From manganese oxidation to water oxidation: assembly and evolution of the water-splitting complex in photosystem II.

The manganese cluster of photosystem II has been the focus of intense research aiming to understand the mechanism of H2O-oxidation. Great effort has also been applied to investigating its oxidative photoassembly process, termed photoactivation that involves the light-driven incorporation of metal ions into the active Mn4CaO5 cluster. The knowledge gained on these topics has fundamental scientific significance, but may also provide the blueprints for the development of biomimetic devices capable of splitting water for solar energy applications. Accordingly, synthetic chemical approaches inspired by the native Mn cluster are actively being explored, for which the native catalyst is a useful benchmark. For both the natural and artificial catalysts, the assembly process of incorporating Mn ions into catalytically active Mn oxide complexes is an oxidative process. In both cases this process appears to share certain chemical features, such as producing an optimal fraction of open coordination sites on the metals to facilitate the binding of substrate water, as well as the involvement of alkali metals (e.g., Ca2+) to facilitate assembly and activate water-splitting catalysis. This review discusses the structure and formation of the metal cluster of the PSII H2O-oxidizing complex in the context of what is known about the formation and chemical properties of different Mn oxides. Additionally, the evolutionary origin of the Mn4CaO5 is considered in light of hypotheses that soluble Mn2+ was an ancient source of reductant for some early photosynthetic reaction centers ('photomanganotrophy'), and recent evidence that PSII can form Mn oxides with structural resemblance to the geologically abundant birnessite class of minerals. A new functional role for Ca2+ to facilitate sustained Mn2+ oxidation during photomanganotrophy is proposed, which may explain proposed physiological intermediates during the likely evolutionary transition from anoxygenic to oxygenic photosynthesis.

Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis.

Efficient foraging by plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism), and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although root electrotropism has been observed in a few species since the end of the 19th century, its molecular and physical mechanisms remain elusive, limiting its comparison with the more well-defined sensing pathways in plants. Here, we provide a quantitative and molecular characterization of root electrotropism in the model system Arabidopsis (Arabidopsis thaliana), showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but instead requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals. Future studies involving more extensive molecular and quantitative characterization of root electrotropism would represent a step toward a better understanding of signal integration in plants and would also serve as an independent outgroup for comparative analysis of electroreception in animals and fungi.

Light-driven formation of manganese oxide by today's photosystem II supports evolutionarily ancient manganese-oxidizing photosynthesis.

Water oxidation and concomitant dioxygen formation by the manganese-calcium cluster of oxygenic photosynthesis has shaped the biosphere, atmosphere, and geosphere. It has been hypothesized that at an early stage of evolution, before photosynthetic water oxidation became prominent, light-driven formation of manganese oxides from dissolved Mn(2+) ions may have played a key role in bioenergetics and possibly facilitated early geological manganese deposits. Here we report the biochemical evidence for the ability of photosystems to form extended manganese oxide particles. The photochemical redox processes in spinach photosystem-II particles devoid of the manganese-calcium cluster are tracked by visible-light and X-ray spectroscopy. Oxidation of dissolved manganese ions results in high-valent Mn(III,IV)-oxide nanoparticles of the birnessite type bound to photosystem II, with 50-100 manganese ions per photosystem. Having shown that even today's photosystem II can form birnessite-type oxide particles efficiently, we propose an evolutionary scenario, which involves manganese-oxide production by ancestral photosystems, later followed by down-sizing of protein-bound manganese-oxide nanoparticles to finally yield today's catalyst of photosynthetic water oxidation.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Covid-19 is a recently-emerged infectious disease caused by the novel severe acute respiratory syndrome coronavirus SARS-CoV2. SARS-CoV2 differs from previous coronavirus infections (SARS and MERS) due to its high infectivity (reproduction value, R0, typically 2-4) and pre- or asymptomatic transmission, properties that have contributed to the current global Covid-19 pandemic. Identified risk factors for disease severity and death from SARS-Cov2 infection include older age, male sex, diabetes, obesity and hypertension. The reasons for these associations are still largely obscure. Evidence is also emerging that SARS-CoV2 infection exacerbates the underlying pathophysiology of hyperglycemia in people with diabetes. Here, we discuss potential mechanisms through which diabetes may affect the risk of more severe outcomes in Covid-19 and, additionally, how diabetic emergencies and longer term pathology may be aggravated by infection with the virus. We consider roles for the immune system, the observed phenomenon of microangiopathy in severe Covid-19 infection and the potential for direct viral toxicity on metabolically-relevant tissues including pancreatic beta cells and targets of insulin action.

Homozygous Hypomorphic HNF1A Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulfonylurea-Sensitive Diabetes.

OBJECTIVE: Heterozygous loss-of-function mutations in HNF1A cause maturity-onset diabetes of the young (MODY). Affected individuals can be treated with low-dose sulfonylureas. Individuals with homozygous HNF1A mutations causing MODY have not been reported. RESEARCH DESIGN AND METHODS: We phenotyped a kindred with young-onset diabetes and performed molecular genetic testing, a mixed meal tolerance test, a sulfonylurea challenge, and in vitro assays to assess variant protein function. RESULTS: A homozygous HNF1A variant (p.A251T) was identified in three insulin-treated family members diagnosed with diabetes before 20 years of age. Those with the homozygous variant had low hs-CRP levels (0.2-0.8 mg/L), and those tested demonstrated sensitivity to sulfonylurea given at a low dose, completely transitioning off insulin. In silico modeling predicted a variant of unknown significance; however, in vitro studies supported a modest reduction in transactivation potential (79% of that for the wild type; P < 0.05) in the absence of endogenous HNF1A. CONCLUSIONS: Homozygous hypomorphic HNF1A variants are a cause of HNF1A-MODY. We thus expand the allelic spectrum of variants in dominant genes causing diabetes.

Adiposity measurements by BMI, skinfolds and dual energy X-ray absorptiometry in relation to risk markers for cardiovascular disease and diabetes in adult males.

BACKGROUND: Choice of adiposity measure may be important in the evaluation of relationships between adiposity and risk markers for cardiovascular disease and diabetes. AIM: We explored the strengths of risk marker associations with BMI, a simple measure of adiposity, and with measures provided by skinfold thicknesses and dual energy X-ray absorptiometry (DXA). SUBJECTS AND METHODS: We evaluated in three subgroups of white males (n = 156-349), participating in a health screening program, the strengths of relationship between measures of total and regional adiposity and risk markers relating to blood pressure, lipids and lipoproteins, insulin sensitivity, and subclinical inflammation. RESULTS: Independent of age, smoking, alcohol intake, and exercise, the strongest correlations with adiposity measures were seen with serum triglyceride concentrations and indices of insulin sensitivity, with strengths of association showing little difference between BMI and skinfold and DXA measures of total and percent body fat (R = 0.20-0.46, P < 0.01). Significant but weaker associations with adiposity were seen for serum HDL cholesterol and only relatively inconsistent associations with adiposity for total and LDL cholesterol and indices of subclinical inflammation. CONCLUSIONS: BMI can account for variation in risk markers in white males as well as more sophisticated measures derived from skinfold thickness measurements or DXA scanning.

Global optimization of distributed output feedback controllers.

When the frequency range over which a reduction in vibration is desired is limited to a particular structural mode of vibration, for example, it is shown that a centralized velocity feedback controller can perform better than a decentralized controller for a given level of control effort. The decentralized controller, however, has the desirable properties of scalability and ease of implementation. A number of strategies for clustering the control locations have been proposed to exploit both the performance of the centralized controller and the scalability of decentralized controllers but these have previously been only locally optimal. This paper describes methods by which these distributed controllers may be designed to be globally optimal and gives examples of simulated results of these optimal distributed controllers.

Destabilization of velocity feedback controllers with stroke limited inertial actuators.

It has been observed when using inertial actuators for the active reduction of structural vibration, that velocity feedback controllers are liable to become unstable if the actuator is subject to stroke saturation. This article presents a simple nonlinear, time domain model of an inertial actuator mounted on a single degree of freedom system. At low amplitudes the actuator, when used in a velocity feedback control loop, increases the effective damping of the structure. At higher amplitudes the system is shown to become unstable, however, and generates limit cycle oscillations having a predictable frequency.