory

We continue numerical studies of the spectrum of the pure U(1) lattice gauge theory in the confinement phase, initiated in our previous work. Using the extended Wilson action $S = -\sum_P [\beta \cos(\Theta_P) + \gamma \cos(2\Theta_P)]$ we address the question of universality of the phase transition line in the ($\beta,\gamma$) plane between the confinement and the Coulomb phases. Our present results at $\gamma= -0.5$ for the gauge-ball spectrum are fully consistent with the previous results obtained at $\gamma= -0.2$. Again, two different correlation length exponents, $\nu_{ng} = 0.35(3)$ and $\nu_{g} = 0.49(7)$, are obtained in different channels. We also confirm the stability of the values of these exponents with respect to the variation of the distance from the critical point at which they are determined. These results further demonstrate universal critical behaviour of the model at least up to correlation lengths of 4 lattice spacings when the phase transition is approached in some interval at $\gamma\leq -0.2$.Comment: 16 page

A subset of Roux-en-Y Gastric Bypass bacterial consortium colonizes the gut of non-surgical rats without inducing host-microbial metabolic changes

Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria. The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome—increased Enterobacteriaceae—was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery. IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable. It is unclear how well these bacteria colonize in an anatomically normal gut. This is a fundamental question in both defining the function of the RYGB microbiota and evaluating its potential as a nonsurgical treatment for obesity. We monitored the dynamic colonization of the RYGB bacterial consortium and observed that while approximately one-third of the bacterial taxa from the RYGB donor colonized in the gut of the nonoperated recipients, Gammaproteobacteria were unable to colonize for longer than 3 days. The study highlighted that a successful long-term colonization of Gammaproteobacteria-rich RYGB microbiota in nonsurgical animals requires key environmental factors that may be dictated by the intestinal anatomical modification by the surgery itself

Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss

Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease

Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metab-olism and Host-Microbial Interactions

The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolic networks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is important to further our understanding of the circulation of the microbial or host–microbial metabolites and their impact on host metabolism. 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was used to probe global metabolic differences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n = 12) and lean (fa/+, n = 12) Zucker rats. Urinary concentrations of host–microbial co-metabolites were found to be significantly higher in lean Zucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid and glycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless of phenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portal vein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observed in portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that the absorption of propionate, acetate, choline, and trimethylamine is independent of the Zucker rat phenotypes. However, urinary host–microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activities in lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity, particularly the metabolic functionality of the gut microbiota in the context of obesity

Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain

<p>Abstract</p> <p>Background</p> <p>AMP-activated protein kinase (AMPK) is a known physiological cellular energy sensor and becomes phosphorylated at Thr-172 in response to changes in cellular ATP levels. Activated AMPK acts as either an inducer or suppressor of apoptosis depending on the severity of energy stress and the presence or absence of certain functional tumor suppressor genes.</p> <p>Results</p> <p>Here we show that energy stress differentially affects AMPK phosphorylation and cell-death in brain tumor tissue and in tissue from contra-lateral normal brain. We compared TSC2 deficient CT-2A mouse astrocytoma cells with syngeneic normal astrocytes that were grown under identical condition <it>in vitro</it>. Energy stress induced by glucose withdrawal or addition of 2-deoxyglucose caused more ATP depletion, AMPK phosphorylation and apoptosis in CT-2A cells than in the normal astrocytes. Under normal energy conditions pharmacological stimulation of AMPK caused apoptosis in CT-2A cells but not in astrocytes. TSC2 siRNA treated astrocytes are hypersensitive to apoptosis induced by energy stress compared to control cells. AMPK phosphorylation and apoptosis were also greater in the CT-2A tumor tissue than in the normal brain tissue following implementation of dietary energy restriction. Inefficient mTOR and TSC2 signaling, downstream of AMPK, is responsible for CT-2A cell-death, while functional LKB1 may protect normal brain cells under energy stress.</p> <p>Conclusion</p> <p>Together these data demonstrates that AMPK phosphorylation induces apoptosis in mouse astrocytoma but may protect normal brain cells from apoptosis under similar energy stress condition. Therefore, using activator of AMPK along with glycolysis inhibitor could be a potential therapeutic approach for TSC2 deficient human malignant astrocytoma.</p