The (un)conscious mouse as a model for human brain functions: key principles of anesthesia and their impact on translational neuroimaging

In recent years, technical and procedural advances have brought functional magnetic resonance imaging (fMRI) to the field of murine neuroscience. Due to its unique capacity to measure functional activity non-invasively, across the entire brain, fMRI allows for the direct comparison of large-scale murine and human brain functions. This opens an avenue for bidirectional translational strategies to address fundamental questions ranging from neurological disorders to the nature of consciousness. The key challenges of murine fMRI are: (1) to generate and maintain functional brain states that approximate those of calm and relaxed human volunteers, while (2) preserving neurovascular coupling and physiological baseline conditions. Low-dose anesthetic protocols are commonly applied in murine functional brain studies to prevent stress and facilitate a calm and relaxed condition among animals. Yet, current mono-anesthesia has been shown to impair neural transmission and hemodynamic integrity. By linking the current state of murine electrophysiology, Ca(2+) imaging and fMRI of anesthetic effects to findings from human studies, this systematic review proposes general principles to design, apply and monitor anesthetic protocols in a more sophisticated way. The further development of balanced multimodal anesthesia, combining two or more drugs with complementary modes of action helps to shape and maintain specific brain states and relevant aspects of murine physiology. Functional connectivity and its dynamic repertoire as assessed by fMRI can be used to make inferences about cortical states and provide additional information about whole-brain functional dynamics. Based on this, a simple and comprehensive functional neurosignature pattern can be determined for use in defining brain states and anesthetic depth in rest and in response to stimuli. Such a signature can be evaluated and shared between labs to indicate the brain state of a mouse during experiments, an important step toward translating findings across species

Symmetry Constraints and the Electronic Structures of a Quantum Dot with Thirteen Electrons

The symmetry constraints imposing on the quantum states of a dot with 13 electrons has been investigated. Based on this study, the favorable structures (FSs) of each state has been identified. Numerical calculations have been performed to inspect the role played by the FSs. It was found that, if a first-state has a remarkably competitive FS, this FS would be pursued and the state would be crystal-like and have a specific core-ring structure associated with the FS. The magic numbers are found to be closely related to the FSs.Comment: 13 pages, 5 figure

Normothermic mouse functional MRI of acute focal thermostimulation for probing nociception

Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus

Myocardial effective transverse relaxation time T(2)* is elevated in hypertrophic cardiomyopathy: a 7.0 T magnetic resonance imaging study

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium and bares the risk of progression to heart failure or sudden cardiac death. Identifying patients at risk remains an unmet need. Recognizing the dependence of microscopic susceptibility on tissue microstructure and on cardiac macromorphology we hypothesized that myocardial T2* might be altered in HCM patients compared to healthy controls. To test this hypothesis, myocardial T2*-mapping was conducted at 7.0 Tesla to enhance T2*-contrast. 2D CINE T2*-mapping was performed in healthy controls and HCM patients. To ensure that T2* is not dominated by macroscopic magnetic field inhomogeneities, volume selective B0 shimming was applied. T2* changes in the interventricular septum across the cardiac cycle were analyzed together with left ventricular radius and ventricular septal wall thickness. The results show that myocardial T2* is elevated throughout the cardiac cycle in HCM patients compared to healthy controls. A mean septal T2* = 13.7 ± 1.1 ms (end-systole: T2*,systole = 15.0 ± 2.1, end-diastole: T2*,diastole = 13.4 ± 1.3 ms, T2*,systole/T2*,diastole ratio = 1.12) was observed in healthy controls. For HCM patients a mean septal T2* = 17.4 ± 1.4 ms (end-systole: T2*,systole = 17.7 ± 1.2 ms, end-diastole: T2*,diastole = 16.2 ± 2.5 ms, T2*,systole/T2*,diastole ratio = 1.09) was found. Our preliminary results provide encouragement that assessment of T2* and its changes across the cardiac cycle may benefit myocardial tissue characterization in HCM

Mappings of least Dirichlet energy and their Hopf differentials

The paper is concerned with mappings between planar domains having least Dirichlet energy. The existence and uniqueness (up to a conformal change of variables in the domain) of the energy-minimal mappings is established within the class $\bar{\mathscr H}_2(X, Y)$ of strong limits of homeomorphisms in the Sobolev space $W^{1,2}(X, Y)$, a result of considerable interest in the mathematical models of Nonlinear Elasticity. The inner variation leads to the Hopf differential $h_z \bar{h_{\bar{z}}} dz \otimes dz$ and its trajectories. For a pair of doubly connected domains, in which $X$ has finite conformal modulus, we establish the following principle: A mapping $h \in \bar{\mathscr H}_2(X, Y)$ is energy-minimal if and only if its Hopf-differential is analytic in $X$ and real along the boundary of $X$. In general, the energy-minimal mappings may not be injective, in which case one observes the occurrence of cracks in $X$. Nevertheless, cracks are triggered only by the points in the boundary of $Y$ where $Y$ fails to be convex. The general law of formation of cracks reads as follows: Cracks propagate along vertical trajectories of the Hopf differential from the boundary of $X$ toward the interior of $X$ where they eventually terminate before making a crosscut.Comment: 51 pages, 4 figure

Chemical and Microbiological Contamination in Limpet (Patella spp.) of the Portuguese Coast

Coastal production areas can be impacted by anthropogenic contamination from urban, agro-industrial and leisure activities. Some contaminants, such as chemical substances might also have a telluric origin. Non filter feeding univalve mollusks, such as limpets, which are collected in rocky shores either for sale or for auto-consumption, are very appreciated in Portugal, but have been excluded from provisions on the classification of production areas, although can present relevant contamination. Thus, the aim of this study was to assess the microbiological and toxic metal contaminations in limpets (Patella spp) of the Portuguese coast, taking into account the production area and seasonal variation, and comparing their contamination levels with those occurring in bivalve mollusk indicator species, mussel (Mytilus edulis). The risks associated to the consumption of limpet meals were also assessed. For that, microbial total and fecal levels and cadmium, lead and mercury contents in limpets and mussels samples from three coastal areas over several months were analyzed based on standard methodologies. Contents of mercury and lead in limpets from the three areas studied, were always below the limits of 0.50 mg kg-1 and 1.5 mg kg-1 allowed by the EU, respectively. Regarding cadmium, levels in limpet were always above the limit of 1.0 mg kg-1, reaching about 3.0 mg kg-1 in some samples. These values probably indicate contamination from telluric origin (soil or rocks) in the coastal studied areas. Results indicated that microbiological contamination of fecal origin was low and in general below the detection level. Contamination levels did not show a clear seasonal pattern. The two mollusk species, limpets and mussels, differed statistically in all contaminants analyzed, being cadmium the most of concern, and always higher in limpets than in mussel samples. Thus, the potential risk associated with limpet consumption, taking into account the cadmium tolerable weekly intake (TWI), was investigated, being possible to reach a reliable recommendation of less than a monthly meal of 160 g. As recreational picking of limpets is common in Portugal, official 4recommendations of maximum periodic human consumption should be published and enforcement increased in forbidden areasinfo:eu-repo/semantics/acceptedVersio

Definitions of quasiconformality

We establish that the infinitesimal “ H -definition” for quasiconformal mappings on Carnot groups implies global quasisymmetry, and hence the absolute continuity on almost all lines. Our method is new even in R n where we obtain that the “limsup” condition in the H -definition can be replaced by a “liminf” condition. This leads to a new removability result for (quasi)conformal mappings in Euclidean spaces. An application to parametrizations of chord-arc surfaces is also given.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46582/1/222_2005_Article_BF01241122.pd