Non-Visual Effects of Light on Melatonin, Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance

Circadian regulation of human cortical excitability

peer reviewe

AMA0076, a Novel, Locally Acting Rho Kinase Inhibitor, Potently Lowers Intraocular Pressure in New Zealand White Rabbits with Minimal Hyperemia

PURPOSE. To determine whether ROCK inhibition for the treatment of glaucoma can be improved by using novel, locally acting Rho kinase (ROCK) inhibitors, such as AMA0076, that lower IOP without inducing hyperemia. METHODS. On-target potency of AMA0076 was compared with other ROCK inhibitors (Y-27632 and Y-39983) and conversion of AMA0076 into its functionally inactive metabolite was evaluated in rabbit eye tissues. Human trabecular meshwork (HTM) cell morphology, actin filaments, and focal adhesion were studied in vitro after exposure to AMA0076. The effect of AMA0076 on IOP was investigated in normotensive rabbits and a new, acute hypertensive rabbit model. Intraocular pressure lowering efficacy of AMA0076 was compared with pharmacologic treatments. Hyperemia after single topical dosing of AMA0076 and Y-39983 was scored. RESULTS. AMA0076 and Y-39983 showed similar on-target potency. AMA0076 was most stable in aqueous humor and converted into its metabolite in other eye tissues. Exposure of HTM cells to AMA0076 led to significant and reversible changes in cell shape and a decrease in actin stress fibers and focal adhesions. Both AMA0076 and Y-39983 provided an equivalent IOP control. Compared with latanoprost and bimatoprost, AMA0076 was more potent in preventing the IOP elevation in the acute hypertensive rabbit model. The degree of hyperemia was significantly lower in rabbits treated with AMA0076 then with Y-39983. CONCLUSIONS. AMA0076 is a locally acting ROCK inhibitor that is able to induce altered cellular behavior of HTM cells. Administration of AMA0076 effectively reduces IOP in ocular normotensive and acute hypertensive rabbits without causing distinct hyperemia

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α–dependent microRNA (miR)–210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210–based therapeutic and diagnostic strategies

Neuronal excitation/inhibition balance is set by the need for sleep and the biological clock

peer reviewe

Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis

Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change

Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks

Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However,much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states

Quantitatively mimicking wet colloidal suspensions with dry granular media

Athermal two-dimensional granular systems are exposed to external mechanical noise leading to Brownian-like motion. Using tunable repulsive interparticle interaction, it is shown that the same microstructure as that observed in colloidal suspensions can be quantitatively recovered at a macroscopic scale. To that end, experiments on granular and colloidal systems made up of magnetized particles as well as computer simulations are performed and compared. Excellent agreement throughout the range of the magnetic coupling parameter Γ is found for the pair distribution as well as the bond-orientational correlation functions. This finding opens new ways to efficiently and very conveniently explore phase transitions, crystallization, nucleation, etc in confined geometries

Navigating the Perinatal Maze: Professionals' perspectives on the Perinatal Period as a Window of Opportunity in Women with Substance Use Problems

Introduction: Recent research has illuminated the perinatal period’s potential as a transformative opportunity for positive change and recovery for women grappling with substance use (SU) and their families, despite the well-documented challenges associated with SU, pregnancy, and parenting. Recognizing the pivotal role of this period, this study aims to delve deeper into its complexities, drawing insights from a diverse array of professionals. Aim of the study: This study aimed to gather perspectives from professionals working across various sectors, including healthcare, addiction rehabilitation, and youth welfare. The goal is to offer a nuanced understanding of the challenges and opportunities during this critical phase, identifying gaps in current practices to inform targeted interventions and policy initiatives, ultimately aiming to enhance support systems and improve outcomes for the vulnerable population affected by SU. Material and Methods: We conducted 39 in-depth interviews with 44 professionals who work with (expecting) mothers with SU problems or children of substance-using parents in Flanders (Belgium). Participants were recruited from various sectors, including healthcare, addiction rehabilitation, organizations within Youth Welfare and Public Social Welfare Centers, using a snowball-sampling approach. Semi-structured interviews were employed to allow in-depth exploration of participant’s perspectives and experiences. Conclusions: Autonomous and controlled motivational factors underscored the importance of the perinatal period for women with SU. Structural and practical factors, such as prenatal follow-up appointments, facilitated care pathways. Early intervention during pregnancy was cited as crucial for aligning caregivers with expectant parents' pace, building trust, managing complex care, and providing psychoeducation. However, discussions with professionals revealed challenges in early care admission that extended beyond structural barriers: the significance of both types of negated pregnancies was highlighted. Lastly, the perinatal period proved variable in its impact, not universally transformative. Stress, fear, shame, and fatigue sometimes led to increased substance use or relapse. Additionally, unresolved childhood issues made recovery during this period particularly difficult for some women

A finite-element reciprocity solution for EEG forward modeling with realistic individual head models

Highlights • Creates EEG forward models suitable for high-resolution source localization. • Automatic T1-based whole-head finite element meshing and leadfield computation. • Pipelines can incorporate conductivity tensors from diffusion-weighted images. • Open-source toolbox shared under a permissive software license. • Accuracy comparable to SimBio FEM and superior to OpenMEEG BEM solutions