Mahi-mahi (Coryphaena hippurus) life development: morphological, physiological, behavioral and molecular phenotypes.

BackgroundMahi-mahi (Coryphaena hippurus) is a commercially and ecologically important fish species that is widely distributed in tropical and subtropical waters. Biological attributes and reproductive capacities of mahi-mahi make it a tractable model for experimental studies. In this study, life development of cultured mahi-mahi from the zygote stage to adult has been described.ResultsA comprehensive developmental table has been created reporting development as primarily detailed observations of morphology. Additionally, physiological, behavioral, and molecular landmarks have been described to significantly contribute in the understanding of mahi life development.ConclusionRemarkably, despite the vast difference in adult size, many developmental landmarks of mahi map quite closely onto the development and growth of Zebrafish and other warm-water, active Teleost fishes

IKKbeta Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology

Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Abeta clearance. However, studies examining innate immunity in Abeta pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKbeta, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKbeta in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Abeta load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKbeta deficiency enhanced microglial recruitment to Abeta deposits and facilitated Abeta internalization, perhaps by inhibiting TGF-beta-SMAD2/3 signaling, but did not affect Abeta production and efflux. Therefore, inhibition of IKKbeta signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Abeta clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression

Sparse representations and harmonic wavelets for stochastic modeling and analysis of diverse structural systems and related excitations

In this thesis, novel analytical and computational approaches are proposed for addressing several topics in the field of random vibration. The first topic pertains to the stochastic response determination of systems with singular parameter matrices. Such systems appear, indicatively, when a redundant coordinate modeling scheme is adopted. This is often associated with computational cost-efficient solution frameworks and modeling flexibility for treating complex systems. Further, structures are subject to environmental excitations, such as ground motions, that typically exhibit non-stationary characteristics. In this regard, aiming at a joint time-frequency analysis of the system response a recently developed generalized harmonic wavelet (GHW)-based solution framework is employed in conjunction with tools originated form the generalized matrix inverse theory. This leads to a generalization of earlier excitation-response relationships of random vibration theory to account for systems with singular matrices. Harmonic wavelet-based statistical linearization techniques are also extended to nonlinear multi-degree-of-freedom (MDOF) systems with singular matrices. The accuracy of the herein proposed framework is further improved by circumventing previous “local stationarity” assumptions about the response. Furthermore, the applicability of the method is extended beyond redundant coordinate modeling applications. This is achieved by a formulation which accounts for generally constrained equations of motion pertaining to diverse engineering applications. These include, indicatively, energy harvesters with coupled electromechanical equations and oscillators subject to non-white excitations modeled via auxiliary filter equations. The second topic relates to the probabilistic modeling of excitation processes in the presence of missing data. In this regard, a compressive sampling methodology is developed for incomplete wind time-histories reconstruction and extrapolation in a single spatial dimension, as well as for related stochastic field statistics estimation. An alternative methodology based on low rank matrices and nuclear norm minimization is also developed for wind field extrapolation in two spatial dimensions. The proposed framework can be employed for monitoring of wind turbine systems utilizing information from a few measured locations as well as in the context of performance-based design optimization of structural systems. Lastly, the problem of with data-driven sparse identification methods of nonlinear dynamics is considered. In particular, utilizing measured responses a Bayesian compressive sampling technique is developed for determining the governing equations of stochastically excited structural systems exhibiting diverse nonlinear behaviors and also endowed with fractional derivative elements. Compared to alternative state-of-the-art schemes that yield deterministic estimates for the identified model, the herein developed methodology exhibits additional sparsity promoting features and is capable of quantifying the uncertainty associated with the model estimates. This provides a quantifiable degree of confidence when employing the proposed framework as a predictive tool

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

The effects of temperature acclimation on swimming performance in the pelagic Mahi-mahi (Coryphaena hippurus)

Mahi-mahi (Coryphaena hippurus) are a highly migratory pelagic fish, but little is known about what environmental factors drive their broad distribution. This study examined how temperature influences aerobic scope and swimming performance in mahi. Mahi were acclimated to four temperatures spanning their natural range (20, 24, 28, and 32{\deg}C; 5-27 days) and critical swimming speed (Ucrit), metabolic rates, aerobic scope, and optimal swim speed were measured. Aerobic scope and Ucrit were highest in 28{\deg}C-acclimated fish. 20{\deg}C-acclimated mahi experienced significantly decreased aerobic scope and Ucrit relative to 28{\deg}C-acclimated fish (57 and 28% declines, respectively). 32{\deg}C-acclimated mahi experienced increased mortality and a significant 23% decline in Ucrit, and a trend for a 26% decline in factorial aerobic scope relative to 28{\deg}C-acclimated fish. Absolute aerobic scope showed a similar pattern to factorial aerobic scope. Our results are generally in agreement with previously observed distribution patterns for wild fish. Although thermal performance can vary across life stages, the highest tested swim performance and aerobic scope found in the present study (28{\deg}C), aligns with recently observed habitat utilization patterns for wild mahi and could be relevant for climate change predictions.Comment: 24 pages, 3 figures main text, 6 figures supplemental text, published in Frontiers in Marine Science https://www.frontiersin.org/articles/10.3389/fmars.2021.654276/ful

Bayesian neural networks for predicting uncertainty in full-field material response

Stress and material deformation field predictions are among the most important tasks in computational mechanics. These predictions are typically made by solving the governing equations of continuum mechanics using finite element analysis, which can become computationally prohibitive considering complex microstructures and material behaviors. Machine learning (ML) methods offer potentially cost effective surrogates for these applications. However, existing ML surrogates are either limited to low-dimensional problems and/or do not provide uncertainty estimates in the predictions. This work proposes an ML surrogate framework for stress field prediction and uncertainty quantification for diverse materials microstructures. A modified Bayesian U-net architecture is employed to provide a data-driven image-to-image mapping from initial microstructure to stress field with prediction (epistemic) uncertainty estimates. The Bayesian posterior distributions for the U-net parameters are estimated using three state-of-the-art inference algorithms: the posterior sampling-based Hamiltonian Monte Carlo method and two variational approaches, the Monte-Carlo Dropout method and the Bayes by Backprop algorithm. A systematic comparison of the predictive accuracy and uncertainty estimates for these methods is performed for a fiber reinforced composite material and polycrystalline microstructure application. It is shown that the proposed methods yield predictions of high accuracy compared to the FEA solution, while uncertainty estimates depend on the inference approach. Generally, the Hamiltonian Monte Carlo and Bayes by Backprop methods provide consistent uncertainty estimates. Uncertainty estimates from Monte Carlo Dropout, on the other hand, are more difficult to interpret and depend strongly on the method\u27s design

Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease

Dual controlled delivery of squalenoyl-gemcitabine and paclitaxel using thermo-responsive polymeric micelles for pancreatic cancer

In this study we report the synthesis of a themroresponsive block copolymer by reversible addition fragmentation transfer polymerization comprising poly(2-ethylhexyl methacrylate)-b-poly[di(ethylene glycol)methyl ether methacrylate-co-oligo(ethylene glycol)methyl ether methacrylate] as hydrophobic and thermoresponsive blocks respectively. The polymer self-assembles into sub-50 micelles and can carry simultaneously two drug molecules, namely squalene-gemcitabine and paclitaxel. Both drugs can be released from the micellar compartment in a thermally controlled manner owing to the controllable disruption of the micellar corona above the lower critical solution temperature of the polymer. We demonstrate that the formulation augments synergistically the cytotoxicity of the two drugs in vitro against a model pancreatic cancer cell line. More importantly, it is shown that the polymer exerts a direct interaction with the cell membrane which further augments the cytotoxicity of the drug cargo in a thermally controlled manne

Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.</p