Browse Articles

Fungal effector disables cathepsin-driven Toll immunity in insects

Plasma attenuates endothelial injury compared to crystalloids in a ventilated rat pneumosepsis model

Background The dysregulated immune response during sepsis involves endothelial injury, which may be augmented by infusion of clear fluids such as crystalloids. Plasma has been suggested as an alternative resuscitation fluid but it is unclear whether previously observed benefits were due to the type of fluid, or due to less volume required to restore tissue perfusion. We hypothesized that resuscitation with plasma reduces endothelial injury, inflammation, and organ injury compared to similar and higher volumes of crystalloids in a rat pneumosepsis model. Methods Rats were intratracheally inoculated with Streptococcus Pneumoniae to induce pneumosepsis. Twenty-four hours after inoculation, animals were randomized to 4 groups: healthy controls (non-resuscitated, n = 6), 10 ml/kg/hr (standard-volume, n = 11) crystalloid resuscitation, 3.33 ml/kg/hr (low-volume, n = 11) crystalloid resuscitation or 3.33 ml/kg/hr plasma resuscitation (n = 11). Plasma markers of inflammation and endothelial injury were measured. Organs were harvested for histology and wet-to-dry weight ratio determination. Results Inoculated animals developed pneumosepsis, with lower mean arterial pressures (p < 0.001) and higher lactate levels (p < 0.001) compared to healthy controls. Animals resuscitated with plasma showed a trend towards lower syndecan-1 levels compared to the standard-volume crystalloid group (82 vs 99 ng/mL, p = 0.06) and had lower levels of VCAM-1 (424 vs 592 ng/mL, p < 0.01) compared to the standard volume crystalloid group, but not when compared to the low-volume crystalloid group. Other markers of endothelial injury or inflammation were not significantly different between groups. No significant differences were observed in histologic injury scores and wet-to-dry ratios. Conclusion Plasma resuscitation modestly reduces endothelial injury compared to crystalloid resuscitation. This effect might be attributed to decreased resuscitation volumes rather than the type of fluid.

Sleep and stress in athletes with disabilities around the 2021 Tokyo Paralympic games during the pandemic

Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR

G protein–coupled receptors (GPCRs) modulate various physiological functions by rewiring cellular gene expression in response to extracellular signals. Control of gene expression by GPCRs has been studied almost exclusively at the transcriptional level, neglecting an extensive amount of regulation that takes place translationally. Hence, little is known about the nature and mechanisms of gene-specific posttranscriptional regulation downstream of receptor activation. Here, we apply an unbiased multiomics approach to delineate an extensive translational regulatory program initiated by the prototypical beta2-adrenergic receptor (β2-AR) and provide mechanistic insights into how these processes are orchestrated. Using ribosome profiling (Ribo-seq), we identify nearly 120 gene targets of adrenergic receptor activity for which expression is exclusively regulated at the level of translation. We next show that all translational changes are induced selectively by endosomal β2-ARs and report that this proceeds through activation of the mammalian target of rapamycin (mTOR) pathway. Specifically, within the set of translational GPCR targets, we find significant enrichment of genes with 5’ terminal oligopyrimidine (TOP) motifs, a gene class classically known to be translationally regulated by mTOR. We then demonstrate that endosomal β2-ARs are required for mTOR activation and subsequent mTOR-dependent TOP mRNA translation. This site-selective crosstalk between the pathways is observed in multiple cell models with native β2-ARs, across a range of endogenous and synthetic adrenergic agonists, and for other GPCRs with intracellular activity. Together, this comprehensive analysis of drug-induced translational regulation establishes a critical role for location-biased GPCR signaling in fine-tuning the cellular protein landscape.

Transcriptomic adaptation of skeletal muscle in response to MICT and HIIT exercise modalities

Skeletal muscle exhibits remarkable plasticity in response to diverse stimuli, with exercise serving as a potent trigger. Varied exercise modalities, including moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), induce distinct structural and functional adaptations on skeletal muscle. However, the underlying molecular mechanisms governing these adaptations remain poorly understood. In this study, we utilized RNA-seq to characterize the transcriptomic profile of murine gastrocnemius muscle following 8-week treadmill-based MICT (M group) and HIIT (H group). A total of 1052 DEGs were screened in H vs. M. Among the top 10 significant DEGs, Foxo1 and Myod1 are closely related to muscular physiology. Through KEGG pathway analysis, distinct adaptations were primarily identified in the FoxO, MAPK, and PI3K-AKT pathways. By analyzing the expression of myokines, a significantly higher Igf-1 expression level was observed in the M group compared to the H group. Therefore, IGF-1, a well-known upstream regulator of both the PI3K-AKT-FoxO and MAPK pathways, might drive distinct muscle adaptations through variations in Igf-1 expression induced by these two exercise modalities.

Publisher Correction: Study on performance of perforated dew point indirect evaporative coolers

Viral circular RNA–encoded protein, ceVP28, divulges an antiviral response in invertebrates

Invertebrates mostly use innate immunity to counteract pathogenic infections. In this study, shrimp was used as a model organism to explore the functions of circular RNAs (circRNAs) derived from white spot syndrome virus (WSSV). We identified four viral circRNAs, termed circWSSV147, circWSSV326, circWSSV458, and circVP28, from transcriptomic data of WSSV-infected shrimp. CircVP28, which contains an internal ribosome entry site, was further characterized to determine its potential as a template for protein translation. We observed the presence of a truncated, circRNA-encoded VP28 (ceVP28) in infected shrimp. Both ceVP28 and its parental counterpart, VP28, share the same host cell binding partner Rab7, which is a host receptor for WSSV. Coadministration of recombinant ceVP28 protein and WSSV to penaeid shrimps reduced both viral copy numbers and mortality upon WSSV challenges. These findings uncovered a host defense mechanism by which a protein encoded by a viral circRNA modulates virus–receptor interactions, resulting in blocking of viral entry.

Chemical composition and biological activity of lemongrass volatile oil and n-Hexane extract: GC/MS analysis, in vitro and molecular modelling studies

Lemon grass, formally identified as Cymbopogon citratus, is a plant that belongs to the Poaceae family. The present work aimed to examine the chemical composition by GC/MS analysis and assess the biological potential of C. citratus volatile oil and n-hexane extract. The volatile oil and n-hexane extract were evaluated for antioxidant potential and tested for their enzyme inhibition against tyrosinase, butyrylcholinesterase (BChE), acetylcholinesterase (AChE), α-amylase, and α-glucosidase. The chemical analysis of the lemongrass n-hexane extract (HE) and volatile oil (VO) revealed that the main constituents in the HE are aliphatic hydrocarbons (42.98%), triterpenoids (20.14%), and aromatic hydrocarbons (17.25%). Conversely, the main constituents of the (VO) are predominantly monoterpenes, namely α-citral (36.08%), β-citral (34.22%), and β-myrcene (13.84%). The oil showed more potent antioxidant potential in DPPH, ABTS, CUPRAC, FRAP, and phosphomolybdenum (10.18, 35.69 mg Trolox equivalent/g, 98.97 and 69.73 mg Trolox equivalent/g and 43.01 mmol Trolox equivalent/g). The HE displayed higher BChE (1.53 mg Galanthamine equivalent)/g), as well as α-amylase and α-glucosidase inhibitory activities (0.39 and 2.40 mmol Acarbose equivalent/g). The VO demonstrated more potent tyrosinase inhibitory activities (57.19 mg Kojic acid equivalent/g) along with acetyl and butyrylcholinesterase inhibition. Dominant compounds exhibited the ability to bind with high affinity to various target proteins, with a particular affinity for AChE and BChE. The volatile oil and n-hexane extract of C. citratus show significant promise as a viable choice for the advancement of novel therapeutic strategies aimed at addressing oxidative stress, neurodegeneration, and diabetes.

Optimizing black cattle tracking in complex open ranch environments using YOLOv8 embedded multi-camera system

Independent effects of the human circadian system and sleep/eating cycles on caloric intake in adolescents vary by weight status

Late-day eating is linked to increased obesity risk; however, whether the endogenous circadian system independently influences caloric intake and if this control differs among individuals based on weight status is unknown. Here, we investigated in adolescents the independent roles of the endogenous circadian system and of the behavioral sleep/wake cycle (sleep/wake, fasting/eating, rest/activity, dark/dim light, social interaction, posture, etc.) on self-selected caloric intake using a Forced Desynchrony protocol. Fifty-one male and female adolescents across three weight status categories (24 with healthy weight, 13 with overweight, and 14 with obesity) completed the protocol where participants lived on seven 28-h sleep/wake cycles in dim light during wake and complete darkness during sleep. Results suggest that the circadian system and the behavioral cycle each affected caloric intake, with a decrease across the wake episode and an increase from circadian morning to circadian evening in caloric intake. The endogenous circadian rhythm in caloric intake showed a circadian peak-to-trough difference of 196 [CI 95% 164, 226] kcal per meal with peak timing of 296° [288°, 304°; equivalent to ~17:30 in these participants]. In those with overweight/obesity, more calories were consumed later in the waking episode and later in the circadian cycle, and with blunted amplitudes compared to those with healthy weight. Results implicate both the endogenous circadian system and the behavioral cycle in shaping the daily rhythm of food intake. Furthermore, these results help explain the increased drive for caloric intake toward the evening, especially in those at risk for obesity.

Differential expression and modulation of EBI2 and 7α,25-OHC synthesizing (CH25H, CYP7B1) and degrading (HSD3B7) enzymes in mouse and human brain vascular cells

The endogenous ligand for the EBI2 receptor, oxysterol 7α,25OHC, crucial for immune responses, is finely regulated by CH25H, CYP7B1 and HSD3B7 enzymes. Lymphoid stromal cells and follicular dendritic cells within T cell follicles maintain a gradient of 7α,25OHC, with stromal cells increasing and dendritic cells decreasing its concentration. This gradient is pivotal for proper B cell positioning in lymphoid tissue. In the animal model of multiple sclerosis, the experimental autoimmune encephalomyelitis, the levels of 7α,25OHC rapidly increase in the central nervous system driving the migration of EBI2 expressing immune cells through the blood-brain barrier (BBB). To explore if blood vessel cells in the brain express these enzymes, we examined normal mouse brain microvessels and studied changes in their expression during inflammation. Ebi2 was abundantly expressed in endothelial cells, pericytes/smooth muscle cells, and astrocytic endfeet. Ch25h, Cyp7b1, and Hsd3b7 were variably detected in each cell type, suggesting their active involvement in oxysterol 7α,25OHC synthesis and gradient maintenance under normal conditions. Significant species-specific differences emerged in EBI2 and the enzyme levels between mouse and human BBB-forming cells. Under acute inflammatory conditions, Ebi2 and synthesizing enzyme modulation occurred in the brain, with the magnitude and direction of change based on the enzyme. Lastly, in an in vitro astrocyte migration model, CYP7B1 inhibitor clotrimazole, as well as EBI2 antagonist, NIBR189, inhibited lipopolysaccharide-induced cell migration indicating the involvement of EBI2 and its ligand in brain cell migration under inflammatory conditions.

Relationship between serum homocysteine, folate and vitamin B12 levels and cognitive function in patients with drug-naive obsessive-compulsive disorder

Modeling energy requirements for oxygen production on the Moon

Spacecraft using combustion engines require substantial amounts of oxygen for their propellant. The Moon could be a source of oxygen for rocket propellant, since the material composing the lunar surface can be processed to extract oxygen. However, little is known about overall energy requirements of the processes described in the literature for oxygen extraction from lunar regolith. This knowledge gap constrains the planning of lunar missions, since the scale of energy infrastructure required for oxygen production facilities is not well characterized. This study presents an energy consumption model for oxygen production via hydrogen reduction of the mineral ilmenite (FeTiO 3 ). We consider an end-to-end production chain starting from dry regolith as the feedstock. The production includes the following process steps: excavation, transportation, beneficiation, hydrogen reduction, water electrolysis, liquefaction, and zero boil-off storage. The model predicts the energy demand per kilogram oxygen produced based on adjustable parameters for each process step. As expected, the model indicates a strong dependence on feedstock composition. For regolith composed of 10 wt% ilmenite, the model predicts that a total of 24.3 (± 5.8) kWh is needed per kg of liquid oxygen produced. This study confirms that the hydrogen reduction and electrolysis steps have the highest energy requirements in the production chain. Sensitivity analysis reveals that the enrichment factor of the beneficiation process is the most critical parameter for optimizing energy utilization. Overall, this study provides a parameterized end-to-end model of energy consumption that can serve as a foundation for various production systems on the Moon.

Co-representation breaks down beyond the dyad in UK adults

Cooperation is so deeply embedded in human psychology that we spontaneously track a partner’s task as well as our own when acting in a pair. This automatic ‘co-representation’ of a partner’s mental representation of their task has been argued to be key to the sophisticated social coordination we see in human adults. However, our day-to-day encounters are not limited to one-to-one interactions. This is the first published study to investigate co-representation in groups, with results from a group Joint Simon task suggesting that co-representation may break down in groups larger than two. Exploratory analyses also suggested a complex interplay between spatial and social relationships between individual members within a group. We propose a novel hypothesis based on these findings: when we lack the capacity to track everyone in a group, we may be able to selectively track those who are the most salient or relevant. This provides key information about the limits of our capacity to keep others in mind, and the psychological underpinnings of how we do so.

Cross-linking of fungal β-glucosidase on Al2O3 nanocrystals synthesized using Cajanus cajan L. Millsp. extracts for in suit genistein manufacture

Simple genetic mechanisms toward more intricate molecular complexes

Enhancing anesthetic techniques for improving whisker stimulation response in the barrel cortex

This study adopts and validates an anesthetic protocol designed for rat whisker stimulation experiments, achieving significant enhancements in the neural response of the barrel field cortex. By combining alpha-chloralose, low-dose Isoflurane (0.5%) and Dexdomitor, the protocol not only maintains a stable anesthetic state but also markedly improves the amplitude and latency of local field potential (LFP) signals. Experimental results reveal that LFP amplitudes in the barrel field under this protocol are twice as high as those achieved with Isoflurane and four times as high as those with Ketamine-Xylazine, with significantly shortened latencies and reduced noise interference. For the first time, power spectral analysis reveals a distinct enhancement of oscillatory power in the alpha (8–13 Hz) and beta (13–30 Hz) bands under alpha-chloralose anesthesia, diverging from the traditional dominance of delta (0.5–4 Hz) oscillations observed with other anesthetics. Mechanistically, this phenomenon may be attributed to alpha-chloralose’s unique modulation of GABAergic and glutamatergic pathways, promoting cortical desynchronization and enhanced sensory processing. This protocol offers new insights into optimizing sensory-evoked neural signal acquisition and provides a reference for future studies exploring neural modulation in sensory neuroscience.

Preparation and characterization of active packaging film containing chitosan/gelatin/brassica crude extract

PSKH1 kinase activity is differentially modulated via allosteric binding of Ca ²⁺ sensor proteins

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we used biochemistry and mass spectrometry to define PSKH1’s consensus substrate motif, protein interactors, and how interactors, including Ca 2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca 2+ -Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca 2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In addition to antagonistic regulation of the PSKH1 kinase domain by Ca 2+ sensing proteins, we identified UNC119B as a protein interactor that activates PSKH1 via direct engagement of the kinase domain. Our findings identify complementary allosteric mechanisms by which regulatory proteins tune PSKH1’s catalytic activity and raise the possibility that different Ca 2+ sensors may act more broadly to tune kinase activities by detecting and decoding extremes of intracellular Ca 2+ concentrations.

Crypto-coding technique based on polar code and secret key generated from wireless channel characteristics for wireless communication systems

The crypto-coding technique is essential for modern digital wireless communications systems, allowing data encryption and channel coding to be performed in only one step without requiring additional hardware. This work proposes a crypto-coding technique combining polar codes with a secret key, which is derived from wireless channel characteristics, to boost the security and reliability characteristics of the systems. The secret key is divided into two parts, one is assigned to the frozen bits, and the other is XORed with the information bits. A simulation with different key lengths and code lengths is carried out in Additive white Gaussian noise (AWGN) that helps us to evaluate this technique by the error correction and security performance, computational complexity. The key benefit is that it achieves the same bit error rate (BER) performance and computational complexity as traditional polar codes and existing methods despite only taking one step. Meanwhile, it ensures completely degraded decoding effectiveness at eavesdroppers, thus it is effective against passive eavesdropping attacks. Furthermore, this method does not require additional hardware overhead for key management and distribution.