Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the “classic” default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.     

Structures of the Bacillus subtilis Glutamine Synthetase Dodecamer Reveal Large Intersubunit Catalytic Conformational Changes Linked to a Unique Feedback Inhibition Mechanism

Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in nitrogen metabolism. There are two main bacterial GS isoenzymes, GSI-α and GSI-β. GSI-α enzymes, which have not been structurally characterized, are uniquely feedback-inhibited by Gln. To gain insight into GSI-α function, we performed biochemical and cellular studies and obtained structures for all GSI-α catalytic and regulatory states. GSI-α forms a massive 600-kDa dodecameric machine. Unlike other characterized GS, the Bacillus subtilis enzyme undergoes dramatic intersubunit conformational alterations during formation of the transition state. Remarkably, these changes are required for active site construction. Feedback inhibition arises from a hydrogen bond network between Gln, the catalytic glutamate, and the GSI-α-specific residue, Arg⁶², from an adjacent subunit. Notably, Arg⁶² must be ejected for proper active site reorganization. Consistent with these findings, an R62A mutation abrogates Gln feedback inhibition but does not affect catalysis. Thus, these data reveal a heretofore unseen restructuring of an enzyme active site that is coupled with an isoenzyme-specific regulatory mechanism. This GSI-α-specific regulatory network could be exploited for inhibitor design against Gram-positive pathogens.     

Differential Expression of Programmed Cell Death on the Follicular Development in Normal and Miniature Pig Ovary

Follicles are important in oocyte maturation. Successful estrous cycle requires remodeling of follicular cells, and proper execution of programmed cell death is crucial for normal follicular development. The objectives of the present study were to understand programmed cell death during follicle development, to analyze the differential follicle development patterns, and to assess the patterns of apoptosis and autophagy expression during follicle development in normal and miniature pigs. Through the analysis of differential patterns of programmed cell death during follicular development in porcine, MAP1LC3A, B and other autophagy-associated genes (ATG5, mTOR, Beclin-1) were found to increase in normal pigs, while it decreased in miniature pigs. However, for the apoptosis-associated genes, progression of genes during follicular development increased in miniature pigs, while it decreased in normal pigs. Thus, results show that normal and miniature pigs showed distinct patterns of follicular remodeling manifesting that programmed cell death largely depends on the types of pathway during follicular development (Type II or autophagy for normal pigs and Type I or apoptosis for miniature pigs).     

Influence of mixed-ligand complexes on retention and distribution of radioniobium in mice

The individual effects of desferrioxamine B (DFOA), Na3Ca diethylenetriaminepentaacetic acid (DTPA), Na-salicylate, DL-penicillamine, and 2-aminoethylisothiouronium bromide hydrobromide, as well as the effect of mixed-ligand treatment on the retention and elimination of 95Nb in mice have been examined. It was found that 95Nb could easily be mobilized by a single dose of DFOA, but the best result was obtained with the DFOA and DTPA combination. Mixed-ligand treatment did not change the deposition characteristics and translocation kinetics of 95Nb.     

A cluster of Ankyrin and Ankyrin-TPR repeat genes is associated with panicle branching diversity in rice

The number of grains per panicle is an important yield-related trait in cereals which depends in part on panicle branching complexity. One component of this complexity is the number of secondary branches per panicle. Previously, a GWAS site associated with secondary branch and spikelet numbers per panicle in rice was identified. Here we combined gene capture, bi-parental genetic population analysis, expression profiling and transgenic approaches in order to investigate the functional significance of a cluster of 6 ANK and ANK-TPR genes within the QTL. Four of the ANK and ANK-TPR genes present a differential expression associated with panicle secondary branch number in contrasted accessions. These differential expression patterns correlate in the different alleles of these genes with specific deletions of potential cis-regulatory sequences in their promoters. Two of these genes were confirmed through functional analysis as playing a role in the control of panicle architecture. Our findings indicate that secondary branching diversity in the rice panicle is governed in part by differentially expressed genes within this cluster encoding ANK and ANK-TPR domain proteins that may act as positive or negative regulators of panicle meristem’s identity transition from indeterminate to determinate state.     

Dietary Patterns and the Metabolic Syndrome in Obese and Non‐obese Framingham Women**

Objectives: To examine the relationship between habitual dietary patterns and the metabolic syndrome (MetS) in women and to identify foci for preventive nutrition interventions. Research Methods and Procedures: Dietary patterns, nutrient intake, cardiovascular disease (CVD), and MetS risk factors were characterized in 1615 Framingham Offspring‐Spouse Study (FOS) women. Dietary pattern subgroups were compared for MetS prevalence and CVD risk factor status using logistic regression and analysis of covariance. Analyses were performed overall in women and stratified on obesity status; multivariate models controlled for age, apolipoprotein E (APOE) genotypes, and CVD risk factors. Results: Food and nutrient profiles and overall nutritional risk of five non‐overlapping habitual dietary patterns of women were identified including Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calories. Rates of hypertension and low high‐density lipoprotein levels were high in non‐obese women, but individual MetS risk factor levels were substantially increased in obese women. Overall MetS risk varied by dietary pattern and obesity status, independently of APOE and CVD risk factors. Compared with obese or non‐obese women and women overall with other dietary patterns, MetS was highest in those with the Empty Calorie pattern (contrast p value: p < 0.05). Discussion: This research shows the independent relationship between habitual dietary patterns and MetS risk in FOS women and the influence of obesity status. High overall MetS risk and the varying prevalence of individual MetS risk factors in female subgroups emphasize the importance of preventive nutrition interventions and suggest potential benefits of targeted behavior change in both obese and non‐obese women by dietary pattern.     

Metabolic flux analysis ofBeijerinckia indica for PS-7 production

In order to investigate central metabolic changes inBeijerinckia indica, cells were grown on different carbon sources and intracellular flux distributions were studied under varying concentrations of nitrogen. Metabolic fluxes were estimated by combining material balances with extracellular substrate uptake rate, biomass formation rate, and exopolysaccharide (EPS) accumulation rate. Thirty-one metabolic reactions and 30 intracellular metabolites were considered for the flux analysis. The results revealed that most of the carbon source was directed into the Entner-Doudoroff pathway, followed by the recycling of triose-3-phosphate back to Hexose-6-phosphate. The pentose phosphate pathway was operated at a minimal level to supply the precursors for biomass formation. The different metabolic behaviors under varying nitrogen concentrations were observed with flux analysis.     

Production of cyclodextrin by poly-lysine fused Bacillus macerans cyclodextrin glycosyltransferase immobilized on cation exchanger

Bacillus macerans cyclodextrin glycosyltransferase (CGTase) fused with 10 lysine residues at its C-terminus (CGTK10ase) was immobilized onto a cation exchanger by ionic interaction and used to produce -cyclodextrin (CD) from soluble starch. Poly-lysine fused immobilization increased the V_m of the immobilized CGTase by 40% without a change in K_m. The activation energies of thermal deactivation (E_a) were 41.4, 28.1, and 25.9 kcal mol⁻¹, respectively, for soluble wild-type (WT) CGTase, soluble CGTK10ase, and immobilized CGTK10ase, suggesting destabilization of CGTase by poly-lysine fusion and immobilization onto a cation exchanger. Maximum -CD productivity of 539.4 g l⁻¹ h⁻¹ was obtained with 2% soluble starch solution which was constantly fed at a flow rate of 4.0 ml min⁻¹ (D = 240 h⁻¹) in a continuous operation mode of a packed-bed reactor. The operational half-life of the packed-bed enzyme reactor was estimated 12 days at 25 °C and pH 6.0.