Topographic Distribution Research Articles

Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis.

Secretory immunoglobulin A (SIgA) interaction with commensal bacteria conditions microbiota composition and function. However, mechanisms regulating reciprocal control of microbiota and SIgA are not defined. Bacteria-derived adenosine triphosphate (ATP) limits T follicular helper (Tfh) cells in the Peyer's patches (PPs) via P2X7 receptor (P2X7R) and thereby SIgA generation. Here we show that hydrolysis of extracellular ATP (eATP) by apyrase results in amplification of the SIgA repertoire. The enhanced breadth of SIgA in mice colonized with apyrase-releasing Escherichia coli influences topographical distribution of bacteria and expression of genes involved in metabolic versus immune functions in the intestinal epithelium. SIgA-mediated conditioning of bacteriaand enterocyte function is reflected by differences in nutrient absorption in mice colonized with apyrase-expressing bacteria. Apyrase-induced SIgA improves intestinal homeostasis and attenuates barrier impairment and susceptibility to infection by enteric pathogens in antibiotic-induced dysbiosis. Therefore, amplification of SIgA by apyrase can be leveraged to restore intestinal fitness in dysbiotic conditions.

Topographical EEG Recordings of Visual Evoked Potentials in Mice using Multichannel Thin-film Electrodes.

Visual evoked potentials (VEP) allow the characterization of visual function in preclinical mouse models. Various methods exist to measure VEPs in mice, from non-invasive EEG, subcutaneous single-electrodes, and ECoG to fully invasive intracortical multichannel visual cortex recordings. It can be useful to acquire a global, topographical EEG-level characterization of visual responses previous to local intracortical microelectrode measurements in acute experimental settings. For example, one use case isto assess global cross-modal changes in VEP topography in deafness models before studying its effects on a local intracortical level. Multichannel epicranial EEG is a robust method to acquire such an overview measure of cortical visual activity.Multichannel epicranial EEG provides comparable results through a standardized, consistent approach to, for example, identify cross-modal, pathological, or age-related changes in cortical visual function. The current study presents a method to obtain the topographical distribution of flash-evoked VEPs with a 32-channel thin-film EEG electrode array in anesthetized mice. Combined with analysis in the time and frequency domain, this approach allows fast characterization and screening of the topography and basic visual properties of mouse cortical visual function, which can be combined with various acute experimental settings.

Morphological basis of Parkinson disease-associated cognitive impairment: an update

Cognitive impairment is one of the most salient non-motor symptoms of Parkinson disease (PD) that poses a significant burden on the patients and carers as well as being a risk factor for early mortality. People with PD show a wide spectrum of cognitive dysfunctions ranging from subjective cognitive decline and mild cognitive impairment (MCI) to frank dementia. The mean frequency of PD with MCI (PD-MCI) is 25.8% and the pooled dementia frequency is 26.3% increasing up to 83% 20years after diagnosis. A better understanding of the underlying pathological processes will aid in directing disease-specific treatment. Modern neuroimaging studies revealed considerable changes in gray and white matter in PD patients with cognitive impairment, cortical atrophy, hypometabolism, dopamine/cholinergic or other neurotransmitter dysfunction and increased amyloid burden, but multiple mechanism are likely involved. Combined analysis of imaging and fluid markers is the most promising method for identifying PD-MCI and Parkinson disease dementia (PDD). Morphological substrates are a combination of Lewy- and Alzheimer-associated and other concomitant pathologies with aggregation of α-synuclein, amyloid, tau and other pathological proteins in cortical and subcortical regions causing destruction of essential neuronal networks. Significant pathological heterogeneity within PD-MCI reflects deficits in various cognitive domains. This review highlights the essential neuroimaging data and neuropathological changes in PD with cognitive impairment, the amount and topographical distribution of pathological protein aggregates and their pathophysiological relevance. Large-scale clinicopathological correlative studies are warranted to further elucidate the exact neuropathological correlates of cognitive impairment in PD and related synucleinopathies as a basis for early diagnosis and future disease-modifying therapies.

Modeling Parkinson's disease-related symptoms in alpha-synuclein overexpressing mice.

BackgroundIntracellular deposition of alpha‐synuclein (α‐syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α‐synucleinopathies. Transgenic mouse models overexpressing human α‐syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α‐syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α‐syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions.PurposeOne of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within‐group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD‐related symptoms in such studies.MethodsWe have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α‐syn in the context of their validity and utility for different types of behavioral studies.ConclusionsBy applying appropriate behavioral tests, α‐syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α‐synucleinopathies.

N-terminally truncated Aβ4-x proteoforms and their relevance for Alzheimer’s pathophysiology

BackgroundThe molecular heterogeneity of Alzheimer’s amyloid-β (Aβ) deposits extends well beyond the classic Aβ1-40/Aβ1-42 dichotomy, substantially expanded by multiple post-translational modifications that increase the proteome diversity. Numerous truncated fragments consistently populate the brain Aβ peptidome, and their homeostatic regulation and potential contribution to disease pathogenesis are largely unknown. Aβ4-x peptides have been reported as major components of plaque cores and the limited studies available indicate their relative abundance in Alzheimer’s disease (AD).MethodsImmunohistochemistry was used to assess the topographic distribution of Aβ4-x species in well-characterized AD cases using custom-generated monoclonal antibody 18H6—specific for Aβ4-x species and blind for full-length Aβ1-40/Aβ1-42—in conjunction with thioflavin-S and antibodies recognizing Aβx-40 and Aβx-42 proteoforms. Circular dichroism, thioflavin-T binding, and electron microscopy evaluated the biophysical and aggregation/oligomerization properties of full-length and truncated synthetic homologues, whereas stereotaxic intracerebral injections of monomeric and oligomeric radiolabeled homologues in wild-type mice were used to evaluate their brain clearance characteristics.ResultsAll types of amyloid deposits contained the probed Aβ epitopes, albeit expressed in different proportions. Aβ4-x species showed preferential localization within thioflavin-S-positive cerebral amyloid angiopathy and cored plaques, strongly suggesting poor clearance characteristics and consistent with the reduced solubility and enhanced oligomerization of their synthetic homologues. In vivo clearance studies demonstrated a fast brain efflux of N-terminally truncated and full-length monomeric forms whereas their oligomeric counterparts—particularly of Aβ4-40 and Aβ4-42—consistently exhibited enhanced brain retention.ConclusionsThe persistence of aggregation-prone Aβ4-x proteoforms likely contributes to the process of amyloid formation, self-perpetuating the amyloidogenic loop and exacerbating amyloid-mediated pathogenic pathways.

Patterns of Focal Amyloid Deposition Using 18F-Florbetaben PET in Patients with Cognitive Impairment.

Accumulation of aggregated amyloid-β (Aβ) in the brain is considered the first pathological event within the pathogenesis of Alzheimer’s disease (AD). It is difficult to accurately identify the initial brain regions of Aβ accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aβ deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aβ accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aβ accumulation in the brain of people with AD continuum.

Evaluating Head Models for Cortical Source Localization of the Face-Sensitive N290 Component in Infants.

Accurate cortical source localization of event-related potentials (ERPs) requires using realistic head models constructed from the participant's structural magnetic resonance imaging (MRI). A challenge in developmental studies is the limited accessibility of participant-specific MRIs. The present study compared source localization of infants' N290 ERP activities estimated using participant-specific head models with a series of substitute head models. The N290 responses to faces relative to toys were measured in 36 infants aged at 4.5, 7.5, 9, and 12months. The substitutes were individual-based head models constructed from age-matched MRIs with closely matched ("close") or different ("far") head measures with the participants, age-appropriate average template, and age-inappropriate average templates. The greater source responses to faces than toys at the middle fusiform gyrus (mFG) estimated using participant-specific head models were preserved in individual-based head models, but not average templates. The "close" head models yielded the best fit with the participant-specific head models in source activities at the mFG and across face-processing-related regions of interest (ROIs). The age-appropriate average template showed mixed results, not supporting the stimulus effect but showed topographical distributions across the ROIs like the participant-specific head models. The "close" head models are the most optimal substitute for participant-specific MRIs.

Topographical Distribution and Morphology of CGRP‐IR Axons in the Flat‐Mounts of Whole Mouse and Rat Hearts

To understand and treat cardiac pain, it is important to have an understanding of the topographical distribution of nociceptive axons in the heart. While previous studies have detected nociceptive axons in the sectioned heart, their full distribution has not yet been determined. In this study, we used a nociceptive marker calcitonin gene‐related peptide (CGRP) to determine the distribution of nociceptive afferent axons in the whole heart. We first removed the hearts of male Sprague‐Dawley rats (n=6), and C57BL/6 mice (n=6). The hearts were dissected into left and right atria and ventricles and interventricular septum, and prepared as flat‐mounts. These samples were then processed with immunohistochemical labeling using a primary antibody which binds to CGRP and an Alexa Fluro 488 secondary antibody for fluorescence. The flat‐mounts were imaged with a Zeiss M2 Imager (automatic fluorescence microscope) using a 488 nm excitation wavelength. In both rats and mice, we found that CGRP‐IR nerve bundles entered the heart and innervated the left and right atria and ventricles. For the right/left atria, CGRP‐IR axons entered as large bundles near the superior/inferior vena cava, left pre‐caval vein and the pulmonary veins before bifurcating into small branches, and finally formed single varicose axons and terminals which distributed throughout the tissue, including cardiac ganglia, the SA/AV nodes, auricles, and the blood vessels. In the right/left ventricles and interventricular septum, CGRP‐IR axons entered as large bundles through the base before bifurcating into small branches towards the apex Ultimately, single varicose axons and terminals innervated myocardium and blood vessels. Our data shows the distribution of CGRP‐IR axons in the whole heart at single cell/axon resolution. With this information, we will gain insight into the function of these axons and the pathways that they follow, paving the way for the development of better treatments for cardiac pain and disease. The first two authors contributed equally to this work.

Enhanced Brain Retention of Aβ4‐x Proteoforms and its Contribution to Amyloid Deposits in Alzheimer’s Disease

The deposition of amyloid‐β (Aβ) in brain parenchyma and cerebral vasculature together with intraneuronal neurofibrillary tangles and the gradual loss of synapsis are central neuropathological hallmarks of Alzheimer’s disease (AD). Although it remains unclear what primarily triggers and drives the progression of AD, different lines of investigation point out to a central role of oligomeric Aβ conformations for the disease pathogenesis. Recent studies revealed that the molecular heterogeneity of Aβ deposits is significantly more complex than originally anticipated, extending well beyond the classic Aβ1‐40/Aβ1‐42 dichotomy and being substantially expanded by the presence of multiple post‐translational modifications that increase the proteome diversity. Although N‐terminal truncations at glutamates 3 and 11 and their subsequent cyclation to pyroglutamate are perhaps the most extensively studied modifications, many others have been reported, with species beginning at phenylalanine 4 and bearing an intact C‐terminus being especially relevant. Indeed, Aβ4‐42 peptides were reported as major components of amyloid plaque cores and the limited studies available seem to indicate their relative abundance in patients with AD, Down’s syndrome, and vascular dementia. In this work we assessed the topographic distribution of these species with in‐house‐generated anti‐Aβ4‐x monoclonal 18H6 – specific for Aβ species starting at position 4 and blind for the full‐length Aβ40 and Aβ42 – and used in conjunction with thioflavin S and antibodies specific for the C‐terminus 40 and 42 in confirmed AD cases. All types of Aβ deposits – parenchymal plaques, pre‐amyloid lesions and CAA – contained the Aβ epitopes tested, albeit expressed in different proportions. These co‐localizations were further stressed by combining double immunohistochemical analysis with Thioflavin S staining, showing the preferential location of Aβ4‐x species in CAA and cored plaques with fibrillar amyloid conformation, strongly suggesting poor clearance characteristics. To investigate the brain clearance of Aβ4‐x species in comparison with full‐length Aβ40 and Aβ42 homologues, peptides were synthesized, biochemically and biophysically characterized, radiolabeled with [125I]Na and utilized for in vivo brain clearance experiments in 5–6‐week‐old C57Bl/6 mice. Brain efflux of all monomeric Aβ species tested was fast, with >80% cleared within the 60 min duration of the experiment whereas retention of oligomeric preparations was consistently higher than that of monomeric forms. Notably, clearance of Aβ4‐40 and Aβ4‐42 was significantly lower (<45%) than the full‐length counterparts (61% ‐ 68%), further supporting a pathogenic role for Aβ oligomerization in AD and specifically highlighting the importance of oligomeric Aβ4‐x species exhibiting higher brain retention compared to their full‐length counterparts. Since the process of multimerization is concentration dependent, failing to remove these oligomeric forms of Aβ from the brain will further contribute to exacerbate the amyloidogenic loop and the persistence of amyloid deposits.

Topographical relocation of adolescent sleep spindles reveals a new maturational pattern in the human brain

Current theories of human neural development emphasize the posterior-to-anterior pattern of brain maturation. However, this scenario leaves out significant brain areas not directly involved with sensory input and behavioral control. Suggesting the relevance of cortical activity unrelated to sensory stimulation, such as sleep, we investigated adolescent transformations in the topography of sleep spindles. Sleep spindles are known to be involved in neural plasticity and in adults have a bimodal topography: slow spindles are frontally dominant, while fast spindles have a parietal/precuneal origin. The late functional segregation of the precuneus from the frontoparietal network during adolescence suggests that spindle topography might approach the adult state relatively late in development, and it may not be a result of the posterior-to-anterior maturational pattern. We analyzed the topographical distribution of spindle parameters in HD-EEG polysomnographic sleep recordings of adolescents and found that slow spindle duration maxima traveled from central to anterior brain regions, while fast spindle density, amplitude and frequency peaks traveled from central to more posterior brain regions. These results provide evidence for the gradual posteriorization of the anatomical localization of fast sleep spindles during adolescence and indicate the existence of an anterior-to-posterior pattern of human brain maturation.

Long-term correlation analysis between monthly precipitable water vapor and precipitation using GPS data over China

Precipitable Water Vapor (PWV) is an important driving factor for the occurrence of precipitation. A deep understanding of the correlation between the PWV and the precipitation helps to understand the regional water cycle based on the theory of atmospheric water balance. This study aims to analyze the correlation between the precipitation and the PWV derived from Global Positioning System (GPS) observations collected from a total of 233 Global Navigation Satellite System (GNSS) stations in China mainland over 10 years. The PWV was calculated through Zenith Total Delay (ZTD) from the Precise Point Positioning (PPP) technique and metrological data from the European Centre for Medium-Range Weather Forecasts (ECMWF). The relationship between PWV derived from GPS and the precipitation from the Tropical Rainfall Measuring Mission (TRMM) at monthly temporal resolution was analyzed through the cross-correlation analysis and the cross-wavelet analysis. Results showes that a 1-month lag was observed between monthly PWV and precipitation at some inland stations in the south-eastern region of China, which is due to the earlier peaks of precipitation caused by the quasi-stationary front in this region. After the time-lag shift, most of the stations showed a cross-correlation coefficient higher than 0.7, indicating that monthly PWV and precipitation are generally correlated over China mainland. Specifically, the cross-correlation coefficients from stations located in western China have a wide range of 0.16–0.95 and a large dispersion degree with the standard deviation (STD) of 0.2, which is due to the variable climatic conditions caused by the topographical distribution. The cross-correlation coefficients from stations located in the middle and north-eastern region of China are generally greater than 0.75 and have an STD of 0.08, while those located in the south-eastern region of China are generally less than 0.65 and have an STD of 0.09. This is because the south-eastern region of China has a relatively longer rainy season caused by the influences from Asian monsoon systems. These results could contribute to the further understanding of the regional water cycle based on the theory of atmospheric water balance within China.

Cloud water path, precipitation amount, and precipitation efficiency derived from multiple datasets on the Qilian Mountains, Northeastern Tibetan Plateau

Orographic clouds and precipitation are critical to the water cycle and ecology of arid and semiarid mountainous regions. This study intended to investigate the spatial and seasonal distribution of the cloud water path (CWP), precipitation amount, and precipitation efficiency (PE) on the Qilian Mountains (QM) of the northeastern Tibetan Plateau, as well as the related mechanisms linked with topographic distribution and water vapor transport. To solve the limitations of rain gauges and radar observations at high elevations of the QM, we used the latest multiple datasets, including the Global Precipitation Measurement (GPM), Advanced Very High Resolution Radiometer, and ECMWF Reanalysis v5 data from 2016 to 2019. The amount of precipitation retrieved from the two GPM products was evaluated using rain gauge data. The results show that the GPM data generally overestimate the precipitation amount on the QM and have a high correlation with rain gauge data in warm seasons and a low correlation in winter seasons, primarily due to the significant influences of snow and ice coverage. The terrain height and water vapor supply below 600 hPa are two critical factors that determine the spatial and seasonal distributions of clouds and precipitation in the QM. The precipitation generally increased with an increase in terrain elevation below 3000 m and decreased above 3000 m on the QM. CWP, precipitation amount, and PE in the mountainous areas are much higher than those in the surroundings and decrease from the southeast to the northwest because of the decrease in low-level water vapor supply. CWP, precipitation amount, and PE were the highest in summer because of the strong moisture transport from the southeast and the lowest in winter because of the weakest water vapor transport. Water vapor fluxes from the eastern, southern, and northern boundaries contributed to the wetness of the eastern and northeastern slopes of the QM. The lack of low-level water vapor in the westerly winds was the main reason for drought in the western QM.

Attentional modulations of alpha power are sensitive to the task-relevance of auditory spatial information

The topographical distribution of oscillatory power in the alpha band is known to vary depending on the current focus of spatial attention. Here, we investigated to what extend univariate and multivariate measures of post-stimulus alpha power are sensitive to the required spatial specificity of a task. To this end, we varied the perceptual load and the spatial demand in an auditory search paradigm. A centrally presented sound at the beginning of each trial indicated the to-be-localized target sound. This spatially unspecific pre-cue was followed by a sound array, containing either two (low perceptual load) or four (high perceptual load) simultaneously presented lateralized sound stimuli. In separate task blocks, participants were instructed either to report whether the target was located on the left or the right side of the sound array (low spatial demand) or to indicate the exact target location (high spatial demand). Univariate alpha lateralization magnitude was neither affected by perceptual load nor by spatial demand. However, an analysis of onset latencies revealed that alpha lateralization emerged earlier in low (vs high) perceptual load trials as well as in low (vs high) spatial demand trials. Finally, we trained a classifier to decode the specific target location based on the multivariate alpha power scalp topography. A comparison of decoding accuracy in the low and high spatial demand conditions suggests that the amount of spatial information present in the scalp distribution of alpha-band power increases as the task demands a higher degree of spatial specificity. Altogether, the results offer new insights into how the dynamic adaption of alpha-band oscillations in response to changing task demands is associated with post-stimulus attentional processing.

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) is a heterogeneous tumor entity that is vastly determined by age and UV-light exposure leading to a great mutational burden in cancer cells. However, the success of immune checkpoint blockade in advanced NMSC and the incidence and disease control rates of NMSC in organ transplant recipients compared to immunologically uncompromised patients point toward the emerging importance of the immunologic activity of NMSC. To gain first insight into the role of T-cell and macrophage infiltration in NMSC of the head and neck and capture their different immunogenic profiles, which appear to be highly relevant for the response to immunotherapy, we conducted a whole slide analysis of 107 basal cell carcinoma (BCC) samples and 117 cutaneous squamous cell carcinoma (cSCC) samples. The CD8+ and CD68+ immune cell expression in both cancer types was evaluated by immunohistochemistry and a topographic distribution profile, and the proportion of both cell populations within the two tumor entities was assessed. The results show highly significant differences in terms of CD8+ T-cell and CD68+ macrophage infiltration in BCC and cSCC and indicate cSCC as a highly immunogenic tumor. Yet, BCC presents less immune cell infiltration; the relation between the immune cells compared to cSCC does not show any significant difference. These findings help explain disparities in local aggressiveness, distant metastasis, and eligibility for immune checkpoint blockade in both tumor entities and encourage further research.

Differences in Evolution of Epileptic Seizures and Topographical Distribution of Tissue Damage in Selected Limbic Structures Between Male and Female Rats Submitted to the Pilocarpine Model.

Epidemiological evidence shows that clinical features and comorbidities in temporal lobe epilepsy (TLE) may have different manifestations depending on the sex of patients. However, little is known about how sex-related mechanisms can interfere with the processes underlying the epileptic phenomenon. The findings of this study show that male rats with epilepsy in the pilocarpine model have longer-lasting and more severe epileptic seizures, while female rats have a higher frequency of epileptic seizures and a greater number of seizure clusters. Significant sex-linked pathological changes were also observed: epileptic brains of male and female rats showed differences in mass reduction of 41.8% in the amygdala and 18.2% in the olfactory bulb, while loss of neuronal cells was present in the hippocampus (12.3%), amygdala (18.1%), and olfactory bulb (7.5%). Another important sex-related finding was the changes in non-neuronal cells with increments for the hippocampus (36.1%), amygdala (14.7%), and olfactory bulb (37%). Taken together, our study suggests that these neuropathological changes may underlie the differences in the clinical features of epileptic seizures observed in male and female rats.

Topographical distribution of spectrotemporal receptive field properties in the bat primary auditory cortex

Spectrotemporal modulations are a prominent feature of natural sounds including animal vocalizations and human speech. Echolocating bats must process spectrotemporal cues such as echo delays and spectrum properties to navigate their environment; however, the neuronal networks in the primary auditory cortex (A1) that process features of natural sounds remain incompletely understood. Here, we investigated the topographical distribution of tuning properties throughout A1 of Mexican free-tailed bats. While the majority of the bats’ A1 neurons are tuned to downward FM sweeps, the entire cortex is required to capture and categorize patterns of spectral details embedded within each biosonar echo. We captured the neural responses of the A1 to complex acoustic stimuli using linear, 16-channel translaminar microelectrode arrays. We analyzed 145 spectrotemporal receptive fields (STRFs) across A1, as well as the spectral and temporal modulation transfer functions (sMTF and tMTF, respectively) to determine neural tuning preferences in the spectral and temporal dimensions. We found evidence of neuronal sub-categories that were classified as having simple or complex (multi-peaked) STRFs. For simple STRFs, sMTFs and tMTFs were evaluated as a function of best frequency, and spatial location and revealed tonotopic trends similar to those reported for non-specialized animals.

Isolated Oculomotor Nuclear Infarction: A Rare Clinical Scenario

Selective infarction of the oculomotor nuclear complex without accompanying long tract involvement is an exceedingly rare event with distinctive clinical features. The complicated topographical distribution of the various nuclei within the complex can result in diverse clinical presentation.

Study on the penetration and diffusion of chloride ions in interface transition zone of recycled concrete prepared by modified recycled coarse aggregates

This work aims at exploring the penetration and diffusion behavior of chloride ions in interfacial transition zones (ITZs) of modified recycled aggregate concrete (RAC). For this purpose, RAC were prepared by using nano-SiO2 and carbonation treated recycled coarse aggregates (RCA, with different strength grades of C30 and C60) and immersed in 3.5% NaCl solution for 45 days and 90 days. The mechanical properties and free chloride ion content of the modified RAC were investigated and the topographic characteristics and element distribution patterns of Ca, Si, and Cl in ITZs of RAC were detailed characterized. The results show that the chloride ion will permeate into the interface in ITZs of RAC in the first instance, and then intrude into mortar matrix through the pores and fractures. In contrast, the internal microscopic structure of ITZs become more compact and the number of the cracks are decreased obviously after nano-SiO2 treatment, which can provide effective barrier and significantly reduce the penetration depth of chloride ions. In addition, the high strength RCA can also effectively reduce the penetration and diffusion of chloride ions to concrete matrix due to the compact and uniform microstructure. This work provides a certain theoretical guidance for further improving the chloride erosion resistance of RAC.

Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood.

The present study demonstrates altered topographic distribution and enhanced neuronal expression of major adenosine-metabolizing enzymes, i.e. ecto-5'-nucleotidase (eN) and tissue non-specific alkaline phosphatase (TNAP), as well as adenosine receptor subtype A2A in the hippocampus and cortex of male rats from early to late adulthood (3, 6, 12 and 15 months old males). The significant effect of age was demonstrated for the increase in the activity and the protein expression of eN and TNAP. At 15-m, enzyme histochemistry demonstrated enhanced expression of eN in synapse-rich hippocampal and cortical layers, whereas the upsurge of TNAP was observed in the hippocampal and cortical neuropil, rather than in cells and layers where two enzymes mostly reside in 3-m old brain. Furthermore, a dichotomy in A1R and A2AR expression was demonstrated in the cortex and hippocampus from early to late adulthood. Specifically, a decrease in A1R and enhancement of A2AR expression were demonstrated by immunohistochemistry, the latter being almost exclusively localized in hippocampal pyramidal and cortical superficial cell layers. We did not observe any glial upregulation of A2AR, which was common for both advanced age and chronic neurodegeneration. Taken together, the results imply that the adaptative changes in adenosine signaling occurring in neuronal elements early in life may be responsible for the later prominent glial enhancement in A2AR-mediated adenosine signaling, and neuroinflammation and neurodegeneration, which are the hallmarks of both advanced age and age-associated neurodegenerative diseases.

Collagenic architecture and morphotraits in a marine basal metazoan as a model for bioinspired applied research.

In some Porifera (Demospongiae: Keratosa), prototypes of the connective system are almost exclusively based on collagenic networks. We studied the topographic distribution, spatial layout, microtraits, and/or morphogenesis of these collagenic structures in Ircinia retidermata (Dictyoceratida: Irciniidae). Analyses were carried out on a clonal strain from sustainable experimental mariculture by using light and scanning electron microscopy. Histology revealed new insights on the widely diversified and complex hierarchical assemblage of collagenic structures. Key evolutionary novelties in the organization of sponge connective system were found out. The aquiferous canals are shaped as corrugate‐like pipelines conferring plasticity to the water circulation system. Compact clusters of elongated cells are putatively involved in a nutrient transferring system. Knob‐ended filaments are characterized by a banding pattern and micro‐components. Ectosome and outer endosome districts are the active fibrogenetic areas, where exogenous material constitutes an axial condensation nucleus for the ensuing morphogenesis. The new data can be useful to understand not only the evolutionary novelties occurring in the target taxon but also the morpho‐functional significance of its adaptive collagenic anatomical traits. In addition, data may give insights on both marine collagen sustainable applied researches along with evolutionary and phylogenetic analyses, thus highlighting sponges as a key renewable source for inspired biomaterials. Therefore, we also promote bioresources sustainable exploitation with the aim to provide new donors of marine collagen, thereby supporting conservation of wild populations/species.