Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies
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Kratochvil, Sven (ORCID:0000000204462371)↗
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System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model
The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.
Source record↗
A Foundational Study for Normal F8 -Containing Mouse Models for the miRNA Regulation of Hemophilia A: Identification and Analysis of Mouse miRNAs that Downregulate the Murine F8 Gene
Hemophilia A (HA) is associated with defects in the F8 gene, encoding coagulation factor VIII (FVIII). Our previous studies show that F8-targeting micro RNAs (miRNAs), a group of small RNAs involved in gene regulation, can downregulate F8 expression causing HA in individuals with normal F8-genotypes and increased HA severity in patients with mutations in F8. Understanding the mechanistic underpinnings of human genetic diseases caused or modulated by miRNAs require a small animal model, such as a mouse model. Here, we report a foundational study to develop such a model system. We identified the mouse 3'untranslated region (3'UTR) on murine F8-mRNA (muF8-mRNA) that can bind to murine miRNAs. We then selected three miRNAs for evaluation: miR-208a, miR-351 and miR-125a. We first demonstrate that these three miRNAs directly target the 3'UTR of muF8-mRNA and reduce the expression of a reporter gene (luciferase) mRNA fused to the muF8-3' UTR in mammalian cells. Furthermore, in mouse cells that endogenously express the F8 gene and produce FVIII protein, the ectopic expression of these miRNAs downregulated F8-mRNA and FVIII protein. These results provide proof-of-concept and reagents as a foundation for using a normal F8-containing mouse as a model for the miRNA regulation of normal F8 in causing or aggravating the genetic disease HA.
59 BASIC BIOLOGICAL SCIENCES↗
Genetically engineered mouse models of esophageal cancer
Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.
60 APPLIED LIFE SCIENCES↗
Evaluation of Immunocompetent Mouse Models for Borrelia miyamotoi Infection
Borrelia miyamotoi is a relapsing fever spirochete that is harbored by Ixodes spp. ticks and is virtually uncharacterized, compared to other relapsing fever Borrelia vectored by Ornithodoros spp. ticks. There is not an immunocompetent mouse model for studying B. miyamotoi infection in vivo or for transmission in the vector-host cycle. Our goal was to evaluate B. miyamotoi infections in multiple mouse breeds/strains as a prelude to the ascertainment of the best experimental infection model. Two B. miyamotoi strains, namely, LB-2001 and CT13-2396, as well as three mouse models, namely, CD-1, C3H/HeJ, and BALB/c, were evaluated. We were unable to observe B. miyamotoi LB-2001 spirochetes in the blood via darkfield microscopy or to detect DNA via real-time PCR post needle inoculation in the CD-1 and C3H/HeJ mice. However, LB-2001 DNA was detected via real-time PCR in the blood of the BALB/c mice after needle inoculation, although spirochetes were not observed via microscopy. CD-1, C3H/HeJ, and BALB/c mice generated an antibody response to B. miyamotoi LB-2001 following needle inoculation, but established infections were not detected, and the I. scapularis larvae failed to acquire spirochetes from the exposed CD-1 mice. In contrast, B. miyamotoi CT13-2396 was visualized in the blood of the CD-1 and C3H/HeJ mice via darkfield microscopy and detected by real-time PCR post needle inoculation. Both mouse strains seroconverted. However, no established infection was detected in the mouse organs, and the I. scapularis larvae failed to acquire Borrelia after feeding on CT13-2396 exposed CD-1 or C3H/HeJ mice. Furthermore, these findings underscore the challenges in establishing an experimental B. miyamotoi infection model in immunocompetent laboratory mice.
60 APPLIED LIFE SCIENCES↗
Chimeric Mouse Models for Space Radiation Risk Investigations
Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).
Radiation effects↗
Chimeric Mouse Models for Space Radiation Risk Investigations
Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).
Radiation effects↗
Chimeric Mouse Models for Space Radiation Risk Investigations
Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.
Honglu Wu↗
Chimeric Mouse Models for Space Radiation Risk Investigations
Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.
Honglu Wu↗
Targeted alpha therapy in a systemic mouse model of prostate cancer - a feasibility study
225 Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of 225 Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq 225 Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. Results: C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p<0.0001) but inferior to that in the early treatment cohort (13 vs. 27 weeks; p<0.001). Late cohort mice succumbed to extensive liver involvement. The 22Rv1 and C4-2B systemic models were not used for treatment due to high kidney metastatic burden or low take rate, respectively. Conclusion: C4-2 cells reproduced metastatic cancer spread most relevantly. Early treatment with 225 Ac-PSMA-617 prevented liver metastases and led to significant survival benefit. Late treatment improved survival without reducing tumor burden in the liver, the main site of metastasis. The current findings suggest that early 225 Ac-PSMA-617 intervention is more efficacious in the setting of widespread metastatic PCa.
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction
Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes. This causes enhanced osteoblast proliferation, followed by disruption in lacunar-canalicular connectivity and massive osteocyte death by 10 wk of age. We hypothesized that reduced viable osteocyte density would decrease the magnitude of systemic bone loss after femur fracture, reduce perilacunar remodeling, and alter callus formation. Bone remodeling was assessed using serum biomarkers of bone formation and resorption at 5 d post-fracture. We used micro-computed tomography, high resolution x-ray microscopy, mechanical testing, and Raman spectroscopy to quantify the magnitude of systemic bone loss, as well as changes in osteocyte lacunar volume, bone strength, and bone composition 2 wk post-fracture. Fracture was associated with a reduction in circulating markers of bone resorption in non-transgenic (TG-) animals. TG+ mice exhibited high bone mass in the limbs, greater cortical elastic modulus and reduced post-yield displacement. After fracture, TG+ mice lost less trabecular bone than TG- mice, but conversely TG+ mice exhibited trends toward a lower yield point and reduced femoral cortical thickness after fracture, though these were not statistically significant. Lacunar density was greater in TG+ mice, but fracture did not alter lacunar volume in TG+ or TG- mice. These findings suggest that osteocytes potentially play a significant role in the post-traumatic systemic response to fracture, though the effects differ between trabecular and cortical bone.
60 APPLIED LIFE SCIENCES↗
The Preclinical Validation of 405 nm Light Parasiticidal Efficacy on Leishmania donovani in Ex Vivo Platelets in a Rag2 -/- Mouse Model
Violet–blue light of 405 nm in the visible spectrum at a dose of 270 J/cm 2 alone has been shown to be an effective microbicidal tool for inactivating several bacteria, HIV-1, and Trypanosoma cruzi in ex vivo plasma and platelets. Unlike chemical- and ultraviolet (UV)-based pathogen inactivation methods for plasma and platelet safety, 405 nm light is shown to be less toxic to host cells at light doses that are microbicidal. In this report, we evaluated the parasiticidal activity of a 405 nm light treatment on platelets spiked with the Leishmania donovani parasite. Following the light treatment, parasite viability was observed to be near zero in both low- and high-titer-spiked platelets relative to controls. Furthermore, to test the residual infectivity after inactivation in vivo, the light-treated low-titer L. donovani-spiked platelets were evaluated in an immunodeficient Rag2 -/- mouse model and monitored for 9 weeks. The parasiticidal efficacy of 405 nm light was evident from the lack of a presence of parasites in the mice spleens. Parasiticidal activity was confirmed to be mediated through 405 nm light-induced reactive oxygen species (ROS), as quantitatively measured by a 2',7'-Dichlorodihydrofluorescein diacetate (H 2 DCFDA)-based assay. Overall, these results confirm the complete inactivation of L. donovani spiked in ex vivo platelets by 405 nm light treatment and exemplify the utility of the Rag2 -/- mouse infection model for the preclinical validation of the parasiticidal efficacy of 405 nm light and this light-based technology as a potential PRT for ex vivo platelets.
405 nm light↗
Mouse models of Ebola virus tolerance and lethality: characterization of CD-1 mice infected with wild-type, guinea pig-adapted, or mouse-adapted virus
Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV resulted in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant did not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice. Furthermore, these data support future investigations of pathogenesis, convalescence, and sequelae in mouse models of virus tolerance.
60 APPLIED LIFE SCIENCES↗
Behavioral consequences of low dose radiation and sex differences in MCAT mouse model
Our study used 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation and were euthanized 12 weeks after. In this study, we used an MCAT mouse model for mitochondrial ROS quenching, which overexpress human catalase. MCAT mice were shown to live longer and age better. Hence, in this study we determined whether quenching ROS in the mitochondria will mitigate the adverse effects of ionizing radiation exposure on spaceflight-relevant tissues. As part of the analysis, we have completed 5 different behavioral tests which focus on memory, physical stance, stress, anxiety, and other mission relevant behaviors. In the Neuro-score battery, performed after both 1and 8 weeks post IR we saw that all female groups had significantly higher scores compared to males. When comparing the baseline vs 8 weeks of radiation, we saw that all the male groups (including the sham) had lower neuro-score, pointing out to aging effect in addition to IR. In the female groups only the female IR group had lower neuro-score and the MCAT group was protected from this effect. In the Nestlet building test we saw similarly that only females were affected by radiation, having lower scores and this effect was mitigated in the MCAT animals as well. In the Catwalk test we saw that females were faster, had higher swing speed and stride length in all four paws. Males had higher stand, step cycle and max contact area. Aging is associated with slowing of gait speed, swing speed and shortening of stride length which we see in males, this is consistent with physical appearance where males look markedly older. In the Light-Dark Box test we saw that females were more frequently present in the light side and altered zones more frequently, pointing out to a more exploratory and less anxious pattern of behavior. Similarly, to what was detected in the Nest building and Neuro-score test, in the Barnes maze test, during the acquisition phase (learning) we saw that IR affected more the females who did not do better in the maze after 4 days. On the other hand, during the probe phase of the test (spatial memory) the females visited the target hole and the box quadrant more often, but also had more errors vs males, which points out to possible serial escape vs spatial escape strategy. Overall, we see that older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was mitigated in the MCAT model pointing out to the importance of ROS in these stressors. In the near future we will focus on corelating these behavioral tests with molecular findings such as for example brain IHC, plasma and hippocampal cytokines in order to find specific biomarkers for behavioral deficits.
radiation↗
Neuro-behavioral Consequences of Low Dose Radiation Social Isolation and Sex Differences in the Longevity MCAT Mouse Model
The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.
radiation↗
Ticking off Lyme disease: OspA mRNA vaccine halts infection in mouse model
Lyme disease, a condition caused by Borrelia burgdorferi sensu lato and transmitted to humans via ticks, affects approximately 676,000 individuals annually in the United States and Western Europe.1 Currently, there is no approved Lyme vaccine available for human use. A promising study by Tahir et al., published in Molecular Therapy Nucleic Acids, investigated the efficacy of mRNA and subunit vaccines targeting Lyme disease.2 This research demonstrated complete protection from infection in a tick-fed mouse model using an outer surface protein A (OspA) mRNA vaccine. Although mRNA vaccines have shown success against viral pathogens, their clinical application against bacterial diseases has been limited.3 Thus, this study represents an important step toward developing an effective mRNA vaccine against Lyme disease.
He, Wei↗
Exposed Phosphatidylserine as a Biomarker for Clear Identification of Breast Cancer Brain Metastases in Mouse Models
Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood–tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, 125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.
Oncology↗
Circadian rhythmicity of amyloid‐beta‐related molecules is disrupted in the choroid plexus of a female Alzheimer's disease mouse model
Abstract The choroid plexus (CP) is part of the blood‐cerebrospinal fluid barrier (BCSFB) and was recently described as an important component of the circadian clock system. It is the principal source of cerebrospinal fluid (CSF) and responsible for the synthesis and secretion of various neuroprotective peptides including those involved in amyloid‐β (Aβ) transport/degradation, contributing to Aβ homeostasis. Inadequate Aβ metabolic clearance and transport across the BCSFB have been associated with circadian dysfunctions in Alzheimer's disease (AD) patients. To investigate whether AD pathology influences Aβ scavengers circadian expression, we collected CP at different time points from an AD mouse model (APP/PS1) (female and male animals, aged 6‐ and 12‐months‐old) and analyzed their mRNA expression by Real‐time RT‐PCR. Only angiotensin‐converting enzyme (Ace) expression in 6‐month‐old female wild‐type mice and transthyretin (Ttr) expression in 12‐month‐old female wild‐type mice presented significant rhythmicity. The circadian rhythmicity of Ace and Ttr, prompt us to analyze the involvement of circadian rhythm in Aβ uptake. A human CP papilloma (HIBCPP) cell line was incubated with Aβ‐488 and uptake was evaluated at different time points using flow cytometry. Aβ uptake displayed circadian rhythmicity. Our results suggest that AD might affect Aβ scavengers rhythmicity and that Aβ clearance is a rhythmic process possibly regulated by the rhythmic expression of Aβ scavengers.
Furtado, André↗