Modular brain network in volitional eyes closing: enhanced integration with a marked impact on hubs.

Volitional eyes closing would shift brain's information processing modes from the "exteroceptive" to "interoceptive" state. This transition induced by the eyes closing is underpinned by a large-scale reconfiguration of brain network, which is still not fully comprehended. Here, we investigated the eyes-closing-relevant network reconfiguration by examining the functional integration among intrinsic modules. Our investigation utilized a publicly available dataset with 48 subjects being scanned in both eyes closed and eyes open conditions. It was found that the modular integration was significantly enhanced during the eyes closing, including lower modularity index, higher participation coefficient, less provincial hubs, and more connector hubs. Moreover, the eyes-closing-enhanced integration was particularly noticeable in the hubs of network, mainly located in the default-mode network. Finally, the hub-dominant modular enhancement was positively correlated to the eyes-closing-reduced entropy of BOLD signal, suggesting a close connection to the diminished consciousness of individuals. Collectively, our findings strongly suggested that the enhanced modular integration with substantially reorganized hubs characterized the large-scale cortical underpinning of the volitional eyes closing.

Functional Formulation of Quantum Theory of a Scalar Field in a Metric with Lorentzian and Euclidean Signatures.

We study the Schrödinger equation in quantum field theory (QFT) in its functional formulation. In this approach, quantum correlation functions can be expressed as classical expectation values over (complex) stochastic processes. We obtain a stochastic representation of the Schrödinger time evolution on Wentzel-Kramers-Brillouin (WKB) states by means of the Wiener integral. We discuss QFT in a flat expanding metric and in de Sitter space-time. We calculate the evolution kernel in an expanding flat metric in the real-time formulation. We discuss a field interaction in pseudoRiemannian and Riemannian metrics showing that an inversion of the signature leads to some substantial simplifications of the singularity problems in QFT.

Mediator1 involved in functional integration of Smad3 and Notch1 promoting enamel mineralization.

Enamel hypoplasia is a tooth development defection due to the disruption of enamel matrix mineralization, manifesting as chalky white phenotype. Multiple genes may be involved in this tooth agenesis. It has been proved that ablation of coactivator Mediator1 (Med1) switches the cell fate of dental epithelia, resulting in abnormal tooth development via Notch1 signaling. Smad3 (-/-) mice displays the similar chalky white incisors. However, the expression of Smad3 in Med1 ablation mice and the impact of Med1 on functional integration between Smad3 and Notch1 remains unclear. Cre-loxP-based C57/BL6 mice with epithelial-specific Med1 knockout (Med1 KO) backgrounds were generated. Mandibles and dental epithelial stem cells (DE-SCs) from incisors cervical loop (CL) were isolated from wild-type (CON) mice and Med1 KO mice. Transcriptome sequencing was used to analyze the differences of CL tissue between KO and CON mice. The results revealed the enrichment of TGF-ß signaling pathway. qRT-PCR and western blot were performed to show the gene and protein expression of Smad3, pSmad3, Notch1 and NICD, the key regulators of TGF-ß and Notch1 signaling pathway. Expression of Notch1 and Smad3 was confirmed to be down-regulated in Med1 KO cells. Using activators of Smad3 and Notch1 on Med1 KO cells, both pSmad3 and NICD were rescued. Moreover, adding inhibitors and activators of Smad3 and Notch1 to cells of CON groups respectively, the protein expressions of Smad3, pSmad3, Notch1 and NICD were synergistically affected. In summary, Med1 participates in the functional integration of Smad3 and Notch1, thus promoting enamel mineralization.

Whole-body variational modularity in the zebrafish: an inside-out story of a model species.

Actinopterygians are the most diversified clade of extant vertebrates. Their impressive morphological disparity bears witness to tremendous ecological diversity. Modularity, the organization of biological systems into quasi-independent anatomical/morphological units, is thought to increase evolvability of organisms and facilitate morphological diversification. Our study aims to quantify patterns of variational modularity in a model actinopterygian, the zebrafish (Danio rerio), using three-dimensional geometric morphometrics on osteological structures isolated from micro-CT scans. A total of 72 landmarks were digitized along cranial and postcranial ossified regions of 30 adult zebrafishes. Two methods were used to test modularity hypotheses, the covariance ratio and the distance matrix approach. We find strong support for two modules, one comprised paired fins and the other comprised median fins, that are best explained by functional properties of subcarangiform swimming. While the skull is tightly integrated with the rest of the body, its intrinsic integration is relatively weak supporting previous findings that the fish skull is a modular structure. Our results provide additional support for the recognition of similar hypotheses of modularity identified based on external morphology in various teleosts, and at least two variational modules are proposed. Thus, our results hint at the possibility that internal and external modularity patterns may be congruent.

Remarks on the principles of statistical fluid mechanics.

This is an idiosyncratic survey of statistical fluid mechanics centering on the Hopf functional differential equation. Using the Burgers equation for illustration, we review several functional integration approaches to the theory of turbulence. We note in particular that some important contributions have been brought about by researchers working on wave propagation in random media, among which Uriel Frisch is not an exception. We also discuss a particular finite-dimensional approximation for the Burgers equation. This article is part of the theme issue ''Scaling the turbulence edifice (part 1)'.

How moral neuroenhancement impacts autonomy and agency.

This paper challenges the role individual autonomy has played in debates on moral neuroenhancement (MN). It shows how John Hyman's analysis of agency as consisting of functionally integrated dimensions allows us to reassess the impact of MN on practical agency. I discuss how MN affects what Hyman terms the four dimensions of agency: psychological, ethical, intellectual, and physical. Once we separate the different dimensions of agency, it becomes clear that many authors in the debate conflate the different dimensions in the concept they call 'autonomous agents'. They contend that, for example, reason-giving and previous autonomous acts are relevant to agency as such, when in fact they capture only one aspect of functionally integrated agency. This paper reconsiders MN in light of the functional integration of reason and emotions in practical agency. To illustrate the impact of MN on different aspects of agency, I consider examples from legal practice, which show that autonomy cannot be our sole focus when evaluating the moral implications of MN.

HISTOINTEGRATION AND OTHER TERMS IN DENTAL IMPLANTATION.

The article describes biological and non-biological factors that affect the long-term stay of the implant in the bone under functional load, quality indicators of artificial teeth implantation. Instead of the term «osseointegration¼, the authors use the terms «histointegration¼ and «histodisintegration¼ defining them. The following concepts are used: time of histointegration achievement, histofunctional and histoaesthetic integration/disintegration, mechanical and biological stability/destability, integration/disintegration of implant and prosthetic structure, morphological and functional stability and destability of the implant.

Acute ischaemic stroke alters the brain's preference for distinct dynamic connectivity states.

Acute ischaemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for the loss of specialized neural tissue and function. Static resting state functional MRI studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we used dynamic resting state functional MRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting state functional MRI data of 31 patients with acute ischaemic stroke and 17 age-matched healthy control subjects. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic functional connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. The dynamic connectivity patterns of stroke patients diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n = 18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n = 13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased interhemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating from static resting state functional MRI studies post-stroke. In summary, acute ischaemic stroke not only prompted changes in connectivity between distinct networks, but it also caused characteristic changes in temporal properties of large-scale network interactions depending on the severity of the individual deficit. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.

Barriers and Facilitators to integrate Oral Health care for Older Adults in General (Basic) Care in East Netherlands. Part 2 Functional Integration.

OBJECTIVE: to synthesise a framework of barriers and facilitators in the functional integration of oral health care (OHC) into general health care for frail older adults at macro (system), meso (organisation and interprofessional integration) and micro (clinical practice) levels. BACKGROUND: Identification of these barriers and facilitators is expected to promote better and more appropriate care. METHODS: For this qualitative study, comprising 41 participants, representatives of 10 different groups of (professional) care providers, and OHC receivers (home-dwelling and nursing-home patients) were interviewed. Transcripts of the in-depth, topic-guided interviews were thematically analysed. In a subsequent workshop with 52 stakeholders, results and interpretations were discussed and refined. RESULTS: Two themes were identified: (1) compartmentalised care systems and (2) poor interprofessional and communication infrastructure. Barriers related to (1) included lack of integrative policies and compartmentalised healthcare education (macro level); poor embedding of OHC in care procedures, instruments and guidelines (meso level); and poor interprofessional skills (micro level). Barriers related to (2) included poor financial incentives for collaborative practices (macro level) and badly connected ICT systems (meso level). Identified facilitators included integration of an OHC professional into care teams, and interdisciplinary consultations (meso level); and integration of OHC in individual care plans (micro level). CONCLUSION: In The Netherlands, OHC for older people is at best poorly integrated into general care practices. Barriers and facilitators are interconnected across macro-, meso- and micro levels and between normative and functional domains and are mainly related to compartmentalisation at all levels and to poor interprofessional and communication infrastructure.

Non-consumptive effects of predation: does perceived risk strengthen the genetic integration of behaviour and morphology in stickleback?

Predators can shape genetic correlations in prey by altering prey perception of risk. We manipulated perceived risk to test whether such non-consumptive effects tightened behavioural trait correlations in wild-caught stickleback from high- compared to low-risk environments due to genetic variation in plasticity. We expected tighter genetic correlations within perceived risk treatments than across them, and tighter genetic correlations in high-risk than in low-risk treatments. We identified genetic variation in plasticity, with genetic correlations between boldness, sociality, and antipredator morphology, as expected, being tighter within treatments than across them, for both of two populations. By contrast, genetic correlations did not tighten with exposure to risk. Tighter phenotypic correlations in wild stickleback may thus arise because predators induce correlational selection on environmental components of these traits, or because predators tighten residual correlations by causing environmental heterogeneity that is controlled in the laboratory. Our study places phenotypic integration firmly into an ecological context.

Functional ecology of congeneric variation in the leaf economics spectrum.

Variation in resource availability can lead to phenotypic plasticity in the traits comprising the world-wide leaf economics spectrum (LES), potentially impairing plant function and complicating the use of tabulated values for LES traits in ecological studies. We compared 14 Carex (Cyperaceae) species in a factorial experiment (unshaded/shaded × sufficient/insufficient P) to analyze how changes in the network of allometric scaling relationships among LES traits influenced growth under favorable and resource-limited conditions. Changes in leaf mass per area (LMA) shifted the scaling relationships among LES traits expressed per unit area vs mass in ways that helped to sustain growth under resource limitation. Increases in area-normalized photosynthetic capacity and foliar nitrogen (N) were correlated with increased growth, offsetting losses associated with mass-normalized dark respiration and foliar N. These shifts increased the contributions to growth associated with photosynthetic N-use efficiency and the N : P ratio. Plasticity in LMA is at the hub of the functional role of the LES as an integrated and resilient complex system that balances the relationships among area- and mass-based aspects of gas exchange and foliar nutrient traits to sustain at least some degree of plant growth under differing availabilities of above- and below-ground resources.

Ketamine affects the integration of developmentally generated granule neurons in the adult stage.

BACKGROUND: Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that developmentally generated granule neurons in the hippocampus dentate gyrus (DG) supported hippocampus-dependent memory. Therefore, this study aimed to investigate whether ketamine affects the functional integration of developmentally generated granule neurons in the DG. For this purpose,the postnatal day 7 (PND-7) Sprague-Dawley (SD) rats were divided into the control group and the ketamine group (rats who received 4 injections of 40 mg/kg ketamine at 1 h intervals). To label dividing cells, BrdU was administered for three consecutive days after the ketamine exposure; NeuN+/BrdU+cells were observed by using immunofluorescence. To evaluate the developmentally generated granule neurons that support hippocampus-dependent memory, spatial reference memory was tested by using Morris Water Maze at 3 months old, after which the immunofluorescence was used to detect c-Fos expression in the NeuN+/BrdU+ cells. The expression of caspase-3 was measured by western blot to detect the apoptosis in the hippocampal DG. RESULTS: The present results showed that the neonatal ketamine exposure did not influence the survival rate of developmentally generated granule neurons at 2 and 3 months old, but ketamine interfered with the integration of these neurons into the hippocampal DG neural circuits and caused a deficit in hippocampal-dependent spatial reference memory tasks. CONCLUSIONS: In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex.

A review on microscale polymerase chain reaction based methods in molecular diagnosis, and future prospects for the fabrication of fully integrated portable biomedical devices.

Since the advent of microfabrication technology and soft lithography, the lab-on-a-chip concept has emerged as a state-of-the-art miniaturized tool for conducting the multiple functions associated with micro total analyses of nucleic acids, in series, in a seamless manner with a miniscule volume of sample. The enhanced surface-to-volume ratio inside a microchannel enables fast reactions owing to increased heat dissipation, allowing rapid amplification. For this reason, PCR has been one of the first applications to be miniaturized in a portable format. However, the nature of the basic working principle for microscale PCR, such as the complicated temperature controls and use of a thermal cycler, has hindered its total integration with other components into a micro total analyses systems (µTAS). This review (with 179 references) surveys the diverse forms of PCR microdevices constructed on the basis of different working principles and evaluates their performances. The first two main sections cover the state-of-the-art in chamber-type PCR microdevices and in continuous-flow PCR microdevices. Methods are then discussed that lead to microdevices with upstream sample purification and downstream detection schemes, with a particular focus on rapid on-site detection of foodborne pathogens. Next, the potential for miniaturizing and automating heaters and pumps is examined. The review concludes with sections on aspects of complete functional integration in conjunction with nanomaterial based sensing, a discussion on future prospects, and with conclusions. Graphical abstract In recent years, thermocycler-based PCR systems have been miniaturized to palm-sized, disposable polymer platforms. In addition, operational accessories such as heaters and mechanical pumps have been simplified to realize semi-automatted stand-alone portable biomedical diagnostic microdevices that are directly applicable in the field. This review summarizes the progress made and the current state of this field.

Why Have Multiple Plastic Responses? Interactions between Color Change and Heat Avoidance Behavior in Battus philenor Larvae.

Having multiple plastic responses to a change in the environment, such as increased temperature, can be adaptive for two major reasons: synergy (the plastic responses perform better when expressed simultaneously) or complementarity (each plastic response provides a greater net benefit in a different environmental context). We investigated these hypotheses for two forms of temperature-induced plasticity of Battus philenor caterpillars in southern Arizona populations: color change (from black to red at high temperatures) and heat avoidance behavior (movement from host to elevated refuges at high host temperatures). Field assays using aluminum models showed that the cooling effect of the red color is greatly reduced in a refuge position relative to that on a host. Field assays with live caterpillars demonstrated that refuge seeking is much more important for survival under hot conditions than coloration; however, in those assays, red coloration reduced the need to seek refuges. Our results support the complementarity hypothesis: refuge seeking facilitates survival during daily temperature peaks, while color change reduces the need to leave the host over longer warm periods. We propose that combinations of rapid but costly short-term behavioral responses and slow but efficient long-term morphological responses may be common when coping with temperature change.

Increased insular connectivity with emotional regions in primary insomnia patients: a resting-state fMRI study.

OBJECTIVE: To explore the abnormal connectivity patterns between the insular and the voxels of the brain in primary insomnia (PI) with insular-based functional connectivity (FC). METHODS: With the resting-state fMRI data acquired from 57 PI patients and 46 healthy controls, a two-sample t test was performed on individual FC correlation maps from two groups. The person correlation analysis was used to evaluate the relationship between the abnormal FC and clinical features. RESULTS: PI patients show enhanced connectivity between the left insula with the right anterior cingulate cortex (p < 0.05 and p < 0.001, AlphaSim-corrected), right frontal sup orb, bilateral thalamus and left precuneus,as well as decreased connectivity with the left middle temporal gyrus and right fusiform (p < 0.05, AlphaSim-corrected). Correlation analysis indicated the enhanced connectivities in the PI patients have significant negative correlations with Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)scores. In addition, the decreased functional connectivities showed positive correlations with SDS and SAS scores. CONCLUSION: Our study showed the increased connectivity regions with insula were mainly in the emotional circle and decreased connectivity was in cognitive-related regions. These provide additional evidence from functional integration view to understand the possible underlying neural- mechanisms of PI. KEY POINTS: • The aberrant insular-based connectivity pattern of PI patients was detected. • Regions showing increased connectivity with left insular were mainly in emotional circle. • Significant correlations between changed FC and SDS and SAS score were found.

Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research.

Conceiving the process of biogenesis as the evolutionary development of highly dynamic and integrated protocell populations provides the most appropriate framework to address the difficult problem of how prebiotic chemistry bridged the gap to full-fledged living organisms on the early Earth. In this contribution we briefly discuss the implications of taking dynamic, functionally integrated protocell systems (rather than complex reaction networks in bulk solution, sets of artificially evolvable replicating molecules, or even these same replicating molecules encapsulated in passive compartments) as the proper units of prebiotic evolution. We highlight, in particular, how the organisational features of those chemically active and reactive protocells, at different stages of the process, would strongly influence their corresponding evolutionary capacities. As a result of our analysis, we suggest three experimental challenges aimed at constructing protocell systems made of a diversity of functionally coupled components and, thereby, at characterizing more precisely the type of prebiotic evolutionary dynamics that such protocells could engage in.

CARMO: a comprehensive annotation platform for functional exploration of rice multi-omics data.

High-throughput technology is gradually becoming a powerful tool for routine research in rice. Interpretation of biological significance from the huge amount of data is a critical but non-trivial task, especially for rice, for which gene annotations rely heavily on sequence similarity rather than direct experimental evidence. Here we describe the annotation platform for comprehensive annotation of rice multi-omics data (CARMO), which provides multiple web-based analysis tools for in-depth data mining and visualization. The central idea involves systematic integration of 1819 samples from omics studies and diverse sources of functional evidence (15 401 terms), which are further organized into gene sets and higher-level gene modules. In this way, the high-throughput data may easily be compared across studies and platforms, and integration of multiple types of evidence allows biological interpretation from the level of gene functional modules with high confidence. In addition, the functions and pathways for thousands of genes lacking description or validation may be deduced based on concerted expression of genes within the constructed co-expression networks or gene modules. Overall, CARMO provides comprehensive annotations for transcriptomic datasets, epi-genomic modification sites, single nucleotide polymorphisms identified from genome re-sequencing, and the large gene lists derived from these omics studies. Well-organized results, as well as multiple tools for interactive visualization, are available through a user-friendly web interface. Finally, we illustrate how CARMO enables biological insights using four examples, demonstrating that CARMO is a highly useful resource for intensive data mining and hypothesis generation based on rice multi-omics data. CARMO is freely available online (http://bioinfo.sibs.ac.cn/carmo).

Estradiol-induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor.

Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice. Aromatase knockout mice (ArKO) presented deficits in olfactory preferences without affecting their olfactory discrimination abilities, and showed no functional involvement of newborn neurons in the accessory olfactory bulb (AOB) in response to the odor of a familiar male. These results suggest that estradiol-induced neurogenesis in the female AOB is required for the learning of the male odor.