Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

The basal proton conductance of mitochondria depends on adenine nucleotide translocase content

Abstract: The basal proton conductance of mitochondria causes mild uncoupling and may be an important contributor to metabolic rate. The molecular nature of the proton-conductance pathway is unknown. We show that the proton conductance of muscle mitochondria from mice in which isoform 1 of the adenine nucleotide translocase has been ablated is half that of wild-type controls. Overexpression of the adenine nucleotide translocase encoded by the stress-sensitive B gene in Drosophila mitochondria increases proton conductance, and underexpression decreases it, even when the carrier is fully inhibited using carboxyatractylate. We conclude that half to two-thirds of the basal proton conductance of mitochondria is catalysed by the adenine nucleotide carrier, independently of its ATP/ADP exchange or fatty-acid-dependent proton-leak functions.

Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer study 22845 with the Medical Research Council study BRO4: An interim analysis

Abstract: Purpose: There is no consensus on the treatment strategy for adult patients with cerebral low-grade glioma. The diagnosis and primary treatment are usually undertaken by surgery. Some investigators doubt the efficacy of postoperative radiotherapy (RT), whereas others advise routine postoperative RT. We report the primary results of a multicenter randomized trial on this controversy. Methods and Materials: From 24 European centers, 311 adult patients with low-grade glioma were randomized centrally after surgery from March 1986 through September 1997, between the two arms of the trial. The irradiated group received 54 Gy in 6 weeks. The other patients did not receive any treatment after surgery until the tumor showed progression, defined as clinical-neurologic deterioration and evidence of progressive tumor on imaging. Results: Of 290 eligible and assessable patients (93%), the irradiated group showed a significant (log-rank p = 0.02) improvement in time to progression but not in overall survival, with a median follow-up of 5 years. The 5-year estimate was, respectively, 63% vs. 66% (overall survival) and 44% vs. 37% (time to progression) for the treated and control arms. Different treatment modalities, including RT, were undertaken for the 85 controls when a progressive tumor was noted. Conclusion: Early postoperative conventional RT such as that used for this protocol appears to improve the time to progression or progression-free survival, but not overall survival, for patients with low-grade glioma. (C) 2002 Elsevier Science Inc.

AMP-activated protein kinase: nature's energy sensor.

Abstract: Maintaining sufficient levels of ATP (the immediate source of cellular energy) is essential for the proper functioning of all living cells As a consequence, cells require mechanisms to balance energy demand with supply In eukaryotic cells the AMP-activated protein kinase (AMPK) cascade has an important role in this homeostasis AMPK is activated by a fall in ATP (concomitant with a rise in ADP and AMP), which leads to the activation of catabolic pathways and the inhibition of anabolic pathways Here we review the role of AMPK as an energy sensor and consider the recent finding that ADP, as well as AMP, causes activation of mammalian AMPK We also review recent progress in structural studies on phosphorylated AMPK that provides a mechanism for the regulation of AMPK in which AMP and ADP protect it against dephosphorylation Finally, we briefly survey some of the outstanding questions concerning the regulation of AMPK

Modeling the perception of concurrent vowels: vowels with different fundamental frequencies.

Abstract: If two vowels with different fundamental frequencies ( f0’s) are presented simultaneously and monaurally, listeners often hear two talkers producing different vowels on different pitches. This paper describes the evaluation of four computational models of the auditory and perceptual processes which may underlie this ability. Each model involves four stages: (i) frequency analysis using an ‘‘auditory’’ filter bank, (ii) determination of the pitches present in the stimulus, (iii) segregation of the competing speech sources by grouping energy associated with each pitch to create two derived spectral patterns, and (iv) classification of the derived spectral patterns to predict the probabilities of listeners’ vowel‐identification responses. The ‘‘place’’ models carry out the operations of pitch determination and spectral segregation by analyzing the distribution of rms levels across the channels of the filter bank. The ‘‘place–time’’ models carry out these operations by analyzing the periodicities in the wavef...