The Type 2 Iodothyronine Deiodinase is Essential for Adaptive Thermogenesis in Brown Adipose Tissue

Type 2 iodothyronine deiodinase (D2) is a selenoenzyme, the product of the recently cloned cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue (BAT). Here we report that despite a normal plasma 3,5,3′-triiodothyronine (T3) concentration, cold-exposed mice with targeted disruption of the Dio2 gene (Dio2–/–) become hypothermic due to impaired BAT thermogenesis and survive by compensatory shivering with consequent acute weight loss. This occurs despite normal basal mitochondrial uncoupling protein 1 (UCP1) concentration. In Dio2–/– brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and O2 consumption are all reduced due to impaired cAMP generation. These hypothyroid-like abnormalities are completely reversed by a single injection of T3 14 hours earlier. Recent studies suggest that UCP1 is primarily dependent on thyroid hormone receptor β (TRβ) while the normal sympathetic response of brown adipocytes requires TRα. Intracellularly generated T3 may be required to saturate the TRα, which has an approximately fourfold lower T3-binding affinity than does TRβ. Thus, D2 is an essential component in the thyroid-sympathetic synergism required for thermal homeostasis in small mammals

Donor Centers and Absorption Spectra in Quantum Dots

We have studied the electronic properties and optical absorption spectra of three different cases of donor centers, D^{0}, D^{-} and D^{2-}, which are subjected to a perpendicular magnetic field, using the exact diagonalization method. The energies of the lowest lying states are obtained as function of the applied magnetic field strength B and the distance zeta between the positive ion and the confinement xy-plane. Our calculations indicate that the positive ion induces transitions in the ground-state, which can be observed clearly in the absorption spectra, but as zeta goes to 0 the strength of the applied magnetic field needed for a transition to occur tends to infinity.Comment: 5 pages, 4 figures, REVTeX 4, gzipped tar fil

Natural boundaries for the Smoluchowski equation and affiliated diffusion processes

The Schr\"{o}dinger problem of deducing the microscopic dynamics from the input-output statistics data is known to admit a solution in terms of Markov diffusions. The uniqueness of solution is found linked to the natural boundaries respected by the underlying random motion. By choosing a reference Smoluchowski diffusion process, we automatically fix the Feynman-Kac potential and the field of local accelerations it induces. We generate the family of affiliated diffusions with the same local dynamics, but different inaccessible boundaries on finite, semi-infinite and infinite domains. For each diffusion process a unique Feynman-Kac kernel is obtained by the constrained (Dirichlet boundary data) Wiener path integration.As a by-product of the discussion, we give an overview of the problem of inaccessible boundaries for the diffusion and bring together (sometimes viewed from unexpected angles) results which are little known, and dispersed in publications from scarcely communicating areas of mathematics and physics.Comment: Latex file, Phys. Rev. E 49, 3815-3824, (1994

Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

\textit{In vivo} spin spin relaxation time ($T_2$) heterogeneity of hyperpolarized \textsuperscript{13}C urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized \textsuperscript{13}C signal with a macromolecular relaxation agent revealed that a long-$T_2$ component of the \textsuperscript{13}C urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the \textsuperscript{13}C urea to be distinguished via multi-exponential analysis. The $T_2$ response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized \textsuperscript{13}C urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-\textsuperscript{13}C-cyclopropane-$^2\textrm{H}_8$. Large $T_2$ increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis suggesting that $T_2$ relaxometry may be used to monitor the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Two high resolution imaging techniques - multiple echo time averaging and ultra-long echo time sub-2 mm$^3$ resolution 3D imaging - were developed to exploit the particularly long relaxation times observed

Localization of nonlinear excitations in curved waveguides

Motivated by the example of a curved waveguide embedded in a photonic crystal, we examine the effects of geometry in a ``quantum channel'' of parabolic form. We study the linear case and derive exact as well as approximate expressions for the eigenvalues and eigenfunctions of the linear problem. We then proceed to the nonlinear setting and its stationary states in a number of limiting cases that allow for analytical treatment. The results of our analysis are used as initial conditions in direct numerical simulations of the nonlinear problem and localized excitations are found to persist, as well as to have interesting relaxational dynamics. Analogies of the present problem in contexts related to atomic physics and particularly to Bose-Einstein condensation are discussed.Comment: 14 pages, 4 figure

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

The fitness consequences of inbreeding in natural populations and their implications for species conservation – a systematic map

Background: Threatened species often have small and isolated populations where mating among relatives can result in inbreeding depression increasing extinction risk. Effective management is hampered by a lack of syntheses summarising the magnitude of, and variation in inbreeding depression. Here we describe the nature and scope of the literature examining phenotypic/fitness consequences of inbreeding, to provide a foundation for future syntheses and management. Methods: We searched the literature for articles documenting the impact of inbreeding in natural populations. Article titles, abstracts and full-texts were assessed against a priori defined criteria, and information relating to study design, quality and other factors that may influence inbreeding responses (e.g. population size) was extracted from relevant articles. Results: The searches identified 11457 articles, of which 614 were assessed as relevant and included in the systematic map (corresponding to 703 distinct studies). Most studies (663) assessed within-population inbreeding resulting from self-fertilisation or consanguineous pairings, while 118 studies assessed among-population inbreeding due to drift load. Plants were the most studied taxon (469 studies) followed by insects (52 studies) and birds (43 studies). Most studies investigated the effects of inbreeding on components of fitness (e.g. survival or fecundity; 648 studies) but measurements were typically under laboratory/greenhouse conditions (486 studies). Observations were also often restricted to the first inbred generation (607 studies) and studies frequently lacked contextual information (e.g. population size). Conclusions: Our systematic map describes the scope and quality of the evidence describing the phenotypic consequences of inbreeding. The map reveals substantial evidence relating to inbreeding responses exists, but highlights information is still limited for some aspects, including the effects of multiple generations of inbreeding. The systematic map allowed us to define several conservation-relevant questions, where sufficient data exists to support systematic reviews, e.g. How do inbreeding responses vary with population size? However, we found that such syntheses are likely to be constrained by incomplete reporting of critical contextual information. Our systematic map employed the same rigorous literature assessment methods as systematic review, including a novel survey of study quality and thus provides a robust foundation to guide future research and syntheses seeking to inform conservation decision-making

Is the Kaiser Permanente model superior in terms of clinical integration?: a comparative study of Kaiser Permanente, Northern California and the Danish healthcare system

<p>Abstract</p> <p>Background</p> <p>Integration of medical care across clinicians and settings could enhance the quality of care for patients. To date, there is limited data on the levels of integration in practice. Our objective was to compare primary care clinicians' perceptions of clinical integration and three sub-aspects in two healthcare systems: Kaiser Permanente, Northern California (KPNC) and the Danish healthcare system (DHS). Further, we examined the associations between specific organizational factors and clinical integration within each system.</p> <p>Methods</p> <p>Comparable questionnaires were sent to a random sample of primary care clinicians in KPNC (n = 1103) and general practitioners in DHS (n = 700). Data were analysed using multiple logistic regression models.</p> <p>Results</p> <p>More clinicians in KPNC perceived to be part of a clinical integrated environment than did general practitioners in the DHS (OR = 3.06, 95% CI: 2.28, 4.12). Further, more KPNC clinicians reported timeliness of information transfer (OR = 2.25, 95% CI: 1.62, 3.13), agreement on roles and responsibilities (OR = 1.79, 95% CI: 1.30, 2.47) and established coordination mechanisms in place to ensure effective handoffs (OR = 6.80, 95% CI: 4.60, 10.06). None of the considered organizational factors in the sub-country analysis explained a substantial proportion of the variation in clinical integration.</p> <p>Conclusions</p> <p>More primary care clinicians in KPNC reported clinical integration than did general practitioners in the DHS. Focused measures of clinical integration are needed to develop the field of clinical integration and to create the scientific foundation to guide managers searching for evidence based approaches.</p