Search Results (83)

Extensive research in laboratory rodents has shown that novelty exposure enhances the consolidation of memories for preceding or following low-arousal events by elevating dopamine release in the dorsal hippocampus (dHipp). Additionally, numerous studies have demonstrated that post-encoding noradrenergic activation of the basolateral amygdala (BLA) can also enhance memory consolidation in dHipp. Since the BLA is most active during emotionally arousing or stress-related situations, it was suggested that this nuclear complex mediates the effects of emotional salience on memory consolidation. However, it is presently unknown whether the reinforcement of memory storage in dHipp induced by novel and arousing environmental conditions results from the interaction between these two modulatory systems. To test the hypothesis of a functional interaction between dopaminergic and noradrenergic systems, this study assessed their combined effects on a low-arousal object-location (OL) task. Rats received post-training intra-BLA infusions of vehicle or clenbuterol (Clen), a selective β-adrenoceptor agonist. Novelty-induced dopamine release in the dHipp was enhanced by omitting habituation prior to training, and the contribution of dopamine signaling was further evaluated using pre-infusion administration of the D1/D5 receptor antagonist SCH 23390. The distribution of two important proteins for memory processing, namely the activity-regulated cytoskeleton-associated protein (Arc) and the phosphorylated form of the transcription factor, cAMP-response element-binding protein (pCREB) in the dHipp, was explored in a subset of rats perfused 60 min after the training phase. Stimulation of the BLA significantly increased the number of Arc- and pCREB-positive cells in several dHipp areas. The preceding application of SCH 23390, however, substantially decreased these effects in the same areas, i.e., the dentate gyrus (DG), CA2, and CA1 subregions for pCREB, and the CA3b, CA3c, CA2, and CA1 subregions for Arc. This interaction is considered essential for the initial stages of memory consolidation. The obtained results indicate the presence of a region-specific interaction between BLA modulatory inputs and intrahippocampal dopaminergic transmission, the mechanisms of which remain to be elucidated. Full article

Background: Cassava (Manihot esculenta Crantz) ranks as the sixth largest food crop worldwide and serves as an important cash and energy crop. Heavy-metal-associated isoprenylated plant proteins (HIPPs) are metallochaperones involved in metal homeostasis and stress adaptation in vascular plants. However, research on the identification and function of HIPPs in cassava has been poorly explored. Methods: This study conducted a pan-genome-wide investigation to identify and characterize MeHIPPs in 31 cassava accessions. Subsequent analyses examined their physicochemical properties, subcellular localization, phylogeny, Ka/Ks, chromosomal localization, synteny, gene structure, and cis-acting elements. Additionally, the expression profiles of MeHIPPs in different tissues and cell subsets and under different stress conditions were analyzed using transcriptome data and quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 59 MeHIPP pan-genes were identified, including five core genes, 22 softcore genes, 17 dispensable genes, and 15 private genes, which were unevenly distributed on chromosomes. Based on phylogenetic analysis, these genes were classified into five major subgroups. Evolutionary analyses indicated that segmental duplication predominated in family expansion and that most members may be subjected to purifying selection. Cis-element analysis highlighted the importance of MeHIPPs in plant adaptation to environmental stress. The expression profiles suggested widespread involvement of MeHIPP genes in response to Xanthomonas phaseoli pv. manihotis (Xpm) infection and drought stress. Different MeHIPP genes exhibited varying transcript levels in different tissues and cell subsets. qRT-PCR analysis revealed that the selected MeHIPP genes had distinct expression patterns under Cd stress. Conclusions: This study provides valuable insights into the functional characteristics of MeHIPP genes and their evolutionary relationships, laying a theoretical foundation for further functional research on stress resistance. Full article

Heavy-metal-associated (HMA) isoprenylated plant proteins (HIPPs) play crucial roles in plant responses to biotic/abiotic stresses and heavy-metal homeostasis. However, the involvement of HIPP genes in the response of soybean (Glycine max) to aluminum (Al) toxicity remains unexplored. This study aimed to comprehensively characterize the GmHIPP gene family and investigate its role in Al toxicity. A total of 76 GmHIPP genes were identified in the soybean genome. Phylogenetic and synteny analyses revealed that HIPP evolution was highly conserved among soybean, Arabidopsis (Arabidopsis thaliana), and rice (Oryza sativa). Cis-element analysis indicated that GmHIPP genes might be involved in phytohormone response, abiotic and biotic stresses, and plant growth. RNA-seq analysis further revealed that the expression of 20 GmHIPPs was up-regulated, and three GmHIPPs were down-regulated under Al stress in roots. Among them, six genes (GmHIPP9/13/29/43/58/73) were highly induced by Al, with GmHIPP29 exhibiting particularly high expression in root tips. Subcellular localization demonstrated that GmHIPP29 is a plasma membrane-localized protein. GmHIPP29-overexpression significantly increased Al accumulation in the cell sap of the transgenic soybean hairy root tips, leading to increased Al sensitivity. Collectively, these results demonstrate that GmHIPP29 acts as a negative regulator of Al tolerance by promoting Al accumulation in soybean roots. Full article

Background: Inflammation is a common reason for dogs to present to veterinary clinics. Early diagnosis of systemic inflammation is important. Acute phase proteins, like C-reactive protein, are useful but not specific to infection. In human medicine, the intensive care infection score (ICIS) offers a faster, cost-effective alternative using advanced hematological parameters. While ICIS is not available for veterinary use, some components (e.g., neutrophil side fluorescent light) can be measured using analyzers like the Sysmex XN-1000V. Objectives: This study aimed to establish a control group of healthy dogs for the novel parameters neutrophil side fluorescent light (NE-SFL), neutrophil side scattered light (NE-SSC), and neutrophil forward scattered light (NE-FSC) and assess their utility in detecting inflammation in diseases such as sepsis, pyometra, steroid-responsive meningitis-arteritis (SRMA), and idiopathic epilepsy. Methods & Results: Value ranges were calculated based on 21 healthy dogs. Compared to controls, NE-SFL levels were significantly elevated in sepsis, pyometra, and SRMA, while NE-SSC was only elevated in sepsis and pyometra and NE-FSC only in sepsis. No increases were observed in idiopathic epilepsy. Manual gating of the white blood cell differential scattergram was necessary in samples showing high neutrophil toxicity and the presence of bands. Conclusion: NE-SFL and NE-SSC, obtainable from routine complete blood count, may serve as novel, accessible markers for inflammation in dogs. Further research is needed to validate their broader diagnostic use. Full article

The increase in electrification and desire for greater electrical motor efficiency under a range of operating conditions for different products (e.g., household appliances, automotive and aerospace) is driving innovative motor designs and demands for higher performing electrical steels. Improvements in the magnetic, electrical and/or mechanical properties of electrical steels are required for high-volume electric motors and recent advances include steels with increased silicon (Si) content (from <3.5 wt% Si up to 6.5 wt%). Whilst the 6.5 wt% Si steels provide increased motor performance at high frequencies, the formation of a brittle BCC B2/D03 phase means that they cannot be cold-rolled, and therefore the production route involves siliconization after the required thickness strip is produced. The advances in computationally driven alloy design, coupled with physical metallurgical understanding, allow for more adventurous alloy design for electrical steels, outside the traditional predominantly Fe-Si compositional space. Two alloys representing a new alloy family called HiPPES (High-Performing and Processable Electrical Steel), based on low cost commonly used steel alloying elements, have been developed, cast, rolled, heat-treated, and both magnetically and mechanically tested. These alloys (with nominal compositions of Fe-3.2Mn-3.61Si-0.63Ni-0.75Cr-0.15Al-0.4Mo and Fe-2Mn-4.5Si-0.4Ni-0.75Cr-0.09Al) offer improvements compared to current ≈3 wt% Si grades: in magnetic performance (>25% magnetic loss reduction at >1 kHz), and in tensile strength (>33% increase in tensile strength with similar elongation value). Most importantly, they are maintaining processability to allow for full-scale commercial production using traditional continuous casting, hot and cold rolling, and annealing. The new alloys also showed improved resilience to grain size, with the HiPPES materials showing a <5% variance in loss at frequencies greater than 400 Hz for grain sizes between 55 and 180 µm. Comparatively, a commercial M250-35A material showed a 40% increase in loss for the same range. The paper reports on the alloy design approach used, the microstructures, and the mechanical, electrical and magnetic properties of the developed novel electrical steels compared to conventional ≈3 wt% Si and 6.5 wt% Si material. Full article

Cadmium (Cd) contamination poses significant threats to aquatic ecosystems. Heavy metal-associated isoprenylated plant proteins (HIPPs) are plant-specific chaperones involved in metal ion homeostasis and stress adaptation. Lotus is an aquatic plant with high biomass and Cd accumulation capacity, showing great potential in water remediation. However, the functional characterization of HIPPs in lotus remains unexplored, limiting its application in phytoremediation. We conducted comprehensive characterization of NnHIPP genes in lotus, integrating comparative genomics, Cd-stress transcriptomics, and heterologous expression assays in transgenic yeast. This study identified 33 NnHIPP genes classified into five subfamilies with conserved motifs and structures. Synteny analysis revealed closer evolutionary relationships with dicots (Arabidopsis and Medicago sativa) than monocots. Abundant stress-responsive elements were found in NnHIPPs promoters. Tissue-specific expression profilings indicated functional diversification across organs and developmental stages. Our transcriptome analysis revealed that most NnHIPPs responded to Cd stress, with stronger induction in roots than leaves. Four Cd-induced NnHIPPs (NnHIPP10/14/21/33) showed both plasma membrane and nuclear localization. Notably, NnHIPP14, NnHIPP21, and NnHIPP33 conferred varying degrees of Cd tolerance when overexpressed in yeast. Our study demonstrates that NnHIPPs participate in Cd stress response. Three candidate NnHIPP genes are proposed for genetic engineering to enhance phytoremediation efficiency in lotus. Full article

As a crucial modeling tool for stochastic financial markets, the Lévy risk model effectively characterizes the evolution of risks during enterprise operations. Through dynamic evaluation and quantitative analysis of risk indicators under specific dividend- distribution strategies, this model can provide theoretical foundations for optimizing corporate capital allocation. Addressing the inadequate adaptability of traditional single-period threshold strategies in time-varying market environments, this paper proposes a dividend strategy based on multiperiod dynamic threshold adjustments. By implementing periodic modifications of threshold parameters, this strategy enhances the risk model’s dynamic responsiveness to market fluctuations and temporal variations. Within the framework of the spectrally negative Lévy risk model, this paper constructs a stochastic control model for multiperiod threshold dividend strategies. We derive the integro-differential equations for the expected present value of aggregate dividend payments before ruin and the Gerber–Shiu function, respectively. Combining the methodologies of the discounted increment density, the operator introduced by Dickson and Hipp, and the inverse Laplace transforms, we derive the explicit solutions to these integro-differential equations. Finally, numerical simulations of the related results are conducted using given examples, thereby demonstrating the feasibility of the analytical method proposed in this paper. Full article

It is widely accepted that chronic inflammation constitutes a significant mechanism that promotes the biological aging process. The pineal gland is regarded as being closely related to the control of the “life clock”. The present study aimed to determine the inflammation associated with pinealectomy in the rat hippocampus and to investigate the extent to which age stage impacts the severity of this inflammation. We evaluated the expression of the Akt/NF-kB signaling pathway in neurons and gliosis level in the dorsal hippocampus (dHipp) of rats subjected to sham surgery or pinealectomy at 3, 14, or 18 months of age. The assessment was conducted using immunohistochemistry. Removal of the pineal gland resulted in significant, region-specific increases in NF-kB expression in neurons of the dHipp in the youngest and middle-aged groups. However, the change in expression of the phosphorylated form of Akt (pAkt1) in neurons went in the opposite direction in these two age groups, and there were also regional differences. Pinealectomy triggered microgliosis in both young and old rats, but middle-aged rats were resistant to microglia activation. Conversely, astrogliosis was observed in young adult and middle-aged groups with melatonin deficiency in certain regions of the dHipp. It is noteworthy that young adult rats demonstrated the highest degree of vulnerability to inflammation associated with the loss of melatonin as a hormone. In contrast, middle-aged rats with pinealectomy exhibited a complex and partial adaptive response. These findings emphasize the dynamic and age-dependent nature of neuroinflammation following pinealectomy, underscoring the developmental stage as a critical determinant of inflammatory susceptibility. Full article

Due to the health-driven demand for fat replacers in meat products, Lycopene (Lyc)-loaded yeast protein (YP) high internal phase Pickering emulsions (HIPPEs) were explored as fat replacers for 3D-printed meat products. HIPPEs with varying Lyc concentrations were formulated, and their encapsulation efficiency and antioxidant activity (DPPH and ABTS assays) were evaluated. The encapsulation efficiency of Lyc exceeded 90% for all samples. Microscopic analysis revealed significant droplet enlargement in emulsions containing Lyc concentrations of 1.25 mg/mL and 1.50 mg/mL. Antioxidant activity peaked at a Lyc concentration of 1.00 mg/mL. Three-dimensional-printed meat products with different fat replacement ratios (0%, 25%, 50%, 75% and 100%) were prepared using both Lyc-loaded and non-loaded emulsions, and their printing precision, cooking loss, color, pH, texture, and lipid oxidation were assessed. The replacement ratio had no significant impact on printing precision, while cooking yield improved with higher fat replacement levels. Lyc emulsions notably influenced meat color, resulting in lower lightness and higher redness and yellowness. pH values remained stable across formulations. Lipid oxidation decreased with increasing fat replacement levels. The results indicate that Lyc-loaded YP Pickering emulsions have great potential as effective fat replacers for 3D-printed meat products, enhancing antioxidant performance while preserving product quality. Full article

Background: With aging populations, the incidence of squamous cell carcinoma of the head and neck (SCCHN) among elderly patients is increasing. Although adjuvant radiotherapy or chemoradiation is a well-established component of multimodal treatment, elderly patients remain underrepresented in clinical trials. This study evaluates the feasibility of adjuvant radiotherapy and chemoradiation in patients over 70 years with SCCHN and explores the correlation between treatment feasibility and various comorbidity scores. Methods: We retrospectively analyzed patients over 70 years of age who received adjuvant radiotherapy or chemoradiation at the University Hospital Regensburg between 2004 and 2018. A total of 71 patients, with a median age of 75 years, were included. The majority were classified as UICC stage IVa. Median follow-up was 27 months. Results: Sixty-two patients completed treatment without interruption, and sixty-five received at least 95% of the prescribed radiation dose. The median total dose was 64 Gy. Acute toxicity of grade III or IV (CTC) occurred in 37 patients. Local tumor control rates were 99% at 12 months, 88% at 24 months, and 76% at 5 years. Overall survival rates were 87% at 12 months, 67% at 24 months, and 41% at 60 months, with a median overall survival of 51 months. The Elixhauser Comorbidity Score showed significant predictive value for treatment feasibility (p = 0.006). Conclusions: Adjuvant radiotherapy and chemoradiation are feasible and effective treatment options for elderly patients with SCCHN. The favorable local and locoregional control rates reported here suggest, in line with other recent reports in the literature, that age alone should not be a justification for treatment de-intensification. Full article

Background: Phytoremediation is an efficient approach for remediating heavy metal-contaminated soils. Heavy metal-associated isoprenylated plant proteins (HIPPs)—crucial for metal ion homeostasis—are unique to vascular plants, featuring a heavy metal-associated (HMA) domain and an isoprenylated CaaX motif. However, ZmHIPP genes have not been systematically or functionally characterized in maize. Methods: This study characterizes ZmHIPP at the genome-wide level, including phylogenetic classification, motif/gene structure, chromosome location, gene duplication events, promoter elements, and tissue expression patterns. Cadmium (Cd) responses were evaluated by specific ZmHIPP expression and Cd accumulation in shoots and roots under Cd treatment. Results: A total of 66 ZmHIPPs were distributed unevenly across ten chromosomes, classified into five phylogenetic groups phylogenetically. Gene collinearity revealed 26 pairs of segmental duplications in ZmHIPPs. Numerous synteny genes were detected in rice and sorghum, but none in Arabidopsis, suggesting high conservation of HIPP genes in crop evolution. Transcriptomic analysis revealed tissue-specific expression patterns of ZmHIPP members in maize. Cis-acting element analysis linked several binding elements to abscisic acid, MeJA response, and MYB and MYC transcription factors. Under Cd stress, 53 out of 66 ZmHIPP genes were significantly induced, exhibiting three expression patterns. Cd exposure confirmed that the expression of ZmHIPP11, ZmHIPP30, and ZmHIPP48 was generally higher in shoots than roots, while ZmHIPP02 and ZmHIPP57 exhibited the opposite. Cd accumulation was higher in roots than shoots, peaking at 72 h (96 mg/kg) in shoots and exceeding 1000 mg/kg in roots after 120 h. Conclusions: This study not only provides fundamental genetic and molecular insights into HIPP function in maize but also identifies specific ZmHIPP genes as promising genetic resources for breeding Cd-tolerant maize, aiding in phytoremediation of Cd-contaminated soils. Full article

Cadmium (Cd) stress poses significant threats to vegetable crops, impacting their growth, physiological processes, and safety as part of the human food chain. This review systematically summarizes the latest advances in the molecular mechanisms of vegetable crops’ resistance to Cd stress. First, physiological and biochemical responses are outlined, including growth inhibition, impaired photosynthesis, oxidative stress, disrupted nutrient absorption, altered phytohormone levels, and gene expression changes. Next, key molecular mechanisms are discussed, focusing on the roles of transporter-related genes (e.g., NRAMP, HIPP, ABCG), transcription factors (e.g., HsfA1a, WRKY, ERF), enzyme-related genes (e.g., E3 ubiquitin ligase, P-type ATPase), microRNAs (e.g., miR398), and potential functional genes in Cd uptake, translocation, and detoxification. Additionally, the regulatory roles of phytohormones and their analogues (e.g., brassinosteroids, gibberellin, salicylic acid) in mitigating Cd toxicity are analyzed, highlighting their involvement in antioxidant defense, gene regulation, and stress signaling pathways. Finally, future research directions are proposed, emphasizing species-specific defense mechanisms, root hair-specific Cd exclusion mechanisms, and interdisciplinary approaches integrating AI and microbiome manipulation. This review provides a comprehensive reference for enhancing Cd stress resistance in vegetable crops and promoting safe crop production. Full article

Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling impact cardiovascular health is still a matter of current research. An inducible, endothelial cell-specific knock-in mouse model expressing a yeast D-amino acid oxidase enzyme was generated (Hipp11-Flox-Stop-Flox-yDAO-Cdh5-CreERT2^+/0 referred to as ecDAO). DAO releases H₂O₂ as a by-product of the conversion of D-amino acids into imino acids. The D-amino acid treatment of DAO-expressing cells therefore increases their intracellular H₂O₂ production. The induction of yDAO in the ecDAO mice was performed with tamoxifen. Subsequently, the mice received D-Alanine (D-Ala, 0.5 M) through drinking water, and the effects on ROS production and vascular and cardiac function were determined. ecDAO induction increased endothelial ROS production as well as ROS production in the lung, which is rich in endothelial cells. The functional consequences of this were, however limited: After minimally invasive myocardial infarction, there was no difference in the outcome between the control (CTL) and ecDAO mice. With respect to vascular function, three days of D-Ala slightly improved vascular function as demonstrated by an increase in the diameter of the carotid artery in vivo and decreased vessel constriction to phenylephrine. Fifty-two days of D-Ala induced cardiac remodelling, increased peripheral resistance, and overoxidation of peroxiredoxins. In conclusion, acute stimulation of endothelial ROS improves cardiovascular function, whereas prolonged ROS exposure deteriorates it. Full article

Hippocampal segmentation is essential in neuroimaging for evaluating conditions like Alzheimer’s dementia and mesial temporal sclerosis, where small volume changes can significantly impact normative percentiles. However, inaccurate segmentation is common due to the inclusion of non-hippocampal structures such as choroid plexus and cerebrospinal fluid (CSF), leading to volumetric overestimation and confounding of functional analyses. Current methods of assessment largely rely on virtual or manual ground truth labels, which can fail to capture these inaccuracies. To address this shortcoming, this study introduces a more direct voxel intensity-based method of segmentation assessment. Using paired precontrast and postcontrast T1-weighted MRIs, hippocampal segmentations were refined by adding marginal gray matter and removing marginal CSF and enhancement to determine a total required correction volume. Six segmentation algorithms—e2dhipseg, HippMapp3r, hippodeep, AssemblyNet, FastSurfer, and QuickNat—were implemented and compared. HippMapp3r and e2dhipseg, followed closely by hippodeep, exhibited the least total correction volumes, indicating superior accuracy. Dedicated hippocampal segmentation algorithms outperformed whole-brain methods. Full article

Background: Tramadol (TRA) is an opioid that is used to manage moderate to severe pain. Long-term use of TRA can lead to the development of opioid use disorder. Objectives: This study investigates the role of forced exercise in reducing TRA-seeking behavior. Methods: Adult male rats (240–260 g) were divided into five groups; the control group received vehicle injections, the TRA group received TRA (75 mg/kg, i.p) every other day for 8 days, and three TRA–exercise groups were forced to run on a treadmill (60 min/day, 5 days/week) for 2, 4, or 6 weeks prior to conditioning with TRA. A tramadol-conditioned place preference (CPP) procedure assessed TRA reinforcement, after which all rats were euthanized, tissue extracted, and mRNA expression for brain-derived neurotrophic factor (Bdnf) and interleukin 1 beta (Il-1β) determined in hippocampus (Hipp), prefrontal cortex (PFC), and nucleus accumbens (NAc). Results: TRA-seeking behavior was seen in the TRA group and the 6 weeks forced exercise group. By contrast, forced exercise for 2 or 4 weeks attenuated TRA-seeking behavior. This attenuation was associated with a significant increase in Bdnf mRNA expression in the Hipp and NAc, but not the PFC. Additionally, the TRA-induced elevations in Il-1β mRNA expression were reversed by all durations of exercise in Hipp. However, only 2 and 4 weeks, but not 6 weeks, of exercise reduced elevations in PFC and NAc Il-1β expression. Conclusion: Forced exercise for 2 and 4 weeks attenuates TRA-seeking behavior partially through the regulation of Bdnf and Il-1β mRNA expression. Full article