Post‐traumatic stress disorder (PTSD) is arguably the most common psychiatric disorder to arise after exposure to a traumatic event. Since its formal introduction in the DSM‐III in 1980, knowledge ...has grown significantly regarding its causes, maintaining mechanisms and treatments. Despite this increased understanding, however, the actual definition of the disorder remains controversial. The DSM‐5 and ICD‐11 define the disorder differently, reflecting disagreements in the field about whether the construct of PTSD should encompass a broad array of psychological manifestations that arise after trauma or should be focused more specifically on trauma memory phenomena. This controversy over clarifying the phenotype of PTSD has limited the capacity to identify biomarkers and specific mechanisms of traumatic stress. This review provides an up‐to‐date outline of the current definitions of PTSD, its known prevalence and risk factors, the main models to explain the disorder, and evidence‐supported treatments. A major conclusion is that, although trauma‐focused cognitive behavior therapy is the best‐validated treatment for PTSD, it has stagnated over recent decades, and only two‐thirds of PTSD patients respond adequately to this intervention. Moreover, most people with PTSD do not access evidence‐based treatment, and this situation is much worse in low‐ and middle‐income countries. Identifying processes that can overcome these major barriers to better management of people with PTSD remains an outstanding challenge.
Modified tetrapyrroles are large macrocyclic compounds, consisting of diverse conjugation and metal chelation systems and imparting an array of colors to the biological structures that contain them. ...Tetrapyrroles represent some of the most complex small molecules synthesized by cells and are involved in many essential processes that are fundamental to life on Earth, including photosynthesis, respiration, and catalysis. These molecules are all derived from a common template through a series of enzyme-mediated transformations that alter the oxidation state of the macrocycle and also modify its size, its side-chain composition, and the nature of the centrally chelated metal ion. The different modified tetrapyrroles include chlorophylls, hemes, siroheme, corrins (including vitamin B12), coenzyme F430, heme d1, and bilins. After nearly a century of study, almost all of the more than 90 different enzymes that synthesize this family of compounds are now known, and expression of reconstructed operons in heterologous hosts has confirmed that most pathways are complete. Aside from the highly diverse nature of the chemical reactions catalyzed, an interesting aspect of comparative biochemistry is to see how different enzymes and even entire pathways have evolved to perform alternative chemical reactions to produce the same end products in the presence and absence of oxygen. Although there is still much to learn, our current understanding of tetrapyrrole biogenesis represents a remarkable biochemical milestone that is summarized in this review.
The Tricarboxylic Acid Cycle in Cyanobacteria Zhang, Shuyi; Bryant, Donald A.
Science (American Association for the Advancement of Science),
12/2011, Volume:
334, Issue:
6062
Journal Article
Peer reviewed
It is generally accepted that cyanobacteria have an incomplete tricarboxylic acid (TCA) cycle because they lack 2-oxoglutarate dehydrogenase and thus cannot convert 2-oxoglutarate to ...succinyl-coenzyme A (CoA). Genes encoding a novel 2-oxoglutarate decarboxylase and succinic semialdehyde dehydrogenase were identified in the cyanobacterium Synechococcus sp. PCC 7002. Together, these two enzymes convert 2-oxoglutarate to succinate and thus functionally replace 2-oxoglutarate dehydrogenase and succinyl-CoA synthetase. These genes are present in all cyanobacterial genomes except those of Prochlorococcus and marine Synechococcus species. Closely related genes occur in the genomes of some methanogens and other anaerobic bacteria, which are also thought to have incomplete TCA cycles.
Summary
Cyanobacteria use three major photosynthetic complexes, photosystem (PS) I, PS II and phycobilisomes, to harvest and convert sunlight into chemical energy. Until recently, it was generally ...thought that cyanobacteria only used light between 400 nm and 700 nm to perform photosynthesis. However, the discovery of chlorophyll (Chl) d in Acaryochloris marina and Chl f in Halomicronema hongdechloris showed that some cyanobacteria could utilize far‐red light. The synthesis of Chl f (and Chl d) is part of an extensive acclimation process, far‐red light photoacclimation (FaRLiP), which occurs in many cyanobacteria. Organisms performing FaRLiP contain a conserved set of 17 genes encoding paralogous subunits of the three major photosynthetic complexes. Far‐red light photoacclimation leads to substantial remodelling of the photosynthetic apparatus and other changes in cellular metabolism through extensive changes in transcription. Far‐red light photoacclimation appears to be controlled by a red/far‐red photoreceptor, RfpA, as well as two response regulators (RfpB and RfpC), one of which is a DNA‐binding protein. The remodelled photosynthetic complexes, including novel phycobiliproteins, absorb light above 700 nm and enable cells to grow in far‐red light. A much simpler acclimation response, low‐light photoacclimation (LoLiP), occurs in some cyanobacteria that contain the apcD4‐apcB3‐isiX cluster, which allows cells to grow under low light conditions.
Because of recent advances in omics methodologies, knowledge of chlorophototrophy (i.e., chlorophyll-based phototrophy) in bacteria has rapidly increased. Chlorophototrophs currently are known to ...occur in seven bacterial phyla:
Cyanobacteria
,
Proteobacteria
,
Chlorobi
,
Chloroflexi
,
Firmicutes
,
Acidobacteria
, and
Gemmatimonadetes
. Other organisms that can produce chlorophylls and photochemical reaction centers may still be undiscovered. Here we summarize the current status of the taxonomy and phylogeny of chlorophototrophic bacteria as revealed by genomic methods. In specific cases, we briefly describe important ecophysiological and metabolic insights that have been gained from the application of genomic methods to these bacteria. In the 20 years since the completion of the
Synechocystis
sp. PCC 6803 genome in 1996, approximately 1,100 genomes have been sequenced, which represents nearly the complete diversity of known chlorophototrophic bacteria. These data are leading to new insights into many important processes, including photosynthesis, nitrogen and carbon fixation, cellular differentiation and development, symbiosis, and ecosystem functionality.
Chlorophyll f (Chl f) permits some cyanobacteria to expand the spectral range for photosynthesis by absorbing far-red light. We used reverse genetics and heterologous expression to identify the ...enzyme for Chl f synthesis. Null mutants of "super-rogue" psbA4 genes, divergent paralogs of psbA genes encoding the D1 core subunit of photosystem II, abolished Chl f synthesis in two cyanobacteria that grow in far-red light. Heterologous expression of the psbA4 gene, which we rename chlF, enables Chl f biosynthesis in Synechococcus sp. PCC 7002. Because the reaction requires light, Chl f synthase is probably a photo-oxidoreductase that employs catalytically useful Chl a molecules, tyrosine YZ, and plastoquinone (as does photosystem II) but lacks a Mn4Ca1O5 cluster. Introduction of Chl f biosynthesis into crop plants could expand their ability to use solar energy.
It has been suggested that certain types of work may increase the risk of common mental disorders, but the exact nature of the relationship has been contentious. The aim of this paper is to conduct ...the first comprehensive systematic meta-review of the evidence linking work to the development of common mental health problems, specifically depression, anxiety and/or work-related stress and to consider how the risk factors identified may relate to each other. MEDLINE, PsychInfo, Embase, the Cochrane Collaboration and grey literature databases were systematically searched for review articles that examined work-based risk factors for common mental health problems. All included reviews were subjected to a quality appraisal. 37 review studies were identified, of which 7 were at least moderate quality. 3 broad categories of work-related factors were identified to explain how work may contribute to the development of depression and/or anxiety: imbalanced job design, occupational uncertainty and lack of value and respect in the workplace. Within these broad categories, there was moderate level evidence from multiple prospective studies that high job demands, low job control, high effort–reward imbalance, low relational justice, low procedural justice, role stress, bullying and low social support in the workplace are associated with a greater risk of developing common mental health problems. While methodological limitations continue to preclude more definitive statements on causation between work and mental disorders, there is now a range of promising targets for individual and organisational-level interventions aimed at minimising mental health problems in the workplace.
The origin and early evolution of photosynthesis are reviewed from an ecophysiological perspective. Earth's first ecosystems were chemotrophic, fueled by geological H2 at hydrothermal vents and, ...required flavin-based electron bifurcation to reduce ferredoxin for CO2 fixation. Chlorophyll-based phototrophy (chlorophototrophy) allowed autotrophs to generate reduced ferredoxin without electron bifurcation, providing them access to reductants other than H2. Because high-intensity, short-wavelength electromagnetic radiation at Earth's surface would have been damaging for the first chlorophyll (Chl)-containing cells, photosynthesis probably arose at hydrothermal vents under low-intensity, long-wavelength geothermal light. The first photochemically active pigments were possibly Zn-tetrapyrroles. We suggest that (i) after the evolution of red-absorbing Chl-like pigments, the first light-driven electron transport chains reduced ferredoxin via a type-1 reaction center (RC) progenitor with electrons from H2S; (ii) photothioautotrophy, first with one RC and then with two, was the bridge between H2-dependent chemolithoautotrophy and water-splitting photosynthesis; (iii) photothiotrophy sustained primary production in the photic zone of Archean oceans; (iv) photosynthesis arose in an anoxygenic cyanobacterial progenitor; (v) Chl a is the ancestral Chl; and (vi), anoxygenic chlorophototrophic lineages characterized so far acquired, by horizontal gene transfer, RCs and Chl biosynthesis with or without autotrophy, from the architects of chlorophototrophy-the cyanobacterial lineage.
There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from ...healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.
FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance HOMA-IR between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.
Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.
ClinicalTrials.gov NCT02530385.
Phycobilisomes (PBS), the major light-harvesting antenna in cyanobacteria, are supramolecular complexes of colorless linkers and heterodimeric, pigment-binding phycobiliproteins. Phycocyanin and ...phycoerythrin commonly comprise peripheral rods, and a multi-cylindrical core is principally assembled from allophycocyanin (AP). Each AP subunit binds one phycocyanobilin (PCB) chromophore, a linear tetrapyrrole that predominantly absorbs in the orange-red region of the visible spectrum (600–700 nm). AP facilitates excitation energy transfer from PBS peripheral rods or from directly absorbed red light to accessory chlorophylls in the photosystems. Paralogous forms of AP that bind PCB and are capable of absorbing far-red light (FRL; 700–800 nm) have recently been identified in organisms performing two types of photoacclimation: FRL photoacclimation (FaRLiP) and low-light photoacclimation (LoLiP). The FRL-absorbing AP (FRL-AP) from the thermophilic LoLiP strain
Synechococcus
sp. A1463 was chosen as a platform for site-specific mutagenesis to probe the structural differences between APs that absorb in the visible region and FRL-APs and to identify residues essential for the FRL absorbance phenotype. Conversely, red light-absorbing allophycocyanin-B (AP-B; ~ 670 nm) from the same organism was used as a platform for creating a FRL-AP. We demonstrate that the protein environment immediately surrounding pyrrole ring A of PCB on the alpha subunit is mostly responsible for the FRL absorbance of FRL-APs. We also show that interactions between PCBs bound to alpha and beta subunits of adjacent protomers in trimeric AP complexes are responsible for a large bathochromic shift of about ~ 20 nm and notable sharpening of the long-wavelength absorbance band.
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