Emergence of the mitochondrial reticulum from fission and fusion dynamics

Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging

A Sampler from the New Historical Atlas of Maine: Religion in Maine

This article offers an example of work-in-progress on a significant project to develop an historical atlas of Maine. Although an article depicting religious settlement in Maine may seem far removed from the policy analyses typically featured in the journal, religious participation is a fundamental aspect of civic engagement in the United States. Thus, we feature here a glimpse of Maine’s religious heritage. We also present Maine Policy Review’s first full color pullout, which is intended to give readers a visual as well as textual portrait of religious settlement in the Kennebec Valley and Portland through the first half of the nineteenth century

Chemical spray pyrolysis of Tl-Ba-Ca-Cu-O high-T(sub c) superconductors for high-field bitter magnets

The deposition of Tl-Ba-Ca-Cu-O thick films by spray pyrolyzing a Ba-Ca-Cu-O precursor film and diffusing thallium into the film to form the superconducting phase is examined. This approach was taken to reduce exposure to thallium and its health and safety hazards. The Tl-Ba-Ca-Cu-O system was selected because it has very attractive features which make it appealing to device and manufacturing engineering. Tl-Ba-Ca-Cu-O will accommodate a number of superconducting phases. This attribute makes it very forgiving to stoichiometric fluctuations in the bulk and film. It has excellent thermal and chemical stability, and appears to be relatively insensitive to chemical impurities. Oxygen is tightly bound into the systems, consequently there is no orthorhombic (conductor) to tetragonal (insulator) transition which would affect a component's lifetime. More significantly, the thallium based superconductors appear to have harder magnetic properties than the other high-Tc oxide ceramics. Estimates using magnetoresistance measurements indicate that at 77 K Tl2Ba2CaCu2O10 will have an upper critical field, H(sub c2) fo 26 Tesla for applied fields parallel to the c-axis and approximately 1000 Tesla for fields oriented in the a-b plane. Results to date have shown that superconducting films can be reproducibly deposited on 100 oriented MgO substrates. One film had a zero resistance temperature of 111.5 K. Furthermore, x ray diffraction analysis of the films showed preferential c-axis orientation parallel to the plane of the substrate. These results have now made it possible to consider the manufacture of a superconducting tape wire which can be configured into a topology useful for high-field magnet designs. The research which leads to the preparation of these films and plans for further development are reviewed

Dupuytren's Disease–Etiology and Treatment

BACKGROUND: The worldwide prevalence of Dupuytren’s disease (DD) is 8%. DD is a chronic disease for which there is no cure. Various treatments are available. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed and Embase. RESULTS: Genetic factors account for 80% of the factors involved in causing this disease. Diabetes mellitus, hepatic diseases, epilepsy, and chronic occupational use of vibrating tools are also associated with it. Limited fasciectomy is the most common treatment and is considered the reference standard. Possible complications include persistent numbness in areas where the skin has been elevated, cold sensitivity, and stiffness, with a cumulative risk of 3.6 –39.1% for all complications taken together. The recurrence rate at 5 years is 12–73%. Percutaneous needle fasciotomy is the least invasive method, with more rapid recovery and a lower complication rate than with limited fasciectomy. 85% of patients have a recurrence after an average of 2.3 years. Radiotherapy can be given before contractures arise in patients with high familial risk, or postoperatively in selected patients with a very high individual risk of recurrence. CONCLUSION: Although DD is not curable, good treatments are available. Recurrences reflect the pathophysiology of the disease and should not be considered complications of treatment. When counseling patients about the available treatment options, particularly the modalities and timing of surgery, the physician must take the patient’s degree of suffering into account. Nowadays, fast recovery from surgery and less postoperative pain are a priority for many patients. Different surgical methods can be used in combination. It remains difficult to predict the natural course and the time to postoperative recurrence in individual patients; these matters should be addressed in future studies

Supersymmetric quantum cosmological billiards

D=11 Supergravity near a space-like singularity admits a cosmological billiard description based on the hyperbolic Kac-Moody group E10. The quantization of this system via the supersymmetry constraint is shown to lead to wavefunctions involving automorphic (Maass wave) forms under the modular group W^+(E10)=PSL(2,O) with Dirichlet boundary conditions on the billiard domain. A general inequality for the Laplace eigenvalues of these automorphic forms implies that the wave function of the universe is generically complex and always tends to zero when approaching the initial singularity. We discuss possible implications of this result for the question of singularity resolution in quantum cosmology and comment on the differences with other approaches.Comment: 4 pages. v2: Added ref. Version to be published in PR

On fundamental domains and volumes of hyperbolic Coxeter-Weyl groups

We present a simple method for determining the shape of fundamental domains of generalized modular groups related to Weyl groups of hyperbolic Kac-Moody algebras. These domains are given as subsets of certain generalized upper half planes, on which the Weyl groups act via generalized modular transformations. Our construction only requires the Cartan matrix of the underlying finite-dimensional Lie algebra and the associated Coxeter labels as input information. We present a simple formula for determining the volume of these fundamental domains. This allows us to re-produce in a simple manner the known values for these volumes previously obtained by other methods.Comment: v2: to be published in Lett Math Phys (reference added, typo corrected

Systematic evaluation of 99mTc-tetrofosmin versus 99mTc-sestamibi to study murine myocardial perfusion in small animal SPECT/CT

Background: The “back-translation” of clinically available protocols to measure myocardial perfusion to preclinical imaging in mouse models of human disease is attractive for basic biomedical research. With respect to singlephoton emission computed tomography (SPECT) approaches, clinical myocardial perfusion imaging protocols are established with different 99mTc-labeled perfusion tracers; however, studies evaluating and optimizing protocols for these tracers in high-resolution pinhole SPECT in mice are lacking. This study aims at evaluating two clinically available 99mTc-labeled myocardial perfusion tracers (99mTc-sestamibi vs. 99mTc-Tetrofosmin) in mice using four different imaging protocols. Methods: Adult C57BL/6 male mice were injected with 99mTc-sestamibi (MIBI) or 99mTc-Tetrofosmin (TETRO) (4 MBq/g body weight) either intravenously through the tail vein (n = 5) or retroorbitally (n = 5) or intraperitoneally (i. p.) under anesthesia (n = 3) or i.p. in an awake state (n = 3) at rest. Immediately after injection, a multi-frame singlephoton emission computed tomography/computed tomography (SPECT/CT) acquisition was initiated with six subsequent time frames of 10 min each. Reconstructed images of the different protocols were assessed and compared by visual analysis by experts and by time-activity-curves generated from regions-of-interest for various organs (normalized uptake values). Results: Visually assessing overall image quality, the best image quality was found for MIBI for both intravenous injection protocols, whereas TETRO only had comparable image quality after retroorbital injections. These results were confirmed by quantitative analysis where left ventricular (LV) uptake of MIBI after tail vein injections was found significantly higher for all time points accompanied with a significantly slower washout of 16% for MIBI vs. 33% for TETRO (p = 0.009) from 10 to 60 min post injection (PI). Interestingly, LV washout from 10 to 60 min PI was significantly higher for TETRO when applied by tail vein injections when compared to retroorbital injections (22%, p = 0.008). However, liver uptake was significant and comparable for both tracers at all time points. Radioactivity concentration in the lungs was negligible for all time points and both tracers. Conclusion: Intravenous MIBI injection (both tail vein and retroorbital) results in the best image quality for assessing myocardial perfusion of the murine heart by SPECT/CT. TETRO has a comparable image quality only for the retroorbital injection route

Ultracold chemical reactions of a single Rydberg atom in a dense gas

Within a dense environment ($\rho \approx 10^{14}\,$atoms/cm$^3$) at ultracold temperatures ($T < 1\,\mu{}\text{K}$), a single atom excited to a Rydberg state acts as a reaction center for surrounding neutral atoms. At these temperatures almost all neutral atoms within the Rydberg orbit are bound to the Rydberg core and interact with the Rydberg atom. We have studied the reaction rate and products for $nS$ $^{87}$Rb Rydberg states and we mainly observe a state change of the Rydberg electron to a high orbital angular momentum $l$, with the released energy being converted into kinetic energy of the Rydberg atom. Unexpectedly, the measurements show a threshold behavior at $n\approx 100$ for the inelastic collision time leading to increased lifetimes of the Rydberg state independent of the densities investigated. Even at very high densities ($\rho\approx4.8\times 10^{14}\,\text{cm}^{-3}$), the lifetime of a Rydberg atom exceeds $10\,\mu\text{s}$ at $n > 140$ compared to $1\,\mu\text{s}$ at $n=90$. In addition, a second observed reaction mechanism, namely Rb$_2^+$ molecule formation, was studied. Both reaction products are equally probable for $n=40$ but the fraction of Rb$_2^+$ created drops to below 10$\,$% for $n\ge90$.Comment: 13 pages, 13 figure