Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation

Mitochondrial DNA (mtDNA) is packaged into DNA-protein assemblies called nucleoids, but the mode of mtDNA propagation via the nucleoid remains controversial. Two mechanisms have been proposed: nucleoids may consistently maintain their mtDNA content faithfully, or nucleoids may exchange mtDNAs dynamically. To test these models directly, two cell lines were fused, each homoplasmic for a partially deleted mtDNA in which the deletions were nonoverlapping and each deficient in mitochondrial protein synthesis, thus allowing the first unequivocal visualization of two mtDNAs at the nucleoid level. The two mtDNAs transcomplemented to restore mitochondrial protein synthesis but were consistently maintained in discrete nucleoids that did not intermix stably. These results indicate that mitochondrial nucleoids tightly regulate their genetic content rather than freely exchanging mtDNAs. This genetic autonomy provides a molecular mechanism to explain patterns of mitochondrial genetic inheritance, in addition to facilitating therapeutic methods to eliminate deleterious mtDNA mutations

Confluence of Depression and Acute Psychological Stress Among Patients With Stable Coronary Heart Disease: Effects on Myocardial Perfusion

Background: Depression is prevalent in coronary heart disease (CHD) patients and increases risk for acute coronary syndrome (ACS) recurrence and mortality despite optimal medical care. The pathways underlying this risk remain elusive. Psychological stress (PS) can provoke impairment in myocardial perfusion and trigger ACS. A confluence of acute PS with depression might reveal coronary vascular mechanisms of risk. We tested whether depression increased risk for impaired myocardial perfusion during acute PS among patients with stable CHD. Methods and Results: Patients (N=146) completed the Beck Depression Inventory‐I (BDI‐I), a measure of depression linked to recurrent ACS and post‐ACS mortality, and underwent single‐photon emission computed tomography myocardial perfusion imaging at rest and during acute PS. The likelihood of new/worsening impairment in myocardial perfusion from baseline to PS as a function of depression severity was tested. On the BDI‐I, 41 patients scored in the normal range, 48 in the high normal range, and 57 in the depressed range previously linked to CHD prognosis. A BDI‐I score in the depressed range was associated with a significantly greater likelihood of new/worsening impairment in myocardial perfusion from baseline to PS (odds ratio =2.89, 95% CI: 1.26 to 6.63, P=0.012). This remained significant in models controlling ACS recurrence/mortality risk factors and medications. There was no effect for selective serotonin reuptake inhibitor medications. Conclusions: Depressed patients with CHD are particularly susceptible to impairment in myocardial perfusion during PS. The confluence of PS with depression may contribute to a better understanding of the depression‐associated risk for ACS recurrence and mortality

Bose-Fermi mixtures in 1D optical superlattices

The zero temperature phase diagram of binary boson-fermion mixtures in two-colour superlattices is investigated. The eigenvalue problem associated with the Bose-Fermi-Hubbard Hamiltonian is solved using an exact numerical diagonalization technique, supplemented by an adaptive basis truncation scheme. The physically motivated basis truncation allows to access larger systems in a fully controlled and very flexible framework. Several experimentally relevant observables, such as the matter-wave interference pattern and the condensatefraction, are investigated in order to explore the rich phase diagram. At symmetric half filling a phase similar to the Mott-insulating phase in a commensurate purely bosonic system is identified and an analogy to recent experiments is pointed out. Furthermore a phase of complete localization of the bosonic species generated by the repulsive boson-fermion interaction is identified. These localized condensates are of a different nature than the genuine Bose-Einstein condensates in optical lattices.Comment: 18 pages, 9 figure

Enantioselective synthesis of N-benzylic heterocycles: a nickel and photoredox dual catalysis approach

Reported herein is a dual nickel- and photoredox-catalyzed modular approach for the preparation of enantioenriched N-benzylic heterocycles. α-Heterocyclic carboxylic acids, easily obtainable from common commercial material, are reported as suitable substrates for a decarboxylative strategy in conjunction with a chiral pyridine–oxazoline (PyOx) ligand, providing quick access to enantioenriched drug-like products. The presence of a directing group on the heterocyclic moiety is shown to be beneficial, affording improved stereoselectivity in a number of cases

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

The theory of manipulations of pure state asymmetry: basic tools and equivalence classes of states under symmetric operations

If a system undergoes symmetric dynamics, then the final state of the system can only break the symmetry in ways in which it was broken by the initial state, and its measure of asymmetry can be no greater than that of the initial state. It follows that for the purpose of understanding the consequences of symmetries of dynamics, in particular, complicated and open-system dynamics, it is useful to introduce the notion of a state's asymmetry properties, which includes the type and measure of its asymmetry. We demonstrate and exploit the fact that the asymmetry properties of a state can also be understood in terms of information-theoretic concepts, for instance in terms of the state's ability to encode information about an element of the symmetry group. We show that the asymmetry properties of a pure state psi relative to the symmetry group G are completely specified by the characteristic function of the state, defined as chi_psi(g)= where g\in G and U is the unitary representation of interest. For a symmetry described by a compact Lie group G, we show that two pure states can be reversibly interconverted one to the other by symmetric operations if and only if their characteristic functions are equal up to a 1-dimensional representation of the group. Characteristic functions also allow us to easily identify the conditions for one pure state to be converted to another by symmetric operations (in general irreversibly) for the various paradigms of single-copy transformations: deterministic, state-to-ensemble, stochastic and catalyzed.Comment: Published version. Several new results added. 31 Pages, 3 Figure

Vitamin A and zinc supplementation among pregnant women to prevent placental malaria: a randomized, double-blind, placebo-controlled trial in Tanzania

BACKGROUND: Malaria causes nearly 200 million clinical cases and approximately half a million deaths each year, primarily in sub-Saharan Africa.1 The risk of malaria increases during pregnancy,2 a period during which its prevention is especially important. Not only do pregnant women experience greater severity of illness compared with nonpregnant women,2 but studies have shown strong associations between prenatal malaria and maternal anemia,2 fetal loss, low birthweight, and infant mortality.2 Improving preventive measures that specifically target malaria in pregnancy is a global health priority.3 METHODS: Study design and participants. This randomized, doubleblind, placebo-controlled trial was implemented at 8 antenatal care clinics in the urban Temeke and Ilala districts of Dar es Salaam, Tanzania. The trial was registered RESULTS: A total of 2,500 screened participants were enrolled in the trial. The trial profile is shown in Figure 1. It was not possible to collect placentas from 875 participants for the following reasons: miscarriages (fetal loss before 28 weeks of gestation) (N = 234), delivery outside of Dar es Salaam or at a non-study hospital (N = 577), or withdrawal from the study (N = 34). Of the remaining 1,589 women, 1,404 placental samples were obtained (88%); histology results were available for 1,361 participants. PCR results were available for 1,158 participants, and 1,404 participants had either histology or PCR results available. CONCLUSION: This study is the first to examine the impact of vitamin A and zinc supplementation starting in early pregnancy on placental malaria. We observed that supplementation with 25 mg zinc per day from the first trimester until delivery was associated with a 36% (95% CI = 9–56%) reduced risk of histopathology-positive placental infection, but not PCRpositive infection. Vitamin A supplementation had no impact on placental malaria, but was associated with an increased risk for severe anemia

Seasonal variability of the warm Atlantic Water layer in the vicinity of the Greenland shelf break

The warmest water reaching the east and west coast of Greenland is found between 200?m and 600?m. Whilst important for melting Greenland's outlet glaciers, limited winter observations of this layer prohibit determination of its seasonality. To address this, temperature data from Argo profiling floats, a range of sources within the World Ocean Database and unprecedented coverage from marine-mammal borne sensors have been analysed for the period 2002-2011. A significant seasonal range in temperature (~1-2?°C) is found in the warm layer, in contrast to most of the surrounding ocean. The phase of the seasonal cycle exhibits considerable spatial variability, with the warmest water found near the eastern and southwestern shelf-break towards the end of the calendar year. High-resolution ocean model trajectory analysis suggest the timing of the arrival of the year's warmest water is a function of advection time from the subduction site in the Irminger Basin

Spitzer Space Telescope Infrared Imaging and Spectroscopy of the Crab Nebula

We present 3.6, 4.5, 5.8, 8.0, 24, and 70 micron images of the Crab Nebula obtained with the Spitzer Space Telescope IRAC and MIPS cameras, Low- and High-resolution Spitzer IRS spectra of selected positions within the nebula, and a near-infrared ground-based image made in the light of [Fe II]1.644 micron. The 8.0 micron image, made with a bandpass that includes [Ar II]7.0 micron, resembles the general morphology of visible H-alpha and near-IR [Fe II] line emission, while the 3.6 and 4.5 micron images are dominated by continuum synchrotron emission. The 24 micron and 70 micron images show enhanced emission that may be due to line emission or the presence of a small amount of warm dust in the nebula on the order of less than 1% of a solar mass. The ratio of the 3.6 and 4.5 micron images reveals a spatial variation in the synchrotron power law index ranging from approximately 0.3 to 0.8 across the nebula. Combining this information with optical and X-ray synchrotron images, we derive a broadband spectrum that reflects the superposition of the flatter spectrum jet and torus with the steeper diffuse nebula, and suggestions of the expected pileup of relativistic electrons just before the exponential cutoff in the X-ray. The pulsar, and the associated equatorial toroid and polar jet structures seen in Chandra and HST images (Hester et al. 2002) can be identified in all of the IRAC images. We present the IR photometry of the pulsar. The forbidden lines identified in the high resolution IR spectra are all double due to Doppler shifts from the front and back of the expanding nebula and give an expansion velocity of approximately 1264 km/s.Comment: 21 pages, 4 tables, 16 figure

peri‐xanthenoxanthene (PXX): a versatile organic photocatalyst in organic synthesis

Recent years have witnessed a continuous development of photocatalysts to satisfy the growing demand of photophysical and redox properties in photoredox catalysis, with complex structures or alternative strategies devised to access highly reducing or oxidising systems. We report herein the use of peri‐xanthenoxanthene (PXX), a simple and inexpensive dye, as an efficient photocatalyst. Its highly reducing excited state allows activation of a wide range of substrates, thus triggering useful radical reactions. Benchmark transformations such as the addition of organic radicals, generated by photoreduction of organic halides, to radical traps are initially demonstrated. More complex dual catalytic manifolds are also shown to be accessible: the β‐arylation of cyclic ketones is successful when using a secondary amine as organocatalyst, while cross‐coupling reactions of aryl halides with amines and thiols are obtained when using a Ni co‐catalyst. Application to the efficient two‐step synthesis of the expensive fluoro‐tetrahydro‐1H‐pyrido[4,3‐b]indole, a crucial synthetic intermediate for the investigational drug setipiprant, has been also demonstrated