Clinical features affecting efficacy of immune checkpoint inhibitors in pretreated patients with advanced NSCLC: a Danish nationwide real-world study.

Background: Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population.

Key components and contrasts in the nitrogen budget across a US-Canadian transboundary watershed.

Watershed nitrogen (N) budgets provide insights into drivers and solutions for groundwater and surface water N contamination. We constructed a comprehensive N budget for the transboundary Nooksack River Watershed (British Columbia, Canada and Washington, US) using locally-derived data, national statistics and standard parameters. Feed imports for dairy (mainly in the US) and poultry (mainly in Canada) accounted for 30 and 29% of the total N input to the watershed, respectively.

Stigmatization of Chinese and Asian-looking people during the COVID-19 pandemic in Germany.

Background: The outbreak and global spread of COVID-19 was accompanied by an increase in reports of stigmatization of Chinese and Asian-looking people. The behavioral immune system provides a framework for stigmatization in response to infectious disease threats. Specifically, stigmatization might increase with rising levels of infectious disease threat.

The Relation of Threat Level and Age With Protective Behavior Intentions During Covid-19 in Germany.

To contain the spread of Covid-19, engagement in protective behaviors across the population is of great importance. The present study investigated protective behavior intentions during the early phases of Covid-19 in Germany (February 2-April 3, 2020) as a function of threat level and age using data from 4,940 participants in the EUCLID project. Results indicated that the intention to engage in social distancing increased sharply with threat level.

Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O) and hypoxic (10% O) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry).

Forest Structure Affects Soil Mercury Losses in the Presence and Absence of Wildfire.

Soil is an important, dynamic component of regional and global mercury (Hg) cycles. This study evaluated how changes in forest soil Hg masses caused by atmospheric deposition and wildfire are affected by forest structure. Pre and postfire soil Hg measurements were made over two decades on replicate experimental units of three prefire forest structures (mature unthinned, mature thinned, clear-cut) in Douglas-fir dominated forest of southwestern Oregon.

Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain.

Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions were combined.

Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males.

Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7).

Chloride and calcium in Photosystem II: from effects to enigma(*).

This minireview focuses on the early evidence for roles of chloride and calcium ions in reactions of photosynthetic electron transport and on the reluctance with which an essential function of these inorganic ions in the process of water oxidation was accepted. For example, Daniel Arnon's group initially refuted the conclusion of Otto Warburg, the discoverer of a 'chloride effect,' that chloride was a 'coenzyme.' Their reasoning was that chloride had not been shown to be an essential mineral nutrient of plants.

Hydrogen metabolism of green algae: discovery and early research - a tribute to Hans Gaffron and his coworkers.

The detection of hydrogen metabolism in green algae more than 60 years ago by Hans Gaffron dispelled the widely accepted dogma at that time that this feature was unique to prokaryotic organisms. Research on this unexpected aspect of algal physiology has continued until today because of its evolutionary implications and possible practical significance. This minireview focuses on the work of Gaffron and his collaborators, whose experiments provided most of the information about the mechanism of hydrogen metabolism in algae during the 35 years following its discovery.

Superoxide contributes to the rapid inactivation of specific secondary donors of the photosystem II reaction center during photodamage of manganese-depleted photosystem II membranes.

The role of superoxide in the mechanism of photoinactivation of the secondary donors of the reaction center of photosystem II membranes depleted of Mn by extraction with NH2OH plus EDTA (NH2OH/EDTA-PSII) was assessed. EPR analyses (g = 2 region) in continuous light, optical kinetic spectrophotometric analyses of P680+ and Car+, and AT-band emission measurements were made after various durations of weak and strong light treatment of NH2OH/EDTA-PSII in the presence and absence of superoxide dismutase, or of PSII electron acceptors to suppress superoxide formation. Additionally, flash-induced variable fluorescence of chlorophyll a and the capabilities of the membranes of photooxidize Mn2+ (in the presence of H2O2) via a high-affinity site (Km approximately 180 nM) and to carry out the photoactivation of the Mn-cluster were determined.

Modification of the thermoluminescence properties of Ca(2+) depleted Photosystem II membranes by the 23 kDa extrinsic polypeptide and by oligocarboxylic acids.

Photosystem II membranes were isolated from chloroplasts of pokeweed (Phytolacca americana) and rendered deficient in Ca(2+), an inorganic cofactor of photosynthetic water oxidation. The thermoluminescence properties of such membranes were found to depend on the Ca(2+)-depleting method used. This feature was analyzed with respect to the thermoluminescence emission that accompanied the recombination reaction between the reduced acceptor QA (-) and the oxidant of the S2 state.

Thermoluminescence properties of the S2-state in chloride-depleted water oxidizing complexes after reconstituting treatments with various monovalent anions.

Under conditions that assured rebinding of the extrinsic 17 and 23 kDa polypeptides, Cl(-)-depleted Photosystem II membranes isolated from spinach chloroplasts were subjected to reconstituting treatments in media containing NaF, NaCl, NaBr, NaI or NaNO3, or they were kept in a medium without any added salt other than the buffer. After removing most of the unbound reconstituting anions by washing, the O2-evolution activities and thermoluminescence properties of the membranes were compared. While the temperature of maximal thermoluminescence emission was lowest for membranes treated with Cl(-), no uniform correlation was evident between the temperature profile of the thermoluminescence emission and the apparent activating effectiveness of the anions in the membranes' water oxidizing machinery.

Stabilization of the water oxidizing polypeptide assembly on Photosystem II membranes by osmolytes and other solutes.

The integrity of Photosystem II membranes isolated from chloroplast thylakoids is profoundly affected by the solute environment. Examples are given for stabilizing effects various solutes have on the binding of the 17 and 23 kDa extrinsic polypeptides under conditions conductive to their dissociation. It is concluded that these and many other solute effects on Photosystem II membranes can be accommodated readily in a concept developed by Timasheff and his coworkers according to which the responses of proteins to their solute environment are consequences of interaction preferences among the constituents of the solvent-protein-solute systems.

Structural Effects of Cl and Other Anions on the Water Oxidizing Complex of Chloroplast Photosystem II.

To further our understanding of the role of Cl(-) and certain other monovalent anions in the oxygen evolving photosystem II of chloroplasts, dissociating and stabilizing anion effects on the extrinsic 17 and 23 kilodalton polypeptides of the photosynthetic water oxidizing complex were investigated. It was found that (a) the dissociation of the two polypeptides in Cl(-) free media of pH approximately 7 was enhanced by millimolar concentrations of the divalent anion SO(4) (2-) and also by divalent cations like Mg(2+) and Ca(2+); (b) the dissociation was opposed by relatively low concentrations of monovalent anions with an order of effectiveness Cl(-) = Br(-) > NO(3) (-) > F(-) > ClO(4) (-); (c) at molar concentrations, SO(4) (2-) stabilized the binding of the 23 kilodalton polypeptide, while Cl(-) and Br(-) became dissociating agents, in agreement with studies by Blough and Sauer (1984 Biochim Biophys Acta 767: 377-381); (d) the binding of the polypeptides was strengthened at room temperature relative to 0 degrees C, indicating an involvement of hydrophobic forces. It is suggested that a specific binding of Cl(-), or certain substitutes, organizes the protein surfaces and/or the adjacent water layers in the water oxidizing complex in a way that not only stabilizes its assembly, but is essential for the catalytic mechanism as well.

Explorations in the "inner sanctum of the photosynthetic process," the water oxidizing system.

This article summarizes the present state of knowledge about the organization of the water oxidizing polypeptide complex of photosynthesis and the mechanism of its operation. Spectacular advances have been made in recent years, but many questions remain to be answered. Among them are those concerned with the organization and binding of the functional Mn, its specific role in the oxidant storage that precedes the formation of one oxygen from two water molecules, and its cooperation with other redox-active constituents.

Chloride relations of photosystem II membrane preparations depleted of, and resupplied with, their 17 and 23 kDa extrinsic polypeptides.

Photosystem II membranes prepared from thylakoids of Phytolacca americana chloroplasts were depleted of their intrinsic 17 and 23 kDa polypeptides, and the effects of a reconstitution of these polypeptides on the Cl(-) requirements of O2 evolution activity were analyzed. It was found that the activating effectiveness of limiting amounts of added Cl(-) was increased several fold by an addition of the 23 kDa polypeptide. When it was supplemented by the 17 kDa species, only a small additional increase occurred, but Cl(-) retention in Cl(-) free media was enhanced greatly.

Intrinsic and artifactual pH buffering in chloroplast thylakoids.

After an increase in pH of the suspension medium, a pH gradient across the membrane of chloroplast thylakoids stored at pH greater than or equal to 6.5 is often maintained for several minutes. The intrinsic hydrogen ion buffering capacity of the thylakoid membranes between pH 6.

The relation between the chloride status of the photosynthetic water splitting complex and the inhibitory effectiveness of amines.

The protective role of chloride ions (Cl(-)) against inhibition of the photosynthetic water splitting complex by amines was investigated with purified photosystem II membrane particles from tobacco chloroplasts. Seemingly competitive interactions occurred between Cl(-) (except at low concentrations) and Tris, but not between Cl(-) and NH3. The rate of Cl(-) release was not increased by the amines but, instead, may have been limited by a labilization under the experimental conditions of the extrinsic 23 kDa polypeptide.

Surface-charge related actions of polylysine on thylakoid membranes.

Polycation binding to the negatively charged surface of chloroplast thylakoid membranes is known to cause an inhibition of photosystem I activity. It also interferes with the cation-dependent rearrangement of chlorophyll proteins in the thylakoid membrane. It was shown that added anions prevented or reversed the inhibition of photosystem I by polylysine without decreasing its binding to the membranes.

The light dependent uptake of N-methylphenazinium cations by the thylakoids of isolated chloroplasts.

The absorption of N-methylphenazinium methylsulfate (MP+ methylsulfate) in suspensions of envelope-free chloroplasts is reversibly lowered in the light. When the electron transport system of the chloroplasts is inhibited by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU), the photobleaching reflects an uptake of MP+ into the thylakoids. Its magnitude is a function of the composition and of the pH of the suspension medium and, most importantly, is controlled by the availability of permeant anions which apparently accompany MP+ into the thylakoid as counterions.