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YidC belongs to an evolutionarily conserved family of insertases, YidC/Oxa1/Alb3, in bacteria, mitochondria, and chloroplasts, respectively. Unlike Gram-negative bacteria, Gram-positives including Streptococcus mutans harbor two paralogs of YidC. The mechanism for paralog-specific phenotypes of bacterial YidC1 versus YidC2 has been partially attributed to the differences in their cytoplasmic domains. However, we previously identified a W138R gain-of-function mutation in the YidC1 transmembrane helix 2. YidC1W138R mostly phenocopied YidC2, yet the mechanism remained unknown. Primary sequence comparison of streptococcal YidCs led us to identify and mutate the YidC1W138 analog, YidC2S152 to W/A, which resulted in a loss of YidC2- and acquisition of YidC1-like phenotype. The predicted lipid-facing side chains of YidC1W138/YidC2S152 led us to propose a role for membrane phospholipids in specific-residue dependent phenotypes of S. mutans YidC paralogs. Cardiolipin (CL), a prevalent phospholipid in the S. mutans cytoplasmic membrane during acid stress, is encoded by a single gene, cls. We show a concerted mechanism for cardiolipin and YidC2 under acid stress based on similarly increased promoter activities and similar elimination phenotypes. Using coarse grain molecular dynamics simulations with the Martini2.2 Forcefield, YidC1 and YidC2 wild-type and mutant interactions with CL were assessed in silico. We observed substantially increased CL interaction in dimeric versus monomeric proteins, and variable CL occupancy in YidC1 and YidC2 mutant constructs that mimicked characteristics of the other wild-type paralog. Hence, paralog-specific amino acid- CL interactions contribute to YidC1 and YidC2-associated phenotypes that can be exchanged by point mutation at positions 138 or 152, respectively.

In June 2018, the Peruvian provinces of Arequipa and Puno in the southern Andean region were affected by heavy snowfall, which caused severe damage to people and livelihoods in several communities. Using the Forecast-based Financing approach, the Peruvian Red Cross implemented its pre-defined early action protocol before this event, after receiving an extreme snowfall warning (Level 4) from the Peruvian meteorological service. Here, we provide a case study of the approach and event itself, documenting the decision-making thresholds as well as the actions taken. This warning activated the thresholds established in the protocol, and Peruvian Red Cross prioritized 10 communities for pre-disaster support based on the forecasted severity of the event in combination with vulnerability and exposure information. The activation took place 2 days before the extreme snowfall in the communities, and the Red Cross distributed veterinary kits for 50 heads of cattle per family, tarpaulins, tool kits to install a temporary awning for alpacas to protect them from the cold wind and snow, protection kits for alpaca herders and warm clothing for children under five, pregnant women, the elderly, and people with chronic and infectious diseases in 430 highly vulnerable households. This article presents the results of a household survey following the impact of the extreme snowfall. We document the early actions taken by these communities to protect their livelihoods, health, and assets. The evaluation also presents descriptive statistics of household-level outcomes for households receiving pre-snowfall support and those that did not receive any intervention or only received post-disaster assistance. While most households took action to protect their assets, there were fewer extreme losses of alpaca herds reported in the communities who received the early support, and these communities also reported fewer adults suffering from respiratory illnesses. More in-depth research on this type of early action is necessary on a wider scale, especially to evaluate the utility of different support measures and the necessary quantity of support needed. This case study can inform government, civil society, and humanitarian actors of how early action is happening before disasters occur and provide a direction for further investment in research and practice to make use of hydro-meteorological forecasts for the benefit of the most vulnerable.

Interventional yoga studies with an active control group remain scarce and are important to clarify the underlying neurobiology. We conducted an interventional study in healthy controls using simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging and psychometric scales. Thirty healthy, female volunteers (28.4 ± 8.4 years) participated and were randomly assigned to a 12-week yoga or indoor cycling intervention. Before and after the intervention, [18F]FDG and [11C]UCB-J PET was performed on a simultaneous GE Signa PET/MR with volumetric imaging. Psychometric scales were evaluated on affect, mindfulness, stress, worrying, self-compassion, and interoceptive awareness. Yoga subjects scored higher on interoceptive awareness compared to baseline (p < 0.001). Cognitive (P = 0.009) and overall cognitive functioning (P = 0.01) improved after the yoga intervention compared to the cycling group. We did not observe significant differences in glucose metabolism, synaptic density, or gray matter (GM) volume. The indoor cycling group did not show changes in psychometric variables, but significant increases in relative glucose metabolism were observed in the parahippocampal/fusiform gyrus and cerebellum (P < 0.001). In conclusion, 12 weeks of yoga practice has significant effects on interoceptive awareness and perceived cognitive function in starters. Longer interventions and/or higher frequency of yoga practice may be needed to detect cerebral metabolic and/or morphologic effects on the macroscopic level.

During photosynthesis, organisms respond to their energy demand and ensure the supply of energy and redox equivalents that sustain metabolism. Hence, the photosynthetic apparatus can, and in fact should, be treated as an integrated supply-demand system. Any imbalance in the energy produced and consumed can lead to adverse reactions, such as the production of reactive oxygen species (ROS). Reaction centres of both photosystems are known sites of ROS production. Here, we investigate in particular the central role of Photosystem I (PSI) in this tightly regulated system. Using a computational approach we have expanded a previously published mechanistic model of C3 photosynthesis by including ROS producing and scavenging reactions around PSI. These include two water to water reactions mediated by Plastid terminal oxidase (PTOX) and Mehler and the ascorbate-glutathione (ASC-GSH) cycle, as a main non-enzymatic antioxidant. We have used this model to predict flux distributions through alternative electron pathways under various environmental stress conditions by systematically varying light intensity and enzymatic activity of key reactions. In particular, we studied the link between ROS formation and activation of pathways around PSI as potential scavenging mechanisms. This work shines light on the role of alternative electron pathways in photosynthetic acclimation and investigates the effect of environmental perturbations on PSI activity in the context of metabolic productivity.

Cholesterol as an allosteric modulator of G protein-coupled receptor (GPCR) function is well documented. This quintessential mammalian lipid facilitates receptor–ligand interactions and multimerization states. Functionally, this introduces a complicated mechanism for the homeostatic modulation of GPCR signaling. Chemokine receptors are Class A GPCRs responsible for immune cell trafficking through the binding of endogenous peptide ligands. CCR3 is a CC motif chemokine receptor expressed by eosinophils and basophils. It traffics these cells by transducing the signal stimulated by the CC motif chemokine primary messengers 11, 24, and 26. These behaviors are close to the human immunoresponse. Thus, CCR3 is implicated in cancer metastasis and inflammatory conditions. However, there is a paucity of experimental evidence linking the functional states of CCR3 to the molecular mechanisms of cholesterol–receptor cooperativity. In this vein, we present a means to combine codon harmonization and a maltose-binding protein fusion tag to produce CCR3 from E. coli. This technique yields ∼2.6 mg of functional GPCR per liter of minimal media. We leveraged this protein production capability to investigate the effects of cholesterol on CCR3 function in vitro. We found that affinity for the endogenous ligand CCL11 increases in a dose-dependent manner with cholesterol concentration in both styrene:maleic acid lipid particles (SMALPs) and proteoliposomes. This heightened receptor activation directly translates to increased signal transduction as measured by the GTPase activity of the bound G-protein α inhibitory subunit 3 (Gαi3). This work represents a critical step forward in understanding the role of cholesterol-GPCR allostery in regulation of signal transduction.

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.

Yoga is becoming increasingly popular worldwide, with several implicated physical and mental benefits. Here we provide a comprehensive and critical review of the research generated from the existing neuroimaging literature in studies of yoga practitioners. We reviewed 34 international peer-reviewed neuroimaging studies of yoga using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT): 11 morphological and 26 functional studies, including three studies that were classified as both morphological and functional. Consistent findings include increased gray matter volume in the insula and hippocampus, increased activation of prefrontal cortical regions, and functional connectivity changes mainly within the default mode network. There is quite some variability in the neuroimaging findings that partially reflects different yoga styles and approaches, as well as sample size limitations. Direct comparator groups such as physical activity are scarcely used so far. Finally, hypotheses on the underlying neurobiology derived from the imaging findings are discussed in the light of the potential beneficial effects of yoga.

Saccharomyces pastorianus lager-brewing yeasts are domesticated hybrids of S. cerevisiae x S. eubayanus that display extensive inter-strain chromosome copy number variation and chromosomal recombinations. It is unclear to what extent such genome rearrangements are intrinsic to the domestication of hybrid brewing yeasts and whether they contribute to their industrial performance. Here, an allodiploid laboratory hybrid of S. cerevisiae and S. eubayanus was evolved for up to 418 generations on wort under simulated lager-brewing conditions in six independent sequential batch bioreactors. Characterization of 55 single-cell isolates from the evolved cultures showed large phenotypic diversity and whole-genome sequencing revealed a large array of mutations. Frequent loss of heterozygosity involved diverse, strain-specific chromosomal translocations, which differed from those observed in domesticated, aneuploid S. pastorianus brewing strains. In contrast to the extensive aneuploidy of domesticated S. pastorianus strains, the evolved isolates only showed limited (segmental) aneuploidy. Specific mutations could be linked to calcium-dependent flocculation, loss of maltotriose utilization and loss of mitochondrial activity, three industrially relevant traits that also occur in domesticated S. pastorianus strains. This study indicates that fast acquisition of extensive aneuploidy is not required for genetic adaptation of S. cerevisiae × S. eubayanus hybrids to brewing environments. In addition, this work demonstrates that, consistent with the diversity of brewing strains for maltotriose utilization, domestication under brewing conditions can result in loss of this industrially relevant trait. These observations have important implications for the design of strategies to improve industrial performance of novel laboratory-made hybrids.