Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been ...found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals ...deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.
This review considers stomatal conductance as an indicator of genotypic differences in the growth response to water stress. The benefits of using stomatal conductance are compared with photosynthetic ...rate and other indicators of genetic variation in water stress tolerance, along with the use of modern phenomics technologies. Various treatments for screening for genetic diversity in response to water deficit in controlled environments are considered. There is no perfect medium: there are pitfalls in using soil in pots, and in using hydroponics with ionic and non-ionic osmotica. Use of mixed salts or NaCl is recommended over non-ionic osmotica. Developments in infrared thermography provide new and feasible screening methods for detecting genetic variation in the stomatal response to water deficit in controlled environments and in the field.
Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, ...mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
Crop improvement efforts are targeting increased above-ground biomass and radiation-use efficiency as drivers for greater yield. Early ground cover and canopy height contribute to biomass production, ...but manual measurements of these traits, and in particular above-ground biomass, are slow and labor-intensive, more so when made at multiple developmental stages. These constraints limit the ability to capture these data in a temporal fashion, hampering insights that could be gained from multi-dimensional data. Here we demonstrate the capacity of Light Detection and Ranging (LiDAR), mounted on a lightweight, mobile, ground-based platform, for rapid multi-temporal and non-destructive estimation of canopy height, ground cover and above-ground biomass. Field validation of LiDAR measurements is presented. For canopy height, strong relationships with LiDAR (
of 0.99 and root mean square error of 0.017 m) were obtained. Ground cover was estimated from LiDAR using two methodologies: red reflectance image and canopy height. In contrast to NDVI, LiDAR was not affected by saturation at high ground cover, and the comparison of both LiDAR methodologies showed strong association (
= 0.92 and slope = 1.02) at ground cover above 0.8. For above-ground biomass, a dedicated field experiment was performed with destructive biomass sampled eight times across different developmental stages. Two methodologies are presented for the estimation of biomass from LiDAR: 3D voxel index (3DVI) and 3D profile index (3DPI). The parameters involved in the calculation of 3DVI and 3DPI were optimized for each sample event from tillering to maturity, as well as generalized for any developmental stage. Individual sample point predictions were strong while predictions across all eight sample events, provided the strongest association with biomass (
= 0.93 and
= 0.92) for 3DPI and 3DVI, respectively. Given these results, we believe that application of this system will provide new opportunities to deliver improved genotypes and agronomic interventions via more efficient and reliable phenotyping of these important traits in large experiments.
A growing number of studies have demonstrated the role of post-translational modifications of proteins, particularly acetylation, in human diseases including neurodegenerative and cardiovascular ...diseases, diabetes, cancer, and in aging. Acetylation of mitochondrial proteins has been shown to be involved in the pathogenesis of cardiac diseases such as myocardial infarction (ischemia-reperfusion) and heart failure. Indeed, over 60% of mitochondrial proteins contain acetylation sites, and most of these proteins are involved in mitochondrial bioenergetics. Mitochondrial non-enzymatic acetylation is enabled by acetyl-coenzyme A abundance and serves as the primary pathway of acetylation in mitochondria. Hence, regulation of enzymatic deacetylation becomes the most important mechanism to control acetylation/deacetylation of mitochondrial proteins. Acetylation/deacetylation of mitochondrial proteins has been regarded as a key regulator of mitochondrial metabolism and function. Proteins are deacetylated by NAD
-dependent deacetylases known as sirtuins (SIRTs). Among seven sirtuin isoforms, only SIRT3, SIRT4, and SIRT5 are localized in the mitochondria. SIRT3 is the main mitochondrial sirtuin which plays a key role in maintaining metabolic and redox balance in the mitochondria under physiological and pathological conditions. SIRT3 regulates the enzymatic activity of proteins involved in fatty acid oxidation, tricarboxylic acid cycle, electron transport chain, and oxidative phosphorylation. Although many enzymes have been identified as targets for SIRT3, cardiac-specific SIRT3 effects and regulations could differ from those in non-cardiac tissues. Therefore, it is important to elucidate the contribution of SIRT3 and mitochondrial protein acetylation/deacetylation in mitochondrial metabolism and cardiac dysfunction. Here, we summarize previous studies and provide a comprehensive analysis of the role of SIRT3 in mitochondria metabolism and bioenergetics under physiological conditions and in cardiac diseases. In addition, the review discusses mitochondrial protein acetylation as a potential target for cardioprotection.
Plant phenomics approaches aim to measure traits such as growth, performance, and composition of plants using a suite of noninvasive technologies. The goal is to link phenotypic traits to the genetic ...information for particular genotypes, thus creating the bridge between the phenome and genome. Application of sensing technologies for detecting specific phenotypic reactions occurring during plant-pathogen interaction offers new opportunities for elucidating the physiological mechanisms that link pathogen infection and disease symptoms in the host, and also provides a faster approach in the selection of genetic material that is resistant to specific pathogens or strains. Appropriate phenomics methods and tools may also allow presymptomatic detection of disease-related changes in plants or to identify changes that are not visually apparent. This review focuses on the use of sensor-based phenomics tools in plant pathology such as those related to digital imaging, chlorophyll fluorescence imaging, spectral imaging, and thermal imaging. A brief introduction is provided for less used approaches like magnetic resonance, soft x-ray imaging, ultrasound, and detection of volatile compounds. We hope that this concise review will stimulate further development and use of tools for automatic, nondestructive, and high-throughput phenotyping of plant-pathogen interaction.
Cancer is one of the primary global causes of death, thus addressing cancer therapy remains a significant challenge, especially in cases where cancers exhibit resistance to treatment ....
Mitochondria are recognized as the main source of ATP to meet the energy demands of the cell. ATP production occurs by oxidative phosphorylation when electrons are transported through the electron ...transport chain (ETC) complexes and develop the proton motive force across the inner mitochondrial membrane that is used for ATP synthesis. Studies since the 1960s have been concentrated on the two models of structural organization of ETC complexes known as “solid-state” and “fluid-state” models. However, advanced new techniques such as blue-native gel electrophoresis, mass spectroscopy, and cryogenic electron microscopy for analysis of macromolecular protein complexes provided new data in favor of the solid-state model. According to this model, individual ETC complexes are assembled into macromolecular structures known as respiratory supercomplexes (SCs). A large number of studies over the last 20 years proposed the potential role of SCs to facilitate substrate channeling, maintain the integrity of individual ETC complexes, reduce electron leakage and production of reactive oxygen species, and prevent excessive and random aggregation of proteins in the inner mitochondrial membrane. However, many other studies have challenged the proposed functional role of SCs. Recently, a third model known as the “plasticity” model was proposed that partly reconciles both “solid-state” and “fluid-state” models. According to the “plasticity” model, respiratory SCs can co-exist with the individual ETC complexes. To date, the physiological role of SCs remains unknown, although several studies using tissue samples of patients or animal/cell models of human diseases revealed an associative link between functional changes and the disintegration of SC assembly. This review summarizes and discusses previous studies on the mechanisms and regulation of SC assembly under physiological and pathological conditions.
Objective
Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity ...worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis.
Methods
We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis.
Results
Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first‐line antibiotic treatment had no such effect on restoring fluid dynamics.
Interpretation
This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021;90:653–669
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