Search Results (51)

Epilepsy is a multifaceted neurological disorder characterized by recurrent seizures and associated with molecular and immune alterations in key brain regions. The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca), a genetic model for audiogenic epilepsy, provides a powerful tool to study seizure mechanisms and resistance in predisposed individuals. This study investigates the proteomic and immune responses triggered by audiogenic kindling in the inferior colliculus, comparing non-responder animals exhibiting reduced seizure severity following repeated stimulation versus GASH/Sal naïve hamsters. To assess auditory pathway functionality, Auditory Brainstem Responses (ABRs) were recorded, revealing reduced neuronal activity in the auditory nerve of non-responders, while central auditory processing remained unaffected. Cytokine profiling demonstrated increased levels of proinflammatory markers, including IL-1 alpha (Interleukin-1 alpha), IL-10 (Interleukin-10), and TGF-beta (Transforming Growth Factor beta), alongside decreased IGF-1 (Insulin-like Growth Factor 1) levels, highlighting systemic inflammation and its interplay with neuroprotection. Building on these findings, a proteomic analysis identified 159 differentially expressed proteins (DEPs). Additionally, bioinformatic approaches, including Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), revealed disrupted pathways related to metabolic and inflammatory epileptic processes and a module potentially linked to a rise in the threshold of seizures, respectively. Differentially expressed genes, identified through bioinformatic and statistical analyses, were validated by RT-qPCR. This confirmed the upregulation of six genes (Gpc1—Glypican-1; Sdc3—Syndecan-3; Vgf—Nerve Growth Factor Inducible; Cpne5—Copine 5; Agap2—Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and Dpp8—Dipeptidyl Peptidase 8) and the downregulation of two (Ralb—RAS-like proto-oncogene B—and S100b—S100 calcium-binding protein B), aligning with reduced seizure severity. This study may uncover key proteomic and immune mechanisms underlying seizure susceptibility, providing possible novel therapeutic targets for refractory epilepsy. Full article

Bengala, a steamer that sank in 1889 near Capo Rizzuto, Italy, was a relatively new vessel for its time, with an unusually short 18-year service life, given that steamers of the period typically operated for 30 to 40 years. Despite its brief history, SS Bengala played a significant role in the development of Italy’s young merchant navy, undergoing multiple ownership changes and serving various Italian shipping companies. Employed mainly along the route to Southeast Asia, it transported Italian migrants overseas and also participated in troop raids during the Italian military expedition to Eritrea in 1887. Despite its historical significance, no iconographic material has yet been found to depict SS Bengala, and archival research conducted in Italy and England has not uncovered any naval plans, photographs, or drawings of the ship. To overcome this gap, the authors employed new technologies and historical information to create a virtual reconstruction. This research combined archival sources with underwater surveys, including a detailed 3D survey by divers and archaeologists. Archival research, including consultation of official documents, provided critical information on the ship’s dimensions, superstructure, rigging, materials, and construction methods. The 3D modelling of the ship’s external hull, based on precise geometric data from the wreck site, offers a first step towards virtual reconstruction. The modelling is grounded in photogrammetric surveying techniques, ensuring high accuracy in the reconstruction process. The model can be used in augmented reality (AR) applications to enhance underwater exploration, allowing divers to visualise the reconstructed ship in its original environment. Additionally, it supports museum exhibits, interactive visualisations, and educational games, making it a valuable resource for engaging the public with maritime history and archaeology. Full article

A submerged elevation located off the coast of Le Castella, a small village on the Ionian Coast of Calabria (Italy) populated for thousands of years that features notable archaeological remains from the Great Greece (Magna Graecia) and the Middle Ages, was investigated through in-depth, multidisciplinary, geoarchaeological research. This submarine elevation, once aligned with the marine terrace MIS 3 of Le Castella and still completely emerged between 10 and 8 ka years ago, slowly sank due to erosion and local tectonic-structural subsidence and was also favoured by a submerged normal fault that cuts the terrace in two. The dismantling and sinking of this part of the marine terrace has significantly changed the Late Holocene shorelines, with notable consequences on a topographic and archaeological level. In fact, one of the consequences of the sinking of this ancient promontory was the disappearance of two small islands that were reported to be right in front of Le Castella by numerous historical and cartographic sources. In the last decades, there has been a scientific debate over the existence of these islets, but no convincing evidence has been found about their actual presence up until now. This research, funded by the Marine Protected Area “Capo Rizzuto”, was conducted by means of underwater archaeological and geological surveys, geophysical seabed mapping systems, and both direct and instrumental optical surveys made with an Autonomous Surface Vehicle. The outcomes allow us to confirm the presence of these two partially emerged rock bodies up to half a millennium ago. In addition, the presence of anthropogenic extrabasinal materials in a marine area corresponding to one of the highest points of the submerged elevation allows us to define the exact position of one of the two islets. These archaeological findings have been subject, for the first time ever, to a thorough topographical and architectural analysis, then compared with other near and very similar submerged structures. On the basis of these comparisons, the findings should be attributed to the Byzantine Age or, at most, to the Middle Ages. In-depth archival research on portolan charts and navigation maps, in many cases unpublished and dating from the Middle Ages to the early 18th century, supports the results of our marine investigations from a historical point of view. Full article

Aeromonas salmonicida is a major pathogenic bacterium that poses a significant threat to salmonid fish. Yadong County, located in the Xizang Autonomous Region, is renowned for its characteristic industry of Salmo trutta aquaculture. In recent years, the outbreak of Bacterial Gill Disease (BGD) has led to substantial economic losses for S. trutta farmers. Our prior research identified A. salmonicida as one of the primary culprits behind BGD. To mitigate the impact of A. salmonicida on S. trutta, we conducted a comprehensive study aimed at identifying genes associated with resistance to A. salmonicida. This involved transcriptome sequencing and 16S rRNA sequencing of intestinal flora, providing valuable insights for the study of disease resistance in S. trutta. In this study, we identified 324 genera with 5171 ASVs in the susceptible group and 293 genera with 5669 ASVs in the resistant group. Notably, Methylobacterium and Sphingomonas were common bacteria present in the salmon’s gut, and their proportions remained relatively stable before and after infection. Shewanella, with its antagonistic relationship with Aeromonas, may play a crucial role in the salmon’s defense against A. salmonicida. Several related genes were identified, including angptl4, cipcb, grasp, ccr9a, sulf1, mtmr11, B3GNT3, mt2, PLXDC1, and ank1b. Full article

Background: Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL. Full article

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress. Full article

Drought stress is one of the significant abiotic stresses that limit soybean (Glycine max [L.] Merr.) growth and production. Ankyrin repeat (ANK) proteins, being highly conserved, occupy a pivotal role in diverse biological processes. ANK genes were classified into nine subfamilies according to conserved domains in the soybean genome. However, the function of ANK-TM subfamily proteins (Ankyrin repeat proteins with a transmembrane domain) in the abiotic-stress response to soybean remains poorly understood. In this study, we first demonstrated the subcellular localization of GmANKTM21 in the cell membrane and nucleus. Drought stress-induced mRNA levels of GmANKTM21, which encodes proteins belonging to the ANK-TM subfamily, Transgenic 35S:GmANKTM21 soybean improved drought tolerance at the germination and seedling stages, with higher stomatal closure in soybean, lower water loss, lower malondialdehyde (MDA) content, and less reactive oxygen species (ROS) production compared with the wild-type soybean (Dongnong50). RNA-sequencing (RNA-seq) and RT-qPCR analysis of differentially expressed transcripts in overexpression of GmANKTM21 further identified potential downstream genes, including GmSPK2, GmSPK4, and GmCYP707A1, which showed higher expression in transgenic soybean, than those in wild-type soybean and KEGG enrichment analysis showed that MAPK signaling pathways were mostly enriched in GmANKTM21 overexpressing soybean plants under drought stress conditions. Therefore, we demonstrate that GmANKTM21 plays an important role in tolerance to drought stress in soybeans. Full article

Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced symptoms of chest pressure, palpitations, and shortness of breath, leading to the eventual diagnosis of myocarditis complicated by recurrent ventricular tachycardia. Treatment with mechanistically driven anti-arrhythmic therapy and beta-blockers suppressed this highly symptomatic ventricular tachycardia. Genetic testing to further risk stratify and influence long term care identified a single nucleotide variant in the ANK-2 gene, which is known to be associated with arrhythmic risk. Discussion: This case study highlights the use of rationally selected anti-arrhythmic therapy, mexiletine, in the management of ventricular tachycardia associated with COVID-19 myocarditis and the presence of a single nucleotide variant in ANK-2, raising the possibility of its contribution to VT susceptibility and severity. Our patient demonstrated significant improvement with administered therapeutics, including the resolution of myocarditis and ventricular tachycardia. The normalization of the QT interval during the resolution phase further supports the potential influence of the genetic variant in ANK-2 on potassium channel activity. Full article

In an effort to enhance growth rates, chicken breeders have undertaken intensive genetic selection. In the selection process, the primary aim is to accelerate growth, inadvertently leading to new chicken breeds having an increased capacity for rapid adipose tissue accumulation. However, little is known about the relationship between changes in gene expression and adipose tissue accumulation and deposition in chickens. Therefore, in this study, RNA-seq analysis was utilized, and transcriptome data were obtained from the abdominal fat, thoracic subcutaneous fat, and clavicular fat on day 1 (d1), day 4, day 7, day 11, and day 15 to reveal the molecular mechanisms regulating the development and deposition of different adipose tissues in broiler chicks. The results showed that the key period for adipocyte differentiation and proliferation was between d4 and d7 (abdominal fat development) and between d1 and d4 (chest subcutaneous fat and clavicular fat). In addition, candidate genes such as MYOG, S100A9, CIDEC, THRSP, CXCL13, and NMU related to adipose tissue growth and development were identified. Further, genes (HOXC9, AGT, TMEM182, ANGPTL3, CRP, and DSG2) associated with the distribution of adipose tissue were identified, and genes (MN1, ANK2, and CAP2) related to adipose tissue growth were also identified. Taken together, the results from this study provide the basis for future studies on the mechanisms regulating adipose tissue development in chickens. Further, the candidate genes identified could be used in the selection process. Full article

The summer of 2022 was one of the hottest and driest summers that Germany experienced in the 21st century. Water levels in rivers sank dramatically with many dams and reservoirs running dry; as a result, fields could not be irrigated sufficiently, and even power generation and supply were affected. The impact of abnormally high temperatures for extended periods (heatwaves) is not restricted to nature and the economy but is also a considerable public health burden. Experts worldwide agree that these extreme weather events are being driven by climate change and will increase in intensity and frequency in the future. The adverse impact of these extreme weather events multiplies among dense urban environments, e.g., through heat islands. This calls for cities to take action to heat-proof and water-secure their urban developments. Water-Sensitive Urban Design (WSUD) is one such approach to mitigate the aforementioned challenges by leveraging the urban water ecosystem with special attention to the subject of water reclamation, retention, treatment and distribution. This paper introduces and builds upon a prototype of WSUD that centers around an artificial lake as an integrated water resource management system (IWRMS) fed by treated grey water and storm water obtained from two housing blocks flanking the water reservoir. Based on the specifications of this prototype, indicators of site suitability are derived and applied to identify potential locations for replicable projects in the city of Darmstadt. The results confirm the impact WSUD can have: a total of 22 sites with 2527 apartments are found suitable for prototype implementation in Darmstadt. Savings in town water consumption from these 22 sites would add up to 147 million liters. Further benefits include the provision of 24 million liters of irrigation water, storm water retention, adiabatic cooling during heatwave, increased biodiversity and the improvement in livability of the sites and the city. Full article

While studying myoblast methylomes and transcriptomes, we found that CDH15 had a remarkable preference for expression in both myoblasts and cerebellum. To understand how widespread such a relationship was and its epigenetic and biological correlates, we systematically looked for genes with similar transcription profiles and analyzed their DNA methylation and chromatin state and accessibility profiles in many different cell populations. Twenty genes were expressed preferentially in myoblasts and cerebellum (Myob/Cbl genes). Some shared DNA hypo- or hypermethylated regions in myoblasts and cerebellum. Particularly striking was ZNF556, whose promoter is hypomethylated in expressing cells but highly methylated in the many cell populations that do not express the gene. In reporter gene assays, we demonstrated that its promoter’s activity is methylation sensitive. The atypical epigenetics of ZNF556 may have originated from its promoter’s hypomethylation and selective activation in sperm progenitors and oocytes. Five of the Myob/Cbl genes (KCNJ12, ST8SIA5, ZIC1, VAX2, and EN2) have much higher RNA levels in cerebellum than in myoblasts and displayed myoblast-specific hypermethylation upstream and/or downstream of their promoters that may downmodulate expression. Differential DNA methylation was associated with alternative promoter usage for Myob/Cbl genes MCF2L, DOK7, CNPY1, and ANK1. Myob/Cbl genes PAX3, LBX1, ZNF556, ZIC1, EN2, and VAX2 encode sequence-specific transcription factors, which likely help drive the myoblast and cerebellum specificity of other Myob/Cbl genes. This study extends our understanding of epigenetic/transcription associations related to differentiation and may help elucidate relationships between epigenetic signatures and muscular dystrophies or cerebellar-linked neuropathologies. Full article

In February 2023, an oil tanker carrying 5660 bbl of industrial fuel oil sank off Naujan in the Philippines, causing an oil spill in the waters of Oriental Mindoro and nearby provinces. The disaster affected fishing communities as well as marine ecosystems including the Verde Island Passage, which is at the “center of the world’s marine biodiversity”. This study assessed the immediate social and economic impacts of this oil spill on various communities of the Naujan coast. We conducted semi-structured interviews and employed a narrative analysis to explore the lived experiences of fisherfolk after the oil spill and to understand the socioeconomic impacts. With the prohibition of fishing and other aquatic activities, the participants lost up to USD 1300 of income per week from fishing. The participants had no other source of income due to the lack of other skills or an opportunity for an alternative livelihood in the community. While the government provided food packs and financial assistance, the participants found these insufficient to sustain their basic family needs including food, utilities, education, and health. Traces of oil were also found in the sources of potable water affecting their daily household activities. The fisherfolk, who live in communities that are vulnerable to natural and human-made hazards, had their subsistence, food security, and human well-being highly compromised. The findings provided recommendations for government interventions to mitigate the impacts of an oil spill and other future disasters, considering social, economic, and human ecological perspectives. Full article

In order to reveal the acute toxicity and physiological changes of the spotted babylon (Babylonia areolata) in response to environmental manipulation, the spotted babylon was exposed to three pH levels (7.0, 8.0 and 9.0) of seawater and four concentrations of nitrite nitrogen (0.02, 2.7, 13.5 and 27 mg/L). The activities of six immunoenzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT), acid phosphatase (ACP), alkaline phosphatase (AKP) and peroxidase (POD), were measured. The levels of pH and nitrite nitrogen concentrations significantly impacted immunoenzyme activity over time. After the acute stress of pH and nitrite nitrogen, the spotted babylon appeared to be unresponsive to external stimuli, exhibited decreased vigor, slowly climbed the wall, sank to the tank and could not stand upright. As time elapsed, with the extension of time, the spotted babylon showed a trend of increasing and then decreasing ACP, AKP, CAT and SOD activities in order to adapt to the mutated environment and improve its immunity. In contrast, POD and GSH-PX activities showed a decrease followed by an increase with time. This study explored the tolerance range of the spotted babylon to pH, nitrite nitrogen, and time, proving that external stimuli activate the body’s immune response. The body’s immune function has a specific range of adaptation to the environment over time. Once the body’s immune system was insufficient to adapt to this range, the immune system collapsed and the snail gradually died off. This study has discovered the suitable pH and nitrite nitrogen ranges for the culture of the spotted babylon, and provides useful information on the response of the snail’s immune system. Full article

Tea is one of the most popular non-alcoholic beverages globally. The leaves of the tea plants serve as the raw materials for tea production, making tea tree cultivation widespread as an economically significant tree species. Nonexpressor of pathogenesis-related genes 1 (NPR1) is a key regulator of the salicylic acid (SA) signaling pathway, playing a significant role in the plant’s response to biotic and abiotic stresses. However, the NPR1-like gene family in tea plants remains elusive. This study aims to systematically analyze the NPR1-like gene family in tea plants. Four CsNPR1-like genes were identified and categorized into three branches based on phylogenetic analysis. Collinearity analysis demonstrated conservation of the NPR1-like gene across different species. Analysis of cis-regulatory elements suggested that CsNPR1-like genes may be involved in various hormonal and stress responses. Protein structure analysis revealed that the CsNPR1-likes exhibited typical ANK and BTB/POZ structural domains. The protein interaction network identified various known and novel NPR1-interacting proteins, including the TGA transcription factor, which was further confirmed in planta. Meta-analysis of transcriptome data indicated that CsNPR1-like genes had spatiotemporal expression patterns and were induced by drought and cold stresses. Additionally, CsNPR1a activates the accumulation of the acidic SA-dependent pathogenic-associated protein PR1 but not the basic chitinase (PR3) in a transient expression assay. This study provides comprehensive information for investigating the NPR1-like gene family in tea plants. Full article

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed. Full article