Hypoxia triggers several mechanisms to adapt cells to a low oxygen environment. Mitochondria are major consumers of oxygen and a potential source of reactive oxygen species (ROS). In response to ...hypoxia they exchange or modify distinct subunits of the respiratory chain and adjust their metabolism, especially lowering the citric acid cycle. Intermediates of the citric acid cycle participate in regulating hypoxia inducible factors (HIF), the key mediators of adaptation to hypoxia. Here we summarize how hypoxia conditions mitochondria with consequences for ROS-production and the HIF-pathway.
Thinking aloud is the concurrent verbalization of thoughts while performing a task. The study of thinking-aloud protocols has a long tradition in cognitive psychology, the field of education, and the ...industrial-organizational context. It has been used rarely in cultural and cross-cultural psychology. This paper will describe thinking aloud as a useful method in cultural and cross-cultural psychology referring to a few studies in general and one study in particular to show the wide applications of this method. Thinking-aloud protocols can be applied for (a) improving the validity of cross-cultural surveys, (b) process analysis of thoughts and the analysis of changes over time, (c) theory development across cultures, (d) the study of cultural meaning systems, and (e) individual as well as group level analyses allowing hypothesis testing cross-culturally. Limitations of the thinking-aloud method are also discussed.
COVID-19 has led to global dramatic shifts in daily life. Following the biopsychosocial model of health, the goal of the current study was to predict people's psychological well-being (PWB) during ...the initial lockdown phase of the pandemic and to investigate which coping strategies were most common among people with low and high PWB. Participants were 938 volunteers in the United States who responded to an online survey during the lockdown in April 2020. The main findings were that all three groups of variables, biological, psychological, and socio-economic, significantly contributed to PWB explaining 53% variance. Social loneliness and sense of agency were the strongest predictors. PWB was significantly predicted by physical health (not gender nor age); by spirituality, emotional loneliness, social loneliness, and sense of agency; by job security (not income, nor neighborhood safety, nor hours spent on social media). Comparing the coping strategies of participants, results show more intentional coping in the high-PWB group and more passive coping in the low-PWB group. During this unprecedented pandemic, the findings highlight that ability to sustainably cope with the global shifts in daily life depends on actively and intentionally attending to PWB by being one's own agent for physical health, spiritual health, and social connection.
Ferroptosis is an iron-dependent form of cell death, which is triggered by disturbed membrane integrity due to an overproduction of lipid peroxides. Induction of ferroptosis comprises several ...alterations, i.e. altered iron metabolism, response to oxidative stress, or lipid peroxide production. At the physiological level transcription, translation, and microRNAs add to the appearance and/or activity of building blocks that negatively or positively balance ferroptosis. Ferroptosis contributes to tissue damage in the case of, e.g., brain and heart injury but may be desirable to overcome chemotherapy resistance. For a more complete picture, it is crucial to also consider the cellular microenvironment, which during inflammation and in the tumor context is dominated by hypoxia. This graphical review visualizes basic mechanisms of ferroptosis, categorizes general inducers and inhibitors of ferroptosis, and puts a focus on microRNAs, iron homeostasis, and hypoxia as regulatory components.
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•Underlying mechanisms of ferroptosis.•Iron metabolism shapes sensitivity towards ferroptosis.•microRNAs fine-tune ferroptotic pathways.•Hypoxia determines ferroptotic capacity.•Overview over inhibitors and inducers.
The COVID-19 pandemic revealed more than anticipated about global human functioning and resiliency. This Philippines-based study replicated a recent U.S. COVID analysis on psychological well-being ...(PWB). Factors examined herein were grouped into categories for analysis: 1) predictors of PWB, 2) areas of greatest stress or worry (biggest concerns), 3) perceived or real losses across SES, and 4) identified "unintended gifts" across PWB. Participants (n = 1345) were volunteers who responded to an online survey from August to September 2021, peak of the Delta variant. Three general groups of predictors (biological, psychological, and socio-economic) contributed to PWB. A regression model containing a total of 11 variables was significant, F(11, 1092) = 116.02, p < .00, explaining 53.9% of the variance. The model indicated PWB was significantly predicted by physical health, age, spirituality, emotional loneliness, social loneliness, sense of agency, and income. The strongest predictors of PWB were a sense of agency, social loneliness, and spirituality. Qualitative data analysis was conducted examining biggest concerns, losses due to COVID, and unintended gifts. Top ranking participant concerns were the health of family and friends, personal wellness, and governmental inefficiency/lack of concern. Losses compared to pre-COVID life were analyzed by SES group, with the most frequent responses being missing face-to-face interactions and the freedom to go/do what they please. Low SES groups were most likely to endorse missing everyday routine and experiencing changes in housing conditions due to the pandemic. Unintended gifts of COVID explored by PWB, high PWB individuals significantly appreciated intentional time with family and friends, deepening their spiritual lives, the ability to work from home, less pollution, and more time for physical exercise. Low PWB individuals reported nothing gained, except more time playing video games and watching TV. Those with higher PWB identified more unintended gifts of COVID and coped more actively.
Cellular iron, at the physiological level, is essential to maintain several metabolic pathways, while an excess of free iron may cause oxidative damage and/or provoke cell death. Consequently, iron ...homeostasis has to be tightly controlled. Under hypoxia these regulatory mechanisms for human macrophages are not well understood. Hypoxic primary human macrophages reduced intracellular free iron and increased ferritin expression, including mitochondrial ferritin (FTMT), to store iron. In parallel, nuclear receptor coactivator 4 (NCOA4), a master regulator of ferritinophagy, decreased and was proven to directly regulate FTMT expression. Reduced NCOA4 expression resulted from a lower rate of hypoxic NCOA4 transcription combined with a micro RNA 6862-5p-dependent degradation of NCOA4 mRNA, the latter being regulated by c-jun N-terminal kinase (JNK). Pharmacological inhibition of JNK under hypoxia increased NCOA4 and prevented FTMT induction. FTMT and ferritin heavy chain (FTH) cooperated to protect macrophages from RSL-3-induced ferroptosis under hypoxia as this form of cell death is linked to iron metabolism. In contrast, in HT1080 fibrosarcome cells, which are sensitive to ferroptosis, NCOA4 and FTMT are not regulated. Our study helps to understand mechanisms of hypoxic FTMT regulation and to link ferritinophagy and macrophage sensitivity to ferroptosis.
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•Hypoxia decreases NCOA4 transcription in primary human macrophages.•NCOA4 mRNA is a target of miR-6862-5p.•Lowering NCOA4 increases FTMT abundance under hypoxia.•FTMT and FTH protect from ferroptosis.•Tumor cells lack the hypoxic decrease of NCOA4 and fail to stabilize FTMT.
Context
. A leading paradigm in planet formation is currently the streaming instability and pebble accretion scenario. Notably, dust must grow into sizes in a specific regime of Stokes numbers in ...order to make the processes in the scenario viable and sufficiently effective. The dust growth models currently in use do not implement some of the growth barriers suggested to be relevant in the literature.
Aims
. We investigate if the bouncing barrier, when effective, has an impact on the timescales and efficiencies of processes such as the streaming instability and pebble accretion as well as on the observational appearance of planet-forming disks.
Methods
. We implemented a formalism for the bouncing barrier into the publicly available dust growth model
DustPy
and ran a series of models to understand the impact.
Results
. We found that the bouncing barrier has a significant effect on the dust evolution in planet-forming disks. In many cases, it reduces the size of the typical or largest particles available in the disk; it produces a very narrow, almost monodisperse, size distribution; and it removes most μm-sized grains in the process, with an impact on scattered light images. It modifies the settling and therefore the effectiveness of and timescales for the streaming instability and for pebble accretion. An active bouncing barrier may well have observational consequences: It may reduce the strength of the signatures of small particles (e.g., the 10 μm silicate feature), and it may create additional shadowed regions visible in scattered light images.
Conclusions
. Modeling of planet formation that leans heavily on the streaming instability and on pebble accretion should take the bouncing barrier into account. The complete removal of small grains in our model is not consistent with observations. However, this could be resolved by incomplete vertical mixing or some level of erosion in collisions.
Aims. Shadows in transitional disks are generally interpreted as signs of a misaligned inner disk. This disk is usually beyond the reach of current day high contrast imaging facilities. However, the ...location and morphology of the shadow features allow us to reconstruct the inner disk geometry. Methods. We derive analytic equations of the locations of the shadow features as a function of the orientation of the inner and outer disk and the height of the outer disk wall. In contrast to previous claims in the literature, we show that the position angle of the line connecting the shadows cannot be directly related to the position angle of the inner disk. Results. We show how the analytic framework derived here can be applied to transitional disks with shadow features. We use estimates of the outer disk height to put constraints on the inner disk orientation. In contrast with the results from Long et al. (2017, ApJ, 838, 62), we derive that for the disk surrounding HD 100453 the analytic estimates and interferometric observations result in a consistent picture of the orientation of the inner disk. Conclusions. The elegant consistency in our analytic framework between observation and theory strongly support both the interpretation of the shadow features as coming from a misaligned inner disk as well as the diagnostic value of near infrared interferometry for inner disk geometry.
Context. Planet-forming disks go from gas-rich, massive disks made of dust and gas into planetary systems containing only small amounts dust. This dust is produced by collisions between smaller ...planetary objects, such as planetesimals, asteroids, and comets. Traditionally, we talk about protoplanetary (age ~1 Myr), transitional (~5-10 Myr), and debris disks (~10-hundreds of Myr) even though the overlap between these phases may be relevant. Aims. We aim to show that in the transition phase of a disk, when the gas surface densities are reduced but not yet negligible, a seemingly small amount of collisional activity may lead to the production of dust on a level that is observationally relevant by creating regions characterised by an optical depth of 1 or above. In particular, we aim to show that the hot dust emission component of transitional disks may in fact be debris dust that has been produced in such collisions. Methods. We developed an analytical model to derive the conditions in which observationally relevant amounts of dust can be produced. We focussed on the effect of the gas surface density during the transition phase of a disk from fully gas-dominated to the gas-poor debris stage. Results. We show that the decrease in the gas surface density has an important effect. It allows for smaller planetesimals to become collisional, initiating a cascade. At the same time, small particles are not destroyed by collisions. This interrupted cascade is critical in terms of preserving the produced dust for significant time intervals, allowing for a seemingly minor amount of planetesimal collisions to be effective in producing detectable amounts of dust. Conclusions. The warm emission of low amounts of dust in many transitional planet-forming disks might be caused entirely by second-generation dust, exposing planetary material at a much earlier time than the age that debris disks have traditionally been characterised by.
Context. In protoplanetary disks micron-size dust grains coagulate to form larger structures with complex shapes and compositions. The coagulation process changes the absorption and scattering ...properties of particles in the disk in significant ways. To properly interpret observations of protoplanetary disks and to place these observations in the context of the first steps of planet formation, it is crucial to understand the optical properties of these complex structures. Aims. We derive the optical properties of dust aggregates using detailed computations of aggregate structures and compare these computationally demanding results with approximate methods that are cheaper to compute in practice. In this way we wish to understand the merits and problems of approximate methods and define the context in which they can or cannot be used to analyze observations of objects where significant grain growth is taking place. Methods. For the detailed computations we used the discrete dipole approximation (DDA), a method able to compute the interaction of light with a complexly shaped, inhomogeneous particle. We compared the results to those obtained using spherical and irregular, homogeneous and inhomogeneous particles. Results. While no approximate method properly reproduces all characteristics of large dust aggregates, the thermal properties of dust can be analyzed using irregularly shaped, porous, inhomogeneous grains. The asymmetry of the scattering phase function is a good indicator of aggregate size, while the degree of polarization is probably determined by the size of the constituent particles. Optical properties derived from aggregates significantly differ from the most frequently used standard (“astronomical silicate” in spherical grains). We outline a computationally fast and relatively accurate method that can be used for a multiwavelength analysis of aggregate dust in protoplanetary disks.
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