Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

Associations between gender, torture, and health: A 5-year retrospective cohort analysis.

Our purpose was to identify longitudinal associations between torture exposure, physical and mental health outcomes, and gender in a cohort of 143 war-affected Karen adults five years post resettlement. Results showed that participants who self-reported primary torture experiences had higher rates of certain mental and physical health diagnoses. We observed gender differences in health over time in the cohort.

The correlation between different ultrasound planes and computed tomography measures of abdominal aortic aneurysms.

Introduction: Ultrasound measurements of the aorta are typically taken in the axial plane, with the transducer perpendicular to the aorta, and diameter measurements are obtained by placing the callipers from the anterior to the posterior wall and the transverse right to the left side of the aorta. While the 'conventional' anteroposterior walls in both sagittal and transverse plains may be suitable for aneurysms with less complicated geometry, there is controversy regarding the suitability of this approach for complicated, particularly tortuous aneurysms, as they may offer a more challenging situation. Previous work undertaken within our research group found that when training inexperienced users of ultrasound, they demonstrated more optimal calliper placement to the abdominal aorta when approached from a decubitus window to obtain a coronal image compared to the traditional ultrasound approach.

Resting mitochondrial complex I from adopts a helix-locked state.

Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway 'deactive' state, whereas complex I from Protostomia cannot.

Catheter-directed thrombolysis for lower limb ischaemia: A retrospective study of treatment outcomes.

Introduction: Lower limb ischaemia secondary to occlusion of a lower limb artery is a limb-threatening condition that can be effectively treated by catheter-directed thrombolysis (CDT). The purpose of this study was to examine treatment outcomes of CDT both at the time of treatment and ongoing patency up to 12 months following treatment. The secondary aim of the study was to investigate the influence of age of occlusion and treatment duration on success and complication rates.

Near Infrared Fluorescence Imaging to Demonstrate Reflux in the Superficial Microvenous Network of the Leg.

Objective: Reflux within the superficial microvenous network may play a critical role in the development of skin changes which can be associated with chronic venous insufficiency. This study aimed to determine if near infrared fluorescence (NIRF) imaging could be used to accurately determine superficial venous reflux in the leg.

Methods: A total of nine limbs were examined ex vivo from patients undergoing limb amputation for peripheral arterial disease.

Structural insights into the assembly and the function of the plant oxidative phosphorylation system.

One of the key functions of mitochondria is the production of ATP to support cellular metabolism and growth. The last step of mitochondrial ATP synthesis is performed by the oxidative phosphorylation (OXPHOS) system, an ensemble of protein complexes embedded in the inner mitochondrial membrane. In the last 25 yr, many structures of OXPHOS complexes and supercomplexes have been resolved in yeast, mammals, and bacteria.

Structures of 's respiratory chain reveal the diversity of eukaryotic core metabolism.

Respiration is a core biological energy-converting process whose last steps are carried out by a chain of multisubunit complexes in the inner mitochondrial membrane. To probe the functional and structural diversity of eukaryotic respiration, we examined the respiratory chain of the ciliate (Tt). Using cryo-electron microscopy on a mixed sample, we solved structures of a supercomplex between Tt complex I (Tt-CI) and Tt-CIII (Tt-SC I+III) and a structure of Tt-CIV.

A Structural Perspective on the RNA Editing of Plant Respiratory Complexes.

The last steps of respiration, a core energy-harvesting process, are carried out by a chain of multi-subunit complexes in the inner mitochondrial membrane. Several essential subunits of the respiratory complexes are RNA-edited in plants, frequently leading to changes in the encoded amino acids. While the impact of RNA editing is clear at the sequence and phenotypic levels, the underlying biochemical explanations for these effects have remained obscure.

The Mysterious Multitude: Structural Perspective on the Accessory Subunits of Respiratory Complex I.

Complex I (CI) is the largest protein complex in the mitochondrial oxidative phosphorylation electron transport chain of the inner mitochondrial membrane and plays a key role in the transport of electrons from reduced substrates to molecular oxygen. CI is composed of 14 core subunits that are conserved across species and an increasing number of accessory subunits from bacteria to mammals. The fact that adding accessory subunits incurs costs of protein production and import suggests that these subunits play important physiological roles.

Health of war-affected Karen adults 5 years post-resettlement.

Background: An estimated 140 000 refugees from Burma have resettled to the USA since 2009, comprising 21% of total resettlement in the USA over the last decade. Our objective was to describe patterns of longitudinal health outcomes in a cohort of Karen refugees resettled in the USA for 5 years, and to translate these findings to a primary healthcare context.

Methods: The study was a retrospective cohort study focused on the analysis of the first 5 years of electronic health records of a sample of 143 Karen refugees who were initially resettled between May 2011 and May 2013.

Atomic structures of respiratory complex III, complex IV, and supercomplex III-IV from vascular plants.

Mitochondrial complex III (CIII) and complex IV (CIV), which can associate into a higher-order supercomplex (SC III+IV), play key roles in respiration. However, structures of these plant complexes remain unknown. We present atomic models of CIII, CIV, and SC III+IV from determined by single-particle cryoEM.

Atomic structure of a mitochondrial complex I intermediate from vascular plants.

Respiration, an essential metabolic process, provides cells with chemical energy. In eukaryotes, respiration occurs via the mitochondrial electron transport chain (mETC) composed of several large membrane-protein complexes. Complex I (CI) is the main entry point for electrons into the mETC.

Intensive psychotherapy and case management for Karen refugees with major depression in primary care: a pragmatic randomized control trial.

Background: Despite an unparalleled global refugee crisis, there are almost no studies in primary care addressing real-world conditions and longer courses of treatment that are typical when resettled refugees present to their physician with critical psychosocial needs and complex symptoms. We studied the effects of a year of psychotherapy and case management in a primary care setting on common symptoms and functioning for Karen refugees (a newly arrived population in St Paul, Minnesota) with depression.

Methods: A pragmatic parallel-group randomized control trial was conducted at two primary care clinics with large resettled Karen refugee patient populations, with simple random allocation to 1 year of either: (1) intensive psychotherapy and case management (IPCM), or (2) care-as-usual (CAU).

Structures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk.

The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.

Conserved residues Arg188 and Asp302 are critical for active site organization and catalysis in human ABO(H) blood group A and B glycosyltransferases.

Homologous glycosyltransferases GTA and GTB perform the final step in human ABO(H) blood group A and B antigen synthesis by transferring the sugar moiety from donor UDP-GalNAc/UDP-Gal to the terminal H antigen disaccharide acceptor. Like other GT-A fold family 6 glycosyltransferases, GTA and GTB undergo major conformational changes in two mobile regions, the C-terminal tail and internal loop, to achieve the closed, catalytic state. These changes are known to establish a salt bridge network among conserved active site residues Arg188, Asp211 and Asp302, which move to accommodate a series of discrete donor conformations while promoting loop ordering and formation of the closed enzyme state.

Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain.

The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII and CIV (SC I+III+IV, known as the respirasome), as well as with CIII alone (SC I+III).

High-resolution crystal structures and STD NMR mapping of human ABO(H) blood group glycosyltransferases in complex with trisaccharide reaction products suggest a molecular basis for product release.

The human ABO(H) blood group A- and B-synthesizing glycosyltransferases GTA and GTB have been structurally characterized to high resolution in complex with their respective trisaccharide antigen products. These findings are particularly timely and relevant given the dearth of glycosyltransferase structures collected in complex with their saccharide reaction products. GTA and GTB utilize the same acceptor substrates, oligosaccharides terminating with α-l-Fucp-(1→2)-β-d-Galp-OR (where R is a glycolipid or glycoprotein), but use distinct UDP donor sugars, UDP-N-acetylgalactosamine and UDP-galactose, to generate the blood group A (α-l-Fucp-(1→2)[α-d-GalNAcp-(1→3)]-β-d-Galp-OR) and blood group B (α-l-Fucp-(1→2)[α-d-Galp-(1→3)]-β-d-Galp-OR) determinant structures, respectively.

Glycosyltransfer in mutants of putative catalytic residue Glu303 of the human ABO(H) A and B blood group glycosyltransferases GTA and GTB proceeds through a labile active site.

The homologous glycosyltransferases α-1,3-N-acetylgalactosaminyltransferase (GTA) and α-1,3-galactosyltransferase (GTB) carry out the final synthetic step of the closely related human ABO(H) blood group A and B antigens. The catalytic mechanism of these model retaining enzymes remains under debate, where Glu303 has been suggested to act as a putative nucleophile in a double displacement mechanism, a local dipole stabilizing the intermediate in an orthogonal associative mechanism or a general base to stabilize the reactive oxocarbenium ion-like intermediate in an SNi-like mechanism. Kinetic analysis of GTA and GTB point mutants E303C, E303D, E303Q and E303A shows that despite the enzymes having nearly identical sequences, the corresponding mutants of GTA/GTB have up to a 13-fold difference in their residual activities relative to wild type.

Atomic structure of the entire mammalian mitochondrial complex I.

Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.

Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation.

NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported.

The architecture of respiratory supercomplexes.

Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIIICIV (the respirasome)-a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.

Gaining mass: the structure of respiratory complex I-from bacterial towards mitochondrial versions.

The 1MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.

War trauma and torture experiences reported during public health screening of newly resettled Karen refugees: a qualitative study.

Background: Karen refugees have suffered traumatic experiences that affect their physical and mental health in resettlement. The United States Centers for Disease Control and Prevention recommends assessing traumatic histories and mental health symptoms during initial public health screening. This article reports the traumatic experiences that Karen refugees were able to describe during a short screening and contributes knowledge to existing human rights documentation systems.

The antigen-binding site of an N-propionylated polysialic acid-specific antibody protective against group B meningococci is consistent with extended epitopes.

Monoclonal antibodies 13D9 and 6B9 are both specific for N-propionylated polysialic acid (NPrPSA); however, while 13D9 is protective against meningitis caused by group B meningococci and Escherichia coli capsular type K1 infection, 6B9 is not. The crystal structures of the Fabs from the two antibodies determined at 2.06 and 2.