Structures of the intermediates in the catalytic cycle of mitochondrial cytochrome c oxidase

Cytochrome c oxidase is the terminal complex of the respiratory chains in the mitochondria of nearly all eu-karyotes. It catalyzes the reduction of molecular O-2 to water using electrons from the respiratory chain, delivered via cytochrome c on the external surface of the inner mitochondrial membrane. The protons required for water formation are taken from the matrix side of the membrane, making catalysis vectorial. This vectorial feature is further enhanced by the fact that the redox catalysis is coupled to the translocation of protons from the inside to the outside of the inner mitochondrial membrane. We are dealing with a molecular machine that converts redox free energy into a protonmotive force (pmf). Here, we review the current extensive knowledge of the structural changes in the active heme-copper site that accompany catalysis, based on a large variety of time-resolved spectroscopic experiments, X-ray and cryoEM structures, and advanced computational chemistry.Peer reviewe

Superweakly interacting dark matter from the Minimal Walking Technicolor

We study a superweakly interacting dark matter particle motivated by minimal walking technicolor theories. Our WIMP is a mixture of a sterile state and a state with the charges of a standard model fourth family neutrino. We show that the model can give the right amount of dark matter over a range of the WIMP mass and mixing angle. We compute bounds on the model parameters from the current accelerator data including the oblique corrections to the precision electroweak parameters, as well as from cryogenic experiments, Super-Kamiokande and from the IceCube experiment. We show that consistent dark matter solutions exist which satisfy all current constraints. However, almost the entire parameter range of the model lies within the the combined reach of the next generation experiments.Comment: 29 pages, 6 figure

Development and validation of two self-reported tools for insulin resistance and hypertension risk assessment in a European cohort : the Feel4Diabetes-study

Early identification of type 2 diabetes mellitus (T2DM) and hypertension (HTN) risk may improve prevention and promote public health. Implementation of self-reported scores for risk assessment provides an alternative cost-effective tool. The study aimed to develop and validate two easy-to-apply screening tools identifying high-risk individuals for insulin resistance (IR) and HTN in a European cohort. Sociodemographic, lifestyle, anthropometric and clinical data obtained from 1581 and 1350 adults (baseline data from the Feel4Diabetes-study) were used for the European IR and the European HTN risk assessment index respectively. Body mass index, waist circumference, sex, age, breakfast consumption, alcohol, legumes and sugary drinks intake, physical activity and sedentary behavior were significantly correlated with Homeostatic Model Assessment of IR (HOMA-IR) and/or HTN and incorporated in the two models. For the IR index, the Area Under the Curve (AUC), sensitivity and specificity for identifying individuals above the 75th and 95th of HOMA-IR percentiles were 0.768 (95%CI: 0.721–0.815), 0.720 and 0.691 and 0.828 (95%CI: 0.766–0.890), 0.696 and 0.778 respectively. For the HTN index, the AUC, sensitivity and specificity were 0.778 (95%CI: 0.680–0.876), 0.667 and 0.797. The developed risk assessment tools are easy-to-apply, valid, and low-cost, identifying European adults at high risk for developing T2DM or having HTN

Oxygen Activation and Energy Conservation by Cytochrome c Oxidase

This review focuses on the type A cytochrome c oxidases (C cO), which are found in all mitochondria and also in several aerobic bacteria. C cO catalyzes the respiratory reduction of dioxygen (O2) to water by an intriguing mechanism, the details of which are fairly well understood today as a result of research for over four decades. Perhaps even more intriguingly, the membrane-bound C cO couples the O2 reduction chemistry to translocation of protons across the membrane, thus contributing to generation of the electrochemical proton gradient that is used to drive the synthesis of ATP as catalyzed by the rotary ATP synthase in the same membrane. After reviewing the structure of the core subunits of C cO, the active site, and the transfer paths of electrons, protons, oxygen, and water, we describe the states of the catalytic cycle and point out the few remaining uncertainties. Finally, we discuss the mechanism of proton translocation and the controversies in that area that still prevail.Peer reviewe

Victimization, crime propensity and deviance: a multinational test of general strain theory

General Strain Theory (GST) identifies victimization as one of the strains most strongly related to crime which, like other sources of strain, is moderated by individual and social factors. Recently, Agnew (2013) extended the theorization of coping strategies by proposing that the effects of strain on deviance are conditioned by individual and social factors in combination, rather than singly, which he labelled crime propensity. Tests of the propensity hypothesis have so far yielded mixed results, highlighting the value of additional studies. Whereas previous tests have focused on single countries, either in North America or Asia, we test the propensity hypothesis using data on adolescents in 25 countries collected through the International Self-Report Delinquency Study (ISRD3; n= 57,760). A series of OLS regressions show that the relationship between victimization and delinquency/substance use is conditioned by the effects of individuals’ crime propensity, thereby supporting the recent extension to GST

Making Code Voting Secure against Insider Threats using Unconditionally Secure MIX Schemes and Human PSMT Protocols

Code voting was introduced by Chaum as a solution for using a possibly infected-by-malware device to cast a vote in an electronic voting application. Chaum's work on code voting assumed voting codes are physically delivered to voters using the mail system, implicitly requiring to trust the mail system. This is not necessarily a valid assumption to make - especially if the mail system cannot be trusted. When conspiring with the recipient of the cast ballots, privacy is broken. It is clear to the public that when it comes to privacy, computers and "secure" communication over the Internet cannot fully be trusted. This emphasizes the importance of using: (1) Unconditional security for secure network communication. (2) Reduce reliance on untrusted computers. In this paper we explore how to remove the mail system trust assumption in code voting. We use PSMT protocols (SCN 2012) where with the help of visual aids, humans can carry out $\mod 10$ addition correctly with a 99\% degree of accuracy. We introduce an unconditionally secure MIX based on the combinatorics of set systems. Given that end users of our proposed voting scheme construction are humans we \emph{cannot use} classical Secure Multi Party Computation protocols. Our solutions are for both single and multi-seat elections achieving: \begin{enumerate}[i)] \item An anonymous and perfectly secure communication network secure against a $t$-bounded passive adversary used to deliver voting, \item The end step of the protocol can be handled by a human to evade the threat of malware. \end{enumerate} We do not focus on active adversaries

Enhanced Sensitivity to Dark Matter Self-annihilations in the Sun using Neutrino Spectral Information

Self-annihilating dark matter gravitationally captured by the Sun could yield observable neutrino signals at current and next generation neutrino detectors. By exploiting such signals, neutrino detectors can probe the spin-dependent scattering of weakly interacting massive particles (WIMPs) with nucleons in the Sun. We describe a method how to convert constraints on neutrino fluxes to a limit on the WIMP-nucleon scattering cross section. In this method all neutrino flavors can be treated in a very similar way. We study the sensitivity of neutrino telescopes for Solar WIMP signals using vertex contained events and find that this detection channel is of particular importance in the search for low mass WIMPs. We obtain highly competitive sensitivities with all neutrino flavor channels for a Megaton sized detector through the application of basic spectral selection criteria. Best results are obtained with the electron neutrino channel. We discuss associated uncertainties and provide a procedure how to treat them for analyses in a consistent way.Comment: 21 pages, 6 figure