Neuronal SKN-1B Modulates Nutritional Signalling Pathways and Mitochondrial Networks to Control Satiety

Correct responses to nutrient type and availability are a crucial mater for all living organisms. In animals, food-related decisions require the communication of the sensory nervous system with internal body cues. Hunger and satiety play an important role here, controlling food intake and maintaining nutrient homeostasis. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones, neurotransmitters, and neuropeptides. These responses have a direct impact in worms’ behaviour and physiology. This study shows that SKN-1B, an ortholog of the mammalian NF-E2 related transcription factors (Nrfs), acts in the two hypothalamus-like ASI chemosensory neurons to sense food, communicate nutritional status to the organism, and control food-related behaviours. SKN-1B modulates IIS and TGF-β pathways to suppress satiety-induced quiescence and promote exploratory behaviour. Finally, SKN-1B influences physiology by promoting a robust mitochondrial network which is required for energy homeostasis. The work presented here, suggests an exciting role for mammalian Nrf proteins in food-sensing and satiety

Influence of Intraocular Lens Asphericity and Blue Light Filtering on Visual Outcome, Contrast Sensitivity, and Aberrometry after Uneventful Cataract Extraction

Purpose: To evaluate the effect of asphericity and blue light filter (BLF) of three different intraocular lenses (IOLs) on the visual performance, second- and third-order aberrations (defocus, coma, trefoil), and contrast sensitivity after uneventful cataract surgery. Methods: One hundred and twenty eyes of 60 patients with clinically significant cataract were randomly assigned to receive one of the three IOL types: Bioline Yellow Accurate (aspheric, with BLF, i-medical, Germany), BioAcryl 60125 (spherical, without BLF, Biotech, France), and H65C/N (aspheric, without BLF, PhysIOL, Belgium). Each IOL was implanted in 40 eyes. Complete ophthalmologic examination, functional acuity contrast testing and wavefront analysis were performed 60 days postoperatively. Results: The mean postoperative best-corrected visual acuity (BCVA) was 0.95 ± 0.08, not differing statistically among the IOL groups (P = 0.83). Mean defocus and coma values did not yield any statistically significant difference through the IOL groups varying from –0.784 to –0.614 μm and 0.129 to 0.198 μm (P = 0.79 and 0.34, respectively). Bioline Yellow Accurate IOL presented less trefoil aberrations, 0.108 ± 0.05 μm, compared to the other two IOL types (BioAcryl [0.206 ± 0.19 μm] and Physiol [0.193 ± 0.17 μm], P < 0.05). Contrast sensitivity values did not differ among the groups under all lighting conditions. Bioline Yellow IOL showed a statistically higher loss of contrast sensitivity (between mesopic and mesopic with glare conditions) compared to the BioAcryl and PhysIOL in 12 and 3 cpd spatial frequencies, respectively (P < 0.05). Conclusion: Bioline Yellow IOL indicated lower contrast sensitivity under mesopic conditions when glare was applied but resulted in less trefoil aberrations after uneventful cataract surgery. No further differences were noted in postoperative visual performance among three IOL groups

Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors

The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases

Calculation of the Pressure Field for Turbulent Flow around a Surface-Mounted Cube Using the SIMPLE Algorithm and PIV Data

The calculation of the pressure field on and around solid bodies exposed to external flow is of paramount importance to a number of engineering applications. However, conventional pressure measurement techniques are inherently linked to problems principally caused by their point-wise and/or intrusive nature. In the present paper, we attempt to calculate a time-averaged two-dimensional pressure field by integrating PIV (particle image velocimetry) velocity measurements into a CFD code and modifying them by the respective correction step of the SIMPLE algorithm. Boundary conditions are applied from the PIV data as a three-layer area of constant velocities adjacent to the boundaries. A novel characteristic of the approach is the straightforward inclusion of the Reynolds stresses into the source terms of the momentum equations, calculated directly from the PIV statistics. The methodology is applied to three regions of the symmetry plane parallel to the main boundary layer flow past a surface-mounted cube. In spite of findings of deviations from the planar 2D flow assumption, the derived pressure fields and the adjusted velocity fields are found to be reliable, while the intrinsic turbulent nature of the flow is considered without modelling the Reynolds stresses

Influence of Intraocular Lens Asphericity and Blue Light Filtering on Visual Outcome, Contrast Sensitivity, and Aberrometry After Uneventful Cataract Extraction

Purpose: To evaluate the effect of asphericity and blue light filter (BLF) of three different intraocular lenses (IOLs) on the visual performance, second- and third-order aberrations (defocus, coma, trefoil), and contrast sensitivity after uneventful Cataract surgery. Methods: One hundred and twenty eyes of 60 patients with clinically significant Cataract were randomly assigned to receive one of the three IOL types: Bioline Yellow Accurate (aspheric, with BLF, i-medical, Germany), BioAcryl 60125 (spherical, without BLF, Biotech, France), and H65C/N (aspheric, without BLF, PhysIOL, Belgium). Each IOL was implanted in 40 eyes. Complete ophthalmologic examination, functional acuity contrast testing and wavefront analysis were performed 60 days postoperatively. Results: The mean postoperative best-corrected visual acuity (BCVA) was 0.95 ± 0.08, not differing statistically among the IOL groups (P = 0.83). Mean defocus and coma values did not yield any statistically significant difference through the IOL groups varying from –0.784 to –0.614 μm and 0.129 to 0.198 μm (P = 0.79 and 0.34, respectively). Bioline Yellow Accurate IOL presented less trefoil aberrations, 0.108 ± 0.05 μm, compared to the other two IOL types (BioAcryl [0.206 ± 0.19 μm] and Physiol [0.193 ± 0.17 μm], P < 0.05). Contrast sensitivity values did not differ among the groups under all lighting conditions. Bioline Yellow IOL showed a statistically higher loss of contrast sensitivity (between mesopic and mesopic with glare conditions) compared to the BioAcryl and PhysIOL in 12 and 3 cpd spatial frequencies, respectively (P < 0.05). Conclusion: Bioline Yellow IOL indicated lower contrast sensitivity under mesopic conditions when glare was applied but resulted in less trefoil aberrations after uneventful Cataract surgery. No further differences were noted in postoperative visual performance among three IOL groups

Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans

Summary: Fasting has emerged as a potent means of preserving tissue function with age in multiple model organisms. However, our understanding of the relationship between food removal and long-term health is incomplete. Here, we demonstrate that in the nematode worm Caenorhabditis elegans, a single period of early-life fasting is sufficient to selectively enhance HSF-1 activity, maintain proteostasis capacity and promote longevity without compromising fecundity. These effects persist even when food is returned, and are dependent on the mitochondrial sirtuin, SIR-2.2 and the H3K27me3 demethylase, JMJD-3.1. We find that increased HSF-1 activity upon fasting is associated with elevated SIR-2.2 levels, decreased mitochondrial copy number and reduced H3K27me3 levels at the promoters of HSF-1 target genes. Furthermore, consistent with our findings in worms, HSF-1 activity is also enhanced in muscle tissue from fasted mice, suggesting that the potentiation of HSF-1 is a conserved response to food withdrawal

Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety

The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins