Abstract The mitochondrial permeability transition pore (MPTP) is a non-specific pore that opens in the inner mitochondrial membrane (IMM) when matrix Ca2+ is high, especially when accompanied by ...oxidative stress, high Pi and adenine nucleotide depletion. Such conditions occur during ischaemia and subsequent reperfusion, when MPTP opening is known to occur and cause irreversible damage to the heart. Matrix cyclophilin D facilitates MPTP opening and is the target of its inhibition by cyclosporin A that is cardioprotective. Less certainty exists over the composition of the pore itself, with structural and/or regulatory roles proposed for the adenine nucleotide translocase, the phosphate carrier and the FoF1 ATP synthase. Here we critically review the supporting data for the role of each and suggest that they may interact with each other through their bound cardiolipin to form the ATP synthasome. We propose that under conditions favouring MPTP opening, calcium-triggered conformational changes in these proteins may perturb the interface between them generating the pore. Proteins associated with the outer mitochondrial membrane (OMM), such as members of the Bcl-2 family and hexokinase (HK), whilst not directly involved in pore formation, may regulate MPTP opening through interactions between OMM and IMM proteins at “contact sites”. Recent evidence suggests that cardioprotective protocols such as preconditioning inhibit MPTP opening at reperfusion by preventing the loss of mitochondrial bound HK2 that stabilises these contact sites. Contact site breakage both sensitises the MPTP to Ca2+ and facilitates cytochrome c loss from the intermembrane space leading to greater ROS production and further MPTP opening. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
From the 1980s onward, neoliberal governance in the United States, Canada, and the United Kingdom has emphasized competitive individualism and people have seemingly responded, in kind, by agitating ...to perfect themselves and their lifestyles. In this study, the authors examine whether cultural changes have coincided with an increase in multidimensional perfectionism in college students over the last 27 years. Their analyses are based on 164 samples and 41,641 American, Canadian, and British college students, who completed the Multidimensional Perfectionism Scale (Hewitt & Flett, 1991) between 1989 and 2016 (70.92% female, Mage = 20.66). Cross-temporal meta-analysis revealed that levels of self-oriented perfectionism, socially prescribed perfectionism, and other-oriented perfectionism have linearly increased. These trends remained when controlling for gender and between-country differences in perfectionism scores. Overall, in order of magnitude of the observed increase, the findings indicate that recent generations of young people perceive that others are more demanding of them, are more demanding of others, and are more demanding of themselves.
The SLC16 gene family has fourteen members. Four (SLC16A1, SLC16A3, SLC16A7, and SLC16A8) encode monocarboxylate transporters (MCT1, MCT4, MCT2, and MCT3, respectively) catalysing the proton-linked ...transport of monocarboxylates such as l-lactate, pyruvate and ketone bodies across the plasma membrane. SLC16A2 encodes a high affinity thyroid hormone transporter (MCT8) and SLC16A10 an aromatic amino acid transporter (TAT1). The substrates and roles of the remaining eight members are unknown. All family members are predicted to have 12 transmembrane helices (TMs) with intracellular C- and N-termini and a large intracellular loop between TMs 6 and 7. This topology has been confirmed for MCT1 and a three-dimensional structure has been modelled that suggests a plausible molecular mechanism. For correct plasma membrane expression and activity MCTs1–4, but not MCT8, require association with basigin or embigin; these are glycoproteins with a single TM and 2–3 extracellular immunoglobulin domains. SLC16 family members are involved in a wide range of metabolic pathways including energy metabolism of the brain, skeletal muscle, heart and tumour cells, gluconeogenesis, T-lymphocyte activation, bowel metabolism, spermatogenesis, pancreatic β-cell malfunction, thyroid hormone metabolism, and drug transport. MCTs 1–4 have distinct properties, tissue distribution and subcellular localisation that are appropriate for these metabolic roles. Their potential as pharmacological targets has been recognised with the discovery of potent and specific MCT1 inhibitors that act as immunosuppressant drugs by preventing proliferation of T-lymphocytes. It is suggested that the development of other drugs specifically targeting different MCT isoforms may provide a novel approach to cancer chemotherapy.
Magnetic mineral diagenesis Roberts, Andrew P.
Earth-science reviews,
December 2015, 2015-12-00, 20151201, Letnik:
151
Journal Article
Recenzirano
Reduction–oxidation (redox) reactions occur during burial because sediments contain reactive mixtures of oxidised and reduced components. Diagenetic chemical reactions represent the approach of all ...sedimentary components toward equilibrium, and control the long-term stability of sedimentary iron-bearing minerals. Magnetic minerals are sensitive indicators of sedimentary redox conditions and of changes in these conditions through time, with diagenetic effects ranging from subtle to pervasive. Despite the importance of magnetic mineral diagenesis in paleomagnetism, rock magnetism, and environmental magnetism, and the usefulness of these subjects in the Earth and environmental sciences, there is no systematic single published treatment of magnetic mineral diagenesis. This paper is an attempt to provide such a treatment for the full range of diagenetic environments. Magnetic mineral diagenesis during early burial is driven largely by chemical changes associated with organic matter degradation in a succession of environments that range from oxic to nitrogenous to manganiferous to ferruginous to sulphidic to methanic, where the free energy yielded by different oxidants decreases progressively in each environment. In oxic environments, the most important diagenetic processes involve surface oxidation of detrital minerals, and precipitation of Fe3+-bearing minerals from solution. In ferruginous environments, the most reactive detrital and authigenic iron oxides undergo dissolution, often mediated by dissimilatory iron-reducing bacteria, which releases Fe2+ that becomes available for other reactions. The Fe2+ in solution can diffuse upward where it is oxidised to form new authigenic iron (oxyhydr-)oxide minerals or it can become bioavailable to enable magnetotactic bacteria to biomineralise magnetite, generally at the base of the overlying nitrogenous zone. Alternatively, dissimilatory iron-reducing bacteria can produce extracellular magnetite within ferruginous environments. In sulphidic environments, iron-bearing detrital mineral assemblages undergo more radical alteration. Hydrogen sulphide, which is a byproduct of bacterial sulphate reduction or of anaerobic oxidation of methane, reacts with the Fe2+ released from iron mineral dissolution or directly with solid iron (oxyhydr-)oxide minerals to form iron sulphide minerals (mackinawite, greigite, and pyrite). Authigenic growth of ferrimagnetic greigite has important implications for paleomagnetic recording. Secondary iron sulphide formation can also occur as a result of anaerobic oxidation of methane. Methane migration through sediments in association with biogenic or thermogenic methane production or in association with gas hydrate dissociation can disrupt the diagenetic steady state and give rise to greigite and monoclinic pyrrhotite formation that remagnetises sediments. Most of the above-described diagenetic processes occur below 50°C. With continuing burial above 50°C, but at sub-metamorphic temperatures, magnetic minerals can undergo further thermally-induced chemical changes that give rise to a wide range of mineralogical transformations that affect the magnetic record of the host sediment. These changes include remagnetisations. Magnetic analysis can provide much valuable information concerning diagenesis in environmental processes. The range of processes discussed in this paper should assist researchers in analysing sediment magnetic properties for which the assessment of diagenetic effects has become a necessary component.
•Whether the hippocampus plays a role in working memory and perception is controversial.•I propose that the hippocampus supports complex high-resolution bindings.•Current patient literature supports ...this proposal.•Hippocampal damage impairs tasks that require complex high-resolution bindings.•Tasks requiring only low-resolution or simple associations are less impaired.
It is well established that the hippocampus plays a critical role in our ability to recollect past events. A number of recent studies have indicated that the hippocampus may also play a critical role in working memory and perception, but these results have been highly controversial because other similar studies have failed to find evidence for hippocampal involvement. Thus, the precise role that the hippocampus plays in cognition is still debated. In the current paper, I propose that the hippocampus supports the generation and utilization of complex high-resolution bindings that link together the qualitative aspects that make up an event; these bindings are essential for recollection, and they can also contribute to performance across a variety of tasks including perception and working memory. An examination of the existing patient literature provides support for this proposal by showing that hippocampal damage leads to impairments on perception and working memory tasks that require complex high-resolution bindings. Conversely, hippocampal damage is much less likely to lead to impairments on tasks that require only low-resolution or simple associations/relations. The current proposal can be distinguished from earlier accounts of hippocampal function, and it generates a number of novel predictions that can be tested in future studies.
ABSTRACT
We present a method to flexibly and self-consistently determine individual galaxies’ star formation rates (SFRs) from their host haloes’ potential well depths, assembly histories, and ...redshifts. The method is constrained by galaxies’ observed stellar mass functions, SFRs (specific and cosmic), quenched fractions, ultraviolet (UV) luminosity functions, UV–stellar mass relations, IRX–UV relations, auto- and cross-correlation functions (including quenched and star-forming subsamples), and quenching dependence on environment; each observable is reproduced over the full redshift range available, up to 0 < z < 10. Key findings include the following: galaxy assembly correlates strongly with halo assembly; quenching correlates strongly with halo mass; quenched fractions at fixed halo mass decrease with increasing redshift; massive quenched galaxies reside in higher-mass haloes than star-forming galaxies at fixed galaxy mass; star-forming and quenched galaxies’ star formation histories at fixed mass differ most at z < 0.5; satellites have large scatter in quenching time-scales after infall, and have modestly higher quenched fractions than central galaxies; Planck cosmologies result in up to 0.3 dex lower stellar – halo mass ratios at early times; and, none the less, stellar mass–halo mass ratios rise at z > 5. Also presented are revised stellar mass – halo mass relations for all, quenched, star-forming, central, and satellite galaxies; the dependence of star formation histories on halo mass, stellar mass, and galaxy SSFR; quenched fractions and quenching time-scale distributions for satellites; and predictions for higher-redshift galaxy correlation functions and weak lensing surface densities. The public data release (DR1) includes the massively parallel (>105 cores) implementation (the UniverseMachine), the newly compiled and remeasured observational data, derived galaxy formation constraints, and mock catalogues including lightcones.
Linking Crystallographic Model and Data Quality Karplus, P. Andrew; Diederichs, Kay
Science (American Association for the Advancement of Science),
05/2012, Letnik:
336, Številka:
6084
Journal Article
Recenzirano
Odprti dostop
In macromolecular x-ray crystallography, refinement R values measure the agreement between observed and calculated data. Analogously, R merge values reporting on the agreement between multiple ...measurements of a given reflection are used to assess data quality. Here, we show that despite their widespread use, R merge values are poorly suited for determining the high-resolution limit and that current standard protocols discard much useful data. We introduce a statistic that estimates the correlation of an observed data set with the underlying (not measurable) true signal; this quantity, CC*, provides a single statistically valid guide for deciding which data are useful. CC* also can be used to assess model and data quality on the same scale, and this reveals when data quality is limiting model improvement.
Plastics recycling with a difference Sardon, Haritz; Dove, Andrew P
Science (American Association for the Advancement of Science),
2018-Apr-27, 2018-04-27, 20180427, Letnik:
360, Številka:
6387
Journal Article
Recenzirano
A novel plastic with useful properties can easily be recycled again and again
Since the synthesis of the first synthetic polymer in 1907, the low cost, durability, safeness, and processability of ...polymers have led to ever-expanding uses throughout the global economy. Polymers, commonly called plastics, have become so widely used that global production is expected to exceed 500 million metric tons by 2050. This rising production, combined with rapid disposal and poor mechanisms for recycling, has led to the prediction that, by 2050, there will be more plastic in the sea than fish (
1
). On page 398 of this issue, Zhu
et al.
(
2
) report an important step toward addressing this problem with the synthesis of a plastic with mechanical properties comparable to those of commercially available plastics, but with an intrinsically infinite recyclability.
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