Leigh Syndrome: Neuropathology and Pathogenesis Lake, Nicole J; Bird, Matthew J; Isohanni, Pirjo ...
Journal of neuropathology and experimental neurology,
2015-June, Letnik:
74, Številka:
6
Journal Article
Recenzirano
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ABSTRACTLeigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of ...bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.
Philanthropy seeks to address deep-rooted social issues and assume responsibility for the creation of public goods not provided by the public sector—and in this way help reduce inequality. Yet ...philanthropy has also been criticized for bypassing democratic mechanisms for the public determination of how to invest in society—and thus may perpetuate other inequities. In both cases, inequality, defined as asymmetries of resources and power, plays a critical role in public goods creation and in the legitimacy of a country’s philanthropic ecosystem. However, little empirical research examines the existence and role of inequality in country-level donation systems. To fill this gap, this study provides evidence of growing donation concentration in Chile’s philanthropic ecosystem, with a focus on the culture sector, characterizes it by mapping systematic differences in ecosystem perceptions by actor type, and identifies and tests statistically structural and organizational factors associated with these perceptions. Inequality in Chile’s donation system operates at multiple geographical, legal, and organizational levels, all of which are reflected in objective donation amounts and subjective ecosystem perceptions. We conclude that in Chile resource asymmetries and power imbalances hinder the fulfillment of philanthropy’s promise and call for further research to identify policies that address inequities in emerging philanthropic ecosystems in Chile, Latin America, and beyond.
Eupotemus tuberculatus sp. nov. is described on the basis of two specimens discovered during recent field work in South Africa. This is the first member of the Epimetopidae to be confirmed in Africa ...south of the Congo Basin and Tanzania. The new species is a member of the Eupotemus carinaticollis Fikek et al., 2021 species group, sharing features of pronotal and aedeagal design. Characters distinguishing the new species from previously described taxa are discussed and notes provided on the collecting circumstances.
Here we report the use of pulse radiolysis and spectroelectrochemistry to generate low-valent nickel intermediates relevant to synthetically important Ni-catalyzed cross-coupling reactions and ...interrogate their reactivities toward comproportionation and oxidative addition processes. Pulse radiolysis provided a direct means to generate singly reduced (dtbbpy)NiBr, enabling the identification of a rapid Ni(0)/Ni(II) comproportionation process taking place under synthetically relevant electrolysis conditions. This approach also permitted the direct measurement of Ni(I) oxidative addition rates with electronically differentiated aryl iodide electrophiles (k OA = 1.3 × 104–2.4 × 105 M–1 s–1), an elementary organometallic step often proposed in nickel-catalyzed cross-coupling reactions. Together, these results hold implications for a number of Ni-catalyzed cross-coupling processes.
Goal setting is a widely used intervention by sport psychology practitioners (SPPs) and coaches aimed at enhancing the performance of their clients and athletes. Many mnemonics and acronyms have been ...suggested to follow when setting goals. These often recommend certain principles or characteristics, such as setting specific, measurable, achievable, realistic, and time-related (SMART) goals. Less attention has been paid to the process of goal setting, or specifically how a SPP or coach goes about setting goals. The purpose of this review was to provide an overview of current goal-setting processes by identifying, describing, and comparing models within the applied sport psychology and professional practice literature. Furthermore, we aimed to synthesize contextual information and critically evaluate stages presented in these processes, while providing further considerations for practitioners and future directions for researchers. Our review shows there are several commonalities in the suggested processes of setting goals and that the stages can be broadly categorized as: (i) preparation; (ii) goal setting; (iii) planning; and (iv) follow-up. Although goal setting should be applied in a dynamic, individualized, and contextually-appropriate manner, the review demonstrates the need for integration of additional evidence-based psychological strategies within each stage of the goal-setting process.
Lay summary: In this paper we provide an overview and synthesis of the different goal setting processes used by SPPs and coaches. We present ideas to consider when setting goals and direction for research in this area.
There are several stages that might be considered when setting goals with athletes.
Numerous additional interventions like helping athletes identify their values, monitoring goal progress, and revising/adjusting goals could take place as part of the process.
Screening new electrocatalysts is key to the development of new materials for next-generation energy devices such as fuel cells and electrolyzers. The counter electrodes used in such tests are often ...made from materials such as Pt and Au, which can dissolve during testing and deposit onto test electrocatalysts, resulting in inaccurate results. The most common strategy for preventing this effect is to separate the counter electrode from the test material using an ion-transporting Nafion membrane. Here, we use X-ray photoelectron spectroscopy, energy-dispersive X-ray analysis, mass spectrometry, and voltammetry to demonstrate the limitations of this approach during constant-current, extended stability testing of electrocatalysts for H2 evolution. We show that Nafion membranes cannot prevent contamination of carbon electrocatalysts by Pt and Au counter electrodes, leading to an apparent increase in the electrocatalytic activity of the carbon. We then demonstrate that carbon counter electrodes in undivided cells can contaminate and deactivate Pt and Au electrocatalysts for H2 evolution. We show that use of a setup composed of a glass frit separating a carbon counter electrode from the test electrocatalyst can prevent these effects. Finally, we discuss these phenomena using H2 evolution at MoS2 and at a K6P2W18O62(H2O)14/carbon nanotube composite as test reactions.
Spectra of the dimer cations naphthalene (Nap2 •+) and ethene (Ethene2 •+) were measured in liquid dichloromethane (DCM). The spectra peak at very different energies, 1.2 and 3.3 eV. In DCM ...dimerization stabilizes Nap2 •+ by ΔG d°(Nap2 •+) = −218 meV relative to the monomer Nap•+ as determined from the dimerization equilibrium constant. Both dimers can transfer a positive charge to hole acceptor molecules, but for both the rate constants rise more gradually with reaction energetics than do many charge transfer reactions previously studied. A striking observation finds that the rate constant for hole transfer from the Nap2 •+ dimer to phenanthrene is smaller by two decades than that from biphenyl•+ monomer to Nap, although both reactions have the same −ΔG° = 0.05 eV. A plausible interpretation for these observations is the presence of an energy of reorganization, λ(M2), for the dimer that involves movement apart of the two partners in the dimer. While the dimerization equilibrium cannot be measured for Ethene2 •+, the charge transfer data imply that both ΔG d°(Ethene2 •+) and λ(Ethene2 •+) are considerably larger, perhaps by factors of 2–4 than for Nap2 •+.
Political trust is an important predictor of compliance with government policies, especially in the face of natural disasters or public health emergencies. During the COVID-19 pandemic, for example, ...multiple studies related political trust to increased compliance with mobility restrictions. Yet these findings come mostly from high-income countries where political trust and wealth correlate positively. In Latin America, both variables correlate negatively, allowing for better testing of competing explanations. Using a difference-in-differences design, we find that in Latin America wealth and, counterintuitively, low political trust predict increased compliance. To understand mechanisms, we decompose political trust and wealth into underlying predictors (social protection, corruption, and education) and reinsert them into the model. While education, as a wealth proxy, predicts decreased mobility across all periods, social protection, which was the strongest predictor of political trust, relates significantly to increased mobility, but only at the beginning of the lockdown prior to distribution of emergency support. This suggests the existence of a public health moral hazard early in the pandemic, whereby citizens who benefited previously from government benefits may have been more risk tolerant in the face of the COVID-19 threat. We interpret these findings within the context of the region's recent “inclusionary turn.” Future studies should explore the distinct relationships between political trust, risk perception, and compliance, especially in low- and middle-income countries, and their implications for policy responses to national emergencies.
Objective(s)
To investigate differences in public stigma, self‐stigma, attitudes (value and discomfort), and intentions to seek help between online and face‐to‐face counseling. To identify a ...difference in the relationship between these variables and both counseling modalities.
Method
An online survey completed by 538 college students from one university in the Southeastern United States. The sample included 412 females and 126 males with a mean age of 20.21 years (standard deviation SD = 1.26).
Results
Significantly higher levels of self‐stigma and discomfort toward online counseling were reported. Significantly higher value and intentions were reported toward face‐to‐face counseling. Self‐stigma was positively related to public stigma, value was negatively related to self‐stigma, and intentions toward seeking help was positively related to value.
Conclusions
Results suggest face‐to‐face counseling is seen as a more favorable method of service delivery compared to online counseling. Value toward online counseling is an important predictor for seeking this type of help.
Carrier mobility in doped conjugated polymers is limited by Coulomb interactions with dopant counterions. This complicates studying the effect of the dopant's oxidation potential on carrier ...generation because different dopants have different Coulomb interactions with polarons on the polymer backbone. Here, dodecaborane (DDB)‐based dopants are used, which electrostatically shield counterions from carriers and have tunable redox potentials at constant size and shape. DDB dopants produce mobile carriers due to spatial separation of the counterion, and those with greater energetic offsets produce more carriers. Neutron reflectometry indicates that dopant infiltration into conjugated polymer films is redox‐potential‐driven. Remarkably, X‐ray scattering shows that despite their large 2‐nm size, DDBs intercalate into the crystalline polymer lamellae like small molecules, indicating that this is the preferred location for dopants of any size. These findings elucidate why doping conjugated polymers usually produces integer, rather than partial charge transfer: dopant counterions effectively intercalate into the lamellae, far from the polarons on the polymer backbone. Finally, it is shown that the IR spectrum provides a simple way to determine polaron mobility. Overall, higher oxidation potentials lead to higher doping efficiencies, with values reaching 100% for driving forces sufficient to dope poorly crystalline regions of the film.
The effect of dopant redox potential on the chemical doping of conjugated polymers is studied using dodecaborane dopants whose potential can be tuned at constant size and shape. The 2‐nm dodecaborane clusters preferentially intercalate into the polymer crystalline lamellae, and the doping efficiency increases with redox potential. The isolation of the counteranion from the hole leads to improved carrier mobility.
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