bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent shear stress and chemical stimulation of mechano-sensitive cells by discontinuous dielectrophoresis
Authors: Soffe Rebecca , Baratchi Sara , Tang Shi-Yang , Mitchell Arnan , McIntyre Peter , Khoshmanesh Khashayar
Published: April 2016

Microfluidic platforms enable a variety of physical or chemical stimulation of single or multiple cells to be examined and monitored in real-time. To date, intracellular calcium signalling research is, however, predominantly focused on observing the response of cells to a single mode of stimulation; consequently, the sensitising/desensitising of cell responses under concurrent stimuli is not well studied. In this paper, we provide an extended Discontinuous Dielectrophoresis procedure to investigate the sensitising of chemical stimulation, over an extensive range of shear stress, up to 63 dyn/cm2, which encompasses shear stresses experienced in the arterial and venus systems (10 to 60 dyn/cm2). Furthermore, the TRPV4-selective agonist GSK1016790A, a form of chemical stimulation, did not influence the ability of the cells' to remain immobilised under high levels of shear stress; thus, enabling us to investigate shear stress stimulation on agonism. Our experiments revealed that shear stress sensitises GSK1016790A-evoked intracellular calcium signalling of cells in a shear-stimulus dependent manner, as observed through a reduction in the cellular response time and an increase in the pharmacological efficacy. Consequently, suggesting that the role of TRPV4 may be underestimated in endothelial cells—which experience high levels of shear stress. This study highlights the importance of conducting studies at high levels of shear stress. Additionally, our approach will be valuable for examining the effect of high levels of shear on different cell types under different conditions, as presented here for agonist activation.
Correlated structural and electronic phase transformations in transition metal chalcogenide under high pressure
Authors: Li Chunyu , Ke Feng , Hu Qingyang , Yu Zhenhai , Zhao Jinggeng , Chen Zhiqiang , Yan Hao
Published: April 2016

Here, we report comprehensive studies on the high-pressure structural and electrical transport properties of the layered transition metal chalcogenide (Cr2S3) up to 36.3 GPa. A structural phase transition was observed in the rhombohedral Cr2S3 near 16.5 GPa by the synchrotron angle dispersive X-ray diffraction measurement using a diamond anvil cell. Through in situ resistance measurement, the electric resistance value was detected to decrease by an order of three over the pressure range of 7–15 GPa coincided with the structural phase transition. Measurements on the temperature dependence of resistivity indicate that it is a semiconductor-to-metal transition in nature. The results were also confirmed by the electronic energy band calculations. Above results may shed a light on optimizing the performance of Cr2S3 based applications under extreme conditions.
Morphology control of perovskite light-emitting diodes by using amino acid self-assembled monolayers
Authors: Wang Nana , Cheng Lu , Si Junjie , Liang Xiaoyong , Jin Yizheng , Wang Jianpu , Huang Wei
Published: April 2016

Amino acid self-assembled monolayers are used in the fabrication of light-emitting diodes based on organic-inorganic halide perovskites. The monolayers of amino acids provide modified interfaces by anchoring to the surfaces of ZnO charge-transporting layers using carboxyl groups, leaving the amino groups to facilitate the nucleation of MAPbBr3 perovskite films. This surface-modification strategy, together with chlorobenzene-assisted fast crystallization method, results in good surface coverage and reduced defect density of the perovskite films. These efforts lead to green perovskite light emitting diodes with a low turn-on voltage of 2 V and an external quantum efficiency of 0.43% at a brightness of ∼5000 cd m−2.
Atomic structure and stoichiometry of In(Ga)As/GaAs quantum dots grown on an exact-oriented GaP/Si(001) substrate
Authors: Schulze C. S. , Huang X. , Prohl C. , Füllert V. , Rybank S. , Maddox S. J. , March S. D. , Bank S. R. , Lee M. L. , Lenz A.
Published: April 2016

The atomic structure and stoichiometry of InAs/InGaAs quantum-dot-in-a-well structures grown on exactly oriented GaP/Si(001) are revealed by cross-sectional scanning tunneling microscopy. An averaged lateral size of 20 nm, heights up to 8 nm, and an In concentration of up to 100% are determined, being quite similar compared with the well-known quantum dots grown on GaAs substrates. Photoluminescence spectra taken from nanostructures of side-by-side grown samples on GaP/Si(001) and GaAs(001) show slightly blue shifted ground-state emission wavelength for growth on GaP/Si(001) with an even higher peak intensity compared with those on GaAs(001). This demonstrates the high potential of GaP/Si(001) templates for integration of III-V optoelectronic components into silicon-based technology.
Drop impact upon superhydrophobic surfaces with regular and hierarchical roughness
Authors: Lv Cunjing , Hao Pengfei , Zhang Xiwen , He Feng
Published: April 2016

Recent studies demonstrate that roughness and morphologies of the textures play essential roles on the dynamics of water drop impacting onto superhydrophobic substrates. Particularly, significant reduction of contact time has greatly attracted people's attention. We experimentally investigate drop impact dynamics onto three types of superhydrophobic surfaces, consisting of regular micropillars, two-tier textures with nano/micro-scale roughness, and hierarchical textures with random roughness. It shows that the contact time is controlled by the Weber number and the roughness of the surface. Compared with drop impact on regular micropillared surfaces, the contact time can be finely reduced by increasing the Weber number on surfaces with two-tier textures, but can be remarkably reduced on surfaces with hierarchical textures resulting from the prompt splash and fragmentation of liquid lamellae. Our study may shed lights on textured materials fabrication, allowing a rapid drop detachment to realize broad applications.
Temperature dependence of perpendicular magnetic anisotropy in CoFeB thin films
Authors: Fu Yu , Barsukov I. , Li Jing , Gonçalves A. M. , Kuo C. C. , Farle M. , Krivorotov I. N.
Published: April 2016

We study perpendicular magnetic anisotropy in thin films of Ta/Co20Fe60B20/MgO by ferromagnetic resonance and find a linear temperature dependence for the first and second order uniaxial terms from 5 to 300 K. Our data suggest the possible hybridization of Fe-O orbitals at the CoFeB/MgO interface for the origin of the first order anisotropy. However, we also find that non-interfacial contributions to the anisotropy are present. An easy-cone anisotropy is found for the entire temperature range in the narrow region of film thicknesses around the spin reorientation transition 1.2–1.35 nm.
Effect of measurement duration in respiration chambers on methane traits of beef cattle
Authors: Arthur P. F. , Donoghue K. A. , Bird-Gardiner T. , Herd R. M. , Hegarty R. S.
Published: April 2016

Records on 1043 young Angus heifer and bull progeny from 73 sires, measured for methane production in respiration chambers, were used to evaluate the accuracy of a 1-day measurement relative to 2-day measurement duration. The traits assessed were dry matter intake (DMI, kg/day), methane-production rate (MPR, g/day), methane yield (MY, MPR per unit DMI) and four residual methane (RMP, g/day) traits. The RMP traits were computed as actual MPR minus expected MPR, where the expected MPR were calculated from three widely used equations. The expected MPR for the fourth RMP trait was computed by regressing MPR on DMI, using the data from the study. Variance components, heritability, phenotypic and genetic correlations, and the efficiency of selection using 1-day compared with 2-day measurement were used as assessment criteria. The environmental variance for the 2-day measurement was slightly lower than that of the 1-day measurement for all the traits studied, indicating that the addition of an extra day of data was effective in reducing the amount of unexplained variation in each trait. However, these minor reductions did not have a major impact on accuracy; hence, very high phenotypic (rp of 0.91–0.99) and genetic (rg of 0.99 for each trait) correlations were obtained between the two measurement durations. The very high genetic correlation between the two durations of measurement indicated that, at the genetic level, the 1-day duration is measuring the same trait as the 2-day measurement duration. Any enteric-methane emission-abatement strategy that seeks to reduce MPR per se, may have a detrimental impact on ruminant productivity through a correlated reduction in feed intake; hence, MY and the RMP traits are likely to be the traits of interest for genetic improvement. Efficiency of selection for MY and the RMP traits ranged from 0.96 to 0.99, which implies that there would be less than 5% loss in efficiency by adopting a 1-day relative to a 2-day methane-measurement duration. While the throughput of the respiration-chamber facility can be increased by adopting a 1-day measurement duration, additional resources, such as holding pens, would be required to take advantage of the extra day.
Interactive effects of dietary protein source and exogenous protease on growth performance, immune competence and jejunal health of broiler chickens
Authors: Cowieson A. J. , Lu H. , Ajuwon K. M. , Knap I. , Adeola O.
Published: April 2016

A total of 672 male 7-day-old broiler chicks were used in a 14-day cage study to evaluate the interactive effects of dietary protein source and exogenous protease on nutrient digestibility and intestinal physiology. Birds were fed a common starter diet from Days 0 to 7 and switched to experimental diets from Days 7 to 21. Four corn-based dietary treatments were arranged in a 2 × 2 factorial arrangement with factors being two major sources of protein [soybean meal (SBM) or canola meal] and diets offered with or without exogenous protease. Bodyweight gain and gain:feed were higher (P < 0.001) in the diets based on SBM than in the diets based on canola meal and protease was more effective (P < 0.05) in enhancing performance in SBM-based diets. Ileal nitrogen digestibility was increased (P < 0.01) by protease use in diets based on both major protein sources. However, ileal digestible energy was increased (P < 0.05) by protease only in the SBM-based diet resulting in an interaction between diet protein source and exogenous protease. Jejunal villus height tended to be higher (P = 0.07) in birds fed diets based on SBM and protease use increased (P < 0.05) crypt depth only in the SBM-free diets resulting in a significant interaction between protein source and protease use. Patterns of gene expression in jejunal tissue suggested that both dietary protein source and exogenous protease influence the expression of genes responsible for mucin secretion, amino acid transport and immune functionality in an age-dependent manner. It can be concluded that SBM may be a more suitable protein source for young broiler chickens than canola meal and that use of canola meal as a major source of dietary protein may have negative implications for performance, nitrogen digestibility and gut health. However, exogenous protease appears to be more compatible with substrates presented by SBM than is the case for canola meal based on advantages conferred in nutrient digestibility and performance. The beneficial effects of exogenous protease may be linked both to enhanced protein and energy digestibility and improved gut morphological characteristics, secretory and absorptive dynamics and immune resilience.
Herbivory and the success of Ligustrum lucidum: evidence from a comparison between native and novel ranges
Authors: Montti Lía , Ayup María Marta , Aragón Roxana , Qi Weilong , Ruan Honghua , Fernández Romina , Casertano Sergio A. , Zou Xiaoming
Published: April 2016

Invasive plant species may benefit from a reduction in herbivory in their introduced range. The reduced herbivory may cause a reallocation of resources from defence to fitness. Here, we evaluated leaf herbivory of an invasive tree species (Ligustrum lucidum Aiton) in its native and novel ranges, and determined the potential changes in leaf traits that may be associated with the patterns of herbivory. We measured forest structure, damage by herbivores and leaf traits in novel and native ranges, and on the basis of the literature, we identified the common natural herbivores of L. lucidum. We also performed an experiment offering leaves from both ranges to a generalist herbivore (Spodoptera frugiperda). L. lucidum was more abundant and experienced significantly less foliar damage in the novel than in the native range, in spite of the occurrence of several natural herbivores. The reduced lignin content and lower lignin : N ratio in novel leaves, together with the higher herbivore preference for leaves of this origin in the laboratory experiment, indicated lower herbivore resistance in novel than in native populations. The reduced damage by herbivores is not the only factor explaining invasion success, but it may be an important cause that enhances the invasiveness of L. lucidum.
Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites
Authors: Hoffman Kelly M. , Trawalter Sophie , Axt Jordan R. , Oliver M. Norman
Published: April 2016

Significance

The present work examines beliefs associated with racial bias in pain management, a critical health care domain with well-documented racial disparities. Specifically, this work reveals that a substantial number of white laypeople and medical students and residents hold false beliefs about biological differences between blacks and whites and demonstrates that these beliefs predict racial bias in pain perception and treatment recommendation accuracy. It also provides the first evidence that racial bias in pain perception is associated with racial bias in pain treatment recommendations. Taken together, this work provides evidence that false beliefs about biological differences between blacks and whites continue to shape the way we perceive and treat black people—they are associated with racial disparities in pain assessment and treatment recommendations.
Photodegradation alleviates the lignin bottleneck for carbon turnover in terrestrial ecosystems
Authors: Austin Amy T. , Méndez M. Soledad , Ballaré Carlos L.
Published: April 2016

Significance

Understanding controls on carbon storage in terrestrial ecosystems is essential to predict and mitigate human impacts on the global carbon cycle. This study identifies a general unifying mechanism to explain how photochemical mineralization of plant litter, photodegradation, affects subsequent biotic decomposition. Previous work has shown that photodegradation can be a major direct control of carbon loss in arid lands. We now demonstrate that, across a wide range of species, exposure to sunlight has large “photopriming” effects, enhancing microbial decomposition, especially due to blue–green light. Photodegradation increased availability of carbohydrates to hydrolytic enzymes, likely through reducing the bottleneck imposed by lignin in secondary cell walls. This mechanistic insight suggests that photodegradation is globally important for carbon turnover in terrestrial ecosystems.
BK
Ca
channel regulates calcium oscillations induced by alpha-2-macroglobulin in human myometrial smooth muscle cells
Authors: Wakle-Prabagaran Monali , Lorca Ramón A. , Ma Xiaofeng , Stamnes Susan J. , Amazu Chinwendu , Hsiao Jordy J. , Karch Celeste M. , Hyrc Krzysztof L. , Wright Michael E. , England Sarah K.
Published: April 2016

Significance

The large-conductance, voltage-gated, calcium (Ca
2+
)-activated potassium channel (BK
Ca
) plays an important role in regulating the membrane potential of uterine muscle cells. We demonstrate that BK
Ca
interacts with the immunomodulator α-2-macroglobulin (α
2
M) and its receptor low-density lipoprotein receptor-related protein 1 in human uterine muscle cells isolated from pregnant women. Furthermore, we report that activated α
2
M regulates BK
Ca
activity and that activated α
2
M and BK
Ca
together control Ca
2+
oscillations in the cells, a process dependent on store-operated Ca
2+
entry. This study reveals a previously unidentified modulator of the BK
Ca
channel and may imply a link between inflammatory processes and excitation changes in the uterine muscle during pregnancy.
Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain
Authors: Baulch Janet E. , Acharya Munjal M. , Allen Barrett D. , Ru Ning , Chmielewski Nicole N. , Martirosian Vahan , Giedzinski Erich , Syage Amber , Park Audrey L. , Benke Sarah N. , Parihar Vipan K. , Limoli Charles L.
Published: April 2016

Significance

Cranial irradiation used during the clinical management of brain cancer is associated with severe cognitive decline and represents a particular concern for pediatric cancer survivors. Irradiation triggers neuroinflammation and compromises the structure of neurons, factors that are contributory if not causal to radiation-induced cognitive dysfunction. Our previous data have shown that intrahippocampal transplantation of human neural stem cells (hNSCs) could ameliorate radiation-induced behavioral deficits and improve neuronal plasticity. These beneficial neurocognitive effects were hypothesized to act through a trophic support mechanism involving the secretion of microvesicles acting on host neuronal circuitry. Here we show that cranial grafting of hNSC-derived microvesicles reverses or prevents radiation-induced cognitive dysfunction through mechanisms involving the suppression of inflammation and the preservation of host neuronal architecture.
Insight into GATA1 transcriptional activity through interrogation ofciselements disrupted in human erythroid disorders
Authors: Wakabayashi Aoi , Ulirsch Jacob C. , Ludwig Leif S. , Fiorini Claudia , Yasuda Makiko , Choudhuri Avik , McDonel Patrick , Zon Leonard I. , Sankaran Vijay G.
Published: April 2016

Significance

Methods for identifying causal variants underlying human diseases have been greatly enhanced by whole-exome sequencing; however, this approach overlooks mutations that occur within noncoding regulatory regions. Moreover, the mechanisms for how such mutations result in disease are poorly understood. In this study, we interrogated binding sites of the blood cell transcription factor GATA1 in regulatory elements that are mutated in cases of human red blood cell disorders by creating small-targeted deletions in model cell lines. These deletions cause a major reduction in target gene expression. We used this initial insight to show that such elements are highly conserved, and that through predictive modeling, we can gain global insight into key determinants of GATA1 transcriptional activity.
Slow climate velocities of mountain streams portend their role as refugia for cold-water biodiversity
Authors: Isaak Daniel J. , Young Michael K. , Luce Charles H. , Hostetler Steven W. , Wenger Seth J. , Peterson Erin E. , Ver Hoef Jay M. , Groce Matthew C. , Horan Dona L. , Nagel David E.
Published: April 2016

Significance

Many studies predict climate change will cause widespread extinctions of flora and fauna in mountain environments because of temperature increases, enhanced environmental variability, and invasions by nonnative species. Cold-water organisms are thought to be at particularly high risk, but most predictions are based on small datasets and imprecise surrogates for water temperature trends. Using large stream temperature and biological databases, we show that thermal habitat in mountain streams is highly resistant to temperature increases and that many populations of cold-water species exist where they are well-buffered from climate change. As a result, there is hope that many native species dependent on cold water can persist this century and mountain landscapes will play an important role in that preservation.
Culture shapes the evolution of cognition
Authors: Thompson Bill , Kirby Simon , Smith Kenny
Published: April 2016

Significance

A central debate in cognitive science concerns the nativist hypothesis: the proposal that universal human behaviors are underpinned by strong, domain-specific, innate constraints on cognition. We use a general model of the processes that shape human behavior—learning, culture, and biological evolution—to test the evolutionary plausibility of this hypothesis. A series of analyses shows that culture radically alters the relationship between natural selection and cognition. Culture facilitates rapid biological adaptation yet rules out nativism: Behavioral universals arise that are underpinned by weak biases rather than strong innate constraints. We therefore expect culture to have dramatically shaped the evolution of the human mind, giving us innate predispositions that only weakly constrain our behavior.
Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors
Authors: Ku Manching , Chang Shih-En , Hernandez Julio , Abadejos Justin R. , Sabouri-Ghomi Mohsen , Muenchmeier Niklas J. , Schwarz Anna , Valencia Anna M. , Kirak Oktay
Published: April 2016

Significance

T cells generate their T-cell receptors (TCR) through somatic rearrangement of their underlying genomic V(D)J regions. Contrary to previous transgenic TCR models, our TCR models generated through somatic cell nuclear transfer are precise copies of the original T cell. Here, we developed a novel somatic cell nuclear transfer model of natural arising regulatory T (nTreg) cells. In our monoclonal model, we found a well-defined nTreg population in the thymus, contradicting previous reports that intraclonal competition and thymic niche are limiting factors in nTreg development. Moreover, we found a novel fate-determining role for the TCR β-chain in nTreg cells. Interestingly, we also discovered a novel T-cell subset that functions as peripheral precursor of nTreg cells.
Accumulation of formamide in hydrothermal pores to form prebiotic nucleobases
Authors: Niether Doreen , Afanasenkau Dzmitry , Dhont Jan K. G. , Wiegand Simone
Published: April 2016

Significance

The aim of this article is to show that prebiotic nucleobases can be formed in hydrothermal pores, through a significant accumulation of formamide resulting from a combination of thermophoresis and convection. We performed numerical finite element calculations for initial formamide concentrations that correspond to early Earth shallow lake conditions and reveal that formamide accumulates at the bottom of hydrothermal pores in about 45–90 d to high concentrated formamide solutions. The conclusion from these findings is that the combination of thermophoretic mass transport and convection is the missing link, which makes the synthesis of prebiotic nucleobases in porous rocks in contact with shallow lakes under early-earth conditions possible.
Kinetic selection vs. free energy of DNA base pairing in control of polymerase fidelity
Authors: Oertell Keriann , Harcourt Emily M. , Mohsen Michael G. , Petruska John , Kool Eric T. , Goodman Myron F.
Published: April 2016

Significance

We address a fundamental biological issue: the source of free energy enabling high-fidelity DNA replication. DNA polymerase errors occur at about 1 per 1,000–10,000 bp, indicating “right” vs. “wrong” free energy differences ΔΔ
G
inc
= 3–5 kcal/mol. A recent paper using high inorganic pyrophosphate concentrations to “equilibrate” right and wrong forward and reverse incorporation reactions concluded that base pairing in DNA alone is sufficient to account for polymerase fidelity. By performing an explicit analysis of forward and reverse reactions, we show that steady-state pol incorporation levels are far from equilibrium for wrong incorporations, so that polymerase fidelity cannot depend solely on intrinsic DNA properties. DNA polymerases must operate under kinetic control to achieve high fidelity.
Tiny individuals attached to a new Silurian arthropod suggest a unique mode of brood care
Authors: Briggs Derek E. G. , Siveter Derek J. , Siveter David J. , Sutton Mark D. , Legg David
Published: April 2016

Significance

The paper reports a remarkable arthropod from the Silurian Herefordshire Lagerstätte of England. The fossil reveals a unique association in an early Paleozoic arthropod involving tethering of 10 tiny individuals each by a single thread to the tergites so that their appearance is reminiscent of kites. The evidence suggests that these are juveniles and that the specimen records a unique brooding strategy. This is part of a diversity of complex brooding behaviors in early arthropods heralding the variety that occurs today. The possibility that the small individuals represent a different arthropod, possibly parasitic, which colonized the larger individual, seems less likely.
Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2
Authors: Hodson Daniel J. , Shaffer Arthur L. , Xiao Wenming , Wright George W. , Schmitz Roland , Phelan James D. , Yang Yandan , Webster Daniel E. , Rui Lixin , Kohlhammer Holger , Nakagawa Masao , Waldmann Thomas A. , Staudt Louis M.
Published: April 2016

Significance

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma and is incurable in roughly 30% of cases. Here we demonstrate the addiction of both major subtypes of DLBCL to the expression of the transcription factor OCT2 (octamer-binding protein 2) and its co-activator OCA-B. We clarify the role of OCT2 in normal germinal center biology and identify the genes and pathways that it regulates in malignant B cells. Our findings suggest that pharmacological agents designed to target OCT2 itself or the OCT2–OCA-B interface would be an effective and nontoxic therapeutic strategy in DLBCL.
Predictability decomposition detects the impairment of brain–heart dynamical networks during sleep disorders and their recovery with treatment
Authors: Faes Luca , Marinazzo Daniele , Stramaglia Sebastiano , Jurysta Fabrice , Porta Alberto , Giandomenico Nollo
Published: April 2016

This work introduces a framework to study the network formed by the autonomic component of heart rate variability (cardiac process
η
) and the amplitude of the different electroencephalographic waves (brain processes
δ
,
θ
,
α
,
σ
,
β
) during sleep. The framework exploits multivariate linear models to decompose the predictability of any given target process into measures of self-, causal and interaction predictability reflecting respectively the information retained in the process and related to its physiological complexity, the information transferred from the other source processes, and the information modified during the transfer according to redundant or synergistic interaction between the sources. The framework is here applied to the
η
,
δ
,
θ
,
α
,
σ
,
β
time series measured from the sleep recordings of eight severe sleep apnoea–hypopnoea syndrome (SAHS) patients studied before and after long-term treatment with continuous positive airway pressure (CPAP) therapy, and 14 healthy controls. Results show that the full and self-predictability of
η
,
δ
and
θ
decreased significantly in SAHS compared with controls, and were restored with CPAP for
δ
and
θ
but not for
η
. The causal predictability of
η
and
δ
occurred through significantly redundant source interaction during healthy sleep, which was lost in SAHS and recovered after CPAP. These results indicate that predictability analysis is a viable tool to assess the modifications of complexity and causality of the cerebral and cardiac processes induced by sleep disorders, and to monitor the restoration of the neuroautonomic control of these processes during long-term treatment.
Central- and autonomic nervous system coupling in schizophrenia
Authors: Schulz Steffen , Bolz Mathias , Bär Karl-Jürgen , Voss Andreas
Published: April 2016

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity.
Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems
Authors: Bari Vlasta , Marchi Andrea , De Maria Beatrice , Rossato Gianluca , Nollo Giandomenico , Faes Luca , Porta Alberto
Published: April 2016

Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.
Multiple-input nonlinear modelling of cerebral haemodynamics using spontaneous arterial blood pressure, end-tidal CO
2
and heart rate measurements
Authors: Marmarelis V. Z. , Mitsis G. D. , Shin D. C. , Zhang R.
Published: April 2016

In order to examine the effect of changes in heart rate (HR) upon cerebral perfusion and autoregulation, we include the HR signal recorded from 18 control subjects as a third input in a two-input model of cerebral haemodynamics that has been used previously to quantify the dynamic effects of changes in arterial blood pressure and end-tidal CO
2
upon cerebral blood flow velocity (CBFV) measured at the middle cerebral arteries via transcranial Doppler ultrasound. It is shown that the inclusion of HR as a third input reduces the output prediction error in a statistically significant manner, which implies that there is a functional connection between HR changes and CBFV. The inclusion of nonlinearities in the model causes further statistically significant reduction of the output prediction error. To achieve this task, we employ the concept of principal dynamic modes (PDMs) that yields dynamic nonlinear models of multi-input systems using relatively short data records. The obtained PDMs suggest model-driven quantitative hypotheses for the role of sympathetic and parasympathetic activity (corresponding to distinct PDMs) in the underlying physiological mechanisms by virtue of their relative contributions to the model output. These relative PDM contributions are subject-specific and, therefore, may be used to assess personalized characteristics for diagnostic purposes.
Brain–heart interactions: physiology and clinical implications
Authors: Silvani Alessandro , Calandra-Buonaura Giovanna , Dampney Roger A. L. , Cortelli Pietro
Published: April 2016

The brain controls the heart directly through the sympathetic and parasympathetic branches of the autonomic nervous system, which consists of multi-synaptic pathways from myocardial cells back to peripheral ganglionic neurons and further to central preganglionic and premotor neurons. Cardiac function can be profoundly altered by the reflex activation of cardiac autonomic nerves in response to inputs from baro-, chemo-, nasopharyngeal and other receptors as well as by central autonomic commands, including those associated with stress, physical activity, arousal and sleep. In the clinical setting, slowly progressive autonomic failure frequently results from neurodegenerative disorders, whereas autonomic hyperactivity may result from vascular, inflammatory or traumatic lesions of the autonomic nervous system, adverse effects of drugs and chronic neurological disorders. Both acute and chronic manifestations of an imbalanced brain–heart interaction have a negative impact on health. Simple, widely available and reliable cardiovascular markers of the sympathetic tone and of the sympathetic–parasympathetic balance are lacking. A deeper understanding of the connections between autonomic cardiac control and brain dynamics through advanced signal and neuroimage processing may lead to invaluable tools for the early detection and treatment of pathological changes in the brain–heart interaction.
Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions
Authors: Lin Aijing , Liu Kang K. L. , Bartsch Ronny P. , Ivanov Plamen Ch.
Published: April 2016

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.
Spontaneous physiological variability modulates dynamic functional connectivity in resting-state functional magnetic resonance imaging
Authors: Nikolaou F. , Orphanidou C. , Papakyriakou P. , Murphy K. , Wise R. G. , Mitsis G. D.
Published: April 2016

It is well known that the blood oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is influenced—in addition to neuronal activity—by fluctuations in physiological signals, including arterial CO
2
, respiration and heart rate/heart rate variability (HR/HRV). Even spontaneous fluctuations of the aforementioned physiological signals have been shown to influence the BOLD fMRI signal in a regionally specific manner. Related to this, estimates of functional connectivity between different brain regions, performed when the subject is at rest, may be confounded by the effects of physiological signal fluctuations. Moreover, resting functional connectivity has been shown to vary with respect to time (dynamic functional connectivity), with the sources of this variation not fully elucidated. In this context, we examine the relation between dynamic functional connectivity patterns and the time-varying properties of simultaneously recorded physiological signals (end-tidal CO
2
and HR/HRV) using resting-state fMRI measurements from 12 healthy subjects. The results reveal a modulatory effect of the aforementioned physiological signals on the dynamic resting functional connectivity patterns for a number of resting-state networks (default mode network, somatosensory, visual). By using discrete wavelet decomposition, we also show that these modulation effects are more pronounced in specific frequency bands.
The pulsatility volume index: an indicator of cerebrovascular compliance based on fast magnetic resonance imaging of cardiac and respiratory pulsatility
Authors: Bianciardi Marta , Toschi Nicola , Polimeni Jonathan R. , Evans Karleyton C. , Bhat Himanshu , Keil Boris , Rosen Bruce R. , Boas David A. , Wald Lawrence L.
Published: April 2016

The influence of cardiac activity on the viscoelastic properties of intracranial tissue is one of the mechanisms through which brain–heart interactions take place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk is not fully explained by current risk factors, including arterial compliance. Cerebrovascular compliance is currently estimated indirectly through Doppler sonography and magnetic resonance imaging (MRI) measures of blood velocity changes. In order to meet the need for novel cerebrovascular disease risk factors, we aimed to design and validate an MRI indicator of cerebrovascular compliance based on direct endogenous measures of blood volume changes. We implemented a fast non-gated two-dimensional MRI pulse sequence based on echo-planar imaging (EPI) with ultra-short repetition time (approx. 30–50 ms), which stepped through slices every approximately 20 s. We constrained the solution of the Bloch equations for spins moving faster than a critical speed to produce an endogenous contrast primarily dependent on spin volume changes, and an approximately sixfold signal gain compared with Ernst angle acquisitions achieved by the use of a 90° flip angle. Using cardiac and respiratory peaks detected on physiological recordings, average cardiac and respiratory MRI pulse waveforms in several brain compartments were obtained at 7 Tesla, and used to derive a compliance indicator, the pulsatility volume index (pVI). The pVI, evaluated in larger cerebral arteries, displayed significant variation within and across vessels. Multi-echo EPI showed the presence of significant pulsatility effects in both
S
0
and

signals, compatible with blood volume changes. Lastly, the pVI dynamically varied during breath-holding compared with normal breathing, as expected for a compliance indicator. In summary, we characterized and performed an initial validation of a novel MRI indicator of cerebrovascular compliance, which might prove useful to investigate brain–heart interactions in cerebrovascular disease and other disorders.
Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study
Authors: Duggento Andrea , Bianciardi Marta , Passamonti Luca , Wald Lawrence L. , Guerrisi Maria , Barbieri Riccardo , Toschi Nicola
Published: April 2016

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow.
Alterations in the coupling functions between cortical and cardio-respiratory oscillations due to anaesthesia with propofol and sevoflurane
Authors: Stankovski Tomislav , Petkoski Spase , Raeder Johan , Smith Andrew F. , McClintock Peter V. E. , Stefanovska Aneta
Published: April 2016

The precise mechanisms underlying general anaesthesia pose important and still open questions. To address them, we have studied anaesthesia induced by the widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics, computing cross-frequency coupling functions between neuronal, cardiac and respiratory oscillations in order to determine their mutual interactions. The phase domain coupling function reveals the form of the function defining the mechanism of an interaction, as well as its coupling strength. Using a method based on dynamical Bayesian inference, we have thus identified and analysed the coupling functions for six relationships. By quantitative assessment of the forms and strengths of the couplings, we have revealed how these relationships are altered by anaesthesia, also showing that some of them are differently affected by propofol and sevoflurane. These findings, together with the novel coupling function analysis, offer a new direction in the assessment of general anaesthesia and neurophysiological interactions, in general.
Brain–heart interactions: challenges and opportunities with functional magnetic resonance imaging at ultra-high field
Authors: Chang Catie , Raven Erika P. , Duyn Jeff H.
Published: April 2016

Magnetic resonance imaging (MRI) at ultra-high field (UHF) strengths (7 T and above) offers unique opportunities for studying the human brain with increased spatial resolution, contrast and sensitivity. However, its reliability can be compromised by factors such as head motion, image distortion and non-neural fluctuations of the functional MRI signal. The objective of this review is to provide a critical discussion of the advantages and trade-offs associated with UHF imaging, focusing on the application to studying brain–heart interactions. We describe how UHF MRI may provide contrast and resolution benefits for measuring neural activity of regions involved in the control and mediation of autonomic processes, and in delineating such regions based on anatomical MRI contrast. Limitations arising from confounding signals are discussed, including challenges with distinguishing non-neural physiological effects from the neural signals of interest that reflect cardiorespiratory function. We also consider how recently developed data analysis techniques may be applied to high-field imaging data to uncover novel information about brain–heart interactions.
Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study
Authors: Sclocco Roberta , Beissner Florian , Desbordes Gaelle , Polimeni Jonathan R. , Wald Lawrence L. , Kettner Norman W. , Kim Jieun , Garcia Ronald G. , Renvall Ville , Bianchi Anna M. , Cerutti Sergio , Napadow Vitaly , Barbieri Riccardo
Published: April 2016

Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain.