•Physiological mechanisms involved in susceptibility of dopaminergic neurons to oxidative stress.•Effects of the PD-causing neurotoxin MPTP on mitochondrial dysfunction and oxidative ...stress.•Extensive compilation of the most recent data linking cell death pathways to neuronal death in PD.•Relevance of mitochondrial dysfunction and oxidative stress for regulated cell death pathways.•Relevant diagnostic and therapeutic strategies targeting regulated cell death in PD.
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Motor deficits usually associated with PD correlate with dopaminergic axonal neurodegeneration starting at the striatum, which is then followed by dopaminergic neuronal death in the substantia nigra pars compacta (SN), with both events occurring already at the prodromal stage.
We will overview the main physiological characteristics responsible for the higher susceptibility of the nigrostriatal circuit to mitochondrial dysfunction and oxidative stress, as hinted by the acting mechanisms of the PD-causing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Then, we will present multiple lines of evidence linking several cell death mechanisms involving mitochondria and production of reactive oxygen species to neuronal loss in PD, namely intrinsic and extrinsic apoptosis, necroptosis, ferroptosis, parthanatos and mitochondrial permeability transition-driven necrosis. We will focus on gathered data from postmortem PD samples and relevant in vivo models, especially MPTP-based models.
Biomechanical analysis of human movement plays an essential role in understanding functional changes in people with Amyotrophic Lateral Sclerosis (ALS), providing information on muscle impairment. ...Studies suggest that surface electromyography (sEMG) may be able to quantify muscle activity, identify levels of fatigue, assess muscle strength, and monitor variation in limb movement. In this article, a systematic review protocol will analyze the psychometric properties of the sEMG regarding the clinical data on the skeletal muscles of people with ALS. This protocol uses the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological tool. A specific field structure was defined to reach each phase. Nine scientific databases (PubMed, Web of Science, Embase, Elsevier, IEEE, Google Scholar, SciELO, PEDro, LILACS E CENTRAL) were searched. The framework developed will extract data (i.e. study information, sample information, sEMG information, intervention, and outcomes) from the selected studies using a rigorous approach. The data will be described quantitatively using frequency and trend analysis methods, and heterogeneity between the included studies will be assessed using the I2 test. The risk of bias will be summarized using the most recent prediction model risk of bias assessment tool. Be sure to include relevant statistics here, such as sample sizes, response rates, P values or Confidence Intervals. Be specific (by stating the value) rather than general (eg, "there were differences between the groups"). This protocol will map out the construction of a systematic review that will identify and synthesize the advances in movement analysis of people with ALS through sEMG, using data extracted from articles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In many vertebrates, social interactions and nutrition can affect the colonization of gut symbionts across generations. In the highly social honey bee, it is unknown to what extent the hive ...environment and older worker individuals contribute to the generational transmission of core gut bacteria. We used high-throughput sequencing to investigate the effect of nest materials and social contact on the colonization and succession of core hindgut microbiota in workers. With only brief exposure to hive materials following natural eclosion, gut bacterial communities at 3 and 7 days contained phylotypes typically found in the guts of mature adults regardless of treatment. Continuous exposure to nest materials or direct social interactions with mature adults did not affect the diversity or abundance of gut bacterial communities at the scale examined. Similarly, a common pollen supplement fed by beekeepers during pollen dearth had no effect. A consideration of unique OTUs revealed extensive microbial succession independent of treatment. The dominant Lactobacillus strain at 3 days was largely replaced by a different strain at day 7, revealing the colonization signature of a pioneer species. Similar but less pronounced patterns were evident in less abundant OTU’s, many of which may influence community succession via alteration of the gut environment. Our results indicate that the process of bacterial community colonization in the hindgut is resilient to changes in the nutritional, hive, and social environment. Greater taxonomic resolution is needed to accurately resolve questions of ecological succession and typical proportional variation within and between core members of the gut bacterial community.
The accurate prediction of genomic breeding values is central to genomic selection in both plant and animal breeding studies. Genomic prediction involves the use of thousands of molecular markers ...spanning the entire genome and therefore requires methods able to efficiently handle high dimensional data. Not surprisingly, machine learning methods are becoming widely advocated for and used in genomic prediction studies. These methods encompass different groups of supervised and unsupervised learning methods. Although several studies have compared the predictive performances of individual methods, studies comparing the predictive performance of different groups of methods are rare. However, such studies are crucial for identifying (i) groups of methods with superior genomic predictive performance and assessing (ii) the merits and demerits of such groups of methods relative to each other and to the established classical methods. Here, we comparatively evaluate the genomic predictive performance and informally assess the computational cost of several groups of supervised machine learning methods, specifically, regularized regression methods, deep, ensemble and instance-based learning algorithms, using one simulated animal breeding dataset and three empirical maize breeding datasets obtained from a commercial breeding program.
Our results show that the relative predictive performance and computational expense of the groups of machine learning methods depend upon both the data and target traits and that for classical regularized methods, increasing model complexity can incur huge computational costs but does not necessarily always improve predictive accuracy. Thus, despite their greater complexity and computational burden, neither the adaptive nor the group regularized methods clearly improved upon the results of their simple regularized counterparts. This rules out selection of one procedure among machine learning methods for routine use in genomic prediction. The results also show that, because of their competitive predictive performance, computational efficiency, simplicity and therefore relatively few tuning parameters, the classical linear mixed model and regularized regression methods are likely to remain strong contenders for genomic prediction.
The dependence of predictive performance and computational burden on target datasets and traits call for increasing investments in enhancing the computational efficiency of machine learning algorithms and computing resources.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, a one-step solvothermal method was applied to produce CuBi2O4/CuO heterojunctions containing nanocolumns with small platelike nanoparticles homogeneously distributed over its surface. The ...photocatalytic activity of the heterojunctions was evaluated through the photodegradation of Methylene Blue (MB) dye and Metronidazole (MTZ) under simulated solar light and visible light irradiation, respectively. The heterojunction CuBi2O4/CuO-b showed an enhanced photocatalytic performance with 98% removal of MB (@2 sun simulated solar irradiation) and 36% removal of MTZ (@1 sun visible light) within 60 min of irradiation, compared to the results obtained with the pristine materials (CuO and CuBi2O4) or the other composite synthesized CuBi2O4/CuO-a. The apparent quantum efficiency for MB photocatalytic degradation using the optimized photocatalyst and 180 min of light irradiation is ∼2.1%, under the excitation wavelength of 540 nm. This enhanced photocatalytic performance is a result of an effective charge separation through a type-II heterojunction, indicating that photoinduced electrons transfer from CuBi2O4 to CuO nanoparticles and the photoholes migrate in the opposite direction. The main reactive species responsible for the photocatalytic degradation of the organic pollutant molecules were the photogenerated holes. Finally, the best photocatalysts were reused and presented good stability over three cycles, endorsing their promise as candidates for photocatalytic applications.
•Bacillus subtilis isolates from Brazilian crude oils produce biosurfactants under reservoir conditions.•Sucrose was found to be the best carbon source for biosurfactant production.•Similar mixtures ...containing C13-, C14- and C15-surfactin were found for the biosurfactants produced.•Biosurfactants have better interfacial activity and lower critical micellar concentrations than chemical surfactants.•The produced biosurfactants are promising for Microbial Enhanced Oil Recovery applications.
Biosurfactant production by three Bacillus subtilis strains (#309, #311 and #573) isolated from Brazilian crude oils was optimized based on different carbon and nitrogen sources. The lowest surface tension values were obtained using sucrose containing media for the three isolates. Biosurfactants produced by each strain were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). The chemical characterization showed that the three isolates produced very similar mixtures, containing C13-, C14- and C15-surfactin, although in different proportions. The structure of surfactins produced by the three strains was shown to be in good agreement with their surface-activities. The interfacial-activities of the biosurfactants were characterized and compared with chemical surfactants. Furthermore, the application of biosurfactants and chemical surfactants in oil recovery was evaluated. The results obtained showed that biosurfactants have better interfacial-activity and oil recovery efficiency than common chemical surfactants, thus being more attractive to be applied in Microbial Enhanced Oil Recovery.
Dysbiosis, defined as unhealthy shifts in bacterial community composition, can lower the colonization resistance of the gut to intrinsic pathogens. Here, we determined the effect of diet age and type ...on the health and bacterial community composition of the honeybee (Apis mellifera). We fed newly emerged bees fresh or aged diets, and then recorded host development and bacterial community composition from four distinct regions of the hosts’ digestive tract. Feeding fresh pollen or fresh substitute, we found no difference in host mortality, diet consumption, development or microbial community composition. In contrast, bees fed aged diets suffered impaired development, increased mortality and developed a significantly dysbiotic microbiome. The consumption of aged diets resulted in a significant reduction in the core ileum bacterium Snodgrassella alvi and a corresponding increase in intrinsic pathogen Frischella perrara. Moreover, the relative abundance of S. alvi in the ileum was positively correlated with host survival and development. The inverse was true for both F. perrara and Parasacharibacter apium. Collectively, our findings suggest that the early establishment of S. alvi is associated with healthy nurse development and potentially excludes F. perrara and P. apium from the ileum. Although at low abundance, establishment of the common midgut pathogen Nosema spp. was significantly associated with ileum dysbiosis and associated host deficiencies. Moreover, dysbiosis in the ileum was reflected in the rectum, mouthparts and hypopharyngeal glands, suggesting a systemic host effect. Our findings demonstrate that typically occurring alterations in diet quality play a significant role in colony health and the establishment of a dysbiotic gut microbiome.
Homosalate (HMS) is a salicylate molecule that is commonly included within commercial sunscreen formulations to provide protection from the adverse effects of ultraviolet (UV) radiation exposure. In ...the present work, the mechanisms by which HMS provides UV photoprotection are unravelled, using a multi-pronged approach involving a combination of time-resolved ultrafast laser spectroscopy in the gas-phase and in solution, laser-induced fluorescence, steady-state absorption spectroscopy, and computational methods. The unique combination of these techniques allow us to show that the
enol
tautomer of HMS undergoes ultrafast excited state intramolecular proton transfer (ESIPT) upon photoexcitation in the UVB (290-320 nm) region; once in the
keto
tautomer, the excess energy is predominantly dissipated non-radiatively. Sharp transitions are observed in the LIF spectrum at close-to-origin excitation energies, which points towards the potential presence of a second conformer that does not undergo ESIPT. These studies demonstrate that, overall, HMS exhibits mostly favourable photophysical characteristics of a UV filter for inclusion in sunscreen formulations.
Homosalate has been found to exhibit favourable photophysics for inclusion in sunscreens, using a combination of spectroscopic and computational approaches.
Myc protooncogenes play important roles in the regulation of cell proliferation, growth, differentiation and survival during development. In various developing organs, c-myc has been shown to control ...the expression of cell cycle regulators and its misregulated expression is detected in many human tumors. Here, we show that c-myc gene (Myc) is highly expressed in developing mouse lens. Targeted deletion of c-myc gene from head surface ectoderm dramatically impaired ocular organogenesis, resulting in severe microphtalmia, defective anterior segment development, formation of a lens stalk and/or aphakia. In particular, lenses lacking c-myc presented thinner epithelial cell layer and growth impairment that was detectable soon after its inactivation. Defective development of c-myc-null lens was not caused by increased cell death of lens progenitor cells. Instead, c-myc loss reduced cell proliferation, what was associated with an ectopic expression of Prox1 and p27(Kip1) proteins within epithelial cells. Interestingly, a sharp decrease in the expression of the forkhead box transcription factor Foxe3 was also observed following c-myc inactivation. These data represent the first description of the physiological roles played by a Myc family member in mouse lens development. Our findings support the conclusion that c-myc regulates the proliferation of lens epithelial cells in vivo and may, directly or indirectly, modulate the expression of classical cell cycle regulators in developing mouse lens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our aim has been to evaluate the effect of cryoprotective agents (CPAs) on the exposure, vitrification (VIT), and in vitro culture (IVC) of ovarian tissue with regard to the expression and ...immunolocalization of aquaporins (AQPs) 3 and 9 in ovine preantral follicles. Tissues were treated as follows: Experiment I: (1) control (without exposure to CPAs), (2) e-EG (exposure to ethylene glycol), (3) er-EG (exposure to and removal of EG), (4) e-DMSO (exposure to dimethyl sulfoxide), (5) er-DMSO (exposure to and removal of DMSO), (6) e-EG+DMSO (exposure to EG+DMSO), (7) er-EG+DMSO (exposure to and removal of EG+DMSO); Experiment II: (1) control, (2) VIT, (3) IVC, (4) VIT-IVC. In Experiment I, following er-EG or er-DMSO, tissue showed the down-regulation (
P
< 0.05) of
AQP3
mRNA. The mRNA transcript levels were reduced (
P
< 0.05) for
AQP9
in tissue following er-EG+DMSO. Immunolocalization was positive for both proteins (AQP3 and AQP9) on ovine preantral follicles following all treatments, except in the e-EG+DMSO group. In Experiment II, the mRNA levels of
AQP3
and
AQP9
following VIT treatment were similar (
P
> 0.05) to that of the control group. Nevertheless, VIT-IVC treatment led to the down-regulation of mRNA of
AQP3
and
AQP9
. Thus, AQP3 and AQP9 act in a mutually dependent way, maintaining the cell homeostasis that is essential for the ovary cryopreservation process. Furthermore, the changes in the expression profiles of mRNA and protein after culture are a strong indicator that in vitro conditions have to be strictly controlled to ensure follicle viability and functionality.
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