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Prosodic clues to syntactic processing--a PET and ERP study.

Syntactic processing of spoken speech often involves prosodic clues processing. In the present PET and ERP study, subjects listened to phrases in which different prosodic segmentation dramatically changed the meaning of the phrase. In the contrast of segmented vs. non-segmented phrases, PET data revealed activation in the right dorsolateral prefrontal cortex and in the right cerebellum. These brain structures, therefore, might be part of the syntactic analysis network involved in prosodic segmentation and pitch processing. ERP results revealed frontal negativity that was sensitive to the position of the segmenting pause, possibly reflecting prosody-based semantic prediction. The present results are discussed in the context of their relation to brain networks of emotions, prosody, and syntax perception.

Adolescent↗

'Supply' and 'demand': breastfeeding as labour.

This paper presents findings from a recent critical ethnographic study conducted in two maternity units in England, UK. The study explored the influences upon 61 women's experiences of breastfeeding within the postnatal ward setting. Participant observations of 97 encounters between midwives and postnatal women, 106 focused interviews with postnatal women and 37-guided conversations with midwives were conducted. Basic, organising and global themes were constructed utilising thematic networks analysis. The metaphor of the production line, with its notions of demand and efficient supply, illustrated the experiences of breastfeeding women. They conceptualised breastfeeding as a 'productive' project, yet expressed deep mistrust in the efficacy of their bodies. Their emphasis centred upon breast milk as nutrition rather than relationality and breastfeeding. Women referred to the demanding and unpredictable ways in which their baby breached their temporal and spatial boundaries. They sought strategies to cope with the uncertainty of this embodied experience in combination with their concerns regarding returning to a 'normal' and 'productive' life. The hospital setting and health worker practices played a contributing and reinforcing role. The paper discusses ways of re-establishing trust in women's bodies and breastfeeding, while respecting difference and diversity. It argues for embracing the concepts of embodiment and relationality whilst avoiding a return to essentialism. This requires collective efforts to erode deeply embedded cultural understandings of women's bodies centering upon disembodied and efficient production.

Adaptation, Psychological↗

Organization, development and function of complex brain networks.

Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might arise in the course of network growth and rewiring. Moreover, we examine the relationship between the structural substrate of neuroanatomy and more dynamic functional and effective connectivity patterns that underlie human cognition. We suggest that network analysis offers new fundamental insights into global and integrative aspects of brain function, including the origin of flexible and coherent cognitive states within the neural architecture.

Brain↗

Chromosomal organization is shaped by the transcription regulatory network.

Transcription regulation, a key step in the control of gene expression, has been the focus of several large-scale studies; however, little attention has been given to its relationship with the chromosomal arrangement of transcription units. We studied this relationship systematically in Escherichia coli and Saccharomyces cerevisiae using network analysis methods. Our analysis reveals links between transcription regulation and chromosomal organization, suggesting that in both organisms transcription regulation has shaped the organization of transcription units on the chromosome. Differences found between the organisms reflect the inherent differences in transcription regulation between prokaryotes and eukaryotes.

Chromosomes, Bacterial↗

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy↗

Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years.

OBJECTIVES: To determine the risk of clinical progressions in men with mild lower urinary tract symptoms of bladder outlet obstruction and identify the predictors for progression in this group of men. METHODS: A total of 397 men who presented to the urology clinics with mild symptoms of bladder outlet obstruction (International Prostate Symptom Score less than 8) were analyzed in this longitudinal study conducted during a 4-year period. They began with the watchful waiting protocol and were followed up every 3 months for 48 months. Age, International Prostate Symptom Score (IPSS), divided into obstructive symptom score and irritative symptom score, serum prostate-specific antigen level, total prostate volume, transitional zone volume, urinary flow rates, and postvoid residual urine volume were documented. RESULTS: The cumulative incidence of clinical progression, defined as worsening of the IPSS with migration to the moderate symptom group (IPSS 8 to 18) or severe symptom group (IPSS 19 to 35) and an increase in IPSS of more than 2 points, was 6%, 13%, 15%, 24%, 28%, and 31% at 6, 12, 18, 24, 36, and 48 months, respectively. Nineteen patients (4.9%) developed acute urinary retention within the 48-month follow-up period. Of these 19 patients, only 2 (0.6%) required transurethral resection of the prostate. The variables of importance for disease progression in the artificial neural network analysis were, in order of statistical significance, prostate-specific antigen level, obstructive symptom score, and transitional zone volume. CONCLUSIONS: The risk for men with mild symptoms of bladder outlet obstruction to progress clinically and develop complications such as acute retention of urine is moderate. Prostate-specific antigen, obstructive symptom score, and transitional zone volume were identified as important risk factors.

Aged↗

Involvement of cross-genus phages in bacterial resistance to chlorine disinfection.

Chlorine disinfection resistance in pathogenic microorganisms poses severe environmental concerns and public health risks. While phages play critical roles in host adaptation to environmental stress, how poly-host phages contribute to bacterial resistance to chlorine disinfectants remains poorly understood. Here, we investigated shifts in the population dynamics, transcriptional profiles, and function potentials of cross-genus phage-bacterial communities under exposure to chlorine disinfectants in a continuously operated anaerobic-anoxic-oxic system over a 92-day period, using integrated metagenomic and metatranscriptomic approaches. In the presence and absence of chlorine disinfectants, the genomic abundance and diversity of phage and bacterial communities showed similar variation trends, and the community structures of both exhibited clear differences. A strong significant positive correlation was observed between phage and bacterial diversity under chlorine exposure (R&#x202f;=&#x202f;0.975, p&#x202f;=&#x202f;0.00,057), whereas no significant correlation was detected in the absence of chlorine disinfection (R&#x202f;=&#x202f;-0.314, p&#x202f;=&#x202f;0.613), suggesting that chlorine disinfectants may enhance phage-bacteria interactions. Host-associated phages exhibited high consistency with their corresponding putative hosts in terms of genomic abundance (M2&#x202f;=&#x202f;0.0945, p&#x202f;=&#x202f;0.001) and transcript abundance (M2&#x202f;=&#x202f;0.3668, p&#x202f;=&#x202f;0.001), and they were also significantly correlated with cross-genus phages in both genomic abundance (R&#x202f;=&#x202f;0.97, p&#x202f;<&#x202f;2.2e-16) and transcript abundance (R&#x202f;=&#x202f;0.83, p&#x202f;<&#x202f;2.2e-16), which collectively suggests the critical role of cross-genus phages in the resistance of microbial communities to chlorine disinfectants. Bipartite association network analysis shows that cross-genus phages carry highly homologous genes to their putative hosts and may be involved in the horizontal transfer of these genes among bacteria. These homologous genes are involved in DNA repair, redox balance regulation, environmental stress adaptation and efflux pump functions, suggesting a synergistic role between cross-genus phages and their putative hosts in chlorine resistance. Our findings reveal that cross-genus phages can contribute to the resistance of bacterial communities to chlorine disinfectants, providing the theoretical foundation for evaluating the role of poly-host phages in microbial communities.

Chlorine resistance↗

Comparative transcriptomic and physiological analyses uncover key regulatory pathways associated with drought tolerance in wheat.

Drought severely limits wheat yield, yet its molecular basis remains incompletely understood. We compared a drought-tolerant line (A25) and a drought-sensitive line (A8) under water deficit across three developmental stages using physiological assays and transcriptomics. A25 exhibited stronger osmotic adjustment and antioxidant defense, with higher proline accumulation and enhanced activities of ascorbate peroxidase, catalase, and other ROS-scavenging enzymes. RNA-seq revealed distinct drought-responsive expression patterns, with differentially expressed genes enriched in MAPK signaling and ABA-dependent pathways. ABA-responsive genes were more abundant and strongly induced in A25, suggesting enhanced ABA signal transduction as a key mechanism. Weighted gene co-expression network analysis identified a drought-associated purple module positively correlated with physiological resistance, from which six hub genes (MAPKKK17, Avr9/Cf-9, RPPL1, RGA1, UBC28, AGPs5) were highlighted as potential regulators. Collectively, coordinated activation of ABA signaling and MAPK cascades, mediated by these hub genes, underlies the robust drought tolerance of A25, providing promising molecular targets for wheat breeding and improvement.

Triticum↗

Integration of gene expression data into genome-scale metabolic models.

A framework for integration of transcriptome data into stoichiometric metabolic models to obtain improved flux predictions is presented. The key idea is to exploit the regulatory information in the expression data to give additional constraints on the metabolic fluxes in the model. Measurements of gene expression from chemostat and batch cultures of Saccharomyces cerevisiae were combined with a recently developed genome-scale model, and the computed metabolic flux distributions were compared to experimental values from carbon labeling experiments and metabolic network analysis. The integration of expression data resulted in improved predictions of metabolic behavior in batch cultures, enabling quantitative predictions of exchange fluxes as well as qualitative estimations of changes in intracellular fluxes. A critical discussion of correlation between gene expression and metabolic fluxes is given.

Databases, Genetic↗

Heterologous expression of Escherichia coli ppsA (phosphoenolpyruvate synthetase) and galU (UDP-glucose pyrophosphorylase) genes in Corynebacterium glutamicum, and its impact on trehalose synthesis.

Trehalose is a disaccharide with a wide range of applications in the food industry. We recently proposed a strategy for trehalose production based on a Corynebacterium glutamicum strain expressing the Escherichia coli enzyme UDP-glucose pyrophosphorylase (GalU). Biochemical network analysis suggest a further bottleneck for trehalose synthesis resulting from the coupling of phosphotransferase (PTS) mediated glucose uptake, and glucose catabolism in C. glutamicum. To overcome this coupling, we propose the expression of E. coli phosphoenolpyruvate synthetase (PpsA), in addition to GalU expression, in C. glutamicum. Although GalU expression improved trehalose synthesis in C. glutamicum, the simultaneous expression of GalU and PpsA did not result in a further increase in trehalose yield, but resulted in an increased catabolic rate of glucose, which could be ascribed to the operation of a futile cycle between phosphoenolpyruvate and pyruvate. The impact of GalU and PpsA expression on polysaccharide content, side product excretion and metabolic fluxes is discussed, as well as alternative ways to decouple glucose uptake and catabolism, in order to increase trehalose yield.

Corynebacterium glutamicum↗

Genetic diversity and origin of Chinese cattle revealed by mtDNA D-loop sequence variation.

To determine the origin and genetic diversity of Chinese cattle, we analyzed the complete mtDNA D-loop sequences of 84 cattle from 14 breeds/populations from southwest and west China, together with the available cattle sequences in GenBank. Our results showed that the Chinese cattle samples converged into two main groups, which correspond to the two species Bos taurus and Bos indicus. Although a dominant lineage was clearly discerned in both B. taurus and B. indicus mtDNAs, network analysis of the lineages in each of the two species further revealed multiple clades that presented regional difference. The B. taurus samples in China could be grouped into clades T2, T3, and T4, whereas B. indicus harbored two clades I1 and I2. Age estimation of these discerned clades showed a time range of 14,100-44,500 years before present (YBP). The phylogenetic pattern of Chinese cattle was consistent with the recently described cattle matrilineal pool from northeast Asia, but suggested that B. indicus contributed more to the cattle from south and southwest China. The genetic diversity of Chinese cattle varied among the breeds studied.

Animals↗

Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glaucomatous damage.

PURPOSE: To investigate the ability of three diagnostic tests: frequency-doubling technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL) photographs to distinguish normal from glaucomatous eyes. METHODS: Data were obtained in a cross-sectional, hospital clinic-based study, including one eye from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and 91 glaucoma patients). We performed a comprehensive ocular examination, as well as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve stereoscopic photographs and high-contrast NFL photographs. RESULTS: The following were significantly different for glaucomatous patients compared with suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p = 0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining features of glaucoma, we found that the optimal mix of sensitivity and specificity values were 84% and 100% for FDT (presence of any defect); 62% and 96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL photographs (presence of any abnormality). FDT testing took the least time to be administered. CONCLUSIONS: The FDT had the best diagnostic performance. Neural network analysis of GDx data outperformed other elements of its software.

Cross-Sectional Studies↗

Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells.

Mitochondria are dynamic organelles that undergo frequent fission and fusion or branching. To analyze the mitochondrial fusion reaction, mitochondria were separately labeled with green or red fluorescent protein (GFP and RFP, respectively) in HeLa cells, and the cells were fused using hemagglutinating virus of Japan (HVJ). The resulting mixing of the fluorescent reporters was then followed using fluorescence microscopy. This system revealed that mitochondria fuse frequently in mammalian cells, and the fusion depends on the membrane potential across the inner membrane. The protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to fragmentation of the mitochondria and inhibited the fusion reaction. Removal of CCCP recovered the fusion activity to reform filamentous mitochondrial networks. Analysis of the effects of GTP-binding proteins, DRP1 and two FZO1 isoforms, and the GTPase-domain mutants on the CCCP-induced mitochondrial morphologic changes revealed that DRP1 and FZO1 are involved in membrane budding and fusion, respectively. Furthermore, a HVJ-dependent cell fusion assay combined with RNA interference (RNAi) demonstrated that both FZO1 isoforms are essential and must be acting in cis for the mitochondrial fusion reaction to occur.

Animals↗

High-pass filtering of small signals by retinal rods. Ionic studies.

The high-pass filtering of small signals by the rod photoreceptor network was studied by intracellular recording in the isolated, perfused retina of the toad, Bufo marinus. Data were analyzed and interpreted in terms of the network analysis described in the preceding paper. External concentrations of Cs+ as high as 10 mM, which blocked the relaxation from peak to plateau of the rod's response to bright light, did not affect the filtering of small signals. The effects of reducing [Na+]o were not consistent with a direct action upon the mechanism underlying this filtering property. By contrast, raising external [K+] from 2.6 to 10 mM, which caused a fourfold reduction in EK, abolished the high-pass filtering of small signals. Analysis of the effects of external [K+] changes indicates that the underlying mechanism involves a K+ conductance that decreases with a delay when the rod is hyperpolarized. This conductance is not blocked by externally applied tetraethylammonium. Other experiments did not rule out the possibility that it might be activated by Ca++.

Animals↗

Use of serum creatinine to predict pathologic stage and recurrence among radical prostatectomy patients.

OBJECTIVES: To assess serum creatinine as a putative marker for staging/prognosis in localized prostate cancer. Although clinical stage, tumor grade, serum prostate-specific antigen (PSA), and tumor volume assessment by biopsy positivity are established prognostic markers in prostate cancer, the need for additional serum markers is clear. In a prior neural network analysis by our group, serum creatinine appeared to improve staging and prognosis. Even though serum creatinine is one of the most common blood tests used by practicing urologists, it has not been tested rigorously as a potential staging/prognosis marker in localized prostate cancer. METHODS: The data on 409 patients who underwent radical prostatectomy at the Walter Reed Army Medical Center between 1990 and 1996 were analyzed. Logistic regression analysis was used to evaluate the ability of serum creatinine to predict the pathologic stage. The ability of creatinine to predict PSA recurrence was also assessed using Cox regression analysis. In multivariable analyses, creatinine was assessed while simultaneously controlling for race, age, prostate weight, clinical stage, Gleason (World Health Organization) grade, prostatism history, treatment of benign prostatic hyperplasia, and pretreatment PSA level. RESULTS: Creatinine ranged from 0.1 to 2.3 mg/dL (mean and median 1.1 mg/dL). The relationship of creatinine to pathologic stage was significant (P = 0.050). As the level of creatinine increased, the proportion of patients with extraprostatic disease generally decreased. In multivariable logistic regression analysis, creatinine was not a significant predictor (P = 0.270). The relationship of the creatinine level to PSA recurrence was not significant in the univariate or multivariable analysis. CONCLUSIONS: Creatinine did not provide independent information for predicting pathologic stage or disease recurrence in patients with early prostate cancer.

Aged↗

An imaging system for monitoring receptive field dynamics.

The paper describes a computerized method, termed receptive field imaging (RFI), for the rapid mapping of multiple receptive fields and their respective sensitivity distributions. RFI uses random stimulation of multiple sites, in combination with an averaging procedure, to extract the relative contribution from each of the stimulated sites. Automated multi-electrode stimulation and recording, with spike detection and counting, are performed on-line by the RFI programme. Direct user interpretation of receptive field changes is made possible by a user-friendly graphic interface. A series of imaging experiments was carried out to evaluate the functional capacity of the system. RFI was tested on the receptive fields in the nociceptive withdrawal reflex (NWR) system in the rat. RFI replicates the results obtained with conventional methods and allows the display of receptive field dynamics induced by topical spinal cord application of morphine and naloxone on a minute-to-minute time scale. Data variance was estimated, and proved to be small enough to yield a stable representation of the receptive field, thereby achieving a high sensitivity in dynamic imaging experiments. The large number of stimulation and registration sites that can be monitored in parallel permits detailed network analysis of synaptic sets, corresponding to 'connection weights' between individual neurones.

Analysis of Variance↗

Synaptic contacts between identified neurons visualized in the confocal laser scanning microscope. Neuroanatomical tracing combined with immunofluorescence detection of post-synaptic density proteins and target neuron-markers.

The axons of neurons in the CNS with their delicate ramification patterns and terminal boutons can be visualized with conventional neuroanatomical techniques with a high degree of accuracy. Whether identified terminal boutons form synaptic contacts with target neurons identified by a second and different marker needs resolution beyond that offered by conventional light microscopy. The morphological elements associated with synaptic connectivity consist of specialized pre- and post-synaptic junctional complexes known as the pre- and post-synaptic densities. Electron microscopy of these junctional complexes consumes much time and resources. In an attempt to increase the speed with which we can analyze networks of neurons we developed a high-resolution triple-fluorescence approach including neuroanatomical tracing, immunofluorescence, confocal laserscanning and 3D-computer reconstruction to pinpoint at the light microscopic level the three elements involved in synaptic connectivity: afferent fibers and their terminal boutons, close apposition with neurons identified by the presence of a fluorescent marker, and sandwiched in between a post-synaptic density marker. We used morphological criteria for the detection of axon terminals (swellings on fibers). Antibodies against ProSAP2/Shank3, a post-synaptic density-associated scaffolding protein, were used to pinpoint the location of the synaptic junctions. The results show the existence of sandwich-like configurations: pre-synaptic fiber, ProSAP2/Shank3, post-synaptic neuron. Thus we feel that we can minimize (and perhaps completely eliminate) the need for electron microscopy and hence dramatically increase the overall efficiency of neuroanatomical tracing and network analysis.

Adaptor Proteins, Signal Transducing↗

Effect of eutrophication upon radionuclide dynamics in the Sacca di Goro lagoon (Po River Delta, Italy): a combined field, experimental and modeling study.

The focus of this paper is on the relationship between eutrophication and radionuclide circulation at the whole ecosystem scale in the shallow estuarine environment of the Sacca di Goro (Po River Delta, Italy). This lagoon is frequently affected by dystrophic crises, due to decomposition of huge amounts of macroalgae (mainly Ulva rigida), and critical conditions created at the interface between sediment and water are such that Cs-137 accumulated in the sediment can be mobilized and made available in the water column. The release of cesium from sediment in this ecosystem has been evaluated through a field experiment in which chemical conditions typical of anoxic crises were artificially created in enclosures. Also a lab experiment was carried out to shed light on possible cesium release by decomposing macroalgae. The two experiments allowed drawing conclusions on crucial factors controlling cesium release in the Sacca di Goro, the first objective of this research. The second objective was understanding the fate of radiocesium once transported in the water column. To this end ecological information gathered during the experiments and a yearly sampling campaign, has been converted into whole-system seasonal networks describing ecosystem flow structure for the Sacca di Goro. Analyzed by network analysis this model has provided clues about the dynamics of Cs-137 in terms of preferential pathways, sinks, sources, and cycling activity. Sediment, together with seston and dissolved cesium, appear to be the most significant components in the circulation of Cs-137; while macroalgal biomasses play a crucial role as an indirect causal factor.

Cesium Radioisotopes↗