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In Alzheimer's disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild‐type and AD mutant human induced pluripotent stem cell (hiPSC)‐derived cerebrocortical neurons (hiN), evidence is found for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS). Isotope‐labeled metabolic flux experiments revealed a major block in activity in the tricarboxylic acid (TCA) cycle at the α‐ketoglutarate dehydrogenase (αKGDH)/succinyl coenzyme‐A synthetase step, metabolizing α‐ketoglutarate to succinate. Associated with this block, aberrant protein S‐nitrosylation of αKGDH subunits inhibited their enzyme function. This aberrant S‐nitrosylation is documented not only in AD‐hiN but also in postmortem human AD brains versus controls, as assessed by two separate unbiased mass spectrometry platforms using both SNOTRAP identification of S‐nitrosothiols and chemoselective‐enrichment of S‐nitrosoproteins. Treatment with dimethyl succinate, a cell‐permeable derivative of a TCA substrate downstream to the block, resulted in partial rescue of mitochondrial bioenergetic function as well as reversal of synapse loss in AD‐hiN. These findings have therapeutic implications that rescue of mitochondrial energy metabolism can ameliorate synaptic loss in hiPSC‐based models of AD. Using human induced pluripotent stem cell (hiPSC)‐derived neurons and postmortem human Alzheimer's disease (AD) brains, the current study links aberrant S‐nitrosylation of tricarboxylic acid (TCA) cycle enzymes to a block in the TCA cycle, compromising energy production. Treatment with a TCA‐cycle substrate to bypass the block partially rescues mitochondrial bioenergetics and synapse loss, suggesting a future therapeutic avenue for AD.

We hypothesized that near-future elevated CO2 would affect the antipredatory behavior of two freshwater organisms; a pulmonate gastropod (Physella columbiana) and a cladoceran crustacean (Daphnia magna). Studies have found that pCO2 and increased acidification due to CO2 impedes fright responses to predators by activating GABAA receptors. After administration of predator-derived kairomones and conspecific alarm cues, we also briefly exposed some of the animals to gabazine which is a GABAA receptor antagonist to restore a fright response. We found that added carbon dioxide negatively affected the antipredatory behavior of both species but gabazine did not reverse this effect. To further examine the effect of CO2 and gabazine, we also tested the effect of stressful crowding, cold, and acidic conditions on the production of male daphnid offspring. An increase in ratio of male to female offspring is a common and expected response to stress by daphnids. We found that stress increased the production of males and gabazine reversed this at a pH of 5.5 but not at pH 6.2 or 6.5. Our study suggest that while the main negative effects of anthropogenic CO2 enrichment can be robust, the myriad indirect effects of CO2 make predictions about future predator prey systems less clear.

Background Preeclampsia and HIV account for a significant proportion of the global burden of disease and pose severe maternal–fetal risks. There is a dearth of literature regarding racial/ethnic disparities in preeclampsia associated with HIV/AIDS in the US. Methods We retrospectively analyzed data from the National Inpatient Sample (NIS) database from 2002 to 2015 on a cohort of hospitalized pregnant women with or without preeclampsia and HIV. Joinpoint regression models were used to identify trends in the rates of preeclampsia among pregnant women living with or without HIV, stratified by race/ethnicity over the study period. We also assessed the association between preeclampsia and various socio-demographic factors. Results We analyzed over 60 million pregnancy-related hospitalizations, of which 3665 had diagnoses of preeclampsia and HIV, corresponding to a rate of 0.61 per 10,000. There was an increasing trend in the diagnosis of preeclampsia among hospitalized, pregnant women without HIV across each racial/ethnic category. The highest prevalence of preeclampsia was among non-Hispanic (NH) Blacks, regardless of HIV status. Conclusion The increase in rates of pre-eclampsia between 2002 and 2015 was mostly noted among pregnant women without HIV. Regardless of HIV status, NH-Blacks experienced the highest discharge prevalence of preeclampsia.

CREB-regulated transcription coactivator 1 (CRTC1) plays an important role in synaptic plasticity, learning and long-term memory formation through regulation of neuronal activity-dependent gene expression, and CRTC1 dysregulation is implicated in Alzheimer’s disease (AD). Here, we show that increased S-nitrosylation of CRTC1 (forming SNO-CRTC1), as seen in cell-based, animal-based, and human induced pluripotent stem cell (hiPSC)-derived cerebrocortical neuron-based AD models, disrupts its binding with CREB and diminishes the activity-dependent gene expression mediated by the CRTC1/CREB pathway. We identified Cys216 of CRTC1 as the primary target of S-nitrosylation by nitric oxide (NO)-related species. Using CRISPR/Cas9 techniques, we mutated Cys216 to Ala in hiPSC-derived cerebrocortical neurons bearing one allele of the APPSwe mutation (AD-hiPSC neurons). Introduction of this non-nitrosylatable CRTC1 construct rescued defects in AD-hiPSC neurons, including decreased neurite length and increased neuronal cell death. Additionally, expression of non-nitrosylatable CRTC1 in vivo in the hippocampus rescued synaptic plasticity in the form of long-term potentiation (LTP) in 5XFAD mice. Taken together, these results demonstrate that formation of SNO-CRTC1 contributes to the pathogenesis of AD by attenuating the neuronal activity-dependent CREB transcriptional pathway, and suggests a novel therapeutic target for AD.

In Alzheimer’s disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild-type and AD mutant human induced pluripotent stem cell (hiPSC)-derived cerebrocortical neurons (hiN), we found evidence for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS). Isotope-labeled metabolic flux experiments revealed a major block in activity in the tricarboxylic acid (TCA) cycle at the α-ketoglutarate dehydrogenase (αKGDH)/succinyl coenzyme-A synthetase step, metabolizing α-ketoglutarate to succinate. Associated with this block we found aberrant protein S-nitrosylation of αKGDH subunits that are known to inhibit enzyme function. This aberrant S-nitrosylation was documented not only in AD-hiN but also in postmortem human AD brains vs. controls, as assessed by two separate unbiased mass spectrometry platforms using both SNOTRAP identification of S-nitrosothiols and chemoselective-enrichment of S-nitrosoproteins. Treatment with dimethyl succinate, a cell-permeable derivative of a TCA substrate (downstream to the block, resulted in partial rescue of mitochondrial bioenergetic function as well as reversal of synapse loss in AD-hiN. Our findings have therapeutic implications that rescue of mitochondrial energy metabolism can ameliorate synaptic loss in hiPSC-based models of AD.

At present, modern society is experiencing a significant transformation. Thanks to the digitization of society and manufacturing, mainly because of a combination of technologies, such as the Internet of Things, cloud computing, machine learning, smart cyber-physical systems, etc., which are making the smart factory and Industry 4.0 a reality. Currently, most of the intelligence of smart cyber-physical systems is implemented in software. For this reason, in this work, we focused on the artificial intelligence software design of this technology, one of the most complex and critical. This research aimed to study and compare the performance of a multilayer perceptron artificial neural network designed for solving the problem of character recognition in three implementation technologies: personal computers, cloud computing environments, and smart cyber-physical systems. After training and testing the multilayer perceptron, training time and accuracy tests showed each technology has particular characteristics and performance. Nevertheless, the three technologies have a similar performance of 97% accuracy, despite a difference in the training time. The results show that the artificial intelligence embedded in fog technology is a promising alternative for developing smart cyber-physical systems.

Higher temperatures lead to an increase of testicular metabolism that results in spermatic damage. Oxidative stress is the main factor responsible for testicular damage caused by heat stress. The aim of this study was to evaluate lasting effects of heat stress on ejaculated sperm and immediate or long-term effects of heat stress on epididymal sperm. We observed decrease in motility and mass motility of ejaculated sperm, as well as an increase in the percentages of sperm showing major and minor defects, damaged plasma and acrosome membranes, and a decrease in the percentage of sperm with high mitochondrial membrane potential in the treated group until one spermatic cycle. An increased enzymatic activity of glutathione peroxidase and an increase of stressed cells were observed in ejaculated sperm of the treated group. A decrease in the percentage of epididymal sperm with high mitochondrial membrane potential was observed in the treated group. However, when comparing immediate and long-term effects, we observed an increase in the percentage of sperm with low mitochondrial membrane potential. In conclusion, testicular heat stress induced oxidative stress that led to rescuable alterations after one spermatic cycle in ejaculated sperm and also after 30 days in epididymal sperm.

This work presents the development of a web system using deep learning (DL) neural networks to solve the inverse kinematics problem of the Quetzal robotic arm, designed for academic and research purposes. Two architectures, LSTM and CNN, were designed, trained, and evaluated using data generated through the Denavit–Hartenberg (D-H) model, considering the robot’s workspace. The evaluation employed the mean squared error (MSE) as the loss metric and mean absolute error (MAE) and accuracy as performance metrics. The CNN model, featuring four convolutional layers and an input of 4 timesteps, achieved the best overall performance (95.9% accuracy, MSE of 0.003, and MAE of 0.040), significantly outperforming the LSTM model in training time. A hybrid web application was implemented, allowing offline training and real-time online inference under one second via an interactive interface developed with Streamlit 1.16. The solution integrates tools such as TensorFlow™ 2.15, Python 3.10, and Anaconda Distribution 2023.03-1, ensuring portability to fog or cloud computing environments. The proposed system stands out for its fast response times (1 s), low computational cost, and high scalability to collaborative robotics environments. It is a viable alternative for applications in educational or research settings, particularly in projects focused on industrial automation.

The genus Flavivirus encompasses several worldwide-distributed arthropod-borne viruses including, dengue virus, Japanese encephalitis virus, West Nile virus, yellow fever virus, Zika virus, and tick-borne encephalitis virus. Infection with these viruses manifest with symptoms ranging from febrile illness to life- threatening hypotensive shock and encephalitis. Therefore, flaviviruses pose a great risk to public health. Currently, preventive measures are falling short to control epidemics and there are no antivirals against any Flavivirus . Flaviviruses carry a single stranded positive-sense RNA genome that plays multiple roles in infected cells: it is translated into viral proteins, used as template for genome replication, it is the precursor of the subgenomic flaviviral RNA and it is assembled into new virions. Furthermore, viral RNA genomes are also packaged into extracellular vesicles, e.g. exosomes, which represent an alternate mode of virus dissemination. Because RNA molecules are at the center of Flavivirus replication cycle, viral and host RNA-binding proteins (RBPs) are critical determinants of infection. Numerous studies have revealed the function of RBPs during Flavivirus infection, particularly at the level of RNA translation and replication. These proteins, however, are also critical participants at the late stages of the replication cycle. Here we revise the function of host RBPs and the viral proteins capsid, NS2A and NS3, during the packaging of viral RNA and the assembly of new virus particles. Furthermore, we go through the evidence pointing towards the importance of host RBPs in mediating cellular RNA export with the idea that the biogenesis of exosomes harboring Flavivirus RNA would follow an analogous pathway.

Background Some breeds of sheep are highly seasonal in terms of reproductive capability, and these changes are regulated by photoperiod and melatonin secretion. These changes affect the reproductive performance of rams, impairing semen quality and modifying hormonal profiles. Also, the antioxidant defence systems seem to be modulated by melatonin secretion, and shows seasonal variations. The aim of this study was to investigate the presence of melatonin and testosterone in ram seminal plasma and their variations between the breeding and non-breeding seasons. In addition, we analyzed the possible correlations between these hormones and the antioxidant enzyme defence system activity. Methods Seminal plasma from nine Rasa Aragonesa rams were collected for one year, and their levels of melatonin, testosterone, superoxide dismutase (SOD), glutathione reductase (GRD), glutathione peroxidase (GPX) and catalase (CAT) were measured. Results All samples presented measurable quantities of hormones and antioxidant enzymes. Both hormones showed monthly variations, with a decrease after the winter solstice and a rise after the summer solstice that reached the maximum levels in October-November, and a marked seasonal variation (P < 0.01) with higher levels in the breeding season. The yearly pattern of GRD and catalase was close to that of melatonin, and GRD showed a significant seasonal variation (P < 0.01) with a higher activity during the breeding season. Linear regression analysis between the studied hormones and antioxidant enzymes showed a significant correlation between melatonin and testosterone, GRD, SOD and catalase. Conclusions These results show the presence of melatonin and testosterone in ram seminal plasma, and that both hormones have seasonal variations, and support the idea that seasonal variations of fertility in the ram involve interplay between melatonin and the antioxidant defence system.