Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is ...the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD accumulation in glia prior to or at the onset of neurodegeneration. The accumulated lipids are peroxidated in the presence of ROS. Reducing LD accumulation in glia and lipid peroxidation via targeted lipase overexpression and/or lowering ROS significantly delays the onset of neurodegeneration. Furthermore, a similar pathway leads to glial LD accumulation in Ndufs4 mutant mice with neuronal mitochondrial defects, suggesting that LD accumulation following mitochondrial dysfunction is an evolutionarily conserved phenomenon, and represents an early, transient indicator and promoter of neurodegenerative disease.
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•Lipid droplets (LD) are transient and occur prior to neurodegeneration in flies and mice•LD are present in glia and induced by neuronal increase of ROS, JNK, and SREBP•Reduction of ROS by antioxidants, lipases, or lower JNK or SREBP, delay degeneration•Neurodegeneration in mice with ROS/lipid droplets can be delayed with antioxidants
Lipid droplet accumulation in glial cells, driven by mitochondrial defects and ROS in neurons, contribute to neurodegeneration in a Drosophila model, with evidence of a conserved mechanism in mice.
B cells are responsible for protective antibody production after differentiation into antibody-secreting cells during humoral immune responses. From early B cell development in the bone marrow, to ...their maturation in the periphery, activation in the germinal center, and differentiation into plasma cells or memory B cells, B cells display ever-changing functions and properties. Autophagy and mitochondria play important roles in B cell development, activation, and differentiation to accommodate the phenotypic and environmental changes encountered over the lifetime of the cell. Among their many functions, mitochondria and autophagy generate energy, mediate cell survival, and produce/eliminate reactive oxygen species that can serve as signal molecules to regulate differentiation. As B cells mature and differentiate into plasma or memory cells, both autophagic and mitochondrial functions undergo significant changes. In this review, we aim to provide an overview of the role of the autophagosome and mitochondria in regulating B cell fate, survival, and function. Moreover, we will discuss the interplay between these two highly metabolic organelles during B cell development, maturation, and differentiation.
We analyze the determinants of adoption of distributed solar photovoltaic systems, focusing on small and medium-sized commercial and service firms. We use monthly billing data that are perfectly ...matched with data from a novel survey that gathers information on electricity consumption, stock of electric equipment, and a rich set of firm characteristics in the Metropolitan Area of Aguascalientes, Mexico. Using an econometric model, we find evidence that a set of explanatory variables such as business characteristics, the economic sector, ownership status, stock and usage of equipment and appliances, presence of other solar technologies, and views about the use of renewable energy are important determinants of the probability of adoption of solar panel systems. Furthermore, using machine learning methods to identify the best predictors of solar adoption, we indirectly validate the theory-driven empirical model by assessing a large set of explanatory variables and selecting a subset of these variables. In addition, we investigate relevant cases where a priori solar panel adoption seems to be cost-effective but structural adoption barriers and adoption gaps might coexist for certain groups of electricity users. We also calculate the social cost savings and the avoided CO2 emissions. Finally, based on our results, we provide several policy implications and recommendations.
•Determinants of solar panel adoption among small and medium-sized firms in Mexico.•Identify best predictors of solar panel adoption using machine learning.•Many non-adopter businesses could profitably invest in solar panels.•Ownership of the premises is a crucial factor for not installing solar panels.•Lack of information and financial resources are also notable key barriers.
Low-income energy efficiency programs have become a major component of cities’ energy policy, with 49 out of 51 largest metropolitan areas in the U.S. offering one. This paper uses data from ...Gainesville Regional Utility to quantify the impacts of the housing investment done by its Low-income Energy Efficiency Program Plus (LEEP Plus) on energy consumption. Our results show that LEEP Plus does not affect natural gas consumption but reduces electricity consumption by approximately 7%, with greater savings occurring in the summer and winter. The effect on electricity consumption is significant to a variety of robustness checks and remains for at least 24 months after the completion of energy efficiency upgrades. We also measure some relevant heterogeneous effects, one of which is the breakdown of the air-conditioning-related investments, the main energy efficiency improvement under the LEEP Plus program. Finally, we evaluate the energy savings in monetary terms considering the private cost changes and the social cost changes. In both cases, the associated energy savings are not enough to offset the investment costs.
A mitocentric view of Parkinson's disease Haelterman, Nele A; Yoon, Wan Hee; Sandoval, Hector ...
Annual review of neuroscience,
01/2014, Letnik:
37
Journal Article
Recenzirano
Odprti dostop
Parkinson's disease (PD) is a common neurodegenerative disease, yet the underlying causative molecular mechanisms are ill defined. Numerous observations based on drug studies and mutations in genes ...that cause PD point to a complex set of rather subtle mitochondrial defects that may be causative. Indeed, intensive investigation of these genes in model organisms has revealed roles in the electron transport chain, mitochondrial protein homeostasis, mitophagy, and the fusion and fission of mitochondria. Here, we attempt to synthesize results from experimental studies in diverse systems to define the precise function of these PD genes, as well as their interplay with other genes that affect mitochondrial function. We propose that subtle mitochondrial defects in combination with other insults trigger the onset and progression of disease, in both familial and idiopathic PD.
Consumers' attitudes about the direction of the economy influence their decisions about discretionary purchases, saving, and investment. This paper uses data from Florida's consumer sentiment index ...to study the role and accuracy of consumer confidence in forecasting consumption, as well as the mechanism behind such a relationship. Spending on durable goods tends to be more discretionary in nature and it is frequently done using credit, thus potentially more sensitive to changes in consumer attitudes. Our results indicate that the in‐sample predictive power of the index and its questions is limited to predicting spending on durable goods, particularly, on autos. Furthermore, consumer confidence does not improve the out‐of‐sample forecast beyond the forecast from a baseline model, which considers economic fundamentals. Finally, the evidence shows that the relationship between shocks in consumer confidence and economic activity arises because confidence measures contain information about the state of the economy, thus rejecting animal spirits.
Role of conservative management of stones Subramonian, Kesavapillai; Barba, Hector Sandoval; Darrad, Maitrey
Turkish journal of urology,
11/2020, Letnik:
46, Številka:
Supp. 1
Journal Article
Recenzirano
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Urinary tract stone disease is one of the most common pathologies of the modern era with a rising prevalence owing to incidentally detected renal stones from imaging for other reasons. Although there ...is consensus on active management of symptomatic and asymptomatic stones in high-risk patient groups, conservative management of stones is still controversial. We have reviewed the literature pertaining to conservative management of 3 groups of stones-asymptomatic calyceal stones, staghorn stones, and ureteric stones-and summarized the findings to provide guidance in the conservative management of stones. In the calyceal stone group, our review showed an average spontaneous stone passage rate of 18% (range, 8%-32%) and an average requirement for surgical intervention of 20% (range, 7%-40%), with 62% of patients remaining safely on surveillance over a mean time of 4 years. In the staghorn group, overall disease-specific mortality was noted to be 16% (range, 0%-30%) and chance of renal deterioration was 21% (range, 0%-34.5%), with a mean incidence of infection of 22%. In case of conservatively managed ureteric stones, the rate of spontaneous passage for stones smaller than 5 mm was 75%, compared with 62% for those larger than 5 mm. Based on the position in the ureter, spontaneous passage rates were 49%, 58%, and 68% for proximal, middle, and distal thirds, respectively. Conservative management may be recommended for asymptomatic patients and those who are deemed unfit for any procedures. However, careful patient selection and thorough counseling about the risks of conservative management could make it a suitable option for an appropriate subset of patients.
As a consequence of the COVID-19 pandemic, some patterns of energy consumption changed in the residential and non-residential sectors. This paper uses data from a local utility company in Florida to ...quantify the heterogeneous impacts of the pandemic on electricity and natural gas consumption across households from different income levels and across essential and non-essential businesses. We found significant increases in the average residential electricity consumption during the lockdown and subsequent reopening phases, which translate into higher cost for households. We found that natural gas consumption dropped abruptly in the business sector and also important differences between the electricity consumption of essential and non-essential businesses, with the former consuming more and the latter less electricity.
Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In ...a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac) mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs) in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC) that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj), causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis.
Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break ...self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.
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