193 research outputs found

    A Chaperonin Subunit with Unique Structures Is Essential for Folding of a Specific Substrate

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    Type I chaperonins are large, double-ring complexes present in bacteria (GroEL), mitochondria (Hsp60), and chloroplasts (Cpn60), which are involved in mediating the folding of newly synthesized, translocated, or stress-denatured proteins. In Escherichia coli, GroEL comprises 14 identical subunits and has been exquisitely optimized to fold its broad range of substrates. However, multiple Cpn60 subunits with different expression profiles have evolved in chloroplasts. Here, we show that, in Arabidopsis thaliana, the minor subunit Cpn60β4 forms a heterooligomeric Cpn60 complex with Cpn60α1 and Cpn60β1–β3 and is specifically required for the folding of NdhH, a subunit of the chloroplast NADH dehydrogenase-like complex (NDH). Other Cpn60β subunits cannot complement the function of Cpn60β4. Furthermore, the unique C-terminus of Cpn60β4 is required for the full activity of the unique Cpn60 complex containing Cpn60β4 for folding of NdhH. Our findings suggest that this unusual kind of subunit enables the Cpn60 complex to assist the folding of some particular substrates, whereas other dominant Cpn60 subunits maintain a housekeeping chaperonin function by facilitating the folding of other obligate substrates

    Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

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    Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes

    Aerobic and anaerobic metabolism during activity in the lizard Dipsosaurus dorsalis

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    1. Oxygen consumption and lactate content of the lizard Dipsosaurus dorsalis were determined under standard conditions and for a bout of maximal activity induced by a 2-min period of electrical stimulation. Observations were made between 25 ° and 45 °C.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47109/1/359_2004_Article_BF00693633.pd

    A universal scaling relationship between body mass and proximal limb bone dimensions in quadrupedal terrestrial tetrapods

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    Quadrupole moments of Cd and Zn nuclei: When solid-state, molecular, atomic, and nuclear theory meet

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    The nuclear quadrupole moment (Q)(Q) of the 5/2+5/2^+ isomeric state of 111^{111}Cd, of particular importance to the interpretation of Perturbed Angular Correlation experiments in condensed matter, was determined by combining existing PAC data with high-level ab initio (CCSD(T)) calculations for Cd-dimethyl and hybrid density functional theory for metallic Cd. A revised value of Q=.641(25) bQ =.641(25)\text{ b} is found, much reduced from earlier estimates. Using the new result together with the values for other Cd isotopes from atomic data, also recently revised, the trend of QQ for the 11/2−11/2^− states in Cd is in perfect agreement with new nuclear covariant density functional theory calculations. Similar theoretical work for metallic Zn and the ZnS molecule, combined with atomic calculations, also results in an equivalent reduction for the reference value of the 67Zn5/2−^{67} \text{Zn} 5/2^− ground-state quadrupole moment to Q=.125(5) bQ=.125(5)\text{ b}

    Electric field gradients of water:a systematic investigation of basis set, electron correlation, and rovibrational effects

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    Electric field gradients at the oxygen and hydrogen nuclei of water have been calculated using high level ab initio methods. Systematic studies of basis set truncation errors have been carried out at the Hartree-Fock and coupled cluster singles and doubles (CCSD) levels using extended correlation consistent basis sets with up to 398 basis functions. Correlation effects are investigated using a hierarchy of correlation methods extending up to the approximate inclusion of triples excitations by means of the CCSD(T) method. Rovibrational effects have been calculated combining accurate ab initio electric field gradient data and accurate experimental force fields. On the basis of the most accurate results for the electric field gradients, the nuclear quadrupole coupling constants for deuterium and oxygen-17 have been discussed including the temperature dependence. The final results are discussed in view of existing experimental data. Our best values for the nuclear quadrupole coupling constants are in excellent agreement (within 1%) of recent experimental results, while some earlier experimental values are shown to be less reliable. (C) 2002 American Institute of Physics
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