Morphological Shifts Research Articles

GOOD MOANING! THE HUMOROUS ALTERATIONS AND TRANSLATION MECHANISMS IN THE LINES OF ‘ALLo ‘ALLo!’S OFFICER CRABTREE

Officer Crabtree is a memorable character from the British sitcom ‘Allo ‘Allo!, char- acterized by his pseudo-English speech. The ways in which his language deviates from the stan- dard English bring about a very humorous effect. This paper introduces the main tenets of the incongruity theory and the main types of wordplay through which Crabtree’s speech is delivered, before defining the relevant morphological and morphosyntactic shifts which dominate his lines in the series. Next, the paper collects all of his original lines from the show, analyzes them for different morphological changes and classifies them accordingly, while the Serbian translation of his lines is also taken into account and analyzed for further morphological and morphosyntactic shifts. Additionally, the direct translation mechanisms from English to Serbian are analyzed and classified as well. The results are first expressed in terms of percentage, and then compared be- tween the two languages, with the aim to discover which of the presented alterations dominate in creating the comical effect for the audience.

Development of Convolutional Neural Network to Segment Ultrasound Images of Histotripsy Ablation.

Histotripsy is a focused ultrasound therapy that ablates tissue via the action of bubble clouds. It is under investigation to treat a number of ailments, including renal tumors. Ultrasound imaging is used to monitor histotripsy, though there remains a lack of definitive imaging metrics to confirm successful treatment outcomes. In this study, a convolutional neural network (CNN) was developed to segment ablation on ultrasound images. A transfer learning approach was used to replace classification layers of the residual network ResNet-18. Inputs to the classification layers were based on ultrasound images of ablated red blood cell phantoms. Digital photographs served as the ground truth. The efficacy of the CNN was compared to subtraction imaging, and manual segmentation of images by two board-certified radiologists. The CNN had a similar performance to manual segmentation, though was improved relative to segmentation with subtraction imaging. Predictions of the network improved over the course of treatment, with the Dice similarity coefficient less than 20% for fewer than 500 applied pulses, but 85% for more than 750 applied pulses. The network was also applied to ultrasound images of ex vivo kidney exposed to histotripsy, which indicated a morphological shift in the treatment profile relative to the phantoms. These findings were consistent with histology that confirmed ablation of the targeted tissue. Overall, the CNN showed promise as a rapid means to assess outcomes of histotripsy and automate treatment. Data collected in this study indicate integration of CNN image segmentation to gauge outcomes for histotripsy ablation holds promise for automating treatment procedures.

The History and Development of Noun Gender in the German Language

This article explores the historical development, cognitive aspects, and sociolinguistic influences on noun gender in the German language. It traces the evolution of grammatical gender from Proto-Indo-European roots through Old High German and Middle High German to Modern German, highlighting key changes and the impact of external influences such as Latin and other languages. The study examines phonological and morphological shifts, semantic roles, and the challenges faced by learners due to inconsistencies in gender assignment. It also delves into ongoing debates about the necessity and complexity of gender, proposed reforms, and the importance of understanding historical context for language learning and teaching. The article concludes with potential future directions for the German gender system, emphasizing the balance between linguistic heritage and inclusivity.

Partial upgrading of bitumen with supercritical water— liquid products characteristics, gas composition and coke morphology

The study aimed to investigate the partial upgrading of bitumen in the absence of water (non-water) and the presence of supercritical water (SCW). Partial upgrading experiments were conducted at the target temperature of 420 °C, with the reaction time varying from zero to 60 min in a batch reactor. The liquid products were analyzed for density, viscosity, composition, total acid number (TAN), olefin content, and elemental analysis. The gas composition and morphology of solid products were also studied. The experimental results revealed that while partial upgrading of bitumen with SCW could accelerate improvement in oil quality, particularly in terms of API and viscosity, it concurrently led to elevated gas and coke formation levels. Moreover, the difference in the distribution of oil fractions between the two environments (absence and presence of SCW) tends to diminish with an extended residence time. Additionally, as the residence time increases, the efficiency of TAN reduction under SCW conditions is less pronounced compared to the non-water conditions. Liquid products obtained in an SCW environment exhibited higher olefin content (between 3 and 4 wt %) compared to non-water conditions (between 1.8 and 2.7 wt %). In both environments, the olefin content was initially increased up to a residence time of 20 min and then decreased. Regarding heteroatoms, the sulphur (S) and nitrogen (N) contents decreased up to 36 % and 72 %, respectively, while a greater reduction was observed in the presence of SCW. More non-hydrocarbon gases (H2S, CO2 and CO) were produced in the presence of SCW. SEM images showed that an extended residence time led to a shift in coke morphology towards a more uniform and compact structure, regardless of the upgrading environment. However, the porous structures of coke samples obtained under SCW are distinguished from those formed without water, which is attributed to the phase inversion of precursors. The findings of this study confirm that SCW plays a beneficial role as a solvent in the partial upgrading of bitumen, expediting the process. However, the increased level of coke formation and olefin contents suggest that it may not function effectively as a hydrogen donor in the process.

Synthesis and characterization of Y and Mn -doped ZnO nanoparticles: Structural, optical, morphological, and gas sensing investigations

ZnO and Mn-doped Zn0.92Y0.08-xMnxO (x = 0, 0.01, 0.02, 0.04, 0.06) nanoparticles were synthesized hydrothermally and thoroughly characterized structurally, morphologically, and optically. X-ray diffraction (XRD) confirmed their crystalline wurtzite structure, with dopant concentration affecting lattice parameters, causing expansion or contraction. X-ray photoelectron spectroscopy (XPS) confirmed Mn and Y integration into the ZnO matrix. Scanning electron microscopy (SEM) showed morphological shifts from rods to flowers with increased Mn doping concentration. UV–visible absorption revealed optical band changes due to doping. Fourier transform infrared spectroscopy (FTIR) identified Zn–O, Y–O, and Mn–O bonds. Photoluminescence (PL) indicated intensity shifts with doping, suggesting dopant influence on defect-related emissions. Doped ZnO nanoparticles displayed superior hydrogen gas sensing, especially x = 0.04 at 250 °C, attributed to smaller size and structural changes.

Synthesis and characterization of ZnCo2O4 nanocomposites with enhanced electrochemical features for supercapacitor applications

Supercapacitors have recently emerged as a promising alternative to conventional batteries due to their improved energy storage capabilities. The optical, electrochemical, and structural properties of ZnCo2O4 nanocomposites produced by hydrothermal synthesis are detailed in this study. In order to study the physicochemical properties of the synthesized goods, the created nanocomposite samples were analyzed using XRD, FT-IR, UV–Vis, SEM with EDAX, HR-TEM, BET, XPS, and charge storage potential. Crystallite size was found to be inversely proportional to increasing range of 5.01 nm to 10.62 nm in the XRD data, which compared the cubic structure. Electron microscopy and high-resolution transmission electron microscopy (HR-TEM) indicated a morphological shift indicative of improved electrochemical capabilities. The absorption research showed that different molar ratios were successful in increasing the optical bandgap from zero to 1.93 eV, whereas functional component adsorption lowered it from 2.35 eV. A maximum specific capacitance of 383.3 Fg−1 was determined by the electrochemical research, which indicated an inherent pseudo capacitance. Experimental results show that the ZnCo2O4 nanocomposite can effectively store charges, which is in line with expectations given its high capacitance and very inexpensive production.

Chronic sleep deprivation impairs retinal circadian transcriptome and visual function

Sleep loss is common in modern society and is increasingly associated with eye diseases. However, the precise effects of sleep loss on retinal structure and function, particularly on the retinal circadian system, remain largely unexplored. This study investigates these effects using a chronic sleep deprivation (CSD) model in mice. Our investigation reveals that CSD significantly alters the retinal circadian transcriptome, leading to remarkable changes in the temporal patterns of enriched pathways. This perturbation extends to metabolic and immune-related transcriptomes, coupled with an accumulation of reactive oxygen species in the retina. Notably, CSD rhythmically affects the thickness of the ganglion cell complex, along with diurnal shifts in microglial migration and morphology within the retina. Most critically, we observe a marked decrease in both scotopic and photopic retinal function under CSD conditions. These findings underscore the broad impact of sleep deprivation on retinal health, highlighting its role in altering circadian gene expression, metabolism, immune response, and structural integrity. Our study provides new insights into the broader impact of sleep loss on retinal health.

Subtle morphological changes in the visual and antennal sensory system of bees and wasps across an urbanisation gradient

Increased temperature and fragmentation of green spaces in urban areas could drive variations in functional traits of insects. Such morphological shifts may occur for sensory systems, which were previously reported to be prone to change with habitat characteristics in non-urban contexts. Here, we measured traits related to the visual and antennal sensory systems in the bees Halictus scabiosae and Osmia cornuta and the wasp Polistes dominula along an urbanisation gradient within Milan (Italy). We hypothesised that fragmentation could filter for better visual properties, and that higher temperature could filter for fewer thermoreceptors and more olfactory hairs. While controlling for body size, results show subtle but appreciable responses to urbanisation in one or more traits in all species, though not always supporting our hypotheses. O. cornuta shows marginally higher ommatidia density and smaller ommatidia diameter (associated with better visual resolution) in more fragmented sites, as well as marginally fewer thermoreceptors in hotter sites, in agreement with our two predictions. On the other hand, H. scabiosae has marginally smaller antennae and P. dominula has smaller eyes at warmer locations, and the wasp also has smaller antennae and 9th flagellomeres in more fragmented areas. Perhaps higher temperatures accelerate development of sensory system at higher speed than the rest of body in these two species. Our results represent the first evidence of urbanisation effects on the visual and antennal sensory systems of bees and wasps and underline how such effects may involve a much broader bouquet of traits then previously observed.

One-Step Preparation of High-Stability CsPbX3/CsPb2X5 Composite Microplates with Tunable Emission.

The core-shell structure is an effective means to improve the stability and optoelectronic properties of cesium lead halide (CsPbX3 (X = Cl, Br, I)) perovskite quantum dots (QDs). However, confined by the ionic radius differences, developing a core-shell packaging strategy suitable for the entire CsPbX3 system remains a challenge. In this study, we introduce an optimized hot-injection method for the epitaxial growth of the CsPb2X5 substrate on CsPbX3 surfaces, achieved by precisely controlling the reaction time and the ratio of lead halide precursors. The synthesized CsPbX3/CsPb2X5 composite microplates exhibit an emission light spectrum that covers the entire visible range. Crystallographic analyses and density functional theory (DFT) calculations reveal a minimal lattice mismatch between the (002) plane of CsPb2X5 and the (10) plane of CsPbX3, facilitating the formation of high-quality type-I heterojunctions. Furthermore, introducing Cl- and I- significantly alters the surface energy of CsPb2X5's (110) plane, leading to an evolutionary morphological shift of grains from circular to square microplates. Benefiting from the passivation of CsPb2X5, the composites exhibit enhanced optical properties and stability. Subsequently, the white light-emitting diode prepared using the CsPbX3/CsPb2X5 composite microplates has a high luminescence efficiency of 136.76 lm/W and the PL intensity decays by only 3.6% after 24 h of continuous operation.

STEATOUS CHANGES IN HEPATOCYTES IN PATIENTS WITH CHRONIC HEPATITIS C

Background. The main consequences of progressing of a chronic hepatitis C are a cirrhosis of a liver and hepatocellular carcinoma. Considering that for last years number of cases of CHC disease among population of the world has essentially increased, creation of adequate methods of an estimation of morphological and metabolic shifts in a liver tissue at CHC is the important clinical problem.
 Aim: to determine the morphological features of steatosis in patients with CHC and assess its effect on the progression of hepatitis.
 Materials and methods. Under supervision there were 46 CHC patients in the age of 19 - 66 years, 36 men and 10 - women. Liver biopsy was carried out under the control of ultrasonic research with local anesthesia.
 Conclusion. Among CHC patients steatosis of a liver is observed in 60, 9% of supervised. Expressiveness of steatosis on Hornboll is distributed: 1-st degree at 13,0% of patients, 2-nd – 28,3%, 3-rd – 19,6%, absence of steatosis- at 39,1%. At initial stages of steatosis in hepatocytes of peripheral zone of segments the significant amount lysosomes, which look like lipofuscin granules which contain lipide, electronically-dense, small-sized granular, pigmentary component, safety of structure of organelles, hyperplasia mitochondrions. At expressed steatosis dense lipid vacuoles which borrow the most part of cytoplasm of hepatocytes, displace organelles, deform a kernel of cells, damage superficial membranes mitochondrions are observed. In periportal zone, on border of contact of hepatocytes which contain lipid granules, and lymphomonocytic infiltrate, the expressed activation of Kupfer cells, insufficiency of granules in cells of ITO, their transformation in fibroblasts, the expressed adjournment of collagenic fibers is observed.

Abstract 5398: Single-cell transcriptomic analysis of partial endothelial-to-mesenchymal transition in sprouting angiogenesis

Abstract Endothelial-to-mesenchymal transition (EndoMT) is a process of morphological, functional, and molecular shift of endothelial cells (EC) towards a mesenchymal identity. This process is critical for embryonic development, and knockout animals lacking copies of the individual master EndoMT transcription factors – including Slug, Snail, and Twist – exhibit significant cardiovascular defects. We previously showed that while Slug knockout animals have a modest developmental vascular phenotype, there is a striking loss of tumor angiogenesis in these animals. Based on these and other data, we hypothesize that sprouting angiogenesis involves transient acquisition of an intermediate state of the EndoMT program –i.e., partial EndoMT (pEndoMT). To test this hypothesis, we used single cell RNA sequencing at day 2 and day 6 following TGF-β activation to map the transcriptomic changes associated with complete endothelial-to-mesenchymal transition. In parallel, we sequenced EC activated to undergo sprouting angiogenesis in vitro at the same timepoints. We show that angiogenic EC transiently acquire a transcriptomic profile of the pEndoMT state, but then later reacquire the transcriptomic profile of committed EC rather than transition completely into mesenchymal cells. We further use this dataset to identify several candidate genes that appear to be regulated by Slug and associated with the pEndoMT state. Future work will use in vitro and in vivo angiogenesis models to identify how pEndoMT is regulated in angiogenesis, and how this regulation may differ in the presence of tumor stroma. Citation Format: Kapil Thapa, Christopher J. Hatch, Christopher Hughes, Jennifer S. Fang. Single-cell transcriptomic analysis of partial endothelial-to-mesenchymal transition in sprouting angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5398.

Prolonged faunal turnover in earliest ants revealed by North American Cretaceous amber

All ∼14,000 extant ant species descended from the same common ancestor, which lived ∼140-120 million years ago (Ma).1,2 While modern ants began to diversify in the Cretaceous, recent fossil evidence has demonstrated that older lineages concomitantly occupied the same ancient ecosystems.3 These early-diverging ant lineages, or stem ants, left no modern descendants; however, they dominated the fossil record throughout the Cretaceous until their ultimate extinction sometime around the K-Pg boundary. Even as stem ant lineages appear to be diverse and abundant throughout the Cretaceous, the extent of their longevity in the fossil record and circumstances contributing to their extinction remain unknown.3 Here we report the youngest stem ants, preserved in ∼77 Ma Cretaceous amber from North Carolina, which illustrate unexpected morphological stability and lineage persistence in this enigmatic group, rivaling the longevity of contemporary ants. Through phylogenetic reconstruction and morphometric analyses, we find evidence that total taxic turnover in ants was not accompanied by a fundamental morphological shift, in contrast to other analogous stem extinctions such as theropod dinosaurs. While stem taxa showed broad morphological variation, high-density ant morphospace remained relatively constant through the last 100 million years, detailing a parallel, but temporally staggered, evolutionary history of modern and stem ants.

The NLRP3 inhibitor, OLT1177 attenuates brain injury in experimental intracerebral hemorrhage

Background and PurposeIt has been reported activation of NLRP3 inflammasome after intracerebral hemorrhage (ICH) ictus exacerbates neuroinflammation and brain injury. We hypothesized that inhibition of NLRP3 by OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could reduce brain edema and attenuate brain injury in experimental ICH. MethodsICH was induced by injection of autologous blood into basal ganglia in mice models. Sixty-three C57Bl/6 male mice were randomly grouped into the sham, vehicle, OLT1177 (Dapansutrile, 200 mg/kg intraperitoneally) and treated for consecutive three days, starting from 1 h after ICH surgery. Behavioral test, brain edema, brain water content, blood–brain barrier integrity and vascular permeability, cell apoptosis, and NLRP3 and its downstream protein levels were measured. ResultsOLT1177 significantly reduced cerebral edema after ICH and contributed to the attenuation of neurological deficits. OLT1177 could preserve blood–brain barrier integrity and lessen vascular leakage. In addition, OLT1177 preserved microglia morphological shift and significantly inhibited the activation of caspase-1 and release of IL-1β. We also found that OLT1177 can protect against neuronal loss in the affected hemisphere. ConclusionsOLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH.

Effect of Passaging on Bovine Chondrocyte Gene Expression and Engineered Cartilage Production.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Exploring the Influence of Morphology on Bipolaron-Polaron Ratios and Conductivity in Polypyrrole in the Presence of Surfactants.

This research aims to deepen the understanding of the relationship between conductivity and morphology in polypyrrole (PPy) via a comparison of the bipolaron to polaron ratios with a focus on the C-H deformation area. PPy samples were synthesized with different surfactants: sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and tween 80 (TW). This study revealed that SDS significantly altered the bipolaron and polaron in the C-H deformation region and showed higher conductivity than other surfactants. Notably, the morphological shifts to a sheet-like structure when using ammonium sulfate (APS) contrasted with the particle-like form observed with ferric chloride (FeCl3). These results showed that if the oxidant changed, the bipolaron and polaron ratios in C-H deformation were unrelated to PPy morphology. However, this work showed a consistent relationship between SDS use, the bipolaron and polaron ratios in the C-H deformation, and the conductivity properties. Moreover, the natural positive charge of PPy and negatively charged SDS molecules may lead to an electrostatic interaction between PPy and SDS. This work assumes that this interaction might cause the transformation of polaron to bipolaron in the C-H deformation region, resulting in improved conductivity of PPy. This work offers more support for the future investigation of PPy characteristics.

Transcriptional responses to salinity-induced changes in cell wall morphology of the euryhaline diatom Pleurosira laevis.

Diatoms are unicellular algae with morphologically diverse silica cell walls, which are called frustules. The mechanism of frustule morphogenesis has attracted attention in biology and nanomaterials engineering. However, the genetic regulation of the morphology remains unclear. We therefore used transcriptome sequencing to search for genes involved in frustule morphology in the centric diatom Pleurosira laevis, which exhibits morphological plasticity between flat and domed valve faces in salinity 2 and 7, respectively. We observed differential expression of transposable elements (TEs) and transporters, likely due to osmotic response. Up-regulation of mechanosensitive ion channels and down-regulation of Ca2+-ATPases in cells with flat valves suggested that cytosolic Ca2+ levels were changed between the morphologies. Calcium signaling could be a mechanism for detecting osmotic pressure changes and triggering morphological shifts. We also observed an up-regulation of ARPC1 and annexin, involved in the regulation of actin filament dynamics known to affect frustule morphology, as well as the up-regulation of genes encoding frustule-related proteins such as BacSETs and frustulin. Taken together, we propose a model in which salinity-induced morphogenetic changes are driven by upstream responses, such as the regulation of cytosolic Ca2+ levels, and downstream responses, such as Ca2+-dependent regulation of actin dynamics and frustule-related proteins. This study highlights the sensitivity of euryhaline diatoms to environmental salinity and the role of active cellular processes in controlling gross valve morphology under different osmotic pressures.

Exceptionally rapid tooth development and ontogenetic changes in the feeding apparatus of the Komodo dragon.

Dental developmental and replacement patterns in extinct amniotes have attracted a lot of attention. Notable among these are Paleozoic predatory synapsids, but also Mesozoic theropod dinosaurs, well known for having true ziphodonty, strongly serrated carinae with dentine cores within an enamel cap. The Komodo dragon, Varanus komodoensis, is the only extant terrestrial vertebrate to exhibit true ziphodonty, making it an ideal model organism for gaining new insights into the life history and feeding behaviours of theropod dinosaurs and early synapsids. We undertook a comparative dental histological analysis of this extant apex predator in combination with computed tomography of intact skulls. This study allowed us to reconstruct the dental morphology, ontogeny, and replacement patterns in the largest living lizard with known feeding behaviour, and apply our findings to extinct taxa where the behaviour is largely unknown. We discovered through computed tomography that V. komodoensis maintains up to five replacement teeth per tooth position, while histological analysis showed an exceptionally rapid formation of new teeth, every 40 days. Additionally, a dramatic ontogenetic shift in the dental morphology of V. komodoensis was also discovered, likely related to changes in feeding preferences and habitat. The juveniles have fewer dental specializations, lack true ziphodonty, are arboreal and feed mostly on insects, whereas the adults have strongly developed ziphodonty and are terrestrial apex predators with defleshing feeding behaviour. In addition, we found evidence that the ziphodont teeth of V. komodoensis have true ampullae (interdental folds for strengthening the serrations), similar to those found only in theropod dinosaurs. Comparisons with other species of Varanus and successive outgroup taxa reveal a complex pattern of dental features and adaptations, including the evolution of snake-like tongue flicking used for foraging for prey. However, only the Komodo dragon exhibits this remarkable set of dental innovations and specializations among squamates.

Light quality induces a shift in coccosphere morphology in Scyphosphaera apsteinii.

The coccolithophore Schyphosphaera apsteinii produces distinct coccolith morphotypes and offers a unique insight into coccolith calcification, as the number of lopadoliths per cell increases under low light intensities. This study employs S. apsteinii to investigate the acclimated impact of light intensity and wavelength on cell physiology and coccosphere morphology. Our findings reveal a marked increase in lopadolith production when grown under reduced light intensity, with lower growth rates, higher chlorophyll concentration and elevated net photosynthetic rates. Reduced blue-light also caused an increase in lopadolith numbers, elevated chlorophyll concentrations and net photosynthetic rates. Conversely, such responses are less pronounced under reduced red-light. Moreover, reduced blue- and red-light treatments exhibited enhanced growth rates compared to the light-replete control, despite a reduction in light intensity. Our findings suggest that changes in light quality cause a shift in the coccosphere morphology, affecting cell physiology and potentially aiding light harvesting in S. apsteinii.

Abstract WP322: GluN2A-NMDAR Mediated Increased Neuronal Prostaglandin E2 Release and Microglial Activation Exacerbates Ischemic Brain Injury Under Hyperhomocysteinemic Condition

Hyperhomocysteinemia (Hhcy), a metabolic disorder is recognized as a risk factor for ischemic stroke. However, the impact of Hhcy on stroke outcome is not known. Using a rodent model of experimental stroke, we recently showed that predisposition to Hhcy exacerbates ischemic brain injury. The findings also showed that Hhcy triggers GluN2A subunit containing NMDA receptor (GluN2A-NMDAR) stimulation that act in conjunction with ischemia-induced pathways involving GluN2B subunit containing NMDAR (GluN2B-NMDAR) stimulation to enhance stroke pathology. The current study evaluated whether GluN2A-NMDAR-mediated increased expression of cyclooxygenase-2 (COX-2) and excessive release of the pro-inflammatory mediator prostaglandin E2 (PGE2) from neurons results in increased microglial activation and exacerbated ischemic brain injury. HHcy was induced by implantation of Alzet pumps with L-homocysteine in adult male Wistar rats. Cerebral ischemia was induced by middle cerebral artery occlusion (60 min) in control and Hhcy rats. In a subset of Hhcy rats, NVP-AAM077, a pharmacological inhibitor of GluN2A-NMDAR was injected intravenously at the onset of stroke. At specified times following reperfusion, brain tissues were processed for FluroJade staining, immunoblotting with COX2 antibody, immunohistochemistry with COX2/NeuN and Iba1 antibodies, prostaglandin E2 (PGE2) assay and RT-PCR. FluroJade staining shows an early onset and exacerbation of ischemic injury in Hhcy rats. This involves increased expression of COX-2 in neurons, release of PGE2, and a shift in microglial morphology from ramified state to active amoeboid state, 6h after reperfusion. Administration of NVP-AAM077 attenuates the increase in COX2 expression and PGE2 levels as well as microglial activation. The findings demonstrate that an early onset of neuroinflammatory response mediated through GluN2A-NMDAR stimulation could contribute to the exacerbation of ischemic brain injury under Hhcy conditions. As GluN2A-NMDAR stimulation is primarily involved in promoting synaptic plasticity, neuronal growth, and survival, establishing their role in promoting neuroinflammatory response could lead to a paradigm shift in our understanding of the consequences of NMDAR signaling.

Lateral shift from turbidite- to contourite-dominated continental slope, a case study from southeast Brazil slope

New bathymetric and subsurface data from the Santos Basin, offshore southeast Brazil, reveal sharp lateral morphological variations facing the margin-parallel (along-margin) flow of the Antarctic Intermediate Water. The data, derived from 3D Pre-Stack Depth Migrated (PSDM) seismic reflection volumes, show on a ~100 km long Southern segment slope gullies, mass transport deposits, and scars. These morphologies sharply shift laterally to a ~50 km long Northern segment, typified by a smooth relief built of plastered contourite drifts with occasional elongated depressions. We examine this sharp lateral shift in the morphology of bottom current indicators in view of the hydrodynamical regime, sediment sources, and their distribution pattern. Results indicate that the sharp lateral morphological shift is attributed to (1) a 30° change in slope orientation, and (2) a northward increase in the across-margin velocity component of the Intermediate Water Boundary Current (IWBC). Subsurface data suggest this flow pattern has persisted since the mid-Miocene. In this case study, the lateral morphological shifts under contemporary hydrodynamic conditions emphasize the importance of understanding the coupling between ocean bottom currents and the seafloor in any marine environment.