The cyanobacterium Synechocystis sp. PCC 6803 (S. 6803) is a well-established model species in oxygenic photosynthesis research and a potential host for biotechnological applications. Despite recent ...advances in genome sequencing and microarray techniques applied in systems biology, quantitative proteomics approaches with corresponding accuracy and depth are scarce for S. 6803. In this study, we developed a protocol to screen changes in the expression of 106 proteins representing central metabolic pathways in S. 6803 with a targeted mass spectrometry method, selected reaction monitoring (SRM). We evaluated the response to the exposure of both short- and long-term iron deprivation. The experimental setup enabled the relative quantification of 96 proteins, with 87 and 92 proteins showing adjusted p-values <0.01 under short- and long-term iron deficiency, respectively. The high sensitivity of the SRM method for S. 6803 was demonstrated by providing quantitative data for altogether 64 proteins that previously could not be detected with the classical data-dependent MS approach under similar conditions. This highlights the effectiveness of SRM for quantification and extends the analytical capability to low-abundance proteins in unfractionated samples of S. 6803. The SRM assays and other generated information are now publicly available via PASSEL and Panorama.
Flavodiiron proteins (FDPs, also called flavoproteins, Flvs) are modular enzymes widely present in Bacteria and Archaea. The evolution of cyanobacteria and oxygenic photosynthesis occurred in concert ...with the modulation of typical bacterial FDPs. Present cyanobacterial FDPs are composed of three domains, the β-lactamase-like, flavodoxin-like and flavin-reductase like domains. Cyanobacterial FDPs function as hetero- and homodimers and are involved in the regulation of photosynthetic electron transport. Whilst Flv2 and Flv4 proteins are limited to specific cyanobacterial species (β-cyanobacteria) and function in photoprotection of Photosystem II, Flv1 and Flv3 proteins, functioning in the "Mehler-like" reaction and safeguarding Photosystem I under fluctuating light conditions, occur in nearly all cyanobacteria and additionally in green algae, mosses and lycophytes. Filamentous cyanobacteria have additional FDPs in heterocyst cells, ensuring a microaerobic environment for the function of the nitrogenase enzyme under the light. Here, the evolution, occurrence and functional mechanisms of various FDPs in oxygenic photosynthetic organisms are discussed.
•We developed a large-scale atlas of human type 2 dopamine receptor (D2R).•D2R availability decreases similarly among males and females and overall females have a higher availability than males ...through age.•Potential sex-dependencies in D2R expression may predispose males and females to different neuropsychiatric conditions.•Striatal 11Craclopride binding potential can be calculated reliably from positron emission tomography (PET) scan without magnetic resonance image (MRI).
The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved.
In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of 11Craclopride PET scans performed between 2004 and 2018.
Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135).
D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
Alterations in the brain’s μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. ...Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. We compiled 11Ccarfentanil positron emission tomography scans from 204 individuals with no neurologic or psychiatric disorders, and estimated the effects of sex, age, body mass index (BMI) and smoking on 11Ccarfentanil binding potential using between-subject regression analysis. We also examined hemispheric differences in MOR availability. Older age was associated with increase in MOR availability in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders. Lateralized MOR system may reflect hemispheric work specialization in central emotion and pain processes.
•Sex, age and smoking have regionally specific influence on human μ-opioid receptor (MOR) availability in the brain.•MOR availabilities have regional asymmetries between the two hemispheres, right hemisphere being more abundant in MORs.•Variability in MOR system may explain why some individuals are vulnerable to chronic pain and neuropsychiatric disorders.
Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. ...Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain's MOR availability was measured with positron emission tomography (PET) using an agonist radioligand
Ccarfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.
•A fully automated method is presented to pinpoint and segment the location of the acute ischemic stroke lesions.•Our computerized segmented lesions demonstrated good agreement with the expert ...delineated lesions.•Supplementary machine learning based classifier can categorize stroke and no stroke patients with high accuracy.•This technique paves the way for straightforward implementations of fast and reliable delineation of brain stroke lesions.
Successful delineation of lesions in acute ischemic strokes (AIS) is crucial for increasing the likelihood of good clinical outcome for the patient.
We developed a fully automated method to localize and segment AIS lesions in variable locations for 192 multimodal 3D-magnetic resonance images (MRI) including 106 stroke and 86 healthy cases. The method works based on the Crawford-Howell t-test and comparison of stroke images to healthy controls. We then developed a classifier to discriminate the images into stroke or non-stroke categories following the lesion segmentation.
The mean Dice similarity coefficient (DSC) for the test set was 0.50 ± 0.21 (min-max: 0.07–0.83) and mean net overlap was 0.66 ± 0.18 (min-max: 0.22–1). The experimental results for the classification of strokes from non-strokes showed mean accuracy, precision, sensitivity, and specificity of 73 %, 0.77 %, 84 %, and 69 %, respectively.
The performance of our methods is comparable with previously published approaches based on machine learning and/or deep learning lesion segmentation techniques. However, most of the previously published methods have yielded low sensitivity, are computationally heavy, and difficult to interpret. The present approach is a significant improvement because it does not require high computation power and memory and can be implemented on a desktop workstation and integrated into the routine clinical diagnostic pipeline.
The current method is straightforward, fast, and shows good agreement with the lesions identified by human experts.
The obligate intracellular pathogen Chlamydia pneumoniae remains a difficult target for antimicrobial therapy. Owing to the permeability barrier placed by bacterial and host vacuolar membranes, as ...well as the propensity of the bacterium for persistent infections, treatment failures are common. Despite the urgent need for new antichlamydial compounds, their discovery is challenged by the technically demanding assay procedures and lack of validated targets. An alternative strategy of using naturally occurring compounds and their derivatives against C. pneumoniae is presented. The strategy consists of the application of ligand-based virtual screening to a natural product library of 502 compounds with the ChemGPS-NP chemography tool followed by in vitro antichlamydial assays. The reference set used for the 2D similarity search was constructed of 19 known antichlamydial compounds of plant origin. Based on the similarity screen, 53 virtual hits were selected for in vitro testing. Six compounds (leads) were identified that cause ≥50% C. pneumoniae growth inhibition and showed no impact on host cell viability. The leads fall into completely new antichlamydial chemotypes, one of them being mycophenolic acid (IC
value 0.3 μM). The outcome indicates that using this flipped, target-independent strategy is useful for facilitating the antimicrobial lead discovery against challenging microbes.
Abstract
Eating behavior varies greatly between individuals, but the neurobiological basis of these trait-like differences in feeding remains poorly understood. Central μ-opioid receptors (MOR) and ...cannabinoid CB
1
receptors (CB
1
R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain’s opioid and endocannabinoid signaling, the variation in MOR and CB
1
R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed
11
Ccarfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and
18
FFMPEP-
d
2
scans of CB
1
Rs from 35 subjects (all males, all also included in the
11
Ccarfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating—individuals with low MORs reported being more likely to eat in response to environment’s palatable food cues. CB
1
R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB
1
Rs overlap anatomically in brain regions regulating food reward, they have distinct roles in mediating individual feeding patterns. Central MOR system might provide a pharmacological target for reducing individual’s excessive cue-reactive eating behavior.
Flavodiiron proteins are known to have crucial and specific roles in photoprotection of photosystems I and II in cyanobacteria. The filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain ...PCC 7120 contains, besides the four flavodiiron proteins Flv1A, Flv2, Flv3A, and Flv4 present in vegetative cells, two heterocyst-specific flavodiiron proteins, Flv1B and Flv3B. Here, we demonstrate that Flv3B is responsible for light-induced O ₂ uptake in heterocysts, and that the absence of the Flv3B protein severely compromises the growth of filaments in oxic, but not in microoxic, conditions. It is further demonstrated that Flv3B-mediated photosynthetic O ₂ uptake has a distinct role in heterocysts which cannot be substituted by respiratory O ₂ uptake in the protection of nitrogenase from oxidative damage and, thus, in an efficient provision of nitrogen to filaments. In line with this conclusion, the Δ flv3B strain has reduced amounts of nitrogenase NifHDK subunits and shows multiple symptoms of nitrogen deficiency in the filaments. The apparent imbalance of cytosolic redox state in Δ flv3B heterocysts also has a pronounced influence on the amounts of different transcripts and proteins. Therefore, an O ₂-related mechanism for control of gene expression is suggested to take place in heterocysts.
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•We compared human striatal and thalamic type 2 dopamine receptor (D2R) availability between healthy controls, and subjects with Parkinson’s disease (PD), antipsychotic-naïve ...schizophrenia, severe violent behavior, pathological gambling, depression, and overweight.•We present the mean brain maps of group specific D2R availabilities in NeuroVault (https://neurovault.org; https://identifiers.org/neurovault.collection:12799).•Dopamine type 2 receptor availability is lowered in PD in caudate nucleus, nucleus accumbens and thalamus.•Subjects with severe violent behavior had decreased correlation between the striatal and thalamic D2R availability.•Altered regional D2R availability in the striatum and thalamus is linked with motor disorders, while lowered interregional coupling in D2R might relate to violence.
Aberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls.
Here, we investigated the variation in striatal (caudate nucleus, nucleus accumbens, and putamen) and thalamic type 2 dopamine receptor (D2R) availability using 11Craclopride positron emission tomography (PET) data from a large sample of 437 humans including healthy controls, and subjects with Parkinson’s disease (PD), antipsychotic-naïve schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We analyzed regional group differences in D2R availability. We also analyzed the interregional correlation in D2R availability within each group.
Subjects with PD showed the clearest decline in D2R availability. Overall, the groups showed high interregional correlation in D2R availability, while this pattern was weaker in violent offenders. Subjects with schizophrenia, pathological gambling, depression, or overweight did not show clear changes in either the regional receptor availability or the interregional correlation.
We conclude that the dopaminergic changes in neuropsychiatric conditions might not only affect the overall receptor availability but also how coupled regions are across people. The region-specific receptor availability more profoundly links to the motor symptoms, while the between-region coupling might be disrupted in violence.
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